Sperm nitric oxide and motility: the effects of nitric oxide synthase stimulation and inhibition

Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes known as the nitric oxide synthases (NOS). We have recently shown a NOS similar to constitutive brain NOS (bNOS) and endothelial NOS (ecNOS) to be present in spermatozoa. The aim of this study is to investigate NO production by human spermatozoa and the effects of stimulation and inhibition of NOS. This was carried out using the Iso-NO, an isolated NO meter and sensor, which provides rapid, accurate and direct measurements of NO. Semen samples with normozoospermic and asthenozoospermic profiles were prepared using a direct swim-up technique. Basal concentrations of NO and stimulated NO production were measured after exposure to the calcium ionophore (A23187; 0.01-10 microM) a potent activator of constitutive NOS. NO production in human spermatozoa was significantly increased by the addition of A23187 30 seconds after stimulation. Furthermore, this response was greatly diminished by pre-incubating the samples with competitive inhibitors of L-arginine, the substrate for NOS, before treatment with calcium ionophore. In the presence of N(G)-nitro-L-arginine methyl ester (L- NAME), N(G)-nitro-L-arginine (L-NA) or N(G)-methyl-L-arginine (L-NMMA; all at 10 microM), NO production was inhibited with a rank order of potency L-NAME > L-NMMA > L-NA which is in accordance with the inhibition of an endothelial type of constitutive NOS.      

m-Trifluoromethyl-diphenyl diselenide attenuates pentylenetetrazole-induced seizures in mice by inhibiting GABA uptake in cerebral cortex slices

The present study investigated the anticonvulsive effect of the disubstituted diaryl diselenides diphenyl diselenide (PhSe)₂, m-trifluoromethyl-diphenyl diselenide (m-CF₃-C₆H₄Se)₂, p-chloro-diphenyl diselenide (p-Cl-C₆H₄Se)₂ and p-methoxyl-diphenyl diselenide (p-CH₃O-C₆H₄Se)₂ on a chemical model of seizure induced by pentylenetetrazol (PTZ) in mice. (PhSe)₂, (p-Cl--C₆H₄Se)₂ and (p-CH₃O-C₆H₄Se)₂ did not abolish seizures induced by PTZ in mice. (m-CF₃-C₆H₄Se)₂ at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the anticonvulsant effect of (m-CF₃-C₆H₄Se)₂, mice were submitted to different associations (all drugs in a sub-effective dose); aminooxyacetic acid hemihydrochloride (AOAA, a -aminobutyric acid (GABA)-T inhibitor), diazepam (a GABA_Areceptor agonist) or DL-2, 4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake) were pre-administered together with (m-CF₃-C₆H₄Se)₂.(m-CF₃-C₆H₄Se)₂ + DABA abolished seizures induced by PTZ in mice. (m-CF₃-C₆H₄Se)₂ administered alone or with PTZ decreased the levels of GABA uptake in cerebral cortex slices. The present study demonstrates that (m-CF₃-C₆H₄Se)₂ exerts anticonvulsant action by decreasing the levels of GABA uptake.     

Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation

Background Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. Objective To develop and characterize a murine model for food‐induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. Methods C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. Results Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of γδ⁺ and CD4⁺CD25⁺Foxp3⁺ cells in Peyer's patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA‐3, IL‐4, IL‐13 and TNF‐α in contrast to low IFN‐γ in the gut. Conclusion A murine model for food‐induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T‐helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food‐related enteropathies like food allergy, focusing on gut‐specific immune response.     

Yoga lifestyle intervention reduces blood pressure in HIV‐infected adults with cardiovascular disease risk factors*

Objective

People living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. We conducted a prospective, randomized, controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors, virological or immunological status, or quality of life (QOL) in HIV‐infected adults relative to standard of care treatment in a matched control group.

Methods

Sixty HIV‐infected adults with mild–moderate CVD risk were assigned to 20 weeks of supervised yoga practice or standard of care treatment. Baseline and week 20 measures were: 2‐h oral glucose tolerance test with insulin monitoring, body composition, fasting serum lipid/lipoprotein profile, resting blood pressures, CD4 T‐cell count and plasma HIV RNA, and the Medical Outcomes Study Short Form (SF)‐36 health‐related QOL inventory.

Results

Resting systolic and diastolic blood pressures improved more (P=0.04) in the yoga group (−5 ± 2 and −3 ± 1 mmHg, respectively) than in the standard of care group (+1 ± 2 and+2 ± 2 mmHg, respectively). However, there was no greater reduction in body weight, fat mass or proatherogenic lipids, or improvements in glucose tolerance or overall QOL after yoga. Immune and virological status was not adversely affected.

Conclusion

Among traditional lifestyle modifications, yoga is a low‐cost, simple to administer, nonpharmacological, popular behavioural intervention that can lower blood pressure in pre‐hypertensive HIV‐infected adults with mild–moderate CVD risk factors.

     

Compressive properties of commercially available polyurethane foams as mechanical models for osteoporotic human cancellous bone

Background  

Polyurethane (PU) foam is widely used as a model for cancellous bone. The higher density foams are used as standard biomechanical test materials, but none of the low density PU foams are universally accepted as models for osteoporotic (OP) bone. The aim of this study was to determine whether low density PU foam might be suitable for mimicking human OP cancellous bone.     

Primary care anticoagulant clinic management using computerized decision support and near patient International Normalized Ratio (INR) testing: routine data from a practice nurse-led clinic

BACKGROUND: Increasing indications for warfarin therapy has led to increased pressure on primary care to undertake therapeutic monitoring. OBJECTIVE: This study evaluates a primary care model of oral anticoagulation monitoring which utilises computerized decision support (CDSS) and near patient testing (NPT) within a practice nurse-led clinic. Whilst this has been shown to be a successful model under trial conditions, this paper reports the first data from a long-standing clinic, outside a formal study. METHOD: A prospective evaluation of therapeutic and clinical control of all patients taking warfarin within one inner city general practice. Data were collected via CDSS. RESULTS: 29 patients were seen in 208 appointments. The mean percentage of patients within therapeutic range was 72%. The costs to the practice were pound sterling 1751. The costs the practice would have incurred had these patients been seen at the hospital with the same frequency would have been pound sterling 2290. CONCLUSIONS: The use of CDSS and NPT for nurse-delivered oral anticoagulation monitoring could enable the safe transfer of the majority of patients from secondary to primary care. Funding mechanisms to support the transfer of costs will be essential for most practices, as will be the maintenance of adequate staff training and quality assurance.