bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects Of Trilinolein On Superoxide Dismutase Activity And Mrna Levels In Aortic Smooth Muscle Cells
Authors: Chan Paul , Chang Jun‐Jen , Chen Fu‐Chean , Wu Ming‐Shun , Tomlinson Brian , Cheng Juei‐Tang 
Published: March 2003

SUMMARY1. Atherosclerotic cardiovascular disease is still the leading cause of death in Western countries. Oxygen free radicals are considered to be intimately involved in the development of atherosclerosis. Anti‐oxidants may help to protect mammalian cells from the damage induced by these reactive oxygen species. Many reports have indicated that anti‐oxidants used in the treatment or prevention of disease could modify the levels of superoxide dismutase (SOD). However, the effects of long‐term anti‐oxidant treatment on the levels of SOD in smooth muscle cells (SMC) is still unclear. In the present study, the effects of the lipophilic anti‐oxidant trilinolein on the activity and gene expression of SOD in SMC were evaluated.2. After 2 days incubation with 0.1 μmol/L trilinolein, the activity and mRNA levels of SOD were increased in rat aortic SMC (A7r5), but there was no significant change in these parameters with a higher concentration of 1 μmol/L trilinolein.3. In contrast, after 7 days incubation with trilinolein, both the activity and mRNA levels of SOD were lowered in a dose‐dependent manner.4. These data emphasize the importance of choosing an optimal dosage for supplementation with anti‐oxidants in humans for the scavenging of oxygen free radicals.
Effect Of A Series Of Novel Sulphonylthioureas On Glucose Tolerance In The Obese fa/fa Zucker Rat
Authors: Farrar Nicole S , Chambers Noel J , Carlsson Anthony R , Denyer Gareth , Johnston Graham Ar 
Published: March 2003

SUMMARY1. The recent development of a series of novel KATP channel modulators, namely sulphonylthioureas and sulphonylureas, is thought to make improvements in potency and tissue selectivity compared with current sulphonylureas, such as glibenclamide, which shares a similar structure to the novel compounds.2. These novel compounds were first examined for their effect on hyperglycaemia and glucose tolerance during an oral glucose tolerance test following 5 days administration in the lean fa/– and obese fa/fa Zucker rat (a model of insulin resistance). Comparisons with present antidiabetic agents, metformin and glibenclamide were performed.3. Several compounds showed improvements in glucose tolerance compared with control and the primary structural prerequisites for the maintenance of this activity were investigated. Of most interest was compound 3–15 ((N‐[(4‐methylphenylsulphonyl]‐N′‐(2‐ethoxypyrid‐4‐yl)thiourea; 0.1 mg/kg per day), which significantly improved glucose tolerance following 5 days administration in the fa/fa Zucker rat. This paralleled the improvement seen in metformin (300 mg/kg per day)‐treated fa/fa rats, but compound 3–15 was up to 3000‐fold more potent than metformin.4. Obese fa/fa Zucker rats were then treated with compound 3–15 for 28 days to determine whether glycaemic control could be maintained over the longer term.5. Compound 3–15 showed a significant improvement in glucose clearance and reduction in insulin concentration following 28 days treatment during an intravenous glucose tolerance test compared with untreated rats, without any change in the rate of weight gain.6. The novel sulphonylthiourea 3–15 appears to improve glucose clearance during acute and chronic treatment in the fa/fa Zucker rat with no effect on the rate of weight gain. It is thought that compound 3–15 may be eliciting its actions by improving insulin sensitivity, but its effects on insulin secretion are still to be elucidated.
Effects Of L‐Arginine And Furosemide On Blood Pressure And Renal Function In Volume‐Expanded Rats
Authors: Costa Ma , Marchetti M , Balaszczuk Am , Arranz Ct 
Published: March 2003

SUMMARY1. The aim of the present study was to investigate the effects of L‐arginine (L‐Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume‐expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L‐Arg in this model.2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L‐Arg, 1 mg/kg NG‐nitro‐L‐arginine methyl ester (L‐NAME), FUR + L‐NAME or FUR + L‐Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined.3. Extracellular fluid volume expansion induced no changes in MAP in control and volume‐expanded rats (92±6 vs 100±8 mmHg, respectively). The hypotension induced by FUR in control and volume‐expanded rats (69±7 and 76±5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L‐Arg (54±3 and 64±3 mmHg, respectively).4. Injection of L‐NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups.5. Furosemide‐induced water and electrolyte excretion was blunted by the administration of L‐NAME.6. The combination of L‐Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33±1.68 vs 12.91± 0.41 μL/min per 100 g, respectively; volume‐expanded rats: 248.5±25.4 vs 112,6±8.3 μL/min per 100 g, respectively; P < 0.01).7. The administration of the combination of L‐Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230±0.018 vs 0.45±0.03, respectively, P < 0.001; volume‐expanded rats: 0.091±0.010 vs 0.22±0.03, respectively, P < 0.01).8. The potassium/water excretion rate induced by FUR alone and in the presence of L‐Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35±0.05 vs 0.20±0.05 μEq/min per 100 g, respectively; volume‐expanded rats: 0.045±0.008 vs 0.014±0.003 μEq/min per 100 g, respectively; P < 0.01).9. The decrease in the electrolyte/water excretion ratio observed with FUR + L‐Arg in volume‐expanded rats was greater than in control animals.10. The results of the present study show that the administration of FUR with L‐Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.
Insulin‐Like Effect Of (–)Epicatechin On Erythrocyte Membrane Acetylcholinesterase Activity In Type 2 Diabetes Mellitus
Authors: Rizvi Syed Ibrahim , Zaid Mohammad Abu 
Published: March 2003

SUMMARY1. Changes in the activity of acetylcholinesterase (AChE) have been reported in diabetes mellitus that have been linked to certain brain defects. The erythrocyte membrane AChE is reported to be similar to AChE present in the brain.2. Epicatechin, a member of a group of polyphenolic compounds collectively known as ‘catechins’ that are present in tea and belong to the flavonoid family, has been reported to possess insulin‐like activity.3. In the present study, the in vitro effect of (–)epicatechin and/or insulin was tested on erythrocyte membrane AChE in normal and type 2 diabetic patients. The aim of the study was to test the efficacy of (–)epicatechin to mimic insulin in its effect on erythrocyte membrane AChE.4. Acetylcholinesterase activity was significantly lower in type 2 diabetic patients than in normal controls and in vitro insulin treatment restored this activity to normal levels. Epicatechin (1 mmol/L) also caused an elevation in AChE activity in diabetic erythrocytes, an effect that was similar to the effect of insulin.5. Epicatechin has a pronounced insulin‐like effect on erythrocyte membrane‐bound AChE in type 2 diabetic patients; however, the mechanism of action of epicatechin remains speculative.
Familial Varieties Of Primary Aldosteronism
Authors: Stowasser Michael , Gunasekera Thanuja G , Gordon Richard D 
Published: March 2003

SUMMARY1. Improved approaches to screening and diagnosis have revealed primary aldosteronism (PAL) to be much more common than previously thought, with most patients normokalaemic. The spectrum of this disorder has been further broadened by the study of familial varieties.2. Familial hyperaldosteronism type I (FH‐I) is a glucocorticoid‐remediable form of PAL caused by the inheritance of an adrenocorticotrophic hormone (ACTH)‐ regulated, hybrid CYP11B1/CYP11B2 gene. Diagnosis has been greatly facilitated by the advent of genetic testing. The severity of hypertension varies widely in FH‐I, even among members of the same family, and has demonstrated relationships with gender, degree of biochemical disturbance and hybrid gene crossover point position. Hormone “day curve” studies show that the hybrid gene dominates over wild‐type CYP11B2 in terms of aldosterone regulation. This may be due, in part, to a defect in wild‐type CYP11B2‐induced aldosterone production. Control of hypertension in FH‐I requires only partial suppression of ACTH and much smaller glucocorticoid doses than previously recommended.3. Familial hyperaldosteronism type II (FH‐II) is not glucocorticoid remediable and is not associated with the hybrid gene mutation. Familial hyperaldosteronism type II is clinically, biochemically and morphologically indistinguishable from apparently non‐familial PAL. Linkage studies in one informative family did not show segregation of FH‐II with the CYP11B2, AT1 or MEN1 genes, but a genome‐wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH‐I, elucidation of causative mutations is likely to facilitate earlier detection of PAL.
Adaptations Of Skeletal Muscle To Prolonged, Intense Endurance Training
Authors: Hawley John A 
Published: March 2003

SUMMARY1. Endurance exercise induces a variety of metabolic and morphological responses/adaptations in skeletal muscle that function to minimize cellular disturbances during subsequent training sessions.2. Chronic adaptations in skeletal muscle are likely to be the result of the cumulative effect of repeated bouts of exercise, with the initial signalling responses leading to such adaptations occurring after each training session.3. Recently, activation of the mitogen‐activated protein kinase signalling cascade has been proposed as a possible mechanism involved in the regulation of many of the exercise‐induced adaptations in skeletal muscle.4. The protein targets of AMP‐activated protein kinase also appear to be involved in both the regulation of acute metabolic responses and chronic adaptations to exercise.5. Endurance training is associated with an increase in the activities of key enzymes of the mitochondrial electron transport chain and a concomitant increase in mitochondrial protein concentration. These morphological changes, along with increased capillary supply, result in a shift in trained muscle to a greater reliance on fat as a fuel with a concomitant reduction in glycolytic flux and tighter control of acid–base status. Taken collectively, these adaptations result in an enhanced performance capacity.
Capsazepine Partially Inhibits Neurally Mediated Gastric Mucus Secretion Following Activation Of Protease‐Activated Receptor 2
Authors: Kawabata Atsufumi , Kinoshita Mitsuhiro , Kuroda Ryotaro , Kakehi Kazuaki 
Published: March 2003

SUMMARY1. Protease‐activated receptor 2 (PAR2), present in capsaicin‐sensitive sensory neurons, induces gastric mucus secretion and mucosal cytoprotection.2. We studied the possible cross‐talk between PAR2 and vanilloid receptor 1 (VR1). The VR1 antagonist capsazepine partially inhibited the PAR2‐mediated increase in gastric mucus secretion.3. Thus, activation of VR1 is responsible, at least in part, for the neurally mediated mucosal cytoprotection following activation of PAR2.
Effect Of α‐Lipoic Acid On Lipid Peroxidation And Anti‐Oxidant Enzyme Activities In Diabetic Rats
Authors: Dinçer Yıldız , Telci Ayşegül , Kayalı Refik , Yılmaz İlker A , Çakatay Ufuk , Akçay Tülay 
Published: March 2003

SUMMARY1. Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. Recently, α‐lipoic acid (ALA) has gained considerable interest as an anti‐oxidant. Various studies have indicated the anti‐ oxidant effects of ALA and its reduced form dihydrolipoic acid. Therefore, it appears that these compounds have important therapeutic potential in conditions where oxidative stress is involved. The aim of the present study was to investigate the effect of ALA supplementation on lipid peroxidation and anti‐oxidant enzyme activities in various tissues in diabetic rats.2. Male Wistar rats were divided into three groups. Diabetes was induced by streptozotocin (STZ) injection in the two groups of rats to be supplemented and not to be supplemented with ALA. Another group of rats, which received saline injection, formed the control group. After 5 weeks of diabetes, rats were killed. In order to assess the redox status of various organs in the diabetic and control rats, thiobarbituric acid‐reactive substances (TBARS) and glutathione (GSH) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (G‐Px) and glutathione reductase (G‐Red) activities were determined in the liver, pancreas and kidney.3. In both diabetic groups, TBARS levels and SOD activity were increased in the liver and pancreas, G‐Px and G‐Red activities were increased in the kidney and GSH levels were decreased in all organs compared with controls. In the ALA‐ supplemented group, TBARS levels were decreased, GSH levels were increased in the liver and pancreas, SOD activity was decreased in the liver, G‐Px activity remained unchanged in all tissues and G‐Red activity was increased in the pancreas compared with the diabetic group that did not receive ALA supplementation.4. In conclusion, ALA supplementation has disparate effects on the redox status of different organs. These data are not sufficient for confirmation the beneficial effects of ALA supplementation on the redox status of various organs in diabetic rats.
Myocardial Energetics In Cardiac Hypertrophy
Authors: Zhang Jianyi 
Published: March 2003

SUMMARY1. This review is presented with the intent of illustrating the representative studies of functional and myocardial energetic consequences of hearts with postinfarction left ventricular (LV) remodelling or with concentric hypertrophy and diastolic LV dysfunction in porcine models.2. Both eccentric and concentric cardiac hypertrophy are associated with the abnormal myocardial energetics that are most severe in hearts with congestive heart failure (CHF). Presently, these abnormalities cannot be satisfactorily explained to be the cause(s) of the dysfunction of failing hearts or cause the progress from compensated cardiac hypertrophy to CHF.3. Mechanisms governing abnormal myocardial high‐energy phosphate (HEP) metabolism in hearts with cardiac hypertrophy and CHF are unclear. Myocardial energy metabolism studies use both kinetic and thermodynamic models. The thermodynamic studies examine the myocardial steady state levels of high‐ and low‐energy phosphate, which indicate myocardial energy state or phosphorylation potential that is defined by the ratio of [ATP]/([ADP][Pi]). The kinetics studies examine the reaction velocity that is regulated by: (i) quantity and activity of the key enzymes; (ii) the concentrations of all the substrates and products; and (iii) the Michaelis–Menten constants of each substrate of the reaction.4. Significant alterations in myocardial concentrations of phosphocreatine (PCr), ATP and ADP, myocardial oxidative phosphorylation (OXPHOS) protein expression and substrate preference are found in hearts with postinfarction LV remodelling and CHF. However, to define a causal relationship is a different matter.5. Future studies of animal models of LV hypertrophy or heart failure using gene manipulation may provide additional insights to answer the persisting question of whether limitations of ATP synthetic or transport capacities contribute to the pathogenesis of LV remodelling or failure.
Role Of Trophic Factors In The Development, Survival And Repair Of Primary Auditory Neurons
Authors: Marzella Phillip L , Gillespie Lisa N 
Published: March 2003

SUMMARY1. Neurotrophic factors have been identified as crucial for the development of the auditory system and have also been proven to be important for continued survival and maintenance of auditory neural connections.2. In addition, both in vitro and in vivo studies have demonstrated that these trophic molecules can prevent the secondary wave of auditory neuron degeneration normally seen following the loss of hair cells.3. Furthermore, neurotrophic factors have been reported to enhance neuronal excitation and to improve the efficacy of synaptic transmission.4. As such, these molecules are strong candidates to be used as therapeutic agents in conjunction with the cochlear implant, or even to repair and/or regenerate damaged or lost auditory nerve and sensory cells.
Thiol reagents and nitric oxide modulate the gating of BKCa channels from the guinea‐pig taenia caeci
Authors: Lang RJ , Harvey JR 
Published: March 2003

Summary1. The site of the direct modulation of the gating of BKCa channels by the nitric oxide donor s‐nitroso‐l‐cysteine (NOCys) was examined in excised membrane patches of the guinea‐pig taenia caeci by the use of various thiol (sulphydryl)‐specific reagents, including N‐ethylmaleimide (NEM) and three charged methanethiosulphonate (MTS) reagents, namely positively charged 2‐aminoethyl MTS hydrobromide (MTSEA) and [2‐(trimethylammonium)ethyl] MTS bromide (MTSET) and negatively charged sodium (2‐sulphonatoethyl) MTS (MTSES), which all specifically convert sulphydryls to a disulphide.2. At 10 µmol/L, NOCys transiently increased the probability of opening (N.Po) of the BKCa channels (at 0 mV) after a delay of 1–2 min.3. Disulphide‐reducing agents, such as dithiothreitol (10 µmol/L), increased N.Po in a manner that was reversed by the sulphide‐oxidizing agent thimerosal (10 µmol/L). Both positively charged MTSET (2.5 mmol/L) and negatively charged MTSES (2.5 mmol/L) rapidly increased N.Po. However, only the MTSES‐evoked increase in N.Po remained after a prolonged washout period.4. The specific alkylating agent of cysteine thiols NEM (1 mmol/L) and the positively charged, but membrane permeable, MTSEA (2.5 mmol/L) decreased N.Po (at 0 mV).5. Pre‐exposure of excised membrane patches to NEM or MTSES prevented the excitatory actions of NOCys (10 µmol/L).6. We conclude that MTSES and NOCys must modify thiols on cysteine residues within basic regions of the channel protein that would electrostatically exclude MTSEA and MTSET. A consensus sequence of various mammalian α‐subunits of the BKCa channel reveals two pairs of cysteine residues surrounded by basic amino acids that could be the site of action for NOCys and MTSES.
Transforming growth factor‐β1 does not relate to hypertension in pre‐eclampsia
Authors: Hennessy A , Orange S , Willis N , Painter DM , Child A , Horvath JS 
Published: March 2003

Summary1. Pre‐eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end‐organ damage, if severe. Pre‐eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed.2. Transforming growth factor (TGF)‐β1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end‐organ disease related to increases in endothelin release. Transforming growth factor‐β1 is also an important factor in placental implantation. Alterations in TGF‐β1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre‐eclampsia.3. The aim of the present study was to examine the placental distribution and serum concentration of TGF‐β1 in patients with pre‐eclampsia compared with normal pregnancy.4. Patients with pre‐eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor‐β1 was determined by TGF‐β1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF‐β1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining.5. Patients with pre‐eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 ± 0.4 weeks. There was no difference in TGF‐β1 concentration between the two groups (mean (±SEM) 27.1 ± 1.0 vs 26.4 ± 0.7 pg/mL for normal pregnancy and pre‐eclampsia, respectively; P = 0.73, Mann–Whitney U‐test). There was no correlation between systolic or diastolic blood pressure and TGF‐β1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and extravillous trophoblast of term placentas.6. Although TGF‐β1 is present in trophoblast cells in early pregnancy during placental development, TGF‐β1 concentrations were not increased in the placenta at term in pre‐eclampsia and there was no correlation between blood pressure and serum TGF‐β1, suggesting that TGF‐β1 does not play a role in the development of late gestation pre‐eclampsia and hypertension.
Intracerebral microdialysis: 30 years as a tool for the neuroscientist
Authors: Bourne James A 
Published: March 2003

Summary1. Microdialysis is an established technique for studying physiological, pharmacological and pathological changes of a wide range of low molecular weight substances in the brain extracellular fluid. Many studies have proven its sensitivity in sampling the extracellular space in discrete brain locations, such as the striatum, and monitoring the action of exogenous substances.2. The two main areas of application of microdialysis are the recovery of endogenous substances, primarily the neurotransmitters, and the infusion of drugs through the microdialysis cannula (retrodialysis).3. Microdialysis in awake animals is the tool of choice for studying the relationship between changes in behaviour and neurotransmitters in certain brain areas. In addition, the concomitant recording of the electroencephalogram at the site of microdialysis has been shown to be extremely useful in determining the role of certain neurotransmitters in paroxysmal activity.4. Clinical applications of microdialysis have included monitoring of ischaemic injury, subarachnoid haemorrhage, trauma and epilepsy. With the recent availability of standardized equipment, the use of microdialysis in the neurological clinic is likely to become more common.
Adenosine inhibits N‐type calcium channels at the rat neuromuscular junction
Authors: Schwartz Andrew D , Whitacre Camron L , Lin Yue , Wilson David F 
Published: March 2003

Summary1. In earlier studies, it has been reported that under in vitro conditions transmitter release at the rat neuromuscular junction is normally suppressed due to the effect of adenosine release from the isolated tissue. In the present study we wanted to determine whether this action may involve the inhibition of calcium influx through adenosine‐sensitive calcium channels.2. In order to test this hypothesis, we examined the role of N‐type calcium channels in regulating nerve‐evoked transmitter release by using the N‐type calcium channel‐specific blocker ω‐conotoxin GVIA (CTX). In order to control the inhibitory action of adenosine, we also used the adenosine A1 receptor antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX). We tested the effect of blocking N‐type calcium channels with CTX in the presence and absence of DPCPX. We examined the effects of these drugs on quantal transmitter release in the transected preparation of the phrenic nerve–hemidiaphragm of the rat using intracellular recording techniques.3. At 10 nmol/L, CTX alone had no effect on nerve‐evoked transmitter release; however, in the presence of 0.1 µmol/L DPCPX, CTX significantly depressed nerve‐evoked transmitter release.4. These data support the view that adenosine inhibits nerve‐evoked transmitter release by inhibiting N‐type calcium channels on nerve terminals.