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Biomedical subjects

D Couri

Publications and source records attributed to D Couri.

At least 37 records · Page 2Linked to original sources
PubMed1982

Metabolism and pharmacokinetics of alternate drinking water disinfectants.

The chlorination of surface waters is known to elevate trihalomethanes; consequently, chlorine dioxide (ClO2) is being considered as an alternative disinfectant. The primary products resulting from ClO2 disinfection of waters are chlorites (ClO2-) and chlorates (ClO3-). Studies in rats revealed that ClO2 is converted to chloride (Cl-), ClO2- and ClO3-. ClO2- and ClO3- are excreted as Cl-, ClO2- and Cl-, ClO2-, ClO3-, respectively. Radioactivity was rapidly absorbed from the gastrointestinal tract following the administration of 36ClO2 orally, and the half-life for the elimination of 36Cl from the rat was 44 hr, corresponding to a rate constant of 0.016/hr. After 72 hr, radioactivity was highest in plasma, followed by kidney, lung, and stomach. 36Cl in plasma reached a peak at 2 hr and 1 hr after oral administration of 36ClO2- and 36ClO3-, respectively. 36Cl excretion was greatest 24 hr after the administration of 36ClO3-, but in the case of 36ClO2-, the excretion probably represented saturation of the biotransformation and excretion pathway. A low activity in packed cells compared to plasma was detected in chlorate ingestion, rather than an even distribution in chlorite treatment. Chloroform determinations in rat blood after one year indicated that chloroform was significantly higher than control in the 100 and 1000 mg/l. ClO2 groups. However, no significant values were observed in the 1 or 10 mg/l. ClO2 and ClO2 metabolites groups. ClO2 and its metabolites are eliminated from the body more rapidly than chlorine, and they do not appear to increase trihalomethane concentrations at low dosages.

Animals↗
PubMed1982

Assessment of maternal toxicity, embryotoxicity and teratogenic potential of sodium chlorite in Sprague-Dawley rats.

Groups of up to 13 pregnant rats were individually caged. Body weight, food and water consumption were recorded at days 1, 8, 15 and 22 of gestation and the dams were treated on days 8-15 with sodium chlorite, 0.1%, 0.5% or 2% in drinking water or by injection of 10, 20, or 50 mg/kg IP or by gavaging with 200 mg/kg. To prevent ingestion of stillborn pups some dams were sacrificed at day 22. Other dams were allowed to deliver at term. Fetuses were weighed, measured and examined for soft tissue and skeletal malformations. Sodium chlorite, 20 or 50 mg/kg daily IP or gavaging with 200 mg/kg, caused vaginal and urethral bleeding. Doses of 10, 20 or 50 mg/kg daily IP caused 0, 50 and 100% mortality of dams, respectively. No deaths were caused by sodium chlorite in the drinking water, but the dams' body weight, water and food consumption decreased during all treatments except 0.1% in the drinking water. Blood smears from the dams injected IP or drinking 2% sodium chlorite showed irregular, bizarre and ruptured erythrocytes. Injection of 10 or 20 mg/kg or drinking 2% resulted in decreased litter size and increased stillbirths and resorption sites. Drinking 0.1% or 0.5% sodium chlorite did not produce any significant embryotoxicity. With all treatments, no significant gross soft tissue or skeletal malformations were observed. Postnatal growth of the pups was not affected by any treatment of the dams during the gestation period.

Administration, Oral↗
PubMed1982

Methapyrilene effects on initiation and promotion of gamma-glutamyl-transpeptidase positive foci in rat liver.

The initiating and promoting effects of methapyrilene were evaluated using the hepatic enzyme-altered foci bioassay. Male Sprague-Dawley rats were partially hepatectomized and 24 hours later were administered either methapyrilene or nitrosodiethylamine by oral gavage. Subsequently, the animals were promoted with 500 ppm2 phenobarbital or 200 ppm methapyrilene in drinking water for eight weeks. Fresh frozen sections of liver were then stained and scored for gamma-glutamyl-transpeptidase (GGT)-positive foci. Methapyrilene, when tested as the nominal initiator at a single dose of 50 mg/kg or at two doses of 130 mg/kg and promoted by phenobarbital, did not induce foci above background levels. However, when substituted for phenobarbital as the promoting agent following nitrosodiethylamine initiation, methapyrilene enhanced enzyme-altered foci formation to an equal or greater extent than did the promoter phenobarbital. These results suggest that the carcinogenic effects of methapyrilene may be related to its ability to enhance hepatic tumorigenesis.

Aminopyridines↗
PubMed1982

Effect of phenobarbital on cytoplasmic and nuclear distribution of 3H-arginine in rat liver.

Rat liver derived from animals receiving phenobarbital (80 mg/kg intraperitoneally) exhibited an increase in the cytoplasmic concentration of radioactive amino acid (initially injected as arginine) as early as 1 hour after the injection. This increase in uptake resulted in an unequal distribution of the radioactivity between the cytoplasmic and nuclear compartments; while other organelles retained their normal (per cent) allotment of the radioactivity. The cytoplasmic and nucleoplasmic protein profiles from gel chromatography show quantitative changes that may be due to increased synthesis and migration of a cytoplasmic protein to the nucleus where its nuclear function remains to be examined more thoroughly.

Animals↗
PubMed1981

Diazepam infusion in tetanus: correlation of drug levels with effect.

A patient with muscle spasms and rigidity associated with tetanus was successfully treated with a continuous infusion of diazepam. This beneficial response was associated with a minimal serum diazepam concentration of 500 ng/ml. The major metabolite of diazepam, DMD, did not appear to exert substantial activity. Guidelines for dosing diazepam are provided.

Adult↗
PubMed1981

Corticosteroid modulation and stress-induced analgesia in rats.

Early evidence has indicated the presence and involvement of specific neural systems which can inhibit the responses to painful stimuli. More recently, further advances suggest that the opiate system may interact with other systems to modulate the analgesia produced by the opiates or various stressors. Since corticosteroids were found to be elevated under the conditions of different stress-induced analgesia (SIA), there may be interactions between the pain-inhibiting systems and the corticosteroids. Recently it was reported that acute stress or long-term adrenalectomy can result in release of beta-endorphin (beta E) and ACTH from the pituitary gland, which can be blocked by dexamethasone. In our early studies we have shown partial antagonism of the SIA by dexamethasone and complete antagonism after naloxone. In this report it was found that chronic treatment of the rats with 0.02% metyrapone in drinking water for 8 weeks resulted in minor hyperalgesia. The chronic pretreatment with metyrapone resulted in a significant potentiation of the analgesia induced via the cold swim stress model, which was reversed by 1 mg/kg (IP) naloxone. Also, hyperalgesia was noted 18 days after the bilateral adrenalectomy of the rats as measured in our laboratory by the hot plate method and as reported by Heybach and Vernikos-Danellis in 1978. These results suggest that the corticosteroid modulation (pituitary-adrenal axis) may have a role in regulating the SIA, and this may implicate the interactions of the corticosteroids with pain-inhibiting systems.

Adrenal Cortex Hormones↗
PubMed1981

Acute toxicity of sodium selenite and selenomethionine in mice after ICV or IV administration.

The acute intracerebroventricular administration of sodium selenite and selenomethionine in conscious mice produced neurotoxicity manifested by hyperreflexia, convulsions and dealth. Selenite was 43-fold more toxic than selenomethionine on the basis of LD50 determination. The intravenous administration of the selenium compounds resulted in predominantly cardio-respiratory effects, hind limb paralysis and death. Selenite was 4-fold more toxic than selenomethionine. A comparison of relative toxicity after icv or iv administration revealed that selenite is more toxic than selenomethionine and greater relative toxicity was noted via the icv route. This toxicity difference may be attributed to the lack or low level of biotransformation of selenite by the CNS.

Animals↗
PubMed1981

Biophysical and electrophysiological studies of hexanedione neurotoxicity.

This study examined the significance of nerve microviscosity changes which occur in 2,5-hexanedione (2,5-HD) neurotoxicity. To establish a correlation between microviscosity changes and neuronal damage, a standard axonal neuropathy (nerve section) was employed. Electrophysiological studies of the sciatic-tibial nerve of rats were carried out to detect the onset of nerve damage. Also, because 2,5-HD may affect membranes in general, with nerve membranes being the most sensitive, red blood cell ghost membranes were prepared from 2,5-HD treated animals and tested for viscosity changes. Results of these studies suggest that 2,5-HD and nerve section have similar effects on myelin microviscosity.

Animals↗
PubMed1980

Inhibition by warfarin of prothrombin synthesis and of lipid-saccharide synthesis in rat liver.

In vivo and in vitro studies using [3H]glucosamine incorporation into prothrombin and into glycolipids were conducted in rat liver to determine the role of lipid-saccharides in the biosynthesis of prothrombin. In vivo studies demonstrated that 10 mg warfarin/kg inhibited the incorporation of radiolabeled glucosamine into liver prothrombin and glycolipids. This inhibition was similar to the kinetics of inhibition of prothrombin synthesis in the liver. In vitro studies demonstrated a time-dependent increase in the incorporation of radiolabeled glucosamine into lipid-saccharides and prothrombin. This incorporation was inhibited 50% by 5 . 10(-4) M warfarin. Warfarin also inhibited the incorporation of radiolabeled glucosamine into glycolipids in a dose-related manner. In all studies, vitamin K-1 reversed the inhibition of glucosamine incorporation into glycolipids and into prothrombin.

Animals↗
PubMed1980

Treatment of childhood epilepsy with valproic acid: results of the first 100 patients in a 6-month trial.

We evaluated valproic acid (VPA) for 6 months as therapy for uncontrolled seizures in 100 children, 38 with partial and 62 with generalized epilepsy. Sixty-one patients experienced more than a 75% decrease in seizures. The improvement in generalized epilepsy paralleled adult VPA studies, but partial epilepsy improved more than expected, even though acceptable seizure control was often achieved only after 6 months of VP therapy. The most significant side effect was gastrointestinal distress, which was alleviated by dietary changes. Limited experience suggested that enteric-coated capsules eliminated gastrointestinal symptoms. Hematologic, hepatic, and behavioral sequelae were minimal.

Adolescent↗
PubMed1979

Neurofibrillary tangles induced by a sclerosing angioma.

A sclerosing angioma in the frontal cortex of a 40 year old woman produced local pressure, with resulting alteration of the blood-brain barrier. In the narrow cortical zone affected by chronic pressure, the level of aluminum was significantly elevated; and all neurons had neurofibrillary tangles of the Alzheimer type.

Adult↗
PubMed1979

Chlorine dioxide metabolism in rat.

Chlorine dioxide (ClO2) is under consideration as an alternative to chlorination as a disinfectant for public water supplies. A new assay was developed to qualitatively and quantitatively measure the metabolites of 36ClO2 in water and biological fluids. Studies in the rat indicated that the metabolites of ClO2 were Cl-, ClO-2, and ClO-b. At maximum absorption the percentage of ClO; formed in plasma from an initial oral dose of 10 mg/l 36ClO, was higher than from a 100 mg/l dose. The 36Cl concentration in washed packed cells indicated that 36Cl readily exchanges with chloride of saline.

Animals↗
PubMed1979

Kinetics of Cl02 and effects of Cl02, Cl02-, and Cl03- in drinking water on blood glutathione and hemolysis in rat and chicken.

Since chlorination of drinking water produces organochlorinated substances (some possibly carcinogenic), the use of chlorine dioxide disinfectant would avoid halogenation. There is scarcely any data published on the effects of ClO2 in drinking water on human or animal health. The kinetics of 36ClO2 was studied in rats. Radioactivity was rapidly absorbed from the gastrointestinal tract following the administration of (0.07 microCi) 36ClO2 orally. 36Cl in plasma reached at peak at 1 hr. The half life for the elimination of 36Cl from the rat was 44 hr, corresponding to a rate constant of 0.016 hr-1. After 72 hr radioactivity was highest in plasma, followed by kidney, lung, stomach, duodenum, ileum, liver, spleen, thymus, and bone marrow. 36Cl excretion was greatest at 24 and 48 hrs after the administration of 36 ClO2. Forty-three percent of the total initial dose was excreted at 72 hr in the urine and feces. No 36 Cl was detected in expired air throughout the 72 hr studied. ClO2, ClO2-, and ClO3- (1, 10, 100, 1000 ppm) given daily in drinking water decreased blood glutathione, decreased osmotic fragility, and changed the morphology of erythrocytes in both chicken and rat after two months. Methemoglobin was not detected throughout these studies.

Animals↗
PubMed1979

Effect of chlorine dioxide and metabolites on glutathione dependent system in rat, mouse and chicken blood.

Chlorine dioxide (Cl02) has been proposed as an alternative disinfectant to chlorine to avoid formation of organohalides. Cl02 and metabolites, chlorite (Cl0-2) and chlorate (Cl0-3) in drinking water produced decreases in rat and chicken blood GSH. The GSH dependent system was studied in rat and chicken blood after chronic treatment for 6 months with CL02 (0, 1, 10, 100, 1000 MG/L), Cl0-2 or Cl0-3 (10, 100 mg/l) in drinking water. There was a 60% increase in GSH reductase in the Cl02 treatment groups of rats and chickens. A similar increase was shown in rats treated with Cl0-2 but with Cl0-3 no change was observed. GSH peroxidase was without change in rat but chickens drinking 1000 mg/l Cl02 had decreased activity. Catalase was significantly higher than control in rat and chicken in the 1000 mg/l groups. However, catalase activity was decreased in rat treated with Cl0-2 and at the same time that GSH was decreased. These studies support the view that catalase is the first line of defense against the oxidative stress of Cl02 in rat and chicken erythrocytes.

Animals↗