RESUMO
Introduction: The placenta is a temporary and unique organ that allows for the physical connection between a mother and fetus; this organ regulates the transport of gases and nutrients mediating the elimination of waste products contained in the fetal circulation. The placenta performs metabolic and excretion functions, on the basis of multiple enzymatic systems responsible for the oxidation, reduction, hydrolysis, and conjugation of xenobiotics. These mechanisms give the placenta a protective role that limits the fetal exposure to harmful compounds. During pregnancy, some diseases require uninterrupted treatment even if it is detrimental to the fetus. Drugs and other xenobiotics alter gene expression in the placenta with repercussions for the fetus and mother's well-being.Areas covered: This review provides a brief description of the human placental structure and function, the main drug and xenobiotic transporters and metabolizing enzymes, placenta-metabolized substrates, and alterations in gene expression that the exposure to xenobiotics may cause.Expert opinion: Research should be focused on the identification and validation of biological markers for the assessment of the harmful effects of some drugs in pregnancy, including the evaluation of polymorphisms and methylation patterns in chorionic villous samples and/or amniotic fluid.
Assuntos
Troca Materno-Fetal/fisiologia , Placenta/metabolismo , Xenobióticos/farmacocinética , Animais , Feminino , Feto/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Placenta/enzimologia , Gravidez , Xenobióticos/efeitos adversosRESUMO
In human spermatozoa, protein kinases have a role in the acrosome reaction (AR) induced by a variety of stimuli. However, there is disagreement or a lack of information regarding the role of protein kinases and phosphatases in the progesterone (P)-induced increase in intracellular calcium concentration ([Ca2+ ]i ). In addition, there are no studies regarding the role of Ser/Thr and Tyr phosphatases and there are contradictory results regarding the role of Tyr kinases in the P-induced acrosome reaction. Here, we performed a simultaneous evaluation of the involvement of protein kinases and phosphatases in the P-induced acrosome reaction and in the P-induced calcium influx. Motile spermatozoa were capacitated for 18 h and different aliquots were allocated to treated or control groups and then evaluated for their ability to undergo the acrosome reaction and to increase [Ca2+ ]i in response to P. The acrosome reaction was evaluated using Pisum sativum agglutinin (PSA)-FITC, and [Ca2+ ]i was evaluated using fura 2AM. At all of the concentrations tested, PKA inhibitors significantly reduced the percentage of the P-induced acrosome reaction (p < 0.001). However, only the highest concentrations of PKA inhibitors reduced the P-induced calcium influx; lower concentrations of PKA inhibitors did not affect it. Similar results were apparent for PKC inhibitors and for tyrosine kinase inhibitors. None of the Ser/Thr phosphatase inhibitors affected the P-induced acrosome reaction or the P-induced calcium influx, except for the PP2B inhibitors that significantly reduced the P-induced acrosome reaction without affecting calcium influx. Finally, the protein tyrosine phosphatase inhibitors significantly blocked the P-induced acrosome reaction and reduced the amplitude of the P-induced calcium transient (p < 0.001) as well as the amplitude of the plateau phase (p < 0.01). The data suggest that protein kinases and possibly PP2B have a role on the acrosome reaction at some point downstream of calcium entry and that Tyr phosphatases have a role on the acrosome reaction upstream of calcium entry.
Assuntos
Reação Acrossômica/fisiologia , Cálcio/metabolismo , Progesterona/farmacologia , Proteínas Quinases/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Espermatozoides/metabolismo , Reação Acrossômica/efeitos dos fármacos , Humanos , Masculino , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Capacitação Espermática/efeitos dos fármacos , Capacitação Espermática/fisiologia , Espermatozoides/efeitos dos fármacosRESUMO
BACKGROUND: We present the first results of our program, which is characterized by its acceptance of any candidate with chronic renal failure. Therefore, we serve all patients, regardless of their social security and socioeconomic status. METHODS: We conducted a retrospective, descriptive, cross-sectional study describing the characteristics of patients who received kidney transplants in the period from 2008 to 2015. Descriptive statistics were used to evaluate our findings. RESULTS: A total of 708 transplants were performed, with 377 (53%) involving a living donor and 331 (47%) involving deceased donors. The patients' mean age was 26 years (±12.7 SD), with a range of 5 to 69 years. Of these patients, 488 were male (68.9%), and 423 (59.7%) had no social security. The replacement therapy prior to transplantation was peritoneal dialysis in 40% of cases, hemodialysis in 57% of cases, and 3% of patients had no prior therapy. The blood group distribution was 436 (61%) type O; 177 (25%) type A; 78 (11%) type B; and 8 (1%) type AB. The average hospital stay for a living donor transplant was 9 days and 13 days in the case of a deceased donor. CONCLUSIONS: This study describes the basic clinical and epidemiological characteristics of our transplant population. These results can be used as a basis for future descriptive and prospective studies at our institution or in other inter-agency and national projects. We also highlight the rapid development of the kidney transplant program at the Bajio Regional High Specialty Hospital.
Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitais Especializados/estatística & dados numéricos , Humanos , Falência Renal Crônica/epidemiologia , Doadores Vivos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Adulto JovemRESUMO
The effects of host biodiversity on disease risk may vary greatly depending on host population structure and climatic conditions. Agricultural diseases such as potato late blight, caused by Phytophthora infestans, provide the opportunity to study the effects of intraspecific host diversity that is relatively well-defined in terms of disease resistance phenotypes and may have functional impacts on disease levels. When these systems are present across a climatic gradient, it is also possible to study how season length and conduciveness of the environment to disease may influence the effects of host diversity on disease risk. We developed a simple model of epidemic progress to evaluate the effects on disease risk of season length, environmental disease conduciveness, and host functional divergence for mixtures of a susceptible host and a host with some resistance. Differences in disease levels for the susceptible vs. resistant genotypes shifted over time, with the divergence in disease levels first increasing and then decreasing. Disease reductions from host diversity were greatest for high host divergence and combinations of environmental disease conduciveness and season length that led to moderate disease severity. We also compared the effects of host functional divergence on potato late-blight risk in Ecuador (long seasons), two sites in Peru (intermediate seasons) in El Niño and La Niña years, and the United States (short seasons). There was some evidence for greater disease risk reduction from host diversity where seasons were shorter, probably because of lower regional inoculum loads. There was strong evidence for greater disease reduction when host functional divergence was greater. These results indicate that consideration of season length, environmental conduciveness to disease, and host functional divergence can help to explain the variability in disease response to host diversity.
Assuntos
Clima , Phytophthora infestans/fisiologia , Doenças das Plantas/microbiologia , Solanum tuberosum/microbiologia , Equador , Interações Hospedeiro-Patógeno , Modelos Biológicos , Peru , Fatores de Risco , Fatores de Tempo , Estados UnidosRESUMO
Potassium channels have a conserved selectivity filter that is important in determining which ions are conducted and at what rate. Although K+ channels of different conductance characteristics are known, they differ more widely in the way their opening and closing, the gating, is governed. TASK and TALK subfamily proteins are two-pore region KCNK K+ channels gated open by extracellular pH. We discuss the mechanism for this gating in terms of electrostatic effects on the pore changing the occupancy and open probability of the channels in a way reminiscent of C-type inactivation gating at the selectivity filter. Essential to this proposed mechanism is the replacement of two highly conserved aspartate residues at the pore mouth by asparagine or histidine residues in the TALK and TASK channels.
Assuntos
Espaço Extracelular/fisiologia , Ativação do Canal Iônico/fisiologia , Canais de Potássio/fisiologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Knockout , Modelos Moleculares , Canais de Potássio/química , Canais de Potássio de Domínios Poros em Tandem/deficiência , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/fisiologia , Estrutura Secundária de ProteínaRESUMO
The objective of this study was to assess the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS). We studied 28 patients with SLE, 10 patients with PAPS, and 24 healthy controls. VEGF plasma levels were measured by ELISA. Immunolocalization of VEGF was done in renal tissue from SLE patients and cadaveric controls. Our results showed that VEGF plasma levels were increased in SLE patients compared with PAPS and controls. The correlation between clinical manifestations and VEGF levels revealed that SLE patients with renal failure had significantly increased plasma VEGF levels (134.1 + 91.0 pg/ml) compared with SLE patients with normal renal function (42.9 + 19.0 pg/ml), PAPS patients (41.9 + 26.6 pg/ml), and controls (36.2 + 27.0 pg/ml; P < 0.01). Immunostaining showed a strong expression of VEGF in SLE renal tissue samples. Our preliminary results indicate that VEGF is increased in plasma from patients with lupus nephritis and a moderate degree of renal failure and is overexpressed in renal tissue from these patients.
Assuntos
Síndrome Antifosfolipídica/sangue , Fatores de Crescimento Endotelial/sangue , Nefrite Lúpica/sangue , Linfocinas/sangue , Adulto , Síndrome Antifosfolipídica/patologia , Fatores de Crescimento Endotelial/análise , Feminino , Humanos , Rim/química , Rim/patologia , Nefrite Lúpica/patologia , Linfocinas/análise , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
In human and experimental CCl4-liver damage, S-adenosyl-l-methionine-synthetase and/or the intrahepatic content of S-adenosyl-l-methionine, are diminished and in human cirrhosis phospholipid methyltransferase is markedly reduced. Therefore the aim of this study was to investigate the effect of S-adenosyl-l-methionine administration on liver damage induced by 15-day bile duct ligation. Liver damage was analyzed by histological, ultrastructural and biochemical techniques. Biliary obstruction produced an increase in collagen content, dilation of the bile canaliculi and disorganization of mitochondria. These effects were not observed in the bile-duct-ligated group receiving S-adenosyl-l-methionine. Biochemical results showed that bile duct ligation increased serum bilirubins, and alkaline phosphatase and gamma-glutamyl transpeptidase activities. These effects were prevented significantly by S-adenosyl-l-methionine. On the other hand, glycogen content in the liver was depleted while lipid peroxidation was increased by biliary obstruction, S-adenosyl-l-methionine administration prevented these effects. In the bile-duct-ligated group, hepatocyte and erythrocyte plasma membrane Na+/K+ and Ca(2+)-ATPase were lower than in the control group (p < 0.05). Administration of S-adenosyl-l-methionine preserved ATPase activities. The exogenous S-adenosyl-l-methionine supply is probably responsible for restoring transmethylation lost in liver diseases.