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Biomedical subjects

E C Dinovo

Publications and source records attributed to E C Dinovo.

At least 19 recordsLinked to original sources
PubMed1987

Modification of certain pharmacological effects of ethanol by lipophilic alpha-1 adrenergic agonists.

The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism. In prazosin-pretreated mice, St 587 failed to reduce the hypnotic effect of ethanol, which provided strong evidence for the role of alpha-1 agonism for the hypnosis reducing effect of St 587. Hyperactivity induced in C57B1/6 mice by a subhypnotic dose of ethanol and St 587 was reported earlier. In the present study, St 587, cirazoline and (-)SKF 89748A produced similar response, but no correlation between this effect and ethanol hypnosis blockade could be established. Interestingly, this hyperactivity response was not exhibited by Swiss-Webster, BALB/c or DBA-2 mice--strains in which St 587 exerted little or no antagonism to ethanol-induced hypnosis. Of the alpha-1 agonists, only St 587 reduced the ethanol-induced hypothermia in C57B1/6 mice. St 587 also blocked this effect of ethanol in BALB/c mice in which this drug failed to reduce the ethanol-induced hypnosis. It was concluded that ethanol-induced hypothermia and hypnosis are not interrelated. None of the alpha-1 agonists modified the pentobarbitone-induced hypnosis or the rate of elimination of ethanol in C57B1/6 mice. In this strain, the reduction of the duration of ethanol-induced hypnosis by the alpha-1 agonists is a selective and centrally-mediated response.

Adrenergic alpha-Agonists↗
PubMed1984

Partitioning of thioridazine and mesoridazine in human blood fractions.

The partitioning of 3H-thioridazine and 3H-mesoridazine in fresh human whole blood was studied. The packed red blood cells were solubilized using the New England Nuclear protocol for whole blood solubilization. The plasma fraction was further fractionated into protein bound and free drug by molecular ultrafiltration. All solutions were counted in Biofluor LSC cocktail and corrected for quenching. Greater than 99% of the labeled drug was bound to the red blood cells and plasma protein. For thioridazine, 59% is bound to RBC, 41% is bound to plasma protein and 0.7% is free; for mesoridazine, 63% is bound to RBC, 37% is bound to plasma protein and 0.9% is free. Though substantial overlap is found in the bound percentage for mesoridazine and thioridazine, more mesoridazine binds to RBC than thioridazine (p less than 0.01). There is no statistically significant relationship between the amount of drug bound to the RBC or to plasma protein and the percent free drug. Though the total drug concentration is the same (1 microgram/ml) the percent free drug is quite variable across subjects by as much as a factor of three. Since free drug is the pharmacologically active portion and therefore determinant of clinical response, the reported variation in free drug concentration at the same total blood concentration invalidates the measurements of total serum or plasma drug concentration as predictive of clinical response.

Blood Proteins↗
PubMed1979

A review of psychoactive drug-involved deaths in nine major United States cities.

Detailed psychosocial and biomedical data were collected in 2,000 psychoactive drug-involved deaths occurring from 1972 through 1974 in nine large cities in the United States. The cases were selected representatively by the medical examiners or coroners in each city. Also, proficiency studies were carried out of the toxicological laboratories associated with these nine cooperating data collection centers. There were striking intercity psychosocial and biomedical differences in these psychoactive drug-involved deaths. These differences were based not simply in demographic regional population differences but also on the kinds of psychoactive drugs used as well as the role of the drug in contributing to death and whether the death was a result of an accident, suicide, homicide, or unknown intent. Also, a lack of uniformity was demonstrated in the quality control of the toxicological laboratories associated with the offices of these nine medical examiners or coroners, which suggests varying degrees of accuracy in resulting medicolegal diagnoses. Hence national programs of drug abuse deterrence or prevention and treatment should deal specifically with the variety of psychoactive drug-involved deaths occurring in different urban areas rather than approaching these problems globally as if they were uniform and homogeneous, and our toxicological proficiency studies accentuate the importance of mandatory quality control studies for all toxicological laboratories in the United States.

Adolescent↗
PubMed1978

Distribution of thioridazine and its metabolites in human tissues and fluids obtained postmortem.

Thioridazine and metabolites were measured in brain, liver, and kidney specimens, obtained postmortem from two subjects whose deaths were related to acute intoxication with thioridazine, by gas-liquid chromatography. Although the absolute concentration measured for thioridazine and metabolites differed in the two cases, the metabolic pattern for each tissue, expressed in terms of the percentage of total drug in each tissue, was quite similar. The brain, liver, and kidney metabolic patterns, however, are in sharp contrast to the plasma metabolite patterns observed for subjects on a therapeutic regimen of thioridazine. As this example demonstrates, postmortem specimens are a valuable (but seldom used) source of human pharmacological data.

Adolescent↗
PubMed1976

GLC analysis of thioridazine, mesoridazine, and their metabolites.

A GLC method for measuring thioridazine, mesoridazine, their metabolites, and possibly other phenothiazines was developed. By using this method, seven different phenothiazine derivatives, thioridazine, and six known thioridazine metabolites were extracted and separated. This method was tested by assaying plasma samples from 30 hospitalized psychiatric patients receiving thioridazine or mesoridazine.

Chromatography, Gas↗
PubMed1976

A comparison of suicide and non-suicide deaths involving psychotropic drugs in four major U.S. cities.

By use of a standard reporting form, extensive data were gathered on 651 deaths involving psychotropic drugs and recorded with the Coroner's or Medical Examiner's Office in each of four major U.S. cities. Thirty-six per cent of these deaths were listed as "Definitely Suicide" and 44% were listed as "Non-Suicide." A comparison was made of the age, sex, race, occupational category, and type of drug involved for each of these two groups, by city. In general, the Suicide group tended to be older, from higher occupational levels, and more often female. Blacks were under-represented among the Suicides but over-represented among the Non-Suicides. Suicide deaths tended to be associated with barbiturates, analgesics, and/or sedatives, while the Non-Suicides usually died from an accidental abuse of narcotics, usually heroin. These findings tended to be similar for each city, although some inter-city differences were noted.

Adult↗
PubMed1976

Results of a nine-laboratory survey of forensic toxicology proficiency.

Toxicological determinations are crucial to coroners' or medical examiners' judgments that drugs are significantly involved in a death. However, differences in laboratory procedures, thoroughness of screening, and limits of detection may result in artifactual differences in the toxicological results and the subsequent interpretations of them. To test this possibility, we conducted a toxicology proficiency-testing survey of nine collaborating laboratories. The results for the proficiency samples point out starting interlaboratory differences in accuracy and precision of detection of drugs. These observed variations in toxicological proficiency may introduce a significant source of error in drug-death statistics and in epidemiological deductions based on these statistics.

Ethanol↗
PubMed1976

Analysis of results of toxicological examinations performed by coroners' or medical examiners' laboratories in 2000 drug-involved deaths in nine major U. S. cities.

Data were collected on 2000 deaths in which psychoactive drugs were involved. The data were submitted by medical examiners or coroners in nine U. S. cities from their case files. The 2000 cases comprise a representative sample from each of these cities of deaths from psychoactive drugs between 1972 through 1974. This report details inter-city differences in methods and practices of the toxicological examination as well as the type and numbers of drugs reported. Even when the same analytical method was used in various cities, there were differences in extraction solvent and extraction pH. Of the 3909 drugs detected, 2945 were quantitated; the number of drugs quantitatively measured per case studied ranged from a low of 0.82 for New York to a high of 2.20 for Washington, D.C. The number of different drugs quantitatively measured varied from 16 for New York to 30 for San Francisco; however, New York qualitatively assayed for the presence of a total of 25 drugs. The number and type of drugs found per case varied. Methadone, for example, was found in 60% of the cases reported by New York and in 49% of the cases from Washington, D.C., but in only about 10% of cases reported by Philadelphia, Dallas, Miami, and San Francisco, and in less than 1% of Los Angeles and Cleveland cases; it was not reported by Chicago. Phenmetrazine-caused deaths were reported only by Dallas (one case) and Washington, D.C. (29 cases). From the data as a whole, information is presented for 33 drugs as to the concentration in physiological tissues and fluids. Analysis of single psychoactive drug cases and single-drug-plus-ethanol cases shows that, in the presence of ethanol, the toxic blood concentration of imipramine, amytriptyline, meprobamate, thioridazine, morphine, propoxyphene, methaqualone, and all barbiturates was decreased by an average of 50%.

Forensic Medicine↗
PubMed1975

Creatine kinase reactivation by thiol compounds.

It is now commonly accepted that thiol activated creatine kinase (CK) assay systems measure CK activity more accurately and more reproducibly than non-activated systems. However, some differences have arisen in the literature in regards to the nature and course of CK activation. Some thiol compounds have been reported to yield higher enzyme activities than others. Dalal et al. (1) reported that mercaptoethanol at 6.5 mM is suboptimal in the Siegel and Cohen assay (2); whereas, dithiothreitol (DTT) at 4 mM yields maximum activity. Warren has shown that DTT and mercaptoethanol produce significantly greater CK activities than cysteine, dithioerythritol (DTE), glutathione, or mercaptoacetate (3). Bishop et al. (4) and Kar and Pearson (5) reported that CK was equally activated independent of the thiol activator. We report here our findings on the relative effectiveness of mercaptoethanol, cysteine, glutathione, and DTT in the reactivation of serum CK using the Oliver-Rosalki method (6,7) and some characteristics of the reaction process.

Creatine Kinase↗