Central administration of melanocortin agonist increased insulin sensitivity in diet-induced obese rats

AbstractIn this study, we examined the effects of intracerebroventricular administration of melanotan II (MTII), a melanocortin agonist, on insulin sensitivity in diet-induced obese (DIO) rats. Although MTII treatment significantly decreased food intake and body weight for 10 days, there was no significant difference in body weight between MTII and pair-fed groups. The insulin tolerance test showed that insulin sensitivity was significantly improved in the MTII group compared to the pair-fed group. Furthermore, MTII treatment increased the number of small-sized adipocytes in epididymal white adipose tissues, suggesting that MTII increased insulin sensitivity through action on the white adipose tissues in DIO rats

External iliac venous aneurysm in a pregnant woman: a case report

AbstractWe report an external iliac venous aneurysm in a young pregnant woman who was diagnosed incidentally by ultrasound scanning. The aneurysm was successfully treated by tangential aneurysmectomy and lateral venorrhaphy. Primary iliac venous aneurysm is a rare vascular abnormality. The clinical significance of the disease is unknown. However, embolism, rupture, and thrombosis might occur as they can occur with popliteal venous aneurysm. In fact, three of four reported patients with iliac venous aneurysms had a thromboembolic event. For those reasons, prophylactic treatment is indicated. This is the first patient with an iliac venous aneurysm to be diagnosed without complication

Hydrophilic statin suppresses vein graft intimal hyperplasia via endothelial cell-tropic Rho-kinase inhibition

BackgroundRecent studies suggest that statins can protect the vasculature in a manner that is independent of their lipid-lowering activity through inhibition of the small guanosine triphosphate-binding protein, Rho, and Rho-associated kinase. Little information is available on the inhibitory effect of statins on vein graft intimal hyperplasia, the main cause of late graft failure after bypass grafting. We therefore examined the effects of a hydrophilic statin on vein graft intimal hyperplasia in vivo and Rho-kinase activity in vitro.MethodsIn the first experiment, rabbits were randomized to a control group (n = 7) that was fed regular rabbit chow or to a pravastatin group (n = 7) that was fed regular rabbit chow supplemented with 10 mg/kg pravastatin sodium. The branches of the jugular vein were ligated and an approximately 3-cm segment of the jugular vein was taken for an autologous reversed-vein graft. The carotid artery was cut and replaced with the harvested autologous jugular vein. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. In the second experiment, human umbilical vein endothelial cells and vascular smooth muscle cells were cultured and then treated with 1 μmol/L and 30 μmol/L pravastatin for 24 hours and harvested. Immunoblotting was performed on the resulting precipitates. Quantitative evaluation of phosphorylated myosin binding subunit and endothelial nitric oxide synthase was performed by densitometric analysis.ResultsWe demonstrated that oral administration of the hydrophilic statin pravastatin to normocholesterolemic rabbits inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (pravastatin group, 39.5 ± 3.5 μm vs control group, 64.0 ± 7.1 μm; n = 7; P < .05) and suppressed cell proliferation and apoptosis in the neointima 2 weeks after implantation. In addition, we found that pravastatin inhibited Rho-kinase activity and accelerated endothelial nitric oxide synthase expression in human umbilical vein endothelial cells but did not inhibit Rho-kinase activity in vascular smooth muscle cells.ConclusionsThese novel findings clearly demonstrate that a hydrophilic statin can suppress intimal hyperplasia of the vein graft in vivo and also show endothelial cell-tropic inhibition of Rho-kinase in vitro. Furthermore, these results strongly support the clinical use of hydrophilic statins to prevent intimal hyperplasia of the vein graft after bypass grafting.Clinical RelevanceLate graft failure caused by neointimal hyperplasia limits the efficacy of vein grafting. Various treatments were examined to reduce neointimal hyperplasia, but a standard clinical treatment has not yet been established. We report here the inhibitory effect of pravastatin on the development of vein graft intimal hyperplasia. In addition, we demonstrate that pravastatin showed endothelial cell-tropic benefits through both the inhibition of Rho-kinase activity and acceleration of eNOS expression in vitro. Because the clinical benefits and safety of pravastatin have been established to a certain extent through long-term clinical usage, pravastatin may soon become standard treatment after vein bypass grafting

Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons

Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER

A BAC-Based Integrated Linkage Map of the Silkworm \u3cem\u3eBombyx mori\u3c/em\u3e

Background: In 2004, draft sequences of the model lepidopteran Bombyx mori were reported using whole-genome shotgun sequencing. Because of relatively shallow genome coverage, the silkworm genome remains fragmented, hampering annotation and comparative genome studies. For a more complete genome analysis, we developed extended scaffolds combining physical maps with improved genetic maps. Results: We mapped 1,755 single nucleotide polymorphism (SNP) markers from bacterial artificial chromosome (BAC) end sequences onto 28 linkage groups using a recombining male backcross population, yielding an average inter-SNP distance of 0.81 cM (about 270 kilobases). We constructed 6,221 contigs by fingerprinting clones from three BAC libraries digested with different restriction enzymes, and assigned a total of 724 single copy genes to them by BLAST (basic local alignment search tool) search of the BAC end sequences and high-density BAC filter hybridization using expressed sequence tags as probes. We assigned 964 additional expressed sequence tags to linkage groups by restriction fragment length polymorphism analysis of a nonrecombining female backcross population. Altogether, 361.1 megabases of BAC contigs and singletons were integrated with a map containing 1,688 independent genes. A test of synteny using Oxford grid analysis with more than 500 silkworm genes revealed six versus 20 silkworm linkage groups containing eight or more orthologs of Apis versus Tribolium, respectively. Conclusion: The integrated map contains approximately 10% of predicted silkworm genes and has an estimated 76% genome coverage by BACs. This provides a new resource for improved assembly of whole-genome shotgun data, gene annotation and positional cloning, and will serve as a platform for comparative genomics and gene discovery in Lepidoptera and other insects

Frequency analyses of CSF flow on cine MRI in normal pressure hydrocephalus

Abstract Our objective was to clarify intracranial cerebrospinal fluid (CSF) flow dynamics in normalpressure hydrocephalus (NPH). Frequency analyses of CSF flow measured with phase-contrast cine MRI were performed. The CSF flow spectra in the aqueduct were determined in patients (n=51) with NPH, brain atrophy or asymptomatic ventricular dilation (VD), and in healthy volunteers (control group; n=25). The changes in CSF flow spectra were also analyzed after intravenous injection of acetazolamide. Moreover, a phase transfer function (PTF) calculated from the spectra of the driving vascular pulsation and CSF flow in the aqueduct were assessed. These values were compared with the pressure volume response (PVR). The amplitude in the NPH group was significantly larger than that in the VD or control group because of a decrease in compliance. The phase in the NPH group was significantly different from that in either the VD or the control group, but no difference was found between the VD and control groups. The amplitude increased in all groups after acetazolamide injection. The PTF in the NPH group was significantly larger than in the control group, and a positive correlation was noted between PTF and PVR. Frequency analyses of CSF flow measured by cine MRI make it possible to noninvasively obtain a more detailed picture of the pathophysiology of NPH