bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF AZUMOLENE ON HYPERCONTRACTILITY AND SARCOPLASMIC RETICULUM CA2+‐DEPENDENT ATPASE ACTIVITY OF MALIGNANT HYPERPYREXIASUSCEPTIBLE PORCINE SKELETAL MUSCLE
Authors: Foster P. S. , Hopkinson K. C. , Payne N. , Denborough M. A. 
Published: June 2007

SUMMARY1. Azumolene sodium is a new water‐soluble derivative of dantrolene sodium that also acts as a skeletal‐muscle relaxant.2. Azumolene (6 μmol/L) inhibited the hypercontractility induced separately by 3% halothane, 2 mmol/L caffeine and 80 mmol/L potassium chloride in isolated malignant hyperpyrexia (MH)‐susceptible muscle. Azumolene was equipotent with dantrolene in inhibiting the abnormal responses.3. Like dantrolene, azumolene (6 μmol/L) not only prevented but reversed the abnormal contractures induced by halothane and caffeine. Contracture responses to caffeine were also modified by azumolene in control preparations.4. In the presence of maximal effective concentrations of dantrolene, azumolene failed to further relax caffeine‐induced contractures, and the converse was also true. This was observed in both MH‐susceptible and control preparations.5. Sarcoplasmic reticulum Ca2+‐dependent ATPase activity from MH‐susceptible and control muscle was not affected by azumolene.6. Like dantrolene, azumolene may inhibit Ca2+ release directly from the sarcoplasmic reticulum and be of therapeutic value for the treatment of MH.
EFFECTS OF TORASEMIDE ON RENAL HAEMODYNAMICS AND FUNCTION IN ANAESTHETIZED DOGS
Authors: Uchida T. , Hayashi K. , Suzuki Y. , Matsumura Y. 
Published: June 2007

SUMMARY1. We examined the effects of torasemide (0.3 and 1 mg/kg i.v.) on renal haemodynamics and function employing renal clearance and stop‐flow techniques in anaesthetized dogs and compared these with furosemide (1 and 3 mg/kg i.v.).2. Torasemide and furosemide did not influence renal haemodynamics, in the renal clearance study, but caused a dose‐related and significant increase in urine flow and urinary excretion of sodium and potassium. Torasemide and furosemide increased fractional excretion of sodium in the distal tubules with a relatively small increase in the fractional excretion of lithium (index of sodium excretion at the proximal tubules, FELi). The diuretic profile of torasemide was of long duration, compared with that of furosemide.3. Torasemide and furosemide inhibited sodium reabsorption at the distal portion of the tubules in the stop‐flow study.4. It is suggested from these results, that the main diuretic site of action of torasemide is the ascending limb of the loop of Henlé.
EFFECT OF DELAPRIL ON THE VASCULAR ANGIOTENSIN II RELEASE IN ISOLATED HIND LEGS OF THE SPONTANEOUSLY HYPERTENSIVE RAT: EVIDENCE FOR POTENTIAL RELEVANCE OF VASCULAR ANGIOTENSIN II TO THE MAINTENANCE OF HYPERTENSION
Authors: Mizuno Kenji , Tani Makio , Niimura Susumu , Fukuchi Soitsu 
Published: June 2007

SUMMARY1. In view of a recent interesting hypothesis that the vascular renin‐angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar‐Kyoto strain (WKY).2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen‐free Krebs‐Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep‐Pak C18 cartridges connected to the perfusion system.3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9±17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5±9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose‐dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR.4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.
CALCIUM METABOLISM IN ELDERLY HYPERTENSIVE PATIENTS: POSSIBLE PARTICIPATION OF EXAGGERATED SODIUM, CALCIUM AND PHOSPHATE EXCRETION
Authors: Imaoka M. , Morimoto S. , Kitano S. , Fukuo F. , Ogihara T. 
Published: June 2007

SUMMARY1. Renal handling of electrolytes, including calcium (Ca), in response to physiological saline infusion (20 mL/kg, i.v., for 2 h) as well as basal circulating levels of Ca‐regulating hormones were compared in 27 hypertensive elderly females (mean age 80±9 years), in 44 normotensive elderly females (79±9 years) and in 19 young normotensive females (23±4 years).2. The hypertensive elderly females showed excessive increase in urine volume and urinary excretions of sodium (Na), Ca and inorganic phosphate (P) in response to saline infusion, associated with slight but significant decrease in circulating levels of Na and ionized Ca compared with those in the other groups. These hypertensive elderly patients also showed characteristic features both in circulating blood pressure and Ca regulating factors; they showed significantly low levels of plasma renin activity and aldosterone concentration, significantly high plasma levels of atrial natriuretic peptide and noradrenalin, compared with those in young controls and normotensive elderly females.3. Moreover they showed significant increase in basal serum levels of parathyroid hormone and 1,25‐dihydroxyvitamin D, and significant decrease in basal serum levels of calcitonin, 25‐hydroxy‐vitamin D and 24,25‐dihydroxyvitamin D, compared with those in the other groups.4. These results suggest that the exaggerated natriuresis associated with excessive loss of Ca and P in urine may participate in the abnormality of Ca metabolism in low‐renin hypertensive elderly patients.
CORONARY VASCULAR RESPONSE TO ENDOTHELIN IN ISOLATED PERFUSED HEARTS OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Takeshita Hiroshi , Nishikibe Masaru , Yano Mitsuo , Ikemoto Fumihiko 
Published: June 2007

SUMMARY1. The coronary vasoconstrictive response to endothelin (ET‐1) was evaluated using the isolated perfused hearts of 15 week old spontaneously hypertensive rats (SHR) and age‐matched Wistar‐Kyoto rats (WKY). Endothelin produced marked increases in perfusion pressure (PP) in both SHR and WKY. The effects of ET‐1 were more potent than those of acetylcholine, vasopressin and angiotensin II. The vascular response to ET‐1, expressed as the increase in PP, was greater in SHR than in WKY.2. Nicardipine (10−8 mol/L) shifted the concentration–PP response curve for ET‐1 to the right. The extent of the rightward shift was greater in SHR than in WKY. Additionally in SHR, Bay K‐8644 elicited a dose‐dependent increase in PP, the effect being more potent than that in WKY.3. The increased response of the coronary vasculature to ET‐1 was observed after 15 weeks of age but not at 6 weeks, indicating that enhancement of the response develops with ageing in SHR.4. Enhancement of the vascular response to ET‐1 in SHR was prevented by chronic (10 weeks) treatment with enalapril (10 mg/kg per day), but not by hydralazine (30 mg/kg per day).5. These results indicate that the coronary vascular response to ET‐1 increases with age in SHR. The mechanism of the enhanced response may involve the activation of dihydropyridine‐sensitive Ca2+ channels, however, this type of mechanism may also be modulated at least in part by the renin–angiotensin system.
GOVERNMENT INITIATIVES IN THE DEVELOPMENT OF A PHARMACEUTICAL INDUSTRY IN AUSTRALIA
Authors: Hirst Christine A. 
Published: June 2007

SUMMARYGovernment policy recognizes that the purchasing power of the government, through the Pharmaceutical Benefits Scheme, has suppressed prices and returns to the pharmaceutical industry in Australia, and that research, development and export activities have been low. The factor (f) scheme is designed to provide some pricing relief to those companies willing and able to undertake particular industry development activities. This scheme, together with the other changes implemented by the government, will result in the restructuring and development of the pharmaceutical industry in Australia.
SYMBIOTIC RELATIONSHIP BETWEEN A RESEARCH INSTITUTE AND A PHARMACEUTICAL COMPANY: THE BAKER INSTITUTE/GLAXO AUSTRALIA STORY
Authors: Angus James A. 
Published: June 2007

SUMMARY1. The Baker Medical Research Institute is a non‐profit, charitable institution to advance knowledge and solve problems in the area of cardiovascular medicine. This allows scientists to collaborate within a critical mass and be flexible in their approach to research.2. The Institute has interactions with the pharmaceutical industry at three levels: (i) contract research on a specific molecule; (ii) clinical trials; and (iii) collaborative basic research agreements.3. The Glaxo Australia‐Baker Medical Research Institute Agreement is for curiosity driven research in specified areas of vascular pharmacology of interest to Glaxo Group Research.4. The relationship between universities, research institutes and the pharmaceutical industry is discussed in terms of the starting point for drug development.5. The enormous cost (US$100 million), lead time (10 years) and uncertainty of a successful profitable drug are compelling reasons why an independent pharmaceutical company is unlikely to succeed in Australia today.
ENDOTHELIN‐3‐INDUCED MICROVASCULAR INCOMPETENCE AND MITOCHONDRIAL DAMAGE IN RAT MYOCARDIUM
Authors: Maxwell Linda , Pratt Katherine , Gavin John 
Published: June 2007

SUMMARY1. To determine the possible role of an endothelin in the development of postischaemic microvascular incompetence, isolated buffer‐perfused rat hearts were perfused with endothelin‐3 (ET‐3) in phosphate buffer.2. ET‐3 produced a reduction in coronary flow rate, heart rate and arrhythmia. There was a marked reduction in the density of competent capillaries, and the myocytes showed vacuolation and mitochondrial damage in regions where microvascular incompetence was most severe.3. These results indicate that ET‐3 can substantially reduce microvascular perfusion in the heart and can also cause damage to the myocyte.
MECHANISM AND PREVENTION OF CHRONIC COLONIC INFLAMMATION WITH TRINITROBENZENE SULFONIC ACID IN RATS
Authors: Hoshino Hiroshi , Sugiyama Satoru , Ohara Atsushi , Goto Hidemi , Tsukamoto Yoshihisa , Ozawa Takayuki 
Published: June 2007

SUMMARY1. The role of prostanoids in experimental colitis with trinitrobenzene sulfonic acid (TNBS) in rats was investigated. The effects of cyclosporine A (CsA) on the development of experimental colitis were also examined.2. Five kinds of prostanoids were detected in rat colonic tissue by high performance liquid chromatography. These were 6‐keto‐prostaglandin (PG) F1α, PGF2α, PGE2, PGD2 and thromboxane B2.3. In TNBS‐induced experimental colitis, all prostanoid concentrations except PGD2 increased, although the time courses differed from each other.4. Medication with indomethacin markedly reduced prostanoid concentrations in TNBS‐induced colitis. However, indomethacin did not show any effect on damage scores.5. Cyclosporine A reduced damage scores 14 days after TNBS treatment, and the protective effects were observed, whereas CsA did not affect colonic tissue prostanoid concentrations.6. Prostanoids might be produced secondarily in the genesis of TNBS‐induced colitis, although they may attenuate the inflammatory response. It was also suggested that CsA was likely to have therapeutic effects on experimental colitis by inhibiting the immune reaction with TNBS, which induced the chronic inflammation.
THE ROLE OF THE RENAL NERVES IN RENIN SYNTHESIS
Authors: Zhang Yanling , Morgan Trefor , Read Gullvig 
Published: June 2007

SUMMARY1. Renin synthesis and secretion were studied in Balb/ c mice with a denervated left kidney.2. Denervation inhibited renin secretion.3. Denervation reduced the renal renin content.4. Denervation reduced renal renin mRNA.5. Renal denervation inhibits renin secretion by blocking the synthetic system prior to mRNA formation.
ACTIVATION OF NORADRENERGIC AND NITRERGIC MECHANISMS IN THE RAT ANOCOCCYGEUS MUSCLE BY NICOTINE
Authors: Rand M. J. , Li C. G. 
Published: June 2007

b1. Nicotine (10 μmol/L) produced rapidly developing but transient contractions of anococcygeus muscle isolated from rats. The magnitude of the response varied considerably between preparations. Tachyphylaxis occurred, such that no response was elicited by the same or a larger concentration in the continued presence of 10 μmol/L nicotine.2. Contractions produced by nicotine were not affected by atropine, but were abolished by Hexamethonium and the α‐adrenoceptor antagonists prazosin and phentolamine. Contractions were absent in the anococcygeus muscles of rats pretreated with reserpine.3. The (α‐adrenoceptor agonist UK 14304, or guanethidine, raised the tone of the anococcygeus muscle, and converted responses to field stimulation and nicotine to relaxations. Nicotine‐induced relaxations were more pronounced in the presence of UK14304 than guanethidine.4. Relaxations produced by nicotine (1–18 μmol/L) were transient, and tachyphylaxis occurred. When precautions were taken to avoid tachyphylaxis, concentration‐response curves could be constructed. The relaxations elicited by nicotine were abolished or greatly reduced by hexamethonium, tetrodotoxin or ω‐conotoxin GVIA.5. The nitric oxide synthase inhibitor l‐NG‐nitroarginine methyl ester (90 μmol/L) enhanced contractile responses to field stimulation and nicotine, and markedly reduced relaxations elicited by field stimulation and nicotine in the presence of UK14304. These relaxations were restored by l‐arginine (270 μmol/L).6. The results suggest that nicotine acts on nicotinic receptors of noradrenergic and nitrergic nerve terminals in the rat anococcygeus muscle, resulting in the release of noradrenaline and nitric oxide respectively.
PROPOFOL ANAESTHESIA IN MALIGNANT HYPERPYREXIA SUSCEPTIBLE SWINE
Authors: Foster P. S. , Hopkinson K. C. , Denborough M. A. 
Published: June 2007

SUMMARY1. Malignant hyperpyrexia (MH) is an inherited muscle abnormality that presents clinically as a syndrome of life‐threatening complications during general anaesthesia.2. Propofol is a new sedative hypnotic used for the induction and maintenance of anaesthesia.3. Propofol did not induce MH in five susceptible pigs. Propofol did not induce contracture in isolated MH susceptible muscle but did modify halothane, caffeine and KCl contractures.
RENAL HANDLING OF ENDOGENOUS LITHIUM IN EXPERIMENTAL DIABETES MELLITUS IN THE RAT
Authors: Pollock Carol A. , Field Michael J. 
Published: June 2007

SUMMARY1. The usefulness of determining the renal handling of endogenous lithium as a marker of proximal tubular sodium reabsorption was assessed in streptozotocin induced diabetes mellitus in the Sprague‐Dawley rat.2. The clearance and fractional excretion of lithium were determined before and following the development of diabetes mellitus, and compared with measurements of proximal tubular reabsorption made directly using micropuncture techniques. Endogenous lithium was measured in order to avoid the toxic tubular effects of exogenously administered lithium salts.3. Although a trend existed for a reduction in the fractional excretion of lithium in diabetic animals (1.8±0.3 vs 2.4±0.5%; P > 0.20), this did not reach statistical significance and did not accurately reflect the change in directly measured tubular Na reabsorption.4. The decrease in proximal tubular Na reabsorption demonstrated in diabetic animals treated with phlorizin was not significantly reflected in the fractional lithium excretion, although again a corresponding trend was evident (1.9 ± 0.8 vs 0.6 ± 0.2%; P > 0.10.5. In summary, the significant alterations in tubular Na handling in diabetes mellitus, previously demonstrated directly using micropuncture techniques, are not reflected in the renal handling of endogenous lithium. This indirect method is inadequate to assess proximal tubular Na transport in experimental diabetes mellitus.
FAILURE OF THE NITROUS OXIDE TISSUE EQUILIBRATION METHOD FOR THE DETERMINATION OF BRAIN AND MYOCARDIAL BLOOD FLOW UNDER CONTROLLED CONDITIONS
Authors: Reid Michael A. , Runciman William B. , McLean Colin F. , Mather Laurence E. 
Published: June 2007

SUMMARY1. Two adult merino ewes were prepared with intravascular cannule for sampling aortic root blood, sagittal sinus blood and coronary sinus blood.2. One week after preparation the animals were anaesthetized then ventilated with a gas mixture containing 10% nitrous oxide (N2O) for 60 min. Serial measurements of brain and myocardial blood flow were made using the N2O tissue equilibration method of Kety and Schmidt.3. N2O failed to achieve matching arteriovenous blood concentration equality and saturation of the relevant tissues. Valid use of the Kety‐Schmidt method, therefore, could not be confirmed.4. Because of the failure of the arteriovenous equilibration, serially determined brain and myocardial blood flows were found to decrease with time.5. The use of this method in circumstances where tissue saturation with the indicator gas cannot be ascertained is arbitrary.
POTASSIUM CHANNEL ACTIVATION IMPROVES BLOOD FLOW PATTERN OF CONSCIOUS RATS IN CUTANEOUS MICROCIRCULATION
Authors: Hertel RolfF. 
Published: June 2007

SUMMARY1. A dose‐dependent mean arterial blood pressure reduction (tailcuff method) to an intravenously administered potassium channel activator (22 or 24 μg/ kg bw) was found in conscious rats.2. Intravital microscopic analysis of skin microcirculation in conscious rats was performed with respect to erythrocyte flow velocity and diameters of capillaries. There was a dose‐dependent increase of erythrocyte flow velocity; diameters of capillaries were dilated following a dosage of 6 and 12 Mg/kg bw, but constricted following a dosage of 24 μg/kg bw.3. Frequency distributions of velocity ranges in capillaries under observation (real time video recordings) proved that the increase of microvascular perfusion is manifested by a shift of maximal values to increasing velocity ranges.4. It is concluded that potassium channel activation plays an important role in the local regulation of perfusion on the peripheral circulation.
INACCURACY OF ELECTRONIC SPHYGMOMANOMETERS
Authors: Mann Stewart 
Published: June 2007

SUMMARY1. Eight electronic sphygmomanometers were purchased locally and evaluated for clinical accuracy during blood pressure recording on volunteer patients.2. Direct comparisons of systolic and diastolic pressure were made in seven devices using a Y‐tube connection to a mercury sphygmomanometer, simultaneous measurements being made by a trained observer on 16–18 subjects.3. Indirect comparisons were made for all eight devices by comparing the average values obtained from all measurements made on each subject by the device with the average value from mercury sphygmomanometric readings made over the same time period.4. Results were analysed by measuring the mean and standard deviation of the differences between device readings and mercury readings. Published criteria were used to grade the devices.5. The most accurate machine was the Omron HEM‐719K, which used the cuff as a sound sensor and had an internal microphone. The least accurate was the Omron HEM‐812F, which used a finger‐cuff method. The other devices (all oscillometric) ranged from fair to poor in performance accuracy.
EVIDENCE FOR PRESYNAPTIC β‐ADRENOCEPTOR STIMULATION 24 HOURS AFTER A 6 HOUR ADRENALINE INFUSION
Authors: Bachmann Anthony W. , Gordon Richard D. , Ballantine Donna M. 
Published: June 2007

SUMMARYM1. The effects of 6 h infusions of adrenaline (INF‐A) and dextrose (INF‐D) were compared in nine normal subjects.2. A significant increase in systolic blood pressure was observed during INF‐A compared with INF‐D and, 24 h after infusion, diastolic blood pressure was higher after INF‐A than after INF‐D.3. Heart rate (HR) was significantly higher during INF‐A than during INF‐D.4. As expected, plasma ADR increased significantly during INF‐A but, unexpectedly, remained elevated 60 min post infusion compared with INF‐D. Levels during activity the next morning were somewhat higher after INF‐A, but not significantly different from INF‐D.5. Plasma NA increased transiently during INF‐A and decreased during INF‐D. Urinary NA was significantly higher during INF‐A than during INF‐D, and insignificantly higher during overnight recumbency, consistent with enhanced noradrenergic transmission.
PROSTAGLANDINS AND SYSTOLIC BLOOD PRESSURE, BUT NOT ANGIOTENSIN II, INDEPENDENTLY AFFECT ATRIAL NATRIURETIC PEPTIDE LEVELS IN MAN
Authors: Klemm Shelley A. , Gordon Richard D. , Tunny Terry J. , Finn Wendy L. , Hornych Antonin 
Published: June 2007

SUMMARY1. Two hours after a single dose of indomethacin (INDO), plasma renin activity (PRA) and atrial natriuretic peptide (ANP) levels decreased, which is consistent with an effect of lowering prostaglandins (PG).2. After 48 h of INDO, PRA remained low but ANP had increased, which is consistent with the known effect of prostaglandin inhibitors to cause sodium retention, with a resulting volume expansion.3. Infusions of angiotensin II (All), which raises diastolic blood pressure (BP) 20 mmHg or more, consistently raised ANP levels. The ANP response to All infusion was reduced 48 h after INDO, which is consistent with an important role for PG in All‐stimulated ANP release.4. After PG were blocked with INDO, the stimulating effect of All on ANP at doses that increased diastolic BP less than 20 mmHg was insignificant, whereas before INDO it was significant.5. In dose‐response studies, INDO increased the systolic BP response but decreased the ANP response to All, which is consistent with a direct effect of PG on ANP that is independent of systolic BP.6. Prostaglandins and BP are important in the ANP response to All infusion in normal subjects, but All itself appears to have little direct effect on ANP.
HAEMODYNAMIC CHANGES IN THE MONCADA MODEL OF ATHEROSCLEROSIS
Authors: Yong A. C. , Townley G. , Boyd G. W. 
Published: June 2007

SUMMARY1. The application of a non‐constricting silastic cuff to the rabbit common carotid artery (CCA; n= 5) results in intimal thickening within 7 days.2. Ultrasonography showed kinking of the CCA at the cuff edges, as well as a 13% arterial narrowing (P < 0.02) within the cuffed segment, both at days 1 and 7. Correspondingly, the time averaged diastolic Doppler velocity (TAV) was 68.8 ± 12.8% higher (P < 0.025) in the cuffed region in comparison with that 1 cm proximal (P 1 cm) on day 1, and 54.2 ± 11.5% higher at day 7(P < 0.05). TAV values along control silastic strips were not significantly changed.3. There was a significant increase (P < 0.025) in intimal area within the cuffed region (0.098 ±0.024 mm3) compared with both the proximal control (0.014 ±0.001 mm3) and with that over control silastic strips (0.021 ±0.004 mm3, P < 0.01).4. Medial area within the cuff (0.433 ±0.017 mm3) was decreased (P < 0.005) compared with P 1 cm control (0.602 ±0.069 mm3).5. There was gross peri‐arteritic thickening involving the adventitia along the non‐constricted cuffed segment. Importantly, it was also noted alongside the control silastic strip.6. Kinking of the CCA and associated vasoconstriction cause changes in blood flow velocity along even a non‐constricting cuff, and this may explain the intimal thickening previously noted in this experimental model. The peri‐arteritic changes, on the other hand, appear to be a reaction to the silastic itself.