bluuebunny/crossref_metadata_2025_split huggingface dataset:
USE OF DIFFERENTIATED CHOLINERGIC AND SECOND MESSENGER ENDPOINTS TO EVALUATE CHOLINESTERASE INHIBITORS
Authors: Blusztajn J. K. , Davis Ross O. 
Published: June 2007

SUMMARY1. The effects of organophosphorus compounds on the cholinergic properties of a mouse septal neuronal cell line, SN56, were investigated. Treatment of the cells with 10 μmol/L paraoxon or 10 μmol/L diisopropylphosphorofluoridate (DFP) resulted, respectively, in rapid 27‐ and 11‐fold increases of intracellular acetylcholine content.2. Time‐course studies showed that paraoxon maintained its efficacy whereas the effects of DFP decayed quickly, possibly due to rapid hydrolysis and inactivation of DFP in the growth medium.
NEUROTOXICITY OF BETA‐AMYLOID PROTEIN: CYTOCHEMICAL CHANGES AND APOPTOTIC CELL DEATH INVESTIGATED IN ORGANOTYPIC CULTURES
Authors: Allen Y. S. , Devanathan P. H. , Owen G. P. 
Published: June 2007

SUMMARY1. This study is an attempt to examine in vitro the cyto chemical changes in hippocampal neurones induced by beta‐amyloid protein (β‐AP).2. The mechanism of cell death, and the vulnerability of different regions of the hippocampus to b‐AP toxicity, has also been explored using TUNEL staining to locate fragmented DNA in both dissociated and organotypic cultures.3. Apoptotic cell profiles and the detection by immunocytochemistry of ubiquitin and tau protein confirmed the acute neurodegenerative effects of b‐AP, and organotypic cultures revealed the dentate gyrus to be especially vulnerable.4. A scrambled sequence of b‐AP, a peptide with similar hydrophobic groups to b‐AP, and islet pancreatic amyloidogenic peptide also showed neurodegenerative effects, although less severely than b‐AP.5. It is concluded that organotypic cultures provide a valuable in vitro model with which to observe and characterize the neurotoxic effects of b‐AP. These effects, however, may be non‐specific and related more to the general amyloidogenicity of the b‐AP molecule.
DEVELOPMENTAL NEUROTOXICITY TO METHAMPHETAMINES
Authors: Weissman Arthur D. , Caldecott‐Hazard Sally 
Published: June 2007

SUMMARY1. To investigate the long‐term changes caused by amphetamines in the developing brain, we used both an in vivo and in vitro model of chronic fetal exposure to methamphetamine and related drugs.2. Offspring of rats, treated with either saline, 2 mg/kg twice a day (b.i.d.) or 10 mg/kg bid. methamphetamine throughout gestation, were examined at 30 days of age for changes in the monoamine system of their brains.3. At the lower dose methamphetamine was neurotoxic to specific neuronal populations, mostly serotonergic. At the higher dose, methamphetamine retained its neurotoxic properties, but also stimulated the growth of axonal terminals in specific regions as evidenced by an increase in monoamine uptake sites. The neurochemical changes at the higher dose were correlated with deficits in adult behavioural measures.4. Corresponding in vitro drug treatments of rat neuroblastomas cells also produced a dose‐related effect on cellular growth and differentiation patterns. Neurotoxic as well as stimulatory effects of methamphetamine and some related compounds were seen in culture.5. Our in vivo and in vitro observations demonstrate neurotoxic effects of amphetamines and the remodelling of synaptic morphology in response.
EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS
Authors: Heller Alfred , Won Lisa , Heller Barbara , Hoffmann Philip C. 
Published: June 2007

SUMMARY1. The rotation‐mediated three‐dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development.2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose‐dependent manner and interrupts normal monoaminergic development.3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug‐induced insults and a deficiency in monoamines persists throughout development.4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype.5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity.
OPIOIDS AND PAIN
Authors: Kanjhan Refik 
Published: June 2007

SUMMARY1. The central nervous system in mammals is able to react to painful stimuli at many levels that are involved in transmission, modulation and sensation of pain. Endogenous opioid peptides and their receptors are located at key points in pain pathways, and response to pain can be modulated by local application of opioids at many sites. Mechanisms of opioid analgesia at peripheral, spinal, medullary and midbrain levels are only incompletely understood; forebrain systems are even less appreciated. Local circuits in the spinal dorsal horn play a critical role in processing nociceptive afferent input and in mediating the actions of descending pain modulating systems.2. The opioid receptors, recently cloned, exert their effects by activating G protein coupled effector systems, such as ion channels and second messenger systems. Although the receptor most commonly associated with pain relief is the μ‐receptor, specific δ‐ and k‐agonists can also mediate antinociception at spinal and supraspinal sites. Acute effects of opioids on target neurons are inhibitory, but excitatory effects have also been reported.3. Noxious stimulation increases neuronal activity and modulates expression of genes, including immediate‐early genes and neuropeptide (i.e. opioid) genes at spinal and supraspinal levels of the somatosensory system. Opioid drugs and endogenously released opioid peptides can modulate signal transduction mechanisms and intracellular processes that lead to alterations in protein phosphorylation and gene expression. These effects of opioids at the cellular level may underlie the mechanisms of pre‐emptive analgesia and neuroplastic changes such as tolerance, dependence, sensitization, hyperalgesia, adaptation, addiction, and modulation of pain memories.
INFLUENCE OF MYOSIN ISOFORMS ON TENSION COST AND CROSSBRIDGE KINETICS IN SKINNED RAT CARDIAC MUSCLE
Authors: Rossmanith G. H. , Hamilton A. M. , Hoh J. F. Y. 
Published: June 2007

SUMMARY1. In attempting to consolidate the role of ventricular isomyosins in regulating the contractility of the myocardium, actomyosin ATPase and crossbridge kinetics were obtained at 24°C in chemically skinned isometrically contracting cardiac muscles containing V1 and V3 isomyosins.2. The ATPase activity was measured at various levels of Ca2+ activation by the enzymatic coupling of ATP hydrolysis with the conversion of NADH to NAD+. The crossbridge kinetics were inferred from small‐amplitude perturbations of muscle length and muscle tension, and characterized by the frequency‐domain parameter fmin.3. The ATPase rates of V1 and V3 muscles obtained at various levels of Ca2+ activation were plotted against the corresponding proportional tensions. The ATPase vs tension plots were linear with slopes of 4.92 nmol/min‐1 per mm per mN and 1.98 nmol/min‐1 per mm per mN, respectively for, V1 and V3 muscles. Individual calculations of ATPase‐to‐tension ratios (nmol/min‐1 per mm per mN) gave corresponding averages of 4.98 ± 0.12 (s.e.m., n = 12) and 2.16 ± 0.12 (s.e.m., n = 10). The myosin isoform induced proportional change in tension cost was accompanied by a similar change in fmin (4.1 ± 0.1 Hz and 1.95 ± 0.03 Hz, means ± s.e.m., for V1 and V3 muscles, respectively).4. The observations and other published kinetic data are discussed in the context of models of crossbridge cycling. It is suggested that the tension economy of V3 muscle arises principally from an increase in the fraction of time, during the crossbridge cycle, when the crossbridge is exerting force.
ENDURANCE TRAINING EFFECTS ON THE CONTRACTILE ACTIVATION CHARACTERISTICS OF SINGLE MUSCLE FIBRES FROM THE RAT DIAPHRAGM
Authors: Lynch Gordon S. , Duncan Noel D. , Campbell Siun P. , Williams David A. 
Published: June 2007

SUMMARY1. Considerable debate exists as to whether the properties of diaphragm muscles can be modified by training. As the diaphragm is chronically activated during normal respiration, it is of interest to determine whether this muscle is resistant to further modification by exercise. The aim of this study was to investigate the contractile activation characteristics of single skinned muscle fibres from the diaphragm of both CONTROL and TRAINED rats.2. Male rats were subjected to a 20 week high‐intensity endurance exercise training programme that consisted of running on a motorized treadmill, 5 days/week, 90–120 min/day, 27–30 m/min, up a 20° incline. At the conclusion of training, rats were killed with an overdose of ether and costal regions of the diaphragm were removed and stored in a glycerol‐based skinning solution at—20° C.3. Single skinned (membrane‐permeabilized) diaphragm muscle fibres were attached to a sensitive force transducer and activated in Ca2+‐ and Sr2+‐buffered solutions in order to determine relative force‐pCa and force‐pSr characteristics. Fibres were allocated into discrete groups (population I, population II, intermediate, mixed) on the basis of their physiological (contractile) properties.4. Population I (slow‐twitch) fibres from the diaphragm of TRAINED rats exhibited a reduced sensitivity to Ca2+ (indicating a rightward shift of the force‐pCa relationship) compared to those diaphragm fibres from CONTROL animals. An increased number of population II (fast‐twitch) fibres were sampled from TRAINED rats, however, training did not affect the activation properties of these fibres.5. The fact that training‐induced alterations in the contractile characteristics did occur in one group of fibres indicates that the intensity of training was sufficient to induce some modifications to the costal fibres of the diaphragm muscle. However, the lack of alterations to the contractile characteristics of the population II (fast‐twitch) fibres may also suggest that the overall properties of the diaphragm are relatively resistant to modification despite high‐intensity training.
HYBRID GENE OR HYBRID STEROIDS IN THE DETECTION AND SCREENING FOR FAMILIAL HYPERALDOSTERONISM TYPE I
Authors: Stowasser Michael , Bachmann Anthony W. , Jonsson Julie R. , Tunny Terry J. , Klemm Shelley A. , Gordon Richard D. 
Published: June 2007

SUMMARY1. Early diagnosis of Familial Hyperaldosteronism Qpe I (FH‐I, glucocorticoid‐suppressible hyperaldosteronism) in asymptomatic, affected individuals is essential if death from stroke is to be prevented.2. In 21 patients with FH‐I (presence of the causative hybrid 11β‐hydroxylase/aldosterone synthase gene confirmed by Southern blot testing), various biochemical parameters were compared as possible screening tests. Hypokalaemia and elevated plasma aldosterone each detected only two (10%) of the affected individuals.3. Plasma renin activity 19 (90%) and aldosterone/renin ratio 18 (86%) were more reliable but not free from false negatives.4. Levels of the urinary ‘hybrid’ steroid, 18‐oxocortisol, were elevated (P <0.01) in all 15 patients tested (138.2 ± 17.4 μg/g creatinine, range 41.6–281.0 μg/g) with no overlap when compared with 11 normals (9.7 ± 1.3μg/g, range 2.8–17.4 μg/g).5. We conclude that measurement of urinary ‘hybrid’ steroids is probably the most rapid and reliable biochemical screening test currently available for FH‐I, with confirmation dependent on demonstration of the hybrid gene by genetic techniques.
HYPERTENSION MANAGEMENT: A COMPARISON OF URBAN VERSUS RURAL GENERAL PRACTITIONERS IN WESTERN AUSTRALIA
Authors: Yapp Caroline K. , Taylor Lynette S. , Ow Cherynne Y. , Jamrozik Konrad , Puddey Ian B. 
Published: June 2007

SUMMARY1. We have conducted a survey of 75 rural and 75 urban randomly selected general practitioners (GPs) in Western Australia to ascertain how closely current practice mirrors published Australian guidelines for the management of hypertension.2. Fifty‐one rural and 49 urban GPs completed the 19 item questionnaire. The two groups were well matched in terms of age and years in general practice. An assessment of the criteria utilized to diagnose hypertension revealed a tendency for much greater scatter in the cut points used to define systolic compared to diastolic hypertension, but no systematic difference between urban and rural GPs.3. After an initial finding of mild hypertension the follow‐up time to the next check‐up was significantly longer for rural patients compared to urban patients (72 ± 13 and 36 ± 5 days respectively, P < 0.01). Urban GPs reviewed established hypertensive patients more commonly at 1–3 monthly intervals (89%) while rural GPs reviewed more commonly at 3–6 monthly intervals (86%).4. In terms of target blood pressure (BP) for BP reduction, 67% rural compared to 83% urban GPs aimed for a systolic BP of < 140mmHg (P= 0.06), while 95% of both groups aimed for diastolic BP < 90mmHg.5. The profile of first line antihypertensive agents most commonly used was also similar in both groups with 46% preferring angiotensin converting enzyme inhibitors, 18.5% diuretics, 18.5% beta blockers, 16% calcium entry blockers and 1% prazosin.6. This study demonstrates a clear preference for the newer anti‐hypertensive agents. Otherwise there was self‐reported broad compliance with Australian guidelines for hypertension management in this randomly selected GP population. Urban and rural practices were more notable for their consistency rather than any systematic differences in approach.
MUTATIONS IN THE FIRST INTRON OF THE SHR RENIN GENE DISRUPT PUTATIVE REGULATORY ELEMENTS
Authors: Yu H. , Nicolantonio R. Di , Lan L. , Wilks A. 
Published: June 2007

SUMMARY1. Four single base mutations unique to the spontaneously hypertensive rat (SHR) were identified in the first 1100 base pairs of its renin gene first intron when compared to that of Wistar‐Kyoto and Sprague‐Dawley normotensive rats.2. These mutations were found to fall within the consensus sequences for a number of transcription factors and thus may alter the affinity of these putative transcription factor binding sites.3. The reported overexpression of the renin gene in the SHR may therefore result from these structural abnormalities and, in turn, result in a tissue angiotensin‐dependent hypertension in this strain.
PAF ANTAGONISTS BLOCK INDUCTION OF NITRIC OXIDE SYNTHASE IN CULTURED MACROPHAGES AND VASCULAR SMOOTH MUSCLE CELLS
Authors: Arthur Jane F. , Shahin Susan , Dusting Gregory J. 
Published: June 2007

SUMMARY1. Nitric oxide (NO) synthase inhibitors and Paf antagonists abrogate hypotension in septic shock. The latter may act by blocking intracellular transduction mechanisms in vascular smooth muscle cells and inflammatory cells. We examined the effect of Paf antagonists on expression of inducible NO synthase.2. A murine macrophage cell line (J774.2) and rat vascular smooth muscle cells (VSMC) were stimulated with lipopoly‐saccharide (LPS), either alone or in combination with Paf or Paf antagonists, BN 50739 or E‐6123.3. NO synthase activity in 5774.2 was measured by the conversion of [3H]l‐arginine to [3H]l‐citrulline. Nitrite accumulation was measured in the culture medium of J774.2 and VSM.4. BN 50739 (10 μmol/L) and E‐6123 (1 μmol/L) both reduced the expression of calcium‐independent NO synthase activity and nitrite accumulation, while Paf alone had no effect.5. Inhibition of NO synthase induction by Paf antagonists might afford therapeutic benefits in the management of septic shock and possibly other cardiovascular disorders.
PARTICIPATION OF THE RENIN‐ANGIOTENSIN SYSTEM IN REGULATING THE EXCRETORY RESPONSE TO ACUTE SODIUM INGESTION
Authors: Duggan K. A. , Jones D. M. , MacDonald G. J. 
Published: June 2007

SUMMARY1. A gastric sodium monitor has been proposed, based upon greater urinary sodium excretion after gastric, compared with intravenous, sodium loading. However, this difference has only been demonstrated in animals and humans on a low sodium diet prior to study. This suggests involvement of a system activated by decreased sodium intake. As the renin‐angiotensin system is the most active of these, this study sought to determine whether angiotensin II (AII) might act as a humoral mediator for this gastric sodium monitor.2. Male New Zealand white rabbits with a gastrostomy tube in situ were placed on a low sodium diet (0.008% NaCl) for 7 days. To determine if differences in plasma AII might explain the different natriuretic responses AII was measured 0, 5,10, 30, 60 and 120 min after a 1.5mmol/kg sodium load given gastrically or intravenously. To determine whether the AII response was specific to low salt diets the gastric salt load was given after equilibration on normal (2.2% NaCl) and high (4.4% NaCl) sodium diets.3. In rabbits on the low sodium diet plasma AII decreased significantly at 5 min after both gastric (P < 0.025) and intravenous (P < 0.05) sodium and returned to baseline by 10 min in the latter. In contrast after gastric sodium AII remained less than in controls throughout (120 min, P < 0.05). In the rabbits on the normal and high sodium diets plasma AII concentration increased non‐significantly after gastric sodium administration.4. We conclude that circulating AII may participate as a mediator of the gastric sodium monitor. Its concentration was reduced and remained persistently lower after gastric but not intravenous sodium. Further, this change was not apparent on sodium diets in which differences in sodium excretion have not been demonstrated previously.
PCR‐SSCP ANALYSIS OF THE ANGIOTENSIN II TYPE 1: RECEPTOR GENE IN PATIENTS WITH ALDOSTERONE‐PRODUCING ADENOMAS
Authors: Klemm S. A. , Ballantine D. M. , Tunny T. J. , Stowasser M. , Gordon R. D. 
Published: June 2007

SUMMARY1. In patients with primary aldosteronism due to angiotensin‐responsive and andotensin‐unresponsive aldosterone‐producing adenomas, no differences in the coding region of the angiotensin II type 1 (AT1) receptor gene were observed compared to normal subjects in peripheral blood leucocyte DNA.2. Furthermore, no differences in the AT1 receptor gene were observed in DNA extracted from tumour tissue of either subgroup.3. Genotypic and allelic frequencies for an RFLP detected in the coding region of the AT1 receptor gene were not significantly different between normal subjects and patients with aldosterone‐producing adenomas as a group, nor between normal subjects and patients of either subgroup when compared with each other.4. In those patients heterozygous in peripheral blood at the RFLP site, tumour DNA showed the same allelic pattern.5. In patients with aldosterone‐producing adenomas either responsive or unresponsive to the renin‐angiotensin system, no differences were detected using SSCP analysis in the coding region of the AT1 receptor gene in peripheral blood or tumour tissue.
PLASMA ALDOSTERONE RESPONSE TO ACTH IN SUBTYPES OF PRIMARY ALDOSTERONISM
Authors: Stowasser Michael , Klemm Shelley A. , Tunny Terry J. , Gordon Richard D. 
Published: June 2007

SUMMARY1. Aldosterone responsiveness to ACTH was compared in eleven patients with angiotensin‐unresponsive (AII‐U) aldosterone‐producing adenomas (APA), 16 with AII‐responsive (AII‐R) APA and 19 with bilateral adrenal hyperplasia (BAH).2. After overnight recumbency, aldosterone levels were highest in AII‐U APA and lowest in BAH. Following 2h of upright posture, however, levels were similar among the three groups.3. During ACTH infusion, aldosterone levels in AII‐U and AII‐R APA were similar, and higher than those in BAH. Because of the higher basal level, the percentage rise in aldosterone was lower in AII‐U APA compared with the other groups, as was the ratio of per cent aldosterone rise to per cent cortisol rise.4. Slightly but significantly reduced plasma cortisol levels observed in the AII‐R APA group may reflect secretion by AII‐R APA of a cortisol‐like substance that is capable of suppressing ACTH and thus adrenal cortisol production.5. The tendency of aldosterone to follow the diurnal rhythm of ACTH in AII‐U APA may thus represent an unmasking of the normal ability of ACTH to regulate aldosterone, secondary to the loss of AII responsiveness, rather than an enhancement of ACTH effect.
EFFECTS OF ISOTONIC SALINE LOADING ON RENAL TUBULAR AND NEUROGENIC DOPAMINE RELEASE IN CONSCIOUS RABBITS
Authors: Akama Hiroyoshi , Noshiro Takao , Sane Naoki , Watanabe Toshiya , Trigg Lisbeth , Kotsonis Peter , Majewski Harry , McGrath Barry P. , Miura Yukio , Abe Keishi 
Published: June 2007

SUMMARY1. This study was designed to investigate the effects of isotonic saline loading on renal tubular and neurogenic dopamine (DA) in conscious rabbits.2. Isotonic saline loading did not affect mean arterial pressure, heart rate or renal blood flow but markedly increased urine volume, sodium excretion and DA excretion.3. Renal DA spillover was not affected by venous emptying, while renal noradrenaline (NA) spillover tended to decrease during saline loading. The ratio of % renal DA spillover to % renal NA spillover increased to 2.3 ± 0.6 (P < 0.05) 3h after saline loading.4. Isotonic saline loading increased renal tubular DA production but had little effect on neurogenic DA release.
THE INFLUENCE OF THE RENIN ANGIOTENSIN SYSTEM ON ABNORMAL EXPRESSION OF NERVE GROWTH FACTOR IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Jeffreson S. , Rush R. , Zettler C. , Frewin D. B. , Head R. J. 
Published: June 2007

SUMMARY1. The levels of the neurotrophic factor, nerve growth factor (NGF) in the mesenteric vascular bed of the spontaneously hypertensive rat (SHR) were greater than those in the corresponding vascular bed of normotensive Wistar‐Kyoto rats (WKY).2. Administration of angiotensin II (200 ng/kg per min, by minipump) for 2 weeks to juvenile WKY rats increased the levels of NGF in the mesenteric vasculature to those seen in untreated SHR.3. Administration of the angiotensin II receptor antagonists losartan (30 mg/kg per day, p.o.) or PD144277 (10 mg/kg per day, p.o.) to juvenile SHR for 4 weeks reduced the levels of NGF such that they were indistinguishable from the values obtained for normotensive WKY rats.4. The results confirm the elevated level of NGF in the mesenteric vasculature of the SHR and suggest that angiotensin II may play a role in regulating the abnormal concentrations of the protein in this tissue.
ANALYSIS OF THE RENIN GENE IN PATIENTS WITH ALDOSTERONE‐PRODUCING ADENOMAS BY POLYMERASE CHAIN REACTION‐SINGLE STRANDED CONFORMATIONAL POLYMORPHISMS AND LONG POLYMERASE CHAIN REACTION
Authors: Ballantine Donna M. , Klemm Shelley A. , Tunny Terry J. , Stowasser Michael , Gordon Richard D. 
Published: June 2007

SUMMARY1. Angiotensin‐responsive aldosterone‐producing adenomas (AII‐R‐APA) have increased expression of renin mRNA compared with angiotensin‐unresponsive aldosterone‐producing adenomas (AII‐U‐APA) or normal adrenals.2. Further, significant associations between the Bgl I, Taq I and Hinf I RFLP and aldosterone responsiveness to the renin‐angiotensin system of the two subgroups of patients have been reported.3. Using the polymerase chain reaction based technique single stranded conformational polymorphism, we detected no alterations in exon 1 of the renin gene in peripheral blood leucocyte DNA from normal AII‐U‐APA and AII‐R‐APA subjects.4. Using long‐PCR, we amplified a fragment of the renin gene consisting of a region covering 500 bp upstream of exon 1, exon 1 and intron A. No gross changes in this area of the renin gene were found in the three groups of subjects studied. However this does not exclude small alterations in this area.