Search results for " P4"

Ksenobiotiku metabolisma enzīmu citohroma P450 aktivitātes audzēju šūnu līnijās

2017

Jaunu zāļu vielu meklējumi pasaulē notiek ļoti aktīvi. Šobrīd jauno savienojumu īpašību, tai skaitā toksiskuma, izpētei plaši izmanto šūnu līniju modeļus in vitro. Viena no šūnu svarīgākajām sistēmām, kurai ir milzīga ietekme uz jebkura preparāta darbību organismā, ir citohroma P450 sistēma. Tai ir svarīga loma ķīmiskās homeostāzes uzturēšanā organismā gan fozioloģiskos, gan pataloģiskos apstākļos. Citohromi piedalās ļoti daudzu ksenobiotiķu eliminācijā no šūnām. Turklāt, zinot, ka ksenobiotiķu biotransformācijas procesā var veidoties organismam bīstami toksiski metabolīti, zināšanas par citohromu aktivitāti kļūst īpaši svarīgas. Šī darba mērķis ir citohroma P450 sistēmas raksturojums šūnu …

Candidate gene study on nicotine dependence in Finnish sibpairs

2008

Targeting Orthosteric and Allosteric Pockets of Aromatase via Dual-Mode Novel Azole Inhibitors

2020

[Image: see text] Breast cancer (BC) is the most diffused cancer type in women and the second leading cause of death among the female population. Effective strategies to fight estrogen responsive (ER+) BC, which represents 70% of all BC cases, rely on estrogen deprivation, via the inhibition of the aromatase enzyme, or the modulation of its cognate estrogen receptor. Current clinical therapies significantly increased patient survival time. Nevertheless, the onset of resistance in metastatic BC patients undergoing prolonged treatments is becoming a current clinical challenge, urgently demanding to devise innovative strategies. In this context, here we designed, synthesized, and performed in …

Breath test using 13C methacetin does not seem to be useful in the assessment of liver function in girls with anorexia nervosa: a case control study

2018

Abstract Background Anorexia nervosa (AN) concerns approximately up to 1.8% of the pediatric female population. One of the complications that can occur in the course of this disease is acute liver failure. This study’s objective was to assess the usefulness of the 13C labeled Methacetin Breath Test (MBT) in the diagnostics of the liver function in girls with eating disorders. Methods For the study 81 girls aged 12 to 17 years were recruited, including 41 patients with confirmed diagnosis of AN (mean age 14.7 ± 1.48 years) and 40 age-matched controls. The diagnosis was based on the present Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Weight and height were measured…

The induction of hepatic microsomal metabolism in rats following acute administration of a mixture of polybrominated biphenyls.

1976

Abstract Firemaster BP6, a mixture of polybrominated biphenyls (PBBs), was administered to female Sprague-Dawley rats (170–180 g) as a single ip injection at 25 and 150 mg/kg. Other animals received phenobarbital (PB), 3-methylcholanthrene (3MC), or PB and 3MC together. Animals were killed at intervals of 12, 24, 48, 192, and 336 hr after treatment with PBBs, or 24 hr after PB, MC, or PB-MC, and various hepatic microsomal parameters were measured. After 150 mg/kg of PBBs, cytochrome P450 concentrations reached a maximum by 48 hr (225% of control), then remained elevated through 336 hr. A similar pattern of induction was observed for epoxide hydratase and aniline hydroxylase activities. In c…

Dynamics of gut mucosal and systemic Th1/Th2 cytokine responses in interferon-gamma and interleukin-12p40 knock out mice during primary and challenge…

2009

Cryptosporidium parvum is an intracellular parasite causing enteritis which can become life-threatening in the immunocompromised host. CD4+ T cells and interferon (IFN)-gamma play dominant roles in host immune response to infection. However, effector mechanisms that are responsible for recovery from infection are poorly understood. In the present study we analyzed mice deficient in IFN-gamma or interleukin (IL)-12 in parallel to C57BL/6 wild type mice as models for murine cryptosporidiosis. Our results identified IFN-gamma as the key cytokine in the innate as well as adaptive immunity during primary and also challenge C. parvum infection. Furthermore, both Th1 and Th2 cytokines appear to co…

Regulation of cytochrome P450 IID by acute phase mediators in C3H/HeJ mice.

1992

Abstract Cytochrome P450 IID6 is a drug metabolizing enzyme and the major target antigen in LKM-1 antibody positive chronic active hepatitis. The histological hallmark of chronic active hepatitis is a lymphocytic infiltrate in the liver. It is unknown whether and how cytokines produced and secreted by these tissue infiltrating mononuclear cells regulate the cellular expression of cytochrome P450 IID6. To study the effect of interleukin 1, tumor necrosis factor and interleukin 6 on the hepatocellular RNA expression of cytochrome P450 IID, we injected each of the cytokines in C3H HeJ mice. We found a time-dependent suppression of the cytochrome in the liver. Six hours after the intraperitonea…

Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients

2011

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder defined clinically by progressive lower limb spasticity and weakness. HSP is a genetically highly heterogeneous condition with at least 46 gene loci identified so far, involving X-linked, autosomal recessive (AR) and autosomal dominant inheritance. For correct diagnosis, molecular testing is essential because clinical parameters by themselves are not reliable to differentiate HSP forms. The purpose of this study was to establish amplicon-based high-throughput genotyping for AR-HSP. A sample of 187 index cases with apparently sporadic or recessive spastic paraplegia were analyzed by applying an array-based amplification stra…

Degradation of an alkaloid pheromone from the pale-brown chafer, Phyllopertha diversa (Coleoptera: Scarabaeidae), by an insect olfactory cytochrome P…

1999

AbstractThe pale-brown chafer, Phyllopertha diversa, utilizes an unusual alkaloid, 1,3-dimethyl-2,4-(1H,3H)-quinazolinedione, as its sex pheromone. This compound is rapidly degraded in vitro by the antennal protein extracts from this scarab beetle. Demethylation at the N-1 position and hydroxylation of the aromatic ring have been identified as the major catabolic pathways. The enzyme responsible for the pheromone degradation is membrane-bound, requires NAD(P)H for activity and is sensitive to cytochrome P450 inhibitors, such as proadifen and metyrapone. The ability to metabolize this unusual pheromone was not detected in 12 species tested, indicating that the P450 system, specific to male P…

Photoinduced lethal and sublethal toxicity of retene, a polycyclic aromatic hydrocarbon derived from resin acid, to coregonid larvae

2004

A comparative investigation on the acute phototoxicity of retene to vendace (Coregonus albula) and whitefish (C. lavaretus), both having pelagial larvae in spring, was conducted. To test the concept of early warning of sublethal biomarkers in relation to lethality to posthatch stages, we examined the effects of ultraviolet-B (UV-B) and retene on the levels of cytochrome P4501A (CYP1A) and heat shock protein 70 (HSP70) by exposing the animals to elevated levels of these factors for 48 and 72 h, respectively. Whereas UV-B and retene on their own were not lethal, simultaneous retene and UV-B exposure caused very high mortality to both species. The median lethal concentration (LC50; i.e., the c…