bluuebunny/crossref_metadata_2025_split huggingface dataset:
AGE‐RELATED CHANGES IN AORTIC SENSITIVITY TO NORADRENALINE AND ACETYLCHOLINE IN RATS
Authors: Hashimoto Michio , Gamoh Shuji , Hossain Shahdat , Okunishi Hideki , Shimoura Keiko , Yasui Yukihiko , Ando Akiro , Masumura Sumio 
Published: June 2007

SUMMARY1. The purpose of the present study was to determine the relationship between plasma and tissue lipid levels and the effects of age on vascular responses to noradrenaline (NA) and acetylcholine (ACh).2. Studies were performed in young and aged rats and the response of endothelium‐intact and ‐denuded aortic rings to NA and to ACh was measured. The plasma concentration of cholesterol (total, high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL)) and 17β‐oestradiol was determined, as was the aortic tissue content of phospholipids, cGMP and cholesterol (total, free and esterified).3. Levels of all types of cholesterol in plasma and aorta increased with age; cholesterol levels in plasma correlated with those in the aorta; levels of phospholipid in the aorta did not increase with age but correlated with those of LDL cholesterol in plasma; levels of 17β‐oestradiol did not change, but those of cGMP increased with age.4. In endothelium‐intact rings, the maximum tension developed by exposure to NA did not change, but the EC50 of NA increased with age and correlated with total cholesterol in the plasma and with the levels of all types of cholesterol in the aorta. In rings precontracted with NA, age decreased the maximum relaxation induced by ACh. The EC50 of ACh decreased with age and was inversely correlated with levels of cholesterol in the plasma and aorta. Treatment with NA increased cGMP levels in aged rats. Removal of the endothelium abolished the response to ACh and heightened the sensitivity to NA in young and aged rats.5. Aortic endothelial cells seem to inhibit amine‐induced contraction, while age‐related changes in the levels of cholesterol in aortic tissue affect the sensitivity of the tissue to NA and ACh.
MOBILIZATION OF LEAD BY CALCIUM VERSENATE AND DIMERCAPTOSUCCINATE IN THE RAT
Authors: Tandon Sushil K. , Singh Surendra , Prasad Satgur , Mathur Neeraj 
Published: June 2007

SUMMARY1. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) and meso‐2,3‐dimercaptosuccinic acid (DMSA) individually and in permutation‐combination in various doses (0.1,0.2 and 0.4 mmol/kg bodyweight) were investigated for their efficacy to mobilize lead from vital tissues into urine and faeces and to restore the lead‐sensitive biochemical parameters in lead pre‐exposed rats with a view to develop the most acceptable treatment regimen for lead poisoning with a minimal loss of endogenous essential elements.2. The combined therapy was more effective than a single chelator treatment.3. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA caused a lower depletion of zinc, calcium and iron but possessed almost equal capability to that of 0.4 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA to produce urinary as well as faecal excretion of lead, to reduce the tissue burden of lead, including that of the brain, and to reverse lead‐induced biochemical alterations.4. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA has shown a definite improvement over previously reported combinations in terms of removal of lead from tissues, particularly the brain, restoration of urinary delta‐aminolevulinic acid levels and a decrease in the loss of body zinc and is, therefore, recommended for the treatment of lead intoxication.
LATE STEPS OF ALDOSTERONE BIOSYNTHESIS: SHEEP ARE NOT RATS
Authors: Boon Wah Chin , Coghlan John P. , McDougall John G. 
Published: June 2007

SUMMARY1. The last three steps of aldosterone biosynthesis have been demonstrated to be catalysed by a single enzyme, referred to as CYP11B (or P45011β) in cow, pig, sheep and bullfrog and as CYP11B2 (or P450aldo) in rat, human, mouse and hamster.2. The related enzyme CYP11B1 (also referred to as P45011β) in rat, human, mouse and hamster does not have aldosterone synthesis activity, but no such enzyme has been reported in the cow, pig or sheep to date.3. Exclusive aldosterone secretion in the zona glomerulosa (ZG) of the adrenal cortex in species such as rat, human, mouse and hamster could be ascribed to the restricted distribution of CYP11B2 to the same region in the adrenal cortex.4. In other species, such as cow, pig and sheep, the CYP11B enzyme is expressed throughout the adrenal cortex and, thus, the exclusive aldosterone biosynthesis in the ZG could not be explained simply by the distribution of the enzyme.5. We have shown in the sheep that potassium loading and acute sodium depletion stimulate the CYP11B transcript levels, which are not further increased by chronic sodium depletion.6. The predominant CYP11B in the sheep adrenal cortex catalyses the synthesis of aldosterone from deoxycorticosterone (DOC) in vitro, is expressed throughout the adrenal cortex and the corresponding transcript levels are increased by K+ loading or sodium depletion. In short, as far as the last step of aldosterone biosynthesis is concerned, sheep are different from rats. In the rat, the CYP11B2 transcript or protein is elevated by K+ loading or sodium depletion, but not the CYP11B1 transcript or protein.7. We propose that during severe sodium deficiency there is a switch in the aldosterone pathway to one preferentially involving 18‐OH‐DOC and not corticosterone.
NITRIC OXIDE IN ATHEROSCLEROSIS: VASCULAR PROTECTOR OR VILLAIN?
Authors: Dusting Gregory J. , Fennessy Paul , Yin Zhan‐Li , Gurevich Vladimir 
Published: June 2007

SUMMARY1. Nitric oxide (NO) has important roles in physiological vasodilatation, cytotoxicity and vascular disease. Nitric oxide and prostacyclin (PGI2), both released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion. These autacoids also inhibit the adhesion and migration of leucocytes and, in some arteries, they synergize in terms of vasodilatation.2. The development of atherosclerosis and hyperlipaemia per se is accompanied by impairment of endothelium‐dependent vasodilatation.3. Atherosclerosis is associated with marked changes in the activity of isoforms of NO synthase (NOS) in the artery wall, including increased expression of the NOS2 (inducible) isoform in complex human lesions as well as in the neointima of experimental animal models.4. Failure of NO release from the endothelium with normal physiological stimuli, which has been attributed to a defect in the operation of the endothelial NOS (NOS3), provides conditions propitious for leucocyte adhesion, vasospasm, thrombosis and, in addition, may promote increased proliferation of intimal cells.5. Nitric oxide and superoxide anions generated by inflammatory cells in atherosclerosis react to form cytodestructive per‐oxynitrite radicals, potentially causing injury to the endothelium and myocytes, and this may be a factor in apoptosis of cells leading to plaque rupture.6. We have been able to reverse these NO defects with therapeutic agents, including angiotensin‐converting enzyme inhibitors, antagonists of platelet‐activating factor and NO donor compounds, all offering promise in protecting against some manifestations of vascular disease.
NATRIURESIS AND INHIBITION OF Na+/K+‐ATPase: MODULATION OF RESPONSE BY PHYSIOLOGICAL MANIPULATION
Authors: McDougall John G. , Yates Neale A. 
Published: June 2007

SUMMARY1. There is considerable evidence for the existence of an endogenous inhibitor of Na+/K+‐ATPase. The exact physiological nature and role of this postulated agent remains unclear although it would be predicted that one of its actions would bi stimulation of renal sodium excretion.2. The natriuretic effect of renal arterial infusion of ouabain is relatively slow in onset and is sustained.3. The natriuresis is not modified by changes in sodium status unlike the natriuretic effect of atrial natriuretic peptide.4. The natriuretic action of ouabain is enhanced dramatically by acute volume expansion or chronic mineralocorticoid treatment, which both result in hypokalemia, hypertension am hypervolemia.5. The natriuretic response to small increments in blood pressure is markedly enhanced by treatment with ouabain.6. We hypothesize that the interaction between the inhibition of Na+/K+‐ATPase and elevated blood pressure could result in the shedding of sodium in conditions where there are increased levels of circulating endogenous digitalis‐like factors.
SCANNING THE GENOME FOR ESSENTIAL HYPERTENSION LOCI
Authors: Morris Brian J. , Griffiths Lyn R. 
Published: June 2007

SUMMARY1. Essential hypertension occurs in people with an underlying genetic predisposition who subject themselves to adverse environmental influences. The number of genes involved is unknown, as is the extent to which each contributes to final blood pressure and the severity of the disease.2. In the past, studies of potential candidate genes have been performed by association (case‐control) analysis of unrelated individuals or linkage (pedigree or sibpair) analysis of families. These studies have resulted in several positive findings but, as one may expect, also an enormous number of negative results.3. In order to uncover the major genetic loci for essential hypertension, it is proposed that scanning the genome systematically in 100–200 affected sibships should prove successful.4. This involves genotyping sets of hypertensive sibships to determine their complement of several hundred microsatellite polymorphisms. Those that are highly informative, by having a high heterozygosity, are most suitable. Also, the markers need to be spaced sufficiently evenly across the genome so as to ensure adequate coverage.5. Tests are performed to determine increased segregation of alleles of each marker with hypertension. The analytical tools involve specialized statistical programs that can detect such differences. Non‐parametric multipoint analysis is an appropriate approach.6. In this way, loci for essential hypertension are beginning to emerge.
BRADYKININ MEDIATES MYOCARDIAL ISCHAEMIC PRECONDITIONING AGAINST FREE RADICAL INJURY IN GUINEA‐PIG ISOLATED HEART
Authors: Jin Zhu‐Qiu , Chen Xiu 
Published: June 2007

SUMMARY 1. Myocardial ischaemic preconditioning (IP) against free radical injury and its possible mediator(s) was investigated in a Langendorff‐perfused guinea‐pig heart. 2. l,l‐Diphenyl‐2‐picryl‐hydrazyl (DPPH) was used for triggering free radical injury in cardiac tissue. It reduced left ventricular developed pressure (LVDP), +dp/dtmax, heart rate (HR) and coronary flow (CF) and increased thiobarbituric acid‐reactive substances (TBARS) in cardiac tissue. 3. Ischaemic preconditioning (5min global ischaemia and 5min reperfusion) exerted cardioprotection against DPPH‐induced functional impairment, with significant improvement in LVDP, +dp/dtmax, HR and CF. The formation of TBARS in cardiac tissue was reduced. Blockade of bradykinin (BK) B2 receptors with icatibant (HOE 140) abolished the cardioprotective effects of IP. 4. Bradykinin (10−7 mol/L) perfusion for 10 min protected the heart against free radical injury. The cardioprotection induced by BK was reversed by HOE 140. 5. Pretreatment with IP and BK results in cardiac protection against free radical injury through the activation of Bi receptors. Endogenously generated BK may mediate IP in the guinea‐pig heart.
ELECTROPHYSIOLOGICAL PROPERTIES OF THE FIBRILLATING ATRIUM: IMPLICATIONS FOR THERAPY
Authors: Tse Hung‐Fat , Lau Chu‐Pak 
Published: June 2007

SUMMARY1. Atrial fibrillation (AF) is the most commonly occurring cardiac dysrhythmia and remains a challenge to medical therapy. Although the disorder has been recognized for over 100 years, surprisingly very little is understood about its pathophysiology. Over the past decade, a variety of experimental and animal models of AF have been developed and these have provided insights into the mechanism of AF.2. The pathophysiology of AF is complex. Atrial fibrillation can be caused either by a single source of very rapid impulses or, in the majority of cases, by multiple random re‐entering wavelets. The notion that AF may be initiated by a single rapid firing focus and the perpetuation of AF may be partly dependent on macro re‐entry around the natural atrial orifices provides a new potential curative therapy for AF by radiofrequency ablation.3. Shortening of atrial wavelength, either by slow atrial conduction velocities, short atrial refractory periods or both, seems to predispose to development of intra‐atrial re‐entry and, thus, AF. The functional mechanism by which anti‐arrhythmic drugs terminate AF appears to be by prolonging the wavelength and decreasing the number of re‐entry wavelets. These understandings are important for the future development of effective anti‐arrhythmic agents against AF.4. The presence of a short and variable excitable gap during AF may be potentially important for termination of AF by pacing.5. New insights are being gained into the potential role and mechanism of electrical remodelling of the atrium due to AF. Repeated induction of AF by rapid atrial pacing leads to a shortening of atrial refractoriness with loss of rate adaptation, which favours the induction and maintenance of AF. These electrophysiological changes were assumed to occur during repeated AF and to facilitate the generation of multiple re‐entrant wavelets. These data suggest that prompt restoration of sinus rhythm and new novel therapy that prevents or diminishes electrical remodelling may promote maintenance of sinus rhythm after successful cardioversion.
ELECTRICAL BASIS OF PERISTALSIS IN THE MAMMALIAN UPPER URINARY TRACT
Authors: Lang RJ , Exintaris B , Teele ME , Harvey J , Klemm MF 
Published: June 2007

SUMMARY1. Peristalsis in the mammalian upper urinary tract (UUT) is mostly myogenic in origin, originating predominately in the proximal pelvicalyceal regions of the renal pelvis, an area that is enriched with specialized smooth muscle cells termed ‘atypical’ smooth muscle cells. Propagating peristaltic contractions are little affected by blockers of either autonomic nerve function or nerve impulse propagation; however, blockers of sensory nerve function or prostaglandin synthesis reduce both the frequency and the strength of the spontaneous contractions underlying peristalsis.2. The electrical drive for these peristaltic contractions has long been considered to involve mechanisms analogous to the heart, such that ‘atypical’ smooth muscle cells generate spontaneous ‘pacemaker’ action potentials. These pacemaker potentials trigger the firing of action potentials and contraction in the muscular regions of the renal pelvis, which propagate distally to the ureter, propelling urine towards the bladder.3. Recent intracellular microelectrode and single cell/channel patch‐clamp studies have revealed that the ionic conductances underlying the action potentials recorded in the UUT are likely to involve the opening and slow closure of voltage‐activated ‘L‐type’ Ca2+ channels, offset by the time‐dependent opening and closure of both voltage‐ and Ca2+‐activated K+ channels.4. In the present review we summarize the current knowledge of the ionic mechanisms underlying action potential discharge in the UUT, as well as present our view on how this electrical activity supports the initiation and conduction of UUT peristalsis.
VASORELAXANT EFFECTS OF SCA40 (A PHOSPHODIESTERASE III INHIBITOR) IN PULMONARY VASCULAR PREPARATIONS IN RATS
Authors: Crilley Trina K , Wanstall Janet C , Bonnet Pierre‐Antoine 
Published: June 2007

SUMMARY1. The novel phosphodiesterase (PDE) inhibitor SCA40 (6‐bromo‐8(methylamino)imidazo[1,2‐α]pyrazine‐2‐carbo‐nitrile) was examined for its vasorelaxant activity on isolated pulmonary vascular preparations from rats.2. SCA40 relaxed ring preparations of main and intralobar pulmonary artery precontracted submaximally with either phenylephrine or U46619 (thromboxane‐mimetic). Based on negative log EC50 values, SCA40 was six‐ to 14‐fold more potent than the PDE III inhibitor milrinone or the non‐selective PDE inhibitor 3‐isobutyl‐1‐methyI xanthine (IBMX). The potency of SCA40 corresponded to its reported potency as a PDE III inhibitor.3. In isolated perfused lungs, SCA40 reversed the vasoconstriction induced by alveolar hypoxia. It was 49‐fold more potent than IBMX.4. In main pulmonary artery the vasorelaxation induced by SCA40 was not blocked by the large‐conductance calcium‐activated potassium channel (BKca) inhibitors iberiotoxin (50 and 100nmoI/L) or charybdotoxin (100 and 300nmol/L). This was in contrast to data on guinea‐pig trachea, where responses to SCA40 were significantly inhibited by charybdotoxin (100nmol/L).5. It is concluded that opening of BKca channels does not contribute to the pulmonary vasorelaxant effects of SCA40 in main pulmonary artery and it is likely that responses reflect the PDE III inhibitory properties of the drug.6. It is postulated that SCA40 may be useful as a pulmonary vasodilator in disorders such as pulmonary hypertension.
Multi‐drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population
Authors: Tahara Tomomitsu , Arisawa Tomiyasu , Shibata Tomoyuki , Hirata Ichiro , Nakano Hiroshi 
Published: June 2007

AbstractBackground and Aims:  Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi‐drug resistance 1 (MDR1) gene mediates the expression of P‐glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P‐glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer.Method:  The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR‐RFLP in all of the patients.Results:  The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23–0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non‐cardiac cancer (OR = 0.42; 95% CI = 0.23–0.79), middle‐third cancer (OR = 0.36; 95% CI = 0.17–0.77), advanced cancer (OR = 0.31; 95% CI = 0.13–0.73), venous invasion (OR = 0.30; 95% CI = 0.10–0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13–0.65).Conclusion:  Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.
Recurrence risk in Autism Spectrum Disorder: A study of parental knowledge
Authors: Whitelaw Charlotte , Flett Peter , Amor David J 
Published: June 2007

Aim:  To describe recurrence risk information currently being obtained by families affected by Autism Spectrum Disorder (ASD).Methods:  Structured telephone interview of parents of 21 children who received a diagnosis of ASD at Calvary Health Care Tasmania, Hobart, Australia between May 2005 and May 2006.Results:  Only one of the 21 parents knew their true recurrence risk. Many overestimated their risk substantially, and in four cases this had led to a decision against increasing family size. Eleven parents said they had received no information about recurrence risk, and only one cited medical practitioners as a source of information about recurrence risk.Conclusion:  Current provision of information about recurrence risk to families affected by ASD is inadequate.
Characteristics of travel to and from school among adolescents in NSW, Australia
Authors: Booth Michael L , Okely Anthony D , Denney‐Wilson Elizabeth , Hardy Louise L , Dobbins Timothy , Wen Li‐Ming , Rissel Christopher 
Published: June 2007

Aim:  Active transport to and from school is frequently identified as an opportunity to increase energy expenditure among young people. The epidemiology of travel behaviours among Grade 6, 8 and 10 students in NSW is reported.Methods:  A representative population survey of students in NSW, Australia was conducted during February to May 2004 (n = 2750) and the prevalence of travelling to and from school by walking, car and public transport was determined for Grade 6, 8 and 10 students.Results:  Among Grade 6 students, approximately 30% travelled by car, 30% walked and 20% used public transport to travel to school (the travel habits of 20% could not be accurately characterised). Among secondary school students, approximately 50% used public transport, 15–20% travelled by car and 15–20% walked. Among those who walked or used public transport, the median times spent walking were 10–15 min and 5 min per trip, respectively.Conclusions:  While there is little scope to increase the prevalence of active transport among secondary school students, there is potential to do so among primary school students. Primary school students who replace travelling to and from school by car with walking will experience an increase in activity energy expenditure of up to 10% and those who change to public transport will experience an increase in activity energy expenditure of up to 3%.
Over‐the‐counter medication use for childhood fever: A cross‐sectional study of Australian parents
Authors: Walsh Anne , Edwards Helen , Fraser Jenny 
Published: June 2007

Aim:  To report Australian parents’ medication (paracetamol, ibuprofen and homeopathic) use in childhood fever management.Methods:  A cross‐sectional survey of 401 Queensland parents of children aged between 6 months and 5 years recruited through advertising (48.4%), face‐to‐face (26.4%) and snowball (24.4%) methods was conducted. A 17‐item instrument was developed; construct and content validity were determined by an expert panel; and item reliability by test–retest with nine parents. Areas targeted were medication use and influences on and barriers to medication use.Results:  Most participants were female, had tertiary education and lived in a major city (mean age 34.6 years). Reducing children’s fever with over‐the‐counter medications was common (91%): 94% of parents reported using paracetamol and 77% reported using ibuprofen. A few (3.7%) used homeopathic remedies. Dosage was determined by weight (86.3%), age (84.3%), temperature (32.4%), illness severity (31.4%) and lethargy (20.9%). Frequency was determined by instructions on the medication label (55.3%), temperature (40.6%) and well‐being (27.7%). Ibuprofen was administered too frequently by 31.5% (four hourly by 22.8%), and paracetamol by 3.8%. Fifty‐two per cent had alternated medications, 65.8% of these for temperatures below 38.5°C. Decisions to alternate were influenced by information from doctors/hospitals (49.5%) and children remaining febrile post‐antipyretic (41.7%). Most parents reported over‐the‐counter medications as potentially harmful (73.2%), citing liver (38.2%), stomach (26.4%) and kidney (18.6%) damage and overdose (35.7%) as concerns. When medications were refused or spat out (44.0%), parents used force (62.4%), different methods (29.5%) or suppositories (20.8%).Conclusions:  Most parents used over‐the‐counter medications to reduce fever, often below 38.5°C. The belief that these medications were harmful was overridden by fears of harmful outcomes from fever.