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Biomedical subjects

G Martin

Publications and source records attributed to G Martin.

At least 19 recordsLinked to original sources

Glycine, a new regulator of glutamine metabolism in isolated rat-liver cells.

Glycine (0.1-10 mM) caused a dose-dependent increase in the removal of 5 mM [1-14C]glutamine by isolated rat-liver cells; at low concentrations of glycine, an increase in the formation of 14CO2, urea and glucose from glutamine occurred. At 2-10 mM, glycine also caused an accumulation of ammonia, a well-established activator of glutaminase (E.C. 3.5.1.2) and, at concentrations found in the presence of glutamine plus glycine, ammonia stimulated glutamine removal. The inhibition of urea synthesis from glutamine observed with 10 mM glycine was relieved by the addition of ornithine, suggesting that this inhibition occurred by reducing the availability of ornithine for the ornithine transcarbamoylase reaction. The metabolism of glycine as sole substrate led to a small increase in the accumulation of ammonia. Glycine did not alter hepatic glutaminase activity but swelling of rat hepatocytes, a factor considered to stimulate glutamine metabolism, was observed in the presence of glycine (1 mM). It is concluded that stimulation by glycine of hepatic utilization of glutamine is mediated by the accumulation of ammonia arising from both glycine and glutamine metabolism and by hepatocyte osmotic swelling secondary to glycine transport.

Ammonia

Release and fixation of CO2 by guinea-pig kidney tubules metabolizing aspartate.

1. The metabolism of L-[U-14C]aspartate, L-[1-14C]aspartate and L-[4-14C]aspartate was studied in isolated guinea-pig kidney tubules. 2. Oxidation of C-1 plus that of C-4 of aspartate accounted for 90-92% of the CO2 released from aspartate, whereas oxidation of the inner carbon atoms of aspartate (which occurs beyond the 2-oxoglutarate dehydrogenase step) represented only 8-10% of aspartate carbon oxidation. 3. The formation of [1-14C]glutamine and [1-14C]glutamate from [1-14C]aspartate and [4-14C]aspartate indicated that about one-third of the oxaloacetate synthesized from aspartate underwent randomization at the level of fumarate. 4. With [U-14C]aspartate as substrate, the percentage of the C-1 of glutamate and glutamine found radiolabelled after 60 min of incubation was 92.7% and 47.5% in the absence and the presence of bicarbonate respectively. 5. That CO2 fixation occurred at high rates in the presence of bicarbonate was demonstrated by incubating tubules with aspartate plus [14C]bicarbonate; under this condition, the label fixed was found in C-1 of glutamate, glutamine and aspartate, as well as in C-4 of aspartate, demonstrating not only randomization of aspartate carbon but also aspartate resynthesis secondary to oxaloacetate cycling via phosphoenolpyruvate carboxykinase, pyruvate kinase and pyruvate carboxylase. 6. The importance of CO2 fixation in glutamine synthesis from aspartate is discussed in relation to the possible role of the guinea-pig kidney in systemic acid-base regulation in vivo.

Acetazolamide

High-performance liquid chromatographic method to resolve and determine lipopolysaccharide sub-groups of Escherichia coli endotoxin in isolated perfused rat liver perfusate.

A high-performance liquid chromatographic method was developed for resolving heterogeneous preparations of fluorescently labelled endotoxin derived from Escherichia coli (Serotype 0111:B4) into separate lipopolysaccharide sub-groups. The endotoxin was chromatographed on an analytical gel permeation column using a mobile phase of acetonitrile (20%, v/v) and 100 mM phosphate buffer (pH 7.75). Four fluorescent peaks were resolved, representing sub-groups of markedly different molecular sizes. Three of the four sub-groups contained the core polysaccharide 2-keto-3-deoxyoctonate, confirming that they contained lipopolysaccharide. Fluorescein isothiocyanate (FITC)-labelled endotoxins derived from Vibrio cholerae and Salmonella minnesota chromatographed using the same system eluted with distinctly different patterns of peaks from each other and from E. coli. Extraction of E. coli FITC-endotoxin from a buffer solution using a phenol-diethyl ether method and subsequent chromatography allowed the determination of three of the four fluorescent sub-groups over the concentration range 1-15 micrograms/ml.

Animals

New mRNA probes for hippocampal responses to entorhinal cortex lesions in the adult male rat: a preliminary report.

Three new mRNA responses were found in the hippocampus of the adult male rat after entorhinal cortex lesions (ECL) that induce synaptic reorganization. Hippocampus cDNA libraries were screened by a subtractive hybridization strategy designed to detect ECL-induced mRNAs. Partial sequencing showed clones with similarities to mouse vimentin, ferritin, and polypeptide 7B-2. A sequence similar to mouse SNAP-25 sequence was also detected. Using a mouse SNAP-25 probe, rat SNAP-25 mRNA increased in the hippocampus after ECL.

Animals

Contrast media-induced effects on blood rheology and their importance in angiography.

Factors which alter blood viscosity may have important consequences during angiography. The differential effects of various concentrations of five different radiocontrast media on the viscosity characteristics of erythrocyte-plasma suspensions were made over a range of applied shear rates. The results showed that, at both high and low shear rates, the rate of change of viscosity with contrast concentration differs markedly between the various types of contrast media. The conventional ionic monomers caused most disturbance to blood viscosity. The monoionic dimer hexabrix was least disturbing to the viscometric characteristics of blood, and the newer non-ionic monomers were intermediate in their effects. Significant effects on blood viscosity may be caused by radiocontrast agents during a number of in vivo angiographic situations, in particular: early after contrast bolus injection into large vessels, in the microcirculation after selective injections, and during angioplasty procedures.

Adult

Ageing has no effect on the volume density of hepatocytes, reticulo-endothelial cells or the extracellular space in livers of female Sprague-Dawley rats.

1. The hepatic reticulo-endothelial cell population is generally assumed to increase in size, along with the liver, during ageing in rats. However, this has not been rigorously established. 2. Using electron microscopy and stereological techniques, the present study has shown that the volume densities of hepatocytes and Kupffer cells (and probably also of endothelial cells, fat storing cells and the extracellular space) of the livers of female Sprague-Dawley rats are the same at 2 and 24-25 months of age. 3. This result indicates that the increase in size of the liver during ageing in the rat is associated with an equivalent increase in the volume of each cell population and the extracellular space.

Aging

Beliefs about smoking and health and attitudes toward tobacco control measures.

The opinions of a representative sample of adult South Africans about the effects of smoking on health and their attitudes toward tobacco control measures were surveyed by means of an interviewer-administered questionnaire. Seventy-five per cent of the respondents were black and 55.3% were female. More than 50% of blacks and Asians (61.7% and 53.2%) were non-smokers, whereas 52.1% of 'coloureds' were current smokers and 23.8% of whites ex-smokers. The majority of smokers (68.5%) acknowledged the harmful effects of direct smoking and a larger percentage of non- and ex-smokers (79.7% and 77% respectively) shared this view. A similar trend was observed in beliefs about passive smoking. Seventy-five per cent of participants felt that tobacco sales to minors should be banned and 55.8% thought that taxes on tobacco products should be increased. There was substantial white opposition to measures that prohibit tobacco companies from sponsoring sporting events. Most respondents felt that tobacco advertising should be banned on television (59.7%), radio (60.1%), in newspapers (58.4%), on billboards (58.7%) and in cinemas (59.3%). The results indicate that in the main the public supports the introduction of the measures proposed in the draft Tobacco Products Control Act and even more extensive legislation to control tobacco consumption. This augurs well for future strategies aimed at tobacco control in South Africa.

Adolescent

[Lowering peripheral vascular resistance by distal arteriovenous fistula surgery. Clinical and experimental studies].

Vascular run off has an important influence on patency rates of infrapopliteal bypasses especially when prosthetic grafts are used. Construction of a distal arteriovenous fistula can improve volume and velocity of graft flow. 39 patients, 14 of them diabetic, had femoro-crural PTFE-bypasses. A distal arteriovenous fistula in common ostium technique was established in 20 cases. The patency rate (early occlusions) was improved, especially diabetic patients seemed to profit by lowering the peripheral outflow resistance, which was measured intraoperatively. The influence of arteriovenous fistulas of different calibre on bypass flow and perfusion was analysed in a circulation model.

Arteriovenous Shunt, Surgical

Involvement of ventromedial medulla "multimodal, multireceptive" neurons in opiate spinal descending control system: a single-unit study of the effect of morphine in the awake, freely moving rat.

In the present work, we have studied the effects of systemic morphine on the electrophysiological properties of ventromedial medulla (VMM) neurons in the awake, freely moving rat. By means of a chronically implanted single-unit recording device, a drug delivery catheter, and the use of controlled innocuous and noxious cutaneous stimuli, we were able to study precisely the spontaneous and evoked VMM neuronal activities. We have particularly focused our attention upon the VMM "multimodal, multireceptive" units, excited by non-noxious and noxious stimuli (VMM MULT ON), which we have already determined as the neuronal class potentially involved in nociceptive processes at VMM level. We found that morphine (3 mg/kg, i.v.) does not affect the spontaneous activity of these neurons whereas their responses to noxious heat are strongly attenuated (70%), over a prolonged period (about 2 hr) associated with an increase in the response latency. This action of morphine appears to be pharmacologically specific since it is dose dependent to some extent, and is reversed by 0.3 mg/kg of naloxone. In parallel with this pharmacological specificity, we have also demonstrated a preferential physiological effect since the response of the VMM MULT ON neurons to light touch application is not affected by morphine. This specificity is emphasized by the fact that morphine does not modify the activity of the other VMM neuronal groups such as the units unresponsive to any kind of peripheral stimuli, and does not reveal "new" neuronal classes such as those we have found in previous studies after barbiturate administration. The differential effect upon the noxious versus innocuous inputs of these units produced by the opiate reinforces their participation in nociceptive processing since similar effects have been reported in well-known nociceptive somatosensory structures such as the dorsal horn of the spinal cord. Furthermore, although the precise mechanisms of action have not yet been determined, the spinal projection of the VMM MULT ON neurons, previously demonstrated by our group, suggests their involvement in an opiate descending spinal control system of nociception. Although speculative, one can imagine either a direct facilitatory MULT ON spinal effect being attenuated by morphine (disfacilitation), or a morphine-induced disinhibition of inhibitory GABAergic neurons acting upon the MULT ON neurons.

Animals

Magnetic resonance spectroscopy in cerebral ischemia.

Magnetic resonance spectroscopy (MRS) has been a fundamental and invaluable tool in the fields of chemistry and physics for over 40 years and has only been applied directly to the field of medicine in the last decade. MRS has contributed significant information on ischemic brain metabolism in the clinical patient. The potential of spectroscopy now extends to the diagnostic monitoring of metabolic change, in identifying markers of a therapeutic window, and establishing prognosis and outcome. This article presents a review of MRS studies of cerebral ischemia in clinical patients.

Blood Glucose

Plasma thromboxane and pulmonary artery pressure in neonates treated with extracorporeal membrane oxygenation.

To examine whether neonates with persistent pulmonary hypertension are subject to a thromboxane-mediated exacerbation of their pulmonary hypertension during extracorporeal membrane oxygenator therapy (a form of partial cardiopulmonary bypass), we performed serial measurements of plasma thromboxane B2 and pulmonary artery pressure before, during, and after extracorporeal membrane oxygenation. Pulmonary artery pressure was high before extracorporeal membrane oxygenation, did not increase after the start of this therapy, but began to decrease after 48 hours of extracorporeal membrane oxygenation. During the course of extracorporeal membrane oxygenation, mean pulmonary artery pressure decreased by 50% and mean plasma thromboxane B2 levels decreased by 70%. In addition, serial plasma thromboxane B2 levels were significantly correlated with pulmonary artery pressures in individual infants with a primary diagnosis of meconium aspiration (r = 0.965 to 0.723). We speculate that the decrease in pulmonary artery pressure and plasma thromboxane B2 levels over time may reflect resolution of acute lung injury and that thromboxane B2 may play a role in regulating pulmonary artery pressure in infants with meconium aspiration.

Echocardiography

Drastic changes of ventromedial medulla neuronal properties induced by barbiturate anesthesia. I. Comparison of the single-unit types in the same awake and pentobarbital-treated rats.

By means of single-unit recordings, as we have already performed in other studies, we have found that in the awake, drug-free, freely moving rat, there is only one neuronal class potentially involved in nociception and its control at the ventromedial medulla level (VMM, a structure involved in the spinal descending control systems of nociception): the 'multireceptive multimodal' units. These neurons are always activated by very light mechanical (air puff, light touch) and mechanical (pinch, pin-prick) or thermal noxious stimuli, in addition to an auditory stimulus. During identical VMM penetrations, performed in the same animals tested first awake and then anesthetized a few days later with 30 mg/kg of i.p. pentobarbital, we once again found the 'multireceptive multimodal' units, but this time with physiological properties that were strongly modified: in particular, we noted a disappearance of the nociceptive responses consecutive to a strong noxious heat pulse application (36-51 degrees C), associated sometimes with a reduction of the responses due to innocuous stimulation. This is in agreement with the classical effects of barbiturates. In light of previous observations reported in the literature devoted to the VMM physiology in the anesthetized rat, the most important observation in our study was that, with pentobarbital anesthesia, we recorded 'new' neuronal classes as compared to the awake condition. In these classes, which appeared to be qualitatively similar to those already reported under anesthesia, we found the units exclusively driven by innocuous stimulation (excited for the majority), the units specifically driven by noxious stimulation (half excited, half inhibited) and a 'multireceptive multimodal' group inhibited or excited-inhibited by non-noxious and noxious stimuli (half of the multireceptive group). All these data demonstrate that barbiturate anesthesia strongly modifies the VMM physiology in relation to nociception. Furthermore, since our results, that were obtained in anesthetized rats, were qualitatively identical to those described in the literature under similar experimental conditions, they raise the question of the appropriateness of using a barbiturate anesthetic in order to study the cellular mechanisms related to nociception at this level. In addition, these findings indicate that the obtention of only one neuronal class in the awake, drug-free, freely moving rat (the excited 'multireceptive' neurons) is not due to an experimental bias, which strongly emphasizes the reliability of using awake animals. However, it remains to be determined by which mechanisms pentobarbital 'distorts' the VMM physiology as compared to the normal, standard physiological conditions of the awake animal.

Anesthesia