bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAPAVERIVE ABOLISHES ENDOTHELIUM‐DEPENDENT DILATATION OF HUMAN INTERNAL MAMMARY ARTERIES IN VITRO
Authors: Schyvens Christopher G. , Owe‐Young Robert A. , Spratt Philip M. , Mundy Julie A. , Farnsworth Alan E. , Macdonald Peter S. 
Published: June 2007

SUMMARY1. The purpose of the present study was to examine the effects of papaverine‐HCl, administered into the lumen of the human internal mammary artery (IMA) during harvesting of this vessel, on vascular reactivity in vitro and to specifically test the hypothesis that intraluminal administration of papaverine‐HCl impairs endothelium‐dependent vasodilation.2. The present study measured in vitro dilator and constrictor responses of terminal segments of human IMA. Internal mammary artery segments were obtained either prior to routine administration of intraluminal papaverine (pre‐P) or after papaverine administration (post‐P) in patients undergoing coronary artery bypass grafting. In addition, the viability of cultured human saphenous vein endothelial cells exposed to papaverine‐HCl was examined.3. Cumulative concentrations of U46619, 5‐hydroxytryptamine and phenylephrine (PE) produced active contractions in post‐P IMA rings. Contractile responses to low concentrations of endothelin‐1 were significantly enhanced in post‐P IMA compared with pre‐P IMA segments.4. Maximal endothelium‐dependent vasodilator responses of pre‐P IMA segments to cumulative concentrations of acetylcholine (ACh) and the calcium ionophore A23187 were 49 ± 7 and 66 ± 4%, respectively, of the initial active tension induced by PE (1 umol/L).5. Maximal endothelium‐dependent vasodilator responses were markedly attenuated in post‐P EVIA (6 ± 6 and 11 ± 10% for ACh and A23187, respectively; P 0.0001 for both vasodilators compared with pre‐P). Post‐P EVIA relaxed completely to the endothelium‐independent vasodilator sodium nitroprusside.6. Exposure of cultured human saphenous vein endothelial cells to papaverine‐HCl (1.2 and 12.0 mg/mL) for 1 h resulted in the reduced viability of these cells.7. The loss of endothelium‐dependent relaxation could dangerously predispose the IMA graft to vasospasm in the postoperative period.
BAROREFLEX CONTROL OF HEART RATE DURING HYPOXIA AND HYPERCAPNIA IN CHRONICALLY HYPERTENSIVE RABBITS
Authors: Groom Andrew S. , Malpas Simon C. 
Published: June 2007

SUMMARY1. It has been proposed that hypertension alters the respiratory and cardiovascular responses to chemoreceptor stimulation. However, in studies of human hypertension or in genetic animal models of hypertension it has been difficult to unequivocally attribute the changes to hypertension per se, rather than to a genetic predisposition towards an altered chemoreflex response independent of hypertension.2. In the present study a group of seven rabbits were made hypertensive via a continuous 7 week infusion of angiotensin II (Angll; 50 ng/kg per min, i.v.). Animals were studied twice before Angll treatment commenced, twice during infusion and 48 h after stopping infusion. At each of these times the relationship between heart rate (HR) and mean arterial pressure (MAP) was determined under normoxic, acute hypoxic (10% O2+ 3% CO2) and acute hypercapnic (18% O2+ 6.5% CO2) conditions for 20 min. A group of six animals also served as time controls.3. Angiotensin II infusion increased arterial pressure from control levels of 80 ± 2 to 114 ± 8 mmHg and maintained it at this level throughout the 7 week period. After 1 week of Angll infusion there was a rightward shift in the heart rate‐baroreflex curve, indicating that the baroreflex was now operating at an increased level of pressure. These changes were associated with reductions in the gain from ‐7.6 ± 1.6 to—3.0 ± 0.2 b.p.m. /mmHg, HR range and curvature of the baroreflex. These effects were maintained throughout the 7 weeks of hypertension and were reversed within 2 days of ceasing Angll infusion. Acute hypoxia and hypercapnia in normotensive animals caused a reduction in the HR range of 19 ± 7 and 15 ± 7 b.p.m., respectively, but caused no change in the gain (sensitivity) of the baroreflex. Despite the marked changes in the baroreflex produced by the hypertension, the effect of hypoxia or hypercapnia on the HR baroreflex was not different in the hypertensive group.4. It is concluded that chronic experimental AngII‐based hypertension does not alter the HR baroreflex response to hypoxia or hypercapnia and suggests that the altered responses seen in other studies is due to a genetic predisposition as opposed to the effect of raised arterial pressure.
ANTI‐AGEING EFFECT OF AGED GARLIC EXTRACT IN THE INBRED BRAIN ATROPHY MOUSE MODEL
Authors: Moriguchi Toru , Saito Hiroshi , Nishiyama Nobuyoshi 
Published: June 2007

SUMMARY1. The effects of chronically administered aged garlic extract (AGE) on the age‐related changes in a novel strain of senescence accelerated mouse (SAM) characterized by age‐related brain atrophy (SAMP10) were investigated.2. A solid diet containing 2% (w/w) AGE was given to SAM from 2 months of age.3. The grading score of senescence in SAMP10 at 10 months of age was significantly higher than that of SAMR1, a reference strain for SAMP10.4. Administration of AGE prevented the increase in the grading score of SAMP10 and SAMR1.5. In behavioural evaluation, AGE improved learning and memory deficits of SAMP10 in both the passive and conditioned avoidance tests as well as the spatial memory test.6. Treatment with AGE in SAMP10 prevented the decrease in brain weight and the atrophic changes in frontal brain at 12 months of age.7. These results raise the possibility that AGE prevents physiological ageing and may be beneficial for age‐related cognitive disorders in humans.
PHYSIOLOGY OF AIRWAY NARROWING
Authors: Mitchell HW 
Published: June 2007

SUMMARY1. Responsiveness of the bronchial tree is measured at the mouth in vivo and represents narrowing responses of multiple airways in the lung. Responsiveness of individual bronchi has not been adequately investigated and the dynamic changes associated with airway narrowing are largely undefined.2. Responsiveness to cholinergic drugs was determined in bronchial segments in vitro, from lumen flow and narrowing, and from the force and shortening of the smooth muscle producing these responses.3. Maximum flow reduction was produced by submaximum smooth muscle force and shortening. In 2 mm inner diameter bronchi, flow was abolished by acetylcholine but the lumen was not physically closed. Flow sensitivity was increased more in small diameter bronchi than in large, but this was not associated with differences in force by smooth muscle. Smooth muscle contraction increased the thickness of the total airway wall via a tensioning and expansion of mural elastic fibres. Flow responses were more sensitive to drugs placed adventitially than luminally.4. Results define a major role for airway geometry and location, the epithelial barrier and the intercellular matrix, which couples the smooth muscle to the cartilaginous airway adventitia, in determining responsiveness of intact airways.
ROLE OF TACHYKININS IN BRONCHIAL HYPER‐RESPONSIVENESS
Authors: Reynolds Paul N. , Holmes Mark D. , Scicchitano Raffaele 
Published: June 2007

SUMMARY1. Sensory afferent fibres mediate important protective reflexes in the lung. Small, unmyelinated C‐fibre nerves have both sensory afferent and effector functions. C‐fibres contain a number of neuropeptides, including the tachykinins, which have proinflammatory effects in the airways. Following stimulation with capsaicin and other stimuli, neuropeptides are released from the nerve endings, either directly or by axonal reflexes.2. Important tachykinin effects include smooth muscle contraction, vasodilatation and oedema, mucus secretion and inflammatory cell activation. There are also trophic effects, including proliferation of fibroblasts, smooth muscle and epithelial cells.3. Tachykinins mediate their effects by binding to G‐protein‐linked receptors. Receptor‐specific agonists and antagonists are available, which have helped clarify the effects of tachykinins. These agents may have therapeutic potential.4. Tachykinins are degraded by the enzyme neutral endo‐peptidase.5. Studies in humans in vivo show an increase in airways resistance following challenge with tachykinins. There is some evidence for an increase in tachykinins and their receptors in airway inflammation, but this has not been found in all studies. A reduction in neutral endopeptidase has been seen in some animal models of airway inflammation, but this has not been shown in human disease.6. Trials of tachykinin receptor antagonists in human asthma have begun, but it is too early to say what their therapeutic impact will be.
USE OF GENE‐MANIPULATED MODELS TO STUDY THE PHYSIOLOGY OF LIPID TRANSPORT
Authors: Mortimer B‐C , Martins I. , Zeng BJ , Redgrave TG 
Published: June 2007

SUMMARY1. In vivo and in vitro gene‐manipulated models were used to study the metabolism of chylomicron remnants. Transgenic mice expressing human apolipoprotein (Apo) A1 or E4, gene knockout mice deficient in ApoE or low density lipoprotein (LDL) receptors and antisense gene inhibition in HepG2 cells were used to evaluate the effect of gene manipulations on the metabolism of chylomicron remnants.2. Mice transgenic for human ApoE4 showed accelerated clearance of chylomicron‐like emulsions when animals were fed a low‐fat diet. When challenged by a high‐fat diet, remnant clearance in ApoE4 transgenic mice was delayed, as in normal or non‐transgenic controls. However, unlike normal non‐transgenic controls, in ApoE4 transgenic mice high density lipoprotein (HDL)‐choIesterol levels remained high after high‐fat feeding, which probably protected the animals from the development of atherosclerosis.1 In contrast, clearance of chylomicron‐like lipid emulsions was not affected by the over‐expression of human ApoAI in transgenic mice.3. Gene knock‐out mice deficient in ApoE or deficient in the LDL receptor were used to show that ApoE and LDL receptors are both essential for the normal, fast catabolism of chylomicron remnants by the liver.2 In the absence of the LDL receptor, an alternative ApoE‐dependent pathway operates to clear chylomicrons from the plasma, with significantly delayed catabolism.4. Antisense gene inhibition techniques were used to suppress the expression of syndecan, a core protein of heparan sulfate proteoglycan, in HepG2 cells. Remnant uptake in cells transfected with the antisense oligodeoxynucleotide complementary to a 20 nucleotide sequence upstream of the initiation site of syndecan cDNA markedly reduced the uptake of chylomicron remnant.
UPDATE: MICROCOMPUTER STATISTICS PACKAGES. A PERSONAL VIEW
Authors: Ludbrook John 
Published: June 2007

SUMMARY1. There have been a number of recent commercial developments and new versions of microcomputer statistical software packages since the last review in December 1995.2. New versions for Windows have been released: SPSS 7.0 (Windows 95), SYSTAT 6.0 (Windows 3.11, 95, NT) and MINITAB 11.0 (Windows 3.11, 95, NT).3. The minimum requirements of microcomputer hardware to run the statistical packages under Windows now include 486 or Pentium processors and 16 Mb of RAM.4. It is now clear to the reviewer that no package that operates under Windows can be recommended unless it is possible to execute analyses by commands as well as by menus.5. The Internet is an important medium for disseminating information about forthcoming new versions of statistical software packages and about flaws in recently released versions of such packages.
NEUROTROPHIC FACTORS ARE REQUIRED BY MATURE SYMPATHETIC NEURONS FOR SURVIVAL, TRANSMISSION AND CONNECTIVITY
Authors: Rush Robert A. , Chie Edward , Liu Dennis , Tafreshi Azita , Zettler Christian , Zhou Xin‐fu 
Published: June 2007

SUMMARY1. Two neuronal growth factors, nerve growth factor (NGF) and neurotrophin 3 (NT3), have been studied for their action on the developing and mature sympathetic nervous system.2. Antibodies to each factor have proved useful as reagents for the detection and quantification of NGF and NT3. They have also proved valuable in uncovering the functional roles of each factor by their ability to neutralize the endogenous molecules.3. Nerve growth factor acts on postnatal neurons to control neurotransmission, connectivity and survival. Like NGF, NT3 is synthesized by effector tissues and is retrogradely transported by post‐ganglionic neurons to prevent cell death. However, the two factors have been shown to have quite distinct functions in mature neurons, indicating the existence of different signalling pathways. This differential action extends to secondary influences on satellite glia.4. Pathological consequences result from excessive growth factor synthesis leading, in the hypertensive rat, to hyperinnerv‐ation and elevated blood pressure. Satellite glial cell synthesis of the factors and their receptors following peripheral nerve damage appears to be responsible for the establishment of inappropriate neuronal connections between sympathetic nerve terminals and sensory somata.5. It is concluded that these potent factors control, by both coincident and independent mechanisms, sympathetic neuronal function throughout the life of the animal.
DETERMINANTS OF THE KINETICS OF VERY LOW‐DENSITY LIPOPROTEIN APOLIPOPROTEIN B‐100 IN NON‐OBESE MEN
Authors: Watts GF , Riches FM , Kelly JM , Powell MA , Croft KD 
Published: June 2007

SUMMARY1. Apolipoprotein B‐100 (ApoB) is the principal structural and functional protein of the pro‐atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low‐density lipoprotein (VLDL) in healthy men.2. We studied 17 non‐obese men who were consuming an ad libitum diet and had the following characteristics: mean (± SD) age 45.5 ± 9.7 years, body mass index (BMI) 25.1 ± 1.4 kg/m2, waist: hip ratio 0.91 ± 0.04, serum cholesterol 5.2 ± 0.6 mmol/L, triglycerides 1.08 ± 0.53 mmol/L and high‐density lipoprotein‐cholesterol 1.24 ± 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 ± 26 g, carbohydrate 238 ± 67 g, protein 103 ± 33 g and alcohol 20 ± 16 g.3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of l‐[13C]‐leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chroma‐tography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (± SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 ± 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 ± 5.6 pools/day. The ASR was significantly correlated with the waist: hip ratio (r= 0.60; P= 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r =—0.53; P= 0.03) and alcohol intake (r = ‐0.48; P= 0.05).4. In conclusion, the hepatic secretion of VLDL ApoB in non‐obese, healthy men is primarily determined by the waist: hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply to the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.
ACTIONS OF NITRIC OXIDE ON RENAL EPITHELIAL TRANSPORT
Authors: Stoos BA , Garvin JL 
Published: June 2007

SUMMARY1. In vivo studies have demonstrated that nitric oxide (NO) induces natriuresis. Nitric oxide‐induced natriuresis occurs independently of changes in renal perfusion pressure, indicating that it is the result of a tubular effect of NO.2. In support of this hypothesis investigators have shown that NO inhibits both Na+‐H+ exchange and Na+/K+‐ATPase activity in the proximal tubule. In the collecting duct, NO has been shown to decrease sodium flux with no effect on Na+/K+‐ATPase activity.3. Thus, direct examination of the actions of NO have shown that NO can inhibit sodium transport in the nephron, which may account for the natriuresis observed in vivo.
PROTEIN KINASE C AND TRANSMITTER RELEASE
Authors: Majewski H. , Kotsonis P. , Iannazzo L. , Murphy TV , Musgrave IF 
Published: June 2007

SUMMARY1. Protein kinase C (PKC) is an important second messenger‐activated enzyme. In noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG) to facilitate transmitter release and the steps in this involve activation of phospholipase C, generation of DAG and activation of PKC. It is suggested that the subsequent facilitation of transmitter release is due to the phosphorylation of proteins involved in the release process distal to Ca2+entry, presumably those involved in vesicle dynamics.2. There are differences between central noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to be tonically active and its inhibition results in a decrease in noradrenaline release under most, if not all, conditions.3. In sympathetic nerves PKC inhibitors only decrease transmitter release during high‐frequency stimulation and not during low‐frequency stimulation. At high frequency there is a gradual increase in the effect of PKC inhibitors on transmitter release during the first 15 s of a stimulation train. It is suggested that this is due to a progressive rise in intracellular Ca2+ and a consequent activation of PKC.4. Activation of PKC by phorbol esters produces a large enhancement in action potential‐evoked noradrenaline release in both the central nervous system and in peripheral tissues. The structural requirements of the phorbol esters for maximal effect suggest that the phorbol esters must access the interior of the nerve terminal to activate PKC and the neural membrane acts as a barrier for highly lipophilic phorbol esters, thereby reducing their activity. Activation of PKC represents one of the most powerful ways to enhance transmitter release and may have therapeutic potential.
PRETREATMENT WITH THE DOPAMINE AGONIST QUINPIROLE INHIBITS CENTRAL ANTIHYPERTENSIVE MECHANISMS IN RATS*
Authors: van den Buuse M. , THtton SB 
Published: June 2007

SUMMARY1. Intravenous or central treatment of spontaneously hypertensive rats (SHR) with the dopamine D2 receptor agonist quinpirole caused a short‐lasting pressor response with little effect on heart rate.2. At 30 min after intravenous administration of quinpirole, the antihypertensive effect of rilmenidine was significantly inhibited. This interaction of quinpirole and rilmenidine was similarly observed when quinpirole was administered either intravenously (0.3 or 0.1 mg/kg), in the lateral cerebral ventricles (0.1 mg/kg) or intracisternally (0.1 mg/kg) or when rilmenidine was administered intravenously (1 mg/kg) or intracisternally (0.1 mg/kg).3. The apparent desensitization to the antihypertensive effect of rilmenidine 30 min after pretreatment with quinpirole was not observed after a 4 or 24 h interval.4. These data suggest that quinpirole has prolonged effects on central sympathetic vasomotor mechanisms that are the target of centrally acting antihypertensive drugs. These and previous results show a functional interaction between central dopamine D2 receptor activation and sympathetic responses mediated by a wide range of different receptors, including imidazoline and 5‐hydroxytryptamine 5‐HT1A‐receptors and (α‐adrenoceptors.
FAULTY INDUCTION OF BLOOD‐BRAIN BARRIER FUNCTIONS BY ASTROCYTES ISOLATED FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Yamagata Kazuo , Tagami Motoki , Nara Yasuo , Fujino Hideaki , Kubota Akiyoshi , Numano Fujio , Kato§ Taiji , Yamori Yukio 
Published: June 2007

SUMMARY1. It has been suggested that astrocytes prompt the induction of blood‐brain barrier (BBB) functions in cerebrovascular endothelial cells.2. In the present study we have tried to elucidate the genetic differences between astrocytes isolated from Wistar‐Kyoto (WKY) control rats and astrocytes isolated from stroke‐prone spontaneously hypertensive rats (SHRSP).3. We show that endothelial cells develop tight junction‐like structures, a reduction in vesicular transport and high electrical resistance when they are co‐cultured with astrocytes isolated from WKY rats. In contrast, SHRSP astrocytes have less of an ability to induce BBB functions than do WKY astrocytes.4. In addition, we demonstrate that SHRSP astrocytes produce enormous quantities of lactic acid when cerebral ischaemia develops. The decrease in pH causes astrocyte swelling and damages BBB functions.5. Consequently, we reason that genetically weak functions in astrocytes cause disruptions of BBB function and result in widespread cerebral lesions in SHRSP.
EFFECTS OF ACIDOSIS OR ALKALOSIS ON THE ACTIONS OF NIFEDIPINE ON EXCITATION‐CONTRACTION COUPLING IN THE RAT TAIL ARTERY
Authors: Achike Francis I. , Mohamad Rohaini , Dai Soter , Ogle Clive W. 
Published: June 2007

SUMMARY1. The clinical success of calcium channel blockers in the management of organ ischaemia is less than theoretically anticipated. Blood gas/pH changes are associated with organ ischaemia; therefore, we studied the possibility that pH changes could alter the pharmacological effects of the calcium channel blocker nifedipine on rat tail artery contracted by either noradrenaline (NA) or potassium.2. Segments (2‐2.5 cm) of the proximal third of the male Sprague‐Dawley rat tail ventral artery were initially bathed and perfused with a physiological salt solution (PSS; pH 7.48) for 25‐30 min, after which time bathing/perfusion was continued with a nominally calcium‐free PSS made acidotic (pH7.20), alkalotic (pH 7.67) or unaltered (control). After equilibration, the perfusion pressure (PP) responses to increasing concentrations of calcium in the presence of NA (3.0 μmoI/L) or potassium (100 mmol/L) with nifedipine or its vehicle were recorded.3. The calcium sensitivity of potassium‐ or NA‐stimulated rat tail arteries was reduced during acidosis, as was the maximum PPin potassium‐ but not NA‐stimulated tissues. Alkalosis reduced the calcium sensitivity in potassium‐ but not NA‐stimulated contraction and had no effect on maximum PP.4. The inhibitory effect of nifedipine (0.6 mUmol/L) on contraction was enhanced during acidosis in either NA‐ or potassium‐stimulated arteries and also during alkalosis in NA‐treated arteries, although it had little effect during normal conditions.5. The results indicate that changes in pH alter the vascular contractility profile in a manner dependent on the excitation‐contraction coupling mode. The calcium antagonistic effect of nifedipine is pH dependent and it is suggested that pH changes associated with ischaemic conditions may alter the therapeutic profile of nifedipine.