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Biomedical subjects

T Balazs

Publications and source records attributed to T Balazs.

At least 37 records · Page 2Linked to original sources
PubMed1986

Adverse effects of theophylline-beta agonist interactions.

Beta-adrenergic agonists, when administered alone or concomitantly with methylxanthines are capable of producing lesions of myocardial necrosis and an increased incidence of cardiac arrhythmias in several species of animals. These drugs, including "beta 2-specific" agonists, also have the potential to produce adverse cardiovascular effects when used clinically. In addition, beta agonists and methylxanthines can interact to potentiate or lessen effectiveness and theoretically increase the risk to the patient. As a result, the extent to which the concomitant administration of these drugs may contribute to adverse clinical effects needs further clarification.

Adrenergic beta-Agonists↗
PubMed1986

Delayed development of reproductive functions and alteration of dopamine receptor binding in hypothalamus of rats exposed prenatally to phenytoin and phenobarbital.

Previous work in experimental animals treated prenatally with phenobarbital revealed reproductive changes in the offspring. Little has been reported on the effect of phenytoin or a combination of both drugs. 75 Pregnant Sprague-Dawley rats were administered either phenytoin (Na salt) at 20, 40 or 80 mg/kg orally (p.o.), phenobarbital (Na salt) at 20, 40 or 80 mg/kg subcutaneously (s.c.) or a combination of both drugs at the same doses daily from 5 to 20 days of pregnancy (4-12 rats/dose level). 24 Control rats received 1% methylcellulose p.o. and distilled water s.c. Regularity of estrous cycles was decreased in all treated groups, with the phenytoin group being most affected. The binding of [3H]spiroperidol, known to label dopamine receptors, was decreased in the hypothalamus of all drug-treated groups, indicating that the alteration in neuroendocrine function may be responsible for the above effects. Data suggest that prenatal exposure of rats to anticonvulsant drugs could lead to reproductive disorders.

Animals↗
PubMed1986

Enhanced myocardial necrosis induced in rats by the combined administration of hydralazine and prenalterol.

The cardiotoxic effects of hydralazine and prenalterol, given alone and in combination, were assessed in rats and rabbits. Acute myocardial necrosis was induced by a single administration of each drug alone in rats. However, the incidence and severity of lesions were markedly enhanced when both drugs were given in combination. Rats that received the same treatment for 10 consecutive days showed minimal or no acute necrosis, demonstrating the development of a resistance to further cardiotoxic effects of the drugs. Rabbits showed only minimal lesions when either drug was used alone and no enhancement of lesions when they were given in combination. From these data, it is concluded that the possibility of a cardiotoxic interaction exists when these drugs are used in combination and that the heavy rat (500-600 g) is a more sensitive model than the rabbit for studies of this nature.

Adrenergic beta-Antagonists↗
PubMed1986

Toxicological studies with 6-mercaptopurine in neonates.

In previous studies, we found that Sprague-Dawley rats injected with 6-MP monohydrate at 2 mg base/kg sc daily from 2 to 22 days of age had atrophy of thigh and sublumbar muscles when killed at 16 months of age. The first sign of this muscle atrophy was detected grossly (flattened croup with or without paresis) at 12 months of age. In one experiment of the present work, using the same treatment in rats as above, we found that the earliest onset of muscle atrophy observed by light microscopy occurred at 2 months of age. By 4 months the atrophy could be detected grossly. The atrophy did not uniformly involve all muscles of the hindquarters; the thigh (especially the semitendinosus), leg (soleus but not the extensor carpi group), and lumbar vertebral (including the psoas) muscles were involved. Foreleg (biceps), intercostal, and tongue muscles as well as the sciatic nerve and internal organs appeared unaffected. In another experiment, weanling Sprague-Dawley rats given large daily doses of 6-MP from 25 to 45 days of age had normal muscles when killed at 8 months. In a third experiment, Wistar rats injected with 6-MP (2 mg base/kg sc) daily from 2 to 22 days of age and killed at 6 months had muscle atrophy similar to that seen in Sprague-Dawley rats. In the last experiment, mice and hamsters given large daily doses of 6-MP from 2 to 22 days of age had normal muscles when killed at 10 months. It appears from these results that the 6-MP-induced muscle atrophy occurs only after treatment during the neonatal period and that the atrophy may be species-specific.

Animals↗
PubMed1986

Muscle atrophy and histopathology of the soleus in 6-mercaptopurine-treated rats.

In this study, male and female Sprague-Dawley rats were treated neonatally with 6-MP-treatment (2 mg/kg s/c, between 2 and 22 days after birth) and evaluated at six months of age. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) muscle fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.

Animals↗
PubMed1986

Ultrastructural changes in skeletal muscles of rats treated neonatally with 6-mercaptopurine.

The purpose of this study was to characterize the ultrastructural changes in the muscles of 2- and 6-month-old rats that were injected with 6-mercaptopurine monohydrate (6-MP) at 2 mg base/kg sc daily from 2 to 22 days of age. The earliest, usually subsarcolemmal alterations, were disorganization of fibrils at the Z-bands with excessive Z-band-like material and loss of myofibrils. In the most extensive lesions, the entire fiber was involved, with vacuoles within the disorganized fibrils. The peripheral nerves and vessels were unremarkable. Thus 6-MP-induced changes appear to be primarily myogenic in origin.

Animals↗
PubMed1986

Macromolecular levels, DNA synthesis and ornithine decarboxylase activity in leg muscles from 6-mercaptopurine-treated rats.

Sprague-Dawley male and female rats were treated with 6-mercaptopurine (6-MP) (2 mg/kg sc) daily from 2 to 22 days of age and killed at 7, 15, 27 and 64 days of age. At 7 and 27 days of age rats were injected with 3H thymidine for measurement of DNA synthesis. Fore- and hindlimb muscles were removed and analyzed for ornithine decarboxylase (ODC) activity (all ages), DNA radioactivity (7 and 27 days), DNA level (27 and 64 days) and RNA level (64 days). As expected, ODC activity and DNA synthesis were higher in muscles of 7-day-old rats than in muscles of the older rats studied. A consistently lower ODC activity was seen in 6-MP-treated vs. control rats for 5-25 days after start of treatment, but the effect was essentially the same for the hindlimb and forelimb muscles. During the 7-27-day time course ODC activity was higher in hindlimb than forelimb muscles. By 27 days of age DNA synthesis was also higher in the hindlimb muscles. DNA synthesis was decreased after 5 days of treatment relative to that of control rats, to an approximately equal extent in forelimb and hindlimb muscles. Five days after the last treatment a trend was seen for slower recovery from inhibition of DNA synthesis in hindlimb muscles, particularly in male rats. DNA levels were reduced in treated rats relative to those in control rats 5 days after the last treatment to approximately the same degree in forelimb and hindlimb muscles. Forty-two days after the last treatment a trend toward increased activity of ODC and increased DNA and RNA levels was seen in muscles of treated rats, probably reflective of recovery processes. These early biochemical effects of 6-MP, which were seen to about the same extent in the forelimb and hindlimb muscles cannot explain by themselves the delayed hindlimb fat atrophy resulting from 6-MP treatment of neonatal rats.

Animals↗
PubMed1986

6-Mercaptopurine treatment affects the membrane potentials of rat skeletal muscle fibers.

6-Mercaptopurine (6-MP) was injected daily (2 mg/kg sc) into 24 Sprague-Dawley rats during the first three weeks of life. There were 23 saline-injected control animals. Atrophy of the muscles of the hindquarters in the 6-MP-treated rats began at about 4 months of age. The membrane potentials (Em) of the isolated extensor digitorum longus (EDL) and the caudofemoralis (CF) muscle (in situ) were measured with intracellular microelectrodes at 6-18 months of age. It was found that there was a wide spectrum of fibers with respect to electrical abnormalities in the 6-MP-treated muscles, some fibers having perfectly normal parameters. However, the mean resting Em of fibers in the EDL muscle of 6-MP-treated rats (-61.1 +/- 0.7 mV) was lower than that of the control rats (-69.7 +/- 0.6 mV). The same was true for the fibers of the CF muscle (-64.9 +/- 1.5 mV for 6-MP-treated fibers vs -71.6 +/- 1.3 mV for controls). Experiments done in the presence and absence of ouabain indicated that the contribution of the electrogenic pump potential to Em was similar in 6-MP-treated and control rats, and therefore could not account for the depolarization observed in 6-MP-treated rats. The data also demonstrated that this depolarization was not due to a decreased intracellular K+ concentration. The Na+/K+ permeability ratio (PNa/PK) was higher in the 6-MP-treated rats, and could account for the decreased resting Em. The APs of 6-MP-treated rats (elicited from the natural Em of the fiber) had more fibers with a lower maximum rate of rise (+Vmax) (330 +/- 20 vs 391 +/- 17 V/sec) and lower amplitude (65.1 +/- 2.9 vs 73.3 +/- 1.8 mV) than in the control muscles. When hyperpolarized to -90 mV before eliciting the AP, fibers from 6-MP-treated rats still displayed depressed AP rates of rise (+Vmax of 382 +/- 19 vs 511 +/- 21 V/sec in controls), depressed AP amplitudes (97 +/- 2.1 vs 105 +/- 1.6 mV in controls) and slightly prolonged duration at 50% amplitude (APD50) (0.66 +/- 0.03 vs 0.60 +/- 0.02 sec in controls). These electrophysiological alterations produced by this chemically-induced myopathy are similar to those observed in murine muscular dystrophy.

Action Potentials↗
PubMed1986

Effects of antiarrhythmic agents on isoproterenol-induced ventricular fibrillation in heavy rats: a possible model of sudden cardiac death.

Heavy male Sprague-Dawley rats die of ventricular fibrillation within 2 to 3 h after isoproterenol administration. Thus, the isoproteronol-treated heavy rat would be a useful model for screening drugs that may prevent sudden cardiac death. Isoproterenol (1 mg/kg s.c.) caused ventricular fibrillation in 79% of 121 vehicle-pretreated heavy rats (greater than 500 g); 82% of the fibrillating rats died, but the remaining 18% spontaneously reverted and survived. A protecting agent should increase the number of survivors by reducing the incidence of ventricular fibrillation and/or by increasing the incidence of spontaneous reversions. Pretreatment (i.p.) with quinidine (40 mg/kg), procainamide (40 mg/kg), phenytoin (40 mg/kg), clofilium (5 mg/kg), verapamil (10 mg/kg), or propranolol (10 mg/kg) reduced the incidence of isoproterenol-induced ventricular fibrillation and death; bretylium (10 mg/kg) and nicotinic acid (100 mg/kg) had no effect. A lower dose of propranolol (2.5 mg/kg) or clofilium (1.5 mg/kg) but not quinidine (10 mg/kg), procainamide (10 mg/kg), or phenytoin (10 mg/kg) also reduced the incidence of ventricular fibrillation. Only clofilium tended to increase the incidence of spontaneous reversions.

Animals↗
PubMed1986

Ionic strength dependence of the polymer solubilities of deoxyhemoglobin S + C and S + A mixtures.

Factors contributing to the clinical differences between sickle cell-hemoglobin C disease (SC) and the benign sickle cell trait (AS) include the higher proportion of hemoglobin (Hb) S and the higher cell Hb concentrations in SC compared with AS red cells. Reports differ, however, about whether Hb C copolymerizes more than Hb A with Hb S when measured by minimum gelling concentrations (MGCs) and polymer solubilities of the deoxy-Hb mixtures. We now show that the MGCs and solubilities of equimolar mixtures of Hb S + Hb C vary much more with the ionic strength (mu) of the solution than those of Hb S + Hb A mixtures. At mu less than or equal to 0.20, but not at mu greater than 0.25, Hb S + Hb C solubilities were significantly lower than those of Hb S + Hb A. These differences which may reflect a greater effect of the beta 6Lys+ in Hb C at lower mu, can account for the reported discrepancies. The solubility differences were similar in the presence or absence of asymmetric hybrids, and since the intratetramerically cross-linked hybrids alpha 2 beta s beta A and alpha 2 beta s beta c had similar solubilities, they did not indicate the usual mechanism, involving greater incorporation of alpha 2 beta s beta c into the polymers. The small solubility differences between the two Hb mixtures at physiologic (red cell) concentrations of Hb and 2,3-diphosphoglycerate probably play a minor role in the clinical differences between SC and AS states.

2,3-Diphosphoglycerate↗
PubMed1985

Muscle atrophy and histopathology of the soleus in 6-mercaptopurine-treated rats.

This study was conducted to examine the histochemical changes occurring due to neonatal 6-mercaptopurine (6-MP) treatment (2 mg/kg, sc, between 2 and 22 days after birth) in the slow-twitch muscle (soleus) of adult male and female rats. At 6 months of age, the control and the 6-MP-treated rats were evaluated for the sciatic nerve conduction to the soleus and for the soleus atrophy and histopathology of the type I (slow-twitch) and type II (fast-twitch) muscle fibers. Compared to the normal controls, the 6-MP-treated male and female rats showed similar sciatic nerve conduction to the soleus. However, there was a significant muscle atrophy (57-60%, P less than 0.01) and a decrease in fiber areas of the type I (42-54%, P less than 0.05) and type II (41-71%, P less than 0.01) fibers. The number of type II fibers declined significantly (7.4-14.8%, P less than 0.05). It is proposed that the soleus muscle atrophy and histopathology in 6-MP-treated rats is unrelated to nerve conduction defects and may be related to growth inhibition caused by an interference of the drug during normal differentiation of muscle fibers.

Adenosine Triphosphatases↗
PubMed1985

Effects of 6-mercaptopurine treatment on the membrane potentials of rat skeletal muscle fibers.

6-Mercaptopurine (6-MP), injected daily (2 mg/kg s.c.) into Sprague-Dawley rats during the first 3 weeks of life, causes atrophy in muscles of the hindquarters beginning at 4 months of age. The extensor digitorium longus (EDL) muscles from 24 rats injected with 6-MP and 23 saline-injected controls, 6-18 months of age, were studied. Electron microscopy showed a number of abnormalities in the EDL muscle of 6-MP-treated rats, such as myocytes with atypical ultrastructure (including disorganized myofibrils) adjacent to structurally normal cells. Membrane potentials (Em) were measured in the isolated EDL and in the caudofemoralis (CF) muscle in situ. The mean Em of fibers in the EDL of 6-MP-treated rats (-61.1 +/- 0.7 (SE) mV) was lower than that of the control rats (-69.7 +/- 0.6 mV). The same was true for the fibers of the CF muscle (-64.9 +/- 1.5 mV for 6-MP-treated fibers vs. -71.6 +/- 1.3 mV for controls). The contribution of the electrogenic pump potential to Em (+/- ouabain) was similar in 6-MP-treated and control rats, and therefore could not account for the depolarization observed in 6-MP-treated rats. This depolarization was not due to a decreased intracellular K+ concentration. The Na+:K+ permeability ratio (PNa/PK) was higher in the 6-MP-treated rats and could account for the decrease in Em.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1985

Inhibition of dopaminergic agonist-induced gnawing behavior by neuroleptic drugs in mice.

Several neuroleptic drugs cause the Parkinsonian syndrome (PS) in humans; however, this effect is not detectable in rodents. PS-inducing drugs inhibit gnawing or biting behavior induced by apomorphine, amphetamine, DOPA, and thozalinone. The effects of five narcoleptic drugs (chlorpromazine, haloperidol, perphenazine, thioridazine, and trifluoperazine) on this behavior were tested in ICR male mice (10 per dose level). The drugs were given ip 30 min before each of the following inducing agents: DL-DOPA (500 mg/kg, iv), apomorphine (100 mg/kg, ip), amphetamine (12.5 mg/kg, ip), and thozalinone (100 mg/kg, ip). The criterion for blocking effectiveness was the prevention of the biting or gnawing behavior. Prevention indexes (PI) were calculated from the LD50/ED50. Data are consistent with the PS-inducing potencies of these five drugs. Another selective index (SI) of each drug was established by the ED50/ND50 ratio. There is some correlation between PI values and clinical symptoms, but it is not as well defined as that between SI values and clinical symptoms. Data from the thozalinone test (SI) appear to provide the best prediction for the PS-inducing potencies of the drugs tested. Thus, this technique appears to be suitable for use as an animal model in preclinical toxicity studies.

Animals↗
PubMed1984

Alteration of convulsive threshold and conditioned avoidance response in mice fed diets containing contraceptive steroids.

Female CD1 mice given the contraceptive steroids mestranol and norethynodrel (1:10) in the diet (0.0033%) for 4 months had a growth reduction of 20% when compared with mice fed a normal diet, and had lower convulsive thresholds when tested with the vitamin B6 antagonists 2,4-dimethyl-5-methyl-hydroxypyrimidine and thiosemicarbazide. In conditioned avoidance response (CAR) tests, mice fed the steroid-containing diets showed a decreased acquisition performance during all six sessions; however, mice fed the same diet supplemented with vitamin B6 (0.04%) performed as well during the last three sessions of the CAR tests as mice fed the normal diet.

Animals↗