RESUMO
The technique of evaluation of metabolism of fatty acids in vivo consists in detection of content of fatty acids in phospholipids of membranes of erythrocytes. The fatty acids are received with food, through synthesis on liver from carbohydrates and by katabolism of very long-chain polyolefinic fatty acids of food in peroxisomes of hepatocytes (oxidation, saturation and desaturation). In position sn-1 phospholipids more often than palmitic fatty acid (14%) stearic fatty acid is esterified (21% of all fatty acids). The palmitic, stearic and lignoceric saturated fatty acids are esterified into sn-1 phospholipids as 2:3:1. The simvastatin (80 mg per day) increased content of margarine, tricosanoic and hexacosanoic fatty acids by decrease of level of palmitic fatty acid. The ratio omega-3 polyolefinic fatty acids/omega-6 polyolefinic fatty acids reliably increased. The statins increase content of omega-3 polyolefinic fatty acids. In practice, it is necessary to differentiate the terms "atherosclerosis" and "atheromatosis". The atherosclerosis is a syndrome of intracellular deficiency of polyolefinic fatty acids, derangement of function of cells in vivo under decrease of biological availability for all cells (absorption blockage). The atheromatosis is such most significant clinically symptom of atherosclerosis as accumulation of non-saturated and polyolefinic fatty acids in pool of collection and utilization of biological "garbage" from blood plasma, in intima of elastic type arteries. The statins activate absorption of low density lipoproteins by cells and normalize biological availability of polyolefinic fatty acids which have a positive effect under atherosclerosis and on formation of atheromatosis.
Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismoRESUMO
In the present work we for the first time on the clinic-genetic material revealed genetic predictors of development of acute disturbance of brain circulation (ADBC) in families of patients with atrial fibrillation (AF) namely polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Genotype CC was significantly more often found among patients with AF and ADBC compared with controls (58.1 and 35.2%, respectively, p=0.02) as well as in relatives of probands compared with the control group (59.3 and 35.2%, respectively, p=0.008). With this in relatives with revealed paroxysmal AF and ADBC we also noted presence of CC genotype. Taking into consideration the relationship obtained between polymorphysms of MTHFR gene and AF it was possible to assume that polymorphic marker CC appeared to be a predictor of ADBC in these families.
Assuntos
Fibrilação Atrial , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Acidente Vascular Cerebral , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/genética , Circulação Cerebrovascular/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genéticaRESUMO
The loss of heterozygosity by p53 gene and the expression of p53 protein have been studied in cancerous pulmonary tissues and congenital cystic adenomatoid malformation by molecular-biologic and immunohistochemial methods. The loss of heterozygosity by p53 gene is confirmation of precocious molecular damage in epithelium of cystic adenomatoid pulmonary malformation.
Assuntos
Malformação Adenomatoide Cística Congênita do Pulmão/genética , Malformação Adenomatoide Cística Congênita do Pulmão/patologia , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor p53/genética , Adulto , Malformação Adenomatoide Cística Congênita do Pulmão/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/metabolismoRESUMO
Rat liver microsomal carboxylesterase catalyzed hydrolysis of butyl methacrylate (BMA), butyl acrylate (BA), methyl acrylate (MA) and methyl methacrylate (MMA). The rate of butanol formation from BA and BMA was 4-fold higher as compared with methanol production from MA and MMA. Methanol was oxidized to formaldehyde at the next step of microsomal metabolism. The rate of methanol oxidation was increased 2.2-fold after addition of the NADPH-generating system into the incubation medium. In the mixture containing MMA, NADPH-generating system and liver microsomes, preinduced with phenobarbital or methyl cholanthrene, the rate of formaldehyde generation was increased 7- and 2-fold, respectively, as compared with the analogous experiments involving liver microsomes of control rats. Production of methanol and generation of formaldehyde were not detected after incubation of MMA with inactivated microsomes. The microsomal MMA-methanol oxidizing system was inhibited by CO or after addition of microsomes from rats pretreated with CoCL2. Sodium azide (0.05 mM) decreased 8-fold the rate of formaldehyde generation.
Assuntos
Formaldeído/metabolismo , Metilmetacrilatos/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Catalase/metabolismo , Sistema Enzimático do Citocromo P-450/biossíntese , Sistema Enzimático do Citocromo P-450/metabolismo , Indução Enzimática , Técnicas In Vitro , Metilmetacrilato , Metilmetacrilatos/toxicidade , Microssomos Hepáticos/enzimologia , NADP/metabolismo , Oxirredução , Ratos , Ratos EndogâmicosRESUMO
Increasing amount of fructose-1-phosphate aldolase activity in rat blood serum and induction of chromosomal aberrations in rat bone marrow cells were observed after injection of acrylamide. The cytotoxic activity of acrylamide in rat depended on the dose. Methylmethacrylate and butyl methacrylate demonstrated no such activity.
Assuntos
Acrilatos/toxicidade , Mutagênicos , Acrilatos/intoxicação , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/ultraestrutura , Aberrações Cromossômicas , Relação Dose-Resposta a Droga , Hidroquinonas/farmacologia , Masculino , RatosRESUMO
Content of cytochrome P-450 was decreased in rat liver microsomes, pretreated with phenobarbital, after incubation with acrylamide, methyl methacrylate and butyl methacrylate in presence of NADPH in vitro. The phenomenon was not observed in the analogous experiments but carried out without NADPH, thus suggesting the microsomal metabolism of the acrylates. At the same time, after intraperitoneal administration of acrylamide 0.4 mmole/kg, methyl methacrylate 6.0 mmole/kg and butyl methacrylate 9.0 mmole/kg within 3 days into intact and protected with phenobarbital rats alterations in total content of cytochrome P-450 were not observed. All the acrylates studied exhibited the slight inducing effect on cytochrome P-450b but did not affect the cytochrome P-450c. Methyl- and butyl methacrylates decreased distinctly the content of cytochrome P-450 isoenzyme with molecular mass of 48,000 daltons.
Assuntos
Acrilatos/toxicidade , Inibidores das Enzimas do Citocromo P-450 , Isoenzimas/antagonistas & inibidores , Microssomos Hepáticos/enzimologia , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Isoenzimas/metabolismo , Masculino , Fenobarbital/farmacologia , RatosRESUMO
Esters of acrylic and methacrylic acids (methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate) binding with cytochrome P-450 in rat liver microsomes, formed the spectral complexes of the first order with maximal extinction at 381-388 nm and minimal--at 416-425 nm. Dimethylaniline, used as a classical substrate of oxidation in reactions catalyzed by cytochrome P-450, inhibited the complexes formation by the mixed type. Acrylates increased the oxygen consumption and NADPH oxidation in rat liver microsomes.
Assuntos
Acrilatos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Microssomos Hepáticos/enzimologia , Acrilatos/toxicidade , Animais , Inativação Metabólica , Masculino , Microssomos Hepáticos/metabolismo , NADP/metabolismo , Oxirredução , Ratos , Especificidade por SubstratoRESUMO
A complex, exhibiting the maximal absorption at 385-388 nm and minimal at 414-420 nm, was formed after interaction between cytochrome P-450 and methylmethacrylate and acrylamide at 5 mM concentration. Acrylamide at concentrations higher than 6 mM induced the formation of modified type 11 differential spectra with maxima at 418 nm and minima at 385 nm. Methylmethacrylate and acrylamide stimulated utilization of NADPH and inhibited hydroxylation of 3,4-benzpyrene. Methylmethacrylate inhibited also N-demethylation of aminopyrine. After treatment of rats with the monomers activities of cytochromes P-450, b5 and NADPH-cytochrome c reductase were unaltered. Methylmethacrylate and acrylamide appear to interact with the microsomal oxidative system.
Assuntos
Acrilamidas/metabolismo , Metilmetacrilatos/metabolismo , Microssomos Hepáticos/metabolismo , Acrilamidas/farmacologia , Aminopirina N-Desmetilase/metabolismo , Animais , Benzo(a)pireno/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Masculino , Metilmetacrilatos/farmacologia , Microssomos Hepáticos/enzimologia , NADP/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Oxirredução , Ratos , EspectrofotometriaRESUMO
Hypoxemia (45-minute) influence in vivo on erythropoietic activity of the kidney, liver, spleen, and sternum was studied by normoxemic perfusion of the isolated organs. The erythropoietic activity proved to increase after 6-hour perfusion of the liver; this confirmed the participation of this organ in the extrarenal secretion of the erythropoietic factor.