RESUMO
The transcription factor KAISO is important for proper development of animal embryos. In the cell, KAISO regulates cell division and apoptosis. KAISO is abundant in the central nervous system. Here we describe the effects of Zbtb33 gene knockout on the transcription of several genes that regulate the development of the central nervous system, including Fgf9, Fgfr3, Sox9, Sox2, c-Myc, NeuroD1 and FoxG1. These genes are related to the Wnt/ß-catenin signaling pathway, which is closely connected to KAISO. Hippocampal, frontal cortical, and striatal tissue from C57BL/6j mice with a knockout in the Zbtb33 gene encoding KAISO (ZBTB33-) and wild-type mice (ZBTB33+) were collected and profiled at different stages of development. Age-dependent and region-specific differences in the mRNA levels of the Fgf9, Fgfr3, c-Myc, FoxG1 genes in the developing brain of ZBTB33- and ZBTB33+ mice were described and discussed.
Assuntos
Encéfalo , Fatores de Transcrição , Animais , Fator 9 de Crescimento de Fibroblastos , Fatores de Transcrição Forkhead/genética , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas c-myc , Fatores de Transcrição/genéticaRESUMO
AIM: This article reports 1-year clinical outcomes of patients with rheumatoid arthritis (RA) receiving abatacept (ABA) therapy. MATERIALS AND METHODS: Patients (n=91) with high RA activity (DAS28 = 5.1 ± 1.0) and an inadequate response on synthetic DMARDs (mainly methotrexate, 70.3%) and biologics (mainly TNF-α inhibitors, 93%) were included in the study. The majority of patients were middle-aged (49 ± 13.5) womens, RF (72.5%) and ACPA (77%) positive, with moderate functional impairment - HAQ = 1.4 (0.9-2). ABA were administered IV, 10 mg/kg according to the standard scheme. The evaluation of the effectiveness of the therapy was carried out according to the EULAR / ACR 2011 criteria using SDAI, CDAI, HAQ and the intention to treat approach. RESULTS: ABA led to a significant (p <0.05) decrease activity of RA. Clinical improvement according to EULAR criteria after 6 months of treatment was registered in 70.9%, after 12 months 63%. Almost a third of patients (28.7%) achieved a good response after 3 months of therapy, 39,2% - after 6 months and 39% - after 12 months. The retention rate of ABA therapy after 6 months was 77%, after 12 months - 60%. There were no significant differences between "bio-naive", 1 Bio and ≥2 Bio groups in achieving EULAR response. A good response was achieved in 38%, 38% and 43%, respectively, but the lowest number of non-responders was registered in ≥2 Bio - 38%, 36% and 43%. ABA significantly improved functional status of patients, after 12 months a marked and moderate improvement in the HAQ was achieved in 39% and 21% of patients, respectively. Adverse events (AE) were registered in 22 patients. The most frequent AE were upper respiratory tract infections - 11 (12%) patients. CONCLUSION: Abatacept was effective in the overall population, and in all subgroups of patients. It has shown significant improvement of clinical and functional status in patients who had an inadequate response to previous therapy. ABA has a good safety profile. AE were registered only in a small number of patients.
Assuntos
Abatacepte , Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Metotrexato , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.
Assuntos
Doenças Autoimunes/terapia , Gonadotropina Coriônica/fisiologia , Gonadotropina Coriônica/uso terapêutico , Gonadotropina Coriônica/química , Gonadotropina Coriônica/metabolismo , Corpo Lúteo/metabolismo , Endométrio/fisiologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Mitógenos/imunologia , Mucina-1/metabolismo , Placenta/fisiologia , Placentação , Gravidez , Progesterona/metabolismo , Transdução de SinaisRESUMO
Studies on mitochondria has revealed apparent violation of laws of osmosis, apparently, related to ion transport. In this context, we studied changes in the content of potassium, sodium, magnesium, and calcium in mitochondria from wheat (Triticum aestivum L.) roots incubated in the buffer without the substrate with 0.3 or 0.5 M sucrose as well as potassium, and phosphate. The most pronounced changes were observed for potassium. Potassium arrival to mitochondria was more active at 0.5 than 0.3 M sucrose. The direction of the cation transport depended on its content in the initial buffer. At the certain threshold level, the inflow was replaced with the outflow; this threshold was lower at 0.3 than 0.5 M sucrose. Magnesium was also released from mitochondria; its stable outflow was primarily observed at its lower initial content in the suspension at 0.3 rather than 0.5 M sucrose. The obtained data demonstrated that the apparent violation of laws of osmosis was false and resulted from ion transport. Passive ion transport as a possible mechanism of adaptation to osmotic properties of the external medium is discussed.
Assuntos
Cátions/metabolismo , Mitocôndrias/metabolismo , Triticum/metabolismo , Meios de Cultura , Transporte de Íons , Concentração Osmolar , Raízes de Plantas/metabolismo , Potássio/metabolismo , Sacarose/químicaRESUMO
We studied the oxidative and phosphorylative activity of mitochondria in the seeds of three sunflower cultivars (Polevik, Peredovik, and Yubileinyi) during development of the seed embryo within 1 to 54 days after flowering. The rates of succinate oxidation by the mitochondria were 1.5-2 times those of malate or alpha-ketoglutarate oxidation. The ratio of substrate oxidation rates underwent changes during the seed growth. The differences were recorded between cultivars as concerns the times when the maximum oxidation rates were reached. Oxidation was coupled with phosphorylation during the entire period of seed development: the value of respiratory control after Chang changed from 1.4 to 7. By the time of transition to maturation, the rates of oxidation of both substrates and the values of respiratory control and ADP/O decreased. The results we obtained suggest that by days 13-15 of seed embryo growth, the rate of ATP production decreases upon oxidation of Krebs cycle products.
Assuntos
Helianthus/metabolismo , Mitocôndrias/metabolismo , Oxigênio/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Respiração Celular/fisiologia , Ciclo do Ácido Cítrico , Helianthus/crescimento & desenvolvimento , Ácidos Cetoglutáricos/metabolismo , Malatos/metabolismo , Oxirredução , Fosforilação , Especificidade da Espécie , Ácido Succínico/metabolismoRESUMO
The levels of succinate dehydrogenase (SDG), lactate dehydrogenase (LDG), glucose-6-phosphate-dehydrogenase (G-6-PDG), myeloperoxydase (MPO), glycogen and cationic proteins were determined in the neutrophilic granulocytes of peripheral blood of 79 rabbits after experimental contamination by endotoxin of S. typhi. The bactericidal system of neutrophils was stimulated due to the depression of SDG, activation of LDG and G-6-PDG levels. Administration of indometacinum and chlotasolum blockaded the cyclooxygenase fermentative system of prostaglandin synthesis and thus decreased the activity of S. typhi endotoxin.
Assuntos
Atividade Bactericida do Sangue , Neutrófilos/imunologia , Neutrófilos/metabolismo , Febre Tifoide/sangue , Febre Tifoide/imunologia , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Hidrato de Cloral/farmacocinética , Inibidores de Ciclo-Oxigenase/farmacocinética , Histocitoquímica , Indometacina/farmacocinética , Masculino , Coelhos , Tiazóis/farmacocinética , Fatores de TempoRESUMO
The water condition of cured and uncured pork, having different ageing times, was studied in the process of heating to 80°C, using nuclear-magnetic resonance methods. In the transverse magnetization decay functions five components could be distinguished, differing from each other by their relative weights and relaxation times. The greatest relative weight (60-70%) was characteristic of the component having relaxation time 35-45 ms ('d'), which could be related to immobilized water. The change of the component's 'd' relative weight while heating was significantly dependent on the ageing time of meat and the factor of curing or not curing before heating. It was shown that the greatest amount of immobilized water and its strongest bonding were observed in uncured pork during the first 6-7 h and after 48 h post mortem. Cured meat possesses the highest amount of immobilized water at room temperature after 48-96 h post mortem, however, its bonding at heating is higher in the case of meat which is cured during the first hours and after 96 h post mortem.
RESUMO
Hyaluronidase and hyaluronic acid activities are markedly changed in influenza, these changes directly depending on the severity of the inflammatory process that depends on the presence of bacterial complications in influenza. The authors' findings correlate with the literature data on the blood mucolytic system status in various infectious diseases. The results recommend measurements of hyaluronidase and hyaluronic acid activities as an additional test for the early diagnosis of influenza complications.
Assuntos
Ácido Hialurônico/sangue , Hialuronoglucosaminidase/sangue , Influenza Humana/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Humanos , Vírus da Influenza A , Vírus da Influenza B , Influenza Humana/enzimologia , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The analysis of data collected from the clinical epidemiological and virological surveys in 1985-1988 on the incidence of arbovirus infection in population provided evidence for circulation of tick-borne encephalitis (TBE) virus in the Crimea. Etiological relevance of TBE virus in the onset of the diseases was revealed. Clinical picture of TBE in the Crimea is characterized by severe forms and diphasic fever with the relapse running more grave and protracted course.
Assuntos
Encefalite Transmitida por Carrapatos/diagnóstico , Reservatórios de Doenças , Encefalite Transmitida por Carrapatos/epidemiologia , Humanos , Federação Russa , Conglomerados Espaço-TemporaisAssuntos
Artrite Reumatoide/tratamento farmacológico , Portador Sadio/imunologia , Dexametasona/efeitos adversos , Infecções Oportunistas/etiologia , Febre Tifoide/etiologia , Dexametasona/uso terapêutico , Feminino , Humanos , Imunossupressores , Pessoa de Meia-Idade , Recidiva , Febre Tifoide/imunologiaAssuntos
Difteria/sangue , Histamina/sangue , Serotonina/sangue , Doença Aguda , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Structural changes caused by heating in the proteins of cured beef longissimus dorsi muscle were examined by fluorescence and differential scanning calorimetry. Denaturation occurred in four temperature ranges-40-55°C, 55-61°C, 62-70°C and above 70°C, in contrast to the three endothermic transitions reported for non-cured meats.