Cornichons modify channel properties of recombinant and glial AMPA receptors

Ionotropic glutamate receptors, which underlie a majority of excitatory synaptic transmission in the CNS, associate with transmembrane proteins that modify their intracellular trafficking and channel gating. Significant advances have been made in our understanding of AMPA-type glutamate receptor (AMPAR) regulation by transmembrane AMPAR regulatory proteins. Less is known about the functional influence of cornichons-unrelated AMPAR-interacting proteins, identified by proteomic analysis. Here we confirm that cornichon homologs 2 and 3 (CNIH-2 and CNIH-3), but not CNIH-1, slow the deactivation and desensitization of both GluA2-containing calcium-impermeable and GluA2-lacking calcium-permeable (CP) AMPARs expressed in tsA201 cells. CNIH-2 and -3 also enhanced the glutamate sensitivity, single-channel conductance, and calcium permeability of CP-AMPARs while decreasing their block by intracellular polyamines. We examined the potential effects of CNIHs on native AMPARs by recording from rat optic nerve oligodendrocyte precursor cells (OPCs), known to express a significant population of CP-AMPARs. These glial cells exhibited surface labeling with an anti-CNIH-2/3 antibody. Two features of their AMPAR-mediated currents-the relative efficacy of the partial agonist kainate (I(KA)/I(Glu) ratio 0.4) and a greater than fivefold potentiation of kainate responses by cyclothiazide-suggest AMPAR association with CNIHs. Additionally, overexpression of CNIH-3 in OPCs markedly slowed AMPAR desensitization. Together, our experiments support the view that CNIHs are capable of altering key properties of AMPARs and suggest that they may do so in glia.     

Role of vagal activation in postprandial glucose metabolism after gastric bypass in individuals with and without hypoglycaemia

Patients who have undergone gastric bypass surgery (GB) have enhanced postprandial hyperinsulinaemia and a greater incretin effect is apparent. In the present study, we sought to determine the effect of vagal activation, a neural component of the enteroinsular axis, on postprandial glucose metabolism in patients with and without hypoglycaemia after GB. Seven patients with documented post-GB hypoglycaemia, seven asymptomatic patients without hypoglycaemia post-GB, and 10 weight-matched non-surgical controls with normal glucose tolerance were recruited. Blood glucose, and islet hormone and incretin secretion were compared during mixed meal tolerance tests (MMTs) with and without prior sham-feeding on two separate days. Sham feeding preceding the MMT caused a more rapid increase in prandial blood glucose levels but lowered overall glycaemia in all three groups (P < 0.05). Sham feeding had a similar effect to increase early (P < 0.05), but not overall, meal-induced insulin secretion in the three groups. Prandial glucagon concentrations were significantly greater in the GB groups, and sham feeding accentuated this response (P < 0.05). The effect of vagal activation on prandial glucose and islet-cell function is preserved in patients who have undergone GB, in those both with and without hypoglycaemia.     

High fat diet deteriorates the memory impairment induced by arsenic in mice: a sub chronic in vivo study

Metabolic Brain Disease - Both arsenic (As) and obesity are associated with brain disorders. However, long term studies to evaluate their concomitant adverse effects on the brain functions are...     

Association between the arrested decline in cardiovascular disease and health and social-care costs: a modelling study

BackgroundDementia and cardiovascular disease generate enormous health and social-care costs and have shared risk factors. Following decades of cardiovascular disease mortality declines in England, improvements slowed after 2011. We investigated the potential economic implications of this slowdown.MethodsWe used the IMPACT better aging model—an open-cohort, stochastic Markov model. We synthesised trends in cardiovascular disease incidence and mortality, dementia, and disability (defined as reported diagnosis, functional impairment, or measured cognitive impairment) from the English Longitudinal Study of Ageing (ELSA) and Office for National Statistics data. We projected trends for adults aged 35–100 years in England and Wales from 2019–29. We modelled undiscounted health and social-care costs (primary outcome), and quality-adjusted life-years (QALYs) under the following two scenarios: age-specific cardiovascular disease incidence continues to decline, recommencing previous downward trends (scenario one); or age-specific cardiovascular disease incidence plateaus after 2006, continuing recent trends, assuming changes in mortality reflect incidence 5 years before (scenario two). We linked 85% of ELSA participants to their Hospital Episode Statistics (HES) data, which were costed and calibrated to national estimates. Age-related social-care costs were estimated by use of reported contact hours from ELSA combined with standard reference costs. Standard catalogues were used for QALY weights.FindingsIn scenario one, changes in population size and health were projected to increase health-care costs by around 12% between 2019 and 2029, from £93·0 billion to £104·6 billion per year (in 2019 prices). Social-care costs were projected to increase by around 27%, from £8·0 billion to £10·2 billion per year. In scenario two, health-care costs were projected to increase by around 15%, from £95·3 billion to £109·6 billion, and social-care costs by around 30%, from £8·2 billion to £10·7 billion, between 2019 and 2029. The overall net monetary cost of this slowdown in cardiovascular disease decline was £17·5 billion per year (made up of 200 000 QALYs and £5·5 billion in health and social-care costs).InterpretationWe predict social-care costs will grow twice as fast as health-care costs over the next decade, even if cardiovascular disease occurrence continues to decline. Understanding the scale of the future health and social-care funding challenge might support proactive policy making. This study represents the first time ELSA data have been linked with HES data. However, we did not assess changes in health and social-care efficiency over time or the effect of spending on improving health.FundingBritish Heart Foundation     

Prevalence of Chronic Diseases and Occupational Injuries and their Influence on the Health-Related Quality of Life Among Farmers Working in Small-Farm Enterprises

Objectives: This study aimed to determine the prevalence of chronic diseases and occupational accidents and injuries, and to examine their association with the quality of life among a sample of Iranian farmers.

Methods: A cross-sectional study was conducted among 736 male farmers. Data on the prevalence of chronic diseases and occupational accidents and injuries was collected using an author-developed questionnaire, and the SF-36 questionnaire was used to obtain information on quality of life.

Results: The prevalence of chronic diseases was 96.1%. Musculoskeletal diseases (MSDs), eye diseases and neurology diseases were the most prevalent diseases. Almost half of the farmers (42.7%) had experienced an occupational accident during the last 12 months and cuts and fractures accounted for the most frequent injuries. Sick leave was reported by 28.2% of the farmers and from those with history of accidents, 21.4% were hospitalized. A significant association was found between age and education level with quality of life. Most of the chronic diseases showed a significant and inverse association with quality of life, however, the strongest association was found for MSDs and mental disorders. Furthermore, the most important injury associated with quality of life was cuts and fractures.

Conclusions: Based on the results, MSDs, mental disorders, and cut and fractures were the main determinants of the farmers’ quality of life. Hence, a better quality of life among farmers is especially dependent on eliminating ergonomics risk factors leading to developing musculoskeletal disorders, improving psychosocial work climate, and promoting occupational and personal safety culture.     

Platelet-rich plasma improves impaired glucose hemostasis,disrupted insulin secretion,and pancreatic oxidative stress in streptozotocin-induced diabetic rat

Abstract

Our study aimed to investigate the effects of platelet-rich plasma (PRP) on impaired glucose homeostasis, disrupted islet insulin secretion, and pancreatic oxidative status in streptozotocin (STZ)-diabetic rats. A total of 64 Sprague-Dawley male were randomized to four groups including controls, diabetes, control-PRP, and diabetes-PRP. The rats received the PRP (0.5?ml/kg, SC injection) twice weekly for 4 weeks. Plasma glucose and insulin levels, pancreatic oxidative stress markers and islet insulin secretion and content were measured. Compared with the control group, in the diabetic group, increased plasma glucose and malondialdehyde (MDA) levels and decreased plasma insulin level, islet insulin secretion, pancreatic superoxide dismutase (SOD), and catalase activities were observed. PRP treatment significantly reduced plasma glucose and MDA levels and enhanced plasma insulin, antioxidant enzyme activity, islet insulin secretion, and content in the diabetic rats. These findings showed that PRP can improve pancreatic islet insulin secretion, pancreatic oxidative stress and regulate plasma insulin and glucose levels in diabetic rats.     

Oestrogen promotes coronary angiogenesis even under normoxic conditions

Angiogenic therapy is one of the new treatments of ischaemic heart disease. Oestrogen has angiogenic properties under hypoxic condition, and if oestrogen also induces angiogenesis under normoxic condition, it could be used in combination with other angiogenic therapies in the treatment of ischaemic heart disease. In this study, we evaluated the angiogenic effect of high-dose oestrogen treatment in normoxic rat heart tissue. Fifty-two ovariectomized rats were randomized in oestrogen-treated and control groups. 17beta-oestradiol (1 mg/week) and normal saline (1 mg/week) were administered intramuscularly in the treatment and control groups for 2 months. After that, coronary capillary density and coronary vessel permeability were measured. The serum vascular endothelial growth factor (VEGF) level was also measured before and after the treatment. The results indicate that coronary capillary density (number of capillary per square millimetre) and coronary vessel permeability (fluorescence intensity) were significantly higher in the oestrogen-treated group than in the control group (628 +/- 26 per mm(2) versus 540 +/- 26 per mm(2); P < 0.05 and 207 +/- 10 versus 147 +/- 19 per gram tissue; P < 0.05). Oestrogen treatment increased serum VEGF level in the oestrogen-treated group compared to the control group (52 +/- 3 versus 33 +/- 6 pg/ml; P < 0.05), but interestingly VEGF was also increased in the control group after placebo treatment. It seems that high-dose oestrogen administration has angiogenic properties even in normoxic conditions. These angiogenic properties may result from oestrogen's direct effect on VEGF or other mechanisms, such as endothelial progenitor cell mobilization. Because of the broad effect of oestrogen on angiogenic growth factors and endothelial cells, more studies are required to clarify angiogenic properties of high-dose oestrogen.     

The Effect of Manual Acupressure (Point UB32) on Pain Associated with Intramuscular Injections of Magnesium Sulfate

The aim of this study was determining the effect of acupressure on the severity of pain associated with intramuscular injections of magnesium sulfate administered by the Z-track technique in patients with eclampsia and preeclampsia. Forty-eight patients participated in this single-group clinical trial, which was conducted in three stages. For each patient, three intramuscular injections were administered by the Z-track technique. The first injection was administered by the conventional method. The second injection at a sham control point and the third injection using acupressure (BL32) were administered. Pain severity was measured on a visual analogue scale. The mean pain intensity was 7.22 in the first, 4.75 in the second and 1.94 in the third injections (p < 0.001). The results of the study showed that acupressure at the BL32 point before intramuscular injection of magnesium sulfate significantly reduced the injection-related pain.