bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasopeptidase Inhibition In A Canine Model Of Exercise‐Induced Left Ventricular Dysfunction
Authors: Holzgrefe Henry H , Arthur Susan R , Powell James R 
Published: March 2003

SUMMARY1. The present study compared the acute efficacies of vasopeptidase inhibition with omapatrilat, nitroglycerin and angiotensin‐converting enzyme (ACE) inhibition in exercise‐induced myocardial dysfunction. Omapatrilat, a vasopeptidase inhibitor, inhibits both neutral endopeptidase and ACE. Whereas vasopeptidase inhibitors have demonstrated clinical efficacy in hypertension and heart failure, their effects in myocardial ischaemia remain unclear.2. Omapatrilat (0.3 mg/kg) was compared with vehicle (saline), an ACE inhibitor (fosinoprilat; 0.44 mg/kg) and nitroglycerin (8.0 μg/kg per min), in an established canine model of exercise‐induced myocardial dysfunction induced by progressive closure of an ameroid constrictor placed about the proximal circumflex coronary artery. Maximal treadmill exercise tests, terminated when heart rate failed to increase with increasing workload or failure to continue exercise, were performed in chronically instrumented dogs.3. During exercise, omapatrilat and nitroglycerin similarly increased ischaemic wall thickening (P≤ 0.0001, ANOVA, 12 d.f.), whereas fosinoprilat and vehicle were without effect. Ischaemic zone ST changes were decreased with nitroglycerin (P = 0.0006, ANOVA, 12 d.f.) and tended to decrease with omapatrilat (P = 0.07, ANOVA, 12 d.f.). Peak exercise capacity was increased with nitroglycerin (9.7 ± 1.1 vs 11.2 ± 1.0 kcal, control vs 4 h, respectively; n = 6) and omapatrilat (9.7 ± 0.8 vs 11.4 ± 0.6 kcal, control vs 4 h, respectively; n = 6) and was unchanged with ACE inhibition (9.0 ± 1.2 vs 9.5 ± 1.1 kcal, control vs 4 h, respectively; n = 7). Omapatrilat differentially increased double product during exercise (P = 0.001, ANOVA, 12 d.f.) compared with other treatments.4. During exercise‐induced myocardial dysfunction, acute ACE inhibition did not attenuate ischaemic changes and failed to improve exercise capacity. Increased exercise capacity with omapatrilat was accompanied by a differential increase in double product, consistent with increased oxygen supply and demand. Improvements in ischaemic function were comparable between omapatrilat and nitroglycerin, suggesting that omapatrilat may represent a novel therapy in demand‐induced ischaemia.
Cardiovascular Responses During Stimulation Of Hindlimb Skeletal Muscle Nerves In Anaesthetized Rats
Authors: Ishide Takeshi , Pearce William J , Ally Ahmmed 
Published: March 2003

SUMMARY1. Cardiovascular responses during static skeletal muscle contraction in anaesthetized rats appear to be contradictory. The present study attempted to explain such variations by stimulating different peripheral nerves supplying the hindlimb skeletal muscles using anaesthetized Sprague‐Dawley rats.2. Muscle contractions were evoked by a 30 s stimulation of the sciatic, tibial, peroneal nerves or the sciatic nerve with transected peroneal branch at threefold the motor threshold, 0.1 msec duration and 40 Hz frequency.3. Contractions during stimulation of the tibial or the sciatic nerve with severed peroneal branch evoked similar increases in arterial pressure and heart rate. Following stimulation of the tibial nerve, blood pressure, heart rate and muscle tension increased by 23 ± 3 mmHg, 31 ± 5 b.p.m. and 789 ± 34 g, respectively. For the sciatic nerve with transected peroneal branch, increases the respective increases were 27 ± 5 mmHg, 32 ± 6 b.p.m. and 802 ± 43 g. In contrast, peroneal nerve stimulation produced depressor and bradycardic responses of –22 ± 5 mmHg and –40 ± 9 b.p.m., respectively. Interestingly, intact sciatic nerve stimulation elicited pressor, depressor or no responses (average being –10 ± 8 mmHg), along with a consistent increase in heart rate of 24 ± 7 b.p.m.4. The results demonstrate that static muscle contraction following stimulation of the tibial or sciatic nerve with transected peroneal branch, elicits consistent increases in blood pressure and heart rate. Furthermore, stimulation of the peroneal nerve elicits a depressor response, while stimulation of the intact sciatic nerve evokes variable cardiovascular responses. Overall, anaesthetized rats can be excellent models to study the variable cardiovascular responses during activation of group III and/or group IV muscle afferents.
Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion
Authors: Costa MA , Loria A , Marchetti M , Balaszczuk AM , Arranz CT 
Published: March 2003

Summary1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of l‐arginine during extracellular fluid volume expansion (10% bodyweight).2. Animals were randomized to non‐expanded and expanded groups. Both groups received different treatments: l‐arginine (250 mg/kg, i.v.), NG‐nitro‐l‐arginine methyl ester (l‐NAME; 1 mg/kg, i.v.), haloperidol (3 mg/kg, i.p.) and l‐arginine + haloperidol (n = 8). Mean arterial pressure (MAP), diuresis, natriuresis, kaliuresis, glomerular filtration rate, renal plasma flow (RPF) and nitrite and nitrate (NOx) excretion were determined.3. The increase in MAP induced by l‐NAME was greater in expanded than in non‐expanded rats (42 ± 3 vs 32 ± 3 mmHg, respectively; P < 0.01). Administration of haloperidol did not modify the l‐arginine hypotensive effect.4. Blockade of nitric oxide synthase diminished urine flow in non‐expanded (4.15 ± 0.56 vs 0.55 ± 0.11 µL/min per 100 g; P < 0.01) and expanded animals (24.42 ± 3.67 vs 17.85 ± 2.16 µL/min per 100 g; P < 0.01). Diuresis induced by l‐arginine was reduced by DA blockade in both non‐expanded (17.15 ± 2.11 vs 6.82 ± 0.61 µL/min per 100 g; P < 0.01) and expanded animals (44.26 ± 8.45 vs 25.43 ± 5.12 µL/min per 100 g; P < 0.01).5. Sodium excretion decreased with l‐NAME treatment in non‐expanded (0.22 ± 0.03 vs 0.06 ± 0.01 µEq/min per 100 g; P < 0.01) and expanded animals (3.72 ± 0.70 vs 1.89 ± 0.23 µEq/min per 100 g; P < 0.01). Natriuresis induced by l‐arginine was diminished by haloperidol both in non‐expanded (0.94 ± 0.13 vs 0.43 ± 0.04 µEq/min per 100 g; P < 0.01) and expanded rats (12.77 ± 0.05 vs 3.53 ± 0.75 µEq/min per 100 g; P < 0.01). Changes in kaliuresis changes seen following treatment with l‐arginine, l‐NAME and l‐arginine + haloperidol followed a pattern similar to that observed for sodium excretion in both groups of rats.6. l‐Arginine enhanced RPF in non‐expanded animals (11.96 ± 0.81 vs 14.52 ± 1.05 mL/min per 100 g; P < 0.01). Glomerular filtration rate was increased by extracellular volume expansion (3.08 ± 0.28 vs 5.42 ± 0.46 mL/min per 100 g; P < 0.01).7. The increase in NOx induced by acute volume expansion (0.18 ± 0.03 vs 0.52 ± 0.08 nmol/min per 100 g; P < 0.01) was diminished following the administration of haloperidol (0.52 ± 0.08 vs 0.26 ± 0.06 nmol/min per 100 g; P < 0.01).8. Although DA does not participate in the actions of nitric oxide on vascular tone, both systems would play an important role in renal function adaptation during extracellular fluid volume expansion.
The guinea‐pig oesophagus is a versatile in vitro preparation for pharmacological studies
Authors: Kerr Karen P 
Published: March 2003

Summary1. The isolated oesophagus of the guinea‐pig is a useful preparation that can be used as an alternative to the phrenic nerve–diaphragm preparations that have been used traditionally in the determination of the actions of drugs and toxins at the neuromuscular junction. The guinea‐pig isolated oesophagus can also provide information about effects at ganglionic nicotinic receptors, which are not present in the diaphragm preparations.2. The muscularis externa of the body of the oesophagus consists exclusively of striated muscle fibres. The myenteric plexus is found between the outer longitudinally arranged layer and the inner circular layer. The muscularis mucosae contains smooth muscle fibres arranged longitudinally.3. The vagal nerves are comprised of special vagal efferents that innervate the striated muscle fibres directly and ‘parasympathetic’ vagal fibres that synapse in the myenteric ganglia and, subsequently, affect the smooth muscle of the muscularis mucosae. Thus, both striated and smooth muscle responses to vagal nerve stimulation can be studied. In addition, afferent neurons run in the vagus.4. Studies using various isolated oesophageal preparations have been reviewed. These consist of the whole oesophagus (including striated muscle, myenteric plexus and smooth muscle), the isolated mucosal layer (striated muscle and the myenteric plexus both absent) and the whole oesophagus with the vagus nerve attached. Comparative studies of the effects of drugs acting directly on the muscularis mucosae and/or indirectly via the intramural plexuses can be performed using the whole oesophagus and the isolated mucosal layer.5. The use of the guinea‐pig isolated vagus nerve–oesophagus preparation allows potency determinations for both neuromuscular and ganglion blockade of various non‐depolarizing muscle relaxants to be performed simultaneously under identical conditions. Furthermore, the phenomenon of fade, a waning of tetanic tension during the stimulation period, can be studied.6. A potential application of this preparation is the simultaneous screening of the constituents of snake venoms for activity at the neuromuscular junction and/or the ganglion. It is also suggested that new calcium channel blockers could be screened in this preparation because different voltage‐sensitive calcium channels are involved in neurotransmitter release from nerve terminals at the neuromuscular junction and autonomic cholinergic neuroeffector sites.
Changes in mRNA expression induced by sustained noradrenaline stimulation are different for α1‐adrenoceptor subtypes in HEK293 cells
Authors: Lei Beilei , Zhang Youyi , Han Chide 
Published: March 2003

Summary1. The aim of the present study was to investigate noradrenaline (NA)‐induced regulation of α1‐adrenoceptor (AR) mRNA expression in human embryonic kidney (HEK) 293 cells stably expressing cloned α1‐AR subtypes with similar receptor densities. Stable transfection was performed by calcium phosphate precipitation. Receptor expression was detected by radioligand binding assay. The mRNA expression was measured by RNase protection assay.2. α1‐Adrenoceptor subtype mRNA respond in distinct ways following prolonged exposure to NA. The mRNA level of the α1A‐AR subtype was unchanged, the mRNA level of the α1B‐AR subtype was increased and the mRNA level of the α1D‐AR subtype declined time dependently. The protein kinase C (PKC) inhibitor calphostin C or RO 31‐8220 abolished the NA‐induced downregulation of α1D‐AR mRNA. Phorbol myristate acetate (PMA), a PKC activator, similarly repressed the effects of NA on α1D‐AR. However, calphostin C, RO 31‐8220 or PMA had no effect on the induction of α1B‐AR mRNA by NA. The Ca2+‐ATPase inhibitor thapsigargin or the calcium chelator 1,2‐bis‐(o‐aminophenoxy) ethane‐N,N,N′,N′‐tetraacetic acid tetra (acetoxymethyl) ester (BAPTA/AM) had no effect on the repression of α1D‐AR mRNA, but did inhibit the induction of α1B‐AR mRNA by NA. Noradrenaline significantly decelerated the degradation of α1B‐AR mRNA, but had no effect on the degradation of α1D‐AR mRNA.3. Thus, the mRNA expression of three α1‐AR subtypes in HEK293 cells is differentially regulated through distinct signal transduction pathways under sustained NA stimulation. The upregulation of α1B‐AR mRNA is via the Ca2+ pathway, whereas the downregulation of α1D‐AR mRNA is via the PKC pathway.
Effect of Undaria pinnatifida (Wakame) on the development of cerebrovascular diseases in stroke‐prone spontaneously hypertensive rats
Authors: Ikeda Katsumi , Kitamura Akiko , Machida Hiroko , Watanabe Miyuki , Negishi Hiroko , Hiraoka Junko , Nakano Takahisa 
Published: March 2003

Summary1. We showed that a nutritional factor was able to attenuate the development of hypertension and its related diseases in stroke‐prone spontaneously hypertensive rats (SHRSP). In the present study, the effect of Wakame, an edible brown seaweed, on the development of stroke was examined in SHRSP.2. We studied the treatment with 5% (w/w in a diet) Wakame powder in salt‐loaded (0.5% NaCl in drinking water) SHRSP. Salt‐loaded animals treated with 5% cellulose or kaolin were used as controls. Wakame significantly delayed the development of stroke signs (P < 0.05) and significantly improved the survival rate of salt‐loaded SHRSP (P < 0.05). There was no significant difference in the elevation of blood pressure among the three groups during the observation period.3. We isolated fucoxanthin, a carotinoid, from Wakame powder and studied its preventive effect on ischaemic cultured neuronal cell death. Fucoxanthin significantly attenuated neuronal cell injury in hypoxia and re‐oxygenation (P < 0.05).4. Based on these results, we conclude that Wakame has a beneficial effect on cerebrovascular diseases in SHRSP, independent of hypertension. It is possible that fucoxanthin in Wakame may have a preventive effect against ischaemic neuronal cell death seen in SHRSP with stroke.
Effect of 6‐hydroxydopamine on gluconeogenesis in the rat renal cortex
Authors: Cojocel C , Thomson MS 
Published: March 2003

Summary1. In the present study, the effects of 6‐hydroxydopamine (6‐OHDA) on renal gluconeogenesis were investigated in vitro using rat renal cortical slices. Cisplatin, a known nephrotoxin, was used as a positive control. The working hypothesis for the present study was that 6‐OHDA, as a reactive oxygen species‐producing agent, could inhibit renal gluconeogenesis.2. 6‐Hydroxydopamine is used for chemical sympathectomy because it selectively destroys adrenergic nerve endings. Long‐term use of levodopa causes a variety of side‐effects in parkinsonian patients. 6‐Hydroxydopamine has been reported to be present in the urine of parkinsonian patients on levodopa medication. The renal toxicity of endogenously formed 6‐OHDA is a matter of concern in these patients.3. In one series of experiments, renal cortical slices were incubated for 60 min in medium containing 0.5, 1.0, 2.08, 5.15, 10.30 or 20.60 mg/mL 6‐OHDA at 37°C under a 100% O2 atmosphere. In another series of experiments, renal cortical slices were incubated in medium containing 10.30 mg/mL 6‐OHDA for 15, 30, 45, 60, 90 or 120 min or in 6‐OHDA‐free medium.4. In a second series of experiments, renal cortical slices were incubated for 60 min in medium containing 0.25, 0.50, 0.75, 1.0, 1.25 or 1.50 mg/mL cisplatin at 37°C under a 100% O2 atmosphere. In another set of experiments, renal cortical slices were incubated in medium containing 1 mg/mL cisplatin for 15, 30, 45, 60, 90 or 120 min or in a cisplatin‐free medium.5. The results of the studies in which slices were incubated in 6‐OHDA‐containing media indicate that 6‐OHDA induced a time‐ and concentration‐dependent decrease in renal gluconeogenesis. Therefore, 6‐OHDA causes functional injury of renal proximal tubule cells responsible for renal gluconeogenesis, thus leading to nephrotoxicity.
Upregulation of muscarinic receptors by long‐term nitric oxide inhibition in the rat ileum
Authors: Bricola Alice AO , Teixeira Simone A , De Luca Iara MS , Muscará Marcelo N , Abdala Fernando MF , Porto Catarina S , Zanesco Angelina , Antunes Edson , De Nucci Gilberto 
Published: March 2003

Summary1. The aim of the present study was to examine the effects of long‐term nitric oxide (NO) blockade on contractions of the rat ileum induced by muscarinic agonists.2. Male Wistar rats received the NO synthesis inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME; 20 mg/rat per day) in drinking water for 7, 15, 30 and 60 days. Concentration–responses curves to methacholine and carbachol were obtained and pEC50 values were calculated. Saturation binding assays were performed in membranes prepared from rat ileum after 60 days of l‐NAME treatment and the dissociation constant (KD) and maximal number of binding sites (Bmax) were determined by Scatchard analysis.3. The NO synthase activity of the ileum was markedly reduced in all l‐NAME‐treated groups. At 60 days after l‐NAME treatment, a significant increase in the potency of methacholine (fourfold) and carbachol (threefold) was observed. In binding studies, we found a significant increase in Bmax for [3H]‐quinuclidinyl benzilate of approximately 57% in the l‐NAME treated group without any significant change in KD values. The contractile response to methacholine was not modified by the soluble guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo‐[4,3‐a]quinoxalin‐1‐one (3 µmol/L). No morphological alterations in the rat ileum were observed in l‐NAME‐treated rats.4. Our findings suggest that treatment with l‐NAME for 60 days induces a marked increase in the potency of methacholine and carbachol, as well as an increase in receptor number in the rat ileum.
Larval antigen molecules recognized by adult immune cells of inbred Xenopus laevis: Partial characterization and implication in metamorphosis
Authors: Izutsu Yumi , Tochinai Shin , Maéno Mitsugu , Iwabuchi Kazuya , Onoé Kazunori 
Published: March 2003

It has been shown that larval skin (LS) grafts are rejected by an inbred strain of adult Xenopus, which suggests a mechanism of metamorphosis by which larval cells are recognized and attacked by the newly differentiating immune system, including T lymphocytes. In an attempt to define the larval antigenic molecules that are targeted by the adult immune system, anti‐LS antibodies (IgY) were produced by immunizing adult frogs with syngeneic LS grafts. The antigen molecules that reacted specifically with this anti‐LS antiserum were localized only in the larval epidermal cells. Of 53 and 59–60 kDa acidic proteins that were reactive with anti‐LS antibodies, a protein of 59 kDa and with an isoelectric point of 4.5 was selected for determination of a 19 amino acid sequence (larval peptide). The rat antiserum raised against this peptide was specifically reactive with the 59 kDa molecules of LS lysates. Immunofluorescence studies using these antisera revealed that the larval‐specific molecules were localized in both the tail and trunk epidermis of premetamorphic larvae, but were reduced in the trunk regions during metamorphosis, and at the climax stage of metamorphosis were detected only in the regressing tail epidermis. Culture of splenocytes from LS‐immunized adult frogs in the presence of larval peptide induced augmented proliferative responses. Cultures of larval tail pieces in T cell‐enriched splenocytes from normal frogs or in natural killer (NK)‐cell‐enriched splenocytes from early thymectomized frogs both resulted in significant destruction of tail pieces. Tissue destruction in the latter was enhanced when anti‐LS antiserum was added to the culture. These results indicate that degeneration of tail tissues during metamorphosis is induced by a mechanism such that the larval‐specific antigen molecules expressed in the tail epidermis are recognized as foreign by the newly developing adult immune system, and destroyed by cytotoxic T lymphocytes and/or NK cells.
New species of the Australian endemic wasp genus Notosigalphus van Achterberg and Austin (Hymenoptera: Braconidae) from Flinders Island, Tasmania
Authors: Iqbal Muhammad , Austin Andrew D 
Published: March 2003

AbstractA new species of the braconid genus Notosigalphus is described from Flinders
Island, Tasmania (N. sophae Iqbal and Austin sp. n). This is the third species
recorded of this rare Australian endemic genus, and the first member of the subfamily
Sigalphinae to be recorded elsewhere than on the mainland. A key to separate species
of Notosigalphus is presented, as is a discussion of relationships, distribution and biology of the subfamily in Australia.
A comparison of the imposed work of breathing in continuous positive pressure ventilation mode between three different ventilators
Authors: Porges Kate J , Kelly Sean L 
Published: March 2003

Abstract Objective: To compare the work of breathing imposed and patient tolerance to the delivery of face mask continuous positive pressure ventilation by three different ventilators. Methods: Eleven healthy volunteers were subject to continuous positive pressure ventilation at levels of 0, 5, 10 and 15 cmH2O on each of the three machines tested (Oxylog 2000, Drägerwerk AG, Lubeck, Germany; Puritan‐Bennett 7200, Puritan Bennett Corp., Carlsbad, CA, USA; Auspap, Ulco Engineering Pty Ltd, Marrickville, NSW, Australia). The work of breathing imposed by the machines was measured using the Bicore‐CP100 pulmonary function monitor (Allied Healthcare Products, CA, USA). After breathing on the three machines, volunteers rated the comfort of breathing on a visual analogue scale. Results: The work of breathing imposed by the Oxylog 2000 was higher in all volunteers receiving face mask continuous positive pressure ventilation when compared with both the Puritan‐Bennett 7200 and the Auspap. The Oxylog 2000 was considered to be the least comfortable. Conclusions: The provision of continuous positive pressure ventilation in the emergency department is becoming increasingly common, but the use of a transport ventilator, such as the Oxylog 2000, to provide this ventilatory support cannot currently be recommended.
Trauma scoring systems explained
Authors: Fani‐Salek Mohammed Hassan , Totten Vicken Y , Terezakis Stephanie A 
Published: March 2003

Objective: To list, describe and classify the extant trauma scoring systems found in the English language literature from the vantage of utility to emergency medicine. Each system is illustrated by a table and a hypothetical case study. Data Sources: Medline citations provided the data. The systems are classified as physiological, anatomical and combined trauma scoring systems. Results: We reviewed the Glasgow Coma Scale, the Paediatric Glasgow Coma Scale, the Trauma Score and Revised Trauma Score, the Circulation, Respiration, Abdominal/Thoracic, Motor and Speech Scale, the Acute Physiology and Chronic Health Evaluation System, Abbreviated Injury Scale, the Injury Severity Score, the Anatomical Profile, A Severity Characterization of Trauma, Revised Trauma Score and Injury Severity Score and its revisions, the Paediatric Trauma Score and the Drug‐Rock Injury Severity Score. Conclusions: This compendium should help emergency physicians become familiar with trauma scoring systems which evaluate the extent and severity of injuries, facilitate inter‐institutional comparisons and facilitate trauma research.
Gamma hydroxybutyrate intoxication: The Gold Coast experience
Authors: Harraway Tim , Stephenson Lauren 
Published: March 2003

AbstractThis paper describes two group presentations of intoxicated patients to the Emergency Department of Gold Coast Hospital in October 1996 and July 1997 respectively. A total of 14 patients received treatment. The clinical features, investigation findings and clinical course of each patient are outlined. A discussion is undertaken of the literature surrounding the emergence of gamma hydroxybutyrate (GHB) as a drug of abuse, and of the major issues involved in the emergency department management of such patients.
History, pathophysiology, clinical presentation and role of hyperbaric oxygen in acute carbon monoxide poisoning
Authors: Doherty Steven 
Published: March 2003

AbstractAcute carbon monoxide poisoning remains a major cause of morbidity and mortality, both due to accidental and deliberate poisoning. This article reviews the current concepts of the pathophysiology of carbon monoxide poisoning and the historical evolution of these concepts. The clinical presentation is discussed as it relates to the various organ systems. Finally, the history and role of hyperbaric oxygen is also discussed. Hyperbaric oxygen remains an established, although inconclusively proven, treatment option.