bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Postnatal Age and a β3‐Adrenergic Agonist (Zeneca D7114) Administration on Uncoupling Protein‐1 Abundance in the Lamb
Authors: Bird J. A. , Mostyn A. , Clarke L. , Juniper D. T. , Budge H. , Stephenson T. , Symonds M. E.
Published: February 2003

We examined the effect of time after birth and β3‐adrenergic agonist (Zeneca D7114) administration on uncoupling protein‐1 (UCP1) abundance and thermoregulation in the lamb. Forty twin lambs, all born normally at term, were maintained at a cold ambient temperature of between 3 and 8 °C. At 0.5, 1.75, 5.25, 11.25 and 23.25 h after birth eight sets of twins were fed 20 ml of formula milk ± 10 mg kg−1 of β3‐adrenergic agonist, and 45 min after feeding brown adipose tissue (BAT) was sampled. Colonic temperature was measured and BAT analysed for UCP1 abundance, GDP‐binding to mitochondrial protein (i.e. thermogenic activity) and catecholamine content. Colonic temperature declined between 1.25 and 6 h from 40.2 °C to 39.2 °C and then increased to 39.8 °C at 12 h, but increased after feeding at all ages. UCP1 abundance increased from 1.25 h after birth, to peak at 2 h after birth in controls, compared with 6 h after birth in β3‐adrenergic agonist‐treated lambs. The level of GDP‐binding to mitochondrial protein did not change significantly with age but was increased by β3‐adrenergic agonist treatment. The noradrenaline (norepinephrine) content of BAT increased between 1.25 and 12 h after birth, irrespective of β3‐adrenergic agonist administration. The total weight of perirenal BAT plus its lipid, protein and mitochondrial protein content declined over the first 6 h of life. UCP1 development continues over the first 24 h of neonatal life, and can be manipulated by β3‐adrenergic agonist administration. This may represent one method of improving thermoregulation in newborn lambs.
The Contribution of Chemoreflex Drives to Resting Breathing in Man
Authors: Mahamed Safraaz , Ali Arshia F. , Ho Dominic , Wang Bernice , Duffin James
Published: February 2003

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as ‘wakefulness’, has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a PET,O2 (end‐tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to PET,CO2 (end‐tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold PET,CO2 was exceeded, ventilation increased linearly with PET,CO2. We considered the sub‐threshold ventilation to be an estimate of the behavioural drives to breathe (mean ± S.E.M. = 3.1 ± 0.5 l min−1), and compared it to ventilation at rest (mean ± S.E.M. = 9.1 ± 0.7 l min−1). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold PCO2 observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean ± S.E.M. = 42.0 ± 0.5 mmHg). However, PET,CO2 during rebreathing estimates mixed venous or tissue PCO2, whereas the resting PET,CO2 during resting breathing estimates Pa,CO2 (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in PET,CO2 at rest and at the start of rebreathing (the plateau estimates the mixed venous PCO2 at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean ± S.E.M. = 26.0 ± 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting PET,CO2 values (mean ± S.E.M. = 34.3 ± 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation.
Role of Ca2+‐Activated Cl− Current in Ventricular Action Potentials of Sheep During Adrenoceptor Stimulation
Authors: Verkerk Arie O. , Schumacher Cees A. , van Ginneken Antoni C. G. , Veldkamp Marieke W. , Ravesloot Jan H.
Published: February 2003

Adrenoceptor stimulation enhances repolarising and depolarising membrane currents to different extents in cardiac myocytes. We investigated the opposing effects of the repolarising Ca2+‐activated Cl− current (ICl(Ca)) and depolarising L‐type Ca2+ current (ICa,L) on the action potential configuration of sheep ventricular myocytes stimulated with noradrenaline. Whole‐cell current‐clamp recordings revealed that noradrenaline accelerated and prolonged phase‐1 repolarisation. We define the minimal potential at the end of phase‐1 repolarisation as ‘notch level’. Noradrenaline (1 μM) caused the notch level to fall from 14 ± 2.6 to 7.8 ± 2.8 mV (n= 24), but left action potential duration, resting membrane potential or action potential amplitude unaffected. Whole‐cell voltage‐clamp recordings showed that 1 μM noradrenaline increased both ICa,L and ICl(Ca), but it had no significant effect on the principal K+ currents. Blockage of ICl(Ca) by 0.5 mM 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS) in both the absence and the presence of noradrenaline abolished phase‐1 repolarisation. In the presence of noradrenaline, DIDS caused elevation of the plateau phase amplitude and an increase in the action potential duration. In conclusion, elevation of the plateau phase amplitude and action potential prolongation associated with an increased ICa,L upon adrenoceptor stimulation is prevented by an increased ICl(Ca) in sheep ventricular myocytes.
A Model for an Ascaris Muscle Cell
Authors: Turner R. E. L.
Published: February 2003

Muscle cells in the nematode Ascaris suum undergo bouts of oscillation in the behaving worm, these being correlated with progressing waves of contraction along the body of the worm. The bouts have three time scales: a rough period of 7‐20 s, 10‐20 short bursts of spikes within a bout, and three to eight spikes per burst. This paper has two aims: showing that there is consistency between measurements of individual currents and measurements on whole muscle cells, and creating a building block to eventually explain the locomotion in this ‘simple’ system. A realistic model for a single Ascaris suum muscle cell is developed using existing data from experiments which have established the types of ionic currents in the muscle cell and many of their kinetic properties. Numerical simulations are carried out. The model cell reproduces the two shorter time scales present. It has some robustness with regard to parameter changes, but also allows for the different numbers of spikes per burst seen in recordings from muscle cells. The third time scale, the length of a bout, may originate from some system effect, a combination of neural and stretch effects and possibly a secondary effect of the calcium‐activated chloride channel.
Nitric Oxide and the Autonomic Regulation of Cardiac Excitability
Authors: Paterson David J.
Published: February 2003

Contents Page

Introduction 1

Cardiac sympathetic imbalance and arrhythmia 2

Nitric oxide‐cGMP pathway and the cholinergic modulation of cardiac excitability 3

Nitric oxide‐cGMP pathway and the sympathetic modulation of cardiac excitability 7

Functional significance of nitric oxide in the autonomic regulation of cardiac excitability 9

Summary 9

References 10
Introduction
Authors: Bernal A. López
Published: February 2003

This issue contains a number of papers based on presentations from a Uterine Contractility Symposium held in Oxford, UK on May 3rd, 2000. They represent an overview of current knowledge on the regulation of uterine smooth muscle. Research in this area is important because disorders of parturition, notably preterm labour, remain a major cause of perinatal mortality and carry a wide range of short‐ and long‐term morbidity in the surviving infants. Available therapies are inefficient or have undesirable side effects for the mother or the baby. A better understanding of the physiology of parturition and the cellular basis of uterine contractility will lead to the development of more efficacious and selective drugs for the management of preterm labour and other disorders of uterine function. The main presentation was the Litchfield Lecture (sponsored by the Medical School), which was given by Professor Barbara Sanborn. There were also presentations of very high standard by scientists and clinicians with a long‐standing interest in this subject, and by young scientists. I am most grateful to all the contributors for their enthusiasm and for making an effort to produce quality manuscripts as a scientific record of this symposium. All the manuscripts have been fully reviewed and I am particularly indebted to Professor Lucilla Poston for coordinating the editorial work. The symposium was supported by educational grants from the Serono Pharmaceutical Research Institute, GlaxoWellcome R&D, Alliance Pharmaceuticals, Ferring Pharmaceuticals, Unipath and Aventis Pharma.
Effect of Losartan on Sodium Appetite of Hypothyroid Rats Subjected to Water and Sodium Depletion and Water, Sodium and Food Deprivation
Authors: Badauê‐Passos D. , Ventura R. R. , Silva L. F. S. , Olivares E. L. , Ramalho M. J. , Rodrigues J. Antunes , Reis L. C.
Published: February 2003

The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg g−1, the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg g−1 did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water‐ and sodium‐depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food‐deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors.
Carotid Baroreceptor Reflexes in Humans During Orthostatic Stress
Authors: Cooper Victoria L. , Hainsworth Roger
Published: February 2003

Orthostatic stress, including standing, head‐up tilting and lower body suction, results in increases in peripheral vascular resistance but little or no change in mean arterial pressure. This study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was enhanced during conditions of decreased venous return. We studied eight healthy subjects and determined responses of pulse interval (ECG) and forearm vascular resistance (mean finger blood pressure divided by Doppler estimate of brachial artery blood velocity) to graded increases and decreases in carotid transmural pressure, effected by a neck suction/pressure device. Responses were determined with and without the application of lower body negative pressure (LBNP) at ‐40 mmHg. Stimulus‐response curves were determined as the responses to graded neck pressure changes and the differential of this provided estimates of reflex sensitivity. Changes in carotid transmural pressure caused graded changes in R‐R interval and vascular resistance. The cardiac responses were unaffected by LBNP. Vascular resistance responses, however, were significantly enhanced during LBNP and the peak gain of the reflex was increased from 1.2 ± 0.3 (mean ± S.E.M.) to 2.2 ± 0.3 units (P < 0.05). The increased baroreflex gain may contribute to maintenance of blood pressure during orthostatic stress and limit the pressure decreases during prolonged periods of such stress.
Impaired Phospholipid‐Related Signal Transduction in Advanced Huntington's Disease
Authors: Puri Basant K.
Published: February 2003

The aim of this study was to test the hypothesis that Huntington's disease is associated with impaired phospholipid‐related signal transduction using the niacin skin flush test. This is the first reported use of this test in this patient group. The response to topical aqueous methyl nicotinate solution was recorded at 5 min intervals over 20 min in six in‐patients with advanced (stage III) Huntington's disease and in 14 age‐ and sex‐matched normal individuals with no history of this or any other major neurological disorder. The volumetric niacin response (VNR) (mean ± S.E.M.) in the patients with Huntington's disease, 16.3 ± 2.6 mol s l−1, was significantly lower than the mean VNR of 28.3 ± 2.1 mol s l−1 in the control group (P = 0.004). These results are consistent with the conclusion that Huntington's disease may be associated with an abnormality of neuronal membrane fatty acid metabolism, possibly as a consequence of an as yet unidentified action of huntingtin.
Short Term Aerobic Exercise Training in Young Males Does Not Alter Sensitivity to a Central Serotonin Agonist
Authors: Dwyer Dan , Flynn John
Published: February 2003

An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5‐HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5‐HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 × 30 min of stationary cycling at 70% of their peak aerobic power (V̇O2,peak) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in V̇O2,peak (3.1 ± 0.16 to 3.6 ± 0.15 l min−1, P < 0.05) and endurance capacity (93 ± 8 to 168 ± 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one‐quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in V̇O2,peak and endurance performance, there was no measurable change in 5‐HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.
Analysis of the Effects of Graded Levels of Hypoxia on Noradrenaline‐Evoked Contraction in the Rat Iliac Artery in vitro
Authors: Bartlett Iain S. , Marshall Janice M.
Published: February 2003

In rings of rat iliac artery, contractions were evoked by noradrenaline (NA), the selective α1 adrenoceptor agonist phenylephrine (PE), and K+, which causes depolarisation‐induced contraction. There was no evidence of α2 adrenoceptor‐evoked contraction. Hypoxia, induced by reducing PO2 in the bath from 100 mmHg to 70, 55 or 40 mmHg, had similar effects on rings with (E+) and without (E‐) endothelium. In E‐ rings, the NA concentration‐response curve was biphasic, whereas that for PE was monophasic. Hypoxia reduced maximum contractions in response to NA and PE (NAmax and PEmax, respectively) without affecting the concentrations that evoked 50% of maximum contraction (EC50). At PO2 of 70 mmHg, NAmax of the high affinity α1 receptor for NA (NAmaxh) and PEmax were reduced by ∼15%, but at PO2 of 55 and 40 mmHg, NAmaxh was severely attenuated while PEmax fell by 45 and 75%, respectively. Similarly, the Ca2+ channel blocker nicardipine depressed NAmaxh and PEmax, but PO2 of 55 mmHg further reduced NAmax and PEmax. Hypoxia also reduced contractions evoked by NA, PE or K+ at the concentrations required to produce 80% of the maximum contraction (EC80), receptor‐mediated contractions being more affected. Ca2+‐free conditions reduced the contractions evoked by NA and PE, at the EC80, to ∼10% of control. The K+ channel inhibitors glibenclamide and tetraethylammonium did not prevent hypoxia‐induced depression of PE‐evoked contraction. Thus, contractions evoked in iliac artery by the high affinity subtype of α1 adrenoceptor for NA, which may respond to circulating levels of NA, and by the single α1 adrenoceptor subtype for PE, are especially vulnerable to PO2 levels ≤ 55 mmHg. We propose that this reflects hypoxia‐induced inhibition of Ca2+ influx through L‐type and receptor‐operated Ca2+ channels; K+ channel opening makes little contribution.
Study of protein–protein interactions by fluorescence of tryptophan analogs: Application to immunoglobulin G binding domain of streptococcal protein G
Authors: Li Qi , Du Hai‐Ning , Hu Hong‐Yu
Published: February 2003

The protein–protein interaction system often contains many fluorophores that may significantly interfere with the quantitative determination of the binding abilities. To solve this perplexing problem, we biosynthetically incorporated the two tryptophan analogs, 5‐hydroxytryptophan and 7‐azatryptophan, into the immunoglobulin G (IgG) binding domain of streptococcal protein G (PGBD). The exclusive excitation and novel fluorescence changes in both the intensity and anisotropy are beneficial to reporting the details of the interactions between PGBD and the IgG fragments and enable assessment of the binding abilities. The dissociation constants are estimated to be 0.28 μM for the binding of human Fc and 8.0 μM for mouse Fc. The results clearly demonstrate that labeling of tryptophan analogs has very little effect on the binding abilities and is broadly applicable to quantitatively studying protein–protein interactions in a whole biomolecular complex. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 116–122, 2003
Detection by circular dichroism of conformational transitions in pH and thermosensitive copolymers based on N‐isopropylacrylamide and N‐methacryloyl‐L‐leucine
Authors: Lebon France , Bignotti Fabio , Penco Maurizio , Gangemi Roberto , Longhi Giovanna , Abbate Sergio
Published: February 2003

Circular dichroism (CD) spectra in the region of 210–250 nm allow visualization of intrachain phase transition of pH‐ and thermosensitive polyelectrolytes. Indeed, in 0.001 M citrate and acetate buffers, at pH 4.0–5.5, aqueous solutions of a poly(N‐isopropylacrylamide‐co‐N‐methacryloyl‐L‐leucine) (NIPAAm‐MALEU) copolymer containing 90.9 mol% of NIPAAm residues exhibit a well‐defined sigmoidal increase in the CD signal at 220 nm with increasing temperature. This phenomenon is suggestive of a highly cooperative transition which occurs at lower temperatures compared to that observed by cloud point measurements. The change in the CD signal is less sharp at higher pH, indicating varying cooperativity with pH. For pH 6.0 and higher, no such phenomena are observed. Chirality 15:251–255, 2003. © 2003 Wiley‐Liss, Inc.
Geometrical approach to central molecular chirality: A chirality selection rule
Authors: Capozziello Salvatore , Lattanzi Alessandra
Published: February 2003

Chirality is of primary importance in many areas of chemistry and has been extensively investigated since its discovery. We introduce here a description of central chirality for tetrahedral molecules using a geometrical approach based on complex numbers. According to this representation, for a molecule having n chiral centers it is possible to define an “index of chirality χ.” Consequently, a “chirality selection rule” has been derived which allows the characterization of a molecule as achiral, enantiomer, or diastereoisomer. Chirality 15:227–230, 2003. © 2003 Wiley‐Liss, Inc.
Kinetics and thermodynamic parameters of the thermal decomposition of imipramine hydrochloride and trimipramine maleate
Authors: Abu‐Eittah Rafie H. , Kamel Laila T.
Published: February 2003

Thermal decomposition of imipramine hydrochloride and trimipramine maleate has been investigated isothermally and nonisothermally. The kinetic parameters, namely the activation energy Ea and the Arrhenius preexponential term A, were calculated. Applying the theory of activated complex to the process of decomposition one calculated ΔS≠, ΔH≠, and ΔG≠ for the reaction. The values of Ea as well as the thermodynamic functions did not vary significantly with temperature of the reaction whereas the preexponential term showed a significant dependence on the reaction temperature. Both imipramine hydrochloride and trimipramine maleate showed two main steps of decomposition. Each step proved to be a first‐order reaction. The rate constant was calculated for each step, and the results were analyzed statistically. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 166–179, 2003
Cross‐reactivity of yeast antigens in human colon and peripheral leukocytes
Authors: Oshitani1 Nobuhide , Hato Fumihiko , Suzuki Kenichi , Sawa Yoshinori , Matsumoto Takayuki , Maeda Kiyoshi , Higuchi Kazuhide , Kitagawa Seiichi , Arakawa Tetsuo
Published: February 2003

Elevation of the serum anti‐Saccharomyces cerevisiae antibody (ASCA) level has been reported in patients with Crohn's disease. This study investigated the antigenic distribution of S. cerevisiae in human colon and peripheral leukocytes. ASCA was isolated from sera from patients with Crohn's disease using immuno‐affinity chromatography and then biotinylated and assayed immunohistologically and immunocytologically to determine the distribution of antigens recognized by ASCA in human colon and peripheral leukocytes. Immunoblot analysis of yeast extract and human peripheral leukocytes was performed. Immunohistological study using biotinylated ASCA revealed the presence of yeast‐like particles in the granulation tissue of inflamed colonic mucosa. Biotinylated ASCA also stained lymphocytes and polymorphonuclear cells infiltrating inflamed intestine. Monocytes in epithelioid granulomas of colon with Crohn's disease were also stained. Polymorphonuclear leukocytes in peripheral blood were also stained with biotinylated ASCA. The antigens reactive to ASCA among heat‐extracted, non‐heat‐extracted yeast antigens, and human leukocyte extract differed. The findings of cross‐reactivity of polymorphonuclear leukocytes with S. cerevisiae antigen and the presence of S. cerevisiae antigen in Crohn's disease granulomas suggest the possibility of involvement of S. cerevisiae in the pathogenesis of Crohn's disease. Copyright © 2003 John Wiley & Sons, Ltd.
Genetic algorithm optimization of a firewater deluge system
Authors: Andrews J. D. , Bartlett L. M.
Published: February 2003

Safety systems are designed to operate when certain conditions occur and to act to prevent their development into a hazardous situation. Failure of a safety system for a potentially hazardous industrial system or process may have catastrophic consequences, possibly injuring members of the work force or public and occasionally resulting in loss of life. The purpose of this paper is to describe a design optimization scheme using genetic algorithms applied to a firewater deluge system, which uses available resources to the best possible advantage to obtain an optimal safety system design. Copyright © 2003 John Wiley & Sons, Ltd.
Changing ideas about the periodic table of elements and students' alternative concepts of isotopes and allotropes
Authors: Schmidt Hans‐Jürgen , Baumgärtner Tim , Eybe Holger
Published: February 2003

The Periodic Table of Elements (PTE) is one of the organizing principles in chemistry. Originally it was a list of elements (as substances). Later, the PTE developed into a list of atoms of the elements. However, isotopes and allotropes are difficult to integrate into the PTE. Therefore, difficulties in understanding these terms can be expected. The investigation set off to study secondary school students' concepts of isotopes and allotropes and how the concepts are linked to the PTE. Three specific research questions were addressed: (a) How do secondary school students describe the relationship between fundamental particles constituting an atom? (b) How do they conceive isotopes? and (c) What are students' concepts of graphite and diamond? Multiple choice items were given to 3074 senior high school students. In addition, six interviews were conducted with senior high school students. The data analysis revealed students' alternative concepts, which distinguished between standard atoms and atoms of isotopes. Standard atoms contain neutrons and protons in equal numbers and are more stable. The atomic masses are expressed as integers. Moreover, students considered graphite and diamond as isotopes. The analysis of the results shows that students actively tried to make sense of what they had experienced. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 40: 257–277, 2003
Cardiovascular Response to Graded Lower Body Negative Pressure in Young and Elderly Man
Authors: van Hoeyweghen R. , Hanson J. , Stewart M. J. , Dethune L. , Davies I. , Little R. A. , Horan M. A. , Kirkman E.
Published: February 2003

Lower body negative pressure (LBNP) reduces central venous pressure (CVP) and cardiac output. The elderly are reported to have a limited capacity to increase cardiac output by increasing heart rate (HR), are especially dependent on end diastolic volume to maintain stroke volume and therefore should be especially vulnerable to LBNP. The present study compared the effects of LBNP in the young and old. Stroke volume was assessed non‐invasively as stroke distance (SD) by aortovelography. Two groups of healthy male volunteers were studied: eight young (29.7 ± 2.0 years, mean ± S.E.M.) and nine old (70.1 ± 0.9 years). LBNP was applied progressively at 17.5, 35 and 50 mmHg in 20 min steps, with measurements taken during each steady state. There were similar, significant, falls in CVP in both groups. SD fell significantly in both groups from respective control values of 24.8 ± 1.6 and 16.6 ± 0.9 cm to 12.5 ± 1.3 and 8.9 ± 0.4 cm at a LBNP of 50 mmHg. Although SD in the elderly was significantly lower than in the young, the LBNP‐induced changes were not different between groups. Both groups produced similar significant increases in vascular resistance, HR, plasma vasopressin (AVP) and noradrenaline. Mean arterial blood pressure (MBP) and plasma adrenaline did not change significantly. Therefore healthy old men respond to LBNP in a similar manner to the young, although MBP and SD are regulated around different baselines in the two groups.
Regional Expression of Inducible Nitric Oxide Synthase in the Kidney Stimulated by Lipopolysaccharide in the Rat
Authors: Chou D. E. , Cai H. , Jayadevappa D. , Porush J. G.
Published: February 2003

The renal medulla contains more mRNA of the inducible isoform of nitric oxide synthase (iNOS) than the cortex, which may be important in preventing ischaemic injury, since blood flow and tissue oxygen tension are normally low in this region. We examined the effects of the bacterial endotoxin E. coli lipopolysaccharide (LPS) on renal function and regional expression of iNOS in male Sprague‐Dawley rats. In six rats, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 0.95 ± 0.09 ml min−1 g−1 and 3.36 ± 0.20 ml min−1 g−1, respectively, and decreased significantly to 0.35 ± 0.09 and 1.74 ± 0.54 ml min−1 g−1, respectively, 1 h after administration of LPS. In an additional seven rats, GFR and ERPF were 0.91 ± 0.07 and 2.97 ± 0.30 ml min−1 g−1, respectively, 18 h after LPS administration; these values were similar to those in control rats. In all rats, arterial pressure was stable throughout all study periods. In control rats, immunoblot analysis revealed expression of the iNOS protein in the cortex and more pronounced expression in the medulla. In rats studied 18 h after LPS treatment, there was a striking increase in the iNOS expression in the outer medulla. Immunohistochemical examination in the LPS‐treated rats showed limited iNOS immunostaining in the cortex, localised to the vascular endothelium and macula densa; however, intense and widespread staining was noted in the tubular and vascular structures of the outer medulla. These findings demonstrated a differential constitutive expression of iNOS protein in different regions of the rat kidney, and marked augmentation of iNOS expression in the outer medulla by LPS.
Surface Action Potential and Contractile Properties of the Human Triceps Surae Muscle: Effect of ‘Dry’ Water Immersion
Authors: Koryak Yuri A.
Published: February 2003

The effects of 7 days of ‘dry’ water immersion were investigated in six subjects. Changes in the contraction properties were studied in the triceps surae muscle. After immersion, the maximal voluntary contraction (MVC) was reduced by 18.9% (P < 0.01), and the electrically evoked (150 impulses s−1) maximal tension during tetanic contraction (Po) was reduced by 8.2% (P > 0.05). The difference between Po and MVC expressed as a percentage of Po and referred to as force deficiency was also calculated. The force deficiency increased by 44.1% (P < 0.001) after immersion. The decrease in Po was associated with increased maximal rates of tension development (7.2%) and relaxation. The twitch time‐to‐peak was not significantly changed, and half‐relaxation and total contraction time were decreased by 5.3% and 2.8%, respectively, but the twitch tension (Pt) was not significantly changed and the Pt/Po ratio was decreased by 8.7%. The 60 s intermittent contractions (50 impulses s−1) decreased tetanic force to 57% (P < 0.05) of initial values, but force reduction was not significantly different in the two fatigue‐inducing tests: fatigue index (the mean loss of force of the last five contractions, expressed as a percentage of the mean value of the first five contractions) was 36.2 ± 5.4% vs. 38.6 ± 2.8%, respectively (P > 0.05). While identical force reduction was present in the two fatigue‐inducing tests, it would appear that concomitant electrical failure was considerably different. Comparison of the electrical and mechanical alterations recorded during voluntary contractions, and in contractions evoked by electrical stimulation of the motor nerve, suggests that immersion not only modifies the peripheral processes associated with contraction, but also changes central and/or neural command of the contraction. At peripheral sites, it is proposed that the intracellular processes of contraction play a role in the contractile impairment recorded during immersion.
Phenotype and Function of Somatic Primary Afferent Nociceptive Neurones with C‐, Aδ‐ or Aα/β‐Fibres
Authors: Lawson S. N.
Published: February 2003

Nociceptive dorsal root ganglion (DRG) neurones have fibres that conduct in the C, Aδ and Aα/β conduction velocity range. The properties of nociceptive compared with non‐nociceptive somatic afferent dorsal root ganglion neurones appear to fall into two patterns, A and B. Pattern A properties of nociceptive neurones, the more common type, include longer action potential duration and slower maximum rate of fibre firing, as well as a greater expression of substance P and calcitonin gene‐related peptide immunoreactivity. The values of pattern A properties appear to be graded according to the conduction velocity group (C, Aδ or Aα/β) of the fibres. The most pronounced forms of A‐type properties are expressed by nociceptive neurones with C‐fibres, and these become less pronounced in nociceptive neurones with Aδ‐fibres and least pronounced in those with Aα/β fibres (C > Aδ > Aα/β). Some of these properties are also expressed in a less extreme but similarly graded manner through C, Aδ and Aα/β groups of non‐nociceptive low threshold mechanoreceptive (LTM) neurone. The less common pattern B properties of nociceptive neurones have similar values in C‐, Aδ‐ and Aα/β‐fibre nociceptive neurones but these clearly differ from LTM units with C‐, Aδ‐ and Aα/β‐fibre conduction velocities. These features of nociceptive neurones include consistently larger action potential overshoots and longer after‐hyperpolarisation durations in nociceptive than in LTM neurones.
The Caudal Medullary Ventrolateral Reticular Formation in Nociceptive‐Cardiovascular Integration. An Experimental Study in the Rat
Authors: Lima Deolinda , Albino‐Teixeira António , Tavares Isaura
Published: February 2003

The endogenous pain control system is composed of multiple functionally distinct brain regions, which are thought to integrate nociceptive information with various brain functions. The clear involvement of some pain control centres in cardiovascular modulation has been claimed as a strong indication of their role in nociceptive‐cardiovascular integration. Particular emphasis has been given to their putative function in triggering cardiovascular reactions to pain. However, the possibility of their participation in the less‐studied influence of cardiovascular conditions in pain perception has been largely ignored. We have recently addressed this issue by investigating the involvement of the caudal ventrolateral medullary reticular formation (cVLM) in hypertension‐induced hypoalgesia. Circuits capable of conveying cVLM‐elicited antinociception include a direct reciprocal cVLM‐spinal loop, and two disynaptic spinal pathways relaying in rostroventromedial medullary (RVM) neurones and A5 noradrenergic neurones. In the three pathways, the cVLM neurones involved are circumscribed to a small area of reticular formation located laterally to the lateral reticular nucleus, the VLMlat. The VLMlat has a vasodepressor effect similar to that obtained from the cVLM. In the spinal cord dorsal horn, c‐fos expression evoked by noxious stimuli is decreased in hypertensive animals, as compared to normotensive animals. In hypertensive animals following lesion of the VLMlat, spinal c‐fos expression is identical to that observed in normotensive animals. The collected data point to a role for the VLMlat in the depression of spinal nociceptive processing in response to rises in blood pressure. Since hypertension‐induced hypoalgesia is mediated by spinal α2‐adrenoreceptors, this effect could be conveyed by the cVLM‐A5‐spinal pathway.
Myocardial Infarction and Cardiac Remodelling in Mice
Authors: Yang Fang , Liu Yun‐He , Yang Xiao‐Ping , Xu Jiang , Kapke Alissa , Carretero Oscar A.
Published: February 2003

We established a mouse model of cardiac dysfunction due to myocardial infarction (MI). For this we ligated the left anterior descending coronary artery in male C57BL/6J mice and assessed healing and left ventricular (LV) remodelling at 1, 2 and 4 days and 1, 2 and 4 weeks after MI. Echocardiography was performed at 1 and 2 weeks and 1, 2, 4 and 6 months after MI. We found that neutrophil infiltration of the infarct border was noticeable at 1‐2 days. Marked macrophage infiltration occurred at day 4, while lymphocyte infiltration was apparent at 7‐14 days. Massive proliferation of fibroblasts and collagen accumulation began by day 7‐14, and scar formation was completed by day 21. LV diastolic dimension increased markedly at 2 weeks and remained at the same level thereafter. LV shortening fraction decreased significantly at 2 weeks and then slowly decreased. In non‐infarcted areas of the LV, myocyte cross‐sectional area and interstitial collagen fraction increased progressively, reaching a maximum at 4 months. This study provides important qualitative and quantitative information about the natural history of cardiac remodelling after MI in mice.
Substrate Channelling in a Creatine Kinase System of Rat Skeletal Muscle Under Various pH Conditions
Authors: Gregor M. , Janovská A. , Stefl B. , Zurmanová J. , Mejsnar J.
Published: February 2003

The aim of this study was to evaluate myofibrillar creatine kinase (CK) activity and to quantify the substrate channelling of ATP between CK and myosin ATPase under different pH conditions within the integrity of myofibrils. A pure myofibrillar fraction was prepared using differential centrifugation. The homogeneity of the preparation and the purity of the fraction were confirmed microscopically and by enzymatic assays for contaminant enzyme activities. The specific activity of myofibrillar CK reached 584 ± 33 nmol PCr min−1 mg−1 at pH 6.75. Two methods were used to detect CK activity: (1) measurement of direct ATP production, and (2) measurement of PCr consumption. This method of evaluation has been tested in experiments with isolated creatine kinase. No discrepancy in CK activity between the methods was observed in the pH range tested (6.0‐7.5). However, the same procedures resulted in a significant discrepancy between the amounts of reacted PCr and produced ATP within the pure myofibrillar fraction. This discrepancy represents the portion of ATP produced by the CK reaction, which is preferentially channelled to the myosin ATPase before diffusing into the bulk solution. The maximum evaluated difference reached 42.3 % at pH 6.95. The substrate channelling between myofibrillar‐bound CK and myosin ATPase was evaluated under various pH levels within the physiological range and it reached a maximum value in a slightly acidic environment. These results suggest that ATP/ADP flux control by the CK system is more important at lower pH, corresponding to the physiological state of muscle fatigue.
Import of Nuclear‐Encoded Proteins into Mitochondria
Authors: Stojanovski Diana , Johnston Amelia J. , Streimann Illo , Hoogenraad Nicholas J. , Ryan Michael T.
Published: February 2003

The majority of mitochondrial proteins are encoded by nuclear genes, synthesized in the cytosol and subsequently imported into mitochondria through protein translocation machineries of the outer and inner membranes. In this review, we discuss the arrangement of the various translocation complexes and the function of individual import components. We also outline the various targeting pathways that preproteins can take in order to reach their appropriate sub‐mitochondrial compartment.
Glutamine and glutamate—their central role in cell metabolism and function
Authors: Newsholme Philip , Procopio Joaquim , Lima Manuela Maria Ramos , Pithon‐Curi Tania Cristina , Curi Rui
Published: February 2003

Glucose is widely accepted as the primary nutrient for maintenance and promotion of cell function. However, we propose that the 5‐carbon amino acids, glutamine and glutamate, should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine are many and include: substrate for protein synthesis, anabolic precursor for muscle growth, acid–base balance in the kidney, substrate for ureogenesis in the liver, substrate for hepatic and renal gluconeogenesis, an oxidative fuel for intestine and cells of the immune system, inter‐organ nitrogen transport, precursor for neurotransmitter synthesis, precursor for nucleotide and nucleic acid synthesis and precursor for glutathione production. Many of these functions are connected to the formation of glutamate from glutamine. We propose that the unique properties regarding concentration and routes of metabolism of these amino acids allow them to be used for a diverse array of processes related to the specialized function of each of the glutamine utilizing cells. In this review we highlight the specialized aspects of glutamine/glutamate metabolism of different glutamine‐utilizing cells and in each case relate key aspects of metabolism to cell function. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of erythropoietin and pentoxifylline on the oxidant and antioxidant systems in the experimental short bowel syndrome
Authors: Noyan Tevfik , Önem Önder , Ramazan Şekeroğlu M. , Köseoğlu Burhan , Dülger Haluk , Bayram İrfan , Sadık Yalçinkaya A. , Bakan Vedat
Published: February 2003

In this study, we investigated the effects of erythropoietin (Epo), and pentoxifylline (Ptx) on the oxidant and antioxidant systems in the experimental short bowel syndrome. Spraque‐Dawley rats were divided into four groups and all animals underwent 75% small bowel resection. Group E was treated with 500 IU kg− 1 Epo subcutaneously (s.c.), group P with 50 mg kg− 1 day− 1 s.c. Ptx and group E+P with 500 IU kg− 1 s.c. Epo plus 50 mg kg− 1 day− 1 s.c. Ptx for a period of 28 days. In group C, which is the control group, no drug treatment was given. At the end of 28 days the experimented rats were killed and ileum samples excised for biochemical and histopathological testing. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) levels were determined in ileum homogenates. When compared to group C, the MDA and GSH‐Px levels were significantly decreased (p < 0.05), but SOD activitiy was not changed (p > 0.05) in groups P and E+P, whereas both MDA and SOD and also GSH‐Px activities were not changed significantly in group E (p > 0.05). The average villous length, crypt depth, muscular thickness and mucosal length were measured in all groups. The average crypt depth and mucosal length were statistically higher in the group P than group C (p < 0.001, p < 0.01, respectively). In addition, the crypt depth was statistically higher in both E and E+P groups as compared to group C (p < 0.001, p < 0.01, respectively). Therefore, our study indicates that Ptx may be more effective than Epo in reducing lipid peroxidation. Moreover, we considered that Ptx may give this protective effect by inhibiting the free oxygen radicals to a greater extent than developing the antioxidant capacity. Copyright © 2002 John Wiley & Sons, Ltd.
Microcapsules made by enzymatically tailored alginate
Authors: Strand Berit L. , Mørch Yrr A. , Syvertsen Kjersti R. , Espevik Terje , Skjåk‐Bræk Gudmund
Published: February 2003

Alginate is widely used for encapsulation of cells. Alginate is a linear block copolymer consisting of mannuronic acid (M) and guluronic acid (G). It has been shown that enzymes known as C‐5 epimerases convert M to G in the polymer chain, giving rise to novel alginates with tailored properties. One of these enzymes, AlgE4, converts M blocks into blocks of strictly alternating M and G. In this study we investigated how alginate epimerized by AlgE4 affected capsule properties such as stability and permeability. Inhomogeneous calcium‐alginate gel beads were made with original and AlgE4‐epimerized alginates of different origin. The epimerized alginates formed initially smaller alginate gels that showed increased resistance to osmotic swelling compared with the original nonmodified alginate samples. The permeability, measured as diffusion of immunoglobulin (Ig) G into Ca/Ba‐alginate gel beads, was reduced by epimerization and further reduced by addition of poly‐L‐lysine (PLL). The osmotic stability of alginate‐poly‐D‐lysine(PDL)‐alginate capsules was enhanced by the use of epimerized alginate; indeed, stable capsules with low permeability to tumor necrosis factor (TNF) could be made with low PDL exposures. Finally, alginate with an alternating structure interacted more strongly with the alginate‐PLL capsule than did alginate with a high content of M blocks or G blocks or than an alginate consisting mainly of M. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 540–550, 2003
Mixed‐ligand modification of polyamidoamine dendrimers to develop an effective scaffold for maintenance of hepatocyte spheroids
Authors: Higashiyama S. , Noda M. , Kawase M. , Yagi K.
Published: February 2003

Compared with a monolayer culture, hepatocyte spheroids are known to maintain liver function for long periods. We found that hepatocytes formed spheroids when cultured on polyamidoamine dendrimers modified with fructose. Because galactose is a ligand for the asialoglycoprotein receptor on the hepatocyte cytoplasmic membrane, it was chosen as another ligand for modification in order to maintain adhesion of spheroids for long periods. Simultaneous modification of dendrimers with fructose and galactose had a marked effect on the time length of spheroid adhesion. Suppression of apoptosis and necrosis was observed in hepatocyte spheroids cultured on a dendrimer modified with fructose and galactose (F/G dendrimer). Moreover, the hepatocyte spheroids cultured on the F/G dendrimer had higher activities of liver‐specific functions, such as urea synthesis and albumin gene expression, than did those cultured on single‐ligand‐modified dendrimers. The expression of heat shock protein (HSP) genes was examined to evaluate the stress response of cells to scaffolds. The hepatocytes cultured on the F/G dendrimer had very low expression levels of both HSP60 and HSP70 mRNAs. Thus immobilization of mixed‐ligand‐modified dendrimers could generate a suitable surface for hepatocyte spheroid formation. These dendrimers could be a powerful tool for generating custom‐made scaffolds for cells other than hepatocytes by selecting the ligands suitable for each cell type. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 475–482, 2003
A meta‐analysis of the effectiveness of bibliotherapy for alcohol problems
Authors: Apodaca Timothy R. , Miller William R.
Published: February 2003

There has been increased interest in the use of brief interventions and the delivery of alcohol treatment services through nonspecialist health care settings. One possible resource for reaching untreated individuals is “bibliotherapy,” the provision of self‐help materials to motivate and guide the process of changing drinking behavior. Research on the effectiveness of self‐help materials for problem drinkers has been done for three decades. This report summarizes a meta‐analytic review of 22 studies evaluating the effectiveness of such self‐help materials. Each study was rated on 12 methodological criteria, and effect sizes of bibliotherapy were computed. The methodological quality of studies was generally high relative to other treatment‐outcome studies. Modest support was found for the efficacy of self‐help materials in decreasing at‐risk and harmful drinking. The weighted mean pre/post‐effect size for bibliotherapy was .80 with self‐referred individuals seeking help for drinking problems, and .65 for individuals identified through health screening. Between‐group comparisons of bibiotherapy with no‐intervention controls appear to have a small to medium effect, with a weighted mean effect size of .31 with self‐referred drinkers; effect size was more variable in opportunistic interventions based on health screening. Finally, between‐group comparisons of effects on drinking of bibliotherapy versus more extensive interventions yielded effect size values near zero. These findings provide support for the cost‐effective use of bibliotherapy with problem drinkers seeking such help to reduce their consumption, and to a lesser extent with drinkers who are identified through screening as at risk. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 289–304, 2003.