Distribution of codeine, morphine, and 6-acetylmorphine in vitreous humor.

Two hundred and twenty-three vitreous humor specimens, which were obtained from a medical examiner's office, were found to be opiate positive (cutoff, 50 ng/mL) by fluorescence polarization immunoassay. All samples were analyzed for their free codeine, morphine, and 6-acetylmorphine contents by a gas chromatography-mass spectrometry protocol. 6-Acetylmorphine was found (cutoff, 10 ng/mL) in 41 specimens in the concentration range of 10-125 ng/mL. Twenty specimens had a free codeine-free morphine concentration ratio > or = 1. Eighty-five samples that were found to contain 50 ng/mL free morphine were further analyzed for their total codeine and total morphine contents. Total codeine-total morphine concentration ratios in 8 (of the 85 samples) were > or = 1, whereas this ratio in the others (only those with a codeine concentration high than 15 ng/mL were included) was significantly lower than 1. The codeine-morphine concentration ratio in vitreous humor appears to resemble that reported for blood and urine and can be used as the basis for differentiating between codeine- and morphine- (heroin-) induced fatalities.

The Interaction of Ethanol with Drugs.

Ethanol is perhaps the most widely used drug in society today. Its reactions in the human body are varied and complex but mainly it depresses the central nervous system, which in turn causes a deleterious effect on psychomotor functions. When any of several classes of drugs is introduced into the body along with ethanol, each drug can affect the other's absorption, distribution, metabolism, and excretion. The toxic effects of the drug combination may be potentiated, depending upon several factors such as whether the ingested level of ethanol was acute or chronic, and the pharmacodynamics of the second drug.

Deaths as a result of a combination of codeine and glutethimide.

Toxicological findings are described in 16 medical examiner cases directly related to the combination of codeine and glutethimide. The cases described represent a six-month period, July through December 1982, showing the epidemic rate of abuse of this drug combination, most prominent in the Newark, NJ area since the late 1970s. Concentrations of codeine and glutethimide, measured by gas liquid chromatography (GLC), in the blood averaged 0.62 and 4.07 mg/L, respectively. Similarly determined urine concentrations averaged 38.06 and 12.68 mg/L, respectively. Specific concentrations of each drug in most cases were in the high therapeutic range, suggesting a possible toxic synergistic effect.

Fibroblast DNA synthesis activation in sponge induced granulation tissue. The effect of antineutrophil serum and cyclophosphamide.

DNA synthesis in rat and rabbit polyvinyl sponge induced granulation tissue has been studied using thymidine (methyl-3H). Synthesis was determined by measurement of thymidine incorporation into cold trichloroacetic acid insoluble material and by autoradiography. Granulation tissue was removed and immediately incubated in vitro in the presence of thymidine (methyl-3H) for three hours. The label was incorporated into the nuclei of fibroblasts and, to a lesser extent, of endothelial cells. The labeled material was 93% lysable by DNase and its synthesis was inhibited by hydroxyurea and bleomycin. In this system synthesis was linear for two hours and then ceased. A marked increase in DNA synthesis occurred in tissue harvested at 44 hours after sponge implantation. This rise was confirmed by autoradiographic studies which showed an increase in nuclear labeling at two days after implantation. Neutropenia produced by injections of antineutrophil serum or cyclophosphamide failed to inhibit activation of DNA synthesis in fibroblasts or endothelial cells. Amonocytosis also had no effect on this process. Rates of thymidine incorporation into DNA and thymidine phosphates in vivo were similar to those found during in vitro incubations of granulation tissue.

Specific oligoribonucleotide synthesis using primer-independent polynucleotide phosphorylase.

Oligoribonucleotides of a predetermined base sequence beginning with adenylyl-3', 5'-adenosine at the 5' end have been synthesized in yields varying between 13% and 42%. The synthesis was carried out using primer-independent polynucleotide phosphorylase from E. coli in the presence of high concentrations of primer and of sodium chloride.