bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational chronic intermittent hypoxia causes asymmetric growth restriction and alters cholesterol homeostasis in the liver of sprague‐dawley rats
Authors: Iqbal Waseem , Barry Eric , Hardy Daniel , Ciriello John 
Published: June 2021

This study was done to investigate the effect of chronic intermittent hypoxia (CIH) during gestation on the development of offspring. Female Sprague‐Dawley rats were mated, housed individually, and kept on a standard rat chow diet during the study. Pregnant females (n=8) were exposed daily to CIH (6.5% O2 nadir; 18 cycles/h; 8 h/day) from gestational day‐1 to day‐20. Control (n=6) mothers were exposed similarly to room air. Postnatal day‐1 offspring from CIH mothers showed significantly lower body weights, and lower liver‐to‐body weight ratios. By 12‐wk of age, body weights of growth restricted offspring were significantly greater, as were the liver‐to‐body weight ratios. These offspring also had greater body fat deposition and elevated circulating cholesterol levels at both 6‐wk and 12‐wk of age. Western blot and qPCR analysis showed that CIH offspring had decreased protein and gene expression of markers vital for cholesterol regulation in the liver, including Liver X Receptor (LXR), ABCA1 (cholesterol efflux) and the LDL receptor (cholesterol catabolism). These data show that alteration of the maternal intrauterine environment by gestational CIH has significant consequences on the long‐term development of offspring and increases the disposition of the animals to metabolic diseases in adulthood.Supported by Heart and Stroke Foundation and Canadian Institutes of Health Research
Effects of K‐deficient diets ± Na supplementation on Na, K, and H2O transporters’ abundance along the nephron
Authors: Nguyen Mien T.X. , Yang Li E. , Fletcher Nicholas K , Lee Donna H. , Silver Randi , McDonough Alicia A. 
Published: June 2021

Previous studies of K deficiency compared chow with 2% KCl, 0.74% NaCl (2K1Na ) to K deficient chow: 0.03% KCl, 0.74% NaCl (0K1Na ). We tested whether previously reported responses to 0K diet are due to low electrolytes, rather than hypokalemia. SD rats were fed 6 d with gelled diet prepared from powdered base adjusted to 2K1Na, 0K1Na, and with added NaCl: 2% KCl, 2% NaCl (2K2Na) and 0.03% KCl, 2% NaCl (0K2Na). Abundance was assessed by immunoblot of homogenates, densities normalized to mean of 2K groups.Results1) In both 0K groups, plasma K fell to 2.5 mM, urine K fell to < 10 μmol/hr and outer medulla hypertrophied. 2) The only differences seen in both 0K groups are: ↓cortex ENaC and ↑medulla Na,K‐ATPase (NKA). 3) The following changed in 0K1Na but not 0K2Na: ↑cortex gastric H,K‐ATPase (HKA), ↑medulla NHE3, NHE3‐P and ↓AQP2. 4) In 0K2Na but not 0K1Na: cortex SPAK and OSR1 ↑ despite lowest plasma aldo in 0K2Na (172 pg/ml) vs. 0K1Na (413 pg/ml) and 2K2Na (417 pg/ml) and with no changes in NCC‐P or NKCC‐P.ConclusionsDespite profound hypokalemia and low urinary K, previously reported changes with 0K diets (↑NHE3, ↓NKCC, ↓NCC, ↓ROMK, ↑c‐Src, ↑HKA, ↓AQP2) were not observed; some may be secondary to low electrolytes. ↓ENaC can decrease driving force for K secretion, and ↑NKA is secondary to hypertrophy. Changes in transporter distribution and activity appear more important for conserving K than changes in abundance. DK0837854
Irbesartan improves autonomic tone in a mouse model of renovascular arterial hypertension
Authors: Pliquett Rainer U. , Brandes Ralf P 
Published: June 2021

ObjectiveActivation of renin‐angiotensin‐aldsterone and sympathetic nervous system are consequences of renovascular arterial hypertension. Here, in a model of renovascular hypertension, the role of Angiotensin‐II blockade on autonomic tone was assessed.MethodsC57bl6n mice with implanted iliac‐artery catheters received a renal‐artery clip (2‐kidneys‐1 clip, 2K1C). Sham‐surgery mice served as normal controls. Blood pressure of unrestrained, conscious animals was recorded using telemetry. Animals were randomized to Irbesartan (10 mg/kg/d per orally) or vehicle for 7 days. Cumulative intensity of the low‐frequency (LF) band of systolic blood pressure variability (SBPV) (0.15 – 0.6 Hz) was considered as sympathetic tone, the high‐frequency band (2.5–5 Hz) of heart rate variability as parasympathetic tone. Spontaneous blood‐pressure changes were used for baroreflex‐sensitivity calculation using Hemolab software. One‐way ANOVA, Newman‐ Keul test were used to assess differences. P<0.05 was deemed significant.ResultsTherapeutic‐dose Irbesartan did not lower blood pressure in the 2K1C model of arterial hypertension (Figure). However, both baroreflex and parasympathetic tone were significantly augmented by Irbesartan. Lastly, the difference of sympathetic tone between 2K1C and normal group partially vanished. Selective blockade of sympathetic tone by Metoprolol and, likewise, parasympathetic tone by Atropine confirmed the changes induced by Irbesartan on either component of autonomic nervous system (data not shown). As a mechanism, baroreflex control of heart rate was shown to be improved by Irbesartan.ConclusionAngiotensin‐receptor blocker partially normalizes both baroreflex function and parasympathetic tone in a renovascular model of arterial hypertension.
Perivascular fat impairs contraction in aorta from obese but not lean adult rats
Authors: Watts Stephanie W , McClain Jonathon L , Dorrance Anne M 
Published: June 2021

Aortic perivascular fat limits the ability of the aorta to contract. We hypothesized that constriction would be further impaired in rats fed a high fat (HF) diet. Male Sprague Dawley (SD) rats were fed a HF diet from 3–20 weeks of age, control rats received normal chow (n=4–6 in each group). Aortae were removed and isometric force generation was measured in the presence and absence of fat. The HF rats weighed more than the controls (401±9 vs 465±10g, control vs HF p<0.05) and had more abdominal fat (5.6±0.3 vs 16.5±1.2g, control vs HF p<0.05). Surprisingly, the presence of fat in the control rats had no effect on the contraction mediated by phenylephrine (PE) or angiotensin II (Ang II). Fat did cause a marked impairment in the contraction in aorta from HF rats. Interestingly, the clean aorta from the HF rats also exhibited impaired PE and Ang II mediated contraction when compared to clean aorta from control rats. We have shown that fat impairs contraction in aorta from young control chow fed SD rats. The present study suggests that fats ability to limit contraction is reduced with age in control but not obese rats; the mechanisms responsible for this remain to be elucidated.

Maximum contraction (mg increase from baseline)

Contractile Agent
Control
Control + Fat
HF
HF+Fat

PE
1580±210
1595±68
1280±76#
855±59*

Ang II
545±90
533±73
367±80#
157±67*

different from clean aorta from HF rats,
different from clean aorta from control rats
FORMATION OF POLYMERS INSULIN IN VITRO IN BLOOD HATCHING TIBOLONE IN MENOPAUSAL PATIENTS
Authors: moral-laguna elia e del , Valencia-Hernandez Ignacio , de la Luz Linares-Perez Maria , Rivera-Llano Aidé , Lugo-Martinez Gabriela , Ocharan-Hernandez Maria Esther , Calzada-Mendoza Claudia Camelia 
Published: June 2021

OBJECTIVEEvaluate in vitro the formation of polymers of insulin after blood incubation in menopausal patients treated with tibolone, also quantify oxidative stress markers and apply anthropometry.METHODSWere selected 18 menopausal patients 45–50 years of age, whose was treated whit tibolone for three months (2.5mg/day), whose blood was incubated in insulin, underwent same nondenaturing electrophoresis and visualize the polymers of the hormone. Additionally we evaluated markers of oxidative stress (malondialdehyde, total sulfhydryl and carbonyl groups) and anthropometric parameters.RESULTSIt was observed that blood from all patients before treatment induced the formation of polymers of insulin and after treatment, only 33% remains. The oxidative stress evaluation shows reduction in damage to lipids (malondialdehyde), increased sulfhydryl groups ( they are part of the antioxidant system), but the proteins damage indicator (carbonyls) still unchanged. Regarding anthropometric assessment was observed weight reduction (p = 0.013), BMI (p = 0,035) and glucose (p =. 016).CONCLUSIONSTibolone reduced the oxidized state of the blood and its ability to induce the formation of polymers of insulin, weight and body mass index and blood glucose.
Reduced NO Bioavailability Hampers Exercise Induced Vasodilation in Familial Hypercholesterolemic Swine
Authors: de Beer Vincent J , Merkus Daphne , Bender Shawn B , Tharp Darla L , Ivey Jan R , Bowles Dougla K , Duncker Dirk J , Laughlin M Harold 
Published: June 2021

Hypercholesterolemia impairs endothelial function (e.g. the NO‐cGMP‐ phosphodiesterase 5 (PDE5) pathway), limits shear stress induced vasodilation, and is thereby expected to reduce exercise induced vasodilation. To assess the actual effects of hypercholesterolemia on endothelial function and exercise induced vasodilation, we compared the effects of eNOS and PDE5 inhibition in chronically instrumented Yorkshire (Y) and Rapacz Familial Hypercholesterolemic (FH) swine, at rest and during exercise.Exercise induced systemic vasodilation, i.e. the increase in systemic vascular conductance index (SVCi = SVC per Kg bodyweight), was markedly reduced in FH swine (27±5%) compared to Y swine (119±4%). As a result, during exercise mean arterial pressure remained constant in Y swine while it significantly increased in FH swine (from 91±6 to 110±8 mmHg). The vasoconstrictor effect of eNOS inhibition, with Nitro‐L‐Arginine, was attenuated in FH compared to Y swine, both at rest and during exercise. Furthermore, the vasodilator effect of PDE5 inhibition, with EMD360527, was also markedly reduced in FH compared to Y swine.In conclusion, hypercholesterolemia hampers exercise‐induced vasodilation via reduced NO bioavailability. The reduced NO bioavailability results in a decreased activation of the NO‐cGMP pathway, as evidenced by a blunted vasodilator response to PDE5 inhibition.
The effects of play‐based physical activity on metabolic signatures in adolescents
Authors: Gulas Maria Eleni , Collier Scott 
Published: June 2021

Exercise has been shown to decrease risk factors and aid in weight management, however little is known regarding the mechanisms influencing these shifts by the metabolic shift. The purpose of this study was to compare the effects of 4 and 8 weeks (4w, 8w respectively) of play based activity versus a typical 8 week (C) summer break activity on key metabolic signatures.METHODSTwenty‐two adolescent children were divided into 8 and 4 week activity and control groups (8w, 4w, C) respectively. Subjects reported to the Vascular Biology and Autonomic Studies Laboratory on two separate visits, at the beginning and the end of 4 or 8 weeks of the exercise program to give urinary samples at which time a graded exercise test was given (GXT) and descriptive characteristics were recorded. A gas chromatography time‐of‐flight mass spectrum analysis was performed on the samples and the results analyzed by special software.RESULTSA valid PLS‐DA model was obtained between post‐exercise subjects in 8 week group and control group. Significant changes were shown in pantothenic acid (fold change, FC 4.19), adenosine (FC 1.66), glyceric acid (FC 2.91), and creatinine (FC 1.61).CONCLUSIONThese data indicate that 8 weeks of play‐based physical activity can positively affect the metabolome of adolescents which may prevent the future development of obesity and CVD. Research was partially supported by a grant from the BeActive North Carolina Partnership (Collier, PI)
Voluntary exercise reduces cachexia and improves muscle function in mice carrying mammary gland tumors
Authors: IVARSSON NIKLAS , Rundqvist Helene , Östman Arne , Westerblad Håkan 
Published: June 2021

Cachexia is a common feature in patients suffering from cancer. Here we use a PyMT knock in mice that develops spontaneous mammary gland tumors to study the effect of voluntary wheel running on skeletal muscle function. Mice were housed with the possibility to engage in voluntary exercise by a running wheel in the cage. Controls were housed with an immovable running wheel. Force at different frequencies and force during fatigue and recover was measured in isolated soleus (Slow twitch) and extensor digitorum longus (fast twitch).In controls, soleus presented with clear atrophy in tumor carrying mice (6.7±0.5vs. 8.0±0.6 mg) and force at 100 Hz was reduced (51.4±5.6 vs. 88.8±16.5 kPa). Mice that exercised had a tendency for increased muscle mass (7.0±0.4 mg) and a compensated muscle force at 100Hz compared to voluntary run wild types (118.3±16.6kPa vs. 117.1±17.0kPa).Western blot of whole muscle indicate that tumor mice had ~30% less PGC‐1α in both Soleus and EDL where a small increase could be seen in tumor carrying mice that had been running.ConclusionSkeletal muscles are afflicted by system wide influence from tumor growth. This effect can however to some extent be prevented by engaging in regular exercise.
Muscle contraction uncouples interactions between skeletal muscle ATGL and lipid droplet protein PLIN2
Authors: MacPherson Rebecca E.K. , Turnbull Patrick C. , Vandenboom Rene , Roy Brian D. , Peters Sandra J. 
Published: June 2021

Skeletal muscle lipid droplet proteins (PLINs) are thought to regulate lipolysis through protein‐protein interactions on the lipid droplet surface. In adipocytes, PLIN1 regulates lipolysis by directly interacting with CGI‐58, an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation PLIN1 is phosphorylated releasing CGI‐58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that this role is undertaken by another PLIN family protein. Our purpose was to examine interactions between PLIN2, ATGL and its co‐activator CGI‐58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation (150 ms volleys at 60 Hz with a train rate of 20 tetani per min (25°C). Co‐precipitation revealed no detectable interaction between PLIN2 and CGI‐58 at rest or following stimulation. PLIN2 co‐precipitated with ATGL at rest, but significantly decreased by 30% following stimulation (p=0.013). Therefore, in skeletal muscle PLIN2 may regulate lipolysis through interacting with ATGL rather than CGI‐58.Supported by NSERC, Canada.
Ventilatory long‐term facilitation following acute intermittent or continuous hypoxaemia in awake humans: the role of carotid chemoreceptors and ventilatory drift to sustained hypercapnia
Authors: Griffin Harry Sebastian , Pugh Keith , Kumar Prem , Balanos George M 
Published: June 2021

In awake humans, acute intermittent hypoxaemia (IH) causes a sustained increase in ventilation upon reoxygenation, known as ventilatory long‐term facilitation (vLTF), but only if combined with mild hypercapnia. It is not known if mild hypercapnia also unmasks vLTF following continuous hypoxia (CH). Carotid chemoreceptor (CC) sensitisation has been proposed as a mechanism for vLTF. We hypothesised that silencing the CC with 100% O2 would transiently abolish vLTF.12 males undertook 3 trials. Mild hypercapnia was maintained in all trials and one minute exposures to 100% O2 occurred at baseline and recovery. Trials differed only in their hypoxic exposure; Trial 1‐Acute IH, Trial 2‐Acute CH, Trial 3‐Euoxia. Ventilation in Trial 1 and 2 increased from baseline to recovery (T1: 20.1 ± 1.1 vs. 25.1 ± 1.6, T2: 20.0 ± 1.2 vs. 25.1 ± 1.4 L/min).Ventilation also increased in Trial 3 but to a lesser extent (19.8 ± 1.17 vs. 22.4 ± 1.84 L/min). Ventilation during 100% O2 increased from baseline to recovery in all trials (T1: 17.1 ± 1.2 vs. 21.8 ± 1.6, T2: 18.0 ± 1.5 vs. 22.5 ± 1.5, T3: 17.6 ± 1.4 vs. 20.2 ± 2.1).In awake humans, during mild hypercapnia, CH induces a similar magnitude of vLTF as IH. However, a gradual positive drift in ventilation to mild hypercapnia accounts for ~50% of the vLTF. Silencing of the CC with 100% O2 exposure does not transiently abolish vLTF following acute IH or CH, suggesting CC sensitisation may not mediate vLTF.
Cystic fibrosis mice display different breathing patterns than non‐CF mice
Authors: Campanaro Cara K , Darrah Rebecca J , Dick Thomas E , Drumm Mitchell L , Jacono Frank J 
Published: June 2021

Cystic fibrosis (CF) mouse models are used to understand disease physiology, but the CF mouse displays only mild pulmonary pathology. Changes in respiratory pattern are associated with health and disease, but ventilatory pattern has not been investigated in mouse models of CF.Breathing patterns were recorded (200Hz) and quantified in CF mouse models (common mutation ΔF508 (n=22); CF mice complemented with human CFTR in the gastrointestinal tract (FABP‐CFTR, n=11); and wild type (WT, n=24)) using whole body plethysmography. If ANOVA p<0.05, then differences between groups were determined using a multiple comparisons procedure.Respiratory rate was higher in ΔF508 as compared to WT mice (203 [187, 263 vs. 179 [164, 197] bpm; p<0.05). ΔF508 mice also exhibited greater coefficient of variation (CV) of respiratory cycle length (0.28±0.08 vs. 0.20±0.06; p<0.01). Similarly, the FABP mouse group had a respiratory rate (261 [216, 284] bpm) and CV (0.36±0.08) that were significantly greater than the WT group (p<0.05 for both).CF mouse lines exhibited faster respiratory rates and greater ventilatory pattern variability than WT mice. Altered breathing patterns in FABP mice which do not succumb to intestinal obstruction suggest that these differences are not the result of the fragile state of the ΔF508 animals. CF mice may be a good model of pre‐clinical pulmonary disease in humans.
Effect of pulses as part of a low glycemic index diet compared to a high fiber diet on HbA1c and blood lipids in type 2 diabetes
Authors: Kendall Cyril WC , Augustin Livia S , Mitchell Sandra , Sahye-Pudaruth Sandhya , Coveney Judy , Cerovic Aleksandra , Blanco Sonia , Jenkins David JA 
Published: June 2021

ObjectivePulses including beans, lentils and chickpeas are low glycemic index (GI) foods however their effect on glycemic control and blood lipids diet has not been evaluated compared to a high fiber in type 2 diabetes.Methods121 subjects with type 2 diabetes were randomized to one of two 12‐week treatments: 1. Dietary advice included pulses (1 cup cooked/day) and other low GI starches and fruit; 2. Dietary advice to consume a high fiber whole grain diet (40g/2000kcal) (control diet). The primary outcomes were changes in HbA1c and blood lipids.ResultsTreatment differences in pulse intakes and dietary GI were significantly different (+169g and −12.5%, respectively, on Pulse‐low GI diet, p<0.0001). The Pulse‐low GI diet reduced HbA1c by 0.5% units (p<0.001 vs. high fiber), total cholesterol by 0.22 mmol/L (p<0.001), LDL by 0.09 mmol/L (p=0.063) and triglycerides by 0.045 mmol/L (p=0.064). Pulse intake was inversely correlated to changes in HbA1c (r=−0.24, p=0.014), total cholesterol (r=−0.27, p=0.004) and triglycerides (r=−0.24, p=0.012).ConclusionsDietary advice to consume pulses within a low GI diet improved both glycemic control and the serum lipid profile in type 2 diabetes.
Dietary protein and risk of elevated blood pressure in adolescent girls
Authors: Buendia Justin G , Hasnain Syed R , Singer Martha R , Moore Lynn L 
Published: June 2021

The prevalence of elevated blood pressure (EBP) has risen steadily for U.S. adults and children during the past 20 years. The goal of this study is to estimate the effect of dietary protein on adolescent blood pressure. Ten years of follow‐up data from 2379 girls in the National Growth and Health Study ages 9–10 years at baseline were used. Eight sets of 3‐day diet records were collected during the study. BP was measured 3–4 times at each annual visit. Outcomes of interest to these analyses include mean SBP, DBP and risk of EBP in late adolescence (mean age=18.3 years). Analysis of covariance and multiple logistic regression models were used to control for potential confounding by age, race, SES, height, physical activity, age at menarche, and TV/video viewing time. Adjusted mean SBP and DBP levels declined linearly with increasing quintiles of protein intake (SBP: 111.8, 109.7, 108.5, 107.7, 107.4 mmHg; DBP: 67.2, 65.8, 65.3, 64.5, 64.6 mmHg, respectively, for quintiles 1–5; p‐trend<0.0001 for both). Girls in the lowest quintile of intake (<1.0 g•kg body weight−1•day−1) vs. the highest quintile (>1.7 g•kg body weight−1•day−1) were 3.3 times as likely to develop EBP in late adolescence (95% CI: 2.1–5.0). These results were largely attenuated by inclusion of BMI in the models. Dietary protein intake above the current RDA had strong beneficial effects on adolescent BP resulting from its intermediate effects on body composition.Grant Funding Source: NIDDK and Small Grants
Decreased Response of Influenza Specific CD8+ T Cells From Overweight and Obese Humans
Authors: Paich Heather , Sheridan Patricia , Beck Melinda 
Published: June 2021

During infection with influenza virus, CD8+ cytotoxic T cells are essential for limiting the severity and spread of virus by killing infected cells. Because obesity is a risk factor for increased mortality from pH1N1 infection, we hypothesized that a decreased CD8+ T cell number and/or activity may have contributed to the increased susceptibility. Peripheral blood mononuclear cells (PBMCs) from healthy weight, overweight, and obese subjects post vaccination with 2009–2010 seasonal vaccine were stimulated ex vivo with influenza A/Brisbane/59/2007, a component of the vaccine. PBMCs were stained with fluorochrome‐conjugated antibodies and analyzed with flow cytometry. PBMCs from obese subjects exhibited a lower percent increase in CD8+ cytotoxic T cells expressing the early activation marker CD69, than from healthy weight participants. Furthermore, PBMCs from obese participants showed a lower percent increase in activated CD8+ T cells expressing granzyme B and PBMCs from obese and overweight participants showed a lower percent increase in CD8+ T cells expressing IFNγ, in comparison to PBMCs from healthy weight participants. Dendritic cells are required to activate CD8+ T cells, however there were no differences in total and activated dendritic cell numbers between groups. These data suggest that obese and overweight individuals would have greater difficulty recovering from influenza virus infection.Grant Funding Source: NIH RO1AI078090 and P30DK056350