Benjaminmoreno4159

Acute renal depletion of sorting nexin 1 (SNX1) in mice results in blunted natriuretic response and hypertension due to impaired dopamine D5 receptor (D5 R) activity. We elucidated the molecular mechanisms for these phenotypes in Snx1-/- mice. These mice had increased renal expressions of angiotensin II type 1 receptor (AT1 R), NADPH oxidase (NOX) subunits, D5 R, and NaCl cotransporter. Basal reactive oxygen species (ROS), NOX activity, and blood pressure (BP) were also higher in Snx1-/- mice, which were normalized by apocynin, a drug that prevents NOX assembly. Renal proximal tubule (RPT) cells from hypertensive (HT) Euro-American males had deficient SNX1 activity, impaired D5 R endocytosis, and increased ROS compared with cells from normotensive (NT) Euro-American males. siRNA-mediated depletion of SNX1 in RPT cells from NT subjects led to a blunting of D5 R agonist-induced increase in cAMP production and decrease in Na+ transport, effects that were normalized by over-expression of SNX1. Among HT African-Americans, three of the 12 single nucleotide polymorphisms interrogated for the SNX1 gene were associated with a decrease in systolic BP in response to hydrochlorothiazide (HCTZ). The results illustrate a new paradigm for the development of hypertension and imply that the trafficking protein SNX1 may be a crucial determinant for hypertension and response to antihypertensive therapy. © 2020 Federation of American Societies for Experimental Biology.BACKGROUND The majority of dogs with idiopathic epilepsy continue to have seizures despite appropriate treatment. OBJECTIVES To assess the use of a commercially available, collar-mounted accelerometer to detect generalized seizures in dogs. ANIMALS Twenty two client-owned dogs with idiopathic epilepsy. METHODS Six-month prospective clinical study during which dogs wore a collar-mounted accelerometer. Seizure documentation was based on owner observations and video recordings. The accelerometer used a predefined algorithm to detect seizures in the first study phase, and an individualized algorithm in the second study phase. Caregivers completed a quality of life (QoL) questionnaire at the initial and final study visit. RESULTS Using the predefined algorithm, the accelerometer detected seizures with a sensitivity of 18.6% (95% CI [13.4%, 23.8%]) and mean false detection rate of 0.096/day. Values did not change significantly with use of an individualized algorithm (sensitivity 22.1%, 95% CI [15.1%, 29.0%]; false detection rate 0.054/day). Mean composite QoL score was significantly improved at study completion (50.42) compared to study initiation (39.53; P = .005), and this change was moderately correlated with a change in weekly exercise (r = 0.46, P = .05). CONCLUSIONS AND CLINICAL IMPORTANCE Generalized seizures in dogs can be detected with a collar-mounted accelerometer, but the overall sensitivity is low. © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.Granular/fuzzy astrocytes (GFAs), a subtype of 'aging-related tau astrogliopathy', are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen, and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N=26), and progressive supranuclear palsy (PSP, N=10), Alzheimer's disease (AD, N=20), and primary age-related tauopathy cases (PART, N=18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD, and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation, and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%), and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without s reserved.Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity-associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Gefitinib price Thus, abnormal accumulation of the small leucine-rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes [endoplasmic reticulum and oxidative stress] in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin-stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot-dependent, pathogenic roles in obesity-associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.BACKGROUND Medium-chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). OBJECTIVE To evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. ANIMALS Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. METHODS A 6-month multicenter, prospective, randomized, double-blinded, placebo-controlled crossover trial was completed, comparing an MCT-DS with a control-DS. A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study.