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Biomedical subjects

P Even

Publications and source records attributed to P Even.

At least 37 records · Page 2Linked to original sources
PubMed1989

Metabolic rate and feeding behavior.

According to the ischymetric hypothesis, hunger is induced by the decrease of overall metabolic rate. In order to assess such a mechanism, it was necessary to monitor the muscular contraction-free metabolic rate designated "métabolisme de fond" (MF) in rats that were either resting or moving. MF was then examined in relation to either spontaneous or induced feeding patterns. A computerized open-circuit gas analysis system allowed us to monitor MF and behavior and to show that the onset of a spontaneous meal was preceded by a decrease of MF and its termination is preceded by a rebound of MF. Pharmacological blockade of utilization of both glucose and lipids enhanced feeding only to the extent that it reduced MF. These findings apply to pharmacotherapy because the anorexigenic effect of dexfenfluramine results from the enhancement of MF induced by the capacity of this drug to mobilize endogenous fat reserves and to so provide an endogenous meal that inhibits the exogenous meal. The ischymetric mechanism of hunger does not exclude important modulatory input from hormonal, circadian, and environmental factors in the control of feeding.

Animals↗
PubMed1988

Effects of cyclosporin on T-cell subsets in human immunodeficiency virus disease.

Cyclosporin (7.5 mg/kg daily) was given to 8 AIDS patients for 17-66 days and to 25 HIV-seropositive non-AIDS patients, 15 with stage II (T4 cells/microliter greater than or equal to 300, less than 600) and 10 with stage III (T4/microliter less than 300), for 3-6 months with the hypothesis that the drug could inhibit both HIV replication and the potential autoimmune component of HIV disease. A sustained increase over 600 T4/microliter occurred in 7 patients with stage II and 1 with stage III. T8 cells significantly decreased in most patients and lymphadenopathy disappeared in 14/16. After cyclosporin withdrawal T4 and T8 cells as well as lymphadenopathy returned to pretreatment status. Cyclosporin side effects (hypertension, creatinine increase, and anemia) were moderate and reversible. These results might stimulate biological research as well as clinical trials with cyclosporin in selected groups of HIV-seropositive subjects with the aim of delaying or preventing AIDS occurrence.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Lipostatic and ischymetric mechanisms originate dexfenfluramine-induced anorexia.

Rats treated with physiological saline or dexfenfluramine (Isoméride, Laboratoires SERVIER, Neuilly, France) (dF), 1.75, 3.50, and 7.00 mg/kg, were studied in a computer-controlled open-circuit metabolic chamber, in which temperature was regulated at 24 degrees C. Total metabolic rate (TMR), respiratory quotient (RQ), locomotor activity (LA), energy cost of LA, and thus, locomotor free metabolic rate, were scanned at 10-second intervals throughout 22-hour uninterrupted recording sessions. The feeding pattern was also measured in relation to the dF-induced changes in the above parameters. It was found that dF induced a sustained decrease in TMR and RQ, while periodically enhancing the increase in TMR and RQ produced by the periods of LA. All phenomena occurred in a dose-dependent fashion. Anorexia was also increased as a function of the dF treatments and metabolic changes. It is concluded that dF-induced anorexia may be related to the enhanced release and utilisation of free fatty acids (lipostatic mechanism), and/or to the enhancement of metabolic rate during locomotor activity (ischymetric mechanism). In addition, it appeared that the increased prandial thermogenesis, previously reported from the measurement of changes in TMR, may be due to the dF-induced increase in the energy cost of LA, rather than to an effect of feeding per se. Indeed, in our experimental conditions, it was measured that the energetic cost of LA accounted for more than 60% of the periprandial increase in TMR.

Animals↗
PubMed1988

Integrated metabolic control of food intake after 2-deoxy-D-glucose and nicotinic acid injection.

We measured the minute-to-minute respiratory quotient (RQ), total metabolic rate, and the intensity and energy cost of locomotor activity in unrestrained rats with a recently developed open-circuit metabolic device. These measures permitted calculation of the resting metabolic rate (designated métabolisme de fond or MF). Simultaneous monitoring of the meal patterns of the animals allowed correlations between MF and feeding behavior. The major hypotheses proposed to account for the onset of feeding were challenged by pharmacological inhibition of the utilization of glucose and/or lipids. When injected together, 2-deoxy-D-glucose, which blocks glucose utilization, and nicotinic acid, which blocks lipid utilization, had a synergistic effect on MF and on the feeding response. The RQ, which reflects the relative rate of glucose-to-lipid utilization, showed that neither the inhibition of utilization of glucose nor the inhibition of utilization of lipids could account for the magnitude of the feeding response. The signal that best accounted for these examples of experimentally induced feeding is ischymetric (power or rate of energy) in nature rather than solely glucostatic or solely lipostatic.

Animals↗
PubMed1988

Serum suppressive activity of HIV seropositive patients.

The mechanisms by which HIV induces immunosuppression are still poorly understood so far. Several pathways of CD4 cell destruction are known, including cytolysis with or without syncitium formation and killing by cytotoxic effectors of HIV infected or non-infected CD4 cells. However, a discrepancy exists between the small number of actually infected cells in vivo and the extent of HIV-related immunodeficiency. Among other possible immunosuppressive factors, serum blocking factors have been reported, but only in AIDS-related opportunistic infections (OI), i.e. in a quite specific type of full-blown HIV disease. The purpose of this work was to determine whether serum blocking activity was unique to this group of patients, or if it was also expressed in other clinical presentations and, moreover, at earlier stages of the disease. We also attempted to delineate the nature of these seric factors. In order to do so, we assessed serum suppressive activity of 50 HIV seropositive patients, seven with OI, eight with Kaposi's sarcoma (KS), and 35 with no clinical AIDS. Our results confirm the existence of serum inhibiting factors in AIDS, and demonstrate their presence at earlier stages of the disease. They also highlight the fact that the level of serum suppression does not correlate with patients clinical status, but increases with the severity of the disease. The lower the CD4 count, the higher the suppression exerted. Furthermore, we showed that the suppression was at least partly mediated by small size molecules, which are not complement-mediated or directly lymphocytotoxic. On the other hand, this activity does not correlate with the serum level of p24 HIV core protein. The possible relation with other viral components is discussed. The relevance of these data to prognosis and pathogenesis of HIV disease deserves further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Correlation between metabolic and behavioral effects of dexfenfluramine treatment.

The consequences of dexfenfluramine (dFF) treatments on food intake (FI), locomotor activity (LA), respiratory quotient (RQ), and on changes in metabolic rate (MR) and in RQ that are induced by LA and FI, were investigated in 12 female Wistar rats fed ad libitum. Reduction of FI induced by dFF was correlated with an overall decrease in RQ that expresses increased lipogenesis. For a given amount of activity, MR and RQ changes were enhanced by dFF. On the other hand, dFF appeared to increase energy expenditure in relation to FI only to the extent that the energetic cost of LA itself was not taken into account. It is concluded that the anorexia induced by dFF may be due to the peripheral consequences of dFF treatments on the peripheral metabolism of glucides and lipids according to a lipostatic, glucostatic, or an ischymetric mechanism, and that the increase in energy expenditure previously reported after feeding, may reflect an increase in the energy produced in relation to LA rather than an increase in the thermic effect of feeding per se.

Animals↗
PubMed1988

Serum HIV antigen and anti-P24-antibodies in 200 HIV seropositive patients: correlation with CD4 and CD8 lymphocyte subsets.

Serum HIV (P24) antigen (Ag) measured by an antigen capture ELISA (Abbott) and anti-P24-antibodies (Abs) measured by a competitive ELISA (Abbott) and by Western Blot (Dupont de Nemours) analysis were correlated with lymphocyte subsets (CD4 and CD8) in 174 HIV seropositive patients without AIDS (non-AIDS) and 26 with AIDS. In the non-AIDS group, 27% of the patients were anti-P24-Ab negative and 21% were Ag positive while in the AIDS group these figures were 62% and 54% respectively (P less than 0.001). Overall, a significant correlation exists between the Ab-Ag profile and the CD4 cell count: the percentage of patients with anti-P24-Ab positive and Ag negative decreases from 90% for patients with more than 900 CD4 cells/microliter to 21% for patients with 100 and less CD4 cells/microliter; on the contrary, the percentage of patients with anti-P24-Ab negative and Ag positive increases from 0% over 800 CD4 cells to 53% under 100 CD4 cells/microliter. A weak correlation may also exist with the CD8 cell count. The subgroup of patients with 1,000 or more CD8 cells/microliter have a higher (but not significant) percentage of subjects with Ag positive and anti-P24-Ab negative than the subgroup with less than 1,000 CD8 cells/microliter. A short-term longitudinal study (mean follow-up: 1 year) was performed on 80 non-AIDS subjects: 77% (10/13) of those who had a CD4 cell decrease (greater than 30%) were initially Ag positive, while only 21% (14/67) of those without a decrease were Ag positive at the beginning (P less than 0.1). Although the relative weight and individual predictive value of each of these parameters need to be classified, they are probably the best biological markers currently available for monitoring clinical trials with experimental drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Pulsatile secretion of growth hormone and insulin in relation to feeding in rats.

In unrestrained male Wistar rats chronically implanted with intracardiac catheters, blood samples were taken every 20 min throughout the 24 h of the diurnal cycle. Plasma concentrations of growth hormone (GH), insulin, and glucose were measured. The pattern of food intake was continuously monitored. The existence of 3-h pulsatile cycles of GH secretion was confirmed. In addition, short bursts of insulin secretion were observed in the middle of every second GH peak-to-peak interval. Food intake appeared to be enhanced during short periods that corresponded with GH release into the blood and was reduced during the GH peak-to-peak periods in which the bursts of insulin secretion were observed. From these observations this study draws a schematic relationship between the rhythmicity of the secretion of GH and insulin and the probability of occurrence of feeding. We speculate that the rhythmic endocrine activity may be causally related to feeding.

Animals↗
PubMed1986

Penetration of ciprofloxacin into bronchial secretions.

The penetration of ciprofloxacin into bronchial secretions was evaluated in 21 patients after a single oral dose of 500 mg of ciprofloxacin. Ten successive serum samples were collected in the interval 0-12 h after administration, and bronchial samples were taken 2, 3, 4 and 6 h after administration. Concentrations were measured in all samples using a standard microbiological assay. The results showed that the kinetics in serum did not differ from those determined in previous studies, a peak level of 2.2 +/- 1.3 mg/l being achieved at 2 h followed by a slow decrease of the levels to 0.6 +/- 0.4 mg/l at 6 h. The bronchial concentrations reached about 0.5 mg/l at 2 h and remained stable until 6 h, ranging between 0.5 and 0.8 mg/l. The ratio between simultaneous bronchial and serum levels ranged from 0.19 at 2 h to 0.95 at 6 h. These data indicate that ciprofloxacin might be suitable for treatment of severe respiratory infections, especially pneumonia caused by Pseudomonas aeruginosa, since the MICs of ciprofloxacin for most bacteria involved in bronchopulmonary infections are very low and tissue diffusion of the drug in the respiratory tract is good.

Aged↗
PubMed1986

Dextrofenfluramine increases energy cost of muscular effort.

A peripheral action of dextrofenfluramine (d.FF) was investigated. The effects of d.FF on total energy expenditure (TEE), locomotor activity (LA), and respiratory quotient (RQ) were quantitatively monitored for 22 hours by a computerized metabolic device. The precise temporal evolution of RQ allowed calculation of glucidic versus lipidic substrates used in all instances. It appeared that in d.FF-treated rats, TEE and resting energy expenditure (REE) were not significantly changed, RQ and LA were significantly decreased. Moreover, in d.FF-treated rats. LA induced a two to five fold increase energy expenditure over vehicle-treated control subjects and it was observed that there was an LA related increase in RQ which was not observed in control subjects. Therefore, d.FF causes LA to be a highly inefficient process by inducing what seems to be an exaggerated catabolism of glucides. These may be only partially used for muscular contraction because it was calculated from relative changes in RQ and TEE during LA that 70% of the catabolized glucides seems to be diverted toward lipogenesis. This process probably represents the way futile cycles are triggered by d.FF in order to exacerbate LA associated energy cost.

Animals↗
PubMed1986

Short-term control of feeding: limitation of the glucostatic theory.

In the rat, the short-term effect on spontaneous feeding of intravenous administration of either glucose or glucose plus insulin was investigated. The infusions lasted 4 hours and covered 170% of rats's previously measured spontaneous caloric intake, while control infusions of saline and saline plus insulin were also made. Feeding patterns in subjects' home cages were recorded. Glycaemia and glycosuria were measured in order to asses glucose utilization. When it was infused alone, glucose was utilized at 95% and so covered 160% of oral caloric requirements, while the reduction of oral intake was only 40%. When insulin was co-infused with glucose, utilization reached 100% and oral feeding was reduced by 70%. Saline infusions did not affect oral feeding, and insulin brought about the expected increase in feeding. It is proposed that the mechanism which sustains feeding should depend on multiple macronutrients utilization rather than on one specific chemical family. Furthermore, the fact that insulin has a clear-cut effect, despite its lipogenetic, i.e., metabolite-sequestering properties, favors the ischymetric hypothesis (based on cellular power-production), rather than the energostatic one (based on yields of nutrients).

Animals↗
PubMed1986

Metabolic mechanism of the anorectic and leptogenic effects of the serotonin agonist fenfluramine.

The purpose of these experiments was to investigate the action of a 5HT-agonist, D-fenfluramine (D-FF) upon energy expenditure in addition to its known anorectic action. Experiment 1 showed that body weight (BW) loss was more than predicted by the anorectic action of D-FF. In pair pattern feeding, D-FF induced a similar BW loss in treated and untreated partners despite the sedation of the former and agitation of the latter. Metabolic measurements (oxygen, carbon dioxide, respiratory quotient and locomotor activity (LA] revealed that D-FF enhances mobilization and intense utilization of endogenous fat reserves during anorexia. Energy expenditure (EE) increased via exaggerated cost of muscular effort which induced high glycolytic-lipogenetic reactions indicative of futile biochemical cycles leading to waste of energy. These locomotion and lipolysis-lipogenesis associated reactions varied as a function of basal body weight, food composition, intensity of LA, ambient temperature and dose of treatment. These data demonstrate that serotonin agonists like D-FF are more than anorectics since they enhance EE and therefore should be referred to as "leptogenic" (leptos = lean) agents since their end effect is the reduction of BW. They also suggest how leptogenic pharmacotherapy could be optimized by acting upon modulatory factors which have been studied in this work, and for example by encouraging LA in treated subjects.

Animals↗
PubMed1985

Spontaneous and 2DG induced metabolic changes and feeding: the ischymetric hypothesis.

A computer-controlled calorimeter which simultaneously measured respiratory exchanges, locomotor activity, and meal patterns, was used to study Total Metabolic Rate (TM), Locomotor Free Metabolic Rate (LFM), and Respiratory Quotient (RQ) in relation to spontaneous and 2DG induced Food Intake in freely-feeding rats. It appeared that spontaneous and 2DG induced feeding was preceded by a consistant drop of LFM starting about five minutes before a meal and reaching its nadir at the onset of a meal. The simultaneous determination of the RQ did not show any systematic change that would have reflected either a lipo- or a gluco-privic origin of the LFM drop and meal onset. Therefore, the results are in agreement with the ischymetric hypothesis of the control of food intake which proposes that the final signal triggering hunger and satiety is the intensity of cell power production (measured in this experiment through the LFM parameter) which is independent of the glucidic lipidic or protidic origin of the substrate(s) supplying power production.

Animals↗
PubMed1985

Physiological determinant of hunger, satiation, and satiety.

The initiation and cessation of feeding behavior is explained on the basis of the ischymetric hypothesis (from ISCHYROS meaning "Mighty One" or power). Cellular production of power or "Metabolisme de Fond" (MF) is measured continuously in terms of total body metabolism minus the metabolic costs of locomotion. A drop in MF signals the onset of eating. Eating initiates a rise in MF and when this signal peaks, the feeding process stops. Control of satiation is described in terms of recent neurophysiologic and neuroendrologic factors that influence MF.

Animals↗