Search results for "CYP"
showing 10 items of 480 documents
Refractory Acne and 21-Hydroxylase Deficiency in a Selected Group of Female Patients.
2009
<i>Background:</i> Excessive androgen production, suspected in women when acne is accompanied by hirsutism and menstrual irregularities, may be due to congenital adrenal hyperplasia. This inherited disorder of cortisol biosynthesis is caused in more than 90–95% of all cases by 21-hydroxylase deficiency (21-OHD). The steroid 21-hydroxylase gene <i>(CYP21)</i> has a high degree of variability. <i>Objective:</i> This study was conducted to evaluate <i>CYP21 </i>gene mutations in a selected group of women with papulopustular and comedonal acne refractory to treatment, irregular menses and hirsutism. <i>Methods:</i> 30 out of 61 women e…
Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver tran…
2013
Objective A meta-analysis was carried out of publishedstudies on the effect of the CYP3A5 6986A>Gpolymorphism in liver donors and transplant recipientson tacrolimus pharmacokinetics.Methods Cohort studies that evaluated the relationshipbetween the CYP3A5 polymorphism in liver donors andtransplant recipients and tacrolimus, trough bloodconcentration normalized for the daily dose (C) perkilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to1 year after transplantation, were included. Data were notrestricted by patient age or the language or journal ofpublication. A literature search was conducted using theCochrane Library, MEDLINE, EMBASE, and grey literature,and articles published up to 24 Ap…
Treatment of hyperandrogenic alopecia in women
2003
Many women with androgenic alopecia have normal circulating androgen levels. Increased scalp sensitivity to androgens may account for these cases. Even when androgen levels are increased, no particular pattern has emerged. Classical anti-androgen measures have proved disappointing, in contrast to the results obtained in women with hirsutism or acne. This study evaluated flutamide and finasteride in 36 premenopausal, hyperandrogenic women presenting with androgenic alopecia. Frontal hair thinning was assessed in photos of the frontoparietal region using the Ludwig grading system. Thirty ovulatory women matched for age and body weight served as a control group. Groups of 12 subjects received …
Upgrading cytochrome P450 activity in HepG2 cells co-transfected with adenoviral vectors for drug hepatotoxicity assessment
2011
In a number of adverse drug reactions leading to hepatotoxicity, drug metabolism is thought to be involved by the generation of reactive metabolites from non-toxic drugs. The use of hepatoma cell lines, such as HepG2 cell line, for the evaluation of drug-induced hepatotoxicity is hampered by their low cytochrome P450 expression which makes impossible the study of the toxicity produced by bioactivable compounds. Genetically manipulated cells constitute promising tools for hepatotoxicity applications. HepG2 cells were simultaneously transfected with recombinant adenoviruses encoding CYP1A2, CYP2C9 and CYP3A4 to confer them drug-metabolic competence. Upgraded cells (Adv-HepG2) were highly able…
Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1.
2006
The hepatic carcinogen aflatoxin B1 (AFB1) is metabolized in the liver by at least four different P450s, all of which exhibit large interindividual differences in the expression levels. These differences could affect the individual risk of hepatocellular carcinoma (HCC). We investigated the metabolism of AFB1 in a panel of 13 human liver microsomal preparations using a hepatic abundance model, which takes into account the specific kinetic parameters and the expression levels of these P450s. We found a 12-fold variability in the production rate of the carcinogenic metabolite AFB1-8,9-epoxide (AFBO) and a 22-fold variability in the production of the detoxification product AFQ1. The ratio betw…
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
2014
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in larg…
Aldosterone synthase activity in the Y-1 adrenal cell line.
1995
The Y-1 adrenal cell line was shown to produce 20 alpha-dihydroaldosterone from deoxycorticosterone. This compound was identified by GC-MS by comparison with the previously synthesized reference compound. Two other 18-hydroxylated metabolites were identified as 11 beta,18-dihydroxy-20 alpha-dihydroprogesterone from endogenous cholesterol and 18-hydroxy-20 alpha-dihydro-11-dehydrocorticosterone from DOC. The conditions necessary for the synthesis of these compounds are culturing in 20% serum-supplemented medium and repeated incubations with the substrate. The production of 11 beta-hydroxylated steroids and that of 18-oxygenated steroids is stimulated differently by ACTH and angiotensin II su…
Recent advances in computational design of potent aromatase inhibitors: open-eye on endocrine-resistant breast cancers.
2019
Introduction: The vast majority of breast cancers (BC) are estrogen receptor positive (ER+). The most effective treatments to fight this BC type rely on estrogen deprivation therapy, by inhibiting the aromatase enzyme, which performs estrogen biosynthesis, or on blocking the estrogens signaling path via modulating/degrading the estrogen's specific nuclear receptor (estrogen receptor-?, ER?). While being effective at early disease stage, patients treated with aromatase inhibitors (AIs) may acquire resistance and often relapse after prolonged therapies. Areas covered: In this compendium, after an overview of the historical development of the AIs currently in clinical use, and of the computati…
Ontogeny of Heterocypris bosniaca (Ostracoda: Cyprididae): description of postembryonic instars and rediscovery of the neglected A-9 stage
2013
Despite being the most common and widespread family of Ostracoda in fresh water, the Cyprididae are still poorly known with respect to species ontogeny. The full series of eight juvenile instars has been described in detail for just five of the approximately 1000 living species, and only in one case did this include the earliest A-9 stage. We aimed to fill this gap with a morphological study of the post-embryonic development of Heterocypris bosniaca Petkowski, Scharf and Keyser, 2000, a species with unusual morphological traits within the genus, including putatively paedomorphic characters such as valves without tubercles and the narrow calcified inner lamella on both valves. Inside the egg…
Indoor air pesticide in dwellings of breastfeeding mothers of the Valencian Region (Spain): Levels, exposure and risk assessment
2021
This study assessed the inhalation risk associated with indoor pesticide concentrations in the dwellings of 41 lactating mothers living in the Valencian Region, Spain, who were participants in the BETTERMILK project. Twenty-eight substances were investigated, including pyrethroid (PYRs), organophosphate (OPPs), and organochlorine (OCPs) pesticides. Bifenthrin, cypermethrin, lambda-cyhalothrin, malathion, permethrin and pyrimethanil were detected with frequencies ranging from 2% (malathion) to 80% (cypermethrin), and with an arithmetic mean concentration ranging from 4.1 ng m(-3) (bifenthrin) to 12.1 ng m-(3) (cypermethrin). The indoor air analysis was combined with several surveys to assess…