bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEVELOPMENT OF PERIPHERAL AUTONOMIC SYNAPSES: NEUROTRANSMITTER RECEPTORS, NEUROEFFECTOR ASSOCIATIONS AND NEURAL INFLUENCES
Authors: Hill Caryl E , Phillips Jacqueline K , Sandow Shaun L 
Published: March 2003

1. The functional innervation of autonomic target tissues occurs early during development, at a time when both the nerves and post‐synaptic target tissues are still differentiating.2. Physiological responses appear soon after the arrival of the first fibres when uptake and release mechanisms within the nerves are already functional. Initial responses differ from those in the mature animal, both in the form and, frequently, in the subtypes of receptors involved.3. Results of a number of studies suggest that the initial expression of neurotransmitter receptors during development is largely independent of neural influences. Changes recorded in neurotransmitter receptor expression during development appear to be similarly independent of neural influences.4. While signal transduction pathways coupling adrenergic neurotransmitter receptors to effector responses appear to develop independently of the nerves, the efficient coupling of muscarinic receptors often requires the action of the neurotransmitter, acetylcholine.5. During the period of synapse formation, the neural plexus continues to expand. While developing varicosities can release the neurotransmitter, the capacity for neurotransmitter retention appears to be restricted. Developmental changes in the neurotransmitters that produce functional responses, while well known in the sweat glands, may also be seen in more subtle forms in other target tissues.6. Ultrastructural studies suggest that close physical associations between the membranes of the release sites of the developing nerves and the target cells may form early during development when physiological responses are still immature. These close associations could enable more specific reciprocal interactions between nerves and target cells involving known and novel growth factors, neuropeptides and cytokines important in shaping the mature synaptic characteristics.
RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO‐CONTROLLED INFUSION
Authors: Garland HO , Hamilton K , Freeman S , Burns C , Cusack M , Balment RJ 
Published: March 2003

SUMMARY1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin.2. Two infusion regimens were used, a conventional constant‐infusion protocol and a novel computer‐driven, servo‐controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo‐ controlled replacement of spontaneous urinary fluid losses.3. The chronically catheterized conscious rat infused using a servo‐controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo‐controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo‐controlled diabetic animals.4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti‐diabetic drugs on the kidney.
EVIDENCE FOR DIRECT NEURAL REGULATION OF THE MAMMALIAN ANTERIOR PITUITARY
Authors: Ju GONG 
Published: March 2003

1. The mammalian anterior pituitary was not known to be directly regulated by nervous elements until recently. Although it is generally acknowledged that there are a small number of nerve fibres in the anterior pituitary, they are considered to be autonomic in nature and are not directly involved in the regulation of the activities of the gland cells.2. A growing body of evidence has been accumulated in the past decade, mainly from our laboratory, indicating that the anterior pituitary can be directly regulated by nerve fibres innervating it. The present article reviews the evidence for the hypothesis that there is neural–humoral dual regulation of the mammalian anterior pituitary.3. Human, macaque monkey, dog and rat anterior pituitaries have been used for immunocytochemical studies at light and electron microscopic levels. Studies of the changes in the nerve fibres in the anterior pituitary following adrenalectomy or ovariectomy have been conducted on rats. The effects of electrical stimulation of the nerve fibres in the anterior pituitary on adrenocorticotropic hormone (ACTH) secretion have also been studied.4. There are substantial amounts of nerve fibres in the anterior pituitary. They are in close proximity to the gland cells, including forming synapses. The number of nerve terminals are large. Adrenalectomy or ovariectomy induces an active response of the nerve fibres and electrical stimulation of the nerve fibres changes ACTH secretion.5. It has been concluded that the anterior pituitary can be directly regulated by the innervating nerve fibres.
GLYCINE RECEPTORS: WHAT GETS IN AND WHY?
Authors: Barry Peter H , Schofield Peter R , Moorhouse Andrew J 
Published: March 2003

SUMMARY1. The glycine receptor channel (GlyR), a member of the ligand‐gated ion channel superfamily, shares many similar permeation properties with the GABAA receptor channel.2. The GlyR is anion permeable, with PK/PCl < 0.05, has a 5–6 Å minimum pore diameter and a permeation selectivity sequence dominated by hydration energies.3. The channels, which display multiple subconductance states, can be multiply occupied.4. Two positive arginine rings at the ends of the pore region may contribute to the anion selectivity of the GlyR.5. Mutation of the extracellular charged arginine ring can impair channel function by decreasing the sensitivity of glycine activation, reducing channel conductance, shifting the normal multi‐subconductance states to lower values and by decoupling the link between ligand binding and channel gating.6. These and other site‐directed mutagenesis studies of recombinant GlyR, together with studies of native GlyR, are providing further insights into what controls gating and ion permeation and selectivity through this channel.
LOW‐DOSE NITRO‐L‐ARGININE ADMINISTRATION IN BABOON (PAPIO HAMADRYAS) PREGNANCY
Authors: Hennessy Annemarie , Gillin Adrian G , Duggin Geoffrey G , Horvath John S , Tiller David J 
Published: March 2003

SUMMARY1. The purpose of the present study was to examine the effect of nitric oxide (NO) inhibition on mean arterial pressure (MAP), endothelin (ET) and the renin–aldosterone system in pregnancy in the non‐human primate (baboon).2. Twenty pregnant baboons (Papio hamadryas) were examined prospectively after the administration of an oral NO inhibitor in different phases of pregnancy. Haemodynamic responses to NO inhibition, evidence of pre‐eclampsia and the renin–aldosterone system were examined under anaesthesia.3. Oral NL‐nitro‐
L‐arginine (NOLA; 5 or 10 mg/kg) was given for 1 week in early (6–8 weeks gestaton), middle (14–16 weeks gestation) and late (22–24 weeks gestation) pregnancy and while non‐pregnant. Mean arterial pressure, heart rate, haematology, biochemistry, ET, plasma renin activity (PRA) and aldosterone were measured. Foetal effects of NOLA were also examined by ultrasound and neonatal measurements.4. Nitric oxide inhibition led to an increase in MAP in non‐pregnant animals (9 mmHg) and in middle and later pregnancy (6 and 7 mmHg, respectively). Mean arterial pressure in early pregnancy was not affected. A reduction in PRA occurred after NO inhibition in all stages of pregnancy. Significant proteinuria occurred only in late pregnancy.5. Nitric oxide is involved in the maintenance of lower blood pressure in late pregnancy and inhibition leads to an increase in blood pressure and proteinuria in the baboon. Nitric oxide insufficiency may contribute to the clinical manifestations of human pre‐eclampsia. Nitric oxide was not involved in the normal vasodilation of early primate pregnancy.
CROSS‐OVER COMPARISON OF NIFEDIPINE OROS® AND FELODIPINE EXTENDED RELEASE WITH BLIND 24 H AMBULATORY BLOOD PRESSURE ASSESSMENTS
Authors: Taverner D , Marley J , Tonkin Al 
Published: March 2003

SUMMARY1. The aim of the present study was to compare the efficacy of nifedipine Oros® and felodipine extended release (ER) in controlling 24 h ambulatory blood pressures (ABP) in hypertensive patients.2. The study was a randomized cross‐over design with a 2 week open placebo run‐in phase and two observer‐blind treatment periods.3. Subjects were males and females, aged between 18 and 65 years, suffering from mild to moderate essential hypertension with a sitting mean diastolic blood pressure (DBP) within the range of 95–114 mmHg. Twenty‐three subjects were randomized to treatment; 15 patients completed the study.4. Treatment intervention was 2 weeks of placebo followed by either 30 mg nifedipine OROS once daily or 5 mg felodipine ER once daily for 6 weeks, which was titrated up to 60 mg nifedipine OROS daily or 10 mg felodipine ER daily after 2 weeks of treatment on the lower doses if the DBP was > 90 mmHg. The main outcome measure was 24 h ABP after 6 weeks of active treatment, evaluated by an independent observer blinded as to treatment allocation.5. Compared with placebo, mean (±SD) 24 h DBP was reduced by 6.2±6.8 and 5.2±5.1 mmHg after nifedipine and felodipine, respectively. The 24 h mean systolic blood pressure (SBP) fell by 11.8±10.9 and 10.1±8.2 mmHg for nifedipine and felodipine, respectively, compared with placebo. There were no significant differences between the two active treatments in the reduction of DBP or SBP during the 24 h period, daytime or night‐time.6. Similar antihypertensive effects are achieved with nifedipine Oros® and felodipine ER when doses are individually titrated, with no significant differences between the two treatments.
ROLE OF ACTION POTENTIAL SHORTENING IN THE PREVENTION OF ARRHYTHMIAS IN CANINE CARDIAC TISSUE
Authors: Mull Kawonia P , Debnam Qadriyyah , Kabir Syeda M , Bhattacharyya Mohit Lal 
Published: March 2003

SUMMARY1. The effects of the K+ channel opener diazoxide and the oxime‐containing Ca2+ and K+ channel blocker salicylaldoxime were tested in canine cardiac Purkinje tissue.2. Both drugs shortened action potential duration (APD). For salicylaldoxime (0.1–1.0 mmol/L), the reductions in APD were statistically significant at the 25% level of repolarization (APD25) for 0.1 mmol/L (P < 0.05, n = 14) and 0.5 and 1.0 mmol/L (P < 0.01, n = 6), at the 50% level of repolarization (APD50) for 0.1 mmol/L (P < 0.05, n = 14) and 0.5 and 1.0 mmol/L (P < 0.01, n = 6) and at the 90% level of repolarization (APD90) for 0.5 and 1.0 mmol/L (P < 0.01, n = 6). In contrast, diazoxide (0.05–0.1 mmol/L) significantly shortened APD at all levels of repolarizations, with the APD50 and APD90 reduced most significantly (P < 0.01, n = 6) for higher concentrations of the drug (0.07–0.1 mmol/L). Both drugs significantly reduced the force of contraction.3. Diazoxide (10 experiments) was more potent in suppressing strophanthidin‐induced arrhythmias than salicylaldoxime (three of seven experiments). Salicylaldoxime reduced APD even further in the presence of diazoxide.4. Although salicylaldoxime and diazoxide modulate different ion channels, it appears APD shortening may be a necessary, but insufficient, factor for the suppression of strophanthidin‐induced arrhythmias.
DOWN‐REGULATION BY BUCILLAMINE OF LAMINA PROPRIA LEUCOCYTES IN THE RAT COLITIS MODEL
Authors: Oshitani Nobuhide , Matsumoto Takayuki , Nakamura Shiro , Arakawa Tetsuo , Kitano Atsuo 
Published: March 2003

SUMMARY1. The efficacy of bucillamine has been reported in various inflammatory models.2. In the present study, the effects of 2 weeks administration of bucillamine on hapten‐induced experimental rat colitis were analysed. The gross morphological damage score was evaluated and the expression of CD4, CD8, CD11a, CD11b, CD25, CD54 and class II major histocompatibility complex (MHC) antigen was investigated by immunohistochemical methods.3. Mean bodyweight was significantly increased in colitic rats given 750 μg bucillamine compared with colitic rats given vehicle (distilled water). Gross morphological damage was significantly less in colitic rats given 250 or 750 μg bucillamine compared with rats given vehicle.4. Immunohistological studies revealed that CD4, CD11a, CD11b, CD54 and class II MHC antigen expression of infiltrating leucocytes was significantly lower in rat colonic mucosa treated with bucillamine.5. From these findings, it appears that bucillamine may act through the down‐regulation of the activation of lamina propria leucocytes in hapten‐induced rat colitis.
XENOGENEIC INFECTIONS AND PUBLIC HEALTH
Authors: Chapman Louisa E 
Published: March 2003

SUMMARY1. The scarcity of available human donor organs for use in allotransplantation has fuelled interest in xenotransplantation, the therapeutic use of living animal tissue in humans. The use of living animal tissue for therapeutic purposes in humans has raised concerns that xenotransplantation clinical trials may pose a presently unquantifiable but undeniable risk to public health.2. Xenotransplantation has the potential to introduce new infections to the human community by infecting human recipients with agents that were not previously endemic in human populations (xenogeneic infections).3. Manipulations intended to prevent xenograft rejection may also facilitate the transmission of agents that rarely or never infect humans under natural circumstances.4. The US Food and Drug Administration (the government agency responsible for monitoring drug safety) has chosen to allow limited numbers of xenotransplantation clinical trials to proceed under carefully monitored conditions outlined in the Public Health Service (PHS) Guideline on Infectious Disease Issues in Xenotransplantation.5. This PHS guideline particularly emphasizes the importance of pretransplantation screening and post‐transplantation surveillance for safety monitoring.6. Laboratory based surveillance for endogenous retroviruses and other identifiable agents that cannot be removed from the xenograft can augment clinical surveillance.7. Laboratory based studies of xenograft survivors increase our ability to quantify xenotransplant‐associated risks and, thereby, expand our capacity to make science‐based assessments of appropriate public policy.
Inhibitory Action Of Ambocarb On Voltage‐Operated Sodium Channels In Rat Isolated Hippocampal Pyramidal Neurons
Authors: Kopanitsa Maksim V , Krishtal Oleg A , Komissarov Igor V 
Published: March 2003

SUMMARY1. A whole‐cell patch‐clamp study of the effects of ambocarb, a novel nootropic β‐carboline, on sodium currents in rat acutely isolated hippocampal pyramidal neurons was performed.2. Ambocarb potently and reversibly suppressed sodium currents in a concentration range of 3–300 μmol/L. The amount of block was dependent on the holding potential, with half‐ maximal inhibition values being 26 and 94 μmol/L at –80 and –120 mV, respectively.3. Ambocarb induced a hyperpolarizing shift in the steady state availability curve, which indicates an increase in the proportion of inactivated sodium channels. This action is presumably mediated by promoting the development of inactivation and slowing the recovery of sodium channels from inactivation.4. Because many neuroprotective drugs were shown to inhibit sodium currents, down‐modulation of voltage‐operated sodium channels that complements the known positive interaction of ambocarb and other related β‐carbolines with GABAA receptors may provide a promising strategy in the treatment of brain disorders associated with trauma and ischaemia.
Renal Acid–Base And Sodium Handling In Hypoxia And Subsequent Mild Metabolic Acidosis In Foetal Sheep
Authors: Gibson Karen J , McMullen Julie R , Lumbers Eugenie R 
Published: March 2003

SUMMARY1. To measure the renal contribution to acid–base homeostasis during hypoxia (not associated with hypercapnia) and in response to the subsequent mild metabolic acidosis and to determine the effects of this hypoxia on the renal handling of sodium, studies were performed in six chronically catheterized foetal sheep (129–138 days gestation) before, during and for 1 h after a 2 h period of hypoxia.2. Hypoxia was induced in the conscious ewe by infusing nitrogen into the trachea. Foetal arterial oxygen tension fell to 12.0±0.6 mmHg (P < 0.001). Carbon dioxide tension fell during hypoxia (P < 0.001) and was still somewhat reduced in the recovery period (P < 0.005). Arterial pH fell progressively to 7.19±0.08 in the recovery period (P < 0.05). Plasma bicarbonate concentrations fell (P < 0.001) and lactate rose (P < 0.001).3. Urinary pH and the excretion rates of bicarbonate, titratable acid, ammonium and net acid did not change during hypoxia. Ammonium excretion and, hence, generation of new bicarbonate increased in the recovery period (P < 0.05).4. Renal sodium excretion progressively increased and was greatest after normoxia was restored (P < 0.05). This natriuresis was due to a fall in the reabsorption of sodium by the proximal tubule (P < 0.05). Proximal reabsorption of sodium was directly related to foetal pH (P < 0.0001) and bicarbonate reabsorption (P < 0.001).5. It was concluded that: (i) the foetal kidneys began to contribute to the maintenance of acid–base balance within the first hour of recovery from a 2 h episode of hypocapnic hypoxia, even though the acidosis was relatively mild; and (ii) a reduction in bicarbonate reabsorption was probably the most important factor that limited sodium reabsorption by the renal tubule during this experiment.
T‐0162, A Novel Free Radical Scavenger, Reduces Myocardial Infarct Size In Rabbits
Authors: Yamashita Kazuya , Minatoguchi Shinya , Uno Yoshihiro , Kariya Tatsuya , Ohno Michiya , Arai Masazumi , Hashimoto Kazuaki , Nishida Yoshio , Nagashima Kenshi , Qiu Xinbin , Takemura Genzou , Suzuki Toshikazu , Fujiwara Takako , Fujiwara Hisayoshi 
Published: March 2003

SUMMARY1. We investigated the effects of 1‐(3‐tert‐butyl‐2‐hydroxy‐ 5‐methoxyphenyl)‐3‐(3‐pyridylmethyl)urea hydrochloride (T‐0162), a novel low‐molecular weight free radical scavenger, on the generation of superoxide anions and hydroxyl radicals in vitro and in vivo and on myocardial infarct (MI) size in an in vivo model of MI in rabbits.2. It was found that T‐0162 scavenged both superoxide anions and hydroxyl radicals in a concentration‐dependent manner in vitro.3. In an in vivo rabbit model with 30 min coronary occlusion and 30 min reperfusion, T‐0162 scavenged hydroxyl radicals generated in the myocardium during reperfusion.4. Anaesthetized open‐chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion. The pretreatment group (n = 10) was infused with T‐0162 dissolved in 10% lecithin solution for 220 min from 10 min before occlusion to 180 min after reperfusion at a rate of 400 μg/kg per min. The post‐treatment group (n = 10) was injected with an i.v. bolus of 10 mg/kg T‐0162 and was then infused with 400 μg/kg per min T‐0162 for 190 min from 10 min before reperfusion to 180 min after reperfusion. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of area at risk (AAR).5. There was no significant difference in haemodynamic parameters among the three groups throughout the experimental period. The per cent infarct size of the AAR in the T‐0162 groups (24.8±4.3 and 30.5±3.9% for pre‐ and post‐ treatment groups, respectively) was significantly reduced compared with control (44.7±4.1%; P < 0.05). There was no significant difference in the AAR among the three groups.6. In conclusion, T‐0162 reduces MI size through the inhibition of reperfusion injury.
Krh‐594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats
Authors: Inada Yoichi , Murakami Makoto , Tazawa Shigeki , Akahane Masuo 
Published: March 2003

SUMMARY1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not.2. The oral administration of KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM‐1K‐SHR.3. In a histological study, KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently improved glomerulosclerosis and the hyalin cast of tubules in DM‐1K‐SHR kidneys. Both KRH‐594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently inhibited cardiac hypertrophy.4. KRH‐594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose‐dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM‐1K‐SHR.5. These results suggest that KRH‐594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.
Relationship Of Cigarette Smoking With Blood Pressure, Serum Lipids And Lipoproteins In Young Japanese Women
Authors: Imamura Hiroyuki , Uchida Kazuhiro , Kobata Daikichi 
Published: March 2003

SUMMARY1. The relationship of cigarette smoking with blood pressure and serum lipids and lipoproteins was studied in 1062 young Japanese women aged 20–39 years of age.2. After adjusting for age, body mass index (BMI), alcohol intake and physical activity scores, the mean systolic and diastolic blood pressures (SBP and DBP, respectively) did not indicate dose‐dependent relationships with cigarette smoking. The largest significant mean differences in SBP (3.5%; P < 0.001), DBP (6.2%; P < 0.018), high‐density lipoprotein– cholesterol (HDL‐C; 13.2%; P < 0.005), ratio of total cholesterol to HDL‐C (13.9%; P < 0.022), triglycerides (TG; 24.1%; P < 0.001) and the logarithmic transformation of TG (log TG; 5.6%; P < 0.001) were found between non‐smokers and smokers.3. When age, BMI, alcohol intake and physical activity scores were included in the forward step‐wise multiple regression analysis, there were negative relationships found for cigarette smoking and SBP and DBP and positive relationships for cigarette smoking and TG and log TG.4. Although the results are somewhat variable, the present study shows that cigarette smoking is negatively associated with SBP and DBP and that there is an association between cigarette smoking and serum lipids and lipoproteins and that smoking has an unfavourable effect on these parameters in young Japanese women.