bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary Modulation of Plasma and Adipose Tissue n‐3:n‐6 PUFA Ratio has no Effect on Insulin Resistance and Inflammation in Obese Gambian Women
Authors: Savy Mathilde , Nyan Ousman , Browning Lucy M. , Chatfield Mark , Prentice Andrew M. 
Published: June 2021

This study examined whether increasing long‐chain n‐3 polyunsaturated fatty acids (LC n‐3 PUFA) intake have benefits on glucose tolerance in obese Gambian women and on their fatty acid and lipid profiles, anthropometrics, blood pressure and inflammation status. Fifty four obese women with impaired glucose tolerance entered a 24‐week randomised intervention study. Women received LC n‐3 PUFA capsules and high n‐3 cooking oil (n = 30) or placebo capsules and high n‐6 cooking oil (n = 24). Measurements were taken at baseline, 12 and 24 weeks intervention and expressed as percentage of baseline values. In the intervention group, LC n‐3 PUFA increased in plasma (208%, p<0.0001) and adipose tissue (168%, p<0.0001), leading to an increase in n‐3:n‐6 PUFA ratio. There was no effect of high n‐3 PUFAs on fasting glucose, 120‐min glucose or fasting insulin, although insulin sensitivity assessed by the homeostasis model assessment improved modestly in the intervention group (p = 119%, p = 0.04 at 24 weeks). No differences were observed in weight, BMI and fat mass between the two groups, or in inflammatory markers, blood pressure or triglycerides. We conclude that although LC n‐3 PUFA supplementation modifies the fatty acid profile in obese Gambian women, there was no evidence that it had benefits on their glucose tolerance, triglycerides or inflammatory status.This work was supported by UK MRC.
Assessment of methylsulfonylmethane (MSM) on the development of osteoarthritis (OA): An animal study
Authors: Amiel David , Healey Robert M , Oshima Yasushi 
Published: June 2021

OA is characterized as articular cartilage degeneration, & a recent study shows that MSM supplementation is clinically effective (1). The mechanism, however, is still unclear. We examined the effect of MSM in OA.The ACL was transected in the right knee joints of mature NZW rabbits (n=10) (2). 5 wks after ACLT, MSM constant delivery system to the joint was created by implanting an Alzet osmotic pump. In the control group no add’l treatment was done. The rabbits were sac’d 9 wks postop, & OA grades of the femoral surface were: (Grade I intact surface; Grade II minimal fibrillation; Grade III overt fibrillation; & Grade IV erosion of the articular cartilage surface) (2).Results showed 2 Grade III & 1 Grade IV (avg 3.3) in the control group (ACLT). The MSM‐treated group showed 1 Grade I, 3 Grade II, 1 Grade III & 2 Grade IV (avg 2.6). Expression of type II collagen and aggrecan on cartilage showed no difference between control (ACLT) & experimental groups, however expression of TNF‐α in both cartilage and synovial tissue was decreased (p<0.01).MSM has preserved the articular cartilage surface during development of OA & relieved the inflammation level (i.e. TNF‐α) in both cartilage & synovium statistically. MSM therapy is a potential application for non‐invasive treatment of OA joints.Support from Bergstrom Nutrition and UCSD Ortho Connective Tissue Rsrch.
Garlic Therapy retards coronary artery calcification
Authors: Budoff Matthew Jay , Ahmadi Naser , Gul Khawar M , Liu Sandy T , Tiano Jima , Flores Ferdinand , Takasu Junichiro 
Published: June 2021

We sought to assess whether a garlic plus homocysteine‐lowering formulation can change the rate of atherosclerosis progression as compared to placebo.The study is a placebo‐controlled, double‐blind, randomized trial to determine whether Aged Garlic Extract (AGE) plus B‐vitamins, L‐Arginine and Folate can change the rate of atherosclerotic plaque burden (CAC) compared to placebo in 65 intermediate risk patients. Four capsules daily each containing either placebo or AGE + vitamins for the duration of 1 year. Patients’ were followed and repeat CAC measure were performed at 1 year.Results: The mean age was 60±9 and 79% of participants were male. AGE Group had less CAC progression (22 ± 18 Agatston Units) than placebo group (62±43) over 1 year(p=0.03). Multivariate regression analysis demonstrated garlic group had less CAC progression (Odds Ratio −0.24, 95% CI 0.06–0.9,P=0.01), lower total cholesterol (0.97, 95% CI 0.92–0.99,P=0.05), LDL‐C(0.96, 95% CI 0.91–0.98,P=0.04), and homocysteine (0.77, 95% CI 0.06–0.9,P=0.03) upon followup than placebo group. Also garlic therapy was associated with a significant increase in HDL‐C compared to the placebo group (1.10 (95% CI 1.02–1.21, p=0.04). This double‐blind, placebo‐controlled study demonstrates the ability of garlic plus vitamins to retard progression of CAC, and biomarkers of atherosclerosis independent of age, gender and conventional risk factors.
Crack Cocaine Use Accelerates CD4 decline and is Associated With Poorer Nutritional Status in HIV+ Drug Users
Authors: Rafie Carlin , Campa Adriana , Sales Sabrina , Baum Marianna K 
Published: June 2021

Objective:To evaluate the effect of crack cocaine use on HIV disease progression and nutritional status.Methods:After consenting, 222 HIV+ drug users were followed for 30 mo. CD4 count, HIV viral load, anthropometries, 24‐hour intake recall, antiretroviral (ARV) treatment, and drug use was assessed every 6 months. Percent of adequate calorie and protein was determined using 3 dietary recalls taken over 12 months. Cox Regression was used to evaluate drug use and time to decline of CD4 to <200cells/μL.Results:Crack use was associated with a faster decline of CD4 to <200cells/μL (RR=2.027, CI: 1.024–4.013), after controlling for baseline CD4 and ARV use. Crack users had lower body mass index (logBMI: 1.38±0.08 vs. 1.40±0.08, p=0.044), greater likelihood of an albumin<4.0g/dL (p=0.032), and higher viral load (logVL: 4.21±1.02 vs 3.80±1.06, p=0.004). BMI and albumin were significantly correlated independent of viral load (r=0.142, p=0.035). Adequacy of energy and protein intake, monthly income, homelessness, food security, and ARVs were not different between crack users and non‐users.Conclusions:Crack use is associated with faster decline of CD4 count, and poorer nutritional status, despite similar energy and protein intake. Crack use may increase nutritional requirements, suggesting a need for specific nutritional intervention in crack users.Support: Funded by NIDA
Effects of folic acid on the myelin basic protein expression in the maternal brain
Authors: Lee Yo A , Lee Ji Hye , Oh Kyung Hee , Chang Namsoo 
Published: June 2021

It is well known that folate is essential for fetal brain development, but the effect of folate on maternal brain is unknown. Myelin basic protein (MBP), a major structural protein of myelin, is thought to be important for the maintenance of myelin in the central nervous system (CNS). The synthesis of MBP requires a universal methyl donor, S‐adenosylmethionine, whose synthesis is dependent on folate and its involvement in one‐carbon metabolism. We investigated the effects of folic acid on the expression of MBP in the maternal CNS during pregnancy and lactation period. Female Sprague‐Dawley rats were fed either folic acid sufficient (8mg/kg diet) or deficient (0mg/kg diet) diet from 2 weeks prior to the mating throughout the entire pregnancy and lactation period. The MBP expression in the cortex, hippocampus and spinal cord was observed by immunohistochemical study and western blot analysis. At gestational day 20, the MBP expression in the spinal cord was increased in both groups, but the increase was greater in animals on a folic acid sufficient diet than those on a deficient diet. In conclusion, the maternal folic acid deficiency might inhibit the MBP synthesis in the spinal cord during pregnancy, and this might affect the maternal neurological function.This work was supported by the second stage of Brain Korea 21 project in 2007
Ethanol feeding enhances the hypotensive action of enalapril in telemetered female rats: Role of bradykinin B2 receptors
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A 
Published: June 2021

We investigsated the effect of chronic ethanol feeding on acute hemodynamic actions of enalapril in telemetered female rats and the role of bradykinin B2 receptors in the interaction. Changes evoked by enalapril (10 mg/kg i.p.) in blood pressure (BP), heart rate (HR), myocardial contractility (dP/dtmax), and power spectral indices of hemodynamic variability were evaluated in female rats receiving liquid diet with or without ethanol (5%, w/v, 8 weeks). Ethanol feeding reduced BP and dP/dtmax versus no effect on HR or hemodynamic variability. Enalapril decreased BP in control rats for at least 5 hrs and increased the low‐frequency (LF, 0.25–0.75 Hz), but not high‐frequency (HF, 0.75–3 Hz), spectral power of interbeat intervals (IBI) and IBILF/HF ratio, suggesting cardiac sympathetic dominance. In ethanol‐fed rats, enalapril elicited significantly greater hypotension and abolished the increase in cardiac sympathetic activity. Blockade of bradykinin B2 receptors by bradyzide (2 mg/kg i.p.) abolished the augmented hypotensive effect of enalapril in ethanol‐fed rats. In control rats, bradyzide eliminated the increase in cardiac sympathetic activity but had no effect on enalapril hypotension. These findings suggest that chronic ethanol enhances enalapril‐evoked hypotension in female rats, at least partly, via facilitation of bradykinin B2 receptor signaling.Supported by Grant R01 AA014441 from NIAAA.
Percutaneous application of carbon dioxide affects skin microcirculatory dynamics in healthy subjects
Authors: Nagashima Yoshinao , Mori Hideki , Yokomichi Hideki , Yada Yukihiro , Tsuchiya Shuuichi , Suzuki Toshiyuki , Oh‐ishi Sachiko , Majima Masataka 
Published: June 2021

Objective: Bathing in carbonated springs is considered to dilate skin blood vessels and increase blood flow. We developed a plaster‐type carbon dioxide CO2‐sheet to apply on a topical skin area, and examined the microcirculatory dynamics of its application.Methods: CO2‐sheets containing different concentration of CO2 (250, 500, and 1000 ppm in solvent) were applied on the flexor aspect of the forearm of healthy subjects, and changes in the microcirculatory dynamics were studied by direct measurement of diameter of subepidermal microvessels using a Capillary Scope System, which irradiates the skin surface with indirect light. Local skin blood flow was measured by the venous occlusion method using near‐infrared spectroscopy, and also by two‐dimensional mapping using a full‐field laser profusion imager.Results: Compared with sham sheets, application of the CO2‐sheets significantly increased the diameter of subepidermal microvessels and increased the blood flow concentration‐dependently.Conclusions: This CO2‐sheets may be useful as a therapeutic device to improve skin microcirculation in the fields of health care as well as clinical medicine.
Microvascular oxygen transport in obese ZDF rats: an early model of type II diabetes
Authors: Benlamri Amina , Milkovich Stephanie , Burger Dylan , Feng Qingping , Goldman Daniel , Ellis Christopher 
Published: June 2021

Sprague et al. (Diabetes 2006) reported impaired ATP release from human red blood cells (RBC) with type II diabetes that may contribute to impaired regulation of O2 delivery. Our goal was to quantify O2 transport in skeletal muscle of obese ZDF‐370 rats. Using dual wavelength intravital video microscopy we measured hemodynamics (RBC velocity, RBC supply rate, hematocrit) and RBC oxygen saturation in capillaries of extensor digitorum longus muscle as well as capillary density, glucose, TNF‐ α levels, arterial blood gases, arterial hemoglobin and hematocrit levels. Results reported as mean±SD. Two groups, 7 lean ZDF‐380 rats (179±13 g) and 8 obese ZDF‐370 rats (240±10 g), were studied at 7 weeks. Both glucose and TNF‐ α levels were elevated in the obese group compared to lean (glucose: 12.3±5.1 vs 6.8±0.6 mmol/L; TNF‐α: 112±43 vs 19±9 pg/mol). There were no significant differences in total capillary density. RBC supply rate was significantly decreased in obese rats (7.2±1.1 vs 9.0±1.8 RBC/s; p < 0.05); other hemodynamic parameters were unchanged (obese vs lean: velocity 130±26 vs 157±29 μm/sRBC, Hct 14.6±3.3 vs 15.3±1.6 %). There was a trend for decreased O2 saturation in the obese group (54±16% vs 64±5%; p = 0.19). The lower RBC supply rate and O2 saturations suggest the start of impaired regulation of O2 transport in this early diabetic model.Supported by NIH grant (HL‐089125) and a CIHR operating grant to Ellis & Goldman.
The relationship between cochlear blood flow disorder and NF‐kB activation by loud sound situation
Authors: Yamamoto Hiroshi , Shi Xiaorui , Omelchenko Irina , Nuttall Alfred 
Published: June 2021

Nuclear factor‐kappa B (NF‐κB) plays an essential role in the regulation of genes involved in various biological processes, such as inflammation, immune responses, neuronal development, and cellular apoptosis. NF‐κB activation can be achieved through two main pathways. The canonical (classical) pathway is known to be involved in the response of various cell types to pathogen associated molecules as well as proinflammatory cytokines, such as tumor necrosis factor alpha (TNF‐α) and interleukin‐1 (IL‐1). The noncanonical (alternative) is activated by a different specific set of stimuli, including B‐cell activating factor (BAFF), lymphotoxinβ, and CD40L.In this study, using immunohistochemistry and immunoblot analysis, we determined whether one or both NF‐κB pathways, canonical (classical) or noncanonical (alternative), involved in loud‐sound induced cellular damages mechanism in guinea pig cochlea. In control (non‐sound stimulated) condition, we found that there was no detectable phosphoralated P65 in canonical pathway or P100 in the noncanonical pathway in both organ of Corti and cochlear lateral wall. However, NF‐κB activation related P65 phosphorylation was detected in the inner ear immediately following loud‐sound exposure at 120dB SPL/3hr for a day. There was no phosphorylation of p100 at any time periods following loud sound stimulation. These results suggest that loud‐sound stress activates NF‐κB dependent on P65 (canonical) pathway but not P100 (non‐canonical) pathway in the response to loud‐sound induced cellular damage. Supported by NIH/NIDCD R01 DC 00105, 008888 and 005983.
Endothelium‐dependent contractions in the carotid artery of young adult spontaneously hypertensive rats are mediated by cyclooxygenase and markedly augmented by nitric oxide inhibition
Authors: Denniss Steven G , Rush James WE 
Published: June 2021

We have recently shown that ACh‐stimulated vasomotor activity in isolated PE‐precontracted common carotid artery (CCA) rings from young adult spontaneously hypertensive rats (SHR) involves a dose‐dependent relaxation phase from −9 to −7 LogM followed by a ‘re’‐contraction phase through to −4 LogM, whereas in normotensive Wistar Kyoto rats (WKY) only a robust relaxation phase existed. The objective of this study was to test the hypothesis that [ACh] >−7 LogM stimulates contractions in quiescent CCA from SHR but not WKY. Reference KCl contractions in CCA were similar between strains and across all drug conditions (0.9−1.0g). [ACh] from −9 to −4 did not elicit vasomotor activity in WKY CCA, nor did [ACh] elicit vasomotor activity in SHR CCA from −9 to −7; however, [ACh] >−7 stimulated a dose‐dependent contraction in SHR CCA reaching a plateau at −4 (0.16±0.03g). Endothelium denudation completely abolished these ACh‐stimulated contractions as did cyclooxygenase (COX) inhibition, whereas blocking endothelial nitric oxide (NO) synthase markedly increased the amplitude (0.61±0.08g) but not the threshold or sensitivity of the contractile response. These data demonstrate that only [ACh] >−7 LogM can stimulate contractions in CCA from young adult SHR (but not WKY) that are endothelium‐dependent, COX‐mediated, and powerfully modulated by the availability of NO.Research Support: HSFO and NSERC
Oxytocin enhances glutamatergic afferent transmission and produces an inward current in second order medial solitary tract neurons
Authors: Peters James Henry , Andresen Michael 
Published: June 2021

Cranial visceral afferents contact neurons within the solitary tract nucleus (NTS) and evoke essential homeostatic reflexes. Descending projections from the paraventricular nucleus (PVN) of the hypothalamus release oxytocin to modulate visceral afferent communication with NTS. The mechanisms through which oxytocin acts are poorly understood. In horizontal brainstem slices, remote electrical shocks to afferent axons in the solitary tract (ST) activated time invariant ST synaptic responses (jitter of < 200 μs) and identified second order NTS neurons. Blocking conducted transmission with tetrodotoxin (TTX), glutamate mediated mEPSC were isolated with the GABAA receptor antagonist gabazine (SR‐95531). Oxytocin concentration dependently (1 – 1000 nM) increased the frequency of mEPSCs but had no effect on the event kinetics – observations consistent with a presynaptic action at afferent terminals. The oxytocin receptor antagonist (d(CH2)51,Tyr(Me)2,Thr4,Orn8,des‐Gly‐NH29‐Vasotocin) blocked this effect. In addition, oxytocin evoked an inward current – observations consistent with postsynaptic modulation of ion channels. Taken together these findings demonstrate oxytocin released from PVN projections may enhance visceral afferent transmission within NTS via both pre‐ and postsynaptic sites of action.Supported by: HL‐088894 (JHP) and HL‐041119 (MCA)
Chronic Hypoxia (CHx) Suppresses the Chemosensitive Response of Individual Nucleus Tractus Solitarius (NTS) Neurons from Adult Rats
Authors: Nichols Nicole Louise , Wilkinson Katie A. , Powell Frank L. , Putnam Robert W. 
Published: June 2021

CHx alters the ventilatory response to hypoxia which is mediated in part by changes in NTS neurons. We hypothesized that the response of NTS neurons to hypercapnia is also increased by CHx. Rats were exposed to hypobaric hypoxia (10–11%) for 7–14 days, and we simultaneously measured the intracellular pH (pHi) and firing rate (FR) of NTS neurons in slices using whole cell patch and fluorescence imaging microscopy techniques. CHx did not affect basal pHi (∼7.30) or FR of NTS neurons (∼1 Hz). Synaptic block (SNB: 0.2 mM Ca2+, 11.4 mM Mg2+) increased the FR of neurons from control (1.4 ± 0.2 to 2.8 ± 0.5 Hz) and CHx rats (1.0 ± 0.2 to 3.0 ± 0.6 Hz). pHi responses to HA (hypercapnia acidosis: 15% CO2; pHo 7.0) were unchanged in neurons from CHx rats. The percentage of NTS neurons activated by HA decreased from 46% (control rats) to 34% (CHx rats). The chemosensitivity index of NTS neurons activated by HA was unchanged by CHx (166 ± 11% for controls and 160 ± 6% by CHx). The percentage of hypercapnia‐inhibited NTS neurons from CHx rats increased markedly (28%) compared to normal (13%). The HA responses of NTS neurons are intrinsic since they were unaffected by SNB. CHx causes neuronal plasticity resulting in suppression of the HA response in individual NTS neurons from adult rats. This is the first example of plasticity at the cellular level in individual chemosensitive neuronal responses to HA.[Supported by NIH grants RO1 HL566683 and RO1 HL081823.]
Role of STIM1 in Regulation of Store‐Operated Ca2+ Entry in PC12 cells
Authors: Prakash Y S , Pabelick Christina M , Thompson Michael A 
Published: June 2021

Store operated calcium entry (SOCE) is important for regulation of intracellular Ca2+ ([Ca2+]i) in neurons. Recent studies in other cell type suggest that stromal interaction molecule (STIM1) triggers SOCE. We examined the role of STIM1 in the sensitivity of SOCE to temperature, pH and glutamate in differentiated, fura‐2 loaded rat pheochromocytoma (PC12) cells, a model for neuronal cells. In STIM1 siRNA‐transfected vs. control cells, SOCE was triggered by introduction of extracellular Ca2+ following endoplasmic reticulum depletion via cyclopiazonic acid in zero Ca2+. Cells were washed and exposed to altered pH (6.0–8.0), altered temperature (34–40oC) or different concentrations of glutamate. In controls, SOCE was progressively inhibited by decreased pH or temperature, while alkalosis and increased temperature stimulated Ca2+ influx. Increasing glutamate concentrations progressively inhibited SOCE. siRNA inhibition of STIM1 substantially blunted both temperature sensitivity (especially increased temperature) and pH sensitivity (especially acidic pH) of SOCE. These data show that SOCE in PC12 cells is susceptible to acidosis, temperature, and agonist stimulation: factors that can adversely affect neuronal function under pathological conditions. In this regard, the SOCE triggering protein STIM1 may play a role in such susceptibility.This work has been supported by NIH grants UL1RR024150‐01(CR to CMP, CR20 and Early Career Development Award to YSP), and the Department of Anesthesiology (CMP, YSP), Mayo Clinic College of Medicine, Rochester, MN
BLOOD PRESSURE INCREASE AFTER SUCROSE FEEDING IS SODIUM‐INDEPENDENT
Authors: Freitas Raphael Ribeiro de Aquino , Oliveira‐Sales Elizabeth Barbosa , Boim Mirian Aparecida , Bergamaschi Cássia Toledo , Donilkoff Miriam Sterman , Campos Ruy Ribeiro 
Published: June 2021

Dysregulation of sodium and/or water reabsorption by the kidney may contribute to hypertension. As chronic sucrose feeding reduces food intake and in consequence of this, the sodium (Na) intake. The objective of the present study was to investigate the role of kidney sodium and water channels on blood pressure increase in sucrose‐fed rats (SC). Wistar rats (150–180g) received, for 30 days, food ad libitum and sucrose solution (20%) (SC =7) or tap water (control group, C =8). The food ingestion was quantified using a metabolic cage and 1 mg of Na was given by gavage for another group of 5 sucrose fed‐rats (SS), also for 30 days (once a day) in order to normalize the sodium ingestion between SS and C. Mean arterial pressure (MAP) was recorded by a Power Lab system. The mRNA expression levels of epithelial sodium channel (ENaC) and water channel protein (AQP2) were analyzed in the cortical kidney tissue by Real Time RT‐PCR technique. MAP increases (P<0.05) in SC (128±1 mmHg) compared to C (102±4 mmHg) rats; MAP was 132±3 mmHg, in SS rats. Compared to C rats the ENaC and AQP2 expression levels were increased (P<0.05) in SC rats (ENaC: SC=1.95±0,19; C=1.03±0,07; AQP2: SC=2.12±0,19, C=1.07±0,10 arbitrary units). However, in SS group the high expression levels of ENaC and AQP2 were reversed (ENaC: 0,74±0,6, AQP2: 0,99±0,12 arbitrary units) but not MAP. Taken altogether, the results presented here indicate that in chronic sucrose fed‐rats the increased MAP is Na‐independent.Supported by FAPESP, CNPq