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Translational Andrology and Urology Jan 2024Implantation of penile prosthesis (PP) into scarred and fibrotic corpora can be a difficult challenge. In this review article, we provide a review of penile fibrosis,... (Review)
Review
BACKGROUND AND OBJECTIVE
Implantation of penile prosthesis (PP) into scarred and fibrotic corpora can be a difficult challenge. In this review article, we provide a review of penile fibrosis, discuss current medical and surgical management and summarize preventative strategies.
METHODS
In this study, we searched PubMed between the years 2000-2023 for publications with search strategy: "penile fibrosis" OR "scarred corpora" OR "fibrosed corpora".
KEY CONTENT AND FINDINGS
This search returned a total of 137 articles. We examine the evidence for preoperative patient evaluation and penile ultrasound (US), oral phosphodiesterase-5 inhibitors, pentoxifylline, and L-arginine, vacuum device therapy and the use of surgical approaches and tools in the context of complex penile fibrosis cases. Severe penile fibrosis is most associated with priapism and infection. Estimating the degree of fibrosis via preoperative US may help set realistic patient expectations. Phosphodiesterase inhibitors and L-arginine reduce fibrosis in animal models however their impact in humans remains unclear despite theoretical advantage for their use. Vacuum device therapy may preserve penile length following priapism and infected PP cases. The use of Coloplast Narrow-Based or AMS-700 CXR implants are used primarily for severe fibrosis. Various surgical excisional/incisional techniques, the Carrion-Rossello, Mooreville Uramix cavernotomes and reverse cutting scissors are all options, and their use varies from case to case. Finally, prevention of penile fibrosis in patients with history of penile implant infection and the safety of early implantation of a penile implant in patients with refractory priapism is encouraged.
CONCLUSIONS
The management of penile fibrosis remains a challenge but there are multiple options to assist clinicians. Complex cases should be managed and studied at high volume centers.
PubMed: 38404545
DOI: 10.21037/tau-23-206 -
Drug Research Mar 2024In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was...
In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.
Topics: Mice; Animals; Antioxidants; Arsenic Trioxide; Liver; Oxidative Stress; Alkaloids; Xanthines
PubMed: 38350632
DOI: 10.1055/a-2247-5232 -
Dermatology Reports Dec 2023A 14-year-old boy presented with a history of non-tender, subcutaneous coalescing nodules located on the ventral-lateral aspects of the penis shaft for one year....
A 14-year-old boy presented with a history of non-tender, subcutaneous coalescing nodules located on the ventral-lateral aspects of the penis shaft for one year. Laboratory investigations for blood count and autoimmunity were within normal limits. Complete excision was performed, and on histology, the dermis showed necrobiotic material composed of altered collagen bundles, surrounded by a palisade of histiocytes and scattered lymphocytes, thus allowing a diagnosis of subcutaneous granuloma annulare. Only 18 published cases reported penile granuloma annulare. Medical management was advocated in 7/18 cases, either as a first-line or adjuvant therapy where surgery was not radical. Three patients received high-potency local steroids: two cases underwent adjuvant sessions of intralesional triamcinolone, and one patient received pentoxifylline orally. Surgery should be considered a second-line option since 5/8 of treated cases eventually recurred. The pentoxifylline-treated case witnessed a relapse after drug discontinuation, while topical steroids lead to complete recovery without relapses.
PubMed: 38348422
DOI: 10.4081/dr.2023.9687 -
Annals of Medicine and Surgery (2012) Feb 2024Pyoderma gangrenosum is an unusual inflammatory pathology, with neutrophilic dermatosis, of unknown etiology. It is associated with diseases such as bowel disease....
INTRODUCTION AND IMPORTANCE
Pyoderma gangrenosum is an unusual inflammatory pathology, with neutrophilic dermatosis, of unknown etiology. It is associated with diseases such as bowel disease. Generally, it is treated with anti-inflammatory drugs, corticosteroids, immunosuppressants, and antibodies against tumor necrosis factor, but relapse and adverse effects are persistent. Pentoxifylline is a drug with immunoregulatory and anti-inflammatory properties.
CASE PRESENTATION
A 47-year-old male with a diagnosis of ulcerative colitis initially managed favorably for 7 years with mesalazine. At 3 years of treatment, he presented a sudden ulcer that affected skin and subcutaneous tissue (13×10 cm) in the lower right limb. During the last 2 years, he was treated with mesalazine and infliximab with partial results and permanent relapses. Therefore, pentoxifylline was added to his treatment.
CLINICAL DISCUSSION
The justification for the addition of pentoxifylline is mainly its action as an inhibitor of Nuclear Factor-kappa Beta (NF-κB) transcription, which stimulates the expression of proinflammatory interleukin genes such as IL-1, IL-6, IL- 8, and TNF-α and showing immunoregulatory and antioxidant activities.
CONCLUSION
With pentoxifylline, this lesion healed at 6 weeks without relapses after 2 years.
PubMed: 38333294
DOI: 10.1097/MS9.0000000000001637 -
European Journal of Pharmacology Mar 2024To investigate whether pentoxifylline (PTX) attenuates cerebral ischaemia-reperfusion injury (IRI) in rats by inhibiting ferroptosis and to explore the underlying...
OBJECTIVE
To investigate whether pentoxifylline (PTX) attenuates cerebral ischaemia-reperfusion injury (IRI) in rats by inhibiting ferroptosis and to explore the underlying molecular mechanisms.
METHODS
Cerebral IRI was induced in male Sprague-Dawley (SD) rats using middle cerebral artery occlusion (MCAO). The effects of PTX on cerebral ischaemia-reperfusion brain samples were detected through neurological deficit score, staining and electron microscopy; levels of ferroptosis biomarkers from brain samples were detected using kits. Additionally, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), transferrin receptor protein 1, divalent metal transporter 1, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting.
RESULTS
Pre-treatment with PTX was found to improve neurological function, evidenced by reduced neurological deficit scores, decreased infarct volume and alleviated pathological features post-MCAO. This improvement was accompanied by reduced lipid peroxidation levels and mitigated mitochondrial damage. Notably, PTX's inhibitory effect on ferroptosis was characterised by enhanced Nrf2 nuclear translocation and regulation of ferroptosis-related proteins. Moreover, inhibition of Nrf2 using ML385 (an Nrf2-specific inhibitor) reversed PTX's neuroprotective effect on MCAO-induced ferroptosis via the SLC7A11/GPX4 signalling pathway.
CONCLUSIONS
Ferroptosis is evident following cerebral ischaemia-reperfusion in rats. Pentoxifylline confers protection against IRI in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signalling pathway.
Topics: Male; Animals; Rats; Rats, Sprague-Dawley; Pentoxifylline; NF-E2-Related Factor 2; Ferroptosis; Reperfusion Injury; Cerebral Infarction
PubMed: 38331339
DOI: 10.1016/j.ejphar.2024.176402 -
American Journal of Physiology. Heart... Mar 2024Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine... (Randomized Controlled Trial)
Randomized Controlled Trial
Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, ∼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg; = 0.021) and isocapnic hypoxia (placebo, 22 ± 5; pentoxifylline, 20 ± 4 mmHg; = 0.029), but not in males. Acute pentoxifylline administration in lowlanders at 3,800 m had no impact on arterial blood gases, hemorheology, inflammation, gCBF, or ventilation. Unexpectedly, however, pentoxifylline reduced PASP in female participants, indicating a potential effect of sex on the pulmonary vascular responses to pentoxifylline. We conducted a double-blind, placebo-controlled study on the rheological, cardiorespiratory and cerebrovascular effects of acute pentoxifylline in healthy lowlanders after 11-14 days at 3,800 m. Although red blood cell deformability was reduced and blood viscosity increased compared with low altitude, acute pentoxifylline administration had no impact on arterial blood gases, hemorheology, inflammation, cerebral blood flow, or ventilation. Pentoxifylline decreased pulmonary artery systolic pressure in female, but not male, participants.
Topics: Male; Humans; Female; Young Adult; Adult; Pentoxifylline; Hemorheology; Tumor Necrosis Factor-alpha; Hypoxia; Oxygen; Acclimatization; Inflammation; Gases; Cerebrovascular Circulation; Altitude
PubMed: 38241007
DOI: 10.1152/ajpheart.00783.2023 -
Cureus Dec 2023In this report, we present the clinical management of a male patient diagnosed with non-obstructive azoospermia (NOA), a condition characterized by the absence of sperm...
In this report, we present the clinical management of a male patient diagnosed with non-obstructive azoospermia (NOA), a condition characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. A 37-year-old patient underwent two surgical procedures: testicular sperm aspiration (TESA) and percutaneous epididymal sperm aspiration (PESA). Surprisingly, the beta-human chorionic gonadotropins (β-HCG) testing that followed produced promising findings suggesting NOA syndrome may be reversible. Theophylline and pentoxifylline, phosphodiesterase inhibitors with immunomodulatory effects, were creatively used in this case study to increase sperm viability and activation after PESA. Hyaluronic acid was also used as an additional therapy because it is well known for aiding in sperm development and binding to oocytes. The patient underwent hyaluronic acid, which can potentially increase the fertilization rate and improve the selection of sperm. This in-depth case study offers insightful information on the effective management of NOA by combining theophylline, pentoxifylline, and hyaluronic acid. The results highlight the ability of these therapies to revive spermatogenesis, offering a cutting-edge method of treating male infertility. More research is required to clarify the underlying processes and confirm the effectiveness of this strategy in more successful reproductive medicine therapies.
PubMed: 38226124
DOI: 10.7759/cureus.50623 -
Clinical Nephrology. Case Studies 2023We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of...
PURPOSE
We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition.
OBSERVATIONS
We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis.
CONCLUSION AND IMPORTANCE
These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).
PubMed: 38169875
DOI: 10.5414/CNCS111088 -
Aging Cell Mar 2024Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with...
Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with interstitial fibrosis as a major contributor to renal myofibroblasts. In this study, we aim to investigate whether the phosphodiesterase inhibitor, pentoxifylline (PTX), can ameliorate aging-related functional and histological deterioration in the kidney. We subjected aging C57BL/6 mice, dividing into young, aging, and PTX-treated aging groups. Renal function, albuminuria, and histological changes were assessed. Interstitial pericytes were assessed by immunohistochemistry analysis. We examined changes in pericytes in elderly patients using human kidney tissue obtained from healthy kidney donors for kidney transplantation. In vitro experiments with human pericytes and endothelial cells were performed. Aging mice exhibited declined renal function, increased albuminuria, and aging-related histological changes including mesangial expansion and tubulointerstitial fibrosis. Notably, number of pericytes declined in aging kidneys, and myofibroblasts increased. PTX treatment ameliorated albuminuria, histological alterations, and microvascular rarefaction, as well as modulated angiopoietin expression. In vitro experiments showed PTX reduced cellular senescence and inflammation. Human kidney analysis confirmed similar pericyte changes in aging kidneys. The phosphodiesterase inhibitor, PTX preserved microvascular density and improved renal interstitial fibrosis and inflammation in aging mice kidneys. These protective effects were suggested to be associated with the amelioration of pericytes reduction and the transition to myofibroblasts. Additionally, the upregulation of angiopoietin-1 expression may exert potential impacts. To the best of our knowledge, this is the first report on the changes in renal interstitial pericytes in aging human kidneys.
Topics: Humans; Mice; Animals; Aged; Pericytes; Phosphodiesterase Inhibitors; Endothelial Cells; Albuminuria; Mice, Inbred C57BL; Kidney; Kidney Diseases; Aging; Fibrosis; Inflammation
PubMed: 38155524
DOI: 10.1111/acel.14075