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Biomedical subjects

A J Cooper

Publications and source records attributed to A J Cooper.

At least 181 records · Page 10Linked to original sources
PubMed1987

Medroxyprogesterone acetate (MPA) treatment of sexual acting out in men suffering from dementia.

Four demented male patients who manifested disruptive sexual behavior, including public masturbation and attempts to molest female patients, and who could not be managed by other means received a therapeutic trial of medroxyprogesterone acetate (MPA) for 1 year and were followed up for an additional year. Their sexual activities were recorded before, during, and after the study, and serum testosterone, luteinizing hormone (LH), and prolactin were monitored regularly. Within 2 weeks of the start of MPA therapy, the sexual acting out had stopped; this was associated with a 90% and a 60% decline, respectively, of serum testosterone and LH. When MPA treatment was stopped, testosterone and LH returned to pretrial levels in all four men. One showed a return of sexual acting out, but this was at a reduced level and was successfully managed by firm nursing. MPA was used without adverse effects. Because of its safety and efficacy, the drug should be considered as a first-line treatment for sexual acting out in demented men.

Acting Out↗
PubMed1987

[13N]cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors.

The biodistribution, blood clearance, and in vivo transformation of cisplatin (cisdiaminedichloroplatinum, DDP) were studied in rats using 13N-labeled and unlabeled DDP. Following the i.v. injection of [13N]DDP, virtually no 13N activity was detected in brain tissue, and no measurable amount of the 13N label was displaced from [13N]DDP. Based on these results, [13N]DDP/positron emission tomographic (PET) scans were performed in two glioblastoma patients undergoing Phase II intra-arterial (i.a.) DDP chemotherapy: [13N]DDP was infused i.v. over 13-15 min, during which time serial PET scans were obtained. One hour later, [13N]DDP mixed with cold DDP (100 mg/m2 therapeutic dose) was infused at the same rate i.a., and a second sequence of PET scans was acquired. The pharmacologic advantage of i.a. administration was calculated as the ratio of integrated tumor/brain count ratios for the i.a. and i.v. studies. Our preliminary results demonstrate the feasibility of quantifying the pharmacologic advantage of i.a. DDP chemotherapy in individual brain tumor patients using [13N]DDP and PET.

Animals↗
PubMed1987

Treatment of coexistent night-terrors and somnambulism in adults with imipramine and diazepam.

Night-terrors and somnambulism are comparatively rare in adults and are most often associated with stage 4 sleep, especially delta activity. Although the data are limited, reports suggest that imipramine, which may control nocturnal enuresis, a stage 4 sleep disorder, and diazepam, which suppresses stage 4 sleep, may effectively treat the condition. This paper describes two patients with night-terrors and somnambulism who responded to imipramine but not to diazepam. Possible mechanisms of diazepam and imipramine, including effects on stage 4 sleep and pervasive anxiolytic actions, are discussed.

Adult↗
PubMed1986

High-performance liquid chromatographic on-line flow-through radioactivity detector system for analyzing amino acids and metabolites labeled with nitrogen-13.

A flow-through radioactivity detector was used for the high-performance liquid chromatographic determination of amino acids and other nitrogenous substances labeled with 13N, a short-lived (t1/2 9.96 min) positron-emitting radionuclide. 13N-Labeled compounds were analyzed using cation, anion and amino columns, or as the o-phthaldialdehyde derivative on an ODS column. Use of column-switching valves and a high-performance liquid chromatographic system with a quaternary eluting capability permits two to three 20-min analyses of labeled samples from a single 13N experiment to be carried out on different columns using a binary or a single mobile phase. Radioactivity in liver metabolites was quantified using an on-line flow-through monitor with data processing capability for integrating peaks and correcting for radioactivity decay. As an example, 1 min following an L-[13N]glutamate injection via the hepatic portal vein, 77% of the label in the liver was in a metabolized form; at least ten labeled products were formed.

Amino Acids↗
PubMed1986

Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors.

The substrate and cofactor requirements and some kinetic properties of the alpha-ketoglutarate dehydrogenase complex (KGDHC; EC 1.2.4.2, EC 2.3.1.61, and EC 1.6.4.3) in purified rat brain mitochondria were studied. Brain mitochondrial KGDHC showed absolute requirement for alpha-ketoglutarate, CoA and NAD, and only partial requirement for added thiamine pyrophosphate, but no requirement for Mg2+ under the assay conditions employed in this study. The pH optimum was between 7.2 and 7.4, but, at pH values below 7.0 or above 7.8, KGDHC activity decreased markedly. KGDHC activity in various brain regions followed the rank order: cerebral cortex greater than cerebellum greater than or equal to midbrain greater than striatum = hippocampus greater than hypothalamus greater than pons and medulla greater than olfactory bulb. Significant inhibition of brain mitochondrial KGDHC was noted at pathological concentrations of ammonia (0.2-2 mM). However, the purified bovine heart KGDHC and KGDHC activity in isolated rat heart mitochondria were much less sensitive to inhibition. At 5 mM both beta-methylene-D,L-aspartate and D,L-vinylglycine (inhibitors of cerebral glucose oxidation) inhibited the purified heart but not the brain mitochondrial enzyme complex. At approximately 10 microM, calcium slightly stimulated (by 10-15%) the brain mitochondrial KGDHC. At concentrations above 100 microM, calcium (IC50 = 1 mM) inhibited both brain mitochondrial and purified heart KGDHC. The present results suggest that some of the kinetic properties of the rat brain mitochondrial KGDHC differ from those of the purified bovine heart and rat heart mitochondrial enzyme complexes. They also suggest that the inhibition of KGDHC by ammonia and the consequent effect on the citric acid cycle fluxes may be of pathophysiological and/or pathogenetic importance in hyperammonemia and in diseases (e.g., hepatic encephalopathy, inborn errors of urea metabolism, Reye's syndrome) where hyperammonemia is a consistent feature. Brain accumulation of calcium occurs in a number of pathological conditions. Therefore, it is possible that such a calcium accumulation may have a deleterious effect on KGDHC activity.

Ammonia↗
PubMed1986

Progestogens in the treatment of male sex offenders: a review.

The literature on the progestogens, medroxyprogesterone acetate (MPA) and cyproterone acetate (CPA), which are currently used in the treatment of deviant male hypersexuality, is reviewed. There are few adequately controlled trials, but clinical observations suggest that the drugs are reasonably effective in suppressing libido and sexual arousal in men. They are approximately equipotent and equivalent in this respect, but differ somewhat in their pharmacology. When used in conjunction with other measures, especially psychotherapy, they may benefit some sex offenders. The best results are likely in self-referred, nonrecidivist hypersexuals, with good social supports and who are motivated for treatment. The need for long-term placebo and comparison trials is stressed.

Canada↗
PubMed1986

Absorption study of pentachlorophenol in persons working with wood preservatives.

Plasma and urinary pentachlorophenol (PCP) was measured in 209 workers who had occupational exposure to wood preservatives containing this compound and 101 workers not exposed occupationally to PCP. Workers were examined for chloracne and blood concentrations of bilirubin, gamma-glutamyltransferase (GGT), cholesterol and high-density lipoproteins (HDL) were determined. All the occupationally exposed groups showed evidence of PCP absorption; highest mean concentrations were found in remedial timber-treatment operatives (6.0 mmol/l for plasma and 274 nmol/mmol of creatinine for urine). Timber-yard workers also showed substantial evidence of absorption (mean plasma concentration 4.8 mmol/l). Persons formulating PCP-containing wood preservatives had the lowest concentrations of any exposed group sampled (mean plasma concentration 1.3 mmol/l, mean urinary concentration 39.6 nmol/mmol of creatinine). The occupational groups studied were not standardized for factors known to affect bilirubin, GGT, cholesterol and HDL. The inference that can be drawn from the results of these measurements is therefore limited. There was, however, no evidence of any disadvantageous effect of PCP on health as measured by these parameters. No overt case of chloracne was found.

Acne Vulgaris↗
PubMed1986

Advances in the assessment of organic causes of impotence.

There are few adequate studies on the causes of impotence. Nevertheless many clinicians continue to assert that up to 90% of cases are of psychosocial origin. It is slowly becoming apparent that psychosocial causes are just one of many diverse possibilities.

Adult↗
PubMed1985

[13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors.

The short-term metabolic fate of labeled nitrogen derived from [13N]ammonia or from L-[amide-13N]glutamine was determined in murine tumors known to be resistant (Ridgeway Osteogenic Sarcoma (ROS] or sensitive (Sarcoma-180 (S-180)) to glutaminase therapy. At 5 min after intraperitoneal injection of [13N]ammonia or of L-[amide-13N]glutamine, only about 0.7% of the label recovered in both tumors was in protein and nucleic acid. After [13N]ammonia administration, most of the label (over 80%) was in a metabolized form; a large portion of this metabolized label (50-57%) was in the urea fraction with a smaller amount in glutamine (37-42%). The major short-term fate of label derived from L-[amide-13N]glutamine was incorporation into components of the urea cycle with smaller amounts in the acidic metabolites and in acidic amino acids. No labeled urea was found during in vitro studies in which S-180 tumor slices were incubated with [13N]ammonia, suggesting that the [13N]urea formed in the tumor in the in vivo experiments was not due to de novo synthesis through carbamyl phosphate in the tumor. Both tumors exhibited very low glutamine synthetase activity. Following glutaminase treatment, glutamine synthetase and gamma-glutamyltransferase activities, while remaining low, increased in the resistant tumor but not in the sensitive tumor; this increase may be related to the insensitivity of the ROS tumor toward glutaminase treatment.

Amino Acids↗
PubMed1985

Interaction of soluble pig heart glutamate-aspartate transaminase with various beta,gamma-unsaturated amino acids.

beta-Ethylidene-DL-aspartate (beta EA) and beta-methylene-DL-glutamate (beta MG) were synthesized and tested as potential suicide inhibitors of soluble pig heart glutamate-aspartate transaminase (sGAT). beta MG was found to be a) a substrate with a very low turnover number relative to glutamate and b) a competitive inhibitor with respect to aspartate (albeit with a large binding constant). At high concentrations beta MG inactivated the enzyme but only very slowly. beta EA was also found to be a substrate with a very low turnover number; it did not inactivate the enzyme (1 hr, 25 degrees C) even at a high concentration. However, beta EA was found to bind to the enzyme with an affinity comparable to that of aspartate and glutamate. beta-Methylene-DL-aspartate (beta MA) has been shown to rapidly inactivate glutamate-aspartate transaminase. Therefore, it appears that glutamate-aspartate transaminase can bind analogues of aspartate with alkene groups in the beta position. The conjugated carbonyl groups of beta MA and beta EA will enhance Michael addition in comparison with that expected for vinylglycine. On the other hand, the presence of the methyl groups should reduce the electrophilicity of the double bond of beta EA compared to beta MA. This deactivation and/or steric hindrance to Michael attack may account for the inability of beta EA to inactivate sGAT. Therefore, it may be possible to design selective suicide inhibitors of glutamate-aspartate++ transaminase with the following structure: HO2CC(= CHX)CH(CO2H)NH2, where X is an electron-withdrawing group. Ideally, X would increase the reactivity of the double bond while affording a minimum of steric hindrance to susceptible enzyme-bound bases.

Amino Acids↗
PubMed1985

Enzymatic oxidation of L-homocysteine.

Homocyst(e)ine, a normal metabolite, accumulates in certain inborn errors of sulfur amino acid metabolism. Since many amino acids are converted by enzymatic oxidation and by transamination to the corresponding alpha-keto acid analogs and related products, which may exert inhibitory effects on metabolism, and because the alpha-keto acid analog of homocysteine has not yet been prepared, the enzymatic oxidation of homocysteine was investigated with the aim of obtaining alpha-keto-gamma-mercaptobutyric acid. Oxidation of DL-homocysteine by L-amino acid oxidase led to formation of at least seven products that react with 2,4-dinitrophenylhydrazine; of these, five were identified: alpha-keto-gamma-mercaptobutyrate, the mono and diketo analogs of homolanthionine, and the mono and diketo analogs of homocystine. In addition, one product was tentatively identified as alpha-ketomercaptobutyric acid gamma-thiolactone. In the course of this work alpha-keto-gamma-mercaptobutyrate was found to be a substrate of lactate dehydrogenase. L-Homocysteine and its alpha-keto acid analog were shown to be substrates of glutamate dehydrogenase and kidney glutamine transaminase. DL-Homocysteine reacts readily with alpha-keto acids to form stable hemithioketals, which were found to be substrates of L- and D-amino acid oxidases. A scheme is presented which integrates some of the complexities involved in the oxidation metabolism of homocyst(e)ine. The significance of these findings is considered in relation to the toxicity of homocysteine, which accumulates in certain pathological states.

Amino Acid Oxidoreductases↗