An investigation of cytochrome p450 (CYP) and glutathione S‐transferase (GST) isoenzyme protein expression and related interactions with phototherapy in patients with psoriasis vulgaris

Oxidative stress may play an important role in the pathogenesis of psoriasis. Glutathione S‐transferases (GSTs) make up a group of antioxidant enzymes. Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We investigated the potential effects of GST and CYP enzymes in the pathogenesis of psoriasis. The study included 32 psoriasis patients and 22 healthy subjects. Psoriasis patients were administered 20 sessions of narrowband ultraviolet B phototherapy. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. Expression levels of GSTK1, GSTM1, and GSTT1 were significantly higher in psoriasis than in control tissues (P = 0.022, P = 0.001, and P = 0.006, respectively). Pre‐ and post‐treatment expression was similar. Expression of CYP1A1 and CYP2E1 was significantly higher in pre‐ (P = 0.003 and P = 0.001, respectively) and post‐treatment (P = 0.003 and P = 0.001, respectively) psoriatic tissues than in control tissues. No significant differences in CYP1B1 levels between the study and control groups were detected before treatment (P > 0.05). However, CYP1B1 levels were higher in post‐treatment psoriatic tissue than in control tissue (P = 0.045). The significant increases in expression of GSTK1, GSTM1, and GSTT1 in psoriasis may reflect the increased activation of GST in response to excessive free radical formation from activated neutrophils or ultraviolet exposure to maintain antioxidant capacity in psoriasis. Furthermore, expressions of CYP1A1 and CYP2E1 represent important enzymatic systems in psoriasis. These findings suggest that psoriasis is an oxidative stress condition, although phototherapy does not affect these enzymatic systems. Further investigation is required.     

Protective Effect of MESNA (2-Mercaptoethane Sulfonate) Against Hepatic Ischemia/Reperfusion Injury in Rats

Purpose Reoxygenation of ischemic tissue generates various reactive oxygen metabolites (ROMs), which have a deleterious effect on various cellular functions. We evaluated the possible protective effect of 2-mercaptoethane sulfonate (MESNA) on hepatic ischemia/reperfusion (I/R) injury.Methods Wistar albino rats were subjected to 45-min hepatic ischemia, followed by 60-min reperfusion. 2-Mercaptoethane sulfonate, 150 mg/kg, or saline was given intraperitoneally (i.p.) twice, 15 min before ischemia and immediately before reperfusioin. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to assess liver function. Liver tissue samples were taken to measure the levels of malondialdehyde (MDA), an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. We also measured hepatic collagen content, as a fibrosis marker.Results Plasma ALT and AST levels were higher in the I/R group than in the control group, but this increase was significantly decreased by MESNA treatment. Hepatic GSH levels, which were significantly depressed by I/R, increased back to the control levels in the MESNA-treated I/R group. Increases in tissue MDA levels and MPO activity caused by I/R injury decreased back to the control levels after MESNA treatment. Similarly, the increased hepatic collagen content in the I/R group decreased to the level of the control group after MESNA treatment.Conclusion The fact that MESNA alleviated I/R-induced injury of the liver and improved hepatic structure and function suggests that its antioxidant and oxidant scavenging properties may be of therapeutic value in protecting the liver against oxidative injury caused by I/R.     

Clinical update on pulmonary embolism

Pulmonary embolism (PE) is a major cause of cardiovascular mortality and financial burden that affects the community. The diagnosis of PE can be difficult because of the nonspecific symptoms, which include cough, dyspnea, hemoptysis and pleuritic chest pain. Hereditary and acquired risk factors are associated with PE. Incidence of PE is increasing, associated with the development in the diagnostic methods. Evidence-based algorithms can help clinicians diagnose PE. Serum D-dimer level, computed tomography pulmonary angiogram (CTPA), ventilation-perfusion scintigraphy or echocardiography help to establish clinical probability and the severity of PE. Anticoagulation is the standard treatment for PE. However, thrombolytic treatment is a significant alternative in high risk of PE as it provides rapid clot resolution. This article reviews the risk factors, diagnostic algorithms, and methods of treatment in PE in the light of current information.     

Guide to drug therapy for lower urinary tract symptoms in patients with benign prostatic obstruction : implications for sexual dysfunction

The relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) caused by benign prostatic obstruction (BPO) has recently gained increasing attention. Both BPO and ED are highly prevalent in older men and both conditions frequently contribute to a reduction in overall quality of life. Current medical treatment of LUTS/BPO consists of monotherapy with alpha(1)-adrenoceptor antagonists or 5alpha-reductase inhibitors, a combination of these two agents or, in some cases, various phytotherapeutic approaches. When choosing a drug therapy, it is important to recognize that while 5alpha-reductase inhibitors increase the risk of ED and ejaculatory disorders, and combined therapy carries the cumulative risk of causing sexual dysfunction, some alpha(1)-adrenergic receptor antagonists have been reported to improve overall sexual function. Therefore, the successful evaluation and management of older men with LUTS associated with BPO should include an assessment of baseline sexual function and subsequent monitoring of medication-induced sexual adverse effects. In this review, we detail the pathophysiological mechanisms involved in LUTS/BPO-associated ED, including reduced nitric oxide/cyclic guanosine monophosphate system activity, enhanced endothelin-1/rhoA/rho kinase pathway activity, sympathetic overactivity, pelvic organ atherosclerosis and potential preventive approaches.     

Chronic inhibition of nitric‐oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil

Study Type – Aetiology (case control)
Level of Evidence 3b

OBJECTIVE

To evaluate the effect of N(G)‐nitro‐l ‐arginine methyl ester (L‐NAME)‐induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)‐5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L‐NAME induces NO‐deficient HT.

MATERIALS AND METHODS

Thirty‐six adult Sprague‐Dawley male rats were divided into three groups, i.e. a control, L‐NAME‐HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil‐treated L‐NAME‐HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L‐NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ‐bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme‐linked immunosorbent assay.

RESULTS

The erectile response was diminished in the HT group. Nitrergic and endothelium‐dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L‐NAME‐treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels.

CONCLUSIONS

Sildenafil treatment did not correct the ED in L‐NAME‐treated HT rats. Under sustained high blood pressure, up‐regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium‐dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT.     

Pituitary apoplexy in an adrenocorticotropin-producing pituitary macroadenoma

Adrenocorticotropin (ACTH) producing macroadenomas and pituitary apoplexy are unusual in Cushing' s disease. A 20-year-old man who had been diagnosed Cushing' s disease 2 months ago, presented with sudden headache, nausea, and vomiting. His serum cortisol level was 0.4 μg/dl and ACTH level was 23.9 pg/ml. Magnetic resonance imaging of the pituitary gland disclosed a hemorrhage in the pituitary macroadenoma (22×19 mm). He was treated with IV methylprednisolone immediately and then the symptoms were relieved within the first day of the treatment. The hemorrhagic lesion was resected by transsphenoidal surgery successfully. Impaired secretion of pituitary hormones may be seen after the pituitary apoplexy. We communicate a case with pituitary apoplexy of an ACTH secreting pituitary macroadenoma, causing acute glucocorticoid insufficiency.