Pirfenidone and Pentoxifylline Attenuate Ischaemia–Reperfusion Injury in Experimental Priapism: Limited Effects of Dexpanthenol

Pirfenidone and Pentoxifylline Attenuate Ischaemia–Reperfusion Injury in Experimental Priapism: Limited Effects of Dexpanthenol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Pirfenidone and Pentoxifylline Attenuate Ischaemia–Reperfusion Injury in Experimental Priapism: Limited Effects of Dexpanthenol Ibrahim Goksoy, Arif Aydın, Fahriye Kilinc, Ibrahim Kilinc, Mehmet Giray Sönmez This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9220334/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Ischaemic priapism is a urological emergency that may lead to irreversible erectile dysfunction due to cavernosal tissue damage. In this experimental study, we evaluated the acute effects of pirfenidone, pentoxifylline, and dexpanthenol on ischaemia–reperfusion injury (IRI) in a rat model of ischaemic priapism. A total of 68 male Wistar albino rats were randomly assigned to seven groups, including sham, control (IRI), and treatment groups receiving pirfenidone, pentoxifylline, dexpanthenol, or combination therapies. Ischaemic priapism was induced under anaesthesia, followed by a reperfusion period. Serum inflammatory (IL-1β, IL-10), oxidative stress (MDA, TOS, TAS), and endothelial (eNOS) markers were analysed, and histopathological evaluation was performed using semi-quantitative scoring. The control group demonstrated significantly higher IL-1β, eNOS, and MDA levels compared with treatment groups. Pirfenidone and pentoxifylline significantly reduced IL-1β and MDA levels and improved histopathological scores, while pentoxifylline also increased IL-10 levels, indicating enhanced anti-inflammatory activity. In contrast, dexpanthenol demonstrated a more limited effect, with significant improvement observed only in MDA levels. Combination therapies did not demonstrate superiority over monotherapy. These findings suggest that pirfenidone and pentoxifylline may have potential as adjunctive therapeutic options for limiting cavernosal tissue injury and preserving erectile function in ischaemic priapism. Health sciences/Medical research/Experimental models of disease Health sciences/Diseases/Urogenital diseases/Sexual dysfunction Health sciences/Health care/Disease prevention/Preventive medicine Figures Figure 1 Figure 2 INTRODUCTION Priapism is defined as a persistent penile erection lasting longer than four hours in the absence of sexual stimulation. Although rare, its incidence appears to be increasing, likely reflecting evolving patterns of medication use and the wider use of vasoactive agents. Priapism is classified into three subtypes: non-ischaemic (high-flow), ischaemic (low-flow), and stuttering (recurrent ischaemic) priapism. Among these, ischaemic priapism (IP) accounts for more than 95% of cases and is characterised by reduced or absent intracavernosal arterial inflow. It represents a true urological emergency associated with tissue ischaemia, hypoxia, acidosis, and severe penile pain, and may lead to irreversible erectile dysfunction if not treated promptly ( 1 , 2 ). Ischaemic priapism lasting longer than four hours is considered a compartment syndrome requiring urgent intervention to prevent irreversible structural damage to cavernosal smooth muscle. In addition to the initial ischaemic insult, reperfusion following detumescence may further exacerbate tissue injury through oxidative stress and inflammatory pathways, a process defined as ischaemia–reperfusion injury (IRI). Restoration of oxygenation and resolution of venous stasis are therefore critical for preserving tissue viability. Although current treatment modalities are effective in achieving detumescence in the acute setting, they do not specifically target the molecular mechanisms underlying cavernosal damage. Consequently, pharmacological strategies aimed at reducing both immediate and long-term tissue injury remain an area of ongoing investigation ( 3 ). Pirfenidone (PFD) is an antifibrotic agent that suppresses transforming growth factor-β1 (TGF-β1) and other profibrotic mediators, and has demonstrated anti-inflammatory and antioxidant properties. Pentoxifylline (PTX), a xanthine-derived non-selective phosphodiesterase inhibitor, enhances tissue perfusion and oxygenation through its vasodilatory effects and has been utilised in models of ischaemic injury due to its antifibrotic potential. Both agents have been investigated in experimental settings for their protective effects on cavernosal tissue, particularly in relation to fibrosis and oxidative stress. Dexpanthenol (DXP), a derivative of pantothenic acid, has been shown to reduce reactive oxygen species, exert anti-inflammatory effects, and promote cellular repair; however, its role in cavernosal ischaemia and priapism has not yet been clearly defined ( 2 – 4 ). The present study aimed to evaluate the acute effects of pirfenidone and pentoxifylline, previously investigated for their chronic effects in experimental models of priapism, on ischaemia–reperfusion injury. In addition, we aimed to investigate the effects of dexpanthenol, which has not previously been evaluated in a priapism model, and to assess the potential synergistic effects of combination therapies. By comparing agents with distinct pharmacological profiles, this study seeks to provide further insight into potential strategies for limiting cavernosal tissue damage in ischaemic priapism. MATERIAL AND METHOD Ethical Approval Approval for the study was obtained from the Animal Experiments Local Ethics Committee All experiments were conducted in the laboratories of the Experimental Medicine Application and Research Center of our university in accordance with institutional and international guidelines. Study Groups and Experimental Design A total of 68 adult male Wistar albino rats (8–10 weeks old, 175–245 g) were included. All animals were maintained under standardised laboratory conditions, including controlled temperature, humidity, and light–dark cycles. Preparation of oral medications is shown in Figure 1A. Rats were randomly assigned into seven groups using a simple randomisation method: Group 1 (Sham): Penectomy only Group 2 (Control): Ischaemic priapism induced under anaesthesia for one hour, followed by a one-hour ischaemia–reperfusion period without treatment and subsequent penectomy Group 3: Oral pirfenidone (325 mg/kg) administered via gastric gavage immediately before induction of priapism; dose based on previous studies (5) Group 4: Oral pentoxifylline (100 mg) administered via gastric gavage immediately before induction; dose selected according to prior studies (6) Group 5: Dexpanthenol (500 mg) administered intraperitoneally 30 minutes after induction; based on previous experimental studies demonstrating its protective effects in ischaemia–reperfusion injury models (7) Group 6: Combination therapy with pirfenidone and dexpanthenol Group 7: Combination therapy with pentoxifylline and dexpanthenol One rat in Group 4 died before termination of priapism and was excluded from the analysis. In all groups except the sham group, priapism was induced under anaesthesia for one hour. Following detumescence, a one-hour period was allowed for the development of ischaemia–reperfusion injury before penectomy. Intracardiac blood samples were collected for biochemical analysis, and penectomy specimens were processed for histopathological evaluation. All animals were sacrificed by exsanguination following sample collection. Anesthesia All animals underwent identical procedures under anaesthesia. Anaesthesia and analgesia were achieved with intramuscular ketamine (50 mg/kg) and xylazine (5 mg/kg). After induction and stabilisation, the lower abdominal and penile regions were shaved, and the surgical procedure was initiated (Figure 1B). Induction of the Ischemic Priapism Model and Reperfusion Injury Ischaemic priapism was induced according to the Şanlı model. This model has been previously validated for reproducing features of ischaemic priapism and cavernosal injury. The tip of a 50-cc irrigation syringe with a conical end was modified to fit the base of the flaccid penis. Prior to vacuum application, a constriction band—prepared from 14 Fr Foley catheters cut into 2-mm segments—was placed on the syringe tip. The syringe was then positioned at the penile base and gently retracted to induce erection. Once adequate erection was achieved, the constriction band was advanced onto the penile base to establish the ischaemic priapism model (8)(Figure 1C). Unlike previous studies, the duration of ischaemia was extended to better reflect clinically relevant severe ischaemic injury and to enhance the detection of treatment effects. Immediately after termination of ischaemia, a one-hour reperfusion period was allowed prior to tissue collection. (Figure 1D) Biochemical Analysis All biochemical analyses were performed by a biochemistry specialist blinded to group allocation. Systemic blood samples (5–6 cc) were collected into tubes without anticoagulant, allowed to clot at room temperature for 15 minutes, and centrifuged at 4°C (4000 rpm for 15 minutes). The separated sera were stored at −20°C until analysis. Serum interleukin-1β (IL-1β) and interleukin-10 (IL-10) levels were measured to assess inflammatory responses. Total oxidant status (TOS), total antioxidant status (TAS), and malondialdehyde (MDA) levels were analysed to evaluate oxidative stress, while endothelial nitric oxide synthase (eNOS) levels were measured to assess nitric oxide pathway activity. All parameters were determined using enzyme-linked immunosorbent assay (ELISA) kits. Histopathological Evaluation Histopathological examinations were performed by an experienced pathologist blinded to group allocation. Following penectomy, cavernosal tissues were fixed in 10% neutral buffered formalin, processed using an automated tissue processor (Leica ASP300S, Germany), and embedded in paraffin blocks. Sections approximately 4 µm thick were obtained using a microtome (Leica RM2245, Germany) and stained with haematoxylin–eosin (H&E) and Masson’s trichrome (MT). All sections were examined under a light microscope (Olympus BX53, Japan), and photomicrographs were obtained using an integrated digital camera system (Olympus SC50, Japan). Each specimen was evaluated for vasocongestion, inflammation, desquamation, oedema, and tunica albuginea separation/haemorrhage. The scoring system was adapted from previously published experimental studies evaluating cavernosal tissue injury. Histopathological changes were graded semi-quantitatively on a scale of 0–3 as follows: 0 = normal, 1 = mild, 2 = moderate, and 3 = severe. Statistical Analysis Statistical analyses were performed using SPSS software. Descriptive statistics were presented as mean ± standard deviation. The normality of data distribution was assessed using skewness and kurtosis coefficients, with values between −2 and +2 considered indicative of normal distribution. The validity of the ischaemia–reperfusion priapism model was evaluated by comparing the Sham group (Group 1) and the Control group (Group 2) using the Mann–Whitney U test for both biochemical and histopathological parameters. Treatment groups were compared with the Control group and with each other. For comparisons involving more than two groups, normally distributed variables were analysed using one-way analysis of variance (ANOVA), followed by appropriate post hoc tests (Tukey HSD or Games–Howell). Homogeneity of variances was assessed using Levene’s test.Variables that did not demonstrate normal distribution were analysed using the Kruskal–Wallis test. When a statistically significant difference was detected, pairwise comparisons were performed using the Mann–Whitney U test.A p value < 0.05 was considered statistically significant. Due to the exploratory nature of this experimental study, a formal sample size calculation was not performed; however, group sizes were determined based on previous similar studies. RESULTS Biochemical Findings Serum IL-1β levels were significantly higher in Group 2 compared with Groups 3, 4, and 7 (p₂–₃=0.01; p₂–₄<0.01; p₂–₇=0.01). Similarly, Group 6 demonstrated higher IL-1β levels than Groups 3, 4, and 7 (p₃–₆=0.02; p₄–₆=0.01; p₆–₇=0.02) (Table 2). Serum IL-10 levels were significantly lower in Group 2 compared with Group 4 (p₂–₄=0.01). Additionally, Group 4 demonstrated higher IL-10 levels than Groups 5 and 6 (p₄–₅=0.01; p₄–₆<0.01) (Table 2). Serum eNOS levels were significantly higher in Group 2 compared with Groups 4 and 7 (p₂–₄=0.01; p₂–₇=0.03). Group 3 also showed higher levels than Groups 4 and 6 (p₃–₄=0.01; p₃–₆=0.03). In contrast, Group 4 demonstrated lower levels than Group 5 (p₄–₅=0.02). Group 6 showed higher levels than Groups 4 and 7 (p₄–₆=0.01; p₆–₇=0.03), whereas Group 7 demonstrated lower levels than Group 4 (p₄–₇=0.02) (Table 2). Serum MDA levels were significantly higher in Group 2 compared with all other groups (p<0.01). Group 3 demonstrated lower MDA levels than Groups 5 and 7 (p₃–₅<0.01; p₃–₇<0.01). Similarly, Group 4 showed lower levels than Group 5 (p₄–₅=0.04), and Group 6 demonstrated lower levels than Groups 5 and 7 (p₅–₆<0.01; p₆–₇<0.01) (Table 2). No significant differences were observed between the Sham and Control groups for TAS and TOS levels; therefore, further comparisons were not performed. Histopathological Findings The validity of the experimental model was confirmed by significantly higher total pathology scores in the Control group compared with the Sham group (p<0.01). While no inflammation, desquamation, oedema, or tunica albuginea separation was observed in the Sham group, the Control group demonstrated mean scores of 1.56, 1.44, 2.22, and 1.11, respectively (Table 3). In the vasocongestion category, the Control group demonstrated higher scores than Group 6 (p₂–₆=0.01), with no significant differences among other groups (Table 4, Figure 2A). In the inflammation category, the Control group showed higher scores compared with Groups 3, 4, 6, and 7 (p₂–₃<0.01; p₂–₄=0.04; p₂–₆<0.01; p₂–₇<0.01), whereas no difference was observed compared with Group 5. Group 4 also demonstrated higher scores than Group 6 (p₄–₆<0.01) (Tables 3–4, Figure 3B). In the desquamation category, the Control group demonstrated higher scores than Groups 3, 4, 6, and 7 (p₂–₃<0.01; p₂–₄=0.01; p₂–₆<0.01; p₂–₇<0.01). Group 5 also showed higher scores compared with these groups (all p<0.01) (Tables 3–4, Figure 2C). In the oedema category, the Control group demonstrated higher scores than Groups 3, 4, 6, and 7 (p₂–₃=0.02; p₂–₄=0.02; p₂–₆<0.01; p₂–₇=0.01). Groups 3 and 5 had higher scores than Group 6 (p₃–₆<0.01; p₅–₆=0.01). Group 5 also showed higher scores than Group 7 (p₅–₇=0.01), and Group 7 had higher scores than Group 6 (p₆–₇=0.02) (Tables 3–4, Figure 2D). In the tunica albuginea separation category, the Control group demonstrated higher scores compared with Groups 3 and 6 (p₂–₃=0.02; p₂–₆<0.01), with no differences compared with other groups. Group 5 showed higher scores than Groups 4 and 6 (p₄–₅=0.01; p₅–₆<0.01) (Tables 3–4, Figure 2E). The total pathology score was higher in the Control group compared with all groups except Group 5 (p=0.93; all others p<0.01). Group 5 also demonstrated higher total scores than all groups except the Control group (Tables 3–4). DISCUSSION Ischaemic priapism may lead to irreversible erectile dysfunction if not treated promptly. In addition to the initial ischaemic insult, reperfusion following detumescence may further exacerbate tissue injury through inflammatory and oxidative mechanisms. In the present study, we demonstrated that ischaemia–reperfusion injury (IRI) in experimental priapism is associated with a significant increase in proinflammatory activity, as reflected by elevated IL-1β levels, and a concomitant decrease in anti-inflammatory response, indicated by reduced IL-10 levels. These findings confirm the pivotal role of inflammatory pathways in cavernosal injury following ischaemic priapism. Inflammation is a complex biological process mediated by cytokine signalling pathways. IL-1β, primarily secreted by macrophages and monocytes, plays a central role in apoptosis, proliferation, and cellular differentiation, whereas IL-10 functions as a key anti-inflammatory mediator(1,9,10). To our knowledge, no previous study has specifically evaluated IL-10 levels in priapism-related IRI. In line with this, our results demonstrated significantly increased IL-1β levels and decreased IL-10 levels in the IRI group (Group 2) compared with the Sham group, further supporting the activation of inflammatory pathways and suppression of anti-inflammatory responses(11–13). Nitric oxide (NO) is a key endothelial mediator regulating vascular tone and cavernosal smooth muscle relaxation. However, under pathological conditions, excessive NO production may contribute to oxidative and nitrosative stress, thereby exacerbating tissue injury. In ischaemic settings, increased oxidative damage and impaired antioxidant defence mechanisms have been consistently reported. Kölükçü et al. demonstrated elevated NO levels following ischaemia–reperfusion injury in a priapism model (14). Consistent with these findings, eNOS levels were significantly higher in the Control group in the present study, suggesting endothelial dysfunction and increased oxidative stress in cavernosal tissue. Furthermore, accumulating experimental evidence indicates that modulation of inflammatory pathways may attenuate IRI-related tissue damage (14,15). In this context, the observed alterations in NO signalling in our study further support the interplay between oxidative stress and inflammation in the pathophysiology of ischaemic priapism. Pirfenidone (PFD), an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis, has been shown to inhibit transforming growth factor-β (TGF-β) and modulate proinflammatory cytokines(15). Although its effects in priapism have previously been evaluated only in chronic experimental settings (3), the present study demonstrates that PFD also exerts beneficial effects during the acute phase of ischaemia–reperfusion injury. In our study, PFD treatment was associated with significant reductions in IL-1β and MDA levels, indicating suppression of both inflammatory and oxidative pathways. These biochemical improvements were supported by favourable histopathological findings, suggesting a protective effect on cavernosal tissue integrity. Taken together, these findings indicate that PFD may play a role in limiting early tissue injury in ischaemic priapism, potentially contributing to the preservation of cavernosal structure and function. Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, is known to improve microcirculatory flow and exert anti-inflammatory and antifibrotic effects (9,11,16). Previous experimental studies in priapism have reported variable results depending on dose and treatment duration(17,18). In the present study, PTX demonstrated consistent anti-inflammatory and antioxidant effects, as evidenced by significant reductions in IL-1β, MDA, and eNOS levels, together with increased IL-10 levels. These findings suggest a modulatory effect on both inflammatory and oxidative pathways during ischaemia–reperfusion injury. Notably, PTX appeared to exert a more pronounced anti-inflammatory effect than PFD in certain parameters, highlighting its potential relevance in the acute phase of injury. Histopathological findings further supported these results, demonstrating significant improvement in cavernosal tissue injury scores. In addition, limited clinical observations, such as those reported by Cooper et al. (19), suggest that PTX may have therapeutic potential in the management of priapism, although further studies are required to confirm these findings. Dexpanthenol (DXP), a derivative of pantothenic acid, is known to enhance cellular energy metabolism and increase intracellular glutathione levels (4,7). Previous studies have demonstrated protective effects of DXP in various ischaemia–reperfusion injury models (4,20,21). In the present study, DXP demonstrated a selective effect, with a significant reduction in MDA levels, indicating an impact on oxidative stress pathways. However, this effect did not translate into significant anti-inflammatory or histopathological improvement when compared with other treatment groups. This discrepancy may reflect tissue-specific responses, differences in timing or dosing, or the severity of the experimental model. These findings suggest that the effects of DXP in cavernosal ischaemia–reperfusion injury may be pathway-specific and more limited compared with other agents, highlighting the need for further investigation. Interestingly, combination therapies did not demonstrate superiority over monotherapy in the present study. This may be explained by overlapping mechanisms of action, particularly within oxidative stress and inflammatory pathways, potentially resulting in a ceiling effect. In addition, pharmacodynamic interactions or variability inherent to the experimental model may have contributed to these findings. The comparison between the Sham and Control groups confirmed the successful establishment of the ischaemia–reperfusion injury model, as evidenced by consistent biochemical and histopathological differences, supporting the reliability of subsequent intergroup comparisons. Overall, PFD and PTX demonstrated significant anti-inflammatory and antioxidant effects, whereas DXP exhibited a more limited, pathway-specific impact. Importantly, histopathological findings were largely consistent with biochemical results, further strengthening the internal validity of the study. This study has several limitations. First, only the acute effects of single-dose drug administration were evaluated, and therefore the long-term impact of these agents on cavernosal tissue and functional outcomes remains unclear. Second, erectile function was not assessed, which represents an important limitation when interpreting the clinical relevance of the findings.Third, although the experimental model was designed to simulate ischaemia–reperfusion injury, it may not fully replicate clinical conditions, particularly with respect to the duration and severity of ischaemia and the dynamics of reperfusion. Finally, detailed molecular pathway analyses were not performed, limiting mechanistic insight into the observed effects.These limitations should be considered when interpreting the results, and further experimental and clinical studies are required to validate and extend these findings. This experimental study demonstrates that pirfenidone and pentoxifylline, previously shown to exert beneficial chronic effects in ischaemia–reperfusion models, also provide significant anti-inflammatory and antioxidant effects in the acute phase and improve histopathological outcomes. In contrast, dexpanthenol demonstrated a more limited, pathway-specific effect, primarily reflected by reductions in oxidative stress markers. These findings suggest that pirfenidone and pentoxifylline may have potential as adjunctive therapeutic options for limiting cavernosal tissue injury in ischaemic priapism. However, further studies evaluating long-term functional outcomes are required to clarify their clinical relevance. Declarations ETHİCAL APPROVAL Approval for this study was obtained from the Animal Experiments Local Ethics Committee of Necmettin Erbakan University KONÜDAM Experimental Medicine Application and Research Center (Decision date: December 22, 2023; Decision No: 2023-060). COMPETİNG INTERESTS The authors declare no competing interests. AUTHOR CONTRİBUTİONS: Concept and design: Ibrahim Goksoy, Mehmet Giray Sonmez Experimental procedures: Ibrahim Goksoy, Arif Aydın Data collection: Arif Aydın, Fahriye Kilinc Biochemical analysis: Ibrahim Kilinc Histopathological evaluation: Fahriye Kilinc Data analysis and interpretation: Mehmet Giray Sönmez, Ibrahim Kilinc Manuscript drafting: Ibrahim Goksoy Critical revision of the manuscript: Mehmet Giray Sonmez, Fahriye Kilinc Supervision: Mehmet Giray Sonmez ACKNOWLEDGMENTS This study was supported by the Scientific Research Projects Coordination Unit of Necmettin Erbakan University (Project No: 24TU18006). DATA AVAİLABİLİTY STATEMENT The data supporting the findings of this study are available from the corresponding author upon reasonable request. References Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R. Priapism: Pathogenesis, epidemiology, and management. 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Ekim 2013;15(5):475–83. doi: 10.1007/s11906-013-0377-9 PubMed PMID: 23917809. Evliyao Y, Kayrin -B Kaya L. Effect of pentoxifylline on veno-occlusive priapism-induced corporeal tissule lipid peroxidation in a rat model. Urol Res. 1997. Report. Erdemir F, Firat F, Markoc F, Atilgan D, Parlaktas BS, Kuyucu YE, vd. The effect of pentoxifylline on penile cavernosal tissues in ischemic priapism-induced rat model. Int Urol Nephrol. 01 Ekim 2014;46(10):1961–7. doi: 10.1007/s11255-014-0769-z PubMed PMID: 25027804. Cooper MA, Carrion RE, Yang C. Partial priapism treated with pentoxifylline. International Braz J Urol. 2015;41(4):804–7. doi: 10.1590/S1677-5538. IBJU.2014.0363 PubMed PMID: 26401875. Aydın A, Sönmez MG, Ecer G, Kılınç F, Kocabaş R, Atılgan AE, vd. The effect of intratesticular dexpanthenol on experimentally-induced testicular ischaemia/reperfusion injury. J Pediatr Urol. Ağustos 2021;17(4):440 .e1-440.e7 . doi:10.1016/j.jpurol.2021.03.031 Etensel B, Özkisacik S, Özkara E, Serbest YA, Öztan O, Yazici M, vd. The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatr Surg Int. Mart 2007;23(3):271–5. doi: 10.1007/s00383-006-1871-9 PubMed PMID: 17205291. Tables Table 1 . Biochemical evaluation of serum samples. Groups Mean±SD Median (min-max) P IL-1β I (Sham) 29.56±2.13 27.20 (22.20-39.70) II (Control) 77.46±9.24 86.80 (108.90-38.60) 1-2: <0.01 III (PFD) 35.58±3.96 33.55 (64.90-23.10) 2-3: 0.01 IV (PTX) 29.08±2.60 26.50 (45.60-21.70) 2-4:<0.01 V (DXP) 47.91±5.71 46.35 (74.80-22.30) 2-5:0.13 VI (PFD+DXP) 71.32±9.27 69.30 (114.90-23.40) 2-6:0.99 VII(PTX+DXP) 34.12±3.32 30.00 (54.30-23.30) 2-7:0.01 IL-10 I (Sham) 134.83±32.75 87.00 (78.90-179.50) II (Control) 91.91±15.63 86.30 (73.00-121.80) 1-2:0.02 III (PFD) 112.02±23.44 105.55 (81.70 -155.20) 2-3:0.41 IV (PTX) 141.87±31.58 147.20 (93.80-180.60) 2-4:0.01 V (DXP) 102.38±23.30 92.95 (79.70-150.10) 2-5:0.24 VI (PFD+DXP) 95.80±16.03 89.80 (78.80-123.70) 2-6:0.98 VII(PTX+DXP) 114.48±29.93 108.00 (82.00-164.00) 2-7:0.07 MDA I (Sham) 173.11±12.96 173.70 (92.40-158.50) II (Control) 253.93±20.55 250.40 (288.60-230.20) 1-2: <0.01 III (PFD) 179.24±12.65 175.80 (202.10-163.20) 2-3: <0.01 IV (PTX) 197.87±14.72 199.20(214.70-175.80) 2-4: <0.01 V (DXP) 222.15±18.78 214.40 (252.20-202.50) 2-5:0.03 VI (PFD+DXP) 182.51±16.57 186.05 (157.50-201) 2-6: <0.01 VII(PTX+DXP) 211.71±20.6 211.35 (183-245.70) 2-7: <0.01 TOS I (Sham) 24.08±0.86 24.90 (27.10-19.90) II (Control) 20.38±0.70 19.80 (25.30-18.20) 1-2:0.06 III (PFD) 20.11±0.81 19.75 (24.50-16.40) IV (PTX) 22.68±1.08 21.80 (27.50-18.80) V (DXP) 19.21±1.16 18.55 (28.90-14.70) VI (PFD+DXP) 19.38±1.15 18.85 (26.90-14.80) VII(PTX+DXP) 22.12±0.80 22.05 (26.20-17.90) TAS I (Sham) 0.32±0.02 0.33 (0.25-0.44) II (Control) 0.43±0.05 0.41 (0.29-0.82) 1-2:0.96 III (PFD) 0.33±0.02 0.31 (0.26-0.50) IV (PTX) 0.33±0.02 0.32 (0.24-0.46) V (DXP) 0.51±0.10 0.31 (0.25-1.01) VI (PFD+DXP) 0.49±0.03 0.49 (0.32-0.62) VII(PTX+DXP) 0.39±0.02 0.41 (0.29-0.51) eNOS I (Sham) 157.10±8.38 158.30 (122.00-198.30) II (Control) 226.23±17.14 206.50 (143.70-288.60) 1-2: <0.01 III (PFD) 184.60±10.34 186.05 (147.00-253.30) 2-3:0.79 IV (PTX) 149.63±14.91 135.80 (120.10-260.90) 2-4:0.01 V (DXP) 191.40±12.84 185.00 (122.80-262.10) 2-5:0.1 VI (PFD+DXP) 219.13±13.76 225.40 (122.30-270.60) 2-6:0.84 VII(PTX+DXP) 180.26±13.09 167.55 (134.40-266.80 2-7:0.03 SD: Standard deviation, PFD: Pirfenidone, PTX: Pentoxifylline, DXP: Dexpanthenol, PFD+DXP: Pirfenidone + Dexpanthenol, PTX+DXP: Pentoxifylline + Dexpanthenol. Table 2. Significant P values regarding IL-1β, IL-10 p, eNOS p and MDA. p Değer IL-1β P 1-2 <0.01* P 2-3 0.01 P 2-4 <0.01 P 2-7 0.01 P 3-6 0.02 P 4-6 0.01 P 6-7 0.02 IL-10 P 1-2 0.01* P 2-4 <0.01 P 2-7 0.026 P 4-6 0.021 eNOS P 1-2 <0.01 P 2-4 0.01 P 2-7 0.03 P 3-4 0.01 P 3-6 0.03 P 4-5 0.02 P 4-6 0.01 P 6-7 0.03 P 4-7 0.02 MDA P 2-3.4.5.6.7 <0.01 P 3-5 <0.01 P 3-7 0.02 P 4-5 0.04 P 5-6 <0.01 P 6-7 <0.01 IL: Interleukin, eNOS: Endothelial nitric oxide synthase, MDA: Malondialdehyde. One-way analysis of variance (ANOVA) post-hoc Games Howel *Mann Whitney-, , Kruskal Wallis-H post-hoc Mann Whitney-U for eNOS P, One-way analysis of variance (ANOVA) post-hoc Tukey HSD for MDA. Table 3. Histopathological evaluation of penectomy specimens. Groups Mean± SD Median (min-max) P Vasocongestion I (Sham) 0.33±0.5 0(0-1) II (Control) 1.78±0.67 2(1-3) 1-2: <0.01 III (PFD) 1.30±0.67 1(1-3) 2-3: 0.13 IV (PTX) 1.78±0.67 1 (1-3) 2-4:1 V (DXP) 1.40±0.52 1 (1-2) 2-5:0.27 VI (PFD+DXP) 0.90±0.57 0 (0-2) 2-6:0.01 VII(PTX+DXP) 1.40±0.52 1 (1-2) 2-7:0.27 Inflamation I (Sham) 0 0 II (Control) 1.56±0.53 2 (1-2) 1-2: <0.01 III (PFD) 0.6±0.52 1 (0-1) 2-3: 0.01 IV (PTX) 1±0 1 (1-1) 2-4:0.05 V (DXP) 0.9±0.57 1 (0-2) 2-5:0.04 VI (PFD+DXP) 0.6±0.52 1 (0-1) 2-6:<0.01 VII(PTX+DXP) 0.1±0.3 0 (0-1) 2-7:<0.01 Descuamation I (Sham) 0 0 II (Control) 1.44±0.53 1 (1-2) 1-2: <0.01 III (PFD) 0.1±0.32 0 (0-1) 2-3: 0.06 IV (PTX) 0.22±0.44 0 (0-1) 2-4:<0.01 V (DXP) 1±0.47 1 (0-2) 2-5:0.21 VI (PFD+DXP) 0.1±0.32 0 (0-1) 2-6:<0.01 VII(PTX+DXP) 0.1±.32 0 (0-1) 2-7: <0.01 Edema I (Sham) 0 0 II (Control) 2.22±0.44 2 (2-3) 1-2: <0.01 III (PFD) 1.50±0.53 1.5 (0-2) 2-3: 0.15 IV (PTX) 1.33±0.87 1 (0-3) 2-4:0.13 V (DXP) 1.80±0.42 2 (1-2) 2-5:0.78 VI (PFD+DXP) 0.70±0.48 1 (0-1) 2-6:<0.01 VII(PTX+DXP) 1.40±0.52 1 (1-2) 2-7:0.09 Separation of Tunika albugineada I (Sham) 0 0 II (Control) 1.22±0.46 1 (1-2) 1-2: <0.01 III (PFD) 0.5±0.53 0.5 (0-1) 2-3: 0.06 IV (PTX) 0.67±0.50 1 (0-1) 2-4:0.19 V (DXP) 1.50±0.71 2 (0-2) 2-5:0.11 VI (PFD+DXP) 0.30±0.48 0 (0-1) 2-6:0.01 VII(PTX+DXP) 1±0.82 1 (0-2) 2-7:0.78 Total pathology score I (Sham) 0.33±0.50 0 (0-1) II (Control) 8.56±1.81 9 (5-11) 1-2: <0.01 III (PFD) 4±1.41 4 (2-7) 2-3: <0.01 IV (PTX) 5±1.58 5 (3-8) 2-4: <0.01 V (DXP) 7.90±1.52 8 (5-10) 2-5:0.93 VI (PFD+DXP) 2.60±1.71 3 (0-5) 2-6: <0.01 VII(PTX+DXP) 4.10±0.99 4 (2-5) 2-7: <0.01 SD: Standard deviation, PFD: Pirfenidone, PTX: Pentoxifylline, DXP: Dexpanthenol, PFD+DXP: Pirfenidone + Dexpanthenol, PTX+DXP: Pentoxifylline + Dexpanthenol. Table 4. Inflammation, desquamation, edema, and tunica albuginea detachment were statistically significant (p-values). p Value Inflamation P 2-3 <0.01 P 2-4 0.04 P 2-6 <0.01 P 2-7 <0.01 P 4-6 <0.01 Descuamation P 1-2 <0.01 p 2-3 <0.01 p 2-4 0.01 p 2-6 <0.01 p 2-7 <0.01 Edema P 2-3 0.02 P 2-4 0.02 P 2-6 <0.01 P 2-7 0.01 P 3-5 0.01 P 3-6 <0.01 P 5-7 0.01 P 6-7 0.02 Separation of Tunika albugineada P 2-3 0.02 P 2-4 <0.01 P 4-5 <0.01 P 5-6 <0.01 Mann Whitney-U. Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9220334","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":614913651,"identity":"5d696d12-cc45-4a59-b389-843badf34ada","order_by":0,"name":"Ibrahim Goksoy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACNgkGBmYGAwYGIM34ACjAw0eKFmYDkBY2gtaAtUBokHYgSUgHn3Tvw88FBdvsZvafMav8mmMnw8bA/PDRDXwOkzluLD3D4HbybIkcs9uy25KBDmMzNs7B65c0BmkeoBY5CR6z25LbmIFaeNikCWhh/g3Wwn/GrFhyWz1RWthAtthJM+SYMX7cdpgILTLH2KyBWhIkZ6QVSzNuO87DxkzAL/Kz25hv8/y5bS9x/vDGjz+3Vdvzszc/fIxPCwwkNjBwGDDzgJjMRCgHAXsGBvYHjD+IVD0KRsEoGAUjCwAAxtk9XNIt608AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-7065-366X","institution":"University of Health Sciences, Van Training and Research Hospital, Van, Turkey","correspondingAuthor":true,"prefix":"","firstName":"Ibrahim","middleName":"","lastName":"Goksoy","suffix":""},{"id":614913652,"identity":"d28aae4b-83d8-443b-9397-4a485baa274e","order_by":1,"name":"Arif Aydın","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Arif","middleName":"","lastName":"Aydın","suffix":""},{"id":614913653,"identity":"94c881bf-231b-4458-a602-55f3a379c53e","order_by":2,"name":"Fahriye Kilinc","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fahriye","middleName":"","lastName":"Kilinc","suffix":""},{"id":614913654,"identity":"23966058-9f10-480c-86f4-396f11993e35","order_by":3,"name":"Ibrahim Kilinc","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ibrahim","middleName":"","lastName":"Kilinc","suffix":""},{"id":614913655,"identity":"1d359b4c-2cb0-4f92-bfc5-901ab629532c","order_by":4,"name":"Mehmet Giray Sönmez","email":"","orcid":"https://orcid.org/0000-0003-4615-7348","institution":" Meram Medical Faculty, Necmettin Erbakan University","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Giray","lastName":"Sönmez","suffix":""}],"badges":[],"createdAt":"2026-03-25 08:30:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9220334/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9220334/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106102386,"identity":"62aae186-e1da-405b-88b9-c6d726a50882","added_by":"auto","created_at":"2026-04-03 12:58:11","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":747494,"visible":true,"origin":"","legend":"\u003cp\u003eStages of oral drug administration(A), anesthesia(B), constrictor band method(C), and penectomy in the rat priapism model(D).\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9220334/v1/64f1990d8cde050dcf16ed31.jpg"},{"id":106724061,"identity":"08b3bb7f-6e42-47ec-80a2-98b0c95371f1","added_by":"auto","created_at":"2026-04-12 18:25:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6613519,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological appearance of desquamation, edema, and separation of the tunica albuginea in the rat priapism model. A1: Group 2 congested appearance, MT (40×), A2: Group 4 non-congested appearance, MT (100×), B1: Group 5 intense inflammatory appearance, B2: Group 3 reduced inflammation, H\u0026amp;E (100×), C1: Group 5 desquamated epithelium, H\u0026amp;E (40×), C2: Group 7 epithelium without desquamation, D1: Group 2 marked edematous appearance, D2: Group 6 absence of edema, H\u0026amp;E (100×), E1: Group 5 separated tunica albuginea appearance, E2: Group 3 normal tunica albuginea appearance, MT (40×).\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9220334/v1/1b28b31165a30340628cf909.jpg"},{"id":109067894,"identity":"6404253e-e269-41e0-955c-f7c415f45928","added_by":"auto","created_at":"2026-05-12 10:02:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7869989,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9220334/v1/86c80cd1-5af0-4fe3-ac5c-c48ebafdd6ac.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Pirfenidone and Pentoxifylline Attenuate Ischaemia–Reperfusion Injury in Experimental Priapism: Limited Effects of Dexpanthenol","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePriapism is defined as a persistent penile erection lasting longer than four hours in the absence of sexual stimulation. Although rare, its incidence appears to be increasing, likely reflecting evolving patterns of medication use and the wider use of vasoactive agents. Priapism is classified into three subtypes: non-ischaemic (high-flow), ischaemic (low-flow), and stuttering (recurrent ischaemic) priapism. Among these, ischaemic priapism (IP) accounts for more than 95% of cases and is characterised by reduced or absent intracavernosal arterial inflow. It represents a true urological emergency associated with tissue ischaemia, hypoxia, acidosis, and severe penile pain, and may lead to irreversible erectile dysfunction if not treated promptly (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIschaemic priapism lasting longer than four hours is considered a compartment syndrome requiring urgent intervention to prevent irreversible structural damage to cavernosal smooth muscle. In addition to the initial ischaemic insult, reperfusion following detumescence may further exacerbate tissue injury through oxidative stress and inflammatory pathways, a process defined as ischaemia\u0026ndash;reperfusion injury (IRI). Restoration of oxygenation and resolution of venous stasis are therefore critical for preserving tissue viability. Although current treatment modalities are effective in achieving detumescence in the acute setting, they do not specifically target the molecular mechanisms underlying cavernosal damage. Consequently, pharmacological strategies aimed at reducing both immediate and long-term tissue injury remain an area of ongoing investigation (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePirfenidone (PFD) is an antifibrotic agent that suppresses transforming growth factor-β1 (TGF-β1) and other profibrotic mediators, and has demonstrated anti-inflammatory and antioxidant properties. Pentoxifylline (PTX), a xanthine-derived non-selective phosphodiesterase inhibitor, enhances tissue perfusion and oxygenation through its vasodilatory effects and has been utilised in models of ischaemic injury due to its antifibrotic potential. Both agents have been investigated in experimental settings for their protective effects on cavernosal tissue, particularly in relation to fibrosis and oxidative stress. Dexpanthenol (DXP), a derivative of pantothenic acid, has been shown to reduce reactive oxygen species, exert anti-inflammatory effects, and promote cellular repair; however, its role in cavernosal ischaemia and priapism has not yet been clearly defined (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe present study aimed to evaluate the acute effects of pirfenidone and pentoxifylline, previously investigated for their chronic effects in experimental models of priapism, on ischaemia\u0026ndash;reperfusion injury. In addition, we aimed to investigate the effects of dexpanthenol, which has not previously been evaluated in a priapism model, and to assess the potential synergistic effects of combination therapies. By comparing agents with distinct pharmacological profiles, this study seeks to provide further insight into potential strategies for limiting cavernosal tissue damage in ischaemic priapism.\u003c/p\u003e"},{"header":"MATERIAL AND METHOD","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval for the study was obtained from the Animal Experiments Local Ethics Committee All experiments were conducted in the laboratories of the Experimental Medicine Application and Research Center of our university in accordance with institutional and international guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Groups and Experimental Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 68 adult male Wistar albino rats (8–10 weeks old, 175–245 g) were included. All animals were maintained under standardised laboratory conditions, including controlled temperature, humidity, and light–dark cycles. Preparation of oral medications is shown in Figure 1A. Rats were randomly assigned into seven groups using a simple randomisation method:\u003c/p\u003e\n\u003cp\u003eGroup 1 (Sham): Penectomy only\u003c/p\u003e\n\u003cp\u003eGroup 2 (Control): Ischaemic priapism induced under anaesthesia for one hour, followed by a one-hour ischaemia–reperfusion period without treatment and subsequent penectomy\u003c/p\u003e\n\u003cp\u003eGroup 3: Oral pirfenidone (325 mg/kg) administered via gastric gavage immediately before induction of priapism; dose based on previous studies (5)\u003c/p\u003e\n\u003cp\u003eGroup 4: Oral pentoxifylline (100 mg) administered via gastric gavage immediately before induction; dose selected according to prior studies (6)\u003c/p\u003e\n\u003cp\u003eGroup 5: Dexpanthenol (500 mg) administered intraperitoneally 30 minutes after induction; based on previous experimental studies demonstrating its protective effects in ischaemia–reperfusion injury models (7)\u003c/p\u003e\n\u003cp\u003eGroup 6: Combination therapy with pirfenidone and dexpanthenol\u003c/p\u003e\n\u003cp\u003eGroup 7: Combination therapy with pentoxifylline and dexpanthenol\u003c/p\u003e\n\u003cp\u003eOne rat in Group 4 died before termination of priapism and was excluded from the analysis.\u003c/p\u003e\n\u003cp\u003eIn all groups except the sham group, priapism was induced under anaesthesia for one hour. Following detumescence, a one-hour period was allowed for the development of ischaemia–reperfusion injury before penectomy. Intracardiac blood samples were collected for biochemical analysis, and penectomy specimens were processed for histopathological evaluation. All animals were sacrificed by exsanguination following sample collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnesthesia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll animals underwent identical procedures under anaesthesia. Anaesthesia and analgesia were achieved with intramuscular ketamine (50 mg/kg) and xylazine (5 mg/kg). After induction and stabilisation, the lower abdominal and penile regions were shaved, and the surgical procedure was initiated (Figure 1B).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInduction of the Ischemic Priapism Model and Reperfusion Injury\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIschaemic priapism was induced according to the Şanlı model. This model has been previously validated for reproducing features of ischaemic priapism and cavernosal injury. The tip of a 50-cc irrigation syringe with a conical end was modified to fit the base of the flaccid penis. Prior to vacuum application, a constriction band—prepared from 14 Fr Foley catheters cut into 2-mm segments—was placed on the syringe tip. The syringe was then positioned at the penile base and gently retracted to induce erection. Once adequate erection was achieved, the constriction band was advanced onto the penile base to establish the ischaemic priapism model (8)(Figure 1C).\u003c/p\u003e\n\u003cp\u003eUnlike previous studies, the duration of ischaemia was extended to better reflect clinically relevant severe ischaemic injury and to enhance the detection of treatment effects. Immediately after termination of ischaemia, a one-hour reperfusion period was allowed prior to tissue collection. (Figure 1D)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiochemical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll biochemical analyses were performed by a biochemistry specialist blinded to group allocation. Systemic blood samples (5–6 cc) were collected into tubes without anticoagulant, allowed to clot at room temperature for 15 minutes, and centrifuged at 4°C (4000 rpm for 15 minutes). The separated sera were stored at −20°C until analysis.\u003c/p\u003e\n\u003cp\u003eSerum interleukin-1β (IL-1β) and interleukin-10 (IL-10) levels were measured to assess inflammatory responses. Total oxidant status (TOS), total antioxidant status (TAS), and malondialdehyde (MDA) levels were analysed to evaluate oxidative stress, while endothelial nitric oxide synthase (eNOS) levels were measured to assess nitric oxide pathway activity. All parameters were determined using enzyme-linked immunosorbent assay (ELISA) kits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHistopathological examinations were performed by an experienced pathologist blinded to group allocation. Following penectomy, cavernosal tissues were fixed in 10% neutral buffered formalin, processed using an automated tissue processor (Leica ASP300S, Germany), and embedded in paraffin blocks. Sections approximately 4 µm thick were obtained using a microtome (Leica RM2245, Germany) and stained with haematoxylin–eosin (H\u0026amp;E) and Masson’s trichrome (MT).\u003c/p\u003e\n\u003cp\u003eAll sections were examined under a light microscope (Olympus BX53, Japan), and photomicrographs were obtained using an integrated digital camera system (Olympus SC50, Japan). Each specimen was evaluated for vasocongestion, inflammation, desquamation, oedema, and tunica albuginea separation/haemorrhage. The scoring system was adapted from previously published experimental studies evaluating cavernosal tissue injury.\u003c/p\u003e\n\u003cp\u003eHistopathological changes were graded semi-quantitatively on a scale of 0–3 as follows: 0 = normal, 1 = mild, 2 = moderate, and 3 = severe.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS software. Descriptive statistics were presented as mean ± standard deviation. The normality of data distribution was assessed using skewness and kurtosis coefficients, with values between −2 and +2 considered indicative of normal distribution.\u003c/p\u003e\n\u003cp\u003eThe validity of the ischaemia–reperfusion priapism model was evaluated by comparing the Sham group (Group 1) and the Control group (Group 2) using the Mann–Whitney U test for both biochemical and histopathological parameters. Treatment groups were compared with the Control group and with each other.\u003c/p\u003e\n\u003cp\u003eFor comparisons involving more than two groups, normally distributed variables were analysed using one-way analysis of variance (ANOVA), followed by appropriate post hoc tests (Tukey HSD or Games–Howell). Homogeneity of variances was assessed using Levene’s test.Variables that did not demonstrate normal distribution were analysed using the Kruskal–Wallis test. When a statistically significant difference was detected, pairwise comparisons were performed using the Mann–Whitney U test.A p value \u0026lt; 0.05 was considered statistically significant. Due to the exploratory nature of this experimental study, a formal sample size calculation was not performed; however, group sizes were determined based on previous similar studies.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eBiochemical Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum IL-1\u0026beta; levels were significantly higher in Group 2 compared with Groups 3, 4, and 7 (p₂\u0026ndash;₃=0.01; p₂\u0026ndash;₄\u0026lt;0.01; p₂\u0026ndash;₇=0.01). Similarly, Group 6 demonstrated higher IL-1\u0026beta; levels than Groups 3, 4, and 7 (p₃\u0026ndash;₆=0.02; p₄\u0026ndash;₆=0.01; p₆\u0026ndash;₇=0.02) (Table 2).\u003c/p\u003e\n\u003cp\u003eSerum IL-10 levels were significantly lower in Group 2 compared with Group 4 (p₂\u0026ndash;₄=0.01). Additionally, Group 4 demonstrated higher IL-10 levels than Groups 5 and 6 (p₄\u0026ndash;₅=0.01; p₄\u0026ndash;₆\u0026lt;0.01) (Table 2).\u003c/p\u003e\n\u003cp\u003eSerum eNOS levels were significantly higher in Group 2 compared with Groups 4 and 7 (p₂\u0026ndash;₄=0.01; p₂\u0026ndash;₇=0.03). Group 3 also showed higher levels than Groups 4 and 6 (p₃\u0026ndash;₄=0.01; p₃\u0026ndash;₆=0.03). In contrast, Group 4 demonstrated lower levels than Group 5 (p₄\u0026ndash;₅=0.02). Group 6 showed higher levels than Groups 4 and 7 (p₄\u0026ndash;₆=0.01; p₆\u0026ndash;₇=0.03), whereas Group 7 demonstrated lower levels than Group 4 (p₄\u0026ndash;₇=0.02) (Table 2).\u003c/p\u003e\n\u003cp\u003eSerum MDA levels were significantly higher in Group 2 compared with all other groups (p\u0026lt;0.01). Group 3 demonstrated lower MDA levels than Groups 5 and 7 (p₃\u0026ndash;₅\u0026lt;0.01; p₃\u0026ndash;₇\u0026lt;0.01). Similarly, Group 4 showed lower levels than Group 5 (p₄\u0026ndash;₅=0.04), and Group 6 demonstrated lower levels than Groups 5 and 7 (p₅\u0026ndash;₆\u0026lt;0.01; p₆\u0026ndash;₇\u0026lt;0.01) (Table 2).\u003c/p\u003e\n\u003cp\u003eNo significant differences were observed between the Sham and Control groups for TAS and TOS levels; therefore, further comparisons were not performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe validity of the experimental model was confirmed by significantly higher total pathology scores in the Control group compared with the Sham group (p\u0026lt;0.01). While no inflammation, desquamation, oedema, or tunica albuginea separation was observed in the Sham group, the Control group demonstrated mean scores of 1.56, 1.44, 2.22, and 1.11, respectively (Table 3).\u003c/p\u003e\n\u003cp\u003eIn the vasocongestion category, the Control group demonstrated higher scores than Group 6 (p₂\u0026ndash;₆=0.01), with no significant differences among other groups (Table 4, Figure 2A).\u003c/p\u003e\n\u003cp\u003eIn the inflammation category, the Control group showed higher scores compared with Groups 3, 4, 6, and 7 (p₂\u0026ndash;₃\u0026lt;0.01; p₂\u0026ndash;₄=0.04; p₂\u0026ndash;₆\u0026lt;0.01; p₂\u0026ndash;₇\u0026lt;0.01), whereas no difference was observed compared with Group 5. Group 4 also demonstrated higher scores than Group 6 (p₄\u0026ndash;₆\u0026lt;0.01) (Tables 3\u0026ndash;4, Figure 3B).\u003c/p\u003e\n\u003cp\u003eIn the desquamation category, the Control group demonstrated higher scores than Groups 3, 4, 6, and 7 (p₂\u0026ndash;₃\u0026lt;0.01; p₂\u0026ndash;₄=0.01; p₂\u0026ndash;₆\u0026lt;0.01; p₂\u0026ndash;₇\u0026lt;0.01). Group 5 also showed higher scores compared with these groups (all p\u0026lt;0.01) (Tables 3\u0026ndash;4, Figure 2C).\u003c/p\u003e\n\u003cp\u003eIn the oedema category, the Control group demonstrated higher scores than Groups 3, 4, 6, and 7 (p₂\u0026ndash;₃=0.02; p₂\u0026ndash;₄=0.02; p₂\u0026ndash;₆\u0026lt;0.01; p₂\u0026ndash;₇=0.01). Groups 3 and 5 had higher scores than Group 6 (p₃\u0026ndash;₆\u0026lt;0.01; p₅\u0026ndash;₆=0.01). Group 5 also showed higher scores than Group 7 (p₅\u0026ndash;₇=0.01), and Group 7 had higher scores than Group 6 (p₆\u0026ndash;₇=0.02) (Tables 3\u0026ndash;4, Figure 2D).\u003c/p\u003e\n\u003cp\u003eIn the tunica albuginea separation category, the Control group demonstrated higher scores compared with Groups 3 and 6 (p₂\u0026ndash;₃=0.02; p₂\u0026ndash;₆\u0026lt;0.01), with no differences compared with other groups. Group 5 showed higher scores than Groups 4 and 6 (p₄\u0026ndash;₅=0.01; p₅\u0026ndash;₆\u0026lt;0.01) (Tables 3\u0026ndash;4, Figure 2E).\u003c/p\u003e\n\u003cp\u003eThe total pathology score was higher in the Control group compared with all groups except Group 5 (p=0.93; all others p\u0026lt;0.01). Group 5 also demonstrated higher total scores than all groups except the Control group (Tables 3\u0026ndash;4).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIschaemic priapism may lead to irreversible erectile dysfunction if not treated promptly. In addition to the initial ischaemic insult, reperfusion following detumescence may further exacerbate tissue injury through inflammatory and oxidative mechanisms. In the present study, we demonstrated that ischaemia\u0026ndash;reperfusion injury (IRI) in experimental priapism is associated with a significant increase in proinflammatory activity, as reflected by elevated IL-1\u0026beta; levels, and a concomitant decrease in anti-inflammatory response, indicated by reduced IL-10 levels. These findings confirm the pivotal role of inflammatory pathways in cavernosal injury following ischaemic priapism. Inflammation is a complex biological process mediated by cytokine signalling pathways. IL-1\u0026beta;, primarily secreted by macrophages and monocytes, plays a central role in apoptosis, proliferation, and cellular differentiation, whereas IL-10 functions as a key anti-inflammatory mediator(1,9,10). To our knowledge, no previous study has specifically evaluated IL-10 levels in priapism-related IRI. In line with this, our results demonstrated significantly increased IL-1\u0026beta; levels and decreased IL-10 levels in the IRI group (Group 2) compared with the Sham group, further supporting the activation of inflammatory pathways and suppression of anti-inflammatory responses(11\u0026ndash;13). Nitric oxide (NO) is a key endothelial mediator regulating vascular tone and cavernosal smooth muscle relaxation. However, under pathological conditions, excessive NO production may contribute to oxidative and nitrosative stress, thereby exacerbating tissue injury. In ischaemic settings, increased oxidative damage and impaired antioxidant defence mechanisms have been consistently reported. K\u0026ouml;l\u0026uuml;k\u0026ccedil;\u0026uuml; et al. demonstrated elevated NO levels following ischaemia\u0026ndash;reperfusion injury in a priapism model (14). Consistent with these findings, eNOS levels were significantly higher in the Control group in the present study, suggesting endothelial dysfunction and increased oxidative stress in cavernosal tissue. Furthermore, accumulating experimental evidence indicates that modulation of inflammatory pathways may attenuate IRI-related tissue damage (14,15). In this context, the observed alterations in NO signalling in our study further support the interplay between oxidative stress and inflammation in the pathophysiology of ischaemic priapism.\u003c/p\u003e\n\u003cp\u003ePirfenidone (PFD), an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis, has been shown to inhibit transforming growth factor-\u0026beta; (TGF-\u0026beta;) and modulate proinflammatory cytokines(15). Although its effects in priapism have previously been evaluated only in chronic experimental settings (3), the present study demonstrates that PFD also exerts beneficial effects during the acute phase of ischaemia\u0026ndash;reperfusion injury. In our study, PFD treatment was associated with significant reductions in IL-1\u0026beta; and MDA levels, indicating suppression of both inflammatory and oxidative pathways. These biochemical improvements were supported by favourable histopathological findings, suggesting a protective effect on cavernosal tissue integrity. Taken together, these findings indicate that PFD may play a role in limiting early tissue injury in ischaemic priapism, potentially contributing to the preservation of cavernosal structure and function.\u003c/p\u003e\n\u003cp\u003ePentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, is known to improve microcirculatory flow and exert anti-inflammatory and antifibrotic effects (9,11,16). Previous experimental studies in priapism have reported variable results depending on dose and treatment duration(17,18). In the present study, PTX demonstrated consistent anti-inflammatory and antioxidant effects, as evidenced by significant reductions in IL-1\u0026beta;, MDA, and eNOS levels, together with increased IL-10 levels. These findings suggest a modulatory effect on both inflammatory and oxidative pathways during ischaemia\u0026ndash;reperfusion injury. Notably, PTX appeared to exert a more pronounced anti-inflammatory effect than PFD in certain parameters, highlighting its potential relevance in the acute phase of injury. Histopathological findings further supported these results, demonstrating significant improvement in cavernosal tissue injury scores. In addition, limited clinical observations, such as those reported by Cooper et al. (19), suggest that PTX may have therapeutic potential in the management of priapism, although further studies are required to confirm these findings.\u003c/p\u003e\n\u003cp\u003eDexpanthenol (DXP), a derivative of pantothenic acid, is known to enhance cellular energy metabolism and increase intracellular glutathione levels (4,7). Previous studies have demonstrated protective effects of DXP in various ischaemia\u0026ndash;reperfusion injury models (4,20,21). In the present study, DXP demonstrated a selective effect, with a significant reduction in MDA levels, indicating an impact on oxidative stress pathways. However, this effect did not translate into significant anti-inflammatory or histopathological improvement when compared with other treatment groups. This discrepancy may reflect tissue-specific responses, differences in timing or dosing, or the severity of the experimental model. These findings suggest that the effects of DXP in cavernosal ischaemia\u0026ndash;reperfusion injury may be pathway-specific and more limited compared with other agents, highlighting the need for further investigation.\u003c/p\u003e\n\u003cp\u003eInterestingly, combination therapies did not demonstrate superiority over monotherapy in the present study. This may be explained by overlapping mechanisms of action, particularly within oxidative stress and inflammatory pathways, potentially resulting in a ceiling effect. In addition, pharmacodynamic interactions or variability inherent to the experimental model may have contributed to these findings. The comparison between the Sham and Control groups confirmed the successful establishment of the ischaemia\u0026ndash;reperfusion injury model, as evidenced by consistent biochemical and histopathological differences, supporting the reliability of subsequent intergroup comparisons. Overall, PFD and PTX demonstrated significant anti-inflammatory and antioxidant effects, whereas DXP exhibited a more limited, pathway-specific impact. Importantly, histopathological findings were largely consistent with biochemical results, further strengthening the internal validity of the study.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, only the acute effects of single-dose drug administration were evaluated, and therefore the long-term impact of these agents on cavernosal tissue and functional outcomes remains unclear. Second, erectile function was not assessed, which represents an important limitation when interpreting the clinical relevance of the findings.Third, although the experimental model was designed to simulate ischaemia\u0026ndash;reperfusion injury, it may not fully replicate clinical conditions, particularly with respect to the duration and severity of ischaemia and the dynamics of reperfusion. Finally, detailed molecular pathway analyses were not performed, limiting mechanistic insight into the observed effects.These limitations should be considered when interpreting the results, and further experimental and clinical studies are required to validate and extend these findings.\u003c/p\u003e\n\u003cp\u003eThis experimental study demonstrates that pirfenidone and pentoxifylline, previously shown to exert beneficial chronic effects in ischaemia\u0026ndash;reperfusion models, also provide significant anti-inflammatory and antioxidant effects in the acute phase and improve histopathological outcomes. In contrast, dexpanthenol demonstrated a more limited, pathway-specific effect, primarily reflected by reductions in oxidative stress markers. These findings suggest that pirfenidone and pentoxifylline may have potential as adjunctive therapeutic options for limiting cavernosal tissue injury in ischaemic priapism. However, further studies evaluating long-term functional outcomes are required to clarify their clinical relevance.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eETHİCAL APPROVAL\u003c/h2\u003e \u003cp\u003e Approval for this study was obtained from the Animal Experiments Local Ethics Committee of Necmettin Erbakan University KON\u0026Uuml;DAM Experimental Medicine Application and Research Center (Decision date: December 22, 2023; Decision No: 2023-060).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCOMPETİNG INTERESTS\u003c/strong\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAUTHOR CONTRİBUTİONS:\u003c/h2\u003e \u003cp\u003eConcept and design: Ibrahim Goksoy, Mehmet Giray Sonmez\u003c/p\u003e \u003cp\u003eExperimental procedures: Ibrahim Goksoy, Arif Aydın\u003c/p\u003e \u003cp\u003eData collection: Arif Aydın, Fahriye Kilinc\u003c/p\u003e \u003cp\u003eBiochemical analysis: Ibrahim Kilinc\u003c/p\u003e \u003cp\u003eHistopathological evaluation: Fahriye Kilinc\u003c/p\u003e \u003cp\u003eData analysis and interpretation: Mehmet Giray S\u0026ouml;nmez, Ibrahim Kilinc\u003c/p\u003e \u003cp\u003eManuscript drafting: Ibrahim Goksoy\u003c/p\u003e \u003cp\u003eCritical revision of the manuscript: Mehmet Giray Sonmez, Fahriye Kilinc\u003c/p\u003e \u003cp\u003eSupervision: Mehmet Giray Sonmez\u003c/p\u003e\u003ch2\u003eACKNOWLEDGMENTS\u003c/h2\u003e \u003cp\u003eThis study was supported by the Scientific Research Projects Coordination Unit of Necmettin Erbakan University (Project No: 24TU18006).\u003c/p\u003e\u003ch2\u003eDATA AVAİLABİLİTY STATEMENT\u003c/h2\u003e \u003cp\u003eThe data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBroderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R. 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Ekim 2013;15(5):475\u0026ndash;83. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11906-013-0377-9\u003c/span\u003e\u003cspan address=\"10.1007/s11906-013-0377-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e PubMed PMID: 23917809.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvliyao Y, Kayrin -B Kaya L. Effect of pentoxifylline on veno-occlusive priapism-induced corporeal tissule lipid peroxidation in a rat model. Urol Res. 1997. Report.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErdemir F, Firat F, Markoc F, Atilgan D, Parlaktas BS, Kuyucu YE, vd. The effect of pentoxifylline on penile cavernosal tissues in ischemic priapism-induced rat model. 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The effect of intratesticular dexpanthenol on experimentally-induced testicular ischaemia/reperfusion injury. J Pediatr Urol. Ağustos 2021;17(4):440\u003cdiv class=\"ExternalRefDOI\"\u003e.e1-440.e7\u003c/div\u003e. doi:10.1016/j.jpurol.2021.03.031\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEtensel B, \u0026Ouml;zkisacik S, \u0026Ouml;zkara E, Serbest YA, \u0026Ouml;ztan O, Yazici M, vd. The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatr Surg Int. Mart 2007;23(3):271\u0026ndash;5. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00383-006-1871-9\u003c/span\u003e\u003cspan address=\"10.1007/s00383-006-1871-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e PubMed PMID: 17205291.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Biochemical evaluation of serum samples.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"575\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (min-max)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eIL-1\u0026beta;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e29.56\u0026plusmn;2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e27.20 (22.20-39.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e77.46\u0026plusmn;9.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e86.80 (108.90-38.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e35.58\u0026plusmn;3.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e33.55 (64.90-23.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-3: 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e29.08\u0026plusmn;2.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e26.50 (45.60-21.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-4:\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e47.91\u0026plusmn;5.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e46.35 (74.80-22.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-5:0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e71.32\u0026plusmn;9.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e69.30 (114.90-23.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-6:0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e34.12\u0026plusmn;3.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e30.00 (54.30-23.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-7:0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eIL-10\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e134.83\u0026plusmn;32.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e87.00 (78.90-179.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e91.91\u0026plusmn;15.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e86.30 (73.00-121.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1-2:0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e112.02\u0026plusmn;23.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e105.55 (81.70 -155.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-3:0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e141.87\u0026plusmn;31.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e147.20 (93.80-180.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-4:0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e102.38\u0026plusmn;23.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e92.95 (79.70-150.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-5:0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e95.80\u0026plusmn;16.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e89.80 (78.80-123.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-6:0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e114.48\u0026plusmn;29.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e108.00 (82.00-164.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-7:0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMDA\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e173.11\u0026plusmn;12.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e173.70 (92.40-158.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e253.93\u0026plusmn;20.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e250.40 (288.60-230.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e179.24\u0026plusmn;12.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e175.80 (202.10-163.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-3: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e197.87\u0026plusmn;14.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e199.20(214.70-175.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-4: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e222.15\u0026plusmn;18.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e214.40 (252.20-202.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-5:0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e182.51\u0026plusmn;16.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e186.05 (157.50-201)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-6: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e211.71\u0026plusmn;20.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e211.35 (183-245.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-7: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eTOS\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e24.08\u0026plusmn;0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e24.90 (27.10-19.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e20.38\u0026plusmn;0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e19.80 (25.30-18.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1-2:0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e20.11\u0026plusmn;0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e19.75 (24.50-16.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e22.68\u0026plusmn;1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e21.80 (27.50-18.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e19.21\u0026plusmn;1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e18.55 (28.90-14.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e19.38\u0026plusmn;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e18.85 (26.90-14.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e22.12\u0026plusmn;0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e22.05 (26.20-17.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eTAS\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cem\u003eI (Sham)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.32\u0026plusmn;0.02\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.33 (0.25-0.44)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.43\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e0.41 (0.29-0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1-2:0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.33\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e0.31 (0.26-0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.33\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e0.32 (0.24-0.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.51\u0026plusmn;0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e0.31 (0.25-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.49\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e0.49 (0.32-0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e0.39\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e0.41 (0.29-0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eeNOS\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e157.10\u0026plusmn;8.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e158.30 (122.00-198.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e226.23\u0026plusmn;17.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e206.50 (143.70-288.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e184.60\u0026plusmn;10.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e186.05 (147.00-253.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-3:0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e149.63\u0026plusmn;14.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e135.80 (120.10-260.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-4:0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e191.40\u0026plusmn;12.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e185.00 (122.80-262.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-5:0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e219.13\u0026plusmn;13.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e225.40 (122.30-270.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-6:0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e180.26\u0026plusmn;13.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e167.55 (134.40-266.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2-7:0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan id=\"_Toc181334164\"\u003eSD: Standard deviation, PFD: Pirfenidone, PTX: Pentoxifylline, DXP: Dexpanthenol, PFD+DXP: Pirfenidone + Dexpanthenol, PTX+DXP: Pentoxifylline + Dexpanthenol.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Significant P values regarding IL-1\u0026beta;, IL-10 p, eNOS p and MDA.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"426\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeğer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-1\u0026beta;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e1-2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e6-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIL-10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e1-2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"9\" valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eeNOS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e1-2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e6-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-3.4.5.6.7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e5-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003eP\u003csub\u003e6-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp id=\"_Toc181334165\"\u003eIL: Interleukin, eNOS: Endothelial nitric oxide synthase, MDA: Malondialdehyde. One-way analysis of variance (ANOVA) post-hoc Games Howel *Mann Whitney-, , Kruskal Wallis-H post-hoc Mann Whitney-U for eNOS P, One-way analysis of variance (ANOVA) post-hoc Tukey HSD for MDA.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Histopathological evaluation of penectomy specimens.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"532\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (min-max)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVasocongestion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.33\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0(0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.78\u0026plusmn;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2(1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.30\u0026plusmn;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1(1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-3:\u0026nbsp;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.78\u0026plusmn;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-4:1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.40\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-5:0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.90\u0026plusmn;0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-6:0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.40\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-7:0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInflamation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.56\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.6\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-3:\u0026nbsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1\u0026plusmn;0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-4:0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.9\u0026plusmn;0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-5:0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.6\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-6:\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.1\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-7:\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDescuamation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.44\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.1\u0026plusmn;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-3:\u0026nbsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.22\u0026plusmn;0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-4:\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1\u0026plusmn;0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-5:0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.1\u0026plusmn;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-6:\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.1\u0026plusmn;.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-7: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEdema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e2.22\u0026plusmn;0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.50\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1.5 (0-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-3:\u0026nbsp;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.33\u0026plusmn;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-4:0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.80\u0026plusmn;0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-5:0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.70\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-6:\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.40\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-7:0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeparation of Tunika albugineada\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.22\u0026plusmn;0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.5\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.5 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-3:\u0026nbsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.67\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-4:0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1.50\u0026plusmn;0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e2 (0-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-5:0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.30\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-6:0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1\u0026plusmn;0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e1 (0-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-7:0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal pathology score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eI (Sham)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0.33\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eII (Control)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e8.56\u0026plusmn;1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e9 (5-11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1-2: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIII (PFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e4\u0026plusmn;1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4 (2-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-3:\u0026nbsp;\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eIV (PTX)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e5\u0026plusmn;1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e5 (3-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-4: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eV (DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e7.90\u0026plusmn;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e8 (5-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-5:0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVI (PFD+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e2.60\u0026plusmn;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e3 (0-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-6: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eVII(PTX+DXP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e4.10\u0026plusmn;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4 (2-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2-7: \u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSD: Standard deviation, PFD: Pirfenidone, PTX: Pentoxifylline, DXP: Dexpanthenol, PFD+DXP: Pirfenidone + Dexpanthenol, PTX+DXP: Pentoxifylline + Dexpanthenol.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Inflammation, desquamation, edema, and tunica albuginea detachment were statistically significant (p-values).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInflamation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDescuamation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e1-2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003ep\u003csub\u003e2-3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003ep\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003ep\u003csub\u003e2-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003ep\u003csub\u003e2-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEdema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e3-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e5-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e6-7\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeparation of Tunika albugineada\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e2-4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e4-5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eP\u003csub\u003e5-6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMann Whitney-U.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9220334/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9220334/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIschaemic priapism is a urological emergency that may lead to irreversible erectile dysfunction due to cavernosal tissue damage. In this experimental study, we evaluated the acute effects of pirfenidone, pentoxifylline, and dexpanthenol on ischaemia\u0026ndash;reperfusion injury (IRI) in a rat model of ischaemic priapism. A total of 68 male Wistar albino rats were randomly assigned to seven groups, including sham, control (IRI), and treatment groups receiving pirfenidone, pentoxifylline, dexpanthenol, or combination therapies. Ischaemic priapism was induced under anaesthesia, followed by a reperfusion period. Serum inflammatory (IL-1β, IL-10), oxidative stress (MDA, TOS, TAS), and endothelial (eNOS) markers were analysed, and histopathological evaluation was performed using semi-quantitative scoring. The control group demonstrated significantly higher IL-1β, eNOS, and MDA levels compared with treatment groups. Pirfenidone and pentoxifylline significantly reduced IL-1β and MDA levels and improved histopathological scores, while pentoxifylline also increased IL-10 levels, indicating enhanced anti-inflammatory activity. In contrast, dexpanthenol demonstrated a more limited effect, with significant improvement observed only in MDA levels. Combination therapies did not demonstrate superiority over monotherapy. These findings suggest that pirfenidone and pentoxifylline may have potential as adjunctive therapeutic options for limiting cavernosal tissue injury and preserving erectile function in ischaemic priapism.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"Pirfenidone and Pentoxifylline Attenuate Ischaemia–Reperfusion Injury in Experimental Priapism: Limited Effects of Dexpanthenol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-03 12:58:07","doi":"10.21203/rs.3.rs-9220334/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b0170837-3abb-4b7c-920d-509bb178ae61","owner":[],"postedDate":"April 3rd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Reject after peer review","date":"2026-05-11T14:24:19+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65428931,"name":"Health sciences/Medical research/Experimental models of disease"},{"id":65428932,"name":"Health sciences/Diseases/Urogenital diseases/Sexual dysfunction"},{"id":65428933,"name":"Health sciences/Health care/Disease prevention/Preventive medicine"}],"tags":[],"updatedAt":"2026-05-11T14:33:25+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-03 12:58:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9220334","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9220334","identity":"rs-9220334","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}