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.      

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.      

Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220- expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.     

Epstein-Barr virus and familial Hodgkin's disease

Several studies suggest that the Epstein-Barr virus (EBV) is etiologically linked to Hodgkin's disease (HD). This study was undertaken to examine the role of EBV in familial HD (FHD). Among 60 FHD patients from 27 families with two or more cases per family, we tested available paraffinized tumor tissues from 46 cases by in situ hybridization for EBV-encoded RNA (EBER1) expression. Thirteen of 46 FHD patients (28%) had EBER1 expressed in the Reed-Sternberg cells. Concordance rate of EBV positivity was evaluated among 34 first-degree related pairs from 17 families for which both cases had available paraffinized tumor tissues. Only two of 17 pairs were concordant for EBER1 positivity. There was no excess of positive concordance (P = .18). Serologically, FHD patients had higher geometric mean antibody titers (GMTs) to the viral capsid antigen (VCA) and early antigen D (EA- D). There was no difference in seroprevalence between patients and control groups, nor was there concordance in elevated serology among 15 pairs of first-degree related FHD cases. Young adult unaffected family members (UFM) may not react to EBV in the same way as the general population as evidenced by the lower titer of VCA, although not statistically significant, and significantly lower titers of EA-D, compared with age-matched controls. While EBV might have some role in a subset of HD, lack of concordance of EBER1 expression and EBV serology among the FHD cases in the same family suggest that EBV does not play an important role in FHD.