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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 289 records · Page 16Linked to original sources
PubMed1985

Pharmacodynamics of the hypnotic effect of salicylamide in rats.

Salicylamide (SAM) can produce sedation and sleep in humans and animals. To explore the potential utility of the drug as a research tool for assessing disease effects on the response of the central nervous system to depressant drugs, and to obtain a better understanding of the clinically evident sedative action of SAM, studies were performed to characterize the relationship between the concentrations and hypnotic effect of this drug in rats. Female Lewis rats weighing 170-200 g received SAM by intravenous infusion at a rate of 0.49, 1.22, or 2.47 mg/min until the onset of loss of the righting reflex. This well-defined pharmacological endpoint occurred from 16.7 +/- 2.3 min (fastest infusion rate) to 110 +/- 27 min (slowest infusion rate) after the start of the infusion. SAM concentrations at that time in serum, serum water, brain, and cerebrospinal fluid (CSF) were similar in animals that had received the 1.22- or 2.47-mg/min infusion and lower in animals that were infused at a rate of 0.49 mg/min. The slowest infusion rate group also exhibited increased serum protein binding of the drug. The SAM concentration ratio, CSF-serum water, was essentially unity in all three groups, indicative of rapid equilibration of the drug across the blood-CSF barrier. Gentisamide, the hydroxylated metabolite of SAM, was found in serum, CSF, and brain, but in low concentrations at which this metabolite alone had no hypnotic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Kinetics of drug action in disease states. XV: Effect of pregnancy on the convulsive activity of pentylenetetrazol in rats.

The purpose of this investigation was to determine whether the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (1) are altered in advanced pregnancy. Lewis rats that were 20 days pregnant and nonpregnant rats of the same age and strain received either a relatively fast or a relatively slow intravenous infusion of 1 until the onset of a maximal seizure, which occurred after about 11 or 31 min, respectively, of infusion. The concentrations of 1 at that time in serum, cerebrospinal fluid, (CSF) and brain were independent of the infusion rate and did not differ significantly between pregnant and nonpregnant animals. The ratio of concentrations of 1 in the cerebrospinal fluid to that in serum was unity in all groups, consistent with negligible serum protein binding and indicative of rapid penetration of 1 into the central nervous system. It is concluded that advanced pregnancy has no apparent effect on the response of the central nervous system of rats to the convulsive activity of 1.

Animals↗
PubMed1985

Salicylate kinetics in old age.

Salicylate kinetics were determined in 28 subjects 25 to 92 years old who received single, oral doses of sodium salicylate (1 gm/1.73 m2). The serum AUCinfinity of total salicylate did not correlate with age. There was a weak positive correlation between the AUCinfinity of free (unbound) drug and age, but there was no apparent difference between the AUCinfinity values of the 15 women and 13 men. Seven of the 16 subjects greater than 70 years of age cleared salicylate at about the same rate as the younger subjects. A comparison of these seven subjects with the nine greater than 70 years old who were slow eliminators of salicylate revealed that the latter group consisted of more bedridden patients and that these patients had somewhat lower serum albumin concentrations, but they did not differ from the more rapid eliminators with respect to serum creatinine or urea nitrogen levels, SGOT, average age, female/male ratio, and average body weight. The serum protein binding of salicylate decreased with increasing age, apparently due mainly to decreasing serum albumin concentrations.

Administration, Oral↗
PubMed1985

Kinetics of drug action in disease states. V. Acute effect of urea infusion on phenobarbital concentrations in rats at onset of loss of righting reflex.

It has been reported that patients suffering from azotemia attributable to urinary obstruction required significantly less thiopental for induction and maintenance of general anesthesia than did a comparable group of patients with normal blood urea concentrations. Moreover, the thiopental requirements of normal subjects could be reduced by urea administration. In rats, experimental renal dysfunction was associated with reduced concentrations of phenobarbital (PB) in serum, serum water, brain and cerebro-spinal fluid at onset of a defined hypnotic effect (loss of righting reflex) produced by a slow i.v. infusion of PB. To determine the mechanism of this effect, these studies have now been repeated in normal rats made azotemic (approximately 170 mg of urea nitrogen/100 ml of serum) by intra-arterial infusion of urea and in control animals infused with saline solution. The total dose of thiopental required to produce loss of righting reflex was significantly reduced in the rats infused with urea. confirming the clinical observations. Similar results were obtained with PB and heptabarbital, two barbiturates that (unlike thiopental) are not racemic mixtures and are therefore more suitable for this investigation. On the other hand, urea infusion had no apparent effect on the concentrations of PB and heptabarbital in serum, brain and cerebrospinal fluid at onset of loss of righting reflex. Urea apparently affects the distribution kinetics of barbiturates and this, rather than increased receptor sensitivity, appears to be responsible for the decreased barbiturate dose requirements in acute experimental azotemia produced by urea infusion.

Animals↗
PubMed1985

Kinetics of drug action in disease states. IV. Effect of pregnancy on phenobarbital concentrations at onset of loss of righting reflex in rats.

This investigation was designed to determine if the acute hypnotic activity of a barbiturate is altered by advanced pregnancy. Twenty-day-pregnant rats and nonpregnant rats of the same age received an i.v. infusion of phenobarbital, 0.824 mg/min/rat, until they lost their righting reflex. The concentrations of total and free phenobarbital in serum at that time were significantly lower in pregnant than in nonpregnant animals. However, pregnancy had no effect on the concentrations of phenobarbital in the brain and cerebrospinal fluid at onset of loss of righting reflex. The difference of the serum phenobarbital concentrations was due to the slower rate of phenobarbital infusion received by the pregnant rats when normalized for body weight. The lack of difference of phenobarbital concentrations in cerebrospinal fluid, a site that reflects the concentration of the free drug at the sites of action, indicates that advanced pregnancy has no apparent effect on the central nervous system response to phenobarbital.

Animals↗
PubMed1985

Kinetics of drug action in disease states. VI. Effect of experimental diabetes on phenobarbital concentrations in rats at onset of loss of righting reflex.

To investigate the effect of diabetes on the sensitivity of the central nervous system to the hypnotic action of a barbiturate, studies were conducted on adult female Lewis rats made diabetic by injection of either streptozotocin or alloxan. The animals then received a slow i.v. infusion of phenobarbital (PB) until the onset of a defined pharmacologic effect [loss of righting reflex (LRR)] and the PB concentrations at that time in serum (total and unbound drug), brain and cerebrospinal fluid (CSF) were determined. In the experiments on rats with streptozotocin-induced diabetes, animals not treated with insulin had significantly lower serum concentrations of total PB at onset of LRR than did animals treated with insulin and nondiabetic control rats. Otherwise, there were no significant differences in PB concentrations between untreated diabetic and control animals. Additional experiments on untreated diabetic rats showed that, as in normal rats, the PB concentrations in CSF (but not in serum and brain) at onset of LRR were independent of PB infusion rate over a 10-fold range, indicating that PB equilibrates very rapidly between CSF and receptor sites. Experiments in rats with alloxan-induced diabetes showed no significant differences between untreated diabetic, insulin-treated diabetic, alloxan-nonresponding and nondiabetic control rats with respect to PB concentrations at onset of LRR in serum (total and unbound drug), brain and CSF and in serum protein binding. These results show that the central nervous system response to the hypnotic effect of PB is not significantly affected in two different experimental models of diabetes.

Animals↗
PubMed1985

Kinetics of drug action in disease states. VII. Effect of experimental renal dysfunction on the pharmacodynamics of ethanol in rats.

This investigation was designed to determine if renal dysfunction is associated with an increased sensitivity to the CNS depressant effect of ethanol. Adult female Lewis rats were given injections of either 2 or 5 mg/kg of uranyl nitrate (saline for controls) or had both ureters ligated (sham operation for controls) to provide different experimental models of renal dysfunction. Normal and renal dysfunction (ureter-ligated) rats were infused i.v. with ethanol at rates of 8.1, 16.3 or 32.6 mg/min; concentrations of ethanol in cerebrospinal fluid, serum and brain at onset of loss of righting reflex were independent of infusion rate in both groups, indicating rapid equilibration of ethanol between the sampling sites and the biophase. Ethanol concentrations in cerebrospinal fluid at onset and offset (after approximately 110 min of sleep) of loss of righting reflex were not significantly different, reflecting negligible acute tolerance development under the experimental conditions. Ethanol concentrations at onset of loss of righting reflex in cerebrospinal fluid, serum and brain of rats with severe renal dysfunction (5 mg/kg of uranyl nitrate-treated and ureterligated groups) were slightly but statistically significantly lower than in normal controls. This difference was relatively much smaller than the difference in phenobarbital concentrations observed in a similar preceding study, which is consistent with the different mechanisms of action of alcohols and barbiturates.

Animals↗
PubMed1985

Kinetics of drug action in disease states. IX. Effect of experimental fever on phenobarbital concentrations at onset of loss of righting reflex in rats.

The purpose of this investigation was to determine the effect of fever on the concentration-pharmacologic activity relationship of phenobarbital (PB). Fever was produced in adult female Lewis rats by either bacterial endotoxin or brewer's yeast. Endotoxin elevated body temperature by 0.9 +/- 0.6 degrees C in one study and by 1.0 +/- 0.4 degrees C in another. Brewer's yeast caused a more pronounced and protracted elevation of temperature averaging 1.8 +/- 0.3 degrees C at the time of the pharmacodynamic measurements. PB was administered by slow i.v. infusion until the rats lost their righting reflex. The concentrations of PB at that time in serum, cerebrospinal fluid and brain were appreciably lower in the hyperpyrexic than in control (saline-treated) animals, irrespective of the method used to produce fever. Thus, fever is associated with an increased sensitivity of the central nervous system to the depressant effect of PB. This observation may be of particular relevance to the use of PB for the treatment and prevention of febrile convulsions.

Animals↗
PubMed1985

Effect of pregnancy on ethanol concentrations at onset of loss of righting reflex in rats.

To determine if the pharmacodynamics of ethanol are altered in advanced pregnancy, 20-days pregnant Lewis rats and nonpregnant rats of the same age received an i.v. infusion of ethanol, 96 mg/min/kg, until they lost their righting reflex. The concentrations of ethanol at that time in adult and fetal serum, and in the cerebrospinal fluid (CSF) and brain of the adult animals were determined. Ethanol concentrations in the pregnant rats were only slightly (less than 10%) but statistically significantly lower than in nonpregnant controls. Brain/serum, CSF/serum, and CSF/brain concentration ratios of ethanol were essentially identical in pregnant and nonpregnant rats, indicating no apparent effect of pregnancy on the distribution kinetics of ethanol. The serum concentrations of ethanol in mothers and their fetuses were similar and significantly correlated. The results of this investigation show that the central nervous system depressant effect of ethanol is not appreciably altered by pregnancy.

Animals↗
PubMed1985

Kinetics of drug action in disease states. XIII. Effect of dialyzable component(s) of uremic blood on phenobarbital concentrations in rats at onset of loss of righting reflex.

The purpose of this investigation was to determine if the previously demonstrated increased sensitivity of the central nervous system of uremic rats to the hypnotic activity of phenobarbital is caused, wholly or in part, by the accumulation of one or more endogenous substances. Blood was obtained from normal donor rats and from rats made uremic by administration of uranyl nitrate 5 days earlier. The serum was dialyzed against water, using a cellophane membrane with a molecular exclusion limit of 12,000 to 14,000 daltons, and the dialysate was lyophilized. A concentrate of the dialysate was administered by i.v. infusion to normal rats who also received a slow i.v. infusion of phenobarbital until they lost their righting reflex. Samples of cerebrospinal fluid, blood (for serum) and the brain were obtained at that time and were assayed for phenobarbital. Compared to the two control groups, i.e., rats infused with serum dialysate from normal animals or with normal saline solution, rats infused with serum dialysate from uremic rats lost their righting reflex at significantly lower phenobarbital concentrations in serum, brain and cerebrospinal fluid. This shows that the serum of uremic rats contains appreciable concentrations of one or more dialysable components capable of potentiating or contributing to the hypnotic activity of phenobarbital.

Age Factors↗
PubMed1985

Kinetics of drug action in disease states. XIV. Effect of infusion rate on pentylenetetrazol concentrations in serum, brain and cerebrospinal fluid of rats at onset of convulsions.

The purpose of this investigation was to develop a method which can be used to determine the effect of various diseases on the concentration-pharmacologic activity relationship of the central nervous system stimulant pentylenetetrazol (PTZ, Metrazol) in a manner that excludes or accounts for pharmacokinetic variables. Adult female rats (approximately 170 g) received an i.v. infusion of PTZ at one of four different rates (0.155-1.53 mg/min) until the animals exhibited the first myoclonic jerk. This occurred after an average of 4.9 to 52 min of infusion. The PTZ concentrations in serum, brain and cerebrospinal fluid at this pharmacologic endpoint were independent of infusion rate. Other groups of rats were infused at three different rates (0.155-1.53 mg/min) to the onset of maximal seizures. Again, the PTZ concentrations in serum, brain and cerebrospinal fluid were not significantly affected by the rate of infusion of the drug. The average (+/- S.D.) PTZ concentration in cerebrospinal fluid was 46 +/- 5 mg/l (n = 22) at the onset of the first myoclonic jerk and 109 +/- 13 mg/l (n = 12) at the onset of maximal seizure. PTZ concentrations in brain and serum were similar to those in cerebrospinal fluid. The total serum clearance of a 20-mg/kg i.v. bolus dose of PTZ was 5.36 +/- 0.34 ml/min/kg, the terminal half-life was 116 +/- 25 min and the apparent volume of distribution was 896 +/- 134 ml/kg (all values are mean +/- S.D.). Serum protein binding was negligible (less than 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[Uncomplicated pregnancies following recovery from acute pregnancy-related hepatic steatosis].

The authors report the case of a patient with acute yellow atrophy of the liver who subsequently had two uncomplicated pregnancies bringing the total number to 8 cases already published in the literature. After reviewing the diagnostic criteria, they discuss the risk of recurrence, considering the course of the illness, clinical, histological, and physiopathological features. The present risk of recurrence of AYAL must be considered to be very low.

Acute Disease↗
PubMed1985

[Asymmetric uterine malformations with menstrual retention. Apropos of a malformation associating atresia of the cervical isthmus and a pseudo-unicornous uterus].

There is now more or less general agreement how to classify and how to work out the development of symmetrical malformations of the female genital tract. On the other hand, asymmetrical malformations, as well as abnormalities of the development of the cervix and the isthmus are only rarely written about in the literature. It has not yet been possible to draw up a system to display the physiopathology and the embryology of these malformations. We here report a rare case of atresia of the cervix and isthmus as well as a pseudo unicornous uterus. This case should take its place as a piece in the embryological puzzle helping to fill in the details which might one day solve this puzzle.

Abnormalities, Multiple↗
PubMed1984

Lactate provocation of panic attacks. I. Clinical and behavioral findings.

To assess the pharmacologic and phenomenologic comparability of lactate-induced and naturally occurring panic attacks, patients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks were infused with 0.5M racemic sodium lactate before and after successful drug treatment. Lactate-induced and naturally occurring panic attacks were symptomatically similar. Following treatment, the patients' response to lactate did not differ from that of normal controls, whereas the pretreatment panic rate was much higher. These data suggest that lactate acts, by as yet unidentified mechanisms, to trigger the same panic attacks as occur spontaneously in vulnerable persons.

Adult↗
PubMed1984

Pharmacokinetics of heparin VII: Effect of pregnancy on the relationship between concentration and anticoagulant action of heparin in rats.

The effect of pregnancy on the anticoagulant action of heparin was determined by comparing the slope of the relationship between the natural logarithm of the activated partial thromboplastin time (APTT) and heparin concentration (the heparin slope) in the plasma of pregnant and nonpregnant female inbred Lewis rats. Also determined were the prothrombin time, hematocrit, and the activities of coagulation factors II, VII, VIII, X, XI, and XII. The heparin slope was significantly decreased in pregnant rats at the 20th day of gestation but not in rats at the 10th day of gestation, indicative of a decreased anticoagulant action of heparin in late pregnancy. The hematocrit and prothrombin time were decreased, and the baseline APTT (i.e., the APTT without added heparin) as well as the activities of factors II, VII, and X were increased in pregnant rats at the 20th day of gestation. Both pregnant and nonpregnant animals showed a significant negative correlation between prothrombin time and factor II activity and a significant positive correlation between the activities of factors II and X. The effects of pregnancy in rats on heparin slope, prothrombin time, hematocrit, and factors VII, VIII, X, and XII are qualitatively the same as those in pregnant women in the third trimester. The increases in factor II activity and baseline APTT found in the rats were not observed in humans. Pregnant rats, like pregnant women, are relatively resistant to the anticoagulant action of heparin.

Animals↗