bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXERCISE AND SKELETAL MUSCLE GLUCOSE TRANSPORTER 4 EXPRESSION: MOLECULAR MECHANISMS
Authors: McGee Sean L , Hargreaves Mark 
Published: March 2006

SUMMARY

Skeletal muscle is a highly plastic tissue that has a remarkable ability to adapt to external demands, such as exercise. Many of these adaptations can be explained by changes in skeletal muscle gene expression. A single bout of exercise is sufficient to induce the expression of some metabolic genes. We have focused our attention on the regulation of glucose transporter isoform 4 (GLUT‐4) expression in human skeletal muscle.
Glucose transporter isoform 4 gene expression is increased immediately following a single bout of exercise, and the GLUT‐4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) transcription factors are required for this response. Glucose transporter isoform enhancer factor and MEF2 DNA binding activities are increased following exercise, and the molecular mechanisms regulating MEF2 in exercising human skeletal muscle have also been examined.
These studies find possible roles for histone deacetylase 5 (HDAC5), adenosine monophosphate–activated protein kinase (AMPK), peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC‐1α) and p38 mitogen‐activated protein kinase (MAPK) in regulating MEF2 through a series of complex interactions potentially involving MEF2 repression, coactivation and phosphorylation.
Given that MEF2 is a transcription factor required for many exercise responsive genes, it is possible that these mechanisms are responsible for regulating the expression of a variety of metabolic genes during exercise. These mechanisms could also provide targets for the treatment and management of metabolic disease states, such as obesity and type 2 diabetes, which are characterized by mitochondrial dysfunction and insulin resistance in skeletal muscle.
EVIDENCE FOR A SUPRASPINAL CONTRIBUTION TO HUMAN MUSCLE FATIGUE
Authors: Taylor Janet L , Todd Gabrielle , Gandevia Simon C 
Published: March 2006

SUMMARY

Muscle fatigue can be defined as any exercise‐induced loss of ability to produce force with a muscle or muscle group. It involves processes at all levels of the motor pathway between the brain and the muscle. Central fatigue represents the failure of the nervous system to drive the muscle maximally. It is defined as a progressive exercise‐induced reduction in voluntary activation or neural drive to the muscle. Supraspinal fatigue is a component of central fatigue. It can be defined as an exercise‐induced decline in force caused by suboptimal output from the motor cortex.
When stimulus intensity is set appropriately, transcranial magnetic stimulation (TMS) over the motor cortex during an isometric maximal voluntary contraction (MVC) of the elbow flexors commonly evokes a small twitch‐like increment in flexion force. This increment indicates that, despite the subject's maximal effort, motor cortical output at the moment of stimulation was not maximal and was not sufficient to drive the motoneurons to produce maximal force from the muscle. An exercise‐induced increase in this increment demonstrates supraspinal fatigue.
Supraspinal fatigue has been demonstrated during fatiguing sustained and intermittent maximal and submaximal contractions of the elbow flexors where it accounts for about one‐quarter of the loss of force of fatigue. It is linked to activity and the development of fatigue in the tested muscles and is little influenced by exercise performed by other muscles.
The mechanisms of supraspinal fatigue are unclear. Although changes in the behaviour of cortical neurons and spinal motoneurons occur during fatigue, they can be dissociated from supraspinal fatigue. One factor that may contribute to supraspinal fatigue is the firing of fatigue‐sensitive muscle afferents that may act to impair voluntary descending drive.
PROTEOMIC ANALYSIS OF RAT AORTA DURING ATHEROSCLEROSIS INDUCED BY HIGH CHOLESTEROL DIET AND INJECTION OF VITAMIN D3
Authors: Almofti Mohamad Radwan , Huang Zhenyu , Yang Pengyuan , Rui Yaocheng , Yang Pengyuan 
Published: March 2006

SUMMARY

Atherosclerosis (AS) in rats displays important clinical similarities to human AS.
After the experimental model of AS in rat was established and using a proteomic approach, we compared the protein profiling of aorta tissues from healthy and AS rats.
Using two‐dimensional electrophoresis (2‐DE), over 1878 protein species were separated; among them, 1239 protein spots were matched between different gels with average matching rate of approximately 66%. Gel analysis and protein characterization have identified 58 protein spots whose abundance is significantly altered in AS rats.
By using matrix‐associated laser desorption ionization time‐of‐flight mass spectrometer (MALDI‐TOF‐MS) and NCBInr database, 46 proteins were successfully identified. Among them, 18 proteins were of increased abundance in diseased tissues including a group of oxidization‐related enzymes such as peroxiredoxin2 and NADH dehydrogenase Fe‐S protein 6, components of inflammatory pathways such as lamin A, while 28 proteins were of decreased abundance in the diseased state, including CaM‐KII inhibitory protein, transferring, fructose‐bisphosphate aldolase.
We believe that these results would give insights into the cellular and molecular mechanisms involved in AS development and might lead to the discovery of novel diagnostic markers and new therapeutic opportunities.
NARINGIN DOES NOT ALTER CAFFEINE PHARMACOKINETICS, ENERGY EXPENDITURE, OR CARDIOVASCULAR HAEMODYNAMICS IN HUMANS FOLLOWING CAFFEINE CONSUMPTION
Authors: Ballard Tasha LP , Halaweish Fathi T , Stevermer Cheryl L , Agrawal Puja , Vukovich Matthew D 
Published: March 2006

SUMMARY

Naringin, a grapefruit constituent interacts with many medications including caffeine, a popular weight loss supplement. The purpose of the current study was to identify changes in caffeine pharmacokinetics, resting energy expenditure (REE), oxygen consumption (VO2) and respiratory exchange ratio (RER) after an acute dosage of caffeine and naringin.
Using a double‐blinded, counterbalanced design, REE, VO2, and RER were measured before and systematically for 8 h after a single dosage of caffeine (CAF, 200 mg) with and without naringin (100 mg (CN100) or 200 mg (CN200)) in 10 apparently healthy individuals. A standardized meal was provided following 240‐minute measurements (400 kcals; 35 g carbohydrate; 27 g protein; 7 g fat).
Caffeine, CN100, CN200 did not alter VO2 or VO2 area under the curve (137 301 ± 8318, 139 729 ± 9300, 134 297 ± 8318, mL/480 min). Resting energy expenditure (k/cals) was 10.0 ± 1.4% higher with CAF versus CN200 (6.0 ± 1.4%) and CN100 (6 ± 1.5%) at 240 min (P = 0.07) which was then negated following a standardized meal. Percent change in RER from pre to 240 min and pre to 480 min was not different between the CAF, CN100, or CN200 (–0.2 ± 1.7%, 1.7 ± 1.7%, –2.8 ± 1.9%).
Although caffeine alone suggests a trend of increased REE, the results of the present study indicate that concurrent consumption of caffeine with naringin in acute dosages does not affect RER, VO2, and prevents the increase of REE in adult humans. The results suggest that the interaction of grapefruit juice and caffeine may be due to constituents of grapefruit juice other than naringin or in addition to naringin.
ISOFLURANE AND OTHER COMMONLY USED ANAESTHETICS DO NOT PROTECT THE ISOLATED BUFFER PERFUSED MOUSE HEART FROM ISCHEMIA‐REPERFUSION INJURY
Authors: Galagudza Michael , Vaage Jarle , Valen Guro 
Published: March 2006

SUMMARY

Some anaesthetic agents such as barbiturates and opioids possess cardioprotective properties in rats, rabbits, dogs and pigs. The purpose of this study was to evaluate the effects of some commonly used anaesthetic agents (pentobarbital, isoflurane and a mixture of midazolam, fentanyl and fluanisone) on the tolerance of the isolated mouse heart to ischaemia‐reperfusion injury.
The isolated, Langendorff‐perfused hearts were subjected to 45 min of global ischaemia followed by 60 min of reperfusion. Left ventricular pressures, heart rate and coronary flow were measured and infarct size was determined using triphenyltetrazolium staining.
There were no differences in haemodynamic variables during reperfusion between groups. Infarct size was not influenced by the choice of anaesthesia.
None of the anaesthesia protocols exerted significant protective effects on the ischaemic‐reperfused isolated mouse heart performance. In mice, isoflurane as well as pentobarbital, opioids and benzodiazepines may be safely used for anaesthesia without a risk of protective side‐effects in isolated mouse heart studies.
CHARACTERIZATION OF RWJ‐351647, A NOVEL NONPEPTIDE VASOPRESSIN V2RECEPTOR ANTAGONIST
Authors: Gunnet Joseph W , Matthews Jay M , Maryanoff Bruce E , De Garavilla Lawrence , Andrade‐Gordon Patricia , Damiano Bruce , Hageman William , Look Richard , Stahle Paul , Streeter Anthony J , Wines Pamela G , Demarest Keith T 
Published: March 2006

SUMMARYAntagonists of the V2vasopressin (AVP) receptor are aquaretic agents, inhibiting water resorption without stimulating electrolyte excretion. In this set of experiments, a novel V2receptor antagonist, RWJ‐351647, was characterizedin vitroandin vivo.RWJ‐351647 displaced3H‐AVP binding from cloned human V2and V1Areceptors withKivalues of 1 nmol/L and 24 nmol/L. In assays using transfected HEK293 cells expressing either human or rat V2receptors, RWJ‐351647 inhibited AVP‐induced cAMP accumulation withKivalues of 3 nmol/L and 6 nmol/L, respectively.RWJ‐351647 was very selective in binding assays and showed only weak functional antagonist activity at either the cloned human V1Band oxytocin receptors or the human platelet V1Areceptor. No agonist activity was seen with the compound at any receptor.Pharmacokinetic studies in rats showed RWJ‐351647 to be 41.9% bioavailable after a single oral administration. After repeated daily dosing over 5 days, the oral bioavailability remained at 43.9% with no change in the compound peak plasma levels or clearance rate.In efficacy studies, RWJ‐351647 increased urine output and decreased urine osmolality with oral doses as low as 0.1 mg/kg and 1.0 mg/kg in rats and cynomolgus monkeys, respectively. In a multiple dose study in primates, RWJ‐351647 maintained a consistent aquaretic effect over 10 days without increasing sodium or potassium excretion.In summary, RWJ‐351647 was shown to be a selective and potent V2receptor antagonist with sustainable aquaretic activity in both rats and primates. The preclinical data suggest that RWJ‐351647 is a potent and effective aquaretic agent with potential for use in diseases characterized by water retention.
EFFECTS OF INSULIN TREATMENT ON HEART RHYTHM, BODY TEMPERATURE AND PHYSICAL ACTIVITY IN STREPTOZOTOCIN‐INDUCED DIABETIC RAT
Authors: Howarth FC , Jacobson M , Shafiullah M , Adeghate E 
Published: March 2006

SUMMARYStreptozotocin (STZ)‐induced diabetic cardiomyopathy is frequently associated with depressed diastolic/systolic function and altered heart rhythm.The effects of insulin treatment on heart rhythm, body temperature and physical activity in STZ‐induced diabetic rats were investigated using biotelemetry techniques.Transmitter devices were surgically implanted in the peritoneal cavity of young adult male Wistar rats. Electrodes from the transmitter were arranged in Einthoven bipolar – Lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded with a telemetry system for 10 days before STZ treatment, for 20 days following administration of STZ (60 mg/kg) and thereafter, for 30 days while rats received daily insulin.Heart rate, physical activity and body temperature declined rapidly 3–5 days after administration of STZ. Pre‐STZ heart rate was 362 ± 7 b.p.m., falling to 266 ± 12 b.p.m. 5–15 days after STZ with significant recovery to 303 ± 14 b.p.m. 10–20 days after commencement of insulin. Pre‐STZ body temperature was 37.5 ± 0.1C, falling to 37.2 ± 0.2C 5–15 days after STZ with significant recovery to 37.5 ± 0.1C 10–20 days after commencement of insulin. Physical activity and heart rate variability were also reduced after STZ but there was no significant recovery during insulin replacement.5. Defective autonomic regulation and/or mechanisms of control that are intrinsic to the heart may underlie disturbances in heart rhythm in the STZ‐induced diabetic rat.
PROTECTIVE EFFECT OF PAEONIFLORIN ON IMMUNOLOGICAL LIVER INJURY INDUCED BY BACILLUS CALMETTE‐GUERIN PLUS LIPOPOLYSACCHARIDE: MODULATION OF TUMOUR NECROSIS FACTOR‐α AND INTERLEUKIN‐6 mRNA
Authors: Liu Dao‐Fang , Wei Wei , Song Li‐Hua 
Published: March 2006

SUMMARY

1. Paeoniflorin is one of the main effective components of the total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora which has been used for gynaecological problems and for cramp, pain and giddiness for over 1 500 years in Chinese medicine. Anti‐inflammatory, antioxidative, antihepatic injury and immunoregulatory activities of TGP have been extensively proved in our laboratory for many years. Our present study investigates the effects and mechanisms of paeoniflorin on immunological liver injury in mice.
A model of immunological liver injury was induced by tail vein injection of bacillus Calmette‐Guérin (BCG) and lipopolysaccharide (LPS) in mice. Activities of serum alanine aminotransferase (ALT) were measured by biochemical methods. Hepatic tissue sections were stained with haematoxylin and eosin and examined under a light microscope. Tumor necrosis factor (TNF)‐a, interleukin (IL)‐6, lipopolysaccharide binding protein (LBP) and CD14 mRNA (messenger ribonucleic acid) expression in mouse liver were determined by semiquantitative reverse transcription polymerase chain reaction (RT‐PCR) analysis.
Immunological liver injury induced by BCG plus LPS was successfully duplicated. Serum ALT activities were significantly decreased by paeoniflorin. (25, 50, 100 mg/kg). Histological examination demonstrated that paeoniflorin could attenuate the area and extent of necrosis and reduce the immigration of inflammatory cells. The increase in TNF‐a, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time‐point. The augmentation of IL‐6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection.
Paeoniflorin could significantly protect against immunological liver injury in mice. TNF‐a, IL‐6, LBP and CD14 mRNA expression in mouse liver may be involved in BCG plus LPS induced liver injury. The protective mechanism of paeoniflorin might be partially related to modulation of TNF‐a, IL‐6, LBP and CD14 mRNA expressions in mouse liver.
ACUTE DILATORY AND NEGATIVE INOTROPIC EFFECTS OF HOMOCYSTEINE ARE INHIBITED BY AN ADENOSINE BLOCKER
Authors: Kennedy Richard H , Owings Richard , Joseph Jacob , Melchert Russell B , Hauer‐Jensen Martin , Boerma Marjan 
Published: March 2006

SUMMARY

Previous studies have shown that homocysteine elicits acute negative inotropic and coronary vasodilatory effects in rat hearts. In addition, this earlier work suggested that the inotropic action is mediated via an endothelium‐derived agent that is neither nitric oxide (NO) nor a cyclooxygenase product, while the coronary actions were found to be antagonized by the NOS inhibitor l‐NNA. Current experiments, which utilized coronary‐perfused rat hearts, were designed to determine if muscarinic or adenosine receptors are involved in these acute actions of homocysteine.
Left ventricular developed pressure was used as a measure of systolic function in electrically paced, Langendorff‐perfused heart with coronary pressure being used to monitor coronary vascular tone. Acute effects of homocysteine (10–300 mmol/L) were examined in the presence and absence of 1 ¥ 10‐6 mol atropine or 7 ¥ 10‐5 mol 8‐(p‐sulfophenyl) theophylline (SPT), a non‐selective adenosine receptor antagonist.
Atropine had no effect on either the inotropic or vascular actions of homocysteine. In contrast, SPT partially antagonized both actions of the amino acid with the antagonism of the vasodilation being much greater than its inhibition of the negative inotropic effect. Experiments with adenosine demonstrated that the selected dose of SPT elicited marked rightward shifts in the dose–response curves for both the inotropic and vascular actions.
Current results suggest that adenosine plays a role in both the negative inotropic and vasodilatory actions of homocysteine. However, the relatively minor antagonistic action of SPT on the inotropic effect of homocysteine suggests that additional endothelium‐derived mediators underlie its effects on contractility.
EARLY STRUCTURAL CHANGES OF AORTIC WALL IN SINOAORTIC‐DENERVATED RATS
Authors: Shen Fu‐Ming , Zhang Shu‐Hui , Xie He‐Hui , Jing Qing , Wang Di‐Song , Su Ding‐Feng 
Published: March 2006

SUMMARY

The present work was designed to observe the early structural changes in the aortic wall in Sprague‐Dawley rats 1, 2 and 4 weeks after sinoaortic denervation (SAD).
Rats were examined 1, 2 and 4 weeks after SAD. Blood pressure (BP) was recorded in the conscious state. The thoracic aortas were taken for investigations, including: light microscopy, electron microscopy, immunohistochemistry and terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling (TUNEL).
Blood pressure variability (BPV) was significantly increased in the SAD groups 1, 2 and 4 after the operation when compared with the sham‐operated ones.
Two weeks after SAD the percentage proportion of smooth muscle cell density (SMC%) was obviously increased.
Four weeks after SAD: the SMC%, percentage proportion of collagen density (CD%) and aortic wall thickness (WT) were obviously increased with vascular smooth muscle cells blebbing concomitantly. Endothelial cells showed degenerative changes and swelling with blebbing of the cell membrane and increased condensation of peripheral nuclear chromatin and cytoplasmic vacuolization. It was also found that the number of apoptotic endothelial cells was increased and expression of eNOS was reduced.
This is the first study that shows the time‐course of aortic wall and endothelial cell changes induced by SAD. Increased BPV might be the priming factor in the development of organ damage induced by SAD.
IN VITRO NEUROTOXIC AND MYOTOXIC EFFECTS OF THE VENOM FROM THE BLACK WHIP SNAKE (DEMANSIA PAPUENSIS)
Authors: Kuruppu S , Fry Bryan G , Hodgson Wayne C 
Published: March 2006

SUMMARY

Black whip snakes belong to the family elapidae and are found throughout the northern coastal region of Australia. The black whip snake (Demansia papuensis) is considered to be potentially dangerous due to its size and phylogenetic distinctiveness. Previous liquid chromatography–mass spectrometry analysis of D. papuensis venom indicated a number of components within the molecular mass ranges compatible with neurotoxins. For the first time, this study examines the in vitro neurotoxic and myotoxic effects of the venom from D. papuensis.
Venom (10 mg/mL) caused significant inhibition of twitches elicited by stimulation (0.2 ms, 0.1 Hz, supramaximal V) of motor nerves in the chick biventer cervicis nerve‐muscle preparation. This neurotoxic effect, which was postsynaptic in origin, was weak in comparison to that of most other Australian elapids. Prior addition (10 min) of polyvalent (PSAV) or tiger snake (TSAV) antivenom (5 units/mL) prevented venom‐induced twitch inhibition. Addition of PSAV (5 units/mL) at t50 failed to reverse the inhibitory effect but prevented further inhibition of nerve‐mediated twitches.
The venom (20–50 mg/mL) is also myotoxic as indicated by a slowly developing contracture and inhibition of twitches elicited by direct stimulation (2 ms, 0.1 Hz, supramaximal V, in the presence of tubocurarine 10 mmol/L) of the chick biventer muscle. This activity was confirmed by histological examination of the muscle.
Fractionation and characterization of venom components is required to further investigate the reasons for the weak neurotoxic activity of D. papuensis venom.
EFFECTS OF ORAL BERAPROST SODIUM, A PROSTAGLANDIN I2 ANALOGUE, ON ENDOTHELIUM DEPENDENT VASODILATATION IN THE FOREARM OF PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Ohata Shuzo , Ishibashi Yutaka , Shimada Toshio , Takahashi Nobuyuki , Sugamori Takashi , Sakane Takeshi , Hirano Yoshifumi , Oyake Nobuyuki , Murakami Yo , Higami Tetsuya 
Published: March 2006

SUMMARY

Previous clinical studies with prostaglandin I2 (PGI2) analogue beraprost sodium suggested the potential effects on protection of cardiovascular events in patients with peripheral artery disease. Although the mechanism is not well known, experimental studies have shown protective effects of endothelial cells. This study was designed to examine the effects of beraprost sodium on vascular endothelial function in the forearm of patients with coronary artery disease.
Beraprost sodium (120 mg/day) was orally administered to 14 coronary artery disease patients for 4 weeks and then stopped for 4 weeks. Eleven control patients did not receive beraprost sodium treatment. Reactive hyperemia was induced in the forearm, endothelium‐dependent vasodilatation was assessed by plethysmography, and urinary 8‐iso‐prostaglandin F2a (8‐iso‐PGF2a) was measured at baseline, 4 weeks and 8 weeks.
Both groups had similar reactive hyperemic responses at baseline. In the control group, reactive hyperemic response and urinary 8‐iso‐PGF2a remained unchanged for 8 weeks. In the beraprost group, maximum forearm blood flow increased significantly (P = 0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater than baseline at 8 weeks (P = 0.02). Urinary 8‐iso‐PGF2a decreased significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P = 0.07). Changes in reactive hyperemia correlated weakly but significantly with changes in 8‐iso‐PGF2a (P < 0.001).
Beraprost sodium decreased oxidative stress and improved forearm endothelium‐dependent vasodilatation in coronary artery disease patients. The favorable effects on vascular endothelium could potentially lead to a decrease in vascular events.