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Biomedical subjects

D J Hoffman

Publications and source records attributed to D J Hoffman.

At least 109 records · Page 6Linked to original sources
PubMed1979

Rapid, sensitive GLC determination of pentobarbital and other barbiturates in serum using nitrogen-specific detector.

A GLC method for the analysis of pentobarbital in serum was developed. After extraction from serum, a methyl derivative was prepared and quantitated by nitrogen-specific detection. The method has a senstivity of 0.08 microgram/ml for pentobarbital with only 0.1 ml of serum. Secobarbital was the internal standard. Derivatives of other barbiturates also were prepared.

Barbiturates↗
PubMed1979

Sensitive GLC assay for pemoline in biological fluids using nitrogen-specific detection.

Extractive alkylation was used to determine intact pemoline in serum and urine. Pemoline was extracted into methylene chloride as an ion-pair with tetrapentylammonium hydroxide under alkaline conditions. Evaporation of the solvent at 70 degrees in the presence of methyl iodide yielded the N,N-dimethylpemoline derivative. GLC analysis was performed on a 5% FFAP column with nitrogen-specific detection. Sensitivity was 0.05 microgram/ml with 1 ml of urine of serum. Calibration curves were linear to at least 4 microgram/ml with serum and 15 microgram/ml with urine. Precision was excellent with a pooled relative standard deviation of +/- 7.5% for serum samples in a 0.1-4 microgram/ml range.

Chromatography, Gas↗
PubMed1979

Teratogenic effects of external egg applications of methyl mercury in the mallard, Anas platyrhynchos.

The embryotoxic potential of external applications of methyl mercury on mallard eggs was investigated to assess the possible impact of mercury transferred from the plumage of effluent-contaminated aquatic birds to their eggs. Eggs were treated on day 3 of development with microliter applications of methyl mercury that was dissolved with ethyl acetate into an aliphatic hydrocarbon vehicle. Mercury analysis by atomic absorption indicated that almost half of the mercury applied entered the eggs past the shell membranes within several days of treatment. Most mortality occurred within this period at doses of 9 microgram of mercury per egg or higher. Decreased embryonic growth resulted with similar doses. A significant incidence of malformations occurred at a dose of 1 microgram per egg. These malformations were mainly minor skeletal aberrations and incomplete ossification. With higher doses of mercury, defects included gross external ones such as micromella, gastroschisis, and eye and brain defects. Application of the aliphatic hydrocarbon vehicle did not result in any of these defects.

Abnormalities, Drug-Induced↗
PubMed1979

Embryotoxic and teratogenic effects of petroleum hydrocarbons in mallards (Anas platyrhynchos).

Egg surface applications of microliter quantities of crude and refined oils of high aromatic content are embryotoxic to mallards (Anas platyrhynchos) and other avian species; applications of aliphatic hydrocarbons have virtually no effect. Mallard eggs at 72 h of development were exposed to a mixture of aromatic hydrocarbons or to aromatic compounds representative to those present in crude oil to assess their toxicity. The class composition of the mixture was similar to that of South Louisiana crude oil, an American Petroleum Institute reference oil. Application of 20 microliter of the mixture reduced embryonic survival by nearly 70%. The temporal pattern of embryonic death was similar to that after exposure to South Louisiana crude oil. Embryonic growth was stunted, as reflected by weight, crown-rump length, and bill length, and there was a significant increase in the incidence of abnormal survivors. When individual classes of aromatic hydrocarbons were tested, tetracyclics caused some embryonic death at the concentrations in the mixture. When classes were tested in all possible combinations of two, no combination appeared to be as toxic as the entire mixture. Addition of the tetracyclic compound chrysene to the aromatic mixture considerably enhanced embryotoxicity, but could not completely account for the toxicity of the crude oil. The presence of additional unidentified polycyclic aromatic hydrocarbons as well as methylated derivatives of polycyclic aromatic compounds such as chrysene may further account for the embryotoxicity of the crude oil.

Animals↗
PubMed1977

Metal mutagens and carcinogens affect RNA synthesis rates in a distinct manner.

Five metal salts (lead, cadmium, cobalt, copper, and manganese),which are mutagenic or carcinogenic, decreasing the fidelity of DNA synthesis in vitro, stimulated chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis. In contrast, other metal salts (zinc, magnesium, lithium, sodium,and potassium) not in this category inhibited chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis.

Carcinogens↗
PubMed1977

Effect of antacids on absorption of clorazepate.

The effect of a magnesia and alumina antacid suspension on the absorption of clorazepate dipotassium was studied in 15 normal healthy adult subjects who ingested a 15-mg dose of clorazepate alone or with single or multiple doses of antacid. The results of this three-period randomized complete crossover study showed a trend of initially slower absorption and lower peak nordiazepam plasma levels when administered with the antacid suspension. However, there were no significant differences among treatments in the extent of absorption as measured by the area under the plasma level-time curves. Clorazepate plasma levels were of relatively short duration and similar for all treatments. The urinary excretion pattern was likewise comparable with conjugated oxazepam, the major species measured. Plasma elimination half-lives of nordiazepam and clorazepate were not affected by the antacid treatments.

Adult↗
PubMed1977

Steady-state bioavailability of two clorazepate dipotassium dosage forms.

A specially designed tablet dosage form of the benzodiazepine clorazepate dipotassium (Tranxene) was developed for once-a-day administration. The drug was administered at a dose of 22.5 mg as (1) the tablet, (2) three 7.5 mg capsules, or (3) one 7.5-mg capsule given every 6 hours. Peak serum levels from the tablet were intermediate between those of the single- and divided-dose capsule regimens. The desired decrease in magnitude of peak levels was obtained without affecting the extent of absorption. Pharmacokinetic analysis of the data according to a two-compartment open model with first-order absorption indicated that the serum half-life (t0.5beta) of nordiazepam, the major biotransformation product present in serum, was about 48 hours and served as a basis for the design of a multiple-dose steady-state study. Multiple-dose administration of the tablet and divided-capsule regimen to two groups of subjects for ten days indicated each dosage form yielded similar minimum steady-state serum levels of about 0.6 micrograms/ml which plateaued following seven days of drug administration. The dosage forms were crossed over between the groups on day 11 and administered for an additional four days. The minimum serum levels obtained with the tablet and capsule were not statistically different. Additionally, the peak serum level and area under the curve (pi=24 hours) at steady state were equivalent between the dosage forms. Good agreement was obtained between model-predicted and observed serum levels during multiple-dose administration for both the tablet and capsule regimens. The serum half-life of nordiazepam following 14 days of clorazepate dipotassium administration was similar to that found after a single dose. These results indicate that a single daily dose of drug as the tablet produced serum levels equivalent to a divided-capsule regimen.

Adult↗
PubMed1977

Rapid GLD determination of ibuprofen in serum.

A rapid procedure for the determination of ibuprofen in human serum was developed using a single extraction with carbon tetrachloride after deproteinization with perchloric acid. The internal standard, 3-methyl-3-phenylbutyric acid, was added directly to the serum. Gas chromatograms were free of interfering peaks. Calibration curves (0--40 micron g/ml) were linear with a sensitivity of 0.5 micron of ibuprofen/ml of serum. Relative standard deviations ranged from 1.1 to 25%.

Chromatography, Gas↗
PubMed1977

Embryotoxicity of irradiated and nonirradiated catalytic convertertreated automotive exhaust.

This study was undertaken to examine the relative embryotoxicity in chick embryos of photochemically reacted and unreacted diluted automotive exhaust emissions from a system equipped with a catalytic converter. Clean air controls and H2SO4 aerosol controls equivalent in concentration to those found in the catalytic exhaust atmosphere were also studied. From day 1 through day 14 of development, continuous exposure to nonirradiated exhause resulted in decreased survival, lowered embryonic weight, a small increase in heart/body weight ratio, and altered hematocrit and serum enzyme activities (LDH and GOT). Irradiated exhaust had little effect on survival or on embryonic weight but resulted in a higher liver/body weight ratio as well as altered hematocrit and serum enzyme activities. Interactions or cumulative effects of different compositions of exhaust atmospheres may play a role in differing biological responses between unreacted and irradiated exhaust. Sulfuric acid aerosol had a minimal effect on survival and resulted in only a slight decrease in embryonic weight and serum LDH activity, with no other apparent effects. In previous studies where the catalytic converter was not used, more pronounced effects on survival, increased heart/body weigh ratio, elevated serum GPT activity, and liver discoloration were observed. Thus, the introduction of an oxidizing catalytic converter appeared to alleviate some but not all of the embryotoxic effects of automotive exhaust.

Aerosols↗
PubMed1975

GLC determination of plasma drug levels after oral administration of clorazepate potassium salts.

Plasma nordiazepam levels resulting from the oral administration of clorazepate potassium salts were determined by a sensitive GLC assay. Nordiazepam and the internal standard (diazepam) were selectively extracted into ether at pH 9.2, hydrolyzed to their respective benzophenones, and quantified by electron-capture detection. The assay was used in a comparative bioavailability study of single equimolar oral doses of monopotassium and dipotassium salts of clorazepate in dogs. Both clorazepate salts were rapidly absorbed and exhibited mean peak total drug levels after 1 hr. Clorazepate levels accounted for about 50% of the total drug levels present. No statistical difference in the plasma drug levels of clorazepate mono- and dipotassium salts and the metabolite was found in dogs.

Administration, Oral↗
PubMed1975

Paramethadione and metabolite serum levels in humans after a single oral paramethadione dose.

A GLC method was developed to determine quantitatively paramethadione and its major metabolite, 5-ethyl-5-methyl-2,4-oxazolidinedione, in serum. The method was reproducible and sensitive to 0.2 mug/ml. After administering a single 300-mg oral dose to human subjects, the average paramethadione serum levels of 6.0 mug/ml occurred at 1 hr and decreased to 0.3 mug/ml after 48 hr. Metabolite serum levels gradually increased to 8.4 mug/ml at 32 hr and were still at this level at 48 hr, which was the last sampling point.

Administration, Oral↗
PubMed1975

Physiological effects of hypoxia and trypan blue in 17-day chick embryos.

Seventeen-day chick embryos were divided into 5 groups and treated as follows: (1) untreated, (2) yolk-sac injected with 0.1 ml of saturated trypan blue solution solution in sterile saline, (3) saline, (4) hypoxia, i.e., 10.5% oxygen, and (5) hypoxia plus trypan blue. After 5 h hypoxia-treated embryos had an increased mortality rate, severe hypoglycemia, reduced blood pH, elevated plasma potassium, and reduced CO2 content. Trypan blue treatment induced few deaths and few physiological imbalances. Hypoxia plus trypan blue was without synergistic effects and had effects that did not differ significantly from hypoxia alone. This lack of response of 17-day chick embryos to high doses of trypan blue may be related to a marked decline in oxygen consumption by the yolk at this age.

Animals↗