bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of and risk factors for erectile dysfunction in Hong Kong diabetic patients
Authors: Siu S. C. , Lo S. K. , Wong K. W. , Ip K. M. , Wong Y. S.
Published: March 2003

Aim  To estimate the prevalence of erectile dysfunction (ED) in Chinese diabetic men and to identify its risk factors, we carried out a cross‐sectional survey of 500 Chinese diabetic men attending a community hospital diabetic clinic in Hong Kong.

Methods  Patients were interviewed and asked to report on their experience of ED as defined in the National Institutes of Health Consensus Conference 1993. Diabetic complications and patient clinical data were obtained from patients' medical records.

Results  Of the 486 patients studied, the prevalence of ED was 63.6% (95% confidence interval 59.3–67.9%). The prevalence of ED increased with age, from 33.3% to 73.8% for diabetic men aged between 21 and 80 years (P = 0.001). Severity of ED also increased with age. Among diabetic men with ED, there was no report of complete ED for diabetic men aged 40 years and below, whereas the proportion of patients with complete ED increased from 7.4% to 71.1% between the ages of 41 and 80 years. ED occurred early in the course of the disease, with a prevalence increasing from 56.0% in men with diabetes mellitus (DM) for < 5 years to 72.0% in those with DM for > 20 years (P = 0.038). Duration of DM was also associated with severity; the proportion of patients with complete ED increased from 30.8% for those with DM for < 5 years to 72.2% for those with DM for ≥ 20 years (P < 0.001). Using logistic regression analysis, DM duration, diabetic complications including retinopathy, abnormal albuminuria and sensory neuropathy, and higher level of education were associated with a higher risk of ED. By polychotomous logistic regression, age was the only factor found to be associated with the severity of ED, after adjusting for other variables.

Conclusions  Chinese diabetic patients have a prevalence of self‐reported ED that appears to be higher than that of Western populations. This may be due to cultural differences and the association of abnormal albuminuria and hypertension.

Diabet. Med. 18, 732–738 (2001)
Phase‐coupled oscillator models can predict hippocampal inhibitory synaptic connections
Authors: Skinner F. K. , Wu C. , Zhang L.
Published: March 2003

What factors are responsible for propagating electrical activity in the hippocampus? Using an intact, isolated hippocampus preparation, it is possible to observe spontaneous delta (≤ 4 Hz) waves of rhythmic field potentials. These rhythmic potentials are inhibitory in nature, mediated by GABAergic inhibitory potentials originating from a population of principal neurons. They start in the ventro‐temporal region and move longitudinally towards the dorso‐septal region with a phase lag of ≈ 10% between the extracellular recordings. We use the mathematical framework of phase‐coupled oscillators (PCO) to gain some insight into the underlying network system. A chain of 15 nearest‐neighbour bidirectionally coupled PCOs is used where each oscillator refers to a segment of the CA1 region of the hippocampus that can generate these slow field potentials. We find that ventro‐dorsal delta waves exist if there is a dominance in coupling strength in one direction. Without a one‐way coupling dominance, ventro‐dorsal waves can still exist, but then the coupling strengths need to be much larger. The relationship between entrained and intrinsic frequencies and the variation of propagation speeds along the longitudinal axis can be used to determine which case applies. Currently available experimental data supports one of the cases, predicting that there is a stronger ventral to dorsal inhibitory effect.
Forced swimming stimulates the expression of vasopressin and oxytocin in magnocellular neurons of the rat hypothalamic paraventricular nucleus
Authors: Wotjak Carsten T. , Naruo Tetsuro , Muraoka Shinichiro , Simchen Renate , Landgraf Rainer , Engelmann Mario
Published: March 2003

Previous studies have shown that a 10‐min forced swimming session triggers the release of both vasopressin and oxytocin into the extracellular fluid of the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) in rats. At the same time oxytocin, but not vasopressin, was released from the axon terminals into the blood. Here we combined forced swimming with in situ hybridization to investigate whether (i) the stressor‐induced release of vasopressin and oxytocin within the PVN originates from parvo‐ or magnocellular neurons of the nucleus, and (ii) central release with or without concomitant peripheral secretion is followed by changes in the synthesis of vasopressin and/or oxytocin. Adult male Wistar rats were killed 2, 4 or 8 h after a 10‐min forced swimming session and their brains processed for in situ hybridization using 35S‐labelled oligonucleotide probes. As measured on photo‐emulsion‐coated slides, cellular vasopressin mRNA concentration increased in magnocellular PVN neurons 2 and 4 h after swimming (P < 0.05). Similarly, oxytocin mRNA concentration was significantly increased in magnocellular neurons of the PVN at 2 and 8 h (P < 0.05). We failed to observe significant effects on vasopressin and oxytocin mRNA levels in the parvocellular PVN and in the SON. Taken together with results from previous studies, our data suggest that magnocellular neurons are the predominant source of vasopressin and oxytocin released within PVN in response to forced swimming. Furthermore, in the case of vasopressin, central release in the absence of peripheral secretion is followed by increased mRNA levels, implying a refill of depleted somato‐dendritic vasopressin stores. Within the SON, however, mRNA levels are poor indicators of the secretory activity of magnocellular neurons during stress.
High levels of oestrogen receptor‐α in tumorigenesis: inhibition of cell growth and angiogenic factors
Authors: Ali S. H. , O'Donnell A. L. , Balu D. , Pohl M. B. , Seyler M. J. , Mohamed S. , Mousa S. , Dandona P.
Published: March 2003

We previously found that the stable overexpression of oestrogen receptor‐α in the human endothelial cell line ECV304* inhibits its growth in vitro, and that this inhibition is possibly mediated through a down‐regulation of the vasoactive agents endothelin‐1 and vascular endothelial growth factor. Here we show an in vivo growth‐inhibitory effect of oestrogen receptor‐α overexpression in tumours initiated in nude mice from the same clone of ECV304. In addition, we show that this growth inhibition is accompanied by an αvβ3‐mediated inhibition of cell migration in vitro, and a down‐regulation of the integrin αvβ3, vascular endothelial growth factor and vascularization in vivo. The levels of vascular endothelial growth factor and integrin αvβ3, through their effect on cell growth and migration, contribute to the process of angiogenesis and to the pathogenesis of atherosclerosis and cancer. The results shown here demonstrate that a higher level of oestrogen receptor‐α in the cell, through its effect on certain angiogenic factors, may play a role in the control of angiogenesis.
Pathophysiology of acute pain: Implications for clinical management
Authors: Jones James B
Published: March 2003

To effectively treat acute pain, emergency medicine practitioners must have a thorough understanding of both the pathophysiology and terminology of the pain experience. The pathophysiology of pain is discussed with an emphasis on the mechanisms of acute, inflammatory pain. The various types of pain receptors, pathways and neurotransmitters are also discussed. See Commentary, page 271.
Gene dropping analysis of founder contributions in a closed Japanese black cattle population
Authors: HONDA Takeshi , NOMURA Tetsuro , FUKUSHIMA Moriyuki , MUKAI Fumio
Published: March 2003

Gene dropping simulation was applied to Japanese Black cattle population in Hyogo prefecture, to examine the survivals of alleles originated from founder animals. In the analysis, unique alleles were assigned to founders, and the genotypes of all descendants along the actual pedigree were generated through Monte Carlo simulation following Mendelian segregation rules. By replicating this process 10 000 times, the distribution of frequencies of alleles from each founder was estimated. From the distribution, several quantities useful for the management of genetic diversity, such as the probability of allele extinction and the probability of alleles surviving at a critically low frequency were derived. The materials used were 68 781 animals born in 1955–1998 and their pedigree records traced back to the population in 1937 or before. The expected number of alleles retained in the population drastically decreased during the analyzed period, and reached to 57.9 in the population of 1998, which was only 3.3% of the total number of alleles assigned to founders. Detailed analysis of major founders with relatively high genetic contributions to the current population revealed that alleles from most of the major founders are now at high risk of future extinction. These results strongly suggest that for the management of genetic diversity, the genetic contributions of founders are not fully informative, and emphasize the importance of the detection of live animals having founder alleles with high extinction possibilities.
Evaluation of transgenic event CBH 351 (StarLink) corn in broiler chicks
Authors: YONEMOCHI Chisato , FUJISAKI Hirokazu , HARADA Chisato , KUSAMA Toyoko , HANAZUMI Michito
Published: March 2003

The influence of transgenic event CBH 351 (StarLink; SL)‐derived hybrid corn on the growth performance, health condition and physiological function in broiler chicks, as well as the possible transfer of the cry9C gene and Cry9C protein to blood, liver and muscle were examined in comparison with chicks fed on a diet with non‐transgenic corn (SL‐F). Bodyweight gain and feed conversion ratio in the chicks fed on a diet with SL were significantly greater than in chicks fed on a diet with SL‐F during the starter phase (0–3 weeks of age), but this significant difference disappeared during the finisher phase (4–7 weeks of age). No abnormalities in health condition in either SL or SL‐F groups were observed, and livability did not differ significantly between SL and SL‐F groups. Moreover, no significant differences in serum biochemical and hematological values, histopathological observation and necropsy findings were observed between SL and SL‐F groups at the end of the experiment. The cry9C gene and Cry9C protein were not detected in blood, liver and muscle of chicks at 3, 5 or 7 weeks of age. The results indicate that feeding SL does not influence growth performance, health condition or physiological function in broiler chicks, and the cry9C gene and Cry9C protein are not transferred to the blood, liver and muscles of broilers.
Breeding distribution and maternal genetic lineages in Lulu, a dwarf cattle population in Nepal
Authors: FUJISE Hiroshi , MURAKAMI Masaru , DEVKOTA Bhuminand , DHAKAL Ishwori Prasad , TAKEDA Kumiko , HANADA Hirofumi , FUJITANI Hideo , SASAKI Masao , KOBAYASHI Kosaku
Published: March 2003

Lulu is a dwarf cattle population bred in the Mustang district of western and central Nepal. This area is located around the habitat boundary between Bos taurus and Bos indicus. The peculiarities of Lulu are their small size (weight range in the adult female: 68–153 kg) and rearing in high mountain areas at 2800 m to 4000 m in altitude. There were 5770 head of Lulu cattle in the Mustang district in 1998, 4333 females and 1437 males. The morphological appearance of Lulu is Bos taurus. However, one of the five Lulu studied in Kagbeni, Mustang had a Bos indicus mitochondrial DNA type based on the D‐loop sequence, while the other four were Bos taurus. It is suggested that there are hybrids of Lulu with Bos indicus maternal lineage in a mostly taurine‐breed genetic background. Steps must be taken to preserve the unique Lulu.
Determination of plasma vitamin C concentration in fattening cattle
Authors: HAIYING Lin , PADILLA Licza , YOSHIMATSU Kazutaka , MATSUI Tohru , KITAGAWA Masayuki , YANO Hideo
Published: March 2003

Plasma vitamin C (ascorbic acid + dehydroascorbic acid) concentration is a good index of the nutritional status of vitamin C. However, the methodologies for storage and analyses have not been investigated in bovine plasma. The validity of an analytical method for bovine plasma using high performance liquid chromatography (HPLC) with a spectrophotometric detector was examined. Exogenous dehydroascorbic acid was almost completely converted to ascorbic acid during the preparation for analysis with a reducing reagent, dithioerythritol. The analytical recoveries of ascorbic acid were high. Ascorbic acid was not detected after treatment with ascorbic acid oxidase. Thus, the specificity of this method is considered to be high. Although vitamin C was stable in plasma treated by dithioerythritol at −20°C for 6 days, vitamin C in untreated plasma significantly decreased during 3‐day storage at −20°C. These results indicate that the HPLC method is suitable for the determination of plasma vitamin C in cattle and that the storage conditions are important for determination of plasma vitamin C. Plasma vitamin C concentration ranged between 1.49 mg/L and 3.33 mg/L in fattening cattle. This result suggests that fattening cattle show large individual variation in plasma vitamin C concentration.
Identification of a novel nonlysosomal sulphatase expressed in the floor plate, choroid plexus and cartilage
Authors: Ohto Tatsuyuki , Uchida Hiroshi , Yamazaki Hiroshi , Keino‐Masu Kazuko , Matsui Akira , Masu Masayuki
Published: March 2003

Background: Sulphated glycosaminoglycans (GAGs) attached to proteoglycan core proteins are implicated in cell adhesion, motility and morphogenesis. Variable sulphation patterns, which are thought to be important for regulating proteoglycan function, are generated by sequential reactions during GAG biosynthesis. However, the mechanism by which such diversity is generated remains unclear.

Results: A novel sulphatase, designated RsulfFP1, was isolated from rat embryos by screening for floor plate specific genes. RsulfFP1 and its orthologues show homology with other sulphatases, and have a distinctive hydrophilic insertion. In situ hybridization showed that RsulfFP1 mRNA is strongly expressed in the floor plate, choroid plexus and cartilage in rat embryos. In vitro transfection experiments revealed that the RsulfFP1 protein is localized to the Golgi apparatus and endoplasmic reticulum, and is not present in the lysosomes. It also appears to be localized on the cell surface.

Conclusions: RsulfFP1, a phylogenetically conserved sulphatase, forms a novel subgroup in the sulphatase family. It shows homology with the lysosomal sulphatases involved in GAG degradation. Localization of the RsulfFP1 protein in the Golgi apparatus and on the cell surface, however, suggests that it may play a role in regulating proteoglycan‐mediated signalling by the desulphation of GAGs during biosynthesis or after GAGs are presented in the extracellular space.
Restoration of circadian behavioural rhythms in a period null Drosophila mutant (per01) by mammalian period homologues mPer1 and mPer2
Authors: Shigeyoshi Yasufumi , Meyer‐Bernstein Elizabeth , Yagita Kazuhiro , Fu Weili , Chen Yifeng , Takumi Toru , Schotland Peter , Sehgal Amita , Okamura Hitoshi
Published: March 2003

Background: Recent molecular studies suggest that mammals and Drosophila utilize similar components to generate circadian (≈ 24 h) rhythms. The first identified circadian clock gene, the period (per) gene, is indispensable for behavioural rhythms in Drosophila and is represented in mammals by three orthologues, the relative roles of which are not known. In this study, we investigated the functional conservation of per by introducing the mouse mPer1 and mPer2 genes, driven by the Drosophila timeless (tim) promoter, into Drosophila melanogaster.

Results: Behavioural assays showed that both mPer constructs restored rhythms in per01 flies that are otherwise arrhythmic due to a lack of endogenous per protein (PER). However, the rhythms restored by mPer2 were generally stronger and differed in periodicity from those restored by mPer1. In rhythmic transgenic flies, mPER proteins were expressed in lateral neurones and/or many cells in optic lobe. In addition, cell culture experiments indicated that the Drosophila PER partner, TIM, can form a complex with each of these two mammalian proteins.

Conclusions: This study demonstrates that both mPer1 and mPer2 can function as clock components, and has implications for a functional analysis of the different per genes.
Quantitative evaluation of nutritional pathways for the posterior cruciate ligament and the lateral collateral ligament in rabbits
Authors: MURAKAMI  , OCHI  , IKUTA  , HIGASHI
Published: March 2003

The cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from the synovial fluid. The contributions of these two routes as nutritional pathways are not known in detail. In this study, we injected [3H]methyl glucose as a tracer intravenously or directly into the knee of rabbits. Tracer concentrations in plasma, synovial fluid, the posterior cruciate ligament (PCL), and the lateral collateral ligament (LCL) were analysed by a pharmacokinetic compartment model. The contribution of [3H]methyl glucose permeation from the synovial fluid during steady state was calculated at 44.3% in the PCL and at 39.0% in the LCL. Although these results indicated that more than half the nutrition for both ligaments is provided by its vascular supply, synovial fluid permeation is also an important transport route for small molecules for the PCL and the LCL, which is an extra‐articular structure.
Potentiation of the contraction following a prolonged depolarization in isolated ferret myocardium
Authors: Arlock P. , Wohlfart B. , Noble M.
Published: March 2003

The contractile force was studied in ferret papillary muscles during voltage clamp depolarizations, using the single sucrose gap method. Prolongation of a test depolarization within a train produced potentiation of the following contraction. The effects of varied duration and membrane potential of the test depolarization upon the potentiated force of the following beat were studied. We assumed that force of a beat was an index of calcium entry on the previous depolarization. The relationship between the peak contractile force of the following potentiated beat and the systolic membrane potential of the test depolarization revealed an equilibrium around −18 mV. This was manifest after l00 ms of no effect. Positive potentials caused potentiation of force of the following beat; negative potentials caused suppression of force of the following beat. Calcium entry, if carried by an electrogenic exchange mechanism, would be revealed as a membrane current developing after l00 ms. Membrane current at these times was always outward. When the duration of the test depolarization was prolonged, outward current prior to repolarisation progressively increased. When the duration of the test depolarization was held constant, outward current was varied by variation in membrane potential. Force of the following beat was proportional to the test clamp membrane potential. The potentiation of the contraction following a prolonged depolarization was abolished by substituting 75% of the sodium in the perfusion medium with lithium. These results are compatible with the hypothesis that potentiation of force following a prolonged depolarization is derived from calcium entry into myocardial cells by reversed sodium‐calcium exchange.
Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure
Authors: BERTUCCIO  , IBARRA  , PIGNATARO  , TOLEDO  , PAZ  , ARRIZURIETA  , MARTIN
Published: March 2003

Chronic renal failure (CRF) is accompanied by adaptive changes in electrolyte reabsorption in the thick ascending limb of Henle of surviving nephrons. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in micro‐dissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF an increase of basal cAMP from 25.6 ± 10.0 in controls to 65.8 ± 11.3 fmol mm−1 tubule in CRF (P < 0.05). Vasopressin and calcitonin stimulated mTAL adenylate‐cyclase in a dose‐dependent manner in controls but failed to stimulate in CRF. Likewise, maximal stimulation with 10−3 M 3‐isobutyl‐1‐methylxanthine (IBMX) plus 10−5 M forskolin increased cAMP in controls to 63.0 ± 16.0 but not in CRF, where maximal stimulated values remained at 63.1 ± 18.8 fmol mm−1 tubule (P NS). Alpha2‐adrenoreceptor activation with clonidine at concentrations ranging from 10−8 to 10−6 M diminished cAMP production by 37% in CRF (P < 0.05), whereas no differences were found in controls. Thus, the basal intracellular cAMP is increased in rat mTAL in CRF. The finding that neither forskolin nor vasopressin were able to further augment intracellular cAMP would suggest that stimulatory pathways of the adenylate‐cyclase system are activated in the basal state. However, mTAL cells in CRF seem to retain the response of normal epithelium to inhibitory pathways such as the one mediated by alpha2‐adrenoreceptors.
Comparison of the cellular electrophysiological characteristics of canine left ventricular epicardium, M cells, endocardium and Purkinje fibres
Authors: BALÁTI  , VARRÓ  , PAPP
Published: March 2003

Electrophysiological differences among M cells, epicardium, endocardium and Purkinje fibres of the canine ventricle were studied over a wide range of stimulation cycle lengths, and the pharmacological response of these cell types to the sodium channel blocker tetrodotoxin, calcium channel blocker nifedipine and ATP‐sensitive potassium channel activator pinacidil was compared. The experiments were carried out by applying standard intracellular microelectrode technique in isolated dog left ventricular preparations. The results confirmed the existence of M cells in the canine ventricle, in addition, the distribution of the rate of rise of the action potential upstroke and action potential amplitude values reflecting probably the inhomogeneity of the fast sodium current in these cells was revealed. It was also demonstrated that M cells differ from Purkinje fibres in some aspects which were not expected from previous investigations: (1) The early portion of the action potential duration restitution curve in M cells is more similar to that of endocardial and epicardial cells than to Purkinje fibres. (2) The plateau phase of the action potentials in Purkinje fibres developed at a more negative potential range than that in the other cell types studied. (3) The pharmacological response to tetrodotoxin and pinacidil in M cells resembles to that in the endocardial and epicardial cells more than in the Purkinje fibres. Our results provide further evidence in support of the existence of M cells but also indicate that there are important electrophysiological as well as pharmacological differences between M cells and Purkinje fibres.
Changes in peak oxygen uptake and plasma volume in fit and unfit subjects following exposure to a simulation of microgravity
Authors: CONVERTINO
Published: March 2003

To test the hypothesis that the magnitude of reduction in plasma volume and work capacity following exposure to simulated microgravity is dependent on the initial level of aerobic fitness, peak oxygen uptake (V˙O2peak) was measured in a group of physically fit subjects and compared with V˙O2peak in a group of relatively unfit subjects before and after 10 days of continuous 6° head‐down tilt (HDT). Ten fit subjects (40 ± 2 year) with mean ± SE V˙O2peak = 48.9 ± 1.7 mL kg−1 min−1 were matched for age, height, and lean body weight with 10 unfit subjects (V˙O2peak = 37.7 ± 1.6 mL kg−1 min−1). Before and after HDT, plasma, blood, and red cell volumes and body composition were measured and all subjects underwent a graded supine cycle ergometer test to determine V˙O2peak period needed. Reduced V˙O2peak in fit subjects (−16.2%) was greater than that of unfit subjects (−6.1%). Similarly, reductions in plasma (−18.3%) and blood volumes (−16.0%) in fit subjects were larger than those of unfit subjects (blood volume = −5.6%; plasma volume = −6.6%). Reduced plasma volume was associated with greater negative body fluid balance during the initial 24 h of HDT in the fit group (912 ± 154 mL) compared with unfit subjects (453 ± 200 mL). The percentage change for V˙O2peak correlated with percentage change in plasma volume (r = +0.79). Following exposure to simulated microgravity, fit subjects demonstrated larger reductions in V˙O2peak than unfit subjects which was associated with larger reductions in plasma and blood volume. These data suggest that the magnitude of physical deconditioning induced by exposure to microgravity without intervention of countermeasures was influenced by the initial fitness of the subjects.
Albumin infusion in humans does not model exercise induced hypervolaemia after 24 hours
Authors: HASKELL  , GILLEN  , MACK  , NADEL
Published: March 2003

We rapidly infused 234 ± 3 mL of 5% human serum albumin in eight men while measuring haematocrit, haemoglobin concentration, plasma volume (PV), albumin concentration, total protein concentration, osmolality, sodium concentration, renin activity, aldosterone concentration, and atrial natriuretic peptide concentration to test the hypotheses that plasma volume expansion and plasma albumin content expansion will not persist for 24 h. Plasma volume and albumin content were expanded for the first 6 h after infusion (44.3 ± 1.9–47.2 ± 2.0 mL kg−1 and 1.9 ± 0.1–2.1 ± 0.1 g kg−1 at pre‐infusion and 1 h, respectively, P < 0.05), but by 24 h plasma volume and albumin content decreased significantly from 1 h post‐infusion and were not different from pre‐infusion (44.8 ± 1.9 mL kg−1 and 1.9 ± 0.1 g kg−1, respectively). Plasma aldosterone concentration showed a significant effect of time over the 24 h after infusion (P < 0.05), and showed a trend to decrease at 2 h after infusion (167.6 ± 32.5−1 06.2 ± 13.4 pg mL−1, P = 0.07). These data demonstrate that a 6.8% expansion of plasma volume and 10.5% expansion of plasma albumin content by infusion does not remain in the vascular space for 24 h and suggest a redistribution occurs between the intravascular space and interstitial fluid space.
Initiation of increase in muscle sympathetic nerve activity delay during maximal voluntary contraction
Authors: HASHIMOTO  , MIYAMURA  , SAITO
Published: March 2003

To investigate the effects of maximal voluntary exercise on sympathetic nerve activity, contraction force and muscle sympathetic nerve activity (MSNA) were recorded during maximal (MVG) and submaximal voluntary isometric handgrip (SVG) for 2 min in eight healthy subjects. MSNA was determined by a microneurographic technique, and handgrip force, heart rate (HR) and arterial blood pressure (ABP) were measured by a non‐invasive method during exercise. Grip force decayed rapidly to 58% of maximal grip force (MGF) at 10 s after commencement of exercise and was almost constant (≈ 30% of MGF) 40 s after exercise. MSNA increase was delayed by 20 s during MVG, followed by a gradual increase. HR was elevated immediately after onset of exercise, while mean ABP rise showed a 20 s lag from initiation of MVG exercise. During SVG increases in MSNA, HR and mean ABP were delayed by 50, 40 and 20 s, respectively, relative to commencement of exercise. Thereafter, these parameters increased time‐dependently. These results suggested that the MSNA increase during MVG may be predominantly because of the metaboreflex.
Intraduodenal neuropeptide levels, but not plasma levels, vary in a cyclic fashion with the migrating motor complex
Authors: NÄSLUND  , BACKMAN  , THEODORSSON  , HELLSTRÖM
Published: March 2003

The neurohormonal control of the migrating motor complex (MMC) is not fully understood. The hypothesis of the present study was that neuropeptide levels might vary with the different phases of the MMC and that a similar variation might be found in the secretions of the gastrointestinal tract. Thus, plasma and intraduodenal concentrations of vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and neurokinin A (NKA) were determined by radioimmunoassay every 10 min during two complete MMC cycles in eight male subjects. For comparison, plasma motilin (MOT) concentrations were measured. Plasma concentrations of MOT (mean peak value ± SEM; 39 ± 6 pmol L−1), but none of the neuropeptides studied, showed a cyclic variation in plasma with the different phases of the MMC. Peak intraduodenal concentrations of VIP (79 ± 23 pmol L−1),␣SOM (2437 ± 432 pmol L−1) and SP (718 ± 326 pmol L−1) occurred at or at the time point before the onset of phase III of the MMC. No such correlation was observed for NKA. These results demonstrate that intraduodenal but not plasma concentrations of the neuropeptides VIP, SOM and SP show an association with phase III of the MMC. The biological relevance of this finding is yet unclear, but the results raise the possibility that gut neuropeptides may regulate fasting motility through a luminal release.
Diabetes affects blood pressure and heart rate responses during acute hypothermia
Authors: KILGOUR  , WILLIAMS
Published: March 2003

Many diabetics are cold‐intolerant and experience dramatic changes in normal systemic function during hypothermia. Little is known of the cardiovascular adjustments in diabetics exposed to an acute cold stress. In an effort to identify the alterations in mean arterial blood pressure (MAP) and heart rate (HR) in the diabetic during environmental cooling (10 ± 2 °C), we compared the in vivo MAP and HR responses of urethane‐anaesthetized (1.5 g kg−1), streptozotocin‐diabetic (STZ, 65 mg kg−1, n = 12) and control (CON, n = 10) rats during acute hypothermia. MAP was measured directly via an indwelling carotid artery cannula and HR was calculated from the peak systolic pressure waves. Overall, the STZ rats were more cold‐intolerant than CON as evidenced by the greater rate of decline in colonic temperature (Tc) from 36 to 28 °C (STZ, 0.16 °C min−1 vs. CON, 0.06 °C min−1; P < 0.05). Prior to cooling, HR was significantly lower (P < 0.05) in STZ (282 ± 9 beats min−1) than in CON rats (399 ± 24 beats min−1); however, during the acute hypothermic period, HR displayed a similar rate of decline in both groups. With respect to MAP, both groups demonstrated similar pre‐experimental pressor responses (CON, 81.7 ± 5.4 vs. STZ, 83.2 ± 5.1 mmHg, P > 0.05). During progressive hypothermia, MAP gradually increased (P < 0.05) in the CON group from baseline (Tc = 36 °C) and reached peak values (118.4 ± 2.5 mmHg) at Tc = 30 °C, while the STZ group failed to exhibit any cold pressor response. At the conclusion of the experiment (Tc = 28 °C), the STZ group pressor response to hypothermia was not different from baseline (Tc = 36 °C, 83.2 ± 5.1 vs. Tc = 28 °C, 77.4 ± 3.4 mmHg; P > 0.05). The absence of any pressor response in the diabetic group during progressive hypothermia reflects the poor overall vasoconstrictive capacity to cooling and could partially explain the rapid decline of core temperature in this group.
Effects of UTP on Na+, Cl− and K+ transport in primary cultures from human sweat gland coils
Authors: HONGPAISAN  , ROOMANS
Published: March 2003

Extracellular ATP and UTP can increase membrane permeability in the sweat gland, but the intracellular signalling regulating the response to these agonists is poorly understood. Stimulation of Cl− transport by nucleotides has been suggested as a pharmacological therapy to improve Cl− secretion in patients with cystic fibrosis. In the present study, regulation of Na+, Cl− and K+ transport in primary cultures of cells from the secretory coil of human sweat glands was investigated by electron probe X‐ray microanalysis. Stimulation with 200 μM UTP for 2 min at room temperature caused a significant increase in intracellular Na but did not affect Cl and K. After 5 min, the Na concentration was still increased, but now also a significant decrease in Cl and K was observed, indicating an increase in Cl− and K+ permeability. The effect of UTP on Cl− secretion was enhanced in Mg2+‐deficient buffer, indicating that the response is elicited by the extracellular fully ionized form of UTP (UTP4+), but not by MgUTP2+. The effects of UTP were abolished in Ca2+‐deficient buffer supplemented with EGTA. Alloxan, an adenylate cyclase inhibitor, did not inhibit the response to UTP. These results indicate that the membrane Cl− and K+ permeability elicited by UTP in primary coil cell cultures is Ca2+‐dependent. The response to UTP did not attenuate at 8 ∘C, suggesting that it could be activated, in part, via ligand‐gated ion channels. The effect of UTP was not decreased in the presence of ouabain. Pre‐treatment of the cells with pertussis toxin (24 h) had minor effects on Cl− secretion activated by UTP, indicating a role for G proteins in the UTP activation of Cl− secretion.
Vasoactive intestinal peptide suppresses migrating myoelectric complex of rat small intestine independent of nitric oxide
Authors: LJUNG  , HELLSTRÖM
Published: March 2003

The involvement of nitric oxide (NO) in the biological response to vasoactive intestinal peptide (VIP) on the migrating myoelectric complex (MMC) of small bowel and systemic arterial blood pressure was investigated in the rat. Animals were supplied with bipolar electrodes for electromyography of the small intestine and blood pressure was assessed by a pressure transducer connected to a carotid artery. In the first session, N ω‐nitro‐
L‐arginine (
L‐NNA) was administered intravenously at 1, 2, 4 and 20 mg kg−1. Effects of
L‐NNA at 1 and 20 mg kg−1 were also studied after
L‐arginine 300 mg kg−1. In the second session, intravenous infusion of VIP 500 pmol kg−1 min−1 was administered before and after
L‐NNA at 1 and 20 mg kg−1.
L‐NNA at increasing doses stimulated myoelectric spiking of the small bowel until at 4 mg kg−1 the MMC was disrupted and irregular spiking induced. Neither at 1 nor 20 mg kg−1 did
L‐NNA affect the inhibitory motility response or decrease of blood pressure induced by VIP at a dose of 500 pmol kg−1 min−1. Our results show that effects of VIP on motility of the small intestine and systemic arterial blood pressure are direct and not dependent on NO as a common final link.
The influence of transmural pressure and longitudinal stretch on K+– and Ca2+–induced coronary artery constriction
Authors: Frøbert  , Mikkelsen  , Bagger
Published: March 2003

The aim of the study was to investigate transmural pressure and longitudinal stretch modulation of K+‐ and Ca2+‐induced constriction of porcine conductance coronary arteries. In a pressure myograph set‐up, left anterior descendent coronary arteries from 70 to 90 kg pigs were investigated at pressures from 20 to 120 mmHg. Longitudinal extension ratio (λ = L/L0–1, where L0 is the in situ length and L the examination length) varied between 0.9 and 1.1. Two protocols were carried out: (1) Outer diameter response to maximal depolarization by K+ 125 m
M at 20–120 mmHg and λ at 0.90–1.10. (2) Concentration–response curves with K+ (4.7–125 m
M) and Ca2+ (0.05–4.0 m
M) at four combinations of P and λ (P = 100 mmHg, λ = 0.9; P = 100 mmHg, λ = 1.1; P = 40 mmHg, λ = 0.9; p = 40 mmHg, λ = 1.1). Results: Endothelial function was preserved. A slight (<5% diameter reduction) basal tone and no myogenic response was found. Protocol 1: the constriction to K+ 125 m
M was maximal in a wide pressure range from 40 to 120 mmHg. Despite the fact that K+‐induced diameter changes were statistically insignificant between 40 and 120 mmHg, there was a linear trend towards smaller diameter changes in this pressure range (r = –0.54, P < 0.01). Stretch influenced constriction at 20 mmHg because λ = 0.90 and 0.95 resulted in smaller diameter‐reductions than λ = 1.00–1.10 (P < 0.05 for all). Contrastingly, at 120 mmHg the constriction at λ = 1.10 was smaller than the responses at λ = 0.90–1.05 (P < 0.05 for all). Protocol 2: EC50 and EC10 values for K+‐ and Ca2+ were generally higher (more sensitive) at 40 compared with 100 mmHg. Stretch was of no significant importance for EC50 and EC10 at 40 and 100 mmHg. It is concluded that porcine coronary artery constriction to non‐metabolized agonists is maximal at 40 mmHg with a trend towards smaller diameter changes with higher pressures. Longitudinal stretch affects responsiveness at pressure extremes.
Electrophysiological changes in rat ventricular and atrial myocardium at different stages of experimental diabetes
Authors: Pacher  , Ungvári  , Nánási  , Kecskeméti
Published: March 2003

Action potential configuration in ventricular and atrial myocardium, as well as rate‐dependent changes in ventricular action potential duration (APD) were studied and compared in healthy and diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 65 mg kg–1 i.v.). Conventional microelectrode techniques were applied to record action potentials after the establishment of diabetes (2, 6, 10 and 18 weeks after STZ‐treatment). Untreated age‐matched animals were used as controls. Both depolarization and repolarization were significantly retarded following STZ‐treatment. However, the time course of development of diabetic changes in atrial and ventricular myocardium was different. APD was significantly lengthened from week 2 of diabetes in ventricular, but only from week 6 in atrial preparations. In atrial myocardium, lengthening of APD was more pronounced at early rather than late phases of repolarization. The maximum rate of depolarization (Vmax) was significantly reduced from the 6th week of diabetes in both preparations. No differences were observed in action potential amplitude (except at week 18) and in the resting membrane potential in diabetic rats. Diabetic ventricular preparations showed a positive APD‐frequency relationship at any level of repolarization, in contrast to control muscles, where APD25 and APD50 values lengthened. But APD75 and APD90 values were not changed significantly with increase in the pacing frequency. The results indicate that development of diabetic alterations are not fully identical in atrial and ventricular myocardium of the rat, probably owing to differences in density and kinetics of ionic currents responsible for atrial and ventricular action potentials.
Activation of renal pelvic chemoreceptors in rats: role of calcitonin gene‐related peptide receptors
Authors: Gontijo  , Kopp
Published: March 2003

Substance P and calcitonin gene‐related peptide (CGRP) increase afferent renal nerve activity (ARNA). A substance P receptor antagonist but not a CGRP receptor antagonist, h‐CGRP (8–37), blocks the ARNA response to renal mechanoreceptor (MR) stimulation. We have examined whether calcitonin gene‐related peptide activates renal pelvic sensory receptors and whether such activation contributes to renal chemoreceptor stimulation. The calcitonin gene‐related peptide receptor antagonist, h‐CGRP (8–37) [0.01–10 μmol L−1] dose‐dependently decreased (29 ± 4–86 ± 13%, P < 0.01) the ipsilateral afferent renal nerve activity in response to the renal pelvic administration of calcitonin gene‐related peptide (0.26 μmol L−1). Renal pelvic perfusion with 900 m
M NaCl also increased ipsilateral ARNA (23 ± 3% increase, P < 0.02) and contralateral urinary sodium excretion (13 ± 4% increase, P < 0.05). However, these responses to hypertonic NaCl were unaltered by h‐CGRP (8–37). Renal pelvic perfusion with 1 or 10 μM h‐CGRP (8–37) also failed to alter the ARNA responses to KCl (31.25, 62.5 and 125 m
M). These results indicate that there are sensory receptors in the renal pelvic area that are responsive to calcitonin gene‐related peptide. The activation of these receptors elicits a contralateral natriuretic response. In contrast, the activation of renal calcitonin gene‐related peptide receptors does not contribute to renal chemoreceptor activation.
Efficacy and economy of inhaled nitric oxide in neonates accepted for extra‐corporeal membrane oxygenation
Authors: Lönnqvist
Published: March 2003

Objective: To study the clinical efficacy as well as the cost‐effectiveness of inhaled nitric oxide (NO) compared with extra‐corporeal membrane oxygenation (ECMO) in neonates with pulmonary hypertension and hypoxic respiratory failure accepted for ECMO treatment. Design: Retrospective study of the first 10 consecutive neonatal patients treated with inhaled NO during 1992–94. Inhaled NO was administered after failure of conventional treatment as a last resort before initiating ECMO. For cost‐effectiveness calculations the above‐described patient population was compared with ECMO patients having a very favourable ECMO course.

Setting: Twelve‐bed neonatal and paediatric intensive care unit with ECMO capabilities at a tertiary university referral hospital.

Results: Inhaled NO was found to significantly decrease the oxygenation index (OI pre‐NO: median 80.5; OI post‐NO: median 22.5; P=0.003) and five of the patients could successfully be handled without the use of ECMO. ECMO was found to be more than four times as expensive as inhaled NO treatment on a per hour basis ($244 vs. $53 per hour) and the net savings from being able to avoid ECMO in five patients was calculated to be $156 200.

Conclusion: Initiation of inhaled NO caused a significant improvement in oxygenation index and reduced the need for ECMO by 50% in critically ill neonatal patients with hypoxic respiratory failure. Inhaled NO was also found to compare very favourably with ECMO regarding cost‐effectiveness ($53 vs. $244 per treatment hour).
Slower fatigue and faster recovery of the adductor pollicis muscle in women matched for strength with men
Authors: Fulco  , Rock  , Muza  , Lammi  , Cymerman  , Butterfield  , Moore  , Braun  , Lewis
Published: March 2003

In previous gender comparisons of muscle performance, men and women rarely have been closely matched, absolute force has not been equalized, and rates of fatigue and early recovery have not been determined. We compared adductor pollicis muscle performance at a similar absolute force development in healthy men and women (both n=9) matched for adductor pollicis maximal voluntary contraction (MVC) force (132 ± 5 N for women and 136 ± 4 N for men, mean ± SE, P > 0.05). Subjects repeated static contractions at a target force of ≈50% of MVC force of rested muscle (68 ± 3 N or 51.9 ± 1.0% MVC for women and 72 ± 2 N or 53.0 ± 2.0% MVC for men, P > 0.05) for 5 s followed by 5 s rest until exhaustion, i.e. inability to maintain the target force for 5 s. MVC force was measured following each minute of exercise, at exhaustion, and after each minute for 3 min of passive recovery. For women compared with men: MVC force fell less after 1 min of exercise (to 93 ± 1% vs. 80 ± 3% of MVC force of rested muscle, respectively, P < 0.05); MVC force (N min–1) fell ≈2‐fold slower (P < 0.05); and endurance time to exhaustion was nearly two times longer (14.7 ± 1.6 min vs. 7.9 ± 0.7 min, P < 0.05). After declining to a similar level of MVC force of rested muscle at exhaustion (56 ± 1% for women and 56 ± 3% for men), MVC force rose faster in women than in men (to 71 ± 2% vs. 65 ± 3% of MVC force of rested muscle, respectively; P < 0.05) during the first minute of recovery. The findings are consistent with the hypothesis that slower adductor pollicis muscle fatigue in women is linked with differences between men and women both in impairment of force generating capacity, per se, and in rates of recovery between contractions.
Chemical hypoxia‐induced increases in dopamine D1A receptor mRNA in renal epithelial cells are mediated by nitric oxide
Authors: Healy  , Jayaraman  , Ashirova
Published: March 2003

Nitric oxide (NO) and dopamine (DA) have similar effects on renal function, with both having natriuretic and diuretic effects mediated by vascular and tubular mechanisms. Renal ischaemia or hypoxia have been shown to influence the activity of both systems. However, it is not known whether there is any crosstalk between the NO and dopaminergic systems in the kidney. Here using the porcine proximal tubule‐like renal epithelial LLC‐PK1 cell line as a model system, we determined whether exposure of cells to chemical hypoxia altered the steady‐state levels of D1A receptor mRNA and whether the changes involved the NO system. Exposure of LLC‐PK1 cells to chemical hypoxia resulted in a marked increase in D1A receptor mRNA levels as measured by reverse transcription‐polymerase chain reaction (RT‐PCR). The increased levels of D1A receptor mRNA following hypoxia were blocked by the NO synthase inhibitors NG‐nitro‐
L‐arginine methylester (
L‐NAME) or NG‐monomethyl‐
L‐arginine (
L‐NMMA). Further evidence that the NO system exerted positive effects on D1A receptor gene expression came from finding that the NO donor sodium nitroprusside, the NO precursor
L‐arginine and the guanosine 3′,5′‐cyclic monophosphate (cyclic GMP) analogue 8‐Br‐cGMP all increased D1A receptor mRNA levels in LLC‐PK1 cells. These results indicate that expression of the D1A receptor in LLC‐PK1 cells can be positively regulated by the NO system. Such an interaction between the renal NO and DA systems may contribute to the reported protective effects that NO and DA exert upon the kidney under conditions of ischaemia.
Relationship between decreased oxyhaemoglobin saturation and exhaled nitric oxide during exercise
Authors: Sheel  , Edwards  , Mckenzie
Published: March 2003

Decreases in oxyhaemoglobin saturation (SaO2) are frequently observed in highly trained male endurance athletes during heavy work and has been termed exercise‐induced hypoxaemia (EIH). Ventilation perfusion (VA/Q) mismatching and diffusion limitations are thought to be responsible. Nitric oxide (NO), a potent vasodilator, is present in the exhaled air of resting and exercising humans. Endogenously produced NO is thought to play a role in VA/Q matching and maintenance of low pulmonary vascular resistance. The purpose of this study was to determine the relationship between exhaled NO and EIH. It was hypothesized that athletes with EIH would have lower NO levels compared with non‐EIH athletes. Eighteen highly trained male cyclists (VO2max=67.7 ±  5.2 mL kg−1 min−1, mean ± SD) were divided into normal (NORM, n=12, SaO2= 93.9 ± 0.8) or low (LOW, n=6, SaO2=90.3 ± 1.0) group, based on significantly different peak exercise SaO2 values (P < 0.05). All other descriptive and physiological characteristics were similar between the groups. Subjects performed a ramped cycle test to exhaustion breathing NO‐free gas. The concentration (CNO) and production rate (VNO) of NO were determined from mixed gas samples at rest and during exercise at 100, 200, 250, 300, 350, 400 and 450 W using a chemiluminescent analyser. CNO remained unchanged from resting values in all subjects. VNO increased significantly during exercise in all subjects but was not different between LOW and NORM groups. The correlation between change in SaO2 and VNO from rest to maximal exercise was not significant (r=−0.12, P > 0.05). Collectively, these data suggest that exhaled NO is not related to decreased SaO2 during heavy exercise in highly trained male cyclists.