bluuebunny/crossref_metadata_2025_split huggingface dataset:
GENERATION AND ENTRAINMENT OF ORCADIAN RHYTHMS
Authors: Kennaway David J. 
Published: June 2007

SUMMARY1. The present brief review examines some of the new developments in the area of circadian rhythm research.2. The discovery of the mouse clock and m‐per genes and their similarity to other clock genes like per and tint has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expressed in the site of the biological clock, the suprachiasmatic nucleus (SCN), and so will now become a focus of research into the generation of rhythmicity.3. Because SCN cells expressing endogenous rhythms have a periodicity different from 24 h, there must be mechanisms in place to reset the rhythms on a daily basis. This is achieved in mammals by retinal light perception and neural transmission through several discrete pathways to the SCN.4. The nature of the neurotransmitters involved in this transfer of environmental information to the timing system is controversial and may even vary between similar species but, in the rat, there is compelling evidence that a serotonergic pathway is pre‐eminent in mediating the effects of light. How the re‐setting is achieved at the cellular level is not known.
RENAL DISEASE AS A METAPHOR: TOWARDS A MORE INTEGRATED VIEW OF ABORIGINAL HEALTH
Authors: Hoy Wendy E. 
Published: June 2007

SUMMARY1. The health of Aboriginal people in the Northern Territory of Australia is among the worst in the world, with mortality rates increased in every ‘disease‐specific’ category and averaging overall approximately five‐fold those of non‐Aboriginal Australians. Health services, which in most regions are rudimentary, fragmented and underresourced, have been slow to recognize and meet this challenge. However, the cost implications of an epidemic of renal failure have stimulated concern that broader mortality statistics could not.2. In one high‐risk Aboriginal community, we found that renal disease can be detected and its course chartered by a simple and reliable screening test. Renal disease arises out of a broad menu of risk factors that reflect poverty, disadvantage and accelerated lifestyle changes and its expression is progressively amplified with the simultaneous operation of more than one risk factor. It is intimately related to other ‘diseases’ through shared risk factors and pathophysiology. We also found that people with established renal disease participated enthusiastically in a pharmacological treatment programme, with excellent clinical responses that predict a marked reduction in renal failure and cardiovascular morbidity and mortality over the intermediate term.3. It is likely that most other causes of excess mortality in Aboriginal people are, like renal disease, multideterminant, with a substantial base of shared risk factors. They are probably equally susceptible to modification. We must move away from ‘single‐cause’ disease models, eliminate counterproductive specialty barriers and rectify the unbalanced focus and resource commitment to hospital‐based, high technology treatments of people with advanced and irreversible disease. We must advocate for coherent, sustained, integrated public health and primary care programmes to improve the whole health profile and for screening and treatment programmes to modify the course of disease in people already afflicted.
PHYSIOLOGICAL EVIDENCE FOR ARTERIOVENOUS ANASTOMOSES IN THE UTERINE CIRCULATION OF LATE‐PREGNANT EWES
Authors: Miller Suzanne L. , Dickson Kerry , Jenkin Graham , Walker David W. 
Published: June 2007

SUMMARY1. The objective of the present study was to determine whether arteriovenous anastomoses (AVA) are present in the uterine circulation of conscious, late‐pregnant ewes.2. Twenty late‐pregnant ewes were assigned to two groups. In group 1, 15 μm coloured microspheres were injected into the uterine artery of the pregnant horn and the relative proportion of microspheres trapped in the uterus and lungs was determined. The percentage shunting of blood measured by this method was 17 ± 3%, representing a blood flow of 164 ± 39 mL/min (n= 12). Any contribution of ovarian, cervical, rectal and other vascular beds was specifically excluded in this group.3. In group 2, total uterine capillary flow was measured using the reference blood flow method, by injecting 15 μm microspheres into the heart. Calibrated flow probes, placed on both main uterine arteries, concurrently measured total uterine blood flow. Total blood flow to the uterus (flow probe) was significantly greater (t= 3.415; P= 0.027) than uterine capillary flow (microspheres), indicating AVA shunting in the uterine circulation. Mean total blood flow to the uterus was 1749 ± 160 mL/min, of which an average 25 ± 5% (n = 5 sheep) was shunted.4. The percentage AVA shunting for groups 1 and 2 was not significantly different (t= 1.219; P= 0.24) and, when combined, the mean percentage of uterine blood flow passing through AVA in the late‐pregnant sheep was determined to be 19 ± 23%.5. The present study shows that AVA are present and patent in the uterine circulation of late‐pregnant ewes and that they account for the shunting of approximately 20% of the uterine blood flow into the maternal venous circulation.
TRILINOLEIN INHIBITS THE ADHESION OF NEUTROPHILS TO ENDOTHELIAL CELLS
Authors: Hang CY , Huang SS , Wang R. , Sung YJ , Kwok CF 
Published: June 2007

SUMMARY1. Trilinolein is a triacylglycerol with linoleic acid as the only type of fatty acid in all three esterified positions of glycerol. It was recently reported to have a myocardial protective effect in coronary ligated rats. We now study its effect on the adhesion of human neutrophils to cultured bovine endothelial cells.2. Pretreatment of an endothelial monolayer with trilinolein at concentrations ranging from 10‐10 to 10‐6 mol/L significantly inhibited neutrophil adhesion to endothelial cells. Trilinolein was less potent than sodium nitroprusside in inhibiting neutrophil adhesion.3. The inhibitory effect of trilinolein was antagonized by methylene blue and NG‐nitro‐L‐arginine methyl ester. The inhibitory effect of trilinolein was not mediated through linoleic acid because linoleic acid did not inhibit neutrophil adhesion.4. Pretreatment of neutrophils with trilinolein did not reduce neutrophil adhesion. However, in neutrophils activated with N‐formyl‐methionyl‐leucyl‐phenylalanine, trilinolein inhibited the neutrophil adhesion to endothelial cells.5. We conclude that trilinolein inhibits neutrophil adhesion to the endothelial monolayer by stimulating the nitric oxide and cyclic GMP pathways in endothelial cells. It may also inhibit neutrophil adhesion by scavenging free radicals. The inhibitory effect of trilinolein on neutrophil adhesion may play a role in its myocardial protective activity.
MECHANISMS OF IMPAIRMENT OF ENDOTHELIUM‐DEPENDENT RELAXATION TO ACETYLCHOLINE IN WATANABE HERITABLE HYPERLIPIDAEMIC RABBIT AORTAS
Authors: Kagota Satomi , Yamaguchi Yu , Shinozuka Kazumasa , Kunitomo Masaru 
Published: June 2007

SUMMARY1. The mechanism of impairment of the endothelium‐dependent relaxation in response to acetylcholine (ACh) in aortas from Watanabe heritable hyperlipidaemic (WHHL) rabbits was investigated using a modified sandwich (layered) technique. Intact aortas from WHHL rabbits or Japanese white (JW) rabbits as the control were used as donor strips of endothelium‐derived relaxing factor (EDFU?) and endothelium‐denuded aortas from JW rabbits were used as detector strips. The EDRF released from a donor strip could be directly detected as the relaxation response in a detector strip.2. The endothelium‐dependent relaxations in all rabbit arteries were almost abolished by treatment with NG‐nitro‐l‐arginine methyl ester (an inhibitor of nitric oxide synthase).3. The ACh‐induced endothelium‐dependent relaxations in the donor strips were impaired in WHHL rabbits in comparison with relaxations in JW and heterozygous WHHL rabbits. Similarly, the relaxation in the detector strips induced by EDRF released from donor strips was reduced in WHHL rabbits. There was a good negative correlation between the aortic total cholesterol content in the donor strips and the degree of relaxation in the detector strips from WHHL rabbits.4. The reduced relaxation in the detector strips when using donor strips with high cholesterol accumulation or atheromatous plaque was not affected by superoxide dismutase plus catalase (scavengers of superoxide anions), indomethacin (an inhibitor of cyclo‐oxygenase), ONO‐3708 (an antagonist of endoperoxide/ thromboxane receptor) and 97–139 (an antagonist of endothelin ETA receptor).5. These results suggest that the mechanism of impaired endothelium‐dependent relaxations in atherosclerotic WHHL rabbit aortas may be due to the reduced amount of EDRF, probably nitric oxide, from the endothelium and not due to its inactivation by oxygen‐derived free radicals or masking by increased production of endothelium‐derived contracting factors.
A PRIMING DOSE OF PROPRANOLOL REDUCES THE AVAILABILITY OF A SUBSEQUENT DOSE IN THE ISOLATED PERFUSED RAT LIVER PREPARATION
Authors: Ghabrial Hany , Sewell Richard B. , Smallwood Richard A. , Morgan Denis J. 
Published: June 2007

SUMMARY1. A 50 μL bolus dose containing (±)‐propranolol hydrochloride (200 μg) and [14C]‐sucrose, or antipyrine (2 mg) and [14C]‐sucrose, or [14C]‐taurocholate sodium was injected into the portal vein of the isolated perfused rat liver preparation and perfusate outflow samples were collected frequently for the next 30min. After a 20 min washout period this procedure was repeated.2. [14C]‐Sucrose, antipyrine and [14C]‐taurocholate each eluted as a single peak at 18, 31 and 28 s, respectively, after each dose. In contrast, propranolol eluted with two peaks at approximately 18 and 128 s after dosing.3. There was no significant difference in dose‐corrected area under the outflow curve (AUC) for [14C]‐sucrose, antipyrine or [14C]‐taurocholate between the first and second doses whereas the mean propranolol AUC for the second dose was only 0.577 ± 0.439 that for the first dose (P <0.05).4. Unmetabolized propranolol accounted for more than 80% of the drug in hepatic tissue for the first and second doses at 18 s and greater than 50% at 128 s, and there was no significant difference in these values at each time between the first and second doses.5. These findings suggest that for an avidly extracted drug, such as propranolol, systemic availability of orally administered drug will be highly dependent on factors that influence the hepatic tissue binding of the drug.
PHOSPHODIESTERASE IV INHIBITORS SYNERGISTICALLY POTENTIATE RELAXATION INDUCED BY FORSKOLIN IN GUINEA‐PIG TRACHEA
Authors: Tanizawa Makoto , Watanabe Takako , Kurne Hiroaki , Yarnaki Kenichi , Miyamoto Kenichi , Takagi Kenzo 
Published: June 2007

SUMMARY1. β‐Adrenoceptor receptor agonists are the principal bronchodilator agents used in the treatment of bronchial asthma. However, the regular use of β‐adrenoceptor agonists in asthmatic patients is likely to increase asthma severity because of a defective β‐adrenoceptor function. Bronchodilators that bypass this defective function are therefore needed.2. Our objectives in this study were: (i) to assess the effects of an agent that directly activates adenylate cyclase (forskolin) on guinea‐pig tracheal smooth muscle; (ii) to study the interactions between selective cyclic nucleotide phosphodiesterase (PDE) inhibitors and forskolin by measuring isometric tension; and (iii) to compare these results with the interaction between PDE inhibitors and terbutaline, a β‐adrenoceptor agonist.3. The relaxant effects of forskolin alone, which is now under development as a new bronchodilator for bronchial asthma therapy, were slightly weaker than those of terbutaline on guinea‐pig tracheal smooth muscle.4. Both denbufylline and Ro 20–1724, cyclic nudeotide PDEIV inhibitors, synergistically increased the relaxant effects of forskolin and terbutaline, while other PDE isozyme inhibitors (amrinone, vinpocetine and zaprinast) had only a minor influence.5. In conclusion, a good synergistic interaction between forskolin and PDE IV inhibitors, especially denbufylline, may provide a means for bypassing β‐adrenoceptors. Thus, the combination of forskolin and PDE inhibitors would become useful in the treatment of bronchial asthma.
ROLE OF NITRIC OXIDE IN THE DEVELOPMENT OF CORTICOTROPIN‐INDUCED HYPERTENSION IN SHEEP
Authors: Tresham JJ , May CN 
Published: June 2007

SUMMARY1. The possibility that altered synthesis of vascular nitric oxide (NO) plays a role in the development of corticotropin‐induced hypertension in sheep was examined by determining the effect of concomitant infusion of L‐arginine, a precursor of NO, on the development of the hypertension.2. Corticotropin (5 μg/kg per h) infused over 2 days increased mean arterial pressure (MAP) from 83 ± 4 to 99 ± 4 mmHg in five conscious sheep. Concomitant infusion of L‐arginine (60 mg/kg per h) did not alter this response; infusion of L‐arginine alone had no effect on blood pressure.3. The dose of L‐arginine (60 mg/kg per h) used blocked the rise in MAP (+16 mmHg) in response to a 5 h infusion of N‐nitro‐L‐arginine (1 mg/kg per h).4. These findings suggest that disruption of NO synthesis does not play a role in the development of corticotropin hypertension in sheep.
ACUTE EFFECTS OF ORAL GLIBENCLAMIDE ON BLOOD PRESSURE AND FOREARM VASCULAR RESISTANCE IN DIABETICS
Authors: Sundaresan Purnima , Lykos Denise , Daher Ali , Morris Richard , Diamond Terence , Howes Laurence G. 
Published: June 2007

SUMMARY1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+atp channel activating vasodilator diazoxide, a placebo‐controlled, double‐blind cross‐over study was performed in eight male volunteers with non‐insulin‐dependent diabetes mellitus.2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75–30 mg/kg per min) and nor‐adrenaline (25–100 ngkg per min) were measured by venous occlusion plethysmography.3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01).4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra‐arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+ atp channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.
VASORELAXATION OF RAT THORACIC AORTA CAUSED BY 14‐DEOXYANDROGRAPHOLIDE
Authors: Zhang CY , Tan BKH 
Published: June 2007

SUMMARY1. The pharmacological effects of 14‐deoxyandrographolide on rat isolated thoracic aorta were examined.2. 14‐Deoxyandrographolide (2.5‐120 μmiol/L) inhibited contractions induced by phenylephrine (PE; 0.1 μmol/L) and high K+ (80mmol/L) in a concentration‐dependent manner in endothelium‐intact aorta. The effect was attenuated in endo‐thelium‐denuded aorta without modifying the maximal response. Like verapamil, 14‐deoxyandrographolide produced a much greater vasorelaxant effect in aorta precontracted by KCI than by PE. 14‐Deoxyandrographolide (20‐60 μmol/L) also inhibited responses of the rat aorta to PE.3. In Ca2+‐free medium (KCI 55mmol/L), 14‐deoxyandrographolide (20‐80 μmol/L) antagonized Ca2+‐induced vasocon‐traction in a concentration‐dependent manner and transient contractions induced by both caffeine (10mmol/L) and noradrenaline (1μmol/L) were suppressed or almost abolished by 14‐deoxyandrographolide.4. The vasorelaxant effect of 14‐deoxyandrographolide was partially antagonized by NG‐nitro‐L ‐arginine methyl ester (25 μmol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 μmol/L), a soluble guanylate cyclase inhibitor, but was not affected by indomethacin (20 μmol/L), a cyclo‐oxygenase inhibitor, or glibenclamide (10 μmol/L), an ATP‐sensitive K+‐channel blocker.5. These results suggest that the vasorelaxant activity of 14‐deoxyandrographolide may be mediated via the activation of NOS and guanylate cyclase, as well as the blockade of Ca2+ influx through both voltage‐ and receptor‐operated Ca2+ channels.
TIME‐DEPENDENT CYCLOSPORINE A‐INDUCED NEPHROTOXICITY IN RATS
Authors: Yamauchi Hitoshi , Kobayashi Eiji , Sugimoto Koh‐ichi , Tsuruoka Shuichi , Yabana Machiko , Ishii Masao , Fujimura Akio 
Published: June 2007

SUMMARY1. We investigated the toxicity of cyclosporine A (CsA) with reference to the timing of its administration in rats.2. To elucidate the time‐dependent effects of CsA on renal function and survival rate, CsA (75 mg/kg per day) or vehicle was orally administered once daily at four different times (3,9, 15 and 21 h after lights on; HALO) over a period of 21 days to male Wistar rats (n= 56) kept in rooms with a 12 h light‐dark cycle.3. On the 7th day after treatment, creatinine clearances (Ccr) of groups dosed at 3 and 9 HALO (inactive period) were not reduced in comparison with clearances of time‐matched control rats, whereas Ccr significantly decreased in rats dosed at 15 and 21 HALO (active period). Cyclosporine A markedly increased urinary N‐acetyl‐β‐D‐glucosaminidase (NAG) excretion in all dosed groups at the 7th day after treatment, except for rats dosed at 3 HALO. In rats dosed at 3 HALO, Ccr decreased progressively; however, it did not decrease progressively in rats dosed at 9 HALO. In surviving rats treated during the inactive period, urine NAG subsequently returned to control levels. Survival rates were greater in animals dosed during inactive periods than those in groups dosed during active periods.4. Significant differences in CsA‐induced toxicity were obvious as a result of the timing of its administration. A different time course between Ccr and urine NAG excretion was observed during repeated CsA administration. Degenerative changes in proximal tubules were demonstrated after chronic administration of CsA, suggesting that severe and persistent tubular damage cannot be assessed by urinary NAG excretion.
IDENTIFICATION OF CARDIOVASCULAR PATHWAYS IN THE SYMPATHETIC NERVOUS SYSTEM
Authors: Anderson CR 
Published: June 2007

SUMMARY1. Sympathetic autonomic neurons show distinct patterns of expression of a range of neurochemicals that can be detected immunohistochemically. Often, functionally homologous neurons in the autonomic nervous system express identical combinations of substances that serve as a chemical code that allows them to be identified among other autonomic neurons.2. In the rat stellate ganglion, where many neurons express either immunoreactivity (IR) to neuropeptide Y (NPY) or the calcium‐binding protein calbindin, a population of large postganglionic neurons found along the medial border of the stellate ganglion, around the origin of the cardiac nerves, expressed intense IR to both substances at all ages examined, from early postnatal to adult.3. In the heart, in the first few postnatal weeks, many nerve terminals were IR for both NPY and calbindin, but, with increasing age, calbindin‐IR was progressively lost from NPY‐IR terminals. Nerve terminals IR for both calbindin and NPY were not seen around pulmonary blood vessels or in the trachea or the thymus.4. Nerve terminals IR for calretinin, another calcium‐binding protein, were present in dense pericellular baskets around neurons in the stellate IR for both calbindin and NPY. The terminals also contained nitric oxide synthase (NOS)‐IR.5. It is suggested that the calbindin‐ and NPY‐IR neurons in the stellate ganglion are the post‐ganglionic neurons that innervate the heart and that the nerve terminal containing calretinin and NOS‐IR that surround them are the cardiac preganglionic terminals. It thus appears possible, in the rat, to identify the sympathetic cardiac pathway arising in the spinal cord and controlling the heart purely on the basis of chemical coding.
NICOTINE EXCITES CARDIAC VAGAL NEURONS VIA THREE SITES OF ACTION
Authors: Mendelowitz David 
Published: June 2007

SUMMARY1. Nicotine is involved in many cardio‐respiratory diseases, including hypertension and sudden infant death syndrome (SIDS), which is the most common cause of death in infants between 1 month and 1 year of age. While the aetiology of SIDS remains largely unknown, recent clinical studies suggest maternal cigarette smoking is a major risk factor in SIDS and an abnormality of cardio‐respiratory control, particularly a centrally mediated slowing of the heart that precedes or accompanies apnoea, is involved.2. Because the sites, mechanisms of action and diverse receptor types of nicotine within the central nervous system are controversial and poorly understood, in the present study we examined the effects of nicotine on specific brainstem neurons that control heart rate. Cardiac vagal neurons were identified in anin vitroslice preparation using a retrograde fluorescent tracer and were studied using both whole‐cell and perforated patch‐clamp electrophysiological techniques.3. We have found there are different pre‐ and post‐synaptic nicotinic receptors that have dramatic effects on glutamatergic neurotransmission as well as directly activating vagal cardio‐inhibitory neurons.
FUNCTIONAL SIGNIFICANCE OF THE 10 Hz RHYTHMIC DISCHARGES IN SYMPATHETIC NERVES
Authors: Kishi Erika , Ootsuka Youichirou , Rong Weifang , Terui Naohito 
Published: June 2007

SUMMARY1. By measuring renal vascular conductance in anaesthetized and immobilized rabbits, the functional significance of the 10 Hz rhythmic discharges in the sympathetic nerves was assessed by electrical stimulation of the renal nerve. This stimulation mimicked the intermittently occurring 10 Hz rhythmic discharges.2. Comparison of high‐frequency (10‐20 Hz) intermittent electrical stimulation with continuous low‐frequency (5 Hz) stimulation showed that the intermittent high‐frequency stimulation evoked faster (smaller time constant) and larger responses of the renal vascular conductance if the total number of stimulus pulses was the same.3. Therefore, the intermittently occurring 10 Hz rhythmic discharges in the sympathetic nerve produces faster and larger effects on peripheral organs than effects produced by continuous discharges if the number of spikes is equal.