The role of oxidants and antioxidants in psoriasis

BACKGROUND: Psoriasis vulgaris is a chronic inflammatory skin disease characterized by well-demarcated erythema and scaly plaques. The pathogenesis of psoriasis still remains unclear. An increased reactive oxygen species (ROS) and insufficient antioxidant activity have been determined in psoriatic lesions. AIM OF THE STUDY: To evaluate and compare superoxide dismutase (SOD) and glutathione peroxidase (GP) activity in erythrocytes, catalase (CAT) activityand malondialdehyde (MDA) levels in serum of subjects with psoriasis and controls as well as MDA levels in skin biopsies from both groups. STUDY POPULATION: Twenty-two psoriatic patients (12 women and ten men) and 22 (12 women and ten men) healthy controls were involved in this study. FINDINGS: Statistically significant decreased levels of erythrocyte SOD and GP activities were noted in psoriatic subjects. Furthermore, a statistically significant increased serum CAT activity was found in the psoriasis group. No statistically significant difference was found in the serum MDA levels in the two groups, however, statistically significant increased tissue levels of MDA were noted in the psoriasis group. CONCLUSIONS: Our results support the hypothesis of an imbalance in the oxidant-antioxidant system in psoriasis.     

A case of sarcomatoid carcinoma of the skin

We describe the histological and immunocytochemical findings of an exophytic cutaneous tumour with mixed features of atypical fibroxanthoma (AFX) and basal cell carcinoma (BCC). A 73-year-old woman presented with a rapidly growing tumour measuring 35 mm in diameter and 10 mm in height on the left forearm. The tumour was excised and histology revealed a biphasic tumour with a pleomorphic spindle cell component and an associated tumour composed of discrete islands of atypical basaloid cells with peripheral palisading consistent with BCC. The two tumours merged into each other at one point. The spindle cell tumour showed a positive immunocytochemical reaction to fibrohistiocytic marker of KP-1 (CD68) and a negative immunocytochemical reaction to AE1/AE3, CAM5.2, S-100 and HMB-45, features consistent with AFX. Immunocytochemistry of the basaloid tumour showed a positive reaction to epithelial markers AE1/AE3 and CAM5.2, and a negative reaction to S-100, HMB-45 and KP-1 (CD68). To date, 15 cases of primary cutaneous carcinosarcoma have been reported in the literature. It has been postulated that these tumours may originate from undifferentiated progenitor cells capable of producing multiple cell lines.     

Favorable female sexual function is associated with patient satisfaction after inflatable penile prosthesis implantation

IntroductionThe interrelationship between male and female sexual function suggests that partner outcomes after inflatable penile prosthesis (IPP) implantation must be assessed.AimWe examined predictors of patient and partner satisfaction, and the relationship between patient satisfaction and female sexual function, after IPP implantation.MethodsWe designed a questionnaire (scored 1–5) assessing satisfaction with various domains related to the IPP (e.g., overall satisfaction and satisfaction related to: length, width, ease of use, and partner perception). Scores ≥3 were classified as satisfied. The Female Sexual Function Index (FSFI) was administered to the female partners of patients that underwent an IPP.Main Outcome MeasuresIndependent samples Students' t‐test was used to compare various FSFI domain scores in relation to male and female satisfaction. Analysis of variance test was used to assess linear regression correlation between various continuous variables.Results45 men and 32 partners with a mean follow‐up of 2.2 years were contacted. Overall satisfaction for men and women was 3.60 and 3.62 (out of 5), respectively. Partner FSFI scores were higher, respectively, in men with higher implant satisfaction than those with lower implant satisfaction (25.09 ± 6.79 vs. 13.67 ± 12.70, P < 0.001). Regression analysis suggests a direct correlation between FSFI scores and the degree of patient (r = 0.50, r² = 0.23; P = 0.001) and partner (r = 0.70 r² = 0.50; P < 0.001) satisfaction with the IPP.ConclusionPatient satisfaction after IPP implantation implies favorable partner sexual function compared to that of unsatisfied patients. The correlation observed suggests that patients not satisfied with their IPP are likely to have female partners at high risk for female sexual dysfunction. Further interventions may be needed to improve patient and partner sexual function, particularly unsatisfied men and their female partners. Moskovic DJ, Gittens P, Avila D, Chandrashekar A, Khera M, and Lipshultz LI. Favorable female sexual function is associated with patient satisfaction after inflatable penile prosthesis implantation. J Sex Med 2011;8:1996–2001.     

Differential expression and activities of cytochrome P450 3A in the rat brain microsomes and mitochondria

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method after validation. Subsequently, Michaelis–Menten kinetics of 1′- and 4-hydroxylation of MDZ were estimated. Western blot (WB) analysis was used to determine the protein expression of CYP3A in the rat brain MC and MT. The MC fractions had 5.93% ± 3.01% mitochondrial impurity, and the MT fractions had 19.3% ± 7.8% microsomal impurity (mean ± SD). The maximum velocity (V_max) values of the formation of the hydroxylated metabolites in the brain MT were 2.4–9-fold higher than those in MC. Further, the V_max values of 4-OH-MDZ in both MC and MT fractions were substantially higher than those of 1′-OH-MDZ. The WB analysis showed that the intensity of the CYP3A immunoreactive band in MT was more than twofold higher than that in MC. It is concluded that compared with MC, rat brain MT contains substantial CYP3A, which may affect the pharmacology or toxicology of centrally acting xenobiotic and endogenous substrates of this enzyme.     

Effects of chronic cirrhosis induced by intraperitoneal thioacetamide injection on the protein content and Michaelis–Menten kinetics of cytochrome P450 enzymes in the rat liver microsomes

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by 30%–50% in cirrhotic animals. Additionally, the protein content and Michaelis–Menten kinetics of the activities of CYP2D, CYP2E1 and CYP3A were investigated. Whereas cirrhosis reduced the microsomal protein contents of CYP2D and CYP3A by 70% and 30%, respectively, the protein contents of CYP2E1 were not affected. However, the activities of all the tested isoenzymes were substantially lower in the cirrhotic livers. It is concluded that the TAA model of cirrhosis that incorporates a 10-day washout period after intraperitoneal injection of the chemical to rats produces isoenzyme-selective reductions in the P450 proteins or activities, which are independent of the direct inhibitory effects of TAA.