Myosin-V colocalizes with MHC class II in blood mononuclear cells and is up-regulated by T-lymphocyte activation

Myosin-V is involved in organelle and vesicle trafficking in Saccharomyces cerevisiae and in other eukaryotic cells from yeast to human. In the present study, we determined by FACS that the major subpopulations of the peripheral blood mononuclear cells express myosin-V with similar fluorescence intensity. Confocal microscopy showed intense labeling for myosin-V at the centrosomal region and a punctate staining throughout the cytoplasm, frequently associated with the central microtubule arrays and the actin-rich cortex. Some degree of overlap with an endolysosomal marker and dynein light-chain 8 k was found at the cell center. Striking colocalization was observed with the major histocompatibility complex (MHC) class II molecules near the cell surface. Treatment with phytohemagglutinin, which induces T-lymphocyte activation, associated with MHC class II expression, increased the levels of myosin-V protein and mRNA for the three members of class V myosins. These data suggest that class V myosins might be involved in relevant functions in the immune response.     

Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites

Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.     

Changes in lipid fractions of blood during the treatment of hypertension with prazosin and trasicor

The paper deals with the study into the benefits of prazosin and trasicor used in arterial hypertension. Their effects on the blood lipid composition were evaluated. With prazosin, the steady antihypertensive effect was reached in 81.0%, whereas with trasicor, it was attained in 46%. When prazosin was given, total cholesterol and triglycerides were statistically significantly decreased by 6.8 and 14.8%, respectively, while high density lipoproteins was increased by 9.1%. When trasicor was administered, no changes were observed in the spectrum of serum lipids. Thus, prazosin is effective in correcting two major risk factors for coronary heart disease, namely arterial hypertension and hyperlipoproteinemia, thereby reducing a risk for coronary heart disease.     

α-terpineol reduces mechanical hypernociception and inflammatory response

α‐Terpineol (TPN), a volatile monoterpene alcohol, is relatively non‐toxic and one of the major components of the essential oils of various plant species. In this study, we tested for the antihypernociceptive activity of TPN (25, 50 or 100 mg/kg, i.p.) in mice using mechanical models of hypernociception induced by carrageenan (CG, 300 μg/paw) and the involvement of important mediators of its cascade signalling, such as tumour necrosis factor‐α (TNF‐α, 100 pg/paw), prostaglandin E₂ (PGE₂, 100 ng/paw) or dopamine (DA, 30 μg/paw). We also investigated the anti‐inflammatory effect of TPN on the model of carrageenan‐induced pleurisy and the LPS‐induced nitrite production in murine macrophages. Pre‐systemic treatment with TPN (25, 50 or 100 mg/kg, i.p.) inhibited the development of mechanical hypernociception induced by CG or TNF‐α. A similar effect was also observed upon PGE₂ and DA administration. In addition, TPN significantly inhibited the neutrophil influx in the pleurisy model. TPN (1, 10 and 100 μg/mL) also significantly reduced (p < 0.01) nitrite production in vitro. Our results provide information about the antinociceptive and anti‐inflammatory properties of TPN on mechanical hypernociception and suggest that this compound might be potentially interesting in the development of new clinically relevant drugs for the management of painful and/or inflammatory disease.     

Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action

The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K⁺ channels (K_ATP channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-l-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, K_ATP channel opening, and antioxidant properties.     

Clinical outcome of long-term renal transplant survivors: a nephrourologic approach

BACKGROUND: Long-term renal transplant survivors display high incidences of hypogonadism, neoplasms, erectile dysfunction, and metabolic syndrome. Although the urologist has a major role in the kidney transplantation surgery and treatment of the graft-related surgical complications, the follow-up of these patients is essentially focused on kidney function and the immunosuppressive regimen. We sought to evaluate the role of a nephrourologic follow-up for kidney transplant recipients. METHODS: We evaluated 27 male patients of mean age of 48.1 +/- 7.5 years and mean renal allograft follow-up of 12.3 +/- 4.3 years. The nephrourologic approach consisted of evaluation of the urinary system, prostate cancer screening, and assessment of voiding function, fertility, erectile dysfunction, hypogonadism, and metabolic syndrome. We also assessed quality of life. RESULTS: Major urologic findings were found in 18 (66.7%) patients. Four patients reported posttransplantation parenthood. The mean serum creatinine was 1.5 +/- 0.6 mg/dL and the calculated clearance, 72.6 +/- 27.4 mL/min/1.73 m(2). Regarding the voiding pattern, 92.6% of patients showed mild to moderate bladder outlet obstruction. Clinically significant increases in prostate volume were observed in 3.7% of patients. Mean serum total prostate-specific antigen was 1.6 +/- 1.5 ng/mL. Erectile dysfunction was displayed by 46.2% and hypogonadism by 74.1% of patients. Metabolic syndrome was diagnosed in 44.4% of patients, and quality of life was generally rated as good (4/5). CONCLUSION: Long-term renal transplantation survivors show high prevalences of treatable urologic diseases. Thus, we strongly recommend routine complete nephrourologic follow-up of this population.     

Small bowel bacterial overgrowth in strongyloidiasis.

Small bowel bacterial growth was studied in patients with strongyloidiasis, and the results were compared to controls. We concluded that in strongyloidiasis there is small bowel bacterial overgrowth, and so it should be considered in the pathogenesis of some of the gastrointestinal manifestations and complications of strongyloidiasis.