The fixed herbal drug composition "Saikokaryukotsuboreito" prevents bone loss with an association of serum IL-6 reductions in ovariectomized mice model.

PURPOSE: Saikokaryukotsuboreito (SRB) is a traditional Japanese herbal medicine that has been used to treat hyperlipidemia. As some studies have shown that lipid-lowering drugs reduce osteoporosis, we investigated the effect of SRB on bone metabolism in the postmenopausal period using an ovariectomized (OVX) murine model. MATERIAL AND METHODS: Fifteen aged 9 weeks female mice were divided into three groups (n=5 each). The OVX group and SRB group underwent bilateral ovariectomy, after which the OVX group was fed a normal diet and the SRB group fed a normal diet containing 2% SRB. The sham group underwent sham surgery and was then fed a normal diet. Eight weeks after surgery, all mice were sacrificed, and bone volume, bone histomorphometric parameters, and bone-associated phenotype were compared among the groups. RESULTS: Compared with the OVX group, the SRB group showed suppression of bone volume loss at the tibia (SRB group: 12.7+/-0.7%, OVX group: 9.8+/-0.4%; p=0.005, ANOVA) and lumbar spine (SRB group: 15.1+/-0.9%, OVX group: 11.3+/-0.1%; p=0.031, ANOVA). A significant decrease in eroded surface was also observed in SRB-treated ovariectomized mice compared with the OVX group (p=0.022, ANOVA). We also found that serum levels of interleukin (IL)-6, a primary mediator of bone resorption, in the SRB group were significantly lower than in the OVX group (SRB: 52.5+/-6.8pg/ml; OVX: 138.0+/-23.1pg/ml; p=0.011, ANOVA). However, unexpectedly, SRB did not affect estradiol and total cholesterol in ovariectomized mice. CONCLUSION: SRB can prevent loss of bone volume and suppress serum IL-6 levels in this postmenopausal model and is a promising candidate for treatment of postmenopausal osteoporosis.

Deletions involving both KCNQ2 and CHRNA4 present with benign familial neonatal seizures.

OBJECTIVE: Mutations of the genes encoding subunits of potassium voltage-gated channel, KCNQ2 and KCNQ3, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine the frequency of microchromosomal deletions of KCNQ2 or KCNQ3 associated with BFNS. METHODS: The study subjects were patients with BFNS (n = 22). Microdeletions were sought by multiplex ligation-dependent probe amplification and then confirmed by fluorescence in situ hybridization and characterized by array-based comparative genomic hybridization. RESULTS: Heterozygous multiple exonic deletions of KCNQ2 were identified in 4 of 22 patients with BFNS. Concomitant deletions of adjacent genes, including nicotinic cholinergic receptor alpha4 (CHRNA4), were detected in 2 of the 4 cases. The clinical courses of patients with deletions of both KCNQ2 and CHRNA4 were those of typical BFNS, and none presented with the phenotype of autosomal dominant nocturnal frontal lobe epilepsy, some of which are caused by mutations of CHRNA4. CONCLUSIONS: Our findings indicate that the clinical courses of patients with deletions of both KCNQ2 and CHRNA4 are indistinguishable from those of patients with deletions of KCNQ2 only.

Pathogenic role of angiotensin II and oxidised LDL in obstructive sleep apnoea.

A sustained elevation of oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) might help to explain their increased risk for cardiovascular diseases. We tested the hypothesis that the values of oxidative stress are increased in otherwise healthy subjects with OSAS when compared with closely matched control subjects. We performed a prospective study of 38 subjects who did not have OSAS and 37 patients with OSAS. Plasma indices of angiotensin (Ang) II, vascular endothelial growth factor (VEGF), oxidised low-density lipoprotein (oxLDL), and circulating endothelial precursor cells (CEPs) were measured in OSAS patients and in matched controls. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups and co-cultured with endothelial cells to examine the effects on tube formation. The OSAS group showed increased levels of Ang II, VEGF, oxLDL and CEPs, which were decreased after nasal continuous positive airway pressure (nCPAP) treatment. In vitro, PBMCs from the OSAS group induced tube formation. Ang II, oxLDL, and Ang II-stimulated PBMCs induced lectin-like oxLDL receptor (LOX-1) expression and VEGF receptor-2 activation on endothelial cells, respectively. These observations suggest an important role of Ang II and oxLDL-mediated LOX-1 upregulation in endothelial cell injury in patients with OSAS.

Helicobacter pylori infection and chronic atrophic gastritis among Japanese blood donors: a cross-sectional study.

To evaluate an association between Helicobacter pylori (H. pylori) infection and chronic atrophic gastritis (CAG), an established precursor of gastric cancer, we performed a cross-sectional study using IgG antibody against H. pylori and pepsinogens of blood donors in four prefectures in Japan. Although a geographic correlation between the age-adjusted prevalence rates for H. pylori infection and those for CAG was not seen, the age-adjusted odds ratios (OR) of H. pylori infection for CAG were high in each area (around five for men and from four to 12.6 for women). The association between them weakened with advancing age; the ORs in the youngest age group (16-29 yrs) and in the oldest age group (50-64 yrs) were 12.5 and 2.8 for men, and 11.5 and 5.2 for women, respectively. These findings suggest that H. pylori infection is strongly associated with CAG, while there are some other factors interacting in the development of CAG. A prospective cohort study in which CAG and H. pylori infection are taken into account will be necessary to assess the risks of gastric cancer.