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At least 19 recordsLinked to original sources
PubMed1979

Acetate intolerance and an inhibitor of acetate utilization in hemodialysis patients.

Diminished ability to utilize acetate (acetate intolerance) developed in a male patient on chronic hemodialysis after five years of maintenance dialysis. His ability to utilize lactate was also subnormal. We studied acetate metabolism in vitro by isolating lymphocytes from the patient's blood before dialysis and measuring their ability to convert [1-14C]acetate to 14CO2. His cells metabolized acetate only 35% as well as did lymphocytes from normal adults. The inhibition appeared when the patient's lymphocytes were cultured, and the ability of normal lymphocytes to oxidize acetate decreased after they had been incubated in the patient's plasma. We conclude that an inhibitor of acetate utilization is present in the plasma and in (or on) the cells of this acetate-intolerant patient. The diminished ability of the patient to utilize lactate and the presence of normal concentrations of pyruvate, citrate, and ketone bodies in his blood suggest that the inhibitor functions at the cell surface to impede the entrance of acetate into the cells. The inhibitor appears to be dialyzable; its nature is unknown. Its accumulation in the plasma of chronic hemodialysis patients has not been thus far associated with any deleterious effects other than prolonging the metabolic acidosis of such patients.

Acetates↗
PubMed1977

An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase.

Under anaerobic conditions, cells of Entamoeba histolytica grown with bacteria produce H2 and acetate while cells grown axenically produce neither. Aerobically, acetate is produced and O2 is consumed by amebae from either type of cells. Centrifuged extracts, 2.4 x 106 x g x min, from both types of cells contain pyruvate synthase (EC 1.2.7.1) and an acetate thiokinase which, together, form a system capable of converting pyruvate to acetate. Pyruvate synthase catalyzes the reaction: pyruvate + CoA leads to CO2 + acetyl-CoA + 2E. Electron acceptors which function with this enzyme are FAD, FMN, riboflavin, ferredoxin, and methyl viologen, but not NAD or NADP. The amebal acetate thiokinase catalyzes the reaction acetyl-CoA + ADP + Pi leads to acetate + ATP + CoA. For this apparently new enzyme we suggest the trivial name acetyl-CoA-synthetase (ADP-forming). Extracts from axenic amebae do not contain hydrogenase, but extracts from cells grown with bacteria do. It is postulated that in bacteria-grown amebae electrons generated at the pyruvate synthase step are utilized anaerobically to produce H2 via the hydrogenase and that the acetyl-CoA is converted to acetate in an energy-conserving step catalyzed by amebal acetyl-CoA synthetase. Aerobically, cells grown under either regimen may utilize the energy-conserving pyruvate-to-acetate pathway since O2 then serves as the ultimate electron acceptor.

Acetate-CoA Ligase↗
PubMed1976

[Liver function tests under the influence of sequential treatment using ethinyl estradiol-norethisterone acetate and ethinyl estradiol-chlormadinone acetate].

30 young healthy women were investigated during the first therapy cycle with ethinyl-estradiol-norethisterone acetate and ethinyl-estradiol-chlormadinone acetate as a sequential regime. The following laboratory data were achieved by each of the investigated group of young women: serum aminotransferase (GOT and GPT), serum alkaline phosphatase and alpha-amylase-activity in serum, serum proteins, serum cholesterol, serum bilirubin, serum ZST, serum TTT and the indocyaningreen-clearance of the liver. The serum protein pattern was determined by the paper electrophoretic method. A significant decrease of the aminotransferase GPT was viable during the sequential therapy with ethinyl-estradiol and norethisterone acetate. This viable decrease of the GPT was induced through the application of norethisterone acetate to estrogen. The alkaline phosphatase was significant lightly lower and the beta-globuline lightly elevated at the end of the therapy cycle. The sequential therapy with ethinyl-estradiol and chlormadinone acetate induced only a significant increase of the ZST in serum.

Adolescent↗
PubMed1977

Comparison of the biological activity of the tumor promotor phorbol myristate acetate and a metabolite, phorbolol myristate acetate, in the cell culture.

Phorbolol myristate acetate, a metabolite of the tumor promotor phorbol muristate acetate in mouse skin, has one-fiftieth the potency of the parent molecule for the induction of cell division in stationary cultures of BALB/c-3T3 mouse embryo cells. Similarly, in a mixed cell culture assay devised for detection of tumor-promoting agents, phorbolol myristate acetate exhibited only a small fraction of the activity of unmetabolized phorbol ester. The results indicate that the biological activity of phorbol esters either does not require metabolic conversion or is converted by the cells used in this system and that phorbolol myristate acetate would be a tumor promotor of low potency for mouse skin compared to phorbol myristate acetate.

3T3 Cells↗
PubMed1979

Metabolic and mutagenicity studies on DDT and 15 derivatives. Detection of 1,1-bis(p-chlorophenyl)-2,2-dichloroethane and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethyl acetate (kelthane acetate) as mutagens in Salmonella typhimurium and of 1,1-bis(p-chlorophenyl) ethylene oxide, a likely metabolite, as an alkylating agent.

Using a novel in vitro technique, whereby microsomal enzymes were embedded in an agar layer to prolong their viability, 1,1-bis(p-chlorophenyl) ethylene(DDNU), a mammalian metabolite of 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), was converted by microsomal mono-oxygenases of mouse liver into 1,1-bis(p-chlorophenyl)-1,2-ethanediol (DDNU-diol). The putative epoxide intermediate, 1,1-bis(p-chlorophenyl)ethylene oxide (DDNU-oxide), a new compound, was synthesized; it showed weak alkylating activity with 4-(4-nitrobenzyl)pyridine but was not mutagenic in Salmonella typhimurium strains TA100 and TA98. DDT and 13 of its metabolites or putative synthetic derivatives, including 1,1-bis(p-chlorophenyl)-2,2-dichloroethylene (DDE), 1 1,1-bis(p-chlorophenyl)-2-chloroethylene (DDMU), 1,1-bis(p-chlorophenyl)-2-chloroethane (DDMS)-DDNU, 2,2-bis(p-chlorophenyl)ethanol (DDOH), bis(p-chlorophenyl)acetic acid (DDA) and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethanol (Kethane), caused no mutagenic effects in S. typhimurium strains TA100 or TA98, either in the presence or absence of a mouse-liver microsomal fraction. 1,1-Bis(p-chlorophenyl)-2,2,2-trichloroethyl acetate (Kelthane acetate) was a direct-acting mutagen in strain TA100, whereas 1,1-bis(p-chlorophenyl)-2,2-dichloroethane (DDD) was mutagenic in TA98, only in the presence of a mouse-liver microsomal system. The results are discussed in relation to possible pathways whereby DDT is activated to mutagenic and/or carcinogenic metabolites.

Alkylation↗
PubMed1977

Isolation and identification of 15-beta-hydroxy cyproterone acetate as a new metabolite of cyproterone acetate in dog, monkey and man.

15-beta-hydroxy cyproterone acetate could be identified by thin layer chromatography, mass spectrum, NMR and IR spectrum as a major unconjugated metabolite of cyproterone acetate in plasma and urine of dog, monkey and man. This metabolite has been found to interferein the Mattingly method for the determination of 11-hydroxy-corticosteroids which suggests, that this method is inadequate in controling the adrenal function of subjects treated with cyproterone acetate.

Animals↗
PubMed1979

Selective catalytic reduction of 7-methyl-6-dehydrotestosterone acetate to 7 beta-methyltestosterone acetate by benzyl alcohol.

Using benzyl alcohol as a hydrogen donor in the presence of Pd on charcoal, 7-methyl-6-dehydrotestosterone acetate was selectively reduced to 7 beta-methyltestosterone acetate in 90% yield. The addition of hydrogen atoms to the 6, 7 double bond proceeded from the less hindered alpha-face of the steroid molecule, giving rise to the 7 beta-methyl product. Gas chromatograph analysis indicated small amounts of the 7 alpha-methyl epimer, 7 beta-methyl-5 alpha-dihydrotestosterone acetate and the 5 beta-epimer. The 6,7 double bond was hydrogenated in preference to 4,5 double bond, although both are trisubstituted.

Benzyl Alcohols↗
PubMed1977

Semisynthetic cephalosporins. Synthesis and structure-activity relationships of analogues with 7-acyl groups derived from 2-(cyanomethylthio)acetic acid or 2-[(2,2,2-trifluoroethyl)thio]acetic acid and their sulfoxides and sulfones.

The synthesis and in vitro and in vivo activities of a series of cephalosporins having side chains derived from 2-[(2,2,2-trifluoroethyl)thio]acetic acid or 2-(cyanomethylthio)acetic acid and with acetoxymethyl or 3-heterocyclic thiomethyl substituents at the 3 position are described. In both series, increasing the oxidation state of the side-chain sulfur atom from sulfide to sulfoxide/sulfone decreased the in vitro gram-positive activity, but the effect on gram-negative activity was variable and less pronounced. The protective effectiveness in mice infected with Escherichia coli increased as the oxidation level of the side-chain sulfur was raised from sulfied to sulfoxide/sulfone. Replacement of the 3-acetoxymethyl by a 3-heterocyclic thiomethyl group resulted in overall improvement of activity both in vitro and in vivo for all oxidation states.

Acetates↗
PubMed1977

A comparative study of three low dose progestogens, chlormadinone acetate, megestrol acetate and norethisterone, as oral contraceptives.

Three low dose progestogens, chlormadinone acetate (0-5 mg), megestrol acetate (0-5 mg) in oil, and norethisterone (0-35 mg), taken daily, were employed as oral contraceptives in postnatal women who desired to postpone their next pregnancy for up to a year. In a lower and middle social class population net pregnancy rates (life table) were five to six per 100 woman-years, of which about half were due to failure to take the tablets. Side effects other than menstrual disturbance were few. Norethisterone was the least likely of the three preparations to lead to discontinuation because of disturbance of menstruation. There were three ectopic gestations amongst 35 pregnancies in 4500 women-months of use. Ninety-five patients with varicose veins, 15 with a history of thrombophlebitis and 23 with a history of liver disease took progestogens without relevant untoward effects.

Adult↗
PubMed1979

Morphometric investigations on endocrine glands. V. Changes in the testes of Wistar rats after application of chlormadinone acetate and norethisterone acetate.

In growth inhibiting tests of rat testes the tubular diameter and, somewhat less sensitive, the nuclear volume of the Leydig cell follow the weight changes. Chlormadinone acetate shows antigonadotropic activity only at high doses and a dose-dependent antiandrogenic activity. The dose-weight curve under norethisterone acetate has a minimum at 4.2 mg/rat/14 days; higher doses seem to be accompanied by androgenic efficiency.

Animals↗
PubMed1977

Changes in insulin receptor concentration in rat fat cells following treatment with the gestagens clomegestone acetate and cyproterone acetate.

Specific insulin receptors were measured in isolated fat cells of rats after treatment with clomegestone acetate. Under conditions when peripheral insulin insensitivity was observed, the number of insulin receptors was simultaneously reduced. A similar though smaller decrease in insulin receptor concentration was seen in rats after treatment with cyproterone acetate, a compound which did not cause insulin resistance. It is concluded that the gestagenic compounds tested decrease insulin receptor concentration. Only drastic reduction of the number of binding sites results in significant perturbations of carbohydrate metabolism.

Adipose Tissue↗
PubMed1979

Analysis of some older Scandinavian formulations of 2,4-dichlorophenoxy acetic acid and 2,4,5-trichlorophenoxy acetic acid for contents of chlorinated dibenzo-p-dioxins and dibenzofurans.

Ten samples of older formulations of 2,4,5-trichlorophenoxy acetic acid and 2,4-dichlorophenoxy acetic acid used in Sweden were analyzed for chlorinated dibenzo-p-dioxins and dibenzofurans. The analyses were performed with gas chromatography/mass spectrometry with a high resolution glass capillary column for maximum isomeric separation and sensitivity. The detection limit was 0.01-0.05 ppm. The amounts of contaminants were of the same order of magnitude as that found earlier in European samples with later production dates (late 1960s and 1970s).

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1979

Studies on the derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid. I. Syntheses and pharmacological analysis of acylderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

A number of new acyl and imidoderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid (II) and its methyl ester (VII) were synthesized. Methyl ester VII heated in benzene solution with acid anhydrides was transformed into adequate acyl derivatives (VIII, IX, X, XIII, XVI). Some of them (X, XIII, XVII) by heating with acetic anhydride underwent cyclization and were transformed into the imido derivatives (XI, XIV, XVIII). Compounds XI, XIV and XVI heated with diluted aqueous solution of sodium hydroxide underwent selective hydrolysis giving the respective dicarboxylic acids XII, XV, XVII. Pharmacological analysis revealed that some of the synthesized preparations exert an anti-inflammatory effect and allow to draw limited relations between chemical structure and pharmacological activity in this group of compounds.

Analgesia↗
PubMed1976

[Concentration of estrone, estradiol and estriol in the blood of pregnant sheep after induction of estrus with chlormadinone acetate and medroxyprogesterone acetate].

The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.

Animals↗
PubMed1979

Studies on the derivatives of thiazole acetic acid. II. Syntheses and pharmacological analysis of 2-N-aralkylidene and 2-N-aralkyl derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

A number of 2-N-aralkylidene, 2-N-aralkyl and 2-N-aralkyl-alpha-sulphoderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid (I, R = H) and its methyl ester (I, R = CH3) were synthesized. As a result of condensation of methyl ester I with various aromatic aldehydes in boiling benzene solution, the Schiff-bases (anils) II--VIII were obtained. After reduction with NaBH4 compounds II--VIII were transformed into adequate amino esters IX--XV. Esters IX--XV heated with diluted aqueous solution of sodium hydroxide underwent selective hydrolysis giving the respective amino acids XVI--XXII. Some of Schiff bases (II, III, V, VII, VIII) reacted with aqueous alcoholic solution of sodium bisulphite after its several (XXIII--XXVII). alpha-sulphoderivatives had been obtained. Several tests were performed in order to detect the anti-inflammatory and immunosuppressive activity of the compounds. The pharmacological analysis allowed us to draw conclusions concerning the relationship between chemical structure and biological activity in this group of compounds. The most efficacious immunosuppressive and anti-inflammatory activity exhibited 2-aralkyl-alpha-sulphoderivatives.

Adjuvants, Immunologic↗