bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of the actions of group I metabotropic glutamate receptor subtype selective ligands on excitatory amino acid release and sodium‐dependent re‐uptake in rat cerebrocortical minislices
Authors: Fazal Abidali , Parker Fred , Palmer Alan M. , Croucher Martin J. 
Published: August 2003

AbstractIn this study we have tested the effects of a wide range of metabotropic glutamate receptor ligands on (i) depolarisation‐evoked efflux of pre‐accumulated d‐[3H]aspartic acid (d‐[3H]asp) from rapidly superfused rat cerebrocortical minislices, and (ii) Na+‐dependent uptake of d‐[3H]asp into cerebrocortical tissue. Transient elevations in extracellular K+ produced concentration‐dependent increases in d‐[3H]asp efflux. A submaximally effective concentration (50 mm) was used in all subsequent experiments. The broad‐spectrum mGlu receptor agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid [(1S,3R)‐ACPD; EC50 17.8 μm], the group I mGlu‐selective agonist (S)‐3,5‐dihydroxyphenylglycine [(S)‐3,5‐DHPG; EC50 0.5 μm] and the mGlu5 receptor subtype‐selective agonist (RS)‐2‐chloro‐5‐hydroxyphenylglycine [(RS)‐CHPG; EC50 7.3 μm] all concentration‐dependently potentiated high K+‐evoked d‐[3H]asp efflux in the absence of effects on basal outflow of radiolabel. At concentrations selective for mGlu1 receptors, the antagonists (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid [(RS)‐AIDA; 10–300 μm]; (+)‐2‐methyl‐4‐carboxyphenylglycine [LY367385; 1–100 μm] and 7‐hydroxyiminocyclopropan[b]chromen‐1a‐carboxylate ethyl ester [CPCCOEt, 1–30 μm] all failed to inhibit responses to (S)‐3,5‐DHPG. However, the broad‐spectrum mGlu receptor antagonist (S)‐α‐methyl‐4‐carboxyphenylglycine [(S)‐MCPG; IC50 88.5 μm] together with the recently described mGlu5‐selective antagonists, 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP; IC50 0.6 μm), 6‐methyl‐2‐(phenyl‐azo)‐3‐pyridinol (SIB‐1757; IC50 4.4 μm) and (E)‐2‐methyl‐6‐(2‐phenylethenyl)pyridine (SIB‐1893; IC50 3.1 μm), at mGlu5‐selective concentrations, all powerfully and concentration‐dependently inhibited (S)‐3,5‐DHPG‐evoked responses. Two selective excitatory amino acid (EAA) uptake inhibitors, l‐trans‐2,4‐pyrrolidine dicarboxylate (l‐trans‐2,4‐PDC; IC50 229 μm) and dl‐threo‐β‐benzyloxyaspartate (dl‐TBOA; IC50 665 μm) both inhibited the Na+‐dependent uptake of d‐[3H]asp into cerebrocortical minislices. Importantly, none of the mGlu ligands utilized in the present study significantly inhibited d‐[3H]asp uptake at concentrations shown to potentiate K+‐evoked efflux. These data demonstrate for the first time that mGlu5 ligands modulate extracellular EAA concentrations by a direct effect on mGlu5‐type autoreceptors on EAA nerve terminals as they evoke clear changes in EAA release in the absence of any effects on EAA uptake. Selective mGlu5 receptor antagonists that show high potency and good central bioavailability may provide novel classes of neuroprotective agents for the treatment of brain disorders associated with abnormal EAAergic neurotransmission.
Role of nitric oxide in rotenone‐induced nigro‐striatal injury
Authors: He Yi , Imam Syed Z. , Dong Zaojun , Jankovic Joseph , Ali Syed F. , Appel Stanley H. , Le Weidong 
Published: August 2003

AbstractRotenone, a widely used pesticide, causes a syndrome in rats that mimics, both behaviorally and pathologically, the symptoms of Parkinson's disease. The present study evaluated the role of nitric oxide in rotenone‐induced nigro‐striatal injury. After administration of rotenone in rats for 40 days, there was a moderate but significant injury of the nigro‐striatal pathway indicated by a 47% decrease in striatal dopamine levels and a 28% loss of substantia nigra tyrosine hydroxylase‐immunopositive neurons. Furthermore, a significant (37%) increase in the number of cells positive for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d) in the striatum was observed, accompanied by a 83% increase in nitric oxide synthase (NOS) activity and a significant increase in the production of 3‐nitrotyrosine (3‐NT). There was a significant increase (45%) in the optical density of NADPH‐d staining and an increase (72%) in NOS activity in the substantia nigra. Moreover, administration of the neuronal NOS inhibitor 7‐nitroindazole significantly attenuated the increased NOS activity and 3‐NT production, and provided significant protection against rotenone‐induced nigro‐striatal injury. Our data suggest that chronic rotenone administration can lead to significant injury to the nigro‐striatal system, mediated by increased generation of nitric oxide.
A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114
Authors: Crystal Adam S. , Giasson Benoit I. , Crowe Alexander , Kung Mei‐Ping , Zhuang Zhi‐Ping , Trojanowski John Q. , Lee Virginia M.‐Y. 
Published: August 2003

AbstractProteinaceous inclusions with amyloidogenic properties are a common link between many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Histological and in vitro studies of amyloid fibrils have advanced the understanding of protein aggregation, and provided important insights into pathogenic mechanisms of these neurodegenerative brain amyloidoses. The classical amyloid dyes Congo Red (CR) and thioflavin T and S, have been used extensively to detect amyloid inclusions in situ. These dyes have also been utilized to monitor the maturation of amyloid fibrils assembled from monomer subunits in vitro. Recently, the compound (trans,trans)‐1‐bromo‐2,5‐bis‐(3‐ hydroxycarbonyl‐4‐hydroxy)styrylbenzene (BSB), derived from the structure of CR, was shown to bind to a wide range of amyloid inclusions in situ. More importantly it was also used to label brain amyloids in live animals. Herein, we show that an analogue of BSB, (trans,trans)‐1‐bromo‐2,5‐bis‐(4‐hydroxy)styrylbenzene (K114), recognizes amyloid lesions, and has distinctive properties which allowed the quantitative monitoring of the formation of amyloid fibrils assembled from the amyloid‐β peptide, α‐synuclein, and tau.
Effect of subthalamic nucleus or entopeduncular nucleus lesion on levodopa‐induced neurochemical changes within the basal ganglia and on levodopa‐induced motor alterations in 6‐hydroxydopamine‐lesioned rats
Authors: Périer Céline , Marin Concepció , Jimenez Anna , Bonastre Mercè , Tolosa Eduardo , Hirsch Etienne C. 
Published: August 2003

AbstractInactivation of the subthalamic nucleus (STN) or the internal segment of the pallidum (GPi)/entopeduncular nucleus (EP) by deep brain stimulation or lesioning alleviates clinical manifestations of Parkinson's disease (PD) as well as reducing the side‐effects of levodopa treatment. However, the effects of STN or entopeduncular nucleus (EP) lesion on levodopa‐related motor fluctuations and on neurochemical changes induced by levodopa remain largely unknown. The effects of such lesions on levodopa‐induced motor alterations were studied in 6‐hydroxydopamine (6‐OHDA)‐lesioned rats and were assessed neurochemically by analyzing the functional activity of the basal ganglia nuclei, using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase as molecular markers of neuronal activity. At the striatal level, preproenkephalin (PPE) mRNA levels were analyzed. We found in 6‐OHDA‐lesioned rats that a unilateral STN or EP lesion ipsilateral to the 6‐OHDA lesion had no effect on either the shortening in the duration of the levodopa‐induced rotational response or the levodopa‐induced biochemical changes in the basal ganglia nuclei. In contrast, overexpression of PPE mRNA due to levodopa treatment was reversed by the STN or EP lesion. Our study thus shows that lesion of the EP or STN may counteract some of the neurochemical changes induced by levodopa treatment within the striatum.
A prolonged postinspiratory pause enhances CO2 elimination by reducing airway dead space
Authors: Uttman Leif , Jonson Björn 
Published: September 2003

SummaryBackground: CO2 elimination per breath (VCO2,T) depends primarily on tidal volume (VT). The time course of flow during inspiration influences distribution and diffusive mixing of VT and is therefore a secondary factor determining gas exchange. To study the effect of a postinspiratory pause we defined ‘mean distribution time’ (MDT) as the mean time given to inspired gas for distribution and diffusive mixing within the lungs. The objective was to quantify changes in airway dead space (VDaw), slope of the alveolar plateau (SLOPE) and VCO2,T as a function of MDT in healthy pigs.Methods: Ten healthy pigs were mechanically ventilated. Airway pressure, flow and partial pressure of CO2 were recorded during resetting of the postinspiratory pause from 10% (baseline) to, in random order, 0, 5, 20 and 30% of the respiratory cycle. The immediate changes in VDaw, SLOPE, VCO2,T, and MDT after resetting were analyzed.Results: V
Daw in percent of VT decreased from 29 to 22%, SLOPE from 0·35 to 0·16 kPa per 100 ml as MDT increased from 0·51 to 1·39 s. Over the same MDT range, VCO2,T increased by 10%. All these changes were statistically significant.Conclusion: MDT allows comparison of different patterns of inspiration on VDaw and gas exchange. Estimation of the effects of an altered ventilator setting on exchange of CO2 can be done only after about 30 minutes, while the transient changes in VCO2,T may give immediate information. MDT affects gas exchange to an important extent. Further studies in human subjects in health and in disease are needed.
Evaluation of oxygen uptake kinetics and oxygen kinetics of peripheral skeletal muscle during recovery from exercise in patients with chronic obstructive pulmonary disease
Authors: Okamoto Takashi , Kanazawa Hiroshi , Hirata Kazuto , Yoshikawa Junichi 
Published: September 2003

SummaryThe biochemical features of skeletal muscle and its contribution to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD) is under active investigation. Near‐infrared spectroscopy (NIRS) can non‐invasively provide information on the oxidative capacity of muscle. To clarify whether oxygenation of peripheral muscle is one determinant of exercise tolerance, we simultaneously examined the oxygen uptake () kinetics and oxygen kinetics of peripheral skeletal muscle evaluated by NIRS during recovery from exercise in COPD patients. Fifteen patients with COPD and five normal control subjects performed a symptom‐limited incremental exercise test. On the following day, all patients performed a constant work rate exercise test while being monitored using NIRS continuously for changes in concentration of oxygenated haemoglobin (HbO2) and during expired gas analysis. We found that the time constant of during recovery from constant work rate exercise () and the time constant of HbO2 during recovery (τHbO2off) were significantly longer in COPD patients than in normal control subjects. was inversely correlated with absolute values of forced expiratory volume in 1 s (FEV1·0) and FEV1·0 (% predicted). However, no significant correlation was found between and FVC (forced vital capacity), FEV1·0/FVC, or diffusing capacity of the lung for CO (DLCO). Moreover, was inversely correlated with maximal and maximal work rate. In contrast, exhibited a significant positive correlation with τHbO2off. These results indicate that kinetics during recovery is related to re‐oxygenation of peripheral skeletal muscle evaluated by NIRS in patients with COPD. Therefore, NIRS may be a useful tool to estimate the impairment of cardiopulmonary responses and re‐oxygenation of peripheral skeletal muscle during the immediate recovery phase after exercise in COPD patients.
Cardiopulmonary alterations in mRNA expression for interleukin‐1β, the interleukin‐6 superfamily and CXC‐chemokines during development of postischaemic heart failure in the rat
Authors: Tønnessen Theis , Florholmen Geir , Henriksen Unni Lie , Christensen Geir 
Published: September 2003

SummaryCytokines and chemokines are believed to play a pathogenic role in heart failure (HF). Although some cytokines and chemokines have been examined in HF, information about others is still lacking. We aimed to examine the expression of cytokines belonging to the interleukin (IL)‐6 superfamily [IL‐6 and ciliary neurotrophic factor (CNTF)], as well as IL‐1β and the CXC‐chemokines monocyte chemoattractant protein‐1 (MCP‐1) and IL‐8. We examined their expression in the heart, lung and spleen during development of postischaemic HF 1 and 6 weeks following left coronary artery ligation. Rats, which after myocardial infarction had a left ventricular end‐diastolic pressure above 15 mmHg, were considered to be in HF. Sham‐operated rats served as controls. A substantial upregulation of cardiac IL‐1β was measured in HF at 1 week, whereas a downregulation was measured in the lungs. At 6 weeks no altered regulation was seen. CNTF was only upregulated in the viable left ventricle at 6 weeks and IL‐6 was upregulated in the infarcted region at 1 week. Cardiac MCP‐1 was upregulated in the viable and the infarcted region of the failing left ventricle at 1 week, with the highest expression in the latter. In the lung, another pattern of regulation was seen with a significant increase in pulmonary MCP‐1 at 6 weeks. IL‐8 was only detected in the infarcted region at 1 week. In the spleen, no regulation of cytokines was found. In conclusion, we report an organ‐specific regulation of cytokines and chemokines in postischaemic HF. Our novel findings of increased cardiac CNTF and cardiopulmonary MCP‐1 mRNA indicate a role for these factors in the pathogenesis of HF.
A new non‐invasive ultrasonic method for simultaneous measurements of longitudinal and radial arterial wall movements: first in vivo trial
Authors: Persson Magnus , Rydén Ahlgren Åsa , Jansson Tomas , Eriksson Anders , Persson Hans W. , Lindström Kjell 
Published: September 2003

SummaryDuring recent years, the radial movement of the arterial wall has been extensively studied, and measurements of the radial movement are now an important tool in cardiovascular research for characterizing the mechanical properties of the arterial wall. In contrast, the longitudinal movement of vessels has gained little or no attention as it has been presumed that this movement is negligible. With modern high‐resolution ultrasound, it can, however, be seen that the intima‐media complex of the arterial wall moves not only in the radial direction, but also in the longitudinal direction during pulse‐wave propagation. This paper describes a new non‐invasive ultrasonic method that is able to measure simultaneously two dimensionally arterial vessel wall movements. The method is demonstrated in a limited in vivo trial. Results from the in vivo trial show that, apart from the well‐known radial movement, there is a distinct longitudinal movement in the human common carotid artery with, in this case, the intima‐media complex moving substantially as compared with the region of the tunica adventitia. Two‐dimensional evaluation of the vessel‐wall movements, taking not only the radial movement, but also the longitudinal movement into account, may provide novel information of importance in the evaluation of vessel‐wall function.
Gas embolism: pathophysiology and treatment
Authors: van Hulst Robert A. , Klein Jan , Lachmann Burkhard 
Published: September 2003

SummaryBased on a literature search, an overview is presented of the pathophysiology of venous and arterial gas embolism in the experimental and clinical environment, as well as the relevance and aims of diagnostics and treatment of gas embolism. The review starts with a few historical observations and then addresses venous air embolism by discussing pulmonary vascular filtration, entrapment, and the clinical occurrence of venous air emboli. The section on arterial gas embolism deals with the main mechanisms involved, coronary and cerebral air embolism (CAE), and the effects of bubbles on the blood–brain barrier. The diagnosis of CAE uses various techniques including ultrasound, perioperative monitoring, computed tomography, brain magnetic resonance imaging and other modalities. The section on therapy starts by addressing the primary treatment goals and the roles of adequate oxygenation and ventilation. Then the rationale for hyperbaric oxygen as a therapy for CAE based on its physiological mode of action is discussed, as well as some aspects of adjuvant drug therapy. A few animal studies are presented, which emphasize the importance of the timing of therapy, and the outcome of patients with air embolism (including clinical patients, divers and submariners) is described.
University of Cincinnati Dyspnea Questionnaire for Evaluation of Dyspnoea during physical and speech activities in patients with chronic obstructive pulmonary disease: a validation analysis
Authors: Hodgev V. , Kostianev S. , Marinov B. 
Published: September 2003

SummaryUniversity of Cincinnati Dyspnea Questionnaire (UCDQ) was developed to measure the impact of dyspnoea during (1) physical activity (Phys), (2) speech activity (Speech) and (3) simultaneous speech and physical activity (Comb). The aim of this study was to evaluate the validity of UCDQ in COPD patients, comparing it to a large set of dyspnoeic indices and functional parameters. Fifty COPD patients (age 58·7 ± 9·1 years, FEV1%pred = 39·3 ± 17·0%, Baseline Dyspnoea Index (BDI) = 4·9 ± 2·5, Six Minute Walk Distance (6MWD) = 373 ± 128 m, Symptoms score = 9·4 ± 2·5; mean ± SD) participated in the study. We found the following mean scores for the three sections of the questionnaire: Phys = 3·5 ± 0·9; Speech = 2·4 ± 1·1; Comb = 4·2 ± 1·0, meaning that patients report the most breathlessness during the combination of speaking and physical activity and the least breathlessness during speech activities. All three section of UCDQ had significant strong correlation with dyspnoea indices (BDI, Borg, MRC, OCD), 6MWD and symptoms score, which proves its concurrent and construct validity. Differentiation of patients by speech section (=3<) discriminated them significantly with respect to all dyspnoeic indices, symptoms score and 6MWD. All three dimensions of UCDQ had high test–retest reliability – ICC between 0·76 and 0·93. Factor analysis yielded three interpretable factors, as all dyspnoeic indices, three sections of UCDQ, symptoms score and 6MWD were loaded on the first factor. In conclusion, UCDQ provides valid and reliable information about the effect of dyspnoea on speech and daily activities.
Effects of simultaneous aortocaval occlusion on oxygen consumption in patients
Authors: Hofland Jan , Tenbrinck Robert , Eggermont Alexander M.M. , van Eijck Casper H.J. , Gommers Diederik , Erdmann Wilhelm 
Published: September 2003

SummaryThe effects of simultaneous occlusion of the thoracic aorta and inferior vena cava on oxygen consumption () have not yet been reported in humans. Ten patients (all ASA II) needed such simultaneous occlusion to allow hypoxic abdominal perfusion in the treatment of pancreatic cancer. With the development of the PhysioFlex® anaesthesia machine for closed‐circuit anaesthesia, intra‐operative real‐time curves of became available. Thus, we can continuously measure , and air consumption. By placing a pulmonary artery catheter, we could also intermittently calculate during the several phases of the perfusion procedure. Immediately after the simultaneous aortocaval occlusion started, decreased by 35% (68 ml min−1 m−2) and decreased below the critical value of 330 ml min−1 m−2. At reperfusion, repayment of the oxygen debt was by a two‐stage pattern: a fast repayment stage with an increase of about 65% was followed by a slow repayment stage of 14% increase (values compared to steady state). Oxygen consumption in women was found to be significantly lower than in men (P = 0·02), with significant variation between the sexes during different stages of the procedure. The oxygen debt was not completely repaid by the end of the procedure. We conclude that the significant variation found in oxygen consumption will have consequences while performing low‐flow anaesthesia, that additional oxygen supply during the recovery period because of the initially incomplete repayment of oxygen debt may be useful and that studies on oxygen consumption must present gender‐specific data because of the gender‐dependent variation found in oxygen consumption.
Prolonged acetylcholine‐induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome
Authors: Khan Faisel , Spence Vance , Kennedy Gwen , Belch Jill J. F. 
Published: September 2003

SummaryAlthough the aetiology of chronic fatigue syndrome (CFS) is unknown, there have been a number of reports of blood flow abnormalities within the cerebral circulation and systemic blood pressure defects manifesting as orthostatic intolerance. Neither of these phenomena has been explained adequately, but recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism. Our group has previously reported enhanced skin vasodilatation in response to cumulative doses of transdermally applied acetylcholine (ACh), implying an alteration of peripheral cholinergic function. To investigate this further, we studied the time course of ACh‐induced vasodilatation following a single dose of ACh in 30 patients with CFS and 30 age‐ and gender‐matched healthy control subjects. No differences in peak blood flow was seen between patients and controls, but the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects. The time taken to decay to 75% of the peak response in patients and controls was 13·7 ± 11·3 versus 8·9 ± 3·7 min (P = 0·03), respectively, and time taken to decay to 50% of the peak response was 24·5 ± 18·8 versus 15·1 ± 8·9 min (P = 0·03), respectively. Prolongation of ACh‐induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.
Assessment of adipose tissue metabolism by means of subcutaneous microdialysis in patients with sepsis or circulatory failure
Authors: Martinez Alexandre , Chiolero Rene , Bollman Marc , Revelly Jean‐Pierre , Berger Mette , Cayeux Christine , Tappy Luc 
Published: September 2003

SummaryTo evaluate the role of adipose tissue in the metabolic stress response of critically ill patients, the release of glycerol and lactate by subcutaneous adipose tissue was assessed by means of microdialysis in patients with sepsis or circulatory failure and in healthy subjects. Patients with sepsis had lower plasma free fatty acid concentrations and non‐significant elevations of plasma glycerol concentrations, but higher adipose‐systemic glycerol concentrations gradients than healthy subjects or patients with circulatory failure, indicating a stimulation of subcutaneous adipose lipolysis. They also had a higher lipid oxidation. Lipid metabolism (adipose‐systemic glycerol gradients, lipid oxidation) was not altered in patients with circulatory failure. These observations highlight major differences in lipolysis and lipid utilization between patients with sepsis and circulatory failure. Hyperlactataemia was present in both groups of patients, but the adipose‐systemic lactate concentration gradient was not increased, indicating that lactate production by adipose tissue was not involved. This speaks against a role of adipose tissue in the development of hyperlactataemia in critically ill patients.