Evaluation of isometric strength and fatty infiltration of the subscapularis in latarjet surgery.

Objective: To evaluate the function of the subscapularis muscle by means of isometric strength, clinical examination and analysis of fatty infiltration in patients with recurrent anterior dislocation of the shoulder undergoing Latarjet-Patte surgery.

Methods: 38 patients operated from March 2011 to March 2012, with minimum follow-up of two years were evaluated, being 26 males and 12 females, with a mean age of 28.7 years old.

Dietary clofibrate stimulates the formation and size of estradiol-induced breast tumors in female August-Copenhagen Irish (ACI) rats.

Administration of 0.4% clofibrate in the diet stimulated estradiol (E(2))-induced mammary carcinogenesis in the August-Copenhagen Irish (ACI) rat without having an effect on serum levels of E(2). This treatment stimulated by several-fold the NAD(P)H-dependent oxidative metabolism of E(2) and oleyl-CoA-dependent esterification of E(2) to 17beta-oleyl-estradiol by liver microsomes.

Strain-specific nicotinic modulation of glutamatergic transmission in the CA1 field of the rat hippocampus: August Copenhagen Irish versus Sprague-Dawley.

Prepulse inhibition (PPI), a measure of sensorimotor gating impaired in patients with schizophrenia, is more sensitive to disruption by apomorphine in prepubertal August Copenhagen Irish (ACI) than Sprague-Dawley (SD) rats. In brain regions including the hippocampus, PPI is modulated by alpha7* nicotinic receptors (nAChRs) and kynurenic acid (KYNA), a kynurenine metabolite that blocks alpha7 nAChRs. Here, KYNA levels and nAChR activities were measured in the hippocampi of 10- to 23-day-old ACI and SD rats of both sexes.

Phase II antioxidant enzyme activities in brain of male and female ACI rats treated chronically with estradiol.

Activities of Phase II antioxidant enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UGT), and phenol sulfotransferase 1A1 (SULT1A1) were measured in brain of August-Copenhagen Irish (ACI) rats exposed chronically to low doses of estradiol (E(2)). ACI rats were selected for study because this strain is highly responsive to treatment with low doses of E(2) as indexed by a high incidence of E(2)-induced mammary tumors compared to other strains. Rats were exposed chronically to 3 mg E(2) contained in cholesterol pellets implanted subcutaneously for 6 weeks.

Phenobarbital treatment inhibits the formation of estradiol-dependent mammary tumors in the August-Copenhagen Irish rat.

Exposure of female August-Copenhagen Irish (ACI) rats for 28 weeks to 3 mg of estradiol (E(2)) contained in cholesterol pellets elevated blood E(2) levels and caused palpable mammary tumors in all animals. Coadministration of phenobarbital (PB) in their drinking water reduced the incidence, number, and size of mammary tumors (MTs) but did not reduce blood E(2) levels. Inhibition of MTs by PB was accompanied by significant changes in total hepatic metabolism of E(2) measured in vitro.

Inhibition of gastric H+,K+-ATPase activity by flavonoids, coumarins and xanthones isolated from Mexican medicinal plants.

Medicinal plants are commonly used in Latin American folk medicine for the treatment of gastric problems. In order to understand the properties of some of their chemical constituents, four natural xanthones, an acetylated derivative, two coumarins (mammea A/BA and mammea C/OA) isolated from Calophyllum brasiliense Cambess and two flavonoids (minimiflorin and mundulin) isolated from Lonchocarpus oaxacensis Pittier, and the chalcone lonchocarpin isolated from Lonchocarpus guatemalensis Benth were tested for their activities on gastric H+,K+-ATPase isolated from dog stomach. All the compounds tested inhibited H+,K+-ATPase activity with varied potency.

Sulfatase activity in the oyster Crassostrea virginica: its potential interference with sulfotransferase determination.

Two sulfatase isoforms, a soluble one with an optimum pH of 5.0, and a microsomal one with an optimum pH of 7.6, were observed in digestive gland, gonads, mantle and gills of the oyster C.

Sulfonation in pharmacology and toxicology.

Sulfonation has a major function in modulating the biological activities of a wide number of endogenous and foreign chemicals, including: drugs, toxic chemicals, hormones, and neurotransmitters. The activation as well as inactivation of many xenobiotics and endogenous compounds occurs via sulfonation. The process is catalyzed by members of the cytosolic sulfotransferase (SULT) superfamily consisting of at least ten functional genes in humans.

The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17beta-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16alpha-hydroxyestradiol, and 4-hydroxyestrone.

Several investigators have suggested that certain hydroxylated metabolites of 17beta-estradiol (E2) are the proximate carcinogens that induce mammary carcinomas in estrogen-sensitive rodent models. The studies reported here were designed to examine the carcinogenic potential of different levels of E2 and the effects of genotoxic metabolites of E2 in an in vivo model sensitive to E2-induced mammary cancer. The potential induction of mammary tumors was determined in female ACI rats subcutaneously implanted with cholesterol pellets containing E2 (1, 2, or 3 mg), or 2-hydroxyestradiol (2-OH E2), 4-hydroxyestradiol (4-OH E2), 16alpha-hydroxyestradiol (16alpha-OH E2), or 4-hydoxyestrone (4-OH E1) (equimolar to 2 mg E2).

Dietary clofibrate inhibits induction of hepatic antioxidant enzymes by chronic estradiol in female ACI rats.

Excess production of H2O2 has been implicated in oncogenesis. The object of the present study was twofold: first, to determine the influence of chronic estradiol (E2) on the activities of selected hepatic antioxidant enzymes in female ACI rats, a strain that is highly sensitive to the induction of estrogen dependent mammary tumors; secondly, to evaluate the actions of dietary clofibrate, a peroxisome proliferator, on activities of these enzymes in control and E2-treated ACI rats. Enzymes selected for study were: NAD(P)H quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and glutathione peroxidase (GPx).

Esterification of vertebrate-like steroids in the eastern oyster (Crassostrea virginica).

The esterification of two model vertebrate steroid hormones - estradiol (E2) and dehidroepiandrosterone (DHEA) - was studied in the oyster Crassostrea virginica. The activity of acyl-CoA:steroid acyltransferase was characterized in microsomal fractions isolated from oyster digestive glands. The apparent Km and Vmax values changed with the fatty acid acyl-CoA used (C20:4, C18:2, C18:1, C16:1, C18:0 or C16:0), and were in the range of 9-17 microM, and 35-74 pmol/min/mg protein for E2, and in the range of 45-120 microM, and 30-182 pmol/min/mg protein for DHEA.

Esterification of vertebrate-type steroids in the Eastern oyster (Crassostrea virginica).

Characteristics of acyl-coenzyme A (acyl-CoA):steroid acyltransferase from the digestive gland of the oyster Crassostrea virginica were determined by using estradiol (E2) and dehydroepiandrosterone (DHEA) as substrates. The apparent Km and Vmax values for esterification of E2 with the six fatty acid acyl-CoAs tested (C20:4, C18:2, C18:1, C16:1, C18:0, and C16:0) were in the range of 9-17 microM E2 and 35-74 pmol/min/mg protein, respectively. Kinetic parameters for esterification of DHEA (Km: 45-120 microM; Vmax: 30-182 pmol/min/mg protein) showed a lower affinity of the enzyme for this steroid.

Inhibition of rat liver sulfotransferases SULT1A1 and SULT2A1 and glucuronosyltransferase by dietary flavonoids.

1. Dietary flavonoids including kaempferol, quercetin, genistein and daidzein were tested for their ability to alter the conjugation of oestradiol (E(2)) via rat liver sulfotransferases and glucuronosyltransferase. 2.

Induction of NAD(P)H quinone oxidoreductase and glutathione S-transferase activities in livers of female August-Copenhagen Irish rats treated chronically with estradiol: comparison with the Sprague-Dawley rat.

Estradiol (E2) has been linked to both, protection against damage associated with chronic diseases or exposure to chemicals, and to the incidence of cancer. In its protective role, E2 appears to attenuate oxidative stress while as a carcinogen, E2 damages macromolecules via formation of reactive catechol metabolites. Alterations in the expression of antioxidant and xenobiotic metabolizing enzymes upon administration of pharmacological doses of E2 have been previously identified, but the effect of chronic exposure to low concentrations of E2 on activities of those enzymes in liver is unclear.

Challenges of cancer drug design: a drug metabolism perspective.

The time course and duration of action of drugs used in cancer chemotherapy are greatly influenced by the molecular and biochemical properties of enzymes associated with their metabolism. Variation in the response of individual patients to cancer chemotherapeutic agents is in large measure due to genetic and environmental factors that impinge on specific enzymes belonging to the two major classes of drug metabolizing enzymes. Current knowledge of the molecular biology and biochemistry of phase I drug metabolizing enzymes (cytochrome P450, flavin-containing and xanthine oxidases, NADPH quinone reductase, and aldehyde and dihydropyridine dehydrogenases), and phase II enzymes (glucuronosyl-, sulfo-, N-acetyl-, and glutathione transferases, and hydrolases) is reviewed briefly.

Catechol estrogen formation in liver microsomes from female ACI and Sprague-Dawley rats: comparison of 2- and 4-hydroxylation revisited.

Estradiol (E(2))-hydroxylation was studied in liver microsomes from ACI and Sprague-Dawley female rats, which differ markedly in their susceptibility to E(2)-induced formation of mammary tumors. NADPH-dependent oxidation of E(2) by liver microsomes from ACI and Sprague-Dawley rats produced several metabolites of which 2-hydroxyestradiol (2-OH-E(2)), estrone (E(1)), and 2-hydroxyestrone (2-OH-E(1)) were predominant. Incubations with either low (9 nM) or high (50 microM) concentrations of radiolabeled E(2) and with varying amounts of microsomal protein indicated the formation of only small amounts of 4-hydroxyestradiol (4-OH-E(2)).

Liarozole markedly increases all trans-retinoic acid toxicity in mouse limb bud cell cultures: a model to explain the potency of the aromatic retinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] benzoic acid.

The remarkable toxicity of (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] benzoic acid (TTNPB) compared to all trans-retinoic acid (tRA) is due to multiple factors, including reduced affinities for cytosolic binding proteins (CRABPs), resistance to metabolism, and prolonged nuclear receptor activation. To further investigate the role of half-life in retinoid toxicity, experiments were performed to determine whether, and to what extent, inhibition of tRA metabolism by liarozole increased its toxicity comparable to that of TTNPB in the mouse limb bud system. Liarozole is a known inhibitor of tRA 4-hydroxylation (CYP26).

Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1.

Calophyllum brasiliense, Lonchocarpus oaxacensis, and Lonchocarpus guatemalensis are used in Latin American folk medicine. Four natural xanthones, an acetylated derivative, and two coumarins were obtained from C. brasiliense.

Mechanism of action of sodium cyanide on rat diaphragm muscle.

The effects of sodium cyanide (NaCN) were investigated on the contractile and electrophysiological properties of rat diaphragm muscles in vitro. Sodium cyanide (0.1-1.

Multiple factors contribute to the toxicity of the aromatic retinoid TTNPB (Ro 13-7410): interactions with the retinoic acid receptors.

The aromatic retinoid, (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1 -propenyl] benzoic acid (TTNPB) is 1000-fold more teratogenic than all trans-retinoic acid (tRA) in several species. Factors that partially explain the potency of this retinoid include binding affinities to retinoid nuclear receptors (RARs) in the nanomolar range, reduced affinities for the cytosolic binding proteins (CRABPs), and slow rate of metabolism (M. A.

Different biochemical properties of nuclear and microsomal estrone-3-sulfatases: evidence for the presence of a nuclear isozyme.

In female rats, total estrone-3-sulfatase activity per liver in the nuclear fraction is comparable to the total activity per liver in the microsomal fraction. The combined estrone-3-sulfatase activity in the other fractions (lysosomal, mitochondrial, and cytosolic fractions) is negligible and only accounts for < 5% of the total nuclear or microsomal sulfatase activity. Nuclear and microsomal estrone-3-sulfatases have different pH optima (pH 8.

Microsomal steroid sulfatase: interactions with cytosolic steroid sulfotransferases.

Net sulfation of 4-methylumbelliferone in intact hepatocytes is regulated, in part, by substrate cycling between sulfotransferases (SULT) and arylsulfatases (ARS). Thus, ARS have the potential to influence rates of net sulfate conjugation of a variety of compounds in intact cells via interaction with SULT. Unlike ARSA and ARSB, which are lysosomal, steroid sulfate sulfatase (ARSC, also known as STS) is localized exclusively in the endoplasmic reticulum (ER).

Ethanol down-regulates the transcription of microsomal triglyceride transfer protein gene.

Microsomal triglyceride transfer protein (MTP) plays a central role in the assembly and secretion of apoB-containing lipoproteins. In this study, we investigated the effect of ethanol on the expression of the large subunit of MTP in a human liver hepatoma cell line, the HepG2 cells. Exposure of HepG2 cells to low concentrations of ethanol reduced MTP mRNA levels in a concentration- and time-dependent manner.

Multiple factors contribute to the toxicity of the aromatic retinoid, TTNPB (Ro 13-7410): binding affinities and disposition.

The aromatic retinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1 -propenyl] benzoic acid (TTNPB) is 1000-fold more potent as a teratogen than all trans-retinoic acid (tRA) in several species and in the inhibition of chondrogenesis in the mouse limb bud cell culture. Factors responsible for the potency of TTNPB were investigated including binding to nuclear retinoic acid receptors (RARs and RXRs), cytosolic binding proteins (CRABPs), and metabolic disposition of TTNPB. For competitive binding assays and saturation kinetics, nucleosol or cytosol fractions were obtained from COS-1 cells transfected with cDNAs encoding the appropriate nuclear receptor or binding protein.

Toxicity of allyl alcohol in primary cultures of freshly isolated and cryopreserved hepatocytes maintained on hydrated collagen gels.

The toxicity of allyl alcohol was compared in freshly isolated and cryopreserved hepatocytes that were either placed in suspension or maintained on hydrated collagen gels in a sandwich configuration. The purpose of this study was to evaluate whether the two types of cells displayed the same sensitivity to allyl alcohol when maintained in vitro over relatively prolonged periods of time. The important differentiated functions of urea synthesis, secretion of albumin, and metabolism of ethoxycoumarin, a model drug substrate, were used as end points of toxicity.