Biomedical subjects

M Rosenthal

Publications and source records attributed to M Rosenthal.

At least 235 records · Page 13Linked to original sources

PubMed1982

Does endogenous norepinephrine regulate potassium homeostasis and metabolism in rat cerebral cortex?

The role of endogenous cerebral norepinephrine (NE) as a modulator of transmembrane cation transport and energy metabolism was evaluated by monitoring extracellular potassium ion activity ([K+[o) in vivo and by measuring cortical Na+,K+-ATPase activity and oxygen consumption in vitro. Ipsilateral cortical NE was depleted by unilateral 6-hydroxydopamine (6-OHDA) lesions of the locus ceruleus (LC). The contralateral cortex was used for control measurements. NE depletion had no effect on resting levels of cortical [K+[o or on the rate of K+ removal from the extracellular space following direct cortical stimulation. There was also no effect of NE depletion on Na+,K+-ATPase activity in cortical homogenates nor on oxygen consumption of cortical slices over a wide range of K+ concentrations. These results indicate tht central NE depletion does not influence movements of cortical K+ either directly through an influence on Na+,K+-ATPase activity or indirectly through effects on oxidative metabolism. It is probable, therefore, that previously described effects of NE on cortical oxidative metabolism are mediated through changes in cerebral perfusion and/or modification of substrate availability in vivo.

Animals↗

PubMed1982

Effect of age on glucose tolerance, insulin secretion, and in vivo insulin action.

The effect of age on glucose tolerance, insulin secretion, and in vivo insulin action (insulin clamp) was studied in 48 nonobese subjects, all of whom were fully ambulatory and in good general health. The observed age-related increase in fasting plasma glucose (r = 0.35, P less than 0.01) was not due to an increase in relative body weight (RBW). Plasma insulin levels, both fasting and postprandial, tended to rise with age, but these changes were not significant. There was a marginally significant correlation (r = -0.21) between age and insulin-stimulated glucose utilization, which fell to -0.13 when controlled for RBW. However, steady-state insulin levels during the insulin-clamp period were higher in the older subjects, suggesting that age leads to an impairment in insulin catabolism; thus it is likely that the impairment of in vivo insulin action with age was underestimated. The variation in in vivo action between individuals was much greater among the older subjects. It was concluded that the glucose intolerance associated with aging is of relatively minor magnitude when ambulatory, generally healthy, nonobese, and nondiabetic subjects are studied. The cause of the glucose intolerance associated with aging seems to be loss of normal in vivo insulin action. On the other hand, this defect is not shared by all older persons, and in many over the age of 70, glucose transport is as efficient as in persons in their 20s.

Adult↗

PubMed1982

Clinical response to therapy with thymopoietin pentapeptide (TP-5) in rheumatoid arthritis.

The effect of thymopoietin pentapeptide (TP-5) was evaluated in patients with rheumatoid arthritis (RA). Ninety-two patients were divided into 3 groups, namely, placebo, TP-5 intramuscularly (IM) 1 mg, TP-5 intravenously (IV) 50 mg, and were evaluated for 6 measures of disease activity at the beginning of the study and at 3 and 6 months. No difference was observed between the placebo group and the group treated with TP-5 IM 1 mg. However, in the group treated with TP-5 IV 50 mg a statistically significant improvement of all parameters except the ESR was observed.

Arthritis, Rheumatoid↗

PubMed1982

Brain potassium ion homeostasis, anoxia, and metabolic inhibition in turtles and rats.

Microelectrode measurements of tissue oxygen tension (PtO2) and extracellular potassium ion concentration ([K+]o) and dual wavelength spectrophotometric measurements of the reduction/oxidation state of cytochrome aa3 were used to compare the resistance of turtle and rat brain to anoxia in vivo. In both species, respiration with 100% N2 resulted in a decrease of tissue oxygen tension to near 0 mmHg and reduction of cytochrome aa3. However, N2 respiration resulted in only moderate elevation of [K+]o in turtle bran while [K+]o in rat brain was elevated to levels greater than 50 mM. In addition, N2 respiration in turtles had no effect on the rate of recovery of [K+]o, which was elevated by direct electrical stimulation of the brain. Electrocorticographic activity (ECoG) of the turtle brain was only moderately depressed during N2 respiration for up to 4 h whereas the ECoG of rat brain became isoelectric within 1 min. Inhibition of glycolysis with iodoacetate (IAA) resulted in rapid elevation of [K+]o in turtle brain during anoxia, but IAA had little effect on [K+]o during normoxia. These results indicate that the remarkable resistance of the diving turtle to anoxia does not result from continued provision of oxygen to the brain either by redistribution of systemic blood flow or from blood O2 storage. In addition, the turtle brain does not rely on cellular stores of high-energy compounds for maintenance of ionic homeostasis. We conclude that potassium ion homeostasis in the anoxic turtle brain must result from increased glycolytic ATP production and from decreased energy utilization.

Animals↗

PubMed1982

Comparative brain oxygenation and mitochondrial redox activity in turtles and rats.

Comparisons were made between brain oxygenation and cytochrome c oxidase (cytochrome aa3) redox status in turtles (Pseudymys scripta) and rats. Although average brain O2 tension (PtO2) during normoxia was similar in turtle telencephalon and rat parietal cortex, a greater frequency of high and low values of PtO2 occurred in rats, which may indicate a steeper O2 gradient between capillaries and cells. When the fractional inspired O2 concentration (FIO2) was increased, PtO2 was elevated and cytochrome aa3 became more oxidized, whereas decreased FIo2 produced opposite changes in both species. In turtle brain, however, the relationship between PtO2 and cytochrome aa3 redox state was nearly linear over a wide range of PtO2 values. In rats, this relationship was steeper at PtO2 below normoxia and approached a plateau at Pto2 values above normoxia. Turtle brain cytochrome aa3 appeared more reduced in normoxia, which may be due either to lower affinity for O2 or to enhanced substrate supply. These results indicate that differences in resistance to hypoxia/anoxia observed between rats and turtles are probably not due to differences in O2 availability. Rather, it is likely that differences in redox activities of cytochrome aa3 and/or in substrate use play a role in the relative insensitivity of turtle brain to O2 deprivation.

Animals↗

PubMed1982

Abnormalities of cerebral oxidative metabolism in animal models of Parkinson disease.

Abnormalities of cerebral oxidative metabolism were investigated in "animal models" of Parkinson disease by in situ optical measurements of local cerebral blood volume and cytochrome oxidase redox shifts in rats two weeks after unilateral 6-hydroxydopamine lesions of the substantia nigra with or without interruption of ascending noradrenergic pathways. The data demonstrate oxidative metabolic dysfunction of ipsilateral cerebral hemispheres caused by lesions that involve both dopaminergic and noradrenergic systems but not when dopaminergic neurons only are affected. We speculate that the dementia of Parkinson disease may be more prevalent when degeneration of catecholaminergic systems is widespread and not restricted to the dopaminergic system.

Animals↗

PubMed1982

Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin-dependent diabetes mellitus.

The effect of glipizide treatment on diabetic control and on in vivo insulin secretion and action was studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were examined before and after a minimum of 3 mo treatment. Mean (+/- SEM) fasting plasma glucose level fell from 264 +/- 12 mg/dl to 172 +/- 10 mg/dl (P < 0.001) after glipizide treatment, and this was associated with a fall in total plasma glucose response to a test meal of approximately 35%. Mean (+/- SEM) fasting plasma insulin levels increased slightly from 15 +/- 2 micronU/ml following sulfonylurea treatment, and the total plasma insulin response to the test meal increased by 63%. However, there was no correlation (r = - 0.20) between the increase in plasma insulin response and the fall in plasma glucose levels that occurred as the result of sulfonylurea therapy. Glipizide treatment also led to enhanced in vivo insulin action, whether measured by the insulin clamp technique (P < 0.001) or the insulin suppression test (P< 0.02). Furthermore, in this instance there was a significant correlation (r - 0.69, P < 0.001) between the enhanced insulin action and the improvement on diabetes control. Thus, chronic therapy with glipizide, a new sulfonylurea agent, led to increased in vivo insulin secretion and insulin action. These results lend direct support to the assumption that sulfonylurea compounds have a substantial extrapancreatic effect on glucose homeostasis, and suggest that this effect contributes to the therapeutic efficacy of these drugs.

Aged↗

PubMed1982

Effect of variations in basal plasma glucose concentration on glucose utilization (M) and metabolic clearance (MCR) rates during insulin clamp studies in patients with non-insulin-dependent diabetes mellitus.

Two insulin clamp studies were performed at different steady-state plasma glucose concentrations in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM). Steady-state plasma insulin concentrations were comparable, with mean +/- SEM levels of 94 +/- 3 and 95 +/- 4 muU/ml being achieved during the two studies. Glucose utilization rate (M) varied directly with plasma glucose concentration in each subject. Thus, the mean +/- SEM value of M was 4.92 +/- 0.73 mg/kg/min when patients were studied at a mean +/- SEM plasma glucose concentration of 226 +/- 15 mg/dl, and M was 2.71 mg/kg/min when the same subjects were studied at a glucose concentration of 118 +/- 6 mg/dl. In contrast, the values for glucose metabolic clearance rate (MCR), which were 2.35 +/- 0.50 and 2.49 +/- 0.47 ml/kg/min, respectively, during the two studies, did not vary significantly with plasma glucose concentration. These data indicate that the glucose metabolic clearance rate (MCR), but not glucose utilization rate (M), can be used to compare in vivo insulin action when insulin clamp studies are performed in subjects with different basal plasma glucose concentrations.

Blood Glucose↗

PubMed1982

Does insulin removal rate from plasma decline with age?

The effect of age on the rate of insulin removal from plasma was studied in both rat and man. The experimental approach was based on measurement of the steady-state plasma insulin concentration achieved during a period in which endogenous insulin secretion was suppressed and exogenous insulin infused. Rats, 1 1/2 and 12 mo of age, were infused with 2.5, 5.0, and 10.0 mU/kg of insulin during a 180-min period in which endogenous insulin secretion was suppressed by epinephrine and propranolol. Steady-state plasma insulin concentrations were approximately twice as high in the older rats at every insulin infusion rate. Similar results were seen in man; significant correlations were observed between height of steady-state plasma insulin concentration and advancing age during infusion of exogenous insulin and suppression of endogenous insulin with either exogenous insulin (r = 0.66, P less than 0.001) or epinephrine and propranolol (r = 0.47, P less than 0.01). Since infusion rates of exogenous insulin were identical in all studies, these results suggest that there is an age-related decrease in insulin catabolism.

Adult↗

PubMed1982

[Cell kinetics and radiosensitivity of goat lymphocytes stimulated by phytohemagglutinin].

The harlequin-staining method has been used to study the cell kinetic of goat peripheral blood lymphocytes stimulated by phytohemagglutinin and to assess their radiosensitivity. At 48 h, the standardized culture time employed for human lymphocytes, 71% of the goat lymphocytes are in first mitosis, 23% are in second mitosis and 5% in third. Irradiation with 200 rads X-rays induces an average of 24.5 dicentric chromosomes per hundred cells in first mitosis.

Animals↗

PubMed1982

Ro 10-9359, an aromatic retinoid in the treatment of psoriatic arthritis. Clinical and immunological studies.

Clinical, general laboratory evaluation and immunological studies were conducted in 13 patients with active psoriatic arthropathy undergoing long-term treatment with aromatic retinoid (ethyl-all-trans-9-) (4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenate (Ro 10-9359). Evaluations were made at the beginning of treatment and at 3 and 6 months following drug therapy. A significant improvement in the clinical and laboratory parameters of inflammation was noted. In addition, immunological studies revealed certain changes suggesting that the treatment with Ro 10-9359 may effect some basic mechanisms of etiopathogenic significance in this disease. However, some undesirable, mostly dose-dependent adverse reactions affecting the muco-cutaneous tissues limit a wide use of this agent.

Adult↗

PubMed1982

The application of an extract of human placenta in the treatment of rheumatic affections.

Iontophoretic application of Placenta-Lucchini in combination with catalase and mucopolysaccharidase for the treatment of acute rheumatic inflammation results in significant clinical improvement. Such improvement is not seen if Placenta is used alone. Intra-articular application of Placenta in the arthritis joints of patients with rheumatoid arthritis results in a significant improvement as compared with placebo. Its efficacy is, however, inferior to that of Triamcinolone. Intra-articular application of Placenta prolongs local arthritic remissions induced by steroids.

Arthritis, Rheumatoid↗

PubMed1982

Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy.

Plasma lipid concentration and lipoprotein composition were studied before and after several months of glipizide treatment in 23 patients with non-insulin-dependent diabetes mellitus. The mean (+/- SEM) plasma glucose level fell 87 mg/dL, and the fall in plasma glucose concentration was correlated with a reduction in plasma triglyceride, very low-density lipoprotein triglyceride, cholesterol, and low-density lipoprotein cholesterol levels. Furthermore, there was a statistically significant increase in the plasma high-density lipoprotein cholesterol to total cholesterol ratio. Thus, improved diabetic control in patients treated with glipizide with non-insulin-dependent diabetes mellitus leads to changes in lipoprotein metabolism thought to be beneficial in terms of known cardiovascular risk factors.

Aged↗

PubMed1981

Local tissue oxygen tension-cytochrome a,a3 redox relationships in rat cerebral cortex in vivo.

Simultaneous measurements were made from rat cerebral cortex, in situ, of focal changes in both tissue oxygen tension (ptO2) and the reduction/oxidation ratio of cytochrome c oxidase (cytochrome a,a3) in order to study relationships between oxygen supply and consumption in small regions of tissue. Local ptO2 was measured with polarographic microelectrodes and the redox state of cytochrome a,a3 with a dual wavelength reflectance spectrophotometer. Increased ptO2, produced by respiration of gas mixtures with elevated O2 and/or CO2 content, was accompanied by increased oxidation of cytochrome a,a3. This confirms that cytochrome oxidase is not fully oxidized in focal brain tissue regions in vivo, as it is in mitochondria isolated in vitro. Decreased ptO2 was accompanied by cytochrome a,a3 reduction. The oxidative changes of cytochrome a,a3 with increases in ptO2 were smaller than the reductive changes associated with decreases in ptO2. Curves relating cytochrome a,a3 redox state to ptO2 were qualitatively alike, regardless of the initial ptO2 value from which they were generated. Thus, the reduction level of cytochrome a,a3 varied with ptO2 on a continuum. This consistent relationship demonstrates that changes in mitochondrial redox state provide an index of relative changes in tissue oxygenation in intact neocortex. The results suggest also that local rates of cerebral oxidative metabolism may not always be constant with changes in local ptO2.

Animals↗

PubMed1981

Oxidative metabolic responses with recurrent seizures in rat cerebral cortex: role of systemic factors.

Simultaneous focal measurements of cerebral oxygen tension and cytochrome a,a3 redox levels were made in rat cortex in order to obtain a direct and continuous assessment of oxidative metabolic changes during serial seizures. Initial seizures evoked by pentylenetetrazol were accompanied by transient increases in tissue pO2 and cytochrome a,a3 oxidation, confirming that oxygen provision is adequate to meet metabolic demand. After some point, subsequent seizures were accompanied by failure of pO2 to increase and failure of cytochrome a,a3 to oxidize, or by decreases in tissue pO2 and shifts in the redox level of cytochrome a,a3 toward reduction, signalling cortical oxygen insufficiency. Whereas early seizures were accompanied by increments in both cerebral blood volume and arterial blood pressure, one or both of these variables failed to increment during later seizures. This was particularly evident following the onset of spontaneously recurring seizures with short intervals between bursts of ECoG activity. These investigations emphasize the importance of systemic factors in determining the cerebral metabolic response to seizures and support the suggestion that neuronal damage in status epilepticus may be the result of derangements of oxidative metabolism.

Animals↗

PubMed1981

Nitrous oxide alters oxidative metabolic activities of rat neocortex in situ.

Nitrous oxide was shown by dual wavelength reflection spectrophotometry to decrease the ratio of reduction/oxidation of cytochrome a,a3 and to increase local blood volume in the cerebral cortex of rats in situ. These changes were in contrast to the decreased local blood volume and increased reduction of cytochrome a,a3 produced by pentobarbital. These effects of nitrous oxide were similar to those produced by respiration of 95% O2 with 5% CO2 except that such inspiration resulted in hemoglobin oxygenation while N2O produced some disoxygenation of hemoglobin. We conclude that the N2O effect on metabolism is likely due to increased energy demand. These results also provide some indication that changes in oxidative functioning in brain tissues may occur without alteration in the concentrations of high energy phosphate compounds.

Animals↗

PubMed1981

Norepinephrine depletion alters cerebral oxidative metabolism in the "active" state.

Unilateral chemical lesion of the nucleus locus coeruleus in rats produced unilateral depletion of ipsilateral cortical norepinephrine. Norepinephrine depletion was not associated with changes in "resting" metabolic balance of the cerebral cortex, as determined by in situ reflection spectrophotometry of the redox state of cytochrome oxidase. Norepinephrine depletion, however, caused slowing of the transient metabolic response to sudden increases in energy demand produced by direct cortical electrical stimulation. The effect was apparent in the redox state of both cytochrome oxidase and NAD, the latter being measured, also in situ, by reflection microfluorometry. These results demonstrate that norepinephrine has a role in modulating the response to increased metabolic demand in the cerebral cortex. Norepinephrine may mediate its effect by potentiating Na+, K+-ATPase or through its effects on vascular reactivity, or both.

Animals↗

PubMed1981

Oxidative metabolic activity of cerebral cortex after fluid-percussion head injury in the cat.

To assess the metabolic and vascular effects of head trauma, fluid-percussion pressure waves were transmitted to the brains of anesthetized, paralyzed, and artificially ventilated cats. Changes in the redox state of cytochrome a,a3, and relative local blood volume were measured in situ by dual-wavelength reflection spectrophotometry of the cortical surface viewed through an acrylic cranial window implanted within the closed skull. Initial fluid-percussion impacts of 0.5 to 2.8 atm peak pressure produced consistent transient oxidation of cytochrome a,a3 and increases of cortical blood volume. These changes occurred despite the presence of transient posttraumatic hypotension i some cases. Also, impact-induced alterations of vascular tone occurred, independent of the presence or absence of transient hypertension in the posttraumatic period. These data demonstrate that hypoxia does not play a role in the immediate posttraumatic period in cerebral cortex, and are consistent with the idea that after injury there is increased cortical energy conservation. These data also support the concept that head trauma alters the relationship of metabolism and cerebral circulation in the period immediately after injury.

Animals↗