bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects Of Prostaglandins On Baroreflex During Reperfusion Of The Ischaemic Myocardium
Authors: Wang You‐Ping , Xu Hui , Mizoguchi Kazuhiro , Tsuruhara Yoshikazu , Oe Masahiro , Maeta Hajime 
Published: March 2003

SUMMARY1. The present study was planned to: (i) determine whether the baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) was attenuated during reperfusion of short‐term ischaemic myocardium; and (ii) study whether blockade of prostaglandin synthesis with indomethacin reversed the inhibitory baroreflex.2. Arterial pressure was lowered with intravenous sodium nitroprusside before coronary occlusion and 3 min after release of a 5 min occlusion of the left circumflex coronary artery in anaesthetized rabbits. The protocol was repeated 20 min after indomethacin (5 mg/kg, i.v.) or indomethacin vehicle (50 mmol/L tris(hydroxymethyl)aminomethane buffer, pH 8.4) treatment. In addition, this study was performed in a group of vagotomized rabbits.3. Before indomethacin treatment, the slope of the mean arterial pressure (MAP)–RSNA relationship decreased from –3.3±0.77 to –2.01±0.69% change in RSNA/mmHg (P < 0.05) during reperfusion of ischaemic myocardium in intact rabbits. The decrease in the slope was reversed by administration of indomethacin. However, the decrease in the slope was not reversed by indomethacin vehicle. Furthermore, the reduction in the slope of the MAP–RSNA relationship during reperfusion of ischaemic myocardium was abolished in vagotomized rabbits. However, there was no inhibition of the slope of the MAP–HR relationship during reperfusion of ischaemic myocardium in either intact or vagotomized rabbits.4. In conclusion, our data suggest that prostaglandins released by ischaemic myocardium can attenuate the baroreflex‐mediated response of RSNA to lowered arterial pressure via vagal afferents during reperfusion of short‐term ischaemic myocardium.
Islet Amyloid Polypeptide (Amylin) Modulates Chylomicron Metabolism In Rats
Authors: Smith D , Mamo Jcl 
Published: March 2003

SUMMARY1. Amylin is a pancreatic peptide that has been shown to be able to induce a state of peripheral insulin resistance. Hyperamylinaemia, which occurs in type 2 diabetes, may be central to a number of metabolic abnormalities present in the diabetic state. Because lipoprotein metabolism is often disturbed in diabetes, we investigated whether amylin was a regulating factor of lipoprotein metabolism in rats; specifically, whether exogenous amylin influences production and clearance of triglyceride (TG)‐rich lipoproteins.2. When amylin was given acutely to rats or by way of infusion, total plasma TG was significantly elevated. Acute doses of amylin decreased fractional clearance rates of TG‐rich lipoproteins by 45%. Hydrolysis of lipoproteins by endothelial lipases was not decreased; rather, amylin appeared to reduce hepatic uptake of TG‐rich lipoproteins, following conversion to the remnant form. Consistent with the kinetic data in vivo, cell culture studies found that amylin reduced the high‐affinity uptake of remnant lipoproteins, probably by inhibiting low‐density lipoprotein receptor expression.3. We have found that amylin can influence the kinetics of TG‐rich lipoproteins in vivo and in vitro. Amylin can reduce chylomicron uptake, most probably by regulating lipoprotein receptors either directly, or via modulation of insulin activity. Increased levels of amylin in type 2 diabetes may contribute to the raised concentration of TG‐rich remnant lipoproteins present in this disease.
Pain Control by Immune‐Derived Opioids
Authors: Machelska H , Stein C 
Published: March 2003

SUMMARY1. The nervous and immune systems communicate with each other by use of cytokines and neuropeptides.2. Interactions between immune cell‐derived opioid peptides and opioid receptors located in peripheral inflamed tissue lead to endogenous analgesia.3. In addition to their immunological functions, immunocytes are involved in intrinsic pain inhibition. This provides new insights into pain associated with a compromised immune system, as in AIDS or in cancer.4. The activation of opioid production and release from immune cells may be a novel approach to the development of peripherally acting analgesics. Because such drugs would be targeted towards events in peripheral injured tissue, these analgesics should lack unwanted central side effects typically associated with opioids.
Biopharmaceutical Considerations In Topical Ocular Drug Delivery
Authors: Davies Nigel M 
Published: March 2003

SUMMARY1. Despite the accessibility of the front of the eye, efficient delivery of drug to treat various ocular disorders is a challenge to the formulation scientist. The majority of ophthalmic medications are formulated as eye drops. Due to anatomical constraints, the volume that can be administered is limited to approximately 30 μL. This, together with the efficient clearance system that exists in the front of the eye, makes it difficult to maintain an effective pre‐ocular drug concentration for a desired length of time. Various formulation strategies have been used to increase pre‐ocular retention of eye drops. The most successful of these has been the inclusion of viscosity enhancing polymers, particularly those able to interact with the mucous layer on the eye surface or those that can undergo a transition from a solution to a gel under the conditions of the pre‐ocular area.2. When the target site is intra‐ocular, drug must be absorbed from the pre‐ocular region into the eye. The main route for absorption is across the cornea. However, absorption of drug across the cornea is inefficient due to its impermeable nature and small surface area. Thus, the intra‐ocular bioavailability of topically administered medications is typically less than 10%.3. Corneal permeability favours moderately lipophilic compounds. These compounds often have a low aqueous solubility. Problems in ocular drug delivery and formulation are compounded for poorly soluble drugs that must be formulated as suspensions.4. Reformulation of ophthalmic suspensions as solutions has many advantages. This may be achieved by complexation using cyclodextrins. Solubilization using cyclodextrins can overcome many of the formulation problems. However, it is unclear as to their potential for improving ocular bioavailability, which is seemingly drug dependent and may be influenced by both the physicochemical properties of the drug and the complex formed.
Role Of Neurotrophin Receptor p75NTR In Mediating Neuronal Cell Death Following Injury
Authors: Coulson Ej , Reid K , Murray Ss , Cheema Ss , Bartlett Pf 
Published: March 2003

SUMMARY1. The neurotrophin receptor p75NTR has been shown to mediate neuronal cell death after nerve injury.2. Down‐regulation of p75NTR by antisense oligonucleotides is able to inhibit both sensory and motor neuron death and this treatment is more effective than treatment with growth factors.3. p75NTR induces cell death by a unique death signalling pathway involving transcription factors (nuclear factor κB and c‐jun), Bcl‐2 family members and caspases.
Spinal Repair In Immature Animals: A Novel Approach Using The South American Opossum Monodelphis Domestica
Authors: Fry Ej , Saunders Nr 
Published: March 2003

SUMMARY1. The adult mammalian central nervous system (CNS) is unable to regenerate following injury and repair has only been seen when implants of peripheral nervous tissue, fetal tissue or Schwann cells are used, or antibodies or trophic molecules applied. However, the immature mammalian CNS has revealed a capacity to repair without extrinsic influence.2. The marsupial mammal provides a unique opportunity to access the immature CNS without invasive in utero surgery. In particular, the South American opossum Monodelphis domestica is an ideal animal for spinal cord injury studies examining the ability of the immature CNS to repair after injury.3. The Monodelphis spinal cord may be examined for its response to injury either as an in vitro or in vivo system and, therefore, is a flexible model, allowing many different questions to be addressed by the most suitable approach.4. The immature Monodelphis CNS was able to support fibre growth that reappeared 4 days after a crush at P3‐P8 in vitro. Conduction was also restored at this time, accompanied by synaptic connections.5. A cut lesion performed in vivo on Monodelphis spinal cords at P7 took longer to repair, with fibres reappearing across the injury site 2 weeks after the lesion; greater disruption to structure was noted both during early stages of repair and in adulthood.6. Neural pathway tracing with dextran amine from the lumbar cord to the brain in adult Monodelphis, which received spinal lesions at P7, revealed a similar distribution of labelled cells in brainstem and mid‐brain nuclei to that of control animals.7. Studies of the locomotor behaviour of adult Monodelphis that had received either a cut or crush lesion at P7‐P8 showed remarkably similar abilities to control animals when performing complex tasks.8. The results of spinal cord injury studies with the immature Monodelphis CNS may help in the development of treatments for spinal injury patients.
Type‐C Natriuretic Peptide Prevents Development Of Experimental Atherosclerosis In Rabbits
Authors: Gaspari Tracey A , Barber Melissa N , Woods Robyn L , Dusting Gregory J 
Published: March 2003

SUMMARY1. We investigated the effect of local administration of type‐C natriuretic peptide (CNP) on the endothelial dysfunction and development of an atheroma‐like neointima induced by a peri‐arterial collar in rabbits.2. Peri‐arterial collars were placed on both common carotid arteries allowing local treatment of the collared region with either CNP (10 μmol/L) or saline. After 7 days, uncollared (control) and collared sections were taken from both arteries for pharmacological and morphological analysis.3. Application of the collar markedly attenuated (P < 0.05) endothelium‐dependent vasorelaxation induced by acetylcholine (ACh); inhibition of 5‐hydroxytryptamine contraction was 80±5% in control sections compared with 44±4% in collared sections from the same arteries. Local infusion of CNP (10 μmol/L) into the collar restored ACh‐induced vasorelaxation (74±3% from collared arteries + CNP vs 77±2% from control sections from the same arteries).4. Type‐C natriuretic peptide treatment also reduced (P < 0.05) intimal thickening compared with contralateral collared arteries (intima/media ratio 0.06±0.01 vs 0.16±0.01).5. These results provide evidence that locally administered CNP is effective in preventing the endothelial dysfunction and development of a neointima in this model.
Assessment Of Gastric Emptying In The Mouse Using The [13C]‐Octanoic Acid Breath Test
Authors: Symonds Erin L , Butler Ross N , Omari Taher I 
Published: March 2003

SUMMARY1. Gastric emptying studies in small laboratory animals are hampered by the deficiency of a technique that is non‐invasive and repeatable. The aim of the present study was to adapt the non‐invasive [13C]‐octanoic acid breath test, which has been validated in humans, to assess both liquid and solid gastric emptying in the mouse.2. Gastric emptying rates were investigated for a liquid meal (Intralipid®; Kabi Pharmacia AB, Stockholm, Sweden; n = 7) and two solid meals (egg yolk and mouse chow; n = 7) incorporating [13C]‐octanoic acid. All meals were analysed for natural enrichment of [13C]. Mathematical analysis of the 13CO2 excretion rate allowed the determination of gastric emptying parameters.3. Gastric emptying of Intralipid® was more rapid than egg yolk (P < 0.0001). Gastric emptying of mouse chow could not be assessed due to intragastric separation of [13C]‐octanoic acid and natural [13C] enrichment of the pellet.4. The [13C]‐octanoic acid breath test can reproducibly assess both liquid and solid gastric emptying non‐invasively in the mouse. This method can now be used to assess gastric emptying in drug studies and disease studies for which there are established mouse models.
Metabolic Variability Among Disease‐Resistant Inbred Rat Strains And In Comparison With Wild Rats (Rattus Norvegicus)
Authors: Brandt Jens van den , Kovács Peter , Klöting Ingrid 
Published: March 2003

SUMMARY1. Inbreeding and optimization of environmental conditions for laboratory rats may have led to the survival of mutants with metabolic aberrations but without evident disease phenotype. Therefore, in the present study, we compared metabolic traits between so‐called disease‐resistant inbred rat strains Dark Agouti (DA), Brown Norway (BN), Lewis (LEW), Wistar‐Kyoto (WKY), Fischer 344 (F344) and wild rats (Rattus norvegicus).2. Twelve males of each strain at 12, 13 and 14 weeks of age were studied for bodyweight, body mass index (BMI), blood glucose, serum triglycerides, total cholesterol, insulin and leptin.3. In comparison with wild rats, the cholesterol values were significantly increased in all inbred rats studied. Except for DA rats, all rats were also significantly heavier than wild rats.4. There were also significant differences between the different disease‐resistant strains and WKY rats were the biggest animals with the highest bodyweight, BMI and cholesterol values.5. The strains could be separated into groups with either very high (F344, LEW, WKY) or low values (DA, BN) of serum insulin and leptin levels.6. Because all rats were studied under the same conditions, the findings suggest a substantial strain dependence in feeding behaviour and energy balance caused by the different genotypes.
The Microvasculature As A Dynamic Regulator Of Volume And Solute Exchange
Authors: Huxley Vh , Rumbaut Re 
Published: March 2003

SUMMARY1. It has long been held that the microvessels are passive pipes through which the formed elements of blood and plasma course and from which exchange occurs. Physiological and structural data from vascular cells in culture to whole organs strongly support the notion that microvessels, whether in their arrangement as networks, in their microvascular phenotypic subtypes or with regard to their permeability properties, are anything but static.2. Examples from different models, organs and species are presented to illustrate the spatial and dynamic nature of the microvasculature.3. Given that the ultimate goal of this cardiovascular research is to apply what is learned from component parts of the microvasculature to understand integrated tissue function, examples of the danger of generalizing results from limited studies are presented.4. Finally, accurate interpretation of most of the research in this area is predicated on the assumption that probe molecules, rendered visible by the binding of dyes, are biologically inert.5. We present data demonstrating that some dyes used widely in microvascular studies can alter the barrier under study and/or alter the physicochemical characteristics of the molecule to which they were bound.
Vasopressin V1A Receptor Antagonism Does Not Reverse Adrenocorticotrophin‐Induced Hypertension In The Rat
Authors: Fraser Tafline B , Turner Steven W , Wen Cheng , Li Ming , Burrell Louise M , Whitworth Judith A 
Published: March 2003

SUMMARY1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)‐induced hypertension in Sprague‐Dawley rats using the non‐peptide AVP V1a receptor antagonist OPC 21268.2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality and electrolyte concentrations were measured after OPC 21268 gavage. In a chronic study, 40 rats were randomly divided into four groups: (i) sham injection + sham gavage; (ii) ACTH + sham gavage; (iii) sham injection + OPC 21268; or (iv) ACTH + OPC‐21268 for 16 days. Systolic blood pressure (SBP), water intake, urine volume (UV), urine osmolality and electrolytes, food intake, bodyweight and plasma osmolality and electrolyte concentrations were measured.3. In the acute study, direct mean arterial blood pressure did not change with OPC 21268 (122±2 and 120±3 mmHg at 0 and 240 min, respectively).4. In the chronic study, OPC 21268 did not affect ACTH‐induced rises in blood pressure (from 125±2 (control) to 145±5 mmHg (group 4) compared with 122±3 (control) to 149±5 mmHg (group2)). Water intake and UV increased (from 29±2 to 83±6 mL/day; and from 5±1 to 36±5 mL/day, respectively) and the change in bodyweight decreased from 0±2 to –107±7 g.5. These results suggest that AVP (at the V1a receptor) does not play a significant role in the maintenance of ACTH‐induced hypertension.
Decreased Left Ventricular Contractility Reserve In Patients With Never‐Treated Essential Hypertension
Authors: Tanaka Mamoru , Hashimoto Yuji , Numano Fujio 
Published: March 2003

SUMMARY1. Left ventricular diastolic dysfunction is often present in patients with essential hypertension. To determine whether left ventricular systolic function is normal or subnormal, we evaluated the global left ventricular contractile reserve in patients with untreated essential hypertension.2. Thirty‐one untreated men with essential hypertension and 12 normotensive healthy men were evaluated. Hypertensives were divided into two groups based on the presence (group Hc; n = 21) or absence (group Hn; n = 10) of concentric left ventricular geometric remodelling, which was defined as a relative wall thickness ≥ 0.45 on M‐mode echocardiography. We compared echocardiographic data of left ventricular function in hypertensive men with those in healthy men under β‐adrenoreceptor activation by up to 10 μg/kg per min dobutamine infusion.3. At baseline, endocardial (eFS) and midwall fractional shortening of the left ventricle, the early peak filling velocity (E), the peak late filling velocity (A) and the ratio E/A were similar in the three groups. During dobutamine infusion, eFS was significantly lower in groups Hc and Hn (54.1±9.2 and 54.1±7.9%, respectively) than that observed in group N (61.7±7.4%). In addition, eFS was highly correlated with circumferential end‐systolic wall stress (ESS) during dobutamine infusion in the three groups. In 11 subjects in group Hc (52%), the eFS‐ESS relationship was lower than the 95% confidence limit of the normal regression. Comparing group Hc with groups N and Hn, it was found that E (0.52±0.12, 0.71±0.16 and 0.63±0.15 m/s, respectively) and E/A (0.74±0.23, 1.24±0.53 and 0.98±0.37, respectively) were significantly lower.4. Our results suggest that, in addition to diastolic dysfunction, the reserve of systolic function decreased under β‐adrenoceptor activation in patients with essential hypertension.
Changes In Absorptive Function Of Rat Intestine Injured By Methotrexate
Authors: Naruhashi Kazumasa , Nadai Masayuki , Nakao Makoto , Suzuki Nagao , Nabeshima Toshitaka , Hasegawa Takaaki 
Published: March 2003

SUMMARY1. Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine. The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino‐β‐lactam antibiotic cephalexin (CEX). Time‐dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg).2. Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration–time curve of CEX (AUCCEX) following oral administration of 20 mg/kg tended to decrease. Thereafter, the AUCCEX increased significantly and the histopathological changes diminished within 5 days.3. Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day. Methotrexate‐induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUCCEX, but did not correlate with mucosal DAO and ALP activity.4. These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX. In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.
Polymorphisms Of The Renin Gene Promoter In Spontaneously Hypertensive And Wistar‐Kyoto Rats
Authors: Leckie Brenda J 
Published: March 2003

SUMMARY1. In the present study, 1.39 kb of the renin gene 5′region in spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats was amplified by polymerase chain reaction from genomic DNA and sequenced. Consistent differences in the renin gene sequence of SHR and WKY rats were found at positions –725, –727, –979 and –1126/–1129 as numbered from the transcription start site (+1). No polymorphism was specific to hypertensive rats.2. Gel‐shift assays were performed using labelled SHR renin promotor DNA and nuclear proteins extracted from rat kidneys. The regions between –1122 and –1139 and between –701 and –797 showed protein binding.
Experimental Biology 2000 Symposium on Differential Control of Sympathetic Outflow MULTIPLE OSCILLATORS, DYNAMIC SYNCHRONIZATION AND SYMPATHETIC CONTROL
Authors: Gilbey Michael P 
Published: March 2003

SUMMARY1. Intermittent bursts of activity are a robust feature of the discharges of sympathetic nerves. There are at least two major mechanisms producing such discharges: (i) phasic inputs influencing sympathetic circuits; and (ii) oscillators embedded within sympathetic networks. The functional significance of patterned and synchronized activity underlying bursts of population activity may reside in their influence on information transfer between excitable cells. At the level of the single neuron, firing pattern appears to be an important determinant of synaptic/neuroeffector function (e.g. the probability of transmitter release, the types of transmitter released, the types of receptor activated and plasticity). Synchronization of inputs at a target favours summation and, therefore, may influence response (short term and long term).2. In the present paper, I review the work from my laboratory that has focused on furthering understanding of the potential functional importance of pattern and synchrony coding in sympathetic nervous control of cardiovascular function. Because the rat tail artery has been used extensively as a model for studying neuroeffector transmission, in our investigations we have recorded from its sympathetic innervation.3. In the anaesthetized preparation, under steady state conditions, we have established that the discharges of these sympathetic neurons have a distinct rhythm (frequency approximately 0.8 Hz). This can be detected both at single neuron and population levels.4. A family of oscillators appears to control their discharge such that under some conditions all neurons do not have the same frequency of rhythmical activity. However, these weakly coupled or uncoupled oscillators can be synchronized dynamically by various inputs, such as central respiratory drive, lung inflation cycle‐related inputs and inputs arising from visceral and somatic afferents.5. The potential functional significance of dynamic synchronization of sympathetic oscillators in relation to sympathetic pattern generation and neuroeffector transmission is discussed.