Development and potential role of type-2 sodium-glucose transporter inhibitors for management of type 2 diabetes

There is a recognized need for new treatment options for type 2 diabetes mellitus (T2DM). Recovery of glucose from the glomerular filtrate represents an important mechanism in maintaining glucose homeostasis and represents a novel target for the management of T2DM. Recovery of glucose from the glomerular filtrate is executed principally by the type 2 sodium-glucose cotransporter (SGLT2). Inhibition of SGLT2 promotes glucose excretion and normalizes glycemia in animal models. First reports of specifically designed SGLT2 inhibitors began to appear in the second half of the 1990s. Several candidate SGLT2 inhibitors are currently under development, with four in the later stages of clinical testing. The safety profile of SGLT2 inhibitors is expected to be good, as their target is a highly specific membrane transporter expressed almost exclusively within the renal tubules. One safety concern is that of glycosuria, which could predispose patients to increased urinary tract infections. So far the reported safety profile of SGLT2 inhibitors in clinical studies appears to confirm that the class is well tolerated. Where SGLT2 inhibitors will fit in the current cascade of treatments for T2DM has yet to be established. The expected favorable safety profile and insulin-independent mechanism of action appear to support their use in combination with other antidiabetic drugs. Promotion of glucose excretion introduces the opportunity to clear calories (80–90 g [300–400 calories] of glucose per day) in patients that are generally overweight, and is expected to work synergistically with weight reduction programs. Experience will most likely lead to better understanding of which patients are likely to respond best to SGLT2 inhibitors, and under what circumstances

Spin-polarized supercurrents for spintronics: a review of current progress

During the past 15 years a new field has emerged, which combines superconductivity and spintronics, with the goal to pave a way for new types of devices for applications combining the virtues of both by offering the possibility of long-range spin-polarized supercurrents. Such supercurrents constitute a fruitful basis for the study of fundamental physics as they combine macroscopic quantum coherence with microscopic exchange interactions, spin selectivity, and spin transport. This report follows recent developments in the controlled creation of long-range equal-spin triplet supercurrents in ferromagnets and its contribution to spintronics. The mutual proximity-induced modification of order in superconductor-ferromagnet hybrid structures introduces in a natural way such evasive phenomena as triplet superconductivity, odd-frequency pairing, Fulde-Ferrell-Larkin-Ovchinnikov pairing, long-range equal-spin supercurrents, $\pi$-Josephson junctions, as well as long-range magnetic proximity effects. All these effects were rather exotic before 2000, when improvements in nanofabrication and materials control allowed for a new quality of hybrid structures. Guided by pioneering theoretical studies, experimental progress evolved rapidly, and since 2010 triplet supercurrents are routinely produced and observed. We have entered a new stage of studying new phases of matter previously out of our reach, and of merging the hitherto disparate fields of superconductivity and spintronics to a new research direction: super-spintronics.Comment: 95 pages, 23 Figures; published version with minor typos corrected and few references adde

Epidemiological study on some environmental and management parameters affecting on WSD occurrence in Fenneropenaeus indicus and Penaeus vannamei

For the first time white spot disease (WSD) was reported in shrimp farms of khoozestan province, in southwest of IRAN in 2002. Then in 2005 the neighbor province, boushehr, was contaminated. In 2008 WSD outbreak reported in sistan-bloochestan province in southeast of Iran. In 2015 all of southern shrimp farms of country except Hormozgan, the middle southern province, which has remained free of WSD, are being contaminated. White Spot disease suspended shrimp culture in thousands hectares of shrimp farms. Considering that white spot disease has not been observed in Hormozgan province yet, the question is; to what extent environmental and management factors participated in preventing WSD outbreak or cause WSD outbreak. In this study (20102012), the effects of environmental factors and management, stressors that decrease immune system function of shrimp are discussed. In addition, the role of pathogen as the main factor of outbreak is discussed. The goal of this study is to define environmental parameters and management practices associates with outbreak of white spot disease in affected provinces and discover reasons of being Hormozgan province free of this disease. In this study the role of the local environmental factors and management practice stressors in susceptibility to WSD was determine. Both the effects of environmental factors in water of ponds including total ammonia, nitrogen, dissolved oxygen, pH, salinity, transparency, and temperature and management issues related to biosecurity are studied. There were overlaps on physical and chemical parameter values obtained in clear areas with contaminated areas .Results of the data analysis suggest that lack of association with WSD incidence was 7 times greater than WSD incidence despite of disease outbreak in sistan-bloochestan province, so other sources of white spot disease virus incidence was suspected in affected areas. Histopathological examinations and polymerase chain reaction (PCR) tests during project performance did not reveal white spot disease virus evidences in post larvae examined from khoozestan province stocked in farms but disease outbreak was happened in that farms , so we suspected to management practice include feed , pond preparation and carrier of disease. Recorded values of temperature and salinity in some months during inspection in Hormozgan province specified stressful condition that may lead to WSD outbreak, however the disease did not appear. Therefore the hypothesis that the water physical and chemical conditions are reasons to prevent disease outbreak in Hormozgan province is being rejected. The policy of Hormozgan’s fishery authorities, to replaced Fenneropenaeus indicus with specific pathogen free Litopenaeus vannamei, that is more resistant to some of diseases, before incidence of WSD in farms and to before being endemic in the Hormozgan province, made an advantage compare to affected southern provinces that introduced Litopenaeus vannamei after WSD prevalence to their farms. However it does not guarantee to maintain current trend of being Hormozgan province farms free of white spot disease. Therefore establishing the principals of biosecurity are strongly emphasized. Strategies taken by the proficient authorities in preparation of SPF shrimp broodstock can be the most important factor in preventing WSD. Regarding biosecurity principals purchased feed must be free of shrimp head powder. Construction the new shrimp farms should be as far as it could be away from contaminated areas

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Correlation between lipid-lowering and bone-protective effects of eicosapentaenoic acid in rats with steroid- induced bone loss

Summary This study was conducted to investigate the correlation between lipid-lowering and bone-protective effects of eicosapentaenoic acid on steroid-induced bone changes in rats. Twenty-one male 10-week-old Wistar rats were divided into 3 groups (n = 7 each) and treated with 0.9% NaCl SC (group 1) or methylprednisolone 7 mg/kg SC once a week (group 2) or methylprednisolone 7 mg/kg SC once a week + eicosapentaenoic acid 160 mg/kg, PO daily (group 3), for 6 weeks. At the end of the experiment, serum total cholesterol and triglycerides concentrations were determined using enzymatic colorimetric assays and bone histomorphometric analyses were performed on cancellous bone of femoral epiphysis and metaphysis using a photomicroscope and a digital camera. Histomorphometric parameters demonstrated a significant bone loss due to methylprednisolone administration, which was partly restored by eicosapentaenoic acid. A strong inverse correlation was observed between the serum total cholesterol concentration and epiphyseal trabecular width and metaphyseal trabecular osteoid width (R = -0.82, P = 0.04 and R = -0.86, P = 0.01, respectively). Serum triglycerides concentration was also strongly and inversely correlated with the above mentioned parameters (R = -0.88, P = 0.02 for epiphyseal trabecular width and R = -0.81, P = 0.02 for metaphyseal trabecular osteoid width). The correlation between the lipid-lowering and bone-protective effects of eicosapentaenoic acid may be helpful in the clarification of its effects on bone and lipid metabolism