bluuebunny/crossref_metadata_2025_split huggingface dataset:
INSULIN RESISTANCE SYNDROME IN AUSTRALIAN ABORIGINAL PEOPLE
Authors: Rowley Kevin G. , Best James D. , McDermott Robyn , Green Elizabeth A. , Piers L Sunil , O'Dea Kerin 
Published: June 2007

SUMMARY1. Like many indigenous populations, Australian Aboriginal people have developed high rates of obesity, non‐insulin‐dependent diabetes mellitus (NIDDM) and cardiovascular and renal disease following the transition from a traditional to an ‘urbanized’ lifestyle. These conditions tend to cluster as part of the insulin resistance syndrome.2. The prevalence of overweight people and obesity in Australian Aboriginal populations ranges from 0% in communities with a traditionally orientated lifestyle to well over 50% in the worst affected communities. There is a predominantly central pattern of fat deposition in both men and women, which is associated with greater insulin resistance and cardiovascular risk than is peripheral fat deposition.3. Data from four previously published, population‐based surveys in Aboriginal communities were combined to give a cohort of 1079 subjects of 15 years and older. Several conditions of the insulin resistance syndrome had a strong, positive association with increasing body mass index (BMI): NIDDM (both cross‐sectionally and longitudinally), hypertension, dyslip‐idaemia and albuminuria. Remaining lean (BMI< 20 kg/m2) protected even older Aboriginal people from these conditions to a large extent.4. Community based programmes to increase physical activity and improve dietary quality are likely to be the major means by which conditions associated with insulin resistance can be prevented in Aboriginal populations.
SYMPATHETIC BURST ACTIVITY: CHARACTERISTICS AND SIGNIFICANCE
Authors: McAllen Robin M. , Malpas Simon C. 
Published: June 2007

SUMMARY1. The activity recorded from mammalian sympathetic nerves comes in bursts, which result from large numbers of fibres firing synchronously.2. Human sympathetic nerve activity behaves similarly to that in animals, although burst rates may be lower.3. Vasomotor, cardiac and sudomotor nerve fibres all fire in bursts. Whether other sympathetic pathways do so is unknown.4. Sympathetic activity is intrinsically ‘bursty’ but not intrinsically regular.5. Bursting is a population phenomenon, not usually evident in the firing of individual neurons.6. Bursts in post‐ganglionic nerves are driven by synchronously firing preganglionic neurons.7. The origin of bursts remains controversial. Preganglionic neuron properties are likely to be important in at least shaping bursts.8. Burst amplitude, which reflects the number of fibres firing together, and burst probability are controlled independently.9. Baroreceptors affect burst probability over a wide range, but have less effect on mean burst amplitude. How they affect burst timing within the cardiac cycle is discussed.10. Burst probability is determined ‘downstream’ of the rostral ventrolateral medulla, implicating either the spinal cord or recurrent brainstem connections in burst generation.11. Neuroeffector responses are too slow to follow individual bursts. However, bursting will promote spatial facilitation at both ganglionic and effector levels, which may increase the dynamic range of neural control.
EFFECT OF DIETARY SALT LOADING AND HIGH‐CALCIUM DIET ON VASCULAR SMOOTH MUSCLE RESPONSES AND ENDOTHELIUM FUNCTION IN RATS
Authors: Adegunloye Banji J. , Sofola Olusoga A. 
Published: June 2007

SUMMARY1. The present study examined the effects of concurrent manipulation of dietary calcium and salt on contractile responses of vascular smooth muscle (VSM) and endothelial function of aortic rings from Sprague‐Dawley rats.2. Salt loading enhanced the contractile response of the aortic rings to noradrenaline (NA), an effect that was blunted by a high calciu. intake.3. Removal of the endothelium and incubation of aortic rings in physiological salt solution containing methylene blue increased the sensitivity of the rings t. NA.4. The increase in the sensitivity of aortic rings induced by endothelium removal was more pronounced in aortic rings from salt‐loade. rats.5. Acetylcholine caused similar degrees of relaxation in all experimental groups, but the relaxation to histamine was smalle. (P < 0.05) in salt‐loaded rats than in other groups of rats; however, after removal of the endothelium, the contractile response to histamine was higher in salt‐loaded rats.6. The results indicate that the hypersensitivity of isolated aortic rings to agonists, as observed in salt‐loaded rats, is due to altered responses of the VSM and not as a result of changes in the endothelium. In addition, salt loading tends to increase the synthesis of endothelium‐dependent relaxing factor. The ability of salt loading to enhance the contractile responses of VSM to agonists can be prevented by supplementing the diet with high calcium.
PREVENTATIVE AND THERAPEUTIC EFFECTS OF AE0047 ON RENAL INJURY IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Hayashi Kazutaka , Koyama Mamoru , Kido Hideaki , Egi Yasuhiro , Kubo Yoshiji , Shinyama Hiroshi , Iwamoto Minori , Nakamura Norifumi , Kagitani Yoshio 
Published: June 2007

SUMMARY1. The present study was designed to investigate the preventative and therapeutic effects of AE0047 on renal injury compared with those of nitrendipine in stroke‐prone spontaneously hypertensive rats (SHRSP).2. In the preventative study, drug administration was started before the appearance of renal injury, such as proteinuria. Treatment for 6 weeks with AE0047 (1 and 3 mg/kg, p.o.) led to a dose‐related reduction in systolic blood pressure (SBP). Nitrendipine, at doses of 10 and 30 mg/kg, also lowered SBP to a similar degree to that seen with AE0047 at 1 and 3 mg/kg, respectively.3. In the vehicle‐administered SHRSP group, urinary excretion of protei. (UproteinV) increased progressively from 14 weeks of age for another 6 weeks. AE0047 at both doses maintained UproteinV within normal levels throughout the experimental period. However, the elevation of UproteinV was only inhibited in the 30 mg/kg nitrendipine‐treated group. Urinary N‐acetyl‐β‐D‐glucosaminide (NAG) activity in the vehicle‐treated SHRSP group was elevated. Urinary NAG activity remained at a low level only in AE0047‐treated groups.4. Histopathological examination revealed severe lesion. (i.e. fibrinoid necrosis, proliferative vasculitis and glomerular lesions) of the kidney in SHRSP. AE0047 treatment at each dose attenuated the development of renal lesions in SHRSP. In contrast, nitrendipine, at 10 mg/kg, was ineffective against the development of renal lesions. Although nitrendipine at 30 mg/kg suppressed the development of renal lesions, this effect was still weaker than that seen with AE0047 at 1 mg/kg.5. In the therapeutic study, drugs were administered to 17‐week‐old SHRSP with moderate renal damage for 10 days. Treatment with AE0047 (1 and 3 mg/kg) produced dose‐dependent decreases in UproteinV. In the nitrendipine‐treated group, UproteinV tended to decrease but the changes were not significant.6. Histopathological studies revealed that 3 mg/kg AE0047 improved renal lesions, such as fibrinoid necrosis, proliferative vasculitis and glomerular lesions, whereas 30 mg/kg nitrendipine di. not.7. Taken together, the results indicate that AE0047 is capable of preventing proteinuria as well as renal lesions, in part via a mechanism independent of its depressor action on SBP. Furthermore, AE0047 improves proteinuria and renal lesions in proteinuria‐established SHRSP. Thus, AE0047 may have therapeutic potential in suppressing either the development or the progression of renal disease in hypertensive patients.
TARGETED DRUG DELIVERY TO THE SKIN AND DEEPER TISSUES: ROLE OF PHYSIOLOGY, SOLUTE STRUCTURE AND DISEASE
Authors: Roberts MS 
Published: June 2007

SUMMARY1. Drug delivery through the skin has been used to target the epidermis, dermis and deeper tissues and for systemic delivery. The major barrier for the transport of drugs through the skin is the stratum corneum, with most transport occurring through the intercellular region. The polarity of the intercellular region appears to be similar to butanol, with the diffusion of solutes being hindered by saturable hydrogen bonding to the polar head groups of the ceramides, fatty acids and other intercellular lipids. Accordingly, the permeability of the more lipophilic solutes is greatest from aqueous solutions, whereas polar solute permeability is favoured by hydrocarbon‐based vehicles.2. The skin is capable of metabolizing many substances and, through its microvasculature, limits the transport of most substances into regions below th. dermis.3. Although the flux of solutes through the skin should be identical for different vehicles when the solute exists as a saturated solution, the fluxes vary in accordance with the skin penetration enhancement properties of the vehicle. It is therefore desirable that the regulatory standards required for the bio‐equivalence of topical products include skin studies.4. Deep tissue penetration can be related to solute protein binding, solute molecular size and dermal bloo. flow.5. Iontophoresis is a promising area of skin drug delivery, especially for ionized solutes and when a rapid effect i. required.6. In general, psoriasis and other skin diseases facilitate drug delivery through th. skin.7. It is concluded that the variability in skin permeability remains an obstacle in optimizing drug delivery by thi. route.
EVIDENCE FOR DIRECT INTERACTION OF KETAMINE WITH α‐ AND β2‐ADRENOCEPTORS
Authors: Bevan RK , Rose MA , Duggan KA 
Published: June 2007

SUMMARY1. Ketamine has a number of effects that suggest that it may interact with α‐ and β‐adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to α‐ and β‐adrenoceptors.2. Membrane preparations o. α1‐ and β2‐adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [3H]‐prazosin for α1‐adrenoceptor binding sites and [125I]‐cyanopindolol (CYP) for the β2‐adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non‐selective antagonists.3. Studies in which ketamine was used to displac. [3H]‐prazosin revealed a Kd of 3.40±1.23× 10−3 mol/L for ketamine binding to ai‐adrenoceptors. Displacement studies of [125I]‐CYP by ketamine showed a Kd of 0.35±0.03× 10−3 mol/L for ketamine binding to β2‐adrenoceptors.4. We conclude that ketamine interacts directly with both ai‐ an. β2‐adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.
RAPID REVERSAL OF ENDOTHELIAL DYSFUNCTION IN HYPERCHOLESTEROLAEMIC RABBITS TREATED WITH SIMVASTATIN AND PRAVASTATIN
Authors: Jorge Paulo A Ribeiro , Osaki Michiko R. , de Almeida Eros 
Published: June 2007

SUMMARY1. The main objective of the present study was to verify the speed with which two 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors, simvastatin and pravastatin, could revert endothelial cell dysfunction in hypercholesterolaemic rabbits. An attempt was also made to correlate the plasma cholesterol level and the tissue cholesterol and malondialdehyde (MDA) contents of the aortae with the endothelium‐dependent relaxation on the assumption that any endothelial dysfunction could be rapidly and partially reversed, even in the presence of relatively high serum cholesterol levels.2. Ninety‐one male New Zealand white rabbits were randomly assigned to hypercholesterolaemic (control), simvastatin or pravastatin groups. All rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for 8 weeks. Simvastatin (10 and 20 mg/day) and pravastatin (15 and 30 mg/day) were administered 6, 4 and 2 days before the end of the experiment. At the end of the 8th week, animals were killed and the aortae were removed for histological examination as well as for the measurement of cholesterol and MDA contents and for endothelium‐dependent relaxation studies.3. The results showed that significant improvement in endothelium‐dependent relaxation was obtained only with pravastatin and only with 4 or 6 days of administration. In these cases, the cholesterol and MDA contents of the vessel wall were reduced, although no significant changes were observed in plasma total cholesterol. Higher doses of the drugs did not alter these results.4. We conclude that pravastatin enhances endothelium‐dependent relaxation when administered to cholesterol‐fed rabbits, probably via an anti‐oxidant action. This effect, which was observed to start on the 4th day of drug administration, may represent a new therapeutic approach for the treatment of acute coronary syndromes in hypercholesterolaemic patients.
EXTRACTS OF GINKGO BILOBA AND GINSENOSIDES EXERT CEREBRAL VASORELAXATION VIA A NITRIC OXIDE PATHWAY
Authors: Chen X , Salwinski S , Lee TJ‐F 
Published: June 2007

SUMMARY1. Extracts from the leaves of Ginkgo biloba (EGb) and ginsenosides (GS) have been reported to be effective at increasing vascular relaxation. In the present study, the actions of EGb and GS on the vascular functions of porcine basilar arteries were investigated in vitro using tissue bath techniques.2. Both EGb and GS relaxed the basilar artery in a concentration‐dependent and partly endothelium‐dependent manner. However, EGb appeared to be more potent than GS. Relaxation induced by transmural nerve stimulation (TNS) was significantly enhanced by EGb (7.5, 15 and 30 μg/mL) and GS (20, 40 and 80 μg/mL| in both endothelium‐intact and ‐denuded basilar arteries. Enhanced TNS‐induced relaxations were abolished by 0.3 mmol/L N‐h ‐arginine.3. The present study demonstrates that nitric oxide plays a primary role in TNS‐induced relaxation as well as in EGb‐ and GS‐enhanced relaxation within the cerebral vasculature. In addition, our data support the potential of these compounds as therapeutic strategies in cerebral ischaemia and other related vascular dysfunctions.
ENDOTHELIUM‐SMOOTH MUSCLE INTERACTIONS IN BLOOD VESSELS
Authors: van Breemen Cornells , Skarsgard Peter , Laher Issy , McManus Bruce , Wang Xiaodong 
Published: June 2007

SUMMARY1. Blood vessel tone is determined both by smooth muscle and endothelial functions. In coronary arteries taken from rat (Fisher‐Lewis) cardiac transplanted hearts, the inducible form of NOS (iNOS) in smooth muscle is more active, while acetylcholine‐induced nitric oxide production in the endothelium is greatly diminished. This causes a greatly reduced myogenic constriction, in pressurized septal arteries taken from immunologically challenged transplanted hearts.2. The sarcoplasmic reticulum (SR) of smooth muscle and the endoplasmic reticulum (ER) of endothelial cells sequeste. Ca2+ from the cytoplasm. This reduces the intracellular concentration of free Ca2+, which is necessary for the activation of cellular processes. The release of Ca2+ from internal stores occurs through ryanodine and IP3 recoptors located on the SR membrane.3. The superficial SR/ER also interacts with ion exchangers and pumps in the plasma membrane. This allows for the superficial SR/ER to function in Ca2+ extrusion; for example, inhibition of the SR/ER Ca2+‐ATPase (SERCA) partially inhibits the rate of loss Ca2+ from the cell. Recent data suggest that the SR Ca2+‐ATPase and the Na+‐Ca2+ exchanger of smooth muscle cells function in series; that is, Ca2+ uptake by the SR followed by release towards the exchanger to mediate extrusion. This interaction between the SERCA of the superficial SR and ion exchangers and pumps creates intracellular Ca2+ gradients.4. The SERCA of the superficial, peripherally distributed SR/ER also serves to regulat. Ca2+ entry from the extracellular space. This occurs in part by inhibition of the superficial buffer barrier function of the SR as well as by depletion of stimulated Ca2+ entry.5. Ca2+ entry is also regulated in endothelial and smooth muscle cells by the membrane potential. Membrane hyperpolar‐ization increases the driving force for Ca2+ entry into endothelial cells, which lack voltage‐gated Ca2+ channels, and reduces open ate probability of voltage‐gated Ca2+ channels in vascular smooth muscle cells. The two cell types have electrical contact and interact in a dynamic manner to regulate blood vessel diameter
ABNORMAL KIDNEY FUNCTION AS A CAUSE AND A CONSEQUENCE OF OBESITY HYPERTENSION
Authors: Hall John E. , Brands Michael W. , Henegar Jeffrey R. , Shek Eugene W. 
Published: June 2007

SUMMARY1. Obesity is the most common nutritional disorder in the US and is a major cause of human essential hypertension. Although the precise mechanisms by which obesity raises blood pressure (BP) are not fully understood, there is clear evidence that abnormal kidney function plays a key role in obesity hypertension.2. Obesity increases tubular reabsorption and this shifts pressure natriuresis towards higher BP. The increased tubular re‐absorption is not directly related to hyperinsulinaemia, but is closely linked to activation of the sympathetic and renin‐angiotensin systems, and possible changes in intrarenal physical forces caused by medullary compression due to accumulation of adipose tissue around the kidney and increased extracellular matrix within the kidney.3. Obesity is also associated with marked renal vasodilation and increased glomerular filtration rate, which are compensatory responses that help overcome the increased tubular re‐absorption and maintain sodium balance. However, chronic renal vasodilation causes increased hydrostatic pressure and wall stress in the glomeruli which, along with increased lipids and glucose intolerance, may cause glomerulosclerosis and loss of nephron function in obese subjects. Because obesity is a primary cause of essential hypertension as well as type II diabetes, there is good reason to believe that obesity may also be the most frequent cause of end‐stage renal disease.4. Future research is needed to determine the mechanisms by which excess weight gain activates the neurohumoral systems and alters renal structure and function. Because of the high prevalence of obesity in most industrialized countries, unravelling these mechanisms will likely provide a better understanding of the pathophysiology of human essential hypertension and chronic renal failure.
DRIVING RESPIRATION: THE RESPIRATORY CENTRAL PATTERN GENERATOR
Authors: Bellingham Mark C. 
Published: June 2007

SUMMARY1. The central pattern generator (CPG) for respiration is located in the brainstem and produces rhythmic synaptic drive for motoneurons controlling respiratory muscles. Based on respiratory nerve discharge, the respiratory cycle can be divided into three phases: inspiration, postinspiration and stage 2 expiration.2. Six basic types of respiratory neuron participate in respiratory rhythmogenesis. Their firing and membrane potential patterns are locked to different phases of the respiratory cycle.3. In adult mammals, respiratory neurons are subject to excitatory and inhibitory synaptic inputs and show extensive synaptic interconnections that are mainly inhibitory. There are differences in the relative importance of excitatory and inhibitory synaptic drives and the neurotransmitters involved in respiratory rhythmogenesis in neonates compared with adults.4. Respiratory neurons possess a number of intrinsic membrane currents that may be involved in central pattern generation, including low‐ and high‐voltage‐activated calcium, potassium, calcium‐dependent potassium, sodium and mixed cationic currents. More quantitative information is needed about the distribution and characteristics of these ionic currents if we are to understand rhythmogenesis.5. The two main theories for the origin of respiratory rhythm are those of pacemaker neuron‐driven and synaptic network‐driven CPG. Evidence derived from in vivo and in vitro experiments exists to support both of these theories. There may be a significant switch in the underlying mechanism driving the respiratory CPG during postnatal development.
AUTOINHIBITION, SYMPATHETIC COTRANSMISSION AND BIPHASIC CONTRACTILE RESPONSES TO TRAINS OF NERVE STIMULATION IN THE RODENT VAS DEFERENS
Authors: Ventura Sabatino 
Published: June 2007

SUMMARY1. The present review critically discusses the evidence for and against the various hypotheses that have been proposed to explain the biphasic contractile response of the rodent vas deferens to trains of electrical field stimulation (EFS).2. It is widely accepted that the initial component of the biphasic response of the rodent isolated vas deferens to trains of EFS is mediated by ATP and the second slower tonic contraction is mediated by noradrenaline (NA). This theory is based on the ability of antagonists of the post‐junctional receptors for these neurotransmitters to inhibit the respective components of the biphasic response and on the ability of exogenous application of either ATP or NA to mimic the responses of each phase.3. Prejunctional autoinhibition has also been proposed as the cause of the biphasic response. This is based primarily on the ability of α2‐adrenoceptor antagonists to transform responses from biphasic to monophasic and on the ability of neuronal NA uptake inhibitors to accentuate the separation of the two phases.4. Atypical or extrajunctional NA receptors have also been proposed to be the mediators of the component of the response to nerve stimulation that is resistant to the traditional α‐adrenoceptor antagonists.5. Different contractile mechanisms and/or sources of calcium have also been postulated to cause the biphasic response. Blockers of intracellular Ca2+ mobilization are able to block the initial component, while blockers of extracellular Ca2+ entry inhibit the second tonic phase.6. It is concluded that because α1‐adrenoceptor antagonists and blockers of P2 purinoceptors have also been shown to block both phases of the response to trains of EFS, prejunctional auto‐inhibitory mechanisms perhaps provide the most sound explanation for the phenomenon of the biphasic contractile response to trains of EFS.
NEUTRAL ENDOPEPTIDASE 3.4.24.11 INHIBITION POTENTIATES THE INHIBITORY EFFECTS OF TYPE‐C NATRIURETIC PEPTIDE ON LEUKOTRIENE D4‐INDUCED AIRWAY CHANGES
Authors: Ohbayashi Hiroyuki , Yamaki Kenichi , Suzuki Ryujiro , Kume Hiroaki , Takagi Kenzo 
Published: June 2007

SUMMARY1. Microvascular leakage, a primary feature of inflammation, is well known for worsening the asthmatic condition. Gene expression of and a specific receptor for type‐C natriuretic peptide (CNP), initially considered a neuropeptide, have been detected in the human vascular wall and secretion of CNP from vascular endothelial cells has recently been demonstrated. These facts suggest the presence of a vascular natriuretic peptide system and led us to expect that CNP may act beneficially on airway microvascular leakage in asthma. In the present study, we investigated the effects of CNP against leukotriene (LT) D4 ‐induced airway microvascular leakage and bronchocon‐striction and how these effects were potentiated by thiorphan, a potent neutral endopeptidase 3.4.24.11 (NEP) inhibitor.2. Anaesthetized male guinea‐pigs, ventilated via a tracheal cannula, were placed into a plethysmograph for 10 min, in order to measure pulmonary mechanics and mean blood pressure, after challenge with 2 μg/kg LTD4 and then the extravasation of 20 mg/kg Evans blue dye into airway tissue was investigated to indicate and evaluate microvascular leakage.3. Intravenous administration of CNP (100, 300 and 1000 μg/kg) significantly inhibited the LTD4‐induced microvascular leakage and bronchoconstriction in a dose‐dependent manner. These inhibitory effects were enhanced by pretreatment with 20 mg/kg thiorphan, suggesting the important role of NEP in the pulmonary metabolism of CNP.4. We believe that these results are encouraging for the further investigation of the therapeutic applications of exogenous CNP in asthma.