The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway / 中国天然药物

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

Vulnerabilidade de pacientes com hiperplasia prostática tratados com dutasterida e finasterida / Vulnerability of patients with prostatic hyperplasia treated with dutasteride and finasteride / Vulnerabilidad de pacientes con hiperplasia prostática tratados con dutasterida y finasterida

Resumo A hiperplasia prostática benigna é uma patologia cuja incidência vem crescendo muito nos últimos anos, em todo o Brasil. A doença está correlacionada a fatores hormonais, e o tratamento farmacológico pode gerar efeitos adversos nos pacientes. O objetivo deste estudo é avaliar fatores socioeconômicos e socioculturais que interferem na cura ou reduzem a qualidade de vida. Analisamos dados de plataformas do Governo Federal entre janeiro de 2009 a setembro de 2019, observando fatores como etnia, nível de escolaridade e situação econômica dos pacientes. Em todas as regiões do Brasil esses fatores se mostraram importantes, pois podem afetar diretamente a incidência da doença e a adesão e continuidade do tratamento.

Summary Benign prostatic hyperplasia is a pathology whose incidence has been increasing in recent years throughout Brazil. The disease is correlated with hormonal factors, and pharmacological treatment can have adverse effects on patients. This study assesses the socioeconomic and socio-cultural factors that interfere with healing or reduce quality of life. We analyzed data from Federal Government platforms between January 2009 and September 2019, looking at factors such as ethnicity, education level and economic status of patients. In all regions of Brazil, these factors proved to be important, as they can directly affect the incidence of the disease and adherence and continuity of treatment.

Resumen La hiperplasia prostática benigna es una patología cuya incidencia ha ido creciendo mucho en los últimos años, en todo Brasil. La enfermedad se correlaciona con factores hormonales, y el tratamiento farmacológico puede generar efectos adversos en los pacientes. El objetivo de este estudio es evaluar factores socioeconómicos y socioculturales que interfieren con la curación o reducen la calidad de vida. Analizamos datos de plataformas del Gobierno Federal entre enero de 2009 y septiembre de 2019, observando factores como el origen étnico, el nivel educativo y la situación económica de los pacientes. En todas las regiones de Brasil, estos factores demostraron ser importantes, ya que pueden afectar directamente la incidencia de la enfermedad y la adherencia y continuidad del tratamiento.

Does treatment with dutasteride or finasteride has impact on renal morphology? Experimental study

ABSTRACT Purpose: To investigate whether renal modifications occur following treatment with dutasteride or finasteride. Methods: Twenty-four male rats were divided into three groups: control (that received distilled water), dutasteride (0.5 mg/kg/day), and finasteride (5 mg/kg/day) groups. All administrations were given by gavage for 40 consecutive days. After inducing euthanasia, blood was collected for urea and creatinine analyses, and both the kidneys were collected for stereological analyses of kidney morphology. Results: Serum urea and creatinine levels were increased in both the finasteride and the dutasteride groups compared with those in the control group. In addition, kidney weight, kidney volume, cortical volume, glomerular volumetric density, and mean glomerular volume were reduced in both treatment groups. Finally, the number of glomeruli per kidney was reduced by 26.8% in the finasteride group and by 51.6% in the dutasteride group compared with that in the control group. Conclusions: The 5-ARIs finasteride and dutasteride promoted morphological and functional damages in rat kidneys. In addition, rats in the dutasteride group showed more severe renal modifications than those in the finasteride group.

Post-finasteride syndrome

Abstract Finasteride is a 5α-reductase enzyme inhibitor that has been approved for the treatment of male androgenic alopecia since 1997. Over time, it has been considered a safe and well-tolerated drug with rare and reversible side effects. Recently there have been reports of adverse drug-related reactions that persisted for at least three months after discontinuation of this drug, and the term post-finasteride syndrome arose. It includes persistent sexual, neuropsychiatric, and physical symptoms. Studies to date cannot refute or confirm this syndrome as a nosological entity. If it actually exists, it seems to occur in susceptible people, even if exposed to small doses and for short periods, and symptoms may persist for long periods. Based on currently available data, the use of 5α-reductase inhibitors in patients with a history of depression, sexual dysfunction, or infertility should be carefully and individually assessed.

RE-ORGA, a Korean Herb Extract, Can Prevent Hair Loss Induced by Dihydrotestosterone in Human Dermal Papilla Cells

BACKGROUND: Androgenic alopecia (AGA) is the most common type of hair loss. It is likely inherited genetically and is promoted by dihydrotestosterone. 5α-reductase has been proven a good target through finasteride use. However, the pathogenesis of AGA cannot be fully explained based only on dihydrotestosterone levels. OBJECTIVE: To identify similar hairloss inhibition activity of RE-ORGA with mode of action other than finasteride. METHODS: We prepared RE-ORGA from Korean herb mixtures. We performed MTT assays for cytotoxicity, Cell Counting Kit-8 assays for cell proliferation, and western blot to identify expression levels of 5α-reductase and Bax. RNA-sequencing was performed for the expression patterns of genes in dihydrotestosterone-activated pathways. Anti-inflammatory activity was also assessed by the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6. RESULTS: REORGA could promote the proliferation of human dermal papilla cells and showed low cytotoxicity. It also inhibited the expression of 5α-reductases and Bax in the cells. RNA-sequencing results verified that the mRNA expressions of SRD5A1, Bax, transforming growth factor-beta 1 (TGF-β1), and TGF-β1 induced transcript 1 (TGFβ1I1) were decreased, whereas expression of protein tyrosine kinase 2 beta (PTK2β) was more elevated. REORGA also showed anti-inflammatory activity through decreased mRNA levels of TNF-α. CONCLUSION: Transcriptionally, up-regulation of PTK2β and concomitant down-regulation of TGFβ1I1 imply that RE-ORGA can modulate androgen receptor sensitivity, decreasing the expression of 5α-reductase type II and Bax together with TGF-β1 transcripts; RE-ORGA also showed partial anti-inflammatory activity. Overall, RE-ORGA is expected to alleviate hair loss by regulating 5α-reductase activity and the receptor's androgen sensitivity.

Finasteride and Erectile Dysfunction in Patients with Benign Prostatic Hyperplasia or Male Androgenetic Alopecia

Finasteride is primarily used to treat benign prostatic hyperplasia (BPH) and male androgenetic alopecia (MAA). Five-alpha reductase inhibitors (5α-RIs) could induce male sexual dysfunction due to their effects on testosterone and dihydrotestosterone. There is evidence suggesting that 5α-RIs may independently increase the risk of erectile dysfunction (ED). However, many investigators believe that side effects of 5α-RIs will disappear with continuous treatment. Considerable controversy exists regarding the severity and persistence of side effects of finasteride on ED. The aim of this review was to summarize current research studies on finasteride associated with ED. The search strategy used each term of finasteride and ED against PubMed database to identify related studies. ED data reported from available trials for finasteride were summarized and reviewed. Although there is not enough evidence to prove the relationship between finasteride and ED, most studies in this review found that finasteride for BPH was correlated with ED. However, most studies included in this review revealed that finasteride for MAA was not correlated with ED. On the other hand, some studies reported side effects of finasteride associated with sexual dysfunction, including ED, male infertility, ejaculation problem, and loss of libido, even in MAA patients. Well-designed randomized controlled trials are needed to further determine the mechanism and effects of finasteride on ED. However, physicians should discuss with their patients possible long-term effects of finasteride on sexual function, although we do not have evidence showing that adverse events of sexual dysfunction are absolutely associated with 5α-RIs.

Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

PURPOSE: The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated with higher rate of permanent erectile dysfunction (ED) in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutasteride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. RESULTS: Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. CONCLUSIONS: Our study showed that recovery from ED depended on the duration of medication, and administration of dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.

Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats

BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.

Finasteride inhibits microvascular density and VEGF expression in the seminal vesicle of rats / 中华男科学杂志

<p><b>Objective</b>To investigate the effect of finasteride on the microvascular density (MVD) and the expression of the vascular endothelial growth factor (VEGF) in the seminal vesicle of rats.</p><p><b>METHODS</b>Forty male SD rats were randomly and equally divided into groups A, B, C and D, those in groups A and B fed with normal saline as the control and those in C and D with finasteride at 40 mg per kg of the body weight per day, A and C for 14 days and B and D for 28 days. Then the seminal vesicles of the animals were harvested for HE staining, measurement of MVD, determination of the expressions of CD34 and VEGF by immunohistochemistry, and observation of histomorphological changes in the seminal vesicle.</p><p><b>RESULTS</b>The expressions of CD34 in groups C and D were decreased by 6.7% and 15.8% as compared with those in A and B (P<0.01), and that in group D decreased by 9.3% in comparison with that in C (P<0.01). The expression indexes of VEGF in groups C and D were decreased by 6.9% and 14.1% as compared with those in A and B (P<0.01), and that in group D decreased by 9.0% in comparison with that in C (P<0.01).</p><p><b>CONCLUSIONS</b>Finasteride can inhibit the expression of VEGF in the seminal vesicle tissue of the rat and hence suppress the angiogenesis of microvessels of the seminal vesicle.</p>

Safety and Efficacy of the Coadministration of Sildenafil and Finasteride

PURPOSE: The 5-alpha reductase inhibitors (5ARI) are one of the most commonly used medications for the treatment of benign prostatic hyperplasia (BPH). Phosphodiesterase type-5 inhibitors are also used to treat BPH. 5ARI is a drug with adverse effects of sexual dysfunction. In this study, we investigated the safety and efficacy of coadministration of finasteride and sildenafil on sexual function and lower urinary symptoms in patients with BPH. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who were receiving finasteride and sildenafil daily regimens for treatment of BPH in 2 university hospitals. Patients with adverse effects, vital sign, physical exam, laboratory test, 5-item version of the international index of erectile function (IIEF-5), International Prostate Symptom Score (IPSS), quality of life (QoL) were analyzed. RESULTS: The number of patients analyzed in this study was 218. The mean age of the patients was 62.63±8.37 years and the mean duration of medication was 18.23±10.97 weeks. Significant changes were not observed in the vital signs measured before and after the drug administration. Compared with before treatment, improvement of lower urinary tract symptom (IPSS: 17.56±4.21 vs. 11.64±5.33, p < 0.001) was observed and improvement of sexual function (IIEF-5: 9.44±5.21 vs. 12.73±6.81, p < 0.001) was also confirmed. CONCLUSIONS: Daily coadministration of finasteride and sildenafil for the treatment of BPH could be used safely, and improvement of lower urinary tract symptom as well as improvement of sexual function could be expected.

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge

Abstract Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation.

Effects of Xialiqi Capsules on the expressions of PCNA and caspase-3 in rats withbenign prostatic hyperplasia / 中华男科学杂志

Objective@#To explore the effects of Xialiqi Capsules(XLQ) on the expressions of the proliferating cell nuclear antigen (PCNA) and caspase-3 in the prostate tissue of the BPH rat model.@*METHODS@#Fifty male SD ratswereequally randomized into groups A (sham operation control), B (BPH model control), C (high-dose XLQ), D (low-dose XLQ), and E (finasteridecontrol) andthe BPH modelswere established by subcutaneous injection of testosterone propionate at 0.5 mg per kilogram of the body weight per day for 30 days after castration. After modeling, the animals in groups A and B were treated intragastricallywith normal saline, while those in C, D, and E with XLQ at 1.20 and 0.61 g per kilogram of the body weight per day or finasterideat 0.8 mg per kilogram of the body weight per day, respectively, all for 30 days. Then,the bilateral prostates were harvestedfrom the rats for calculation of the prostatic index (prostate wet weight/ body weight) and determination of the expressions of PCNA and caspase-3 in the prostate tissue by immunohistochemistry and immunofluorescence staining, respectively.@*RESULTS@#The prostate wet weight and prostate index were significantly increased in group B as compared with group A, (［1326±60］ vs［471±17］ g, P<0.01; ［2.89±0.18］ vs ［1.06±0.06］ mg/g, P<0.01), but decreased in groups C (［914±36］ g;［2.02±0.08］ mg/g), D (［1 099±46］g;［2.39±0.11］ mg/g), and E (［817±53］ g;［1.83±0.10］ mg/g)in comparison with B (P<0.01), with statistically significant differences among groups C, D, and E(P<0.01) and most significantly in E.The PCNA level in the prostate tissue wasremarkably higher in group B than in A, but lower in groups C, D and E than in B. The expression of caspase-3 was down-regulatedin group B as compared with A, but up-regulated in groups C, D and E in comparison with B, most significantly in E.@*CONCLUSIONS@#Xialiqi Capsules can effectively reduce the prostate wet weight and prostatic index of in rats with BPH by inhibiting the level of PCNA and promoting the expression of caspase-3.

Effects of Kudzu Root plus Cinnamon Granules on prostatic hyperplasia in mice / 中华男科学杂志

Objective@#To explore the effects of Kudzu Root plus Cinnamon Granules (KR+C) on prostatic hyperplasia (PH) in mice.@*METHODS@#Sixty 4-week-old Kunming male mice were randomly divided into six groups: blank control, PH model, high-, medium- and low-dose KR+C, and finasteride control. All the mice except those in the blank control group were subcutaneously injected with testosterone propionate (5 mg / ［kg·d］) at 7 days after surgical castration. The animals of different groups were treated intragastrically with different doses of KR+C, finasteride, and normal saline respectively for 3 weeks and then sacrificed for weighing of the prostate, calculation of the prostatic index, observation of the morphological changes in the prostate after HE staining, determination of the expressions of FGF2, Ki67 and TGF-β1 by immunohistochemistry, detection of 5α-reductase activity by ELISA, and measurement of the apoptosis index of the prostatic cells by TUNEL.@*RESULTS@#Compared with the model controls, the mice of the other groups showed significantly reduced prostatic volume (P 0.05).@*CONCLUSIONS@#KR+C can reduce the prostatic volume of PH mice by decreasing the activity of 5α- reductase, inhibiting the expressions of FGF2, Ki67 and TGF-β1, and promoting the apoptosis of prostatic cells.

Corn silk extract improves benign prostatic hyperplasia in experimental rat model

BACKGROUND/OBJECTIVES: This study was conducted to investigate the effect of a corn silk extract on improving benign prostatic hyperplasia (BPH). MATERIALS/METHODS: The experimental animals, 6-week-old male Wistar rats, were divided into sham-operated control (Sham) and experimental groups. The experimental group, which underwent orchiectomy and received subcutaneous injection of 10 mg/kg of testosterone propionate to induce BPH, was divided into a Testo Only group that received only testosterone, a Testo+Fina group that received testosterone and 5 mg/kg finasteride, a Testo+CSE10 group that received testosterone and 10 mg/kg of corn silk extract, and a Testo+CSE100 group that received testosterone and 100 mg/kg of corn silk extract. Prostate weight and concentrations of dihydrotestosterone (DHT), 5α-reductase 2 (5α-R2), and prostate specific antigen (PSA) in serum or prostate tissue were determined. The mRNA expressions of 5α-R2 and proliferating cell nuclear antigen (PCNA) in prostate tissue were also measured. RESULTS: Compared to the Sham group, prostate weight was significantly higher in the Testo Only group and decreased significantly in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05), results that were consistent with those for serum DHT concentrations. The concentrations of 5α-R2 in serum and prostate as well as the mRNA expression of 5α-R2 in prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups than that in the Testo Only group (P < 0.05). Similarly, the concentrations of PSA in serum and prostate were significantly lower in the Testo+Fina, Testo+CSE10, and Testo+CSE100 groups (P < 0.05) than in the Testo Only group. The mRNA expression of PCNA in prostate dose-independently decreased in the Testo+CSE-treated groups (P < 0.05). CONCLUSIONS: BPH was induced through injection of testosterone, and corn silk extract treatment improved BPH symptoms by inhibiting the mRNA expression of 5α-R2 and decreasing the amount of 5α-R2, DHT, and PSA in serum and prostate tissue.

A Case of Combination Therapy with Finasteride and Low Dose Dutasteride in the Treatment of Androgenetic Alopecia / 대한피부과학회지

No abstract available.

Efectos adversos de finasteride: mitos y realidades. una revisión actualizada / Finasteride adverse effects: an update

Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

Nocebo effect in dermatology.

Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specifi c neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of ‘permanent cure’ and frequent relapses of skin disorders. While fi nasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the confl ict between patients’ right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

Improvement of tissue survival of skin flaps by 5 alpha-reductase inhibitors: possible involvement of nitric oxide and inducible nitric oxide synthase

Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5alpha-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase [iNOS] in graft survival mediated by these agents. A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid [100 mg/flap]; 3, finasteride [1 mg/flap]; 4, injection of L-N[G]-nitroarginine methyl ester [L-NAME] [i.p., 20 mg/kg]; 5, L-NAME [20 mg/kg, i.p.] + azelaic acid [100 mg/flap, topical]; 6, L-NAME [20 mg/kg, i.p.] + finasteride [1 mg/flap, topical]. Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide [NO] levels in graft tissue [P < 0.05]. These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps