Biomedical subjects
Publications and source records attributed to L E Davis.
Adverse drug reactions occasionally occur in the horse. The majority can be anticipated and avoided. The practicing veterinarian should understand the various types of adverse reactions as well as their mechanisms so that should such a reaction occur, the practitioner can promptly recognize the problem and institute corrective measures.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Aminophylline dissolved in water, propylene glycol, or dimethyl sulfoxide was administered intravenously to goats in a randomized cross-over experiment. Model-dependent and model-independent pharmacokinetic parameters for theophylline were compared on the basis of the solvent used in the dosage form administered. No difference was found in any pharmacokinetic parameter. Thus, we found no evidence for the possibility that the organic solvents studied would confound pharmacokinetic investigations of theophylline and similar lipophilic drugs.
Serial blood samples were collected and plasma concentrations of florfenicol (FLO) were measured following the administration of an intravenous bolus of 50 mg/kg FLO to five healthy non-lactating dairy cows. A triexponential equation provided the best fit of the data for four of the five cows. The mean value for beta corresponded to a half-life of 3.2 h. The mean apparent volume of distribution was 0.67 l/kg, and the mean body clearance was 0.15 l/kg/h. The extent of binding of FLO to bovine plasma proteins was determined in vitro at concentrations of 5 micrograms/ml and 50 micrograms/ml by equilibrium dialysis and ultrafiltration. The drug was 18% and 19% bound by equilibrium dialysis, and 23% and 19% bound by ultrafiltration, at 5 micrograms/ml and 50 micrograms/ml, respectively. Phagocytosis of 32phosphorus-labelled Staphylococcus aureus by bovine blood neutrophils was compared in vitro between neutrophils incubated in phosphate-buffered saline alone or in combination with 5, 125, or 1000 micrograms/ml chloramphenicol or FLO. There was no significant effect of chloramphenicol at any concentration. Florfenicol significantly inhibited phagocytosis at all concentrations, but the percentage inhibition was small. The clinical significance, if any, of this effect of FLO remains to be demonstrated.
Explore the source record for details and available documents.
The disposition of fenbendazole was studied in goats after oral or IV administration. Plasma concentration vs time profiles were determined for fenbendazole and all of its metabolites. The total excretion of the drug and its metabolites in urine and feces was also measured for 6 days. A biliary cannula was inserted in 1 goat to study the excretion of fenbendazole and its metabolites into the bile. Fenbendazole was converted to its sulfoxide (oxfendazole), and the sulfone, primary amine, and p-hydroxylated metabolites. The active metabolite, oxfendazole, appeared in plasma, but only trace amounts were found in feces or urine. The major excretory metabolite was p-hydroxyfenbendazole.
Fenbendazole (FBZ) was administered to cattle IV and orally in a crossover design. Plasma concentration vs time profiles were reported for FBZ and its major metabolites, the sulfoxide (oxfendazole) and the sulfone. The total excretion of FBZ and its metabolites in urine and feces was also measured for 6 days after administration. All known metabolites were identified in urine and feces except for fenbendazole amine. Neither this minor metabolite nor p-hydroxyfenbendazole (FBZ-OH) appeared in plasma. The major excretory product was FBZ-OH. After oral administration, only 44.6% of the dose was eliminated after 6 days, indicating a fairly high degree of sequestration, probably within the gastrointestinal tract.
Nonpermissive or abortive viral infections seldom have been recognized as damaging to organs. Concentrated infectious influenza B/Lee virus injected intravenously into Balb/c mice causes a microvesicular fatty metamorphosis of the liver and produces many features of Reye's syndrome. Evidence for a nonpermissive infection in brain and liver includes the following points: (a) no viral replication occurs in either organ; (b) no inflammation develops; (c) no virions are seen by electron microscopy; (d) influenza B viral hemagglutinin increases in the liver; (e) immunofluorescent and immunoperoxidase staining demonstrate viral antigens within hepatocytes and brain capillary endothelial cells; (f) viral antigens appear at 12 hours and disappear by 4 days without spread to adjacent cells; (g) inactivated influenza B virus does not kill mice; (h) mouse alpha- and beta- interferon and homologous B/Lee antiserum given before but not 2 hours after virus inoculation protects mice. These observations suggest a nonpermissive viral infection in hepatocytes and brain capillary endothelial cells which is important in the pathogenesis of the mouse illness and may play a role in the pathogenesis of Reye's syndrome.
Two chemical methods, diazocoupling and reaction with isocyanates, are commonly used to conjugate primary aromatic amines with carrier proteins in order to elicit antibody responses against the aromatic amine haptenic group. Limitations of these conjugation techniques include the requirement for specific functional groups on the carrier protein which generally limits the degree of haptenic substitution obtainable, the many possible side reactions yielding hapten-hapten and carrier-carrier conjugates which waste valuable materials and lower desired hapten-carrier conjugate yields, and, in some cases, conjugation conditions which may denature the carrier protein (e.g., alkaline coupling conditions). We report here a photolabeling approach for conjugating primary aromatic amines to carrier proteins which avoids some of the problems of other conjugation methods and which was used to elicit antibodies against the primary aromatic amine hapten. The method described here is of general application for coupling primary aromatic amines to the carrier proteins and circumvents many of the problems inherent in the isocyanate or diazocoupling methods. 3-Azido-N-ethylcarbazole (ANEC), the azido analog of 3-amino-N-ethylcarbazole, was conjugated to bovine serum albumin (BSA), human transferrin (TR), thyroglobulin (TH), poly-(lysine X tyrosine), and poly-(lysine X phenylalanine) using standard photolabeling procedures. After photolysis, the conjugated proteins or polypeptides were separated from the unbound products of ANEC photolysis on a Sephadex G-10 column. The conjugated proteins were extracted with isobutanol which demonstrated that approximately 20% of the ANEC was covalently coupled to the protein carriers and that the larger portion of the aromatic haptens was non-covalently and hydrophobically bound to the carriers. The ANEC-protein conjugates used for immunization demonstrated a total covalently and non-covalently bound ANEC epitope density of 90 per BSA, 107 per TR and 800 per TH molecule. Rabbits were immunized with the three conjugated proteins and the production of antibody specific for the 3-amino-N-ethylcarbazole hapten was demonstrated by enzyme-linked immunosorbent assay and by inhibition studies using hapten-carrier conjugates of free hapten. The results demonstrate that antibodies against aromatic amine haptens may be raised by immunizing animals with hapten-carrier protein conjugates produced by photolabeling. Since the coupling conditions are very mild and the functional group requirements are so general (requiring only the presence of C-H, N-H, C = O, C = S, or S-H bonds) most carrier proteins should be suitable for use in this method.(ABSTRACT TRUNCATED AT 400 WORDS)
Atypical ocular bobbing resulted from an intentional poisoning from dimpylate (Diazinon), an organophosphate compound. In discussing the possible foci and mechanism for atypical ocular bobbing associated with acute organophosphate poisoning, we suggest acetylcholine as a neurotransmitter substance within the ocular motor pathway. A literature review has not shown any previous reported cases with this sign.
Biochemical evidence is presented for the autophagic destruction of liver mitochondria in the influenza B virus model of Reye's syndrome in mice. Separation of lysosomes and autophagic vacuoles from mitochondria was accomplished by prior treatment of the mice with Triton WR-1339, resulting in uptake of detergent by these organelles (tritosomes), reducing their densities. The organelles were banded in a discontinuous sucrose gradient. Total protein in the heavy tritosomal fraction increased from 1-2% in controls to 7-8% in virus-treated animals. Ornithine carbamoyl transferase (OCTase), a mitochondrial marker, increased from 2-3% (controls) to 11-15% (virus-treated), and glucose-6-phosphatase, a marker for endoplasmic reticulum, increased from 1-2% (controls) to 8-10% (virus-treated). beta-Galactosidase, a soluble enzyme in the lysosome, and OCTase also increase in the cell extract fraction following virus treatment, indicating that there was turnover of heavy lysosomal contents.
Biochemical studies of a female who died at 2 years of age from a possible genetic variant of ornithine carbamoyltransferase (OCTase) deficiency are reported. The patient had severe psychomotor retardation with plasma ammonia levels throughout life reaching as high as 500 mumole/liter. The average OCTase level in the patient's liver was 2% of that in normal livers. Preincubation with 0.05 M MgCl2 resulted in a 570% increase in OCTase activity (13% of control). Citrate synthase and carbamoyl-phosphate synthase I were present at essentially normal levels. Unusual Mg2+ requirements have not been recognized in previous reports of OCTase deficiency, suggesting a genetic variant in this patient.
This article presents important clinical pharmacologic aspects of drug therapy during pregnancy. It reviews the potential adverse effects on the mother and conceptus caused by drugs and includes specific recommendations for therapy. Extensive tables are included that list drugs that are safe and those that are contraindicated during pregnancy.
Explore the source record for details and available documents.
The pharmacokinetics of lithium were determined in eight adult dogs. The data were fitted to a two-compartment model. Single intravenous doses of lithium chloride, and single oral doses of lithium carbonate were used. The mean plasma lithium half-life (t1/2) following the single intravenous dose was 21.6 h, and the mean apparent specific volume of distribution of the central compartment (V'c) was 0.189 l/kg. Mean bioavailability was 78.8% following oral administration.
The arrhythmogenic dose of epinephrine (ADE) was determined in six dogs during halothane (1.35%) anesthesia before and after xylazine administration (1.1 mg/kg, i.v. bolus; 1.1 mg/kg/hr, i.v. infusion). The arrhythmogenic dose was determined by constant infusion of freshly mixed epinephrine (100 microgram/ml). The ADE was defined as the total dose of epinephrine which produced four or more intermittent or continuous premature ventricular contractions within a 15-sec period. Total dose was calculated as a function of infusion rate and time to arrhythmia. Following xylazine administration, ADE significantly decreased from 6.28 +/- 0.522 to 4.17 +/- 0.679 micrograms/kg. At the end of i.v. xylazine bolus administration, heart rate significantly decreased (115 +/- 4 to 99 +/- 4.9 b.p.m.), and mean arterial pressure significantly increased (83 +/- 4.0 to 122 +/- 3.4 mm Hg). Heart rate measured immediately prior to epinephrine-induced arrhythmia formation was significantly increased following xylazine administration (177 +/- 8 vs 78 +/- 3 b.p.m.). Mean arterial blood pressure was unchanged. Apparently, xylazine, a mixed alpha agonist, potentiated halothane-induced myocardial sensitization to ventricular arrhythmogenesis and was associated with a significant increase in heart rate, but not blood pressure, during subsequent epinephrine infusions.
Procainamide hydrochloride was administered to ouabain-intoxicated dogs to determine an antiarrhythmic plasma concentration of procainamide. Ventricular arrhythmias were produced in dogs following intravenous injections of ouabain. After a sustained ventricular tachycardia was achieved, procainamide was administered and plasma samples collected for assay. Plasma procainamide was assayed by fluorescence polarization immunoassay. Procainamide was administered at increasingly higher constant rate infusions in order to achieve intermittent, steady-state plasma concentrations. Infusion rates were calculated on the basis of previous pharmacokinetic information. All six dogs that received procainamide converted to a normal sinus cardiac rhythm after attaining a mean plasma concentration of 33.8 micrograms/ml with a range of 48.5 micrograms/ml-25.0 micrograms/ml. It was observed that the computer-generated prediction of plasma concentrations based upon previous pharmacokinetic data produced an underestimate of the actual plasma concentrations. These data may suggest that plasma concentrations of procainamide for controlling some cardiac arrhythmias in dogs may be higher than plasma concentrations cited for human patients.