Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia The effects of halothane and dantrolene

AbstractCalcium-induced calcium release and halothane-induced calcium release from pig sarcoplasmic reticulum (SR) were studied. The SR prepared from pig susceptible to malignant hyperthermia (MH) was shown to release calcium at a much lower level of calcium content than in normal pig SR. The concentration above which halothane can release calcium is 40 μM for both MH-SR and normal SR, although the latter required a high calcium content to demonstrate the calcium release. Dantrolene was shown to inhibit the halothane-induced calcium release. Results suggests that SR plays an importnat role in pathogenesis of MH

Effects of cortisol and dexamethasone on insulin signalling pathways in skeletal muscle of the ovine fetus during late gestation.

Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling proteins in skeletal muscle of fetal sheep during late gestation. Experimental manipulation of fetal plasma glucocorticoid concentration was achieved by fetal cortisol infusion and maternal dexamethasone treatment. Cortisol infusion significantly increased muscle protein levels of Akt2 and phosphorylated Akt at Ser473, and decreased protein levels of phosphorylated forms of mTOR at Ser2448 and S6K at Thr389. Muscle GLUT4 protein expression was significantly higher in fetuses whose mothers were treated with dexamethasone compared to those treated with saline. There were no significant effects of glucocorticoid exposure on muscle protein abundance of IR-β, IGF-1R, PKCζ, Akt1, calpastatin or muscle glycogen content. The present study demonstrated that components of the insulin signalling pathway in skeletal muscle of the ovine fetus are influenced differentially by naturally occurring and synthetic glucocorticoids. These findings may provide a mechanism by which elevated concentrations of endogenous glucocorticoids retard fetal growth

The Impact of Natural Ventilation During Winter on Thermal Comfort: A systematic literature review

The COVID-19 pandemic has highlighted the importance of ventilation as a transmission mitigation strategy. However, there is a widely-held concern that a drop in outdoor temperatures during wintertime may impact thermal comfort in the context of naturally ventilated classrooms. This is a concern which has not been widely investigated by peer-reviewed empirical studies. The aim of this paper is to review the available literature on the impact of natural ventilation during winter on thermal comfort. Using the replicable search processes of a systematic literature review adopted from medical research practice, 142 articles were retrieved from four search databases (Science direct, Scopus, PubMed, and Google Scholar). Analysis of these 142 articles revealed that most studies have particularly focused on the assessment of ventilation conditions, especially in non-naturally ventilated spaces, and that there were only 5 articles that empirically investigated the impact of natural ventilation on thermal comfort during winter in sufficient detail. This shows a significant gap within the body of literature, meaning that the findings from this study can only be treated as tentative, with further research required

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist

Classroom Ventilation: The Effectiveness of Preheating and Refresh Breaks: An analysis of 169 spaces at 43 schools across New Zealand

The COVID-19 pandemic has highlighted the importance of ventilation as a transmission mitigation strategy. However, there was a widely held concern that a drop in outdoor temperatures during winter may impact thermal comfort in the context of naturally ventilated classrooms. This concern has not been widely investigated by peer-reviewed empirical studies (Sutherland et al., 2022b). The aim of the Ministry’s ventilation monitoring initiative was to assess ventilation performance and thermal comfort by continuously measuring indoor CO2 levels, air temperature, and relative humidity in classrooms during winter, without obstructing teaching activities. A total of 43 schools, which represent a broad mix of property attributes and located across the 6 Climate Zones in New Zealand, were selected for the monitoring initiative. The CO2 monitors were deployed in about 4-6 pre-selected and representative spaces in each school. Data was retrieved from 213 spaces; of these, 44 spaces were excluded, because the initiative concentrated on teaching environments (classrooms) and those spaces were categorised as non-teaching environments (e.g., staff rooms, meeting rooms, etc.). From the 213 spaces, the data from 169 teaching spaces retrieved for the period 23 May to 26 August 2022 were analysed to ascertain the impacts of inferred human behaviours considered to be able to improve natural ventilation and detected from features of CO2 and temperature data. This analysis does not (and did not intend to) corroborate independent observation of behaviours

Profile of Lipid and Protein Autacoids in Diabetic Vitreous Correlates With the Progression of Diabetic Retinopathy

OBJECTIVE: This study was aimed at obtaining a profile of lipids and proteins with a paracrine function in normal and diabetic vitreous and exploring whether the profile correlates with retinal pathology. RESEARCH DESIGN AND METHODS: Vitreous was recovered from 47 individuals undergoing vitreoretinal surgery: 16 had nonproliferative diabetic retinopathy (NPDR), 15 had proliferative diabetic retinopathy, 7 had retinal detachments, and 9 had epiretinal membranes. Protein and lipid autacoid profiles were determined by protein arrays and mass spectrometry-based lipidomics. RESULTS: Vitreous lipids included lipoxygenase (LO)- and cytochrome P450 epoxygenase (CYP)-derived eicosanoids. The most prominent LO-derived eicosanoid was 5-hydroxyeicosate traenoic acid (HETE), which demonstrated a diabetes-specific increase (P = 0.027) with the highest increase in NPDR vitreous. Vitreous also contained CYP-derived epoxyeicosatrienoic acids; their levels were higher in nondiabetic than diabetic vitreous (P < 0.05). Among inflammatory, angiogenic, and angiostatic cytokines and chemokines, only vascular endothelial growth factor (VEGF) showed a significant diabetes-specific profile (P < 0.05), although a similar trend was noted for tumor necrosis factor (TNF)-alpha. Soluble VEGF receptors R1 and R2 were detected in all samples with lowest VEGF-R2 levels (P < 0.05) and higher ratio of VEGF to its receptors in NPDR and PDR vitreous. CONCLUSIONS: This study is the first to demonstrate diabetes-specific changes in vitreous lipid autacoids including arachidonate and docosahexanoate-derived metabolites indicating an increase in inflammatory versus anti-inflammatory lipid mediators that correlated with increased levels of inflammatory and angiogenic proteins, further supporting the notion that inflammation plays a role the pathogenesis of this disease