Lincoln Chin

Role of brain 5-hydroxytryptamine in audiogenic seizure in the rat.

Arastirmanin amaci gebe okulu’na basvuran gebelerin yasadigi gebelige bagli fiziksel saglik sorunlarini incelemektir. Calismanin v erileri gebe okulunun kayit sisteminden elde edilmistir. Verilerin analizi tanimlayici istatistikler ve ki-kare testi ile yapilmistir. Bu arastirma gebelerin onemli bir bolumunun bulanti-kusma, sik idrara cikma, vajinal kanama, memelerde hassasiyet, konstipasyon, gaz, hemoroid, sirt agrisi, bacak kramplari gibi sorunlari yasadiklari sonucunu aciga cikarmistir. Saglik profesyonellerinin gebe okulu ya da diger egitim ve danismanlik hizmetleri sirasinda bu saglik sorunlarini da dikkate almalari ile gebelik surecinin saglikli gecirilmesine katki saglanabilir.

Enhancement of audiogenic seizure by 6-hydroxydopamine

in our laboratory (Symchowicz & Wong, 1966a, b), that in rat urine both 4-DM and DM were present as the major metabolites. The rate of urinary drug excretion in rat was also similar to that of the mouse. Therefore, the mouse and the rat appear to have a similar metabolic pattern for griseofulvin. The unidentified metabolite with an R, value of 0.12 observed in mouse urine was probably also present in rat urine but in a much smaller amount.

Activated charcoal vs. “universal antidote” as an antidote for poisons

Abstract The results of the present investigation demonstrate that activated charcoal alone is more effective as an adsorbent for pentobarbital, strychnine, and malathion than “universal antidote” which contains an equivalent amount of activated charcoal. Apparently, the tannic acid and/or the magnesium oxide component of “universal antidote” interferes with the adsorptive activity of activated charcoal. It is recommended that activated charcoal replace “universal antidote” in the treatment of poisoning.

Optimal antidotal dose of activated charcoal.

Abstract Activated charcoal is an effective antidote for reducing the gastrointestinal absorption of numerous ingested chemicals. However, the dose of activated charcoal for clinical use has often been recommended on the basis of in vitro data. Use of such data tends to overestimate the antidotal capacity of activated charcoal and may result in undertreatment with the adsorbent, whereas in vivo data are believed to be more reliable. The present study quantifies the capacity of activated charcoal to bind 3 drugs, pentobarbital sodium, chloroquine phosphate, and isoniazid in vivo. A fixed dose of each drug was administered to rats and mean control tissue concentrations of the drugs were determined at peak time. The identical dose of each drug was then administered to groups of rats which were immediately antidoted with activated charcoal in a dose of 1, 2,4 or 8 times the weight of the drug. Tissue concentrations of the drugs were then determined and the results were calculated and expressed as percent reduction of tissue drug concentrations, on the basis of the control tissue drug concentration values. Charcoal-drug ratios of 1:1, 2:1, 4:1 and 8:1 reduced absorption as follows: pentobarbital sodium, 7, 38, 62 and 89%; chloroquin phosphate, 20, 30, 70 and 96%; and isoniazid, 1.2, 7.2, 35 and 80%. Binding of drugs by activated charcoal at the 3 lower charcoal-drug ratios was highly variable between drugs. Only the highest charcoal-drug ratio provided uniform and nearly complete binding of the 3 drugs. The results suggest that the optimal activated charcoal-drug ratio for the treatment of pentobarbital, chloroquine, and isoniazid is at least 8:1.

Evaluation of activated charcoal-sorbitol suspension as an antidote.

Studies in rats were performed to evaluate the effect of sorbitol on the antidotal efficacy of activated charcoal against four test drugs and to investigate the influence of storage upon the antidotal effect of activated charcoal-sorbitol suspension. The antidotal potency of activated charcoal was not diminished by sorbitol solution 70% w/v. In fact, it was enhanced by the sorbitol solution, as indicated by greater decrease in peak tissue drug concentration, compared to the effect produced by activated charcoal in aqueous suspension. Furthermore, storage of activated charcoal in sorbitol for as long as 1 year did not reduce the antidotal-efficiency of the absorbent.

Saline Cathartics and Saline Cathartics Plus Activated Charcoal as Antidotal Treatments

The results of this experimental study indicate that Na2SO4 reduces the gastrointestinal absorption of aspirin, but not that of pentobarbital, chlorpheniramine, or chloroquine. Activated charcoal (AC) and the combination of AC + Na2SO4 were effective in reducing gastrointestinal absorption of all four test drugs. The combination treatment was more effective than AC treatment in reducing gastrointestinal absorption of aspirin, pentobarbital, and chloroquine. We believe that saline cathartics should not be used in lieu of AC for treatment of poison ingestions, and their routine use to treat poison ingestion should be reevaluated. On the other hand, saline cathartics may be used in conjunction with AC to enhance the antidotal effect of the adsorbent.

The action of activated charcoal on poisons in the digestive tract

Abstract Time course blood- or liver-drug analyses were performed to investigate the action of activated charcoal on poisons in the gastrointestinal tract. Blood was obtained from dogs treated orally with aspirin, pentobarbital, barbital, or glutethimide, and liver was obtained from rats treated orally with chloroquine, chlorpheniramine, or chlorpromazine. Test animals were treated with activated charcoal 1 min after drug administration. Control animals were given only the drugs. All the drug concentration curves of test animals were markedly lower than those of corresponding control animals. Semilogarithmic plots of the data suggest that dissociation of charcoal-drug complexes, if it does occur, is inconsequential. Administration of activated charcoal 1 min after poisoning is markedly more effective in reducing gastrointestinal absorption of drugs than the administration of charcoal 30 min after poisoning. Repeated administration of activated charcoal at 1- or 12-hr intervals, after an initial antidotal treatment, appears to exert no additional inhibition of gastrointestinal absorption of poisons. Activated charcoal, in a dose 5 times that of each poison, administered 30 min after poisoning, effectively reduced mortality in dogs given lethal doses of pentobarbital, barbital, or chloroquine. Intoxication developed so rapidly in some dogs that the administration of charcoal, 30 min after poisoning, was ineffective in preventing death. This investigation confirms the effectiveness of activated charcoal in the treatment of poisoning. It also emphasizes the need for immediate treatment with an adequate dose of the absorbent in the management of ingested poisons.

Convulsions as the etiology of lactic acidosis in acute isoniazid toxicity in dogs

Abstract The mechanism by which acute isoniazid (INH) overdose causes lactic acidosis is unknown. This study examines the role of convulsion in the development of lactic acidosis in dogs given po lethal doses of INH (75 mg/kg). Following INH, dogs did not develop acidosis until after they had experienced clonic-tonic convulsions. Acidosis, which became more pronounced with successive convulsions, was associated with marked increase of serum lactate (immediate postconvulsive level, 12.3 meq/liter, compared to control of 1.83 meq/liter). Diazepam, 0.5 mg/kg, plus pyridoxine HCl, 150 mg/kg, injected iv immediately following po INH, prevented both convulsions and changes in pH and lactate. When the antidotes were administered after the second convulsion of INH toxicity no further convulsions occurred and blood pH and lactate returned to control levels in 2 hr. “Curarization” of INH-treated dogs prevented both motor seizures and marked increase of lactate. In animals treated with INH and allowed to convulse two times to develop severe acidosis, correction of the acidosis with NaHCO 3 failed to prevent further convulsions and death. Diazepam and pyridoxine combinations, in doses that were ineffective for terminating INH-induced convulsions, became effective when given after correction of acidosis with NaHCO 3 . It is concluded that convulsion is the main cause of lactic acidosis in acute INH toxicity and that correction of acidosis does not terminate acute INH toxicity. Although correction of acidosis increases the antidotal effectiveness of diazepam plus pyridoxine, increasing the dose of either or both of these two drugs achieves the same antidotal advantage without the potential problems of metabolic alkalosis which may result from NaHCO 3 administration.

Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs.

Abstract Because information regarding efficacious treatment of acute isoniazid (INH) toxicity is incomplete and controversial, diazepam and pyridoxine were investigated as iv antidotes in rats and dogs following administration of po lethal doses of INH. There is a marked species variation in the lethality of INH; the lowest consistently lethal dose is 1500 mg/kg for rats and 75 mg/kg for dogs. Of the two species, the dog more closely approximates mans sensitivity to the lethal effect of INH overdose (80–150 mg/kg). Species variation was also observed in the effects of the antidotes. Diazepam exerted dose-related protection against convulsions in rats; paradoxically, survival was increased by the lowest dose (1 mg/kg) but not by higher doses. In dogs, however, diazepam failed to prevent convulsions but provided dose-related protection against death. Pyridoxine, in rats, did not protect against INH toxicity, but in dogs it showed dose-related effectiveness against convulsions, and all doses (75–300 mg/kg) prevented lethality. Significantly, the highest dose of pyridoxine tested in rats (750 mg/kg) was substantially below the optimal pyridoxine-to-INH antidotal ratio recommended for man (a dose that at least equals the amount of INH ingested), but that dose of pyridoxine would be larger than its LD50 for rats. Combined administration of diazepam with pyridoxine protected against convulsions and death in rats and dogs. Used concurrently, the two antidotes are clearly synergistic for controlling the manifestations of experimental INH overdose. These results have important implications for the management of acute INH intoxication in man.

Δ9-Tetrahydrocannabinol, EEG and behavior: The importance of adaptation to the testing milieu

Delta-9-Tetrahydrocannabinol (delta-9-THC) in doses of 0.01, 0.05, 0.1, 0.5, and 1.0 mg/kg, i.v. was administered to adult rabbits previously adapted to the testing chamber. Additionally, a group of rabbits not adapted to any part of the testing regimen was administered 1.0 mg/kg delta-9-THC. Cortical and hippocampal electroencephalographs as well as postural and activity behaviors of the unrestrained animals were recorded. In the adapted rabbits, there were dose-related increased in cortical voltage output, disruption of hippocampal theta rhythm and cortical polyspike bursts. Behaviorally, there was a dose-related tendency for standing and exploration to decrease, and at 0.5 and 1.0 mg/lh, delta-9-THC produced sprawling. In the nonadapted rabbits, administration of 1.0 mg/kh of the drug caused EEG and behavioral stimulation followed by depression of both, The results suggest that the bahavioral actions of cannabinols are largely dependent upon the animals existing state of arousal.