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Biomedical subjects

J G Carter

Publications and source records attributed to J G Carter.

18 recordsLinked to original sources
PubMed1992

Glucose metabolism assessed with 2-deoxyglucose and the effect of glutamate in subdivisions of rat hippocampal slices.

A new approach to the study of glucose phosphorylation in brain slices is described. It is based on timed incubation with nonradioactive 2-deoxyglucose (DG), after which the tissue levels of DG and 2-deoxyglucose-6-phosphate (DG6P) are measured separately with sensitive enzymatic methods applied to specific small subregions. The smallest samples had dry weights of approximately 0.5 microgram. Direct measurements in different regions of hippocampal slices showed that within 6 min after exposure to DG, the ratios of DG to glucose in the tissue were almost the same as in the incubation medium, which simplifies the calculation of glucose phosphorylation rates and increases their reliability. Data are given for ATP, phosphocreatine, sucrose space, and K+ in specific subregions of the slices. DG6P accumulation proceeded at a constant rate for at least 10 min, even when stimulated by 10 mM glutamate in the medium. The calculated control rate of glucose phosphorylation was 2 mmol/kg (dry weight)/min. In the presence of 10 mM glutamate it was twice as great. The response to 10 mM glutamate of different regions of the slice was not uniform, ranging from 164% of control values in the molecular layer of CA1 to 256% in the stratum radiatum of CA1. There was a profound fall in phosphocreatine levels (75%) in response to 10 mM glutamate despite a 2.4-fold increase in glucose phosphorylation. Even in the presence of 1 mM glutamate, the increase in glucose phosphorylation (50%) was not great enough to prevent a significant drop in phosphocreatine content.

Adenosine Triphosphate↗
PubMed1991

Distribution in brain and retina of four enzymes of acetyl CoA synthesis in relation to choline acetyl transferase and acetylcholine esterase.

Eleven regions of mouse brain and twelve layers of monkey retina were assayed for choline acetyl transferase (ChAT), acetylcholine esterase (AChE), and 4 enzymes that synthesize acetyl CoA. The purpose was to seek evidence concerning the source of acetyl CoA for acetylcholine generation. In brain ATP citrate lyase was strongly correlated with ChAT as well as AChE (r = 0.914 in both cases). Weak, but statistically significant correlation, was observed between ChAT and both cytoplasmic and mitochondrial thiolase, whereas there was a significant negative correlation between ChAT and acetyl thiokinase. In retina ChAT was essentially limited to the inner plexiform and ganglion cell layers, whereas substantial AChE activity extended as well into inner nuclear, outer plexiform and fiber layers, but no further. ATP citrate lyase activity was also highest in the inner four retinal layers, but was not strongly correlated with either ChAT or AChE (r = 0.724 and 0.761, respectively). Correlation between ChAT and acetyl thiokinase was at least as strong (r = 0.757), and in the six inner layers of retina, the correlation between ChAT and acetylthiokinase was very strong (r = 0.932).

Acetate-CoA Ligase↗
PubMed1991

Enzyme levels in cultured astrocytes, oligodendrocytes and Schwann cells, and neurons from the cerebral cortex and superior cervical ganglia of the rat.

Data are presented for 16 enzymes from 8 metabolic systems in cell cultures consisting of approximately 95% astrocytes and 5% oligodendrocytes. Nine of these enzymes were also measured in cultures of oligodendrocytes, Schwann cells, and neurons prepared from both cerebral cortex and superior cervical ganglia. Activities, in mature astrocyte cultures, expressed as percentage of their activity in brain, ranged from 9% for glycerol-3-phosphate dehydrogenase to over 300% for glucose-6-phosphate dehydrogenase. Creatine phosphokinase activity in astrocytes was about the same as in brain, half as high in oligodendrocytes, but 7% or less of the brain level in Schwann cells and superior cervical ganglion neurons and only 16% of brain in cortical neurons. Three enzymes which generate NADPH, the dehydrogenases for glucose-6-phosphate and 6-phosphogluconate, and the NADP-requiring isocitrate dehydrogenase, were present in astrocytes at levels at least twice that of brain. Oligodendrocytes had enzyme levels only 30% to 70% of those of astrocytes. Schwann cells had much higher lactate dehydrogenase and 6-phosphogluconate dehydrogenase activities than oligodendrocytes, but showed a remarkable similarity in enzyme pattern to those of cortical and superior cervical ganglion neurons.

Animals↗
PubMed1991

Increased carbamazepine plasma concentrations after fluoxetine coadministration.

The interaction between fluoxetine and carbamazepine was investigated in six normal, healthy male volunteers (aged 23 to 40 years). Subjects were given carbamazepine, 400 mg every morning, for 3 weeks. Venous carbamazepine blood samples were obtained at baseline and 1, 2, 4, 6, 8, 10, 12, and 24 hours after the morning dose. Fluoxetine, 20 mg every morning, was then coadministered with carbamazepine for 7 days. Venous carbamazepine blood samples were again obtained as described. Carbamazepine and carbamazepine-10,11-epoxide (CBZE) were assayed by HPLC. Addition of fluoxetine resulted in a significant increase in the area under the concentration-time curve of carbamazepine (105.93 +/- 18.05 micrograms/ml.hr versus 134.97 +/- 12.15 micrograms/ml.hr; t = 3.284; df = 5; p = 0.022) and CBZE (11.6 +/- 1.93 micrograms/ml.hr versus 15.2 +/- 2.4 micrograms/ml.hr; t = 2.805; df = 5; p = 0.038). Both oral and intrinsic clearance of carbamazepine was decreased significantly on fluoxetine addition (3.87 +/- 0.68 L/hr versus 2.98 +/- 0.26 L/hr; t = 3.025; df = 5; p = 0.029 and 17.90 +/- 4.9 L/hr versus 11.92 +/- 1.4 L/hr; t = 3.037; df = 5; p = 0.029, respectively). No significant changes were determined for fraction of absorbed dose, volume of distribution, absorption rate constant, and elimination rate constant. These findings suggest that fluoxetine can inhibit the metabolism of carbamazepine. Careful monitoring of patients is recommended when these two drugs are coadministered.

Administration, Oral↗
PubMed1990

Measurement of 2-deoxyglucose and 2-deoxyglucose 6-phosphate in tissues.

The enzymatic methods previously described for 2-deoxyglucose (DG) and 2-deoxyglucose 6-phosphate have been refined and adapted to measurements of brain samples ranging from 50 mg wet weight to less than a microgram dry weight. Procedures for preparing such samples for assay are described. Analytical properties of the enzymes employed are given together with means for overcoming their possible short comings. Emphasis is placed on information useful for employing DG to assess rapid changes in glucose metabolism.

Animals↗
PubMed1990

A prospective study of the risk of an immediate adverse reaction to protamine sulfate during cardiopulmonary bypass surgery.

Protamine sulfate administration may cause life-threatening reactions. We prospectively examined the incidence of immediate adverse reaction after protamine in 243 patients who underwent cardiopulmonary bypass surgery. Twenty-six patients (10.7%) had reactions, and 1.6% had a precipitous drop in blood pressure immediately after protamine administration. Risk factors were previous exposure to protamine, diabetes, history of receiving protamine-containing insulin, and possibly vasectomy. However, neither a positive skin test nor a positive IgE ELISA for antiprotamine antibody predicted that a patient would have a reaction. C4a levels were increased in patients who had reactions as compared with age-, sex-, and cardiac disease-matched patients who did not have reactions, suggesting a role for complement in some reactions. Immediate adverse reactions to protamine are very common, and alternative therapies are urgently needed to eliminate the use of protamine.

Adult↗
PubMed1990

Use of nonradioactive 2-deoxyglucose to study compartmentation of brain glucose metabolism and rapid regional changes in rate.

A method is presented for measuring rapid changes in the rate of glucose phosphorylation in mouse brain with nonradioactive 2-deoxyglucose (DG). After times as short as 1 min after DG injection, the mouse is frozen rapidly, and selected brain regions are analyzed enzymatically for DG, 2-deoxyglucose 6-phosphate (DG6P), and glucose. The rate of glucose phosphorylation can be directly calculated from the rate of change in DG6P, the average levels of DG and glucose, and a constant derived from direct comparison of the rate of changes in glucose and DG6P after decapitation. Experiments with large brain samples provided evidence for a 2% per min loss of DG6P and at least two compartments differing in their rates of glucose metabolism, one rapidly entered by DG with glucose phosphorylation almost double that of average brain and another more slowly entered with a much lower phosphorylation rate. The method is illustrated by changes in phosphorylation within 2 min after injection of a convulsant or an anesthetic and over a 48-min time course with and without anesthesia. The sensitivity of the analytical methods can be amplified as much as desired by enzymatic cycling. Consequently, the method is applicable to very small brain samples. Examples are given for regions with volumes of 5 x 10(-4) microliters, but studies with samples as small as single large cell bodies are feasible.

Anesthesia, General↗
PubMed1989

A cost/benefit analysis of randomized invasive monitoring for patients undergoing cardiac surgery.

The aim of this study was to determine the effect of choice of invasive monitoring on cost, morbidity, and mortality in cardiac surgery. Two hundred and twenty-six adults undergoing elective cardiac surgery were initially assigned at random to receive either a central venous pressure monitoring catheter (group I), a conventional pulmonary artery (PA) catheter (group II), or a mixed venous oxygen saturation (SvO2) measuring PA catheter (group III). If the attending anesthesiologist believed that the patient initially randomized to group I should have a PA catheter, that patient was then reassigned to receive either a conventional PA catheter (group IV) or SvO2 measuring PA catheter (group V). The total costs were defined as the total amount billed to the patient for the catheter used; the professional cost of its insertion; and the determinations of cardiac output, arterial blood gas tensions, hemoglobin level, and hematocrit. Mean total monitoring and laboratory costs in Group I ($591 +/- 67) were statistically significantly (P less than 0.05) less than costs in Group II ($856 +/- 231). Further, mean monitoring and laboratory costs in Group II were statistically significantly (P less than 0.05) less than those in Group III ($1128 +/- 759). Patients in group IV incurred mean total costs of $986 +/- 578, while those in group V had mean total costs of $1126 +/- 382 (NS). There were no significant differences between any of the groups with respect to length of stay in the intensive care unit, morbidity, or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Analysis↗
PubMed1988

Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation.

We have developed an experimental paradigm to study the mechanism by which nerve growth factor (NGF) allows the survival of sympathetic neurons. Dissociated sympathetic neurons from embryonic day-21 rats were grown in vitro for 7 d in the presence of NGF. Neurons were then deprived of trophic support by adding anti-NGF antiserum, causing them to die between 24 and 48 h later. Ultrastructural changes included disruption of neurites, followed by cell body changes characterized by an accumulation of lipid droplets, changes in the nuclear membrane, and dilation of the rough endoplasmic reticulum. No primary alterations of mitochondria or lysosomes were observed. The death of NGF-deprived neurons was characterized biochemically by assessing [35S]methionine incorporation into TCA precipitable protein and by measuring the release of the cytosolic enzyme adenylate kinase into the culture medium. Methionine incorporation began to decrease approximately 18 h post-deprivation and was maximally depressed by 36 h. Adenylate kinase began to appear in the culture medium approximately 30 h after deprivation, reaching a maximum by 54 h. The death of NGF-deprived neurons was entirely prevented by inhibiting protein or RNA synthesis. Cycloheximide, puromycin, anisomycin, actinomycin-D, and dichlorobenzimidazole riboside all prevented neuronal death subsequent to NGF deprivation as assessed by the above morphologic and biochemical criteria. The fact that sympathetic neurons must synthesize protein and RNA to die when deprived of NGF indicates that NGF, and presumably other neurotrophic factors, maintains neuronal survival by suppressing an endogenous, active death program.

Animals↗
PubMed1979

Cardio-circulatory effects of enflurane anesthesia in health and disease.

The circulatory effects of enflurane (Ethrane) were studied in 10 unmedicated volunteers during anesthesia over a period of 90 min or more. Cardiac output did not change significantly at a mean alveolar concentration of 2.3 vol.%. Heart rate was increased in all cases. Enflurane causes negative inotropic activity in the heart muscle but has little influence on the pump performance of the heart.

Anesthesia, Inhalation↗
PubMed1979

Malignant hyperthermia.

A short review of the history, incidence, and present-day concept of the etiology of malignant hyperthermia is presented. Protocols for diagnosis, treatment of the unexpected occurrence, and management of known malignant hyperthermic patients is presented. The exact etiology of the syndrome is still unknown.

Anesthesia, Inhalation↗
PubMed1975

Intrarenal redistribution of blood flow in the early postburn period.

We interpret the findings of the present study and other studies reported here to indicate that alterations of renal outer to inner cortical blood flow distribution develop in the early postburn period. These alterations are similar to those observed by other investigators in animals subjected to various other traumatic events. Such flow redistributions were observed in both untreated animals and those receiving intravenous fluid resuscitation. Sharp reductions in urinary chloride and sodium concentrations observed in conjunction with these blood flow shifts may be a reflection of the relatively greater perfusion of juxtamedullary nephrons, which are alleged to have greater salt-retaining characteristics than their outer cortical counterparts.

Analysis of Variance↗