146 resultados para interleukin 12 receptor
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Este trabalho objetivou caracterizar um sistema de solos, evidenciando a propriedades que possam esclarecer sua dinâmica e contribuir para a definição de critérios que condicionem a aptidão destes solos como receptores de efluentes. Trata-se de uma área experimental de estudos, contígua à Estação de Tratamento de Esgoto do município de Lins (SP), onde o efluente é gerado a partir do tratamento de esgoto por sistema de lagoas de estabilização. Os solos, situados ao longo de uma vertente com ligeira inclinação, foram caracterizados por meio de análises, morfológica, granulométrica, química, mineralógica e micromorfológica, realizadas em amostras coletadas em cinco trincheiras em toposseqüência. Os solos são desenvolvidos a partir dos sedimentos arenosos da Formação Adamantina (Grupo Bauru) e constituem um sistema Latossolo - Argissolo onde a transição Bw - Bt ocorre lateralmente do topo para a base da vertente. Foram identificadas três fases pedogenéticas nesta associação de solos. A primeira, argiluviação e adensamento de partículas, responsável pela formação dos horizontes texturais, foi superposta pelos processos de latossolização e hidromorfismo, atuantes na dinâmica atual destes solos. Análises micromorfológicas mostraram tratar-se de solos com intensa porosidade, caracterizada pelo empilhamento dos grãos do esqueleto quartzoso amplamente predominante e pelo arranjo entre os microagregados granulares. A permeabilidade é ainda favorecida pela intensa ação da mesofauna. Os solos são distróficos e compostos por caulinita e óxidos de Fe na fração argilosa. Por constituírem um sistema frágil, a disposição de quaisquer tipos de resíduos nestes solos requer o monitoramento constante de suas propriedades, tanto para a manutenção, quanto para a recuperação da qualidade desta cobertura pedológica.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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1. The effect of endotoxin, interleukin-1 beta and prostaglandin on fever response was studied in 80 broilers (Hubbard strain). Endotoxin (E. coli, LPS) was injected iv (1.5 mu g/kg) and icv (1.5 mu g/bird); interleukin-1 (human recombinant IL-1 beta, 80 pg/bird) and prostaglandin E(2) (5 mu g/bird) were injected icv. Indomethacin (10 mg/kg, iv) pretreatment was also used before iv endotoxin injection. 2. The results showed that indomethacin was able to block the fever response induced by iv endotoxin injection, and IL-1 beta and PGE(2) were both effective in producing fever when injected icv. These data suggest a prostaglandin-mediated fever response by broilers, and also a strong evidence of the involvement of endogenous pyrogen (interleukin-1) in fever response in birds.
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The rat tail artery has been used for the study of vasoconstriction mediated by alpha(1A)-adrenoceptors (ARs). However, rings from proximal segments of the tail artery (within the initial 4 cm, PRTA) were at least 3- fold more sensitive to methoxamine and phenylephrine (n = 6 - 12; p < 0.05) than rings from distal parts (between the sixth and 10th cm, DRTA). Interestingly, the imidazolines N-[ 5-( 4,5- dihydro- 1H- imidazol-2-yl)-2-hydroxy-5,6,7,8- tetrahydronaphthalen- 1- yl] methanesulfonamide hydrobromide (A-61603) and oxymetazoline, which activate selectively alpha(1A)- ARs, were equipotent in PRTA and DRTA (n = 4 - 12), whereas buspirone, which activates selectively alpha(1D)-AR, was approximate to 70-fold more potent in PRTA than in DRTA (n = 8; p < 0.05). The selective alpha(1D)-AR antagonist 8-[2-[4-(methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9-dione dihydrochloride (BMY- 7378) was approximate to 70- fold more potent against the contractions induced by phenylephrine in PRTA (pK(B) of approximate to 8.45; n = 6) than in DRTA (pK B of approximate to 6.58; n = 6), although the antagonism was complex in PRTA. 5-Methylurapidil, a selective alpha(1A)-antagonist, was equipotent in PRTA and DRTA (pK(B) of approximate to 8.4), but the Schild slope in DRTA was 0.73 +/- 0.05 ( n = 5). The noncompetitive alpha(1B)-antagonist conotoxin rho-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for alpha(1A)-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of alpha(1D)-ARs in PRTA and alpha(1B)-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding alpha(1A)- and alpha(1B)-ARs are similarly distributed in PRTA and DRTA, whereas mRNA for alpha(1D)-ARs is twice more abundant in PRTA. Therefore, alpha(1)-ARs subtypes are differentially distributed along the tail artery. It is important to consider the segment from which the tissue preparation is taken to avoid misinterpretations on receptor mechanisms and drug selectivities. antagonism was complex in PRTA. 5- Methylurapidil, a selective alpha(1A)-antagonist, was equipotent in PRTA and DRTA (pK(B) of approximate to 8.4), but the Schild slope in DRTA was 0.73 +/- 0.05 ( n = 5). The noncompetitive alpha(1B)-antagonist conotoxin rho-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not in PRTA. These results indicate a predominant role for alpha(1A)-ARs in the contractions of both PRTA and DRTA but with significant coparticipations of alpha(1D)-ARs in PRTA and alpha(1B)-ARs in DRTA. Semiquantitative reverse transcription-polymerase chain reaction revealed that mRNA encoding alpha(1A)- and alpha(1B)- ARs are similarly distributed in PRTA and DRTA, whereas mRNA for alpha(1D)-ARs is twice more abundant in PRTA. Therefore, alpha(1)-ARs subtypes are differentially distributed along the tail artery. It is important to consider the segment from which the tissue preparation is taken to avoid misinterpretations on receptor mechanisms and drug selectivities.
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The presence of tyrosine-phosphorylated proteins was studied in cultured rat pancreatic islets, Immunoblotting performed with total extracts of islets cultured in the presence of 1.8 or 5.6 mM glucose revealed at least three distinct tyrosine-phosphorylated bands (25 kDa, 95 kDa and 165-185 kDa). After 12 h incubation in medium containing 1.8 mM glucose, a pulse exposition to 11 or 22 mM glucose or to 10(-7) M insulin led to a substantial increase in the phosphorylation of all three bands, with no appearance of novel bands. Immunoprecipitation with specific antibodies demonstrated that the signal detected at 95 kDa corresponds to the beta subunit of the insulin receptor (IR) while the band at 165-185 kDa corresponds to the early substrates of the insulin receptor, IRS-1 and IRS-2. Immunoprecipitation with IRS-I or IRS-2 antisera detected their association with the lipid metabolizing enzyme phosphatidylinositol 3-kinase (PI 3-kinase), Thus, this is the first demonstration that elements involved in the insulin-signalling pathway of traditional target tissues are also present in pancreatic islets and are potentially involved in auto- and paracrine-signalling in this organ.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PAR2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR2 activation may participate in periodontal disease in vivo. We investigated the role of PAR2 activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR2 agonist causes periodontitis but also exacerbates existing periodontitis, leading to significant alveolar bone loss and gingival granulocyte infiltration. Inhibition of matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) decreased PAR2 agonist-induced periodontitis. More specifically, the overexpression of COX-1, COX-2, MMP-2, and MMP-9 in gingival tissues suggests that they are involved in PAR 2-induced periodontitis. In conclusion, PAR2 agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR2 may represent a novel approach to modulate host response in periodontitis.
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Single nucleotide polymorphisms in the promoter region of the human interleukin (IL)-2 (T-330G) and IL-6 (G-174C) genes have modified the transcriptional activity of these cytokines and are associated with several diseases. The aim of this study was to investigate the possible relationship between these single nucleotide polymorphisms and early implant failure. A sample of 74 nonsmokers was divided into 2 groups: test group comprising 34 patients (mean age 49.3 years) with ĝ‰¥1 implants that failed and control group consisting of 40 patients (mean age 43.8 years) with ĝ‰¥1 healthy implants. Genomic deoxyribonucleic acid from oral mucosa was amplified by polymerase chain reaction and analyzed by restriction fragment length polymorphism. Monte Carlo simulations (P < 0.05) were used to assess differences in allele and genotypes frequencies of the single nucleotide polymorphisms between the 2 groups. No significant differences were observed in the allele and genotypes distribution of both polymorphisms when the 2 groups were compared. The results indicate that polymorphisms in the IL-2 (T-330G) and IL-6 (G-174C) genes are not associated with early implant failure, suggesting that the presence of those single nucleotide polymorphisms does not constitute a genetic risk factor for implant loss in the studied population. Copyright © 2005 by Lippincott Williams & Wilkins.
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Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.Methods/design: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.Discussion: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number: ClinicalTrials.gov: NCT00971165. © 2011 Fuchs et al; licensee BioMed Central Ltd.
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Aim. This study aimed to observe the morphological and molecular effect of laminin-1 doping to nanostructured implant surfaces in a rabbit model. Materials and Methods. Nanostructured implants were coated with laminin-1 (test; dilution, 100 g/mL) and inserted into the rabbit tibiae. Noncoated implants were used as controls. After 2 weeks of healing, the implants were removed and subjected to morphological analysis using scanning electron microscopy (SEM) and gene expression analysis using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results. SEM revealed bony tissue attachment for both control and test implants. Real-time RT-PCR analysis showed that the expression of osteoblast markers RUNX-2, osteocalcin, alkaline phosphatase, and collagen I was higher (1.62-fold, 1.53-fold, 1.97-fold, and 1.04-fold, resp.) for the implants modified by laminin-1 relative to the control. All osteoclast markers investigated in the study presented higher expression on the test implants than controls as follows: tartrate-resistant acid phosphatase (1.67-fold), calcitonin receptor (1.35-fold), and ATPase (1.25-fold). The test implants demonstrated higher expression of inflammatory markers interleukin-10 (1.53-fold) and tumour necrosis factor-α (1.61-fold) relative to controls. Conclusion. The protein-doped surface showed higher gene expression of typical genes involved in the osseointegration cascade than the control surface. © 2012 Humberto Osvaldo Schwartz-Filho et al.
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Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci). The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs), HLA-DR, and CD80. Cytokine production (TNF-α and IL-10) and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF-α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF-α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities. © 2013 Bruno José Conti et al.
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The association of genetic polymorphism in the estrogen receptor alpha (ERα) gene and risk for diseases including breast cancer (BC) has been the subject of great interest. Objective: Checking on women with high breast density after menopause, the frequency of the Pvull and Xbal polymorphisms of the ERα gene and the correlation between them and the known risk factors for breast cancer. Method: Observational study with 308 women between 45 and 65 years old with high breast density, without hormonal therapy, menstruation for a year or more, breast and ovarian cancer history. It was characterized in clinical history and physical examination: menarche, menopause, parity, family history of BC, smoking, alcohol intake and body mass index. Results: The allelic and genotypic frequencies for ERα-Pvull and Xbal: p=43.99%; p=56.01%; pp=32.14%; Pp=47.73% and PP=20.13%; X=41.56%; x=58.44%; xx=33.44%; Xx=50.00% and XX=16.56%, respectively. The most frequent risk factors for BC: menarche before 12 years old (35.38%), nulliparity or first child after 28 years old (41.66%), family history of BC (19.16%) and overweight/obesity (62.01%). Conclusion: Allelic and genotypic distribution similar to literature. The risk factors for BC were more prevalent in women with high breast density but without significant associations with these polymorphisms. © 2013 Informa UK Ltd. All rights reserved.
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Exposure to environmental chemicals may contribute to reproductive disorders, especially when it occurs in critical periods of development. The female reproductive system can be a target for androgens derived from environmental contaminants or pathological conditions. The purpose of this study was to assess the long-term effects of androgens on uterine tissue after maternal exposure limited to the time of gestation and lactation. Pregnant Wistar rats were treated with testosterone propionate (TP) at 0.05. mg/kg, 0.1. mg/kg, 0.2. mg/kg or corn oil (vehicle), s.c., from gestational day 12 until the end of lactation. The results show changes in the pattern of expression of receptors for estrogen, progesterone, and androgen at all doses tested, and decreases in both apoptosis and cell proliferation indices at 0.1 and 0.2. mg/kg. We conclude that early TP exposure, under these experimental conditions, causes changes in cellular and molecular parameters that are essential for normal uterine function in the adult. © 2013 Elsevier Inc.