Prevalence and risk factors of erectile dysfunction in cirrhotic patients: An observational study.

Background: Erectile dysfunction (ED) is a prevalent complication observed in male patients with liver cirrhosis; however, there is limited understanding of the etiological determinants responsible for its occurrence. The objective of this investigation is to explore potential contributory factors that underlie the development of ED in male patients with liver cirrhosis. Method: A cross-sectional study was conducted on 200 male patients with liver cirrhosis, who were divided into three groups according to the Child score. ED was studied using the International Index of Erectile Function (IIEF-5) Questionnaire and penile Doppler. Results: The prevalence of ED among the cirrhotic patients was 80%, and it was more frequent in patients with advanced liver disease (Child C). Penile venous leakage was observed in 20% of cirrhotic patients, which increased to 28.6% in those with advanced liver cirrhosis. Multivariate logistic regression analysis showed that age, low albumin levels, elevated INR, high hemoglobin levels, and Child C were predictors of ED in cirrhotic patients. Conclusion: Several clinical variables have been identified as potential contributors to the development of erectile dysfunction (ED) in patients with cirrhosis. These variables include advanced age, decreased levels of albumin, elevated INR, increased hemoglobin levels, and Child C classification. Early identification and treatment of these factors could potentially improve the quality of life for cirrhotic patients with ED. Notably, patients with ED in this population were observed to have elevated levels of INR, serum bilirubin, and hemoglobin, as well as reduced levels of serum albumin.

Downregulation of IL-1ß/p38 mitogen activated protein kinase pathway by diacerein protects against kidney ischemia/reperfusion injury in rats.

Renal ischemia-reperfusion (I/R) can be precipitated by multiple clinical situations that lead to impaired renal function and associated mortality. The resulting tubular cell damage is the outcome of complex disorders including, an inflammatory process with an overproduction of cytokines. Here, diacerein (DIA), an inhibitor of proinflammatory cytokine interleukin-1 beta (IL-1ß), was investigated against renal I/R in rats. DIA was orally administrated (50 mg/kg/day) for ten days before bilateral ischemia for 45 min with subsequent 2 hr. reperfusion. Interestingly, DIA alleviated the renal dysfunction and histopathological damage in the renal tissues. Pretreatment with DIA corrected the oxidative imbalance by prevented reduction in antioxidant levels of GSH and SOD, while it decreased the elevation of the oxidative marker, MDA. In addition, DIA downregulated IL-1ß and TNF-α expression in the renal tissues. Consequent to inhibition of the oxidative stress and inflammatory cascades, DIA inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Therefore, downstream targets for p38 MAPK were also inhibited via DIA which prevented further increases of inflammatory cytokines and the apoptotic marker, caspase-3. Collectively, this study revealed the renoprotective role of DIA for renal I/R and highlighted the role of p38 MAPK encountered in its therapeutic application in renal disease.

TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats.

PURPOSE: Pulmonary fibrosis (PF) is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on PF injury has not yet been fully clarified. Therefore, the current study aimed to detect its protective effect on lung tissue with the explanation of possible underlying mechanisms. METHODS: Adult male albino rats were assigned to four groups: control group, diacerein control group, PF non-treated group, and PF diacerein pretreated group. Lung tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and myeloid differentiation factor 88 (MyD88) levels were determined. Histopathological examination of lung tissue and immunohistochemical studies of nuclear factor-kappa B (NF-κB), and transforming growth factor- ß (TGF-ß) were also done. RESULTS: Diacerein pretreatment has the ability to restore the PF damaging effect, proved by the reduction of the oxidative stress and lung tissue inflammation via downregulation of TLR4/NF-κB signaling pathway together with the restoration of TGF-ß level and improvement of the histopathological and immunohistochemical study findings in the lung tissue. CONCLUSION: These results suggested the protective effect of diacerein on PF relies on its antioxidant and anti-inflammatory effects reducing TLR4/NF-κB signaling pathway.

Efficacy of topical calcipotriol betamethasone dipropionate as a new adjuvant therapy to follicular unit extraction technique in treatment of stable vitiligo: clinical, dermoscopic and immunohistological study.

BACKGROUND: Follicular unit extraction (FUE) grafting is a surgical procedure which provides the vitiliginous patches with undifferentiated stem cells of the hair follicles. It has been postulated that adjuvant therapy enhances the results. This is the first study to assess two different adjuvant therapies vs FUE alone. AIMS: To study the efficiency of FUE alone or combined with either topical calcipotriol betamethasone dipropionate (CBD) or NB-UVB phototherapy in cases of nonsegmental stable vitiligo. To assess the role of dermoscopy in monitoring the pattern and degree of repigmentation. PATIENTS/ METHODS: 53 patients with 94 lesions with stable nonsegmental vitiligo were divided into three groups. Group 1 (n = 16) with 30 lesions received FUE alone. Group 2 (n = 18) with 32 lesions received FUE plus topical CBD. Group 3 (n = 19) with 32 lesions received FUE plus NB-UVB phototherapy. Assessment was done by grades of repigmentation, color match, percent of size reduction, and immunohistochemical evaluation of perilesional CD8+T lymphocytes. RESULTS: The fastest onset of repigmentation was observed in both groups 2 and 3 in the second week (16.7%, 10.5%, respectively).Group 2 achieved the best response by all methods of assessment. Perifollicular diffuse repigmentation was the commonest dermoscopic pattern in 60 lesions (63.8%). There was a statistically significant decrease in perilesional CD8+T lymphocytes after 4 months. CONCLUSION: FUE is an effective method of surgical treatment of stable vitiligo, and topical CBD as a new adjuvant therapy is successful in targeting the immunological background of vitiligo. Dermoscopy has an essential role in monitoring the repigmentation response.

Novel marker for the detection of sickle cell nephropathy: soluble FMS-like tyrosine kinase-1 (sFLT-1).

BACKGROUND: Given the burden and poor outcome of end-stage renal disease in sickle cell disease (SCD), early markers of sickle cell nephropathy (SN) are desirable. Disordered angiogenesis underlies many complications of SCD. We aimed to determine the relationship between serum FMS-like tyrosine kinase-1 (sFLT-1) and other biomarkers of renal damage for the early diagnosis of SN. METHODS: Forty-seven SCD patients and 49 healthy controls were enrolled. Microalbuminuria was determined in patient urine samples. Blood samples were tested for sFLT-1, serum creatinine, and various hemolysis and inflammation markers. Peripheral blood monocyte expression of sFLT-1 was measured using real-time polymerase chain reaction (PCR). RESULTS: The serum level of sFLT-1 (pg/ml) in SCD patients was higher than controls (median/range/IQR = 142/ 60-1300/61 pg/ml vs. 125/ 110-187/52 pg/ml, respectively) (p = 0.006). Median (range) of sFLT-1 level was higher in SCD patients with microalbuminuria compared to SCD patients with normoalbuminuria, 185 (140-1300) vs. 125 (60-189) mg/g, respectively) (p = 0.004). There was a significant positive correlation between serum sFLT-1 and microalbuminuria, lactate dehydrogenase (LDH), and indirect bilirubin (r = 0.59, 0.39, 0.30, and p = <0.001, 0.007, 0.041, respectively). sFLT-1 sensitivity in early detection of renal affection in SCD was 93.6%, while specificity was 68.6%. Finally, peripheral blood monocytes (PBM) sFLT-1 expression was significantly higher in SCD patients compared to controls (p = 0.05). CONCLUSIONS: sFLT-1 may contribute to pathogenesis of albuminuria in SCD patients and constitute a novel renal biomarker of SN.

T cells are depleted in HCV-Induced hepatocellular carcinoma patients: possible role of apoptosis and p53.

Egypt has possibly the highest Hepatitis C Virus (HCV) prevalence worldwide. A high proportion of HCV infections become chronic and lead to liver cirrhosis and hepatocellular carcinoma (HCC). The cellular and molecular mechanisms behind HCV infection complication are not completely understood although apoptosis has been implicated in this process. Using flowcytometry, we examined whether T lymphocyte; isolated from patients with HCV and HCV-associated HCC (HCV-HCC); are predestined in vivo to undergo spontaneous apoptosis. Also, the role of p53; a key protein in apoptotic process; in the development of HCC was examined. Our data showed that T cells were severely depleted in HCV-HCC patients and its spontaneous apoptosis was higher in patient groups as compared to normal controls. In addition, p53 expression in liver tissue (determined by ELISA) was higher in the HCC patient groups as compared to normal controls and correlated well with the HCC grade. In conclusion, HCV infection induces peripheral T cell apoptosis, depletion and subsequently immune-suppression and this may lead to persistence of infection. Also, p53 is implicated in the poor prognosis of HCV-HCC and could be used as a predictive marker to assess the prognosis of HCC patients.