Windegholm2923

High-dose of NBTI (15 mg/kg) reduced brain infarction volume and improved neurologic deficits both at 24 h and 72 h post MCAO. Moreover, NBTI significantly increased the level of CREB phosphorylation and extracellular adenosine concentration, and decreased the neuronal apoptosis 24 h after MCAO. NBTI treatment reduced the expression of Bax and cleaved caspase-3, while up-regulated Bcl-2 compared with vehicle group. These effects were abolished by H89 pretreatment. Conclusions ENT1 inhibition prevented neuronal apoptosis and improves neurological deficits through cAMP/PKA/CREB/Bcl-2 signaling pathway after MCAO in rats. ENT1 might be an effective target in the treatment strategy for ischemic stroke.The Autobiographical Interview (AI) separates internal (episodic) and external (non-episodic) details from transcribed protocols using an exhaustive and reliable scoring system. While the details comprising the internal composite are centered on elements of episodic memory, external details are more heterogeneous as they are meant to capture a variety of non-episodic utterances general semantics, different types of personal semantics details, metacognitive statements, repetitions, and details about off topic events. Elevated external details are consistently observed in aging and in neurodegenerative diseases. In the present study, we augmented the AI scoring system to differentiate subtypes of external details to test whether the elevation of these details in aging and frontotemporal lobar degeneration (including mixed frontotemporal/semantic dementia [FTD/SD] and progressive non-fluent aphasia [PNFA]) would be specific to general and personal semantics or would concern all subtypes. Specifically, we separated general semantic details from personal semantic details (including autobiographical facts, self-knowledge, and repeated events). With aging, external detail elevation was observed for general and personal semantic details but not for other types of external details. In frontotemporal lobar degeneration, patients with FTD/SD (but not PNFA) generated an excess of personal semantic details but not general semantic details. The increase in personal but not general semantic details in FTD/SD is consistent with prevalent impairment of general semantic memory in SD, and with the personalization of concepts in this condition. Under standard AI instructions, external details were intended to capture off-topic utterances and were not intended as a direct measure of semantic abilities. Future investigations concerned with semantic processing in aging and in dementia could modify standard instructions of the AI to directly probe semantic content.Indirect flight muscles (IFMs) are the largest muscles in Drosophila and are made up of hundreds of myonuclei. The generation of these giant muscles requires a large pool of wing disc associated adult muscle precursors (AMPs), however the factors that control proliferation to form this myoblast pool are incompletely known. Here, we examine the role of fibroblast growth factor (FGF) signaling in the proliferation of wing disc associated myoblasts. We find that the components of FGF signaling are expressed in myoblasts and surrounding epithelial cells of the wing disc. Next, we show that attenuation of FGF signaling results in a diminished myoblast pool. This reduction in the pool size is due to decreased myoblast proliferation. By contrast, activating the FGF signaling pathway increases the myoblast pool size and restores the proliferative capacity of FGF knockdown flies. Finally, our results demonstrate that the FGF receptor Heartless acts through up-regulating β-catenin/Armadillo signaling to promote myoblast proliferation. Our studies identify a novel role for FGF signaling during IFM formation and uncover the mechanism through which FGF coordinates with Wingless signaling to promote myoblast proliferation.Objective The hyperinsulinemic euglycemic clamp (HEC) is the "gold standard" for measuring insulin sensitivity (Si-clamp). Here, we determined the reproducibility of serial HEC data in healthy subjects. Research design and methods The Pathobiology of Prediabetes in A Biracial Cohort study assessed incident prediabetes in healthy African Americans (AA) and European Americans (EA) with parental type 2 diabetes mellitus during 5.5 years of follow-up. Assessments included anthropometry, OGTT, and HEC. Ninety subjects (44 AA, 46 EA) who underwent Year-1 HEC consented to Year-3 HEC. We calculated coefficients of variation (CVs), 95% limits of agreement, and repeatability coefficients for Year-1 and Year-3 data, and assessed the association of change in Si-clamp with incident prediabetes. selleck chemicals Results The mean (SD) baseline age was 47.5 ± 8.13y, body mass index was 30.4 ± 9.16 kg/m2, fasting plasma glucose was 93.7 ± 7.82 mg/dl and 2-hrPG was 126 ± 26.8 mg/dl. Si-clamp (umol/kg/min.pmol/L-1) was 0.071 ± 0.04 in Year 1 and 0.067 ± 0.04 in Year 3 (P = .22). Year 1 and Year 3 values were strongly correlated (r = 0.81, P less then .0001); the CV was 13.6% and repeatability coefficient was ±0.025. Intrasubject differences in serial Si-clamp were less than the repeatability coefficients and within the 95% limits of agreement. After 5.5 years of follow-up, 40 subjects progressed to prediabetes and 50 were nonprogressors. The change in Si-clamp was greater in progressors than nonprogressors (-10% vs. -2.5%, P = .02). Conclusions The HEC is reproducible over ~2 years in free-living individuals, with a temporal decline in Si-clamp that predicts prediabetes risk.Bisphosphonates (BPs) are pyrophosphate analogues widely used in diseases related to bone loss and increased bone turnover. Their high affinity for bone hydroxyapatite makes them ideal agents for bone diseases, while preventing them from reaching other cells and tissues. Data of the last decade, however, have demonstrated extra-skeletal tissue deposition and a variety of non-skeletal effects have been recently recognized. As such, BPs have been shown to exert anti-tumor, immunomodulatory, anti-inflammatory and anti-diabetic effects. In addition, new delivery systems (liposomes, nanoparticles, hydrogels) are being developed in an effort to expand BPs clinical application to extra-skeletal tissues and enhance their overall therapeutic spectrum and effectiveness. In the present review, we outline current data on extra-skeletal actions of bisphosphonates and attempt to unravel the underlying pathophysiological mechanisms.