bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is hypertension a leading cause of heart failure in Chinese?
Authors: Nicholls M Gary , Richards A Mark 
Published: March 2003

Summary1. There is considerable uncertainty regarding the importance of various risk factors in the development of heart failure. Most data are from Caucasian populations, where hypertension and coronary artery disease appear dominant.2. Because it cannot be presumed that risk factor profiles will be identical for all races, we reviewed the literature on the aetiology of heart failure in Chinese.3. There are, apparently, no long‐term prospective studies defining the risk factors for heart failure in Chinese. Studies from Hong Kong in the 1990s point to an overlap of risk factors (especially hypertension, ischaemic heart disease and diabetes) and a high prevalence of diastolic heart failure (66%). Antihypertensive drug treatment appears likely to protect against the development of heart failure but end‐points from formal trials are too small to be certain.4. Available data, short of being definitive, point to hypertension being the most important identifiable risk factor in Chinese with heart failure. This may change with diabetes mellitus becoming more prevalent in the Chinese population.
Ion channel formation and membrane‐linked pathologies of misfolded hydrophobic proteins: The role of dangerous unchaperoned molecules
Authors: Kourie Joseph I , Henry Christine L 
Published: March 2003

Summary1. Protein–membrane interaction includes the interaction of proteins with intrinsic receptors and ion transport pathways and with membrane lipids. Several hypothetical interaction models have been reported for peptide‐induced membrane destabilization, including hydrophobic clustering, electrostatic interaction, electrostatic followed by hydrophobic interaction, wedge × type incorporation and hydrophobic mismatch.2. The present review focuses on the hypothesis of protein interaction with lipid membranes of those unchaperoned positively charged and misfolded proteins that have hydrophobic regions. We advance the hypothesis that protein misfolding that leads to the exposure of hydrophobic regions of proteins renders them potentially cytotoxic. Such proteins include prion, amyloid β protein (AβP), amylin, calcitonin, serum amyloid and C‐type natriuretic peptides. These proteins have the ability to interact with lipid membranes, thereby inducing membrane damage and cell malfunction.3. We propose that the most significant mechanism of membrane damage induced by hydrophobic misfolded proteins is mediated via the formation of ion channels. The hydrophobicity based toxicity of several proteins linked to neurodegenerative pathologies is similar to those observed for antibacterial toxins and viral proteins.4. It is hypothesized that the membrane damage induced by amyloids, antibacterial toxins and viral proteins represents a common mechanism for cell malfunction, which underlies the associated pathologies and cytotoxicity of such proteins.
Spiders of medical importance in the Asia–Pacific: Atracotoxin, latrotoxin and related spider neurotoxins
Authors: Nicholson Graham M , Graudins Andis 
Published: March 2003

Summary1. The spiders of medical importance in the Asia–Pacific region include widow (family Theridiidae) and Australian funnel‐web spiders (subfamily Atracinae). In addition, cupboard (family Theridiidae) and Australian mouse spiders (family Actinopodidae) may contain neurotoxins responsible for serious systemic envenomation. Fortunately, there appears to be extensive cross‐reactivity of species‐specific widow spider antivenom within the family Theridiidae. Moreover, Sydney funnel‐web antivenom has been shown to be effective in the treatment of mouse spider envenomation.2. α‐Latrotoxin (α‐LTx) appears to be the main neurotoxin responsible for the envenomation syndrome known as ‘latrodectism’ following bites from widow spiders. This 120 kDa protein binds to distinct receptors (latrophilin 1 and neurexins) to induce neurotransmitter vesicle exocytosis via both Ca2+‐dependent and ‐independent mechanisms, resulting in vesicle depletion. This appears to involve disruption to a process that normally inhibits vesicle fusion in the absence of Ca2+. Precise elucidation of the mechanism of action of α‐LTx will lead to a major advancement in our understanding of vesicle exocytosis.3. δ‐Atracotoxins (δ‐ACTX) are responsible for the primate‐specific envenomation syndrome seen following funnel‐web spider envenomation. These peptides induce spontaneous repetitive firing and prolongation of action potentials in excitable cells. This results from a hyperpolarizing shift of the voltage‐dependence of activation and a slowing of voltage‐gated Na+ channel inactivation. This action is due to voltage‐dependent binding to neurotoxin receptor site‐3 on insect and mammalian voltage‐gated Na+ channels in a manner similar, but not identical, to scorpion α‐toxins and sea anemone toxins. δ‐Atracotoxins provide us with highly specific tools to study Na+ channel structure and function4. ω‐ and Janus‐faced ACTX, from funnel‐web spider venom, are novel neurotoxins that show selective toxicity to insects. In particular ω‐ACTX define a new insecticide target due to a specific action to block insect voltage‐gated Ca2+ channels. Both these ACTX show promise for the development of baculoviral recombinant biopesticides expressing these toxins for the control of insecticide‐resistant agricultural pests. In addition, they should provide valuable tools for the pharmacological and structural characterization of insecticide targets.
Pirfenidone attenuates ischaemia–reperfusion injury in the rat small intestine
Authors: Arumugam Thiruma V , Shiels Ian A , Margolin Solomon B , Taylor Stephen M , Brown Lindsay 
Published: March 2003

Summary1. Pirfenidone, an antifibrotic compound with anti‐inflammatory effects, has been investigated in a rat model of acute experimental ischaemia–reperfusion injury of the small intestine.2. Occlusion of the superior mesenteric artery in young adult female rats for 30 min followed by reperfusion for 120 min induced significant local and systemic effects, including tissue haemorrhage with oedema, elevated serum concentrations of tumour necrosis factor (TNF)‐α, neutropenia, hypotension and bradycardia.3. Administration of pirfenidone (200 mg/kg, p.o., i.v. or i.p.) 30 min before occlusion completely inhibited the increase in serum TNF‐α concentrations. Pirfenidone inhibited, but did not completely prevent, tissue damage in the small intestine, as well as hypotension and oedema, but neutropenia and bradycardia were not significantly changed by treatment.4. Thus, pirfenidone effectively moderates both local and some systemic effects of ischaemia–reperfusion injury in the rat small intestine model.
Survival, haemodynamics and cardiac remodelling follow up in mice after myocardial infarction
Authors: Pons S , Fornes P , Hagege AA , Heudes D , Giudicelli J‐F , Richer C 
Published: March 2003

Summary1. In the present study, the time‐course, over a 1 year period, of postischaemic dilated cardiomyopathy and/or development of congestive heart failure was investigated in mice in terms of survival and cardiac functional and structural characteristics.2. C57BL/6 mice with myocardial infarction (MI mice; coronary ligation n = 78) or sham‐operated animals (n = 45) were used and echocardiographic, haemodynamic and histomorphometric parameters were assessed at 3, 6 and 12 months post‐MI.3. At 12 months, the survival rate was 70% in MI mice. Left ventricular dysfunction was evidenced by a strong decrease in ejection fraction (EF; −48 and −53% at 6 and 12 months, respectively; both P < 0.05) and an increase in left ventricular end‐diastolic pressure (+100% at both 6 and 12 months; both P < 0.05). There was no major worsening in cardiac function between 6 and 12 months, suggesting strong compensatory mechanisms. Cardiac remodelling was observed, characterized by strong left ventricular hypertrophy (+38 and +62% at 6 and 12 months, respectively; both P < 0.05) and dilatation (+53% at 6 months; P < 0.05), but collagen was not significantly increased. Significant correlations were found between EF (echocardiography) and dP/dtmax, between end‐diastolic volume (echocardiography) and left ventricular internal perimeter (histomorphometry) and between left ventricular mass (echocardiography) and weight.4. In conclusion, despite a high survival rate, the MI mouse model displays most of the hallmarks of postischaemic dilated cardiomyopathy and/or congestive heart failure, thus affording the necessary background for the subsequent evaluation of gene manipulation and/or drug effects. In addition, two‐dimensional echocardiography appears to be a suitable tool for the long‐term follow up of cardiac function and remodelling in this model.
RNA interference may be more potent than antisense RNA in human cancer cell lines
Authors: Aoki Y , Cioca DP , Oidaira H , Kamiya J , Kiyosawa K 
Published: March 2003

Summary1. RNA interference (RNAi) is a newly discovered cellular pathway for the silencing of sequence‐specific genes at the mRNA level by the introduction of the cognate double‐stranded (ds) RNA . Because antisense (AS) mechanisms have similar effects, we compared these two effects in human cancer cell lines, considering a possible application of RNAi for cancer therapy.2. We tested RNAi effects by transfecting human hepatoma and pancreatic cancer cell lines with AS and sense (S) RNA expression plasmids corresponding to the exogenous luciferase gene or the endogenous c‐raf gene in the form of complexes with a cationic lipopolyamine or a tumour‐targeting peptide vector we developed. In addition, we compared the effects of small interfering RNA and AS oligoDNA complexed with the peptide vector.3. From the viewpoint of AS actions, the effect of the AS RNA may be cancelled by the S RNA, although, interestingly, we found that the combination of the AS and S RNA expression plasmids was more effective than the AS RNA expression plasmids alone in reducing target gene expression, whereas the S RNA expression plasmids had no effects. The combination of the luciferase AS and S RNA had no effects on the expression of either the β‐galactosidase gene or the c‐raf gene. In the presence of 2‐aminopurine (an inhibitor of dsRNA‐activated protein kinase), the inhibitory effect of the combination of AS and S RNA on gene expression did not change in the case of the endogenous c‐raf gene, but was reduced in the case of the exogenous luciferase gene. The effect of 22 nucleotide RNA duplexes corresponding to the luciferase gene was by one order stronger than that of the phosphorothioate AS DNA.4. Thus, it is suggested that RNAi may be more potent than AS RNA in reducing target gene expression in human cancer cell lines, regardless of the length of dsRNA. With further studies on the RNAi phenomenon in cancer cells, RNAi could provide a novel approach for cancer gene therapy.
Disposition kinetics of ketotifen from liposomal dry powder for inhalation in rat lung
Authors: Joshi Mayank , Misra Ambikanandan 
Published: March 2003

Summary1. The aim of the present study was to understand the benefit of liposomal dry powder for inhalation (LDPI) of ketotifen fumarate (KF) over plain drug dry powder for inhalation as a pulmonary targetted drug‐delivery system.2. The KF liposomes, composed of egg phosphatidyl choline and cholesterol, were prepared by the lipid film hydration technique. The liposomal dispersion was freeze dried and formulated to a dry powder for inhalation. Values of 89.0–65.3% drug entrapment of freeze‐dried liposomes were estimated in prepared batches.3. Rehydrated KF liposomes formed by the hydration of LDPI or the plain KF solution was delivered to rat lungs by intratracheal instillation. Simultaneous monitoring of drug levels in the bronchoalveolar lavage and lung tissue enabled assessment of pulmonary drug disposition.4. Cumulative drug levels in lung tissue after intratracheal administration revealed that with liposomes targetting factors were between 1.36 and 1.54. The maximal drug concentration in lung homogenate for LDPI was 42.0 µg compared with 73.6 µg for plain drug solution.5. Similarly, the time to reach maximum drug concentration in the lung homogenate for liposomal dry powder was 9–12 h compared with 3 h for plain drug.6. Hence, the use of LDPI of KF was found to provide desired drug levels in the lung for a long time and thereby increased pulmonary targetting7. This is expected to enhance the therapeutic index of the drug and probably reduce the dose administered and the cost of therapy.
In vitro cultivation of spermatocysts to matured sperm in the silkworm Bombyx mori
Authors: Kawamura Naoko , Sahara Ken 
Published: March 2003

Bombyx spermatogonia are bipotential, producing nucleate eupyrene sperm and anucleate apyrene sperm. An in vitro cultivation of spermatocysts of Bombyx mori from spermatocytes to matured sperm was established. The present experiment made clear that: (i) spermatocysts must be isolated; (ii) constant shaking at 45 r.p.m. was necessary; and (iii) the addition of Bombyx hemolymph (BH) was indispensable for successful cultivation. In the absence of BH, spermatogenesis proceeded normally for 2 or 3 days and, thereafter, spermatocytes and sperm bundles began to degenerate. The best results for normal eupyrene spermatogenesis were obtained when culture medium containing BH of the corresponding stage was used in every exchange of the medium at 72 h intervals. None or only a small number of apyrene sperm bundles was produced by this culture system when spermatocysts from larval testes were used, although eupyrene spermatogenesis proceeded normally to form matured, or squeezed, sperm bundles.
Localization and functional role of a 41 kDa collagenase/gelatinase activity expressed in the sea urchin embryo
Authors: Mayne Janice , Robinson John J. 
Published: March 2003

The egg storage compartment of the sea urchin embryo was investigated for a protein destined for export to the extracellular matrices. Using an antiserum prepared against a 41 kDa collagenase/gelatinase localized to the extraembryonic matrices (the hyaline layer and basal lamina), the egg storage compartment was mapped for this antigen. Indirect immunofluorescence analysis revealed the 41 kDa collagenase/gelatinase in the cortical granules as well as a second compartment which was dispersed throughout the egg cytoplasm. High resolution immunogold labeling defined this cytoplasmic compartment as the yolk granule organelle. Gelatin substrate gel zymography revealed the presence of a 41 kDa gelatin cleavage activity in purified yolk granules. These results suggest a role for yolk granules in regulated protein export and challenge the traditional view of this organelle as a benign storage compartment for nutrients. In additional experiments, embryos grown in the presence of the 41 kDa cleavage activity or the anti‐41 kDa antiserum had severely delayed gut formation and spicule elongation. These results demonstrate a requirement for defined levels of the 41 kDa activity in the extracellular matrices of the developing embryo.
Association of ants with juvenile Ogyris amaryllis amaryllis Hewitson (Lepidoptera: Lycaenidae) in south‐eastern Queensland
Authors: Schmidt Daniel J , Rice Steven J 
Published: March 2003

AbstractThe life history of the mistletoe‐feeding butterfly Ogyris amaryllis is commonly thought to involve an obligate association with ants. The distribution of eggs of subspecies O. a. meridionalis Bethune‐Baker, which occurs over much of the Australian interior, is strongly associated with Iridomyrmex ants. This study examined the level and frequency of ant association exhibited by larvae and pupae of O. a. amaryllis, which occurs in coastal areas of eastern Australia. The distribution of juveniles was compared with that of ants at the scale of sites, mistletoe host trees, and larval sheltering locations. A significant positive association between larvae and ants was detected, although this association was weak and non‐specific, indicating that O. a. amaryllis is facultatively myrmecophilous. Observed ant attendance of larvae was uncommon (5.6%). Available evidence suggests that either plasticity exists in the degree of myrmecophily of O. amaryllis, with different degrees of association expressed under different ecological circumstances, or different degrees of myrmecophily are characteristic of subspecific status.
Athlete’s heart syndrome: A diagnostic dilemma in the emergency department
Authors: O’Brien Debra L , Rogers Ian R 
Published: March 2003

AbstractAthletic training can cause morphological cardiac changes as part of physiological adaptation. When these changes result in abnormalities of physical examination, the electrocardiogram, chest radiography or echocardiographic findings the individual is said to have athlete’s heart syndrome. Many of these changes mimic significant cardiovascular disease, including myocardial ischaemia, hypertrophic cardiomyopathy (the most common cause of sudden cardiac death), dilated cardiomyopathy and pericarditis. Recognizing and distinguishing physiological changes from significant cardiovascular disease is extremely important in an emergency medicine setting. Inappropriate or withheld treatment can affect morbidity and mortality significantly; detection of genuine cardiovascular disease usually requires exclusion from athletic competition to reduce the risk of sudden death. A number of criteria and methods have been proposed to assist in the task of differentiating physiological from pathological changes. Three case reports of ultra‐endurance athletes, which highlight these dilemmas, are presented. These patients had significant electrocardiogram changes, including marked ST segment elevation, T wave inversion and evidence of left ventricular hypertrophy. This paper discusses the morphological and clinical changes associated with athlete’s heart syndrome and the current criteria and methods available to help differentiate this from cardiovascular disease. In many emergency department situations, a clinical history and examination may be all that is required. More complex cases are best resolved by use of echocardiography. Emergency physicians need to be aware of this syndrome and the diagnostic difficulties they may face when managing such patients.
A comparison of Australasian and United States emergency medicine training programmes
Authors: Taylor David McD , Jelinek George A 
Published: March 2003

AbstractTraining in emergency medicine differs from country to country. This article compares the emergency medicine training programmes of Australasia and the United States of America. The perceived advantages of programmes are highlighted, but no attempt is made to determine which is the better programme. The Australasian programme is significantly longer and places greater emphasis on the basic clinical sciences, physical examination skills and academic output. Australasian College for Emergency Medicine regulations are relatively flexible, and allow trainees to design their own programmes. Australasian trainees are encouraged to arrange accredited positions in a variety of hospitals. Overseas and part‐time training may be acceptable. In the US, trainees rotate within and from one parent institution which provides a rigid teaching structure for a ‘critical mass’ of trainees, based upon a core curriculum. Rotations tend to be much shorter than in the Australasian programme but ensure exposure to a broader range of clinical experience. In the US programme, evaluation of trainees and teaching faculty is more frequent and documentation of procedural and resuscitation skills is required. In addition, trainees are under the close supervision of the teaching faculty at all times when working in an emergency department.
Analysis of serious injuries caused by stairway falls
Authors: Ragg Michael , Hwang Stephen , Steinhart Brian 
Published: March 2003

Abstract Objective: To study the demographics of patients who sustained serious injuries from falling down stairs. Method: This study is a retrospective analysis of all patients who presented to an urban hospital with an injury severity score of equal to or greater than 16 after falling down stairs during the period January 1992 to December 1996. Patient demographics, stair location and number, severity and anatomical nature of injuries, serum ethanol levels, patient referral characteristics and mortality rates were examined. Results: A total of 113 patients were studied; 74% were male. Sixty‐five per cent of falls occurred at the patient’s place of residence. Ethanol may have been a contributing factor in 55% of injuries. Ninety‐five per cent of victims had an injury severity score of equal to or less than 30. Head injuries were common with acute subdural haematoma occurring in 57% of patients. Head‐injured patients had a significantly higher mortality rate than non‐head‐injured patients (P = 0.02). Increasing age and higher injury severity score correlated with poor outcome in all patients. Thirty‐nine of the 113 stairway‐fall patients (35%) died in hospital compared with 207 of 1091 non‐stairway‐fall patients (19%) during the same period (P < 0.001). Conclusion: In the adult population, falls down stairs may result in serious injuries, particularly head trauma. In the present study, this group of patients had a significantly higher mortality than other trauma patients.
Management of venous thromboembolic disease in the lower limb
Authors: May Christopher R 
Published: March 2003

AbstractThromboembolic disease continues to cause significant morbidity and mortality in our community, despite extensive research into the aetiological factors and significant resources invested in the development of pharmacological agents for treating this condition. Development of more sensitive and specific modalities for identifying venous thromboses has improved their early detection, particularly in the commonest site, the lower limb. A rational evidence‐based management pathway has not been formulated as debate continues over the most appropriate method of treatment. This review outlines the pathophysiology of the disease, provides a clinical pathway for the management of lower limb thromboembolic disease using reliable available evidence and briefly discusses the efficacy of drug therapy.