bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leucine contents of isonitrogenous protein sources predict changes in body composition and muscle mass in rats
Authors: Norton Layne Eiseman , Layman Donald K , Wilson Gabriel J , Moulton Chris , Rupassara S. Indu , Garlick Peter J 
Published: June 2021

Increases in intracellular leucine (leu) concentrations stimulate mTOR phosphorylation regulation of skeletal muscle protein synthesis (MPS) and leu content of isonitrogenous complete meals predict MPS potential of individual proteins (J Nutr 139:1103–9, 2009). While the molecular mechanism is established, direct effect of leu on long‐term changes in muscle weight or body composition are unknown. This study evaluated 4 isonitrogenous, isoenergtic diets containing wheat (supplemented with lys), soy, egg, or whey with 6.8, 8.0, 8.8, and 10.9% leu respectively, to determine meal effects of leu on signaling and MPS and long‐term impact on body composition. Male rats (275g) were fed 3 meals/d for 76d consisting of 16/54/30% of energy from protein, carbohydrates and fats. Blood and tissue were taken before or 90min after the breakfast meal at wk 2 and 11. Measurements included muscle weights, body composition by DXA, MPS by D5‐Phe incorporation, and phosphorylation of initiation factors 4E‐BP1 and S6K. Leu content of the meals increased muscle weights and was inversely correlated with bodyfat and these outcomes were associated with greater phosphorylation of 4E‐BP1 and S6K and MPS in animals fed egg and whey. These findings establish that leu content is a crucial factor defining the quality of proteins influencing muscle mass and body composition in adults. Supported by National Dairy Council and Egg Nutrition Center.Grant Funding Source: National Dairy and Egg Nutrition Center
Liposomal Amikacin (Arikace™) in the Treatment of Lower Respiratory Tract Escherichia Coli in A Patient with Cystic Fibrosis
Authors: Laskoski John , Landon Chris 
Published: June 2021

ObjectiveAerosolized antibiotics are directed against Pseudomonas aeruginosa in cystic fibrosis (CF). E. coli decolonization was attempted in a colonized CF patient with multiple IV and oral drugs, including aminoglycosides, cephalosporins, and carbapenems prior to the use of Arikace™. We hypothesized that novel drug formulation nebulized liposomal Amikacin (Arikace™) will eliminate E‐coli from the lower airways.MethodsFour Arikace™ treatment cycles were administered over a 7 month period in three treatment cycles of 28 d, and the fourth of 56 d. A non‐treatment cycle of 28 d was observed between each of the treatment cycles.ResultsQuantitative analysis of sputum confirmed a reduction in the bacterial load of one strand of E.coli from 2.4 x 10E6 cfu/gram to 1.0–10E3 cfu/gram. The density of a second strand of E. coli increased from16 x 10E6 cfu/gram to 18 x 10E6 cfu/gram post‐treatment. Decreased levels of multiple other pathogens were observed. The patient's sputum mass decreased from a pre‐treatment value of 11.1 g to 4.66 g following treatment.ConclusionsArikace™ is a valuable tool to decrease E. coli infection of the lower airways.
Lymph Flow In Instrumented Dogs Varies With Exercise Intensity
Authors: Desai Pratikkumar Vrajeshbhai , Williams Arthur , Prajapati Parna R , Downey H. Fred 
Published: June 2021

ObjectiveTo determine the relationship between exercise intensity and thoracic duct lymph flow.MethodsFive dogs were surgically instrumented with an ultrasonic flow transducer on the thoracic lymph duct and a catheter in the descending thoracic aorta. After recovery from surgery, data were collected at rest and as the dogs ran on a treadmill at speeds from 0 to 10 mph for 1 min at each speed with 15 min rest intervals.ResultsHeart rate increased significantly during exercise, whereas mean aortic pressure did not change. Resting lymph flow was 1.7 ± 0.2 ml/min. Exercise at 1.5 mph significantly raised lymph flow to 3.9 ± 0.6 ml/min (P < 0.01), 121% higher than resting flow. Lymph flow was further elevated at higher treadmill speeds, reaching 9.0 ± 1.6 ml/min (P < 0.01) at 10 mph, 419% higher than resting flow. Regression analysis demonstrated a linear relationship between treadmill speed and the percent increase in lymph flow (see Figure). After exercise, lymph flow returned rapidly to the resting value, but at higher speeds, lymph flow remained significantly greater than resting flow for 1 min (P < 0.01).ConclusionExercise increases lymph flow, and this increase is positively correlated with exercise intensity. (Support: NIH grant U19 AT002023 and Osteopathic Research Center.)
Lymphatic Pump Treatment Increases Thoracic Duct Lymph Flow in Conscious Dogs with Edema Due to Constriction of the Inferior Vena Cava
Authors: Prajapati Parna Ramprasad , Shah Pankhil Virenkumar , King Hollis H. , Williams Arthur G. , Desai Pratikkumar Vrajeshbhai , Downey H. Fred 
Published: June 2021

ObjectiveTo examine the effects of osteopathic lymphatic pump treatment (LPT) on lymph flow in the thoracic duct of instrumented conscious dogs in the presence of edema produced by constriction of the inferior vena cava (IVC).MethodsSix dogs were surgically instrumented with an ultrasonic flow transducer on the thoracic lymph duct and catheters in the descending thoracic aorta and in the IVC. After post‐operative recovery, lymph flow and hemodynamic variables were measured 1) pre‐LPT, 2) during 4 min LPT, 3) post‐LPT, in the absence and presence of edema produced by IVC constriction.ResultsIVC constriction increased abdominal girth from 60±2.6 to 75±2.9 cm. Before IVC constriction, LPT increased lymph flow (P<0.05) from 1.9±0.2 ml/min to a maximum of 4.7±1.2 ml/min, whereas after IVC constriction, LPT increased lymph flow (P<0.05) from 7.9±2.2 to a maximum of 11.7±2.2 ml/min. The incremental lymph flow mobilized by 4 min of LPT, i.e., the flow that exceeded 4 min of baseline flow, was 10.6 ml after IVC constriction (not different from before IVC constriction).ConclusionsEdema caused by IVC constriction markedly increased lymph flow in the thoracic duct. LPT increased thoracic duct lymph flow before and after IVC constriction. The lymph flow mobilized by 4 min of LPT in presence of edema was not significantly greater than that mobilized prior to edema. (Support: NIH grant U19 AT002023 and Osteopathic Research Center.)
Loss of glycocalyx barrier properties impairs insulin‐mediated recruitment of microvascular blood volume in rat hind limb muscle
Authors: Eskens Bart , Cobelens Hanneke , Vink Hans , VanTeeffelen Jurgen 
Published: June 2021

Experimental data suggest that a rapid increase in capillary blood volume underlies the insulin‐mediated glucose uptake in skeletal muscle. We hypothesize that loss of glycocalyx properties impairs the ability of insulin to increase microvascular blood volume in skeletal muscle.In anesthetized rats, the hind limb muscle microcirculation was visualized with a Sidestream Dark Field camera before and during a 30 minute infusion of insulin (6mU/min/kg). Median values and dynamic range of red blood cell (RBC) column widths were measured to determine functional microvascular diameters and glycocalyx barrier function, respectively.In control rats (n=5), insulin infusion increased within five minutes the dynamic range of RBC width with 0.56 μm ± 0.19 μm (mean ± SEM) (P<0.05). Hereafter, microvascular diameter increased with 0.69 μm ± 0.22 μm (P<0.05), while the dynamic range of RBC width returned to pre‐insulin values. In rats, in which the glycocalyx was degraded with a bolus of hyaluronidase (500U; n=7), the dynamic range was already increased at baseline levels with 0.30 μm ± 0.02 μm (p<0.05), with no further effect of insulin. Rapid insulin‐mediated increases in microvascular blood filling in rat skeletal muscle appear to be preceeded by an attenuation of glycocalyx barrier properties. This ability of insulin is impaired after enzymatic degradation of the glycocalyx.Supported by DFN 2006.00.027 and NHF 2005T037
Flow‐Mediated, Redox‐Dependent AT1R Regulation Determines Collateral Growth Capacity
Authors: Unthank Joseph L. , Miller Steven J. , Labarrere Carlos A. 
Published: June 2021

We previously observed flow‐related suppression of AT1R mRNA in collaterals of the SHR (Miller, 2008) which is characterized by oxidative stress, metabolic abnormalities and impaired collateral growth (CG). This study was undertaken to determine the role of flow‐related AT1R regulation in both the promotion of CG in normotensive WKY and CG impairment in SHR.RT‐PCR demonstrated upregulation (3.0±0.7X) in WKY but suppression in SHR (−2.4±0.5X). Immunostaining for AT1R demonstrated significant upregulation throughout the arterial wall in WKY but not SHR collaterals (see table). Losartan prevented CG and the associated endothelial proliferation in WKY. Captopril but not losartan restored CG in SHR and prevented AT1R down‐regulation. Captopril also restored normal p22phox expression in SHR. We propose that AT1R upregulation and stretch‐dependent AT1R activation is induced by elevated shear stress in WKY but prevented by oxidative stress in SHR.
Number of cells in each wall layer with significant immunoreactivity, as percent of total cells. A remarkable increase is observed in all wall layers of the WKY collateral.

% Cells with AT1R Immunoreactivity

Intima
Media
Adventitia

WKY‐Control
8±2.0
10±2.1
10±1.2

WKY‐Collateral
45±5.6*
74±8.2*
43±8.2*

SHR‐Control
6±0.6
9±1.1
11±2.1

SHR‐Collateral
3±0.4
9±1.8
3±2.6*

N=3
p≤0.05.

Supported by HL42898.
The ZDSD, a New Rat Model of Metabolic Syndrome: Altered Arterial Muscle Mechanics
Authors: Packer C Subah , Boice Alexa M , Meulen Leeanna M , Coy Kathy , Peterson Richard G 
Published: June 2021

The goal was to determine if altered arterial muscle contractility or compliance plays a role in cardiovascular disease reported for ZDSD. ZDSD and control SD systemic BP were not different from 18 to 24 weeks of age. At the end of the study period, ZDSD were found to have larger hearts but lower heart/body weight ratios indicating that increase in heart size did not keep pace with body mass increase. ZDSD had elevated right/left ventricular weight ratios (RV/LV+S) indicating right heart hypertrophy and pulmonary hypertension. ZDSD and SD caudal arterial muscle resting length‐tension (L‐T) curves were similar indicating no change in tissue compliance. The ZDSD active L‐T curve was elevated above the SD active L‐T curve indicating that ZDSD arterial muscle is more contractile. Hypercontractile arterial muscle could be causally related to systemic hypertension. Systemic arterial muscle hypercontractility, enlarged hearts, low heart/body weight, pulmonary hypertension, trend towards systemic hypotension are consistent with an initial phase of diabetes‐associated systemic hypertension followed by cardiac insufficiency and congestive heart failure in ZDSD.Supported by PreClinOmics. A Boice and L Meulen were 2009 Indy Project SEED Scholars supported by American Chemical Society (ACS), Lilly, DowAgroSciences, IUPUI Indiana Clinical and Translational Sciences Institute (CTSI)
Niacin reduces renal damage and insulin insensitivity in Charles River Obese SHR (SHROB/cp): a model of the metabolic syndrome
Authors: Kang Youn‐Jung , Manero Tabitha , Levine Seymour , Owens Dwight , Chander Praveen , Stier Charles 
Published: June 2021

Niacin is a hypolipemic drug which lowers triglyceride levels. We examined the effect of niacin (5% in chow) from 8 to 15 weeks of age on renal damage in SHROB/cp from Charles River Laboratories. SHROB/cp (n=4) exhibited increased body weight, urinary protein excretion (UPE), focal segmental glomerulosclerosis (FSGS) and plasma insulin as compared with lean control rats SHROB/kol (n=5, Table). Plasma triglyceride (605 ± 101 v 140 ± 12 mg %) and blood glucose (147 ± 21 v 114 ± 4 mg %) levels were also greater in SHROB/cp than SHROB/kol, respectively. Niacin (n=5) markedly reduced UPE, FSGS and plasma insulin while blood glucose was unaffected. Niacin strikingly reduced renal inflammation and tubular scarring. SBP did not differ between SHROB/kol and SHROB/cp and was unaffected by niacin treatment of SHROB/cp. Niacin reduced hepatic steatosis and plasma 8‐isoprostane levels in SHROB/cp.

SHROB/kol
SHROB/cp
SHROB/cp &Niacin

Body Weight (g)
349±15
462±15 **
418±10 **†

UPE (mg/day)
19±3
225±45 **
48±12 ††

SBP (mmHg)
211±4
199±5
192±4 *

FSGS (%)
0.5±0.2
16.6±5.9 **
1.4±0.4 ††

Plasma Insulin (ng/ml)
5.9±2.1
76.1±9.1 **
26.5±7 *††

Plasma Isoprostane (pg/ml)
8.4±0.6
27±10 **
10.4±0.8 ††

P≤.05
P≤.01 v SHROB/kol;
P≤.05
P≤.01 v SHROB/cp

In conclusion, niacin may be of particular benefit in combating renal damage in the metabolic syndrome and diminished oxidative stress may be an important mechanism for this effect.
Telmisartan improves cognitive function through the increase in neurotrophic factor and inhibition of apoptosis in hippocampus of rats with metabolic syndrome
Authors: Kishi Takuya , Hirooka Yoshitaka , Sunagawa Kenji 
Published: June 2021

BackgroundIn metabolic syndrome (MetS), impaired cognitive function has been indicated. We investigated whether telmisartan, an AT1 receptor blocker, improves cognitive function of MetS.Methods and ResultsMale Sprague‐Dawley rats were fed on a high‐fat diet and segregated into obesity‐prone (OP) showed a MetS profile with hypertension and obesity‐resistant (OR) after 13 weeks. OP was treated either with telmisartan (TLM‐OP) or hydralazine (HYD‐OP) for 12 weeks. Morris water maze test, a cognitive function test determined by latency (the shorter the better) to reach platform, was significantly longer in OP than in OR (42±3 sec vs. 29±2 sec, n=4, P<0.01), and significantly shorter in TLM‐OP than in HYD‐OP despite of similar blood pressure. Brain‐derived neurotrophic factor (BDNF) in hippocampus was significantly lower in OP than in OR, and significantly higher in TLM‐OP than in HYD‐OP. Apoptosis in hippocampus was significantly higher in OP than in OR, and significantly lower in TLM‐OP than in HYD‐OP.ConclusionTelmisartan improves cognitive function through the increase in BDNF and inhibition of apoptosis in hippocampus in rats with MetS independent of blood pressure lowering effect.
Akt/Bcl‐2 signaling is critical for anti‐apoptotic effects of carbon monoxide (CO) against TNF‐alpha‐mediated inflammatory damage in cerebral vascular endothelial cells.
Authors: Basuroy Shyamali , Bhattacharya Sujoy , Leffler Charles W. , Parfenova Helena 
Published: June 2021

The pro‐inflammatory cytokine TNF‐alpha causes oxidative stress and apoptosis in cerebral vascular endothelium. CO, an endogenous gaseous mediator, provides cytoprotection from inflammatory endothelial damage. Phosphorylation signaling via Protein Kinase B/Akt and the anti‐apoptotic protein Bcl‐2 is involved in various cell survival mechanisms. We addressed the hypothesis that Akt/Bcl‐2 signaling mediates anti‐apoptotic effects of CO and promotes endothelial cell survival during brain inflammatory disease. In primary cultures of cerebral microvascular endothelial cells from newborn pigs, TNF‐alpha (15 ng/ml) caused transient phosphorylation of Akt at Ser473 (5–10 min) and increased Bcl‐2 protein (3h). Triciribine, an Akt phosphorylation inhibitor, or Akt siRNA knockdown potentiated TNF‐evoked DNA fragmentation and blocked the anti‐apoptotic capacity of a CO‐releasing molecule (CORM‐A1), indicating Akt is essential for endothelial survival and is required for COmediated cytoprotection during inflammation. Triciribine reduced CO‐evoked increase in Bcl‐2 protein suggesting Akt is an upstream regulator of Bcl‐2. Bcl‐2 inhibitors (gossipol, Bcl2‐I, and HA14‐1) blocked the anti‐apoptotic capacity of CORM‐A1. These data indicate Akt/Bcl‐2 signaling is critical for CO‐mediated cytoprotection against TNF‐alpha‐mediated inflammatory damage in cerebral vascular endothelium.Grant support: NIH/NINDS and NIH/NHLBI. S. Basuroy is supported by the Beginning‐Grant‐in‐Aid from AHA.
Gender specific regulation of hepatic aquaglyceroporin 9 and glycerol kinase expression
Authors: Lebeck Janne , Lund Sten A. , Praetorius Jeppe 
Published: June 2021

Increased hepatic glucose production plays a pivotal role in the pathophysiology of diabetes. AQP9 has been suggested to facilitate the transport of glycerol into hepatocytes where glycerol kinase (GK) catalyses the initial step for its conversion into either glucose or glycerolipids. Hence, the regulation of AQP9 and thereby glycerol uptake could be a potential modulator of hepatic glucose production. This study aims to investigate the role of gender in regulation of hepatic AQP9 and GK protein. Immunoblotting showed that starvation of male rats resulted in increased hepatic AQP9 and GK abundance, whereas, starved female rats displayed no increase in AQP9 or GK. In contrast, plasma glycerol levels were doubled in female rats in response to starvation, whereas no statistically significant changes were found in male rats. Interestingly, immunoblotting revealed that castration of male rats resulted in a 1.5 fold increase in hepatic AQP9 expression, but a decrease in GK abundance. This was accompanied by a marked reduction in plasma glycerol together with a small but significant increase in plasma glucose when compared with controls. We conclude that sexual dimorphism exists in hepatic glycerol handling in response to starvation and that castration of male rats has a diverse effect upon liver abundance of AQP9 and GK.Supported by the Danish National Research Foundation
Endothelin‐1 and the Metalloproteases ECE and NEP in DOCA‐Salt Hypertensive Rats
Authors: Nelissen Jelly , Lemkens Pieter , Debets Jacques , van Essen Helma , Bost Jet , Schiffers Paul , De Mey Jo , Janssen Ben 
Published: June 2021

Endothelin‐1 (ET‐1) is thought to be a key player in DOCA‐salt induced hypertension. We hypothesized that the bioavailability of ET‐1 is controlled by tissue specific expression of the metalloproteases endothelin converting enzyme (ECE) and neutral endopeptidase (NEP). To test this hypothesis we measured ECE and NEP protein content in kidneys and hearts of DOCA‐salt treated rats 3 and 6 weeks after implantation of a 100 mg DOCA pellet combined with high salt drinking water. In addition, ET‐1 content was determined in these organs by RIA. During DOCA‐salt treatment, blood pressure was significantly elevated in association with increased kidney and heart weight. Despite the occurrence of structural damage in these organs (verified by histology), ECE, NEP, and ET‐1 content were not significantly altered 3 and 6 weeks after DOCA treatment (n=6/organ/group). These data indicate that both ET‐1 and metalloprotease content in the heart and kidneys do not contribute to the maintenance of hypertension in the DOCA‐salt rat model.This research was performed within the framework of project T2‐108 of the Dutch Top Institute Pharma.
Kinetics of nitrosation of GSH using NO donors
Authors: Madrasi Kumpal Jagdish , Joshi Mahesh S , Tsoukias Nikolaos 
Published: June 2021

Modification of critical thiols by reactive nitrogen species (RNS) act as regulators of protein mediated signaling. Nitrosothiols are also believed to act as vasodilators which can release NO and activate the heme protein guanylate cyclase, thus initiating the mechanism for vasodilation. Nitrosation is thought to be mediated by dinitrogen trioxide (N2O3). Combination of NO with thiyl radical (GS.) following oxidation of the thiyl anion by NO2 has also been suggested as a mechanism for nitrosothiol formation. We investigate the kinetic mechanism of GSH (0–20mM) nitrosation in vitro by NO donor PAPA/NO (0.5 – 10 mM). GSNO formation was assessed spectrophotometrically at 338 nm. Results suggest a Michaelis‐Menten dependence of the rate on GSH concentration with a half‐maximum constant (Km,GSH) that depends on NO concentration. If there were solely one mechanism of nitrosation, one would expect a constant Km GSH value. Increasing [NO] up to 10 fold showed a proportional increase in Km,GSH. Pseudo steady state approximation yields the following kinetic rate for GS mediated nitrosation:
urn:x-wiley:08926638:media:fsb2fasebj241supplement98422:fsb2fasebj241supplement98422-math-0001The reported increase in Km,GSH with NO concentration suggest a significant contribution of GS.mediated nitrosation in the formation of GSNO.(Supported by NIH SC1HL95101)
Downrgulation of L‐type calcium channels increase media thicknes and change smooth muscle phenotype in rat resistance arteries in vivo.
Authors: Aalkjær Christian , Møller Kate , Matchkov Vladimir 
Published: June 2021

The voltage‐gated L‐type Ca channels (LTCCs) are important in smooth muscle excitation‐transcription coupling. We have developed a method for downregulation of the LTCC in rat small mesenteric arteries in vivo by the use of siRNA. Transfection with specific siRNA decreased LTCC expression by ~75%. The downregulated arteries developed reduced wall stress in response to K‐induced depolarization which resembled control arteriess pre‐treated with nifedipine. Changes in wall stress correlated with smaller changes in [Ca2+]i in the arteries downregulated for LTCC. Similar changes were seen with noradrenalin and vasopressin.In contrast to the effect of LTCC blocker chronic treatment, the LTCC downregulated arteries had increase in media thickness in comparison to the controls. The remodeling was associated with phenotypic changes of the VSMCs: contractile phenotype markers (myocardin, tropomyosin 4, smooth muscle myosin heavy chain, smooth muscle α‐actin and h‐caldesmon) were significantly downregulated, while marker genes for the proliferative phenotype (l‐caldesmon and ki‐67) were significantly upregulated. In α‐toxin permeabilized arteries downregulated for LTCC the force development to calcium was reduced compared to control arteries. We conclude that LTCC expression and/or activity are crucial in determining VSMC phenotype as well as the structure of small resistance arteries.
Effects of hibernation‐induced bradycardia on cardiac myosin heavy‐chain and myocardial mRNA expression in grizzly bears
Authors: Barrows Nathan David , Nelson Lynne , Robbins Charles , Rourke Bryan 
Published: June 2021

Grizzly bears, Ursus arctos horribilis, tolerate extended periods of low heart rate during hibernation without developing congestive heart failure or chamber dilation. We evaluated myocardial response to hibernation‐induced bradycardia by measuring myosin heavy‐chain (MyHC) isoform expression in the left atria and left ventricles of active and hibernating bears, as well as relative mRNA expression of a set of genes important to muscle plasticity. We supplemented these data with echocardiographic measurements of systolic and diastolic function in unanesthetized bears. Relative MyHC‐α protein expression increased by 10% in the atria during hibernation, uncharacteristic of bradycardia in non‐hibernators. The left ventricle expressed 100% MyHC‐β protein in both groups. Insulin‐like growth factor (IGF‐I) mRNA expression was reduced by ~50% in both chambers during hibernation, consistent with observed ventricular atrophy. A 50% decrease in atrial creatine kinase mRNA expression occurred in hibernators. Taken in context with hemodynamic assessment of increased atrial afterload and ventricular stiffness, these data suggest a potential downregulation of atrial chamber function during hibernation to prevent fatigue and dilation due to excessive work against an optimally filled ventricle.Supported by NIH MBRS SCORE 2 S06 GM063119, the Autzen Foundation and the WSU Bear Center.