Triphenyltin and intra-axonal Ca2+ mobilization

Triphenyltin (TPT) is an organotin compound causing environmental hazard to many wild creatures. Our previous findings show that TPT increases of the frequency of spontaneous glycinergic inhibitory postsynaptic currents (sIPSCs) in rat spinal neurons without changing the amplitude and 1/e decay time. In our study, the effects of 2-aminoethoxydiphenyl borate (2-APB), dantrolene sodium, and thapsigargin on sIPSC frequency were examined to reveal the contribution of intra-axonal Ca2+ mobilization by adding TPT. 2-APB considerably attenuated the TPT-induced facilitation of sIPSC frequency while dantrolene almost completely masked the TPT effects, suggesting that the TPT-induced synaptic facilitation results from the activation of both IP3 and ryanodine receptors on endoplasmic reticulum (ER) membrane, though inositol triphosphate (IP3) receptor is less sensitive to TPT. Thapsigargin itself significantly increased the sIPSC frequency without affecting the current amplitude and decay time. Successive addition of TPT could not further increase the sIPSC frequency in the presence of thapsigargin, indicating that thapsigargin completely masked the facilitatory action of TPT. Results suggest that TPT activates the IP3 and ryanodine receptors while TPT inhibits the Ca2+-pump of ER membranes, resulting in the elevation of intra-axonal Ca2+ levels, leading to the increase of spontaneous glycine release from synaptic vesicles

Charge-Order Pattern of the Low-Temperature Phase of NaV2O5 Uniquely Determined by Resonant X-Ray Scattering from Monoclinic Single Domain

The present resonant x-ray scattering from each of monoclinically-split single domains of NaV2O5 has critically enhanced contrast between V4+ and V5+ ions strong enough to lead to unambiguous conclusion of the charge-order pattern of its low-temperature phase below Tc = 35 K. The zig-zag type charge-order patterns in the $ab$-plane previously confirmed have four kinds of configurations (A, A', B and B') and the stacking sequence along the c-axis is determined as the AAA'A' type by comparison with model calculations. By assigning the A and A' configurations to Ising spins, one can reasonably understand the previously discovered "devil's staircase"-type behavior with respect to the modulation of the layer-stacking sequences at high pressures and low temperatures, which very well resembles the global phase diagram theoretically predicted by the ANNNI model.Comment: 4 pages, 3 figure

Triphenyltin and glycinergic transmission

Glycine is a fast inhibitory transmitter like γ-aminobutyric acid in the mammalian spinal cord and brainstem, and it is involved in motor reflex, nociception, and neuronal development. Triphenyltin (TPT) is an organometallic compound causing environmental hazard to many wild creatures. Our previous findings show that TPT ultimately induces a drain and/or exhaustion of glutamate in excitatory presynaptic nerve terminals, resulted in blockage of neurotransmission as well as methylmercury. Therefore, we have investigated the neurotoxic mechanism how TPT modulates inhibitory glycinergic transmission in the synaptic bouton preparation of rat isolated spinal neurons using a patch clamp technique. TPT at environmentally relevant concentrations (3–300 nM) significantly increased the number of frequency of glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC and mIPSC) without affecting the current amplitude and decay time. The TPT effects were also observed in external Ca2+-free solution containing tetrodotoxin (TTX) but removed in Ca2+-free solution with both TTX and BAPTA-AM (Ca2+ chelator). On the other hand, the amplitude of glycinergic evoked inhibitory postsynaptic currents (eIPSCs) increased with decreasing failure rate (Rf) and paired pulse ratio (PPR) in the presence of 300 nM TPT. At a high concentration (1 μM), TPT completely blocked eIPSCs after a transient facilitation. Overall, these results suggest that TPT directly acts transmitter-releasing machinery in glycinergic nerve terminals. Effects of TPT on the nerve terminals releasing fast transmitters were greater in the order of glycinergic > glutamatergic > GABAergic ones. Thus, TPT is supposed to cause a strong synaptic modulations on glycinergic neurotransmission in wild creatures

Study of Minimal String Unification in Z8Z_8 Orbifold Models

We study the construction of the minimal supersymmetric standard model from the $Z_8$ orbifold models. We use a target-space duality anomaly cancellation and a unification of gauge couplings as constraints. It is shown that some models obtained through a systematical search realize the unification of SU(3) and SU(2) coupling constants.Comment: 11 pages, KANAZAWA-93-08, LaTeX fil

HIV prevalence and factors associated with HIV infection among male injection drug users under 30: a cross-sectional study in Long An, Vietnam

BACKGROUND: Sufficient targeted HIV prevention activities aiming at reducing HIV transmission within and from an extremely marginalized population of injection drug users (IDUs) must urgently and efficiently be implemented in Vietnam. This study was conducted to facilitate the development of such activities by describing transmission risks of young IDUs and evaluating factors in association with HIV infection. METHODS: Thirty clusters were selected from 29 hotspot communes in Long An province by probability proportional to size (PPS) sampling method. The snowball technique was used for enrolling participants in each cluster. The cross-sectional association of factors obtained during direct structured interviews to 248 male IDUs aged 14 to 29 years old and with their HIV test results were examined. RESULTS: The HIV prevalence among the studied IDUs was 32%. Age range of 18–20 years old, low educational level, sharing injection equipment or injection drug use in the other cities were independently associated with HIV serostatus in the multivariate analysis. Sexual behaviors did not differ between HIV-positive and -negative IDUs. Among HIV seropositive IDUs who had sexual contact with primary (n = 37), casual (n = 6), and commercial (n = 15) partners, only 5.4% (n = 2), 33.3% (n = 2), and 46.7% (n = 7), respectively, responded that they had used condoms every time. CONCLUSION: About one-third of young IDUs aged less than 30 identified in the hotspot communes in Long An, Vietnam was found to be infected with HIV, and socio-demographic and injection-related factors might account for the infection risk. Prevailing risky sexual behavior of this extremely marginalized population highlights the need to reduce their high transmission risks as a public health priority

Expression of vascular endothelial growth factor in patients with acute myocardial infarction

AbstractOBJECTIVEThe purpose of this study was to investigate the clinical significance of vascular endothelial growth factor (VEGF) in acute myocardial infarction (AMI). We also examined the involvement of peripheral blood mononuclear cells (PBMCs), which are a possible source of VEGF in AMI.BACKGROUNDVEGF is a potent endothelial cell–specific mitogen and could affect the outcome of AMI.METHODSThirty patients with AMI were used for this study. Serum and PBMCs were isolated from peripheral blood on days 1, 7, 14 and 21 after the onset of AMI. PBMCs were cultured at a density of 5 × 106cells/ml for 24 h. VEGF levels in serum and the culture media were measured by enzyme-linked immunosorbent assay using a specific anti-human VEGF antibody.RESULTSSerum VEGF levels elevated gradually after the onset of AMI and reached a peak on day 14. VEGF levels in the culture medium of PBMCs after incubation for 24 h (PBMC-VEGF) were maximally elevated 7 days after the onset. Maximum serum VEGF levels showed significant positive correlations with maximum creatine phosphokinase (CPK) levels (r = +0.70, p < 0.001), but maximum PBMC-VEGF levels did not correlate with maximum CPK levels. Patients showing improvement in left ventricular systolic function during the course of AMI showed significantly higher PBMC-VEGF levels than patients without improvement.CONCLUSIONSThe extent of myocardial damage contributes to the elevation of serum VEGF levels in AMI. VEGF produced by PBMCs may play an important role in the improvement of left ventricular function by promoting angiogenesis and reendothelialization after AMI

Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells

Vascular endothelial growth factor receptor 2 (VEGFR2) transmits signals of crucial importance to vasculogenesis, including proliferation, migration, and differentiation of vascular progenitor cells. Embryonic stem cell–derived VEGFR2+ mesodermal cells differentiate into mural lineage in the presence of platelet derived growth factor (PDGF)–BB or serum but into endothelial lineage in response to VEGF-A. We found that inhibition of H-Ras function by a farnesyltransferase inhibitor or a knockdown technique results in selective suppression of VEGF-A–induced endothelial specification. Experiments with ex vivo whole-embryo culture as well as analysis of H-ras−/− mice also supported this conclusion. Furthermore, expression of a constitutively active H-Ras[G12V] in VEGFR2+ progenitor cells resulted in endothelial differentiation through the extracellular signal-related kinase (Erk) pathway. Both VEGF-A and PDGF-BB activated Ras in VEGFR2+ progenitor cells 5 min after treatment. However, VEGF-A, but not PDGF-BB, activated Ras 6–9 h after treatment, preceding the induction of endothelial markers. VEGF-A thus activates temporally distinct Ras–Erk signaling to direct endothelial specification of VEGFR2+ vascular progenitor cells

Cable externalization at the proximal portion of the superior vena cava coil in Riata implantable cardioverter defibrillator leads

Many Riata (St. Jude Medical, St. Paul, MN, USA) implantable cardioverter defibrillator (ICD) leads have reportedly developed cable externalization. The most likely cause of cable externalization is insulation abrasion, which often occurs at the can or between the right ventricular coil and superior vena cava (SVC) coil. We report a rare case of an adult male whose ICD lead cable was externalized at the proximal portion of the SVC coil. This lead became fixed to the wall at the subclavian vein and SVC and became bent between these adhesions. Furthermore, the motion of this lead was affected by pulsation of the aortic arch. The ICD lead might develop inside-out abrasion due to mechanical stress evoked by pulsation of the aortic arch at this site.. © 2016 Japanese College of Cardiology.Embargo Period 12 month

Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus

Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n=133, 115 men and 18 women; age 64.7±11.5 years; HbA1c 8.1±1.6%). Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2±22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r=−0.450, P<0.01), triglyceride (r=0.445, P<0.01), and high sensitive C-reactive protein (r=0.316, P<0.01) but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (β=−0.411, P<0.01) and high sensitive C-reactive protein (β=0.193, P<0.05). Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus