Liberação de óxido nítrico e tnf-α em macrófagos peritoneais na presença de Melampodium divaricatum (Asteraceae)

The immune responses are mediated by a variety cells and molecules that cells secreted. Macrophages are the first cells that participate in the immune response, and, when are activated, release more than hundred compounds at the extracelular medium, such as cytokine (TNF-α) and the intermediate compounds of the nitrogen (NO). In this paper the release of nitric oxide (NO) and necrose tumoral factor (TNF-α) were determined in peritoneal macrophage cultures of mice in the presence of the 70% ethanolic extract obtained from the flowers of the Melampodium divaricatum (Asteraceae) in the concentrations of 20, 10 and 5 mg/mL. The 70% ethanolic extracts from flowers of the Melampodium divaricatum presented higher liberation of NO and TNF-α in the concentration of the 20 mg/mL when compared with LPS. We conclude that this extract is a potente stimulator of macrophage, could be immunomodulatory activity.

Secretion of tumor necrosis factor-alpha by mouse peritoneal macrophages in the presence of dental sealers, sealapex and endomethasone

After filling root canals, the healing process depends on the chemical composition or physical-chemical properties of the material used, among other factors. All root canal sealers, whether solid or plastic, are foreign matter for the body if they remain in permanent contact with apical and periapical tissues. As a result, the first organic reaction that occurs is an attempt to phagocytize the material. During phagocytosis, macrophages release a large number of cell mediators into the area, among which are cytokines that are essential in intercellular communication and in many physiological and pathophysiological processes. One of these cytokines is tumor necrosis factor-alfa (TNF-α), which acts through links to specific receptors on the cell membrane initiating a cascade of events leading to induction, activation, or inhibition of numerous cytokine-regulated genes in the cell nucleus. The release of TNF-α in a cell culture of mouse peritoneal macrophages incubated with three concentrations (25, 50, and 100 mg/ml) of two endodontic sealers was measured. The solutions containing the calcium hydroxide-based root canal sealer (Sealapex) released fewer units of TNF-α than solutions containing the zinc oxide and eugenol-based sealer (Endomethasone).

Neutrophil migration induced by IL-1β depends upon LTB4 released by macrophages and upon TNF-α and IL-1β released by mast cells

In the present study, we investigate whether mast cells and macrophages are involved in the control of IL-1β-induced neutrophil migration, as well as the participation of chemotactic mediators. IL-1β induced a dose-dependent neutrophil migration to the peritoneal cavity of rats which depends on LTB 4, PAF and cytokines, since the animal treatment with inhibitors of these mediators (MK 886, PCA 4248 and dexamethasone respectively) inhibited IL-1β-induced neutrophil migration. The neutrophil migration induced by IL-1β is dependent on mast cells and macrophages, since depletion of mast cells reduced the process whereas the increase of macrophage population enhanced the migration. Moreover, mast cells or macrophages stimulated with IL-1β released a neutrophil chemotactic factor, which mimicked the neutrophil migration induced by IL-1β. The chemotactic activity of the supernatant of IL-1β-stimulated macrophages is due to the presence of LTB4, since MK 886 inhibited its release. Moreover, the chemotactic activity of IL-1β-stimulated mast cells supernatant is due to the presence of IL-1β and TNF-α, since antibodies against these cytokines inhibited its activity. Furthermore, significant amounts of these cytokines were detected in the supernatant. In conclusion, our results suggest that neutrophil migration induced by IL-1β depends upon LTB4 released by macrophages and upon IL-1β and TNFα released by mast cells. © 2007 Springer Science+Business Media, LLC.

Dornase alfa improves the health-related quality of life among Brazilian patients with cystic fibrosis - A one-year prospective study

Background: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. Patients and Methods: One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T 0), and at 3 (T 1), 6 (T 2), 9 (T 3), and 12 (T 4) months of follow-up. Eighteen patientswere excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis. Results: After 1 year of follow-up, there was significant improvement in respiratory symptoms (T 4-T 0=8.1; 95% confidence interval (95% CI)=[2.1;14.0]; effect size (ES)=0.35; P<0.001), Emotional Functioning (T 4-T 0=5.6; 95% CI=[1.1;10.1]; ES=0.31; P<0.05), Social Functioning (T 4-T 0=6.0; 95% CI=[1.3;11.7]; ES=0.31; P<0.05), Body Image (T 4-T 0=11.9; 95% CI=[4.1;19.7]; ES=0.42; P<0.05), and Treatment Burden (T 4-T 0=5.3; 95% CI=[0.3;10.3]; ES=0.24; P<0.05) domains in the younger group. A significant improvement in Role Functioning (T 4-T 0=6.1; 95% CI=[1.1;11.1]; ES=0.40; P<0.05), Body Image (T 4-T 0=12.6; 95% CI=[3.5;21.7]; ES=0.46; P<0.05), and Weight (T 4-T 0=11.7; 95% CI=[1.8;21.6]; ES=0.40; P<0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T 4-T 0=5.5; 95% CI=[1.5;9.4]; ES=0.30; P<0.05), Respiratory Symptoms (T 4-T 0=7.6; 95% CI=[3.9;11.4]; ES=0.48; P<0.05), and Weight (T 4-T 0=10.1; 95% CI=[1.6;18.6]; ES=0.26; P<0.05) domains. Conclusion: The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment. © 2010 Wiley-Liss, Inc.

Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

O papel das argininas alfa-92 e alfa-141 na regulação das propriedades funcionais de hemoglobinas por íons cloreto

The oxygenation of human Hb (HbA) demands a three state model: two deoxy states To and Tx, free and complexed with anions respectively, and an oxy R state. The regulation between these states is modulated by the presence of anions, such as chloride, that binds to T state. The b inding if chloride, however, remains controversial. The aim of this work is the study of arginines 92a (a1ß2 interface) and 141a (C-terminal) as chloride binding sites. To investigate that, we have studied 92 and 141 site directed mutant species: natural mutants Hb J-Cape-Town (R92Q), desArg (R141Δ), Chesapeake (R92L), and the constructed Chesapeake desArg (R92L,141Δ). We expressed Hbs in Escherichia coli and purified. Through oxygen binding curves we measured affinity and cooperativity, in function of water effect and Bohr effect in presence and absence of chloride. Structural features were obtained through 1H NMR spectroscopy Oxygen binding properties and Bohr effect measured indicated a higher affinity and lower cooperativity in absence and presence of chloride for all mutants. Structural changes represent functional aspects of mutant Hbs, such as a significant rise in affinity or a change in cooperativity. Water activity studies conducted as a function of chloride concentration showed that the only Hb desArg follows the thre state model. The other mutant Hbs do not exhibit the Tx state, a fact confirmed by the number of water molecules bound to each Hb during the deoxy-oxy transition. This behavior suggests that the Arginine 92 site could be responsible for chloride binding to Hb, since oxygenation of 92 mutant Hbs cannot be adjusted by the three state model. However, Bohr effect showed that all mutant Hbs released~1 proton in chloride presence, different from HbA that releases ~2, suggesting a role for 141 arginine in the tertiary and quaternary Bohr effect.

Participação da via alfa-2 adrenérgica no controle da secreção do hormônio do crescimento no período prépúbere em novilhas da raça Nelore

This study investigated GH secretion after clonidine (alpha-2 adrenergic agonist) treatment in pre-pubertal Nelore heifers. Clonidine (10 mg/kg, IV, 15 min samples for 4 h) was administrated in the same Nelore heifers at eight (n = 4), 12 (n = 5) and 15 (n = 4) months of age. The GH concentration was measured by radioimmunoassay (sensivity = 0.25 ng/mL, CV = 16%). At eight months, clonidine increased GH average concentration, total area of peaks, the total area of GH secretion and increased peak amplitude and reduced time to onset of peak (P < 0.05). At 15 months, the administration of clonidine increased the GH average concentration and at 12 months the increased occurred only in restricted intervals (P < 0.05). Clonidine injection stimulated GH secretion in prepubertal heifers and this effect was more evident in Nelore heifers at eight months compared to 12 and 15 months of age.

BI-ALFA, estrategias y aplicación de una propuesta para el desarrollo indígena

Incluye Bibliografía

Influence of TNF-α blockers on the oral prevalence of opportunistic microorganisms in ankylosing spondylitis patients

Objectives: To compare the oral prevalence and antimicrobial susceptibility of Candida spp., staphylococci, enterobacteriaceae, and pseudomonas spp.from ankylosing spondylitis (AS) patients receiving conventional and anti-TNF-α therapy. Methods: The study included 70 AS patients, diagnosed according to the modified New York criteria (1984). The volunteers were divided into 2 groups: a biological group (AS BioG) (n=35) (on anti-TNF-α therapy) and a conventional group (AS ConvG) (n=35). The control group (ContG) (n=70) was made up of healthy individuals matched for age, gender, and oral conditions. After clinical examination, oral rinse samples were collected and plated in specific culture media. The number of colony-forming units per milliliter (cfu/ml) was obtained, and isolates were identified using the API system. Antimicrobial susceptibility tests were performed according to the NCCLS guidelines. Prevalence and counts of microorganisms were statistically compared between the 3 groups, using the Mann-Whitney and Chi-square tests. Significance level was set at 5%. Results: In both the AS BioG and the AS ConvG, staphylococci counts were higher than that in the ContG (p<0.0001). Candida albicans and staphylococcus epidermidis were the most commonly found species in all the groups. Serratia marcescens and klebsiella oxytoca were more prevalent in the AS BioG and the AS ConvG, respectively. Two Candida isolates (2.8%) from the AS BioG and 5 (10.8%) from the AS ConvG were resistant to amphotericin B and 5-fluorocytosine. A low percentage of staphylococci isolates was resistant to amoxicillin, ciprofloxacin, and doxycycline. Conclusion: Higher counts of staphylococci were observed in both AS groups, regardless of the current therapy, age, sex, and oral conditions. Anti-TNF-α therapy could not be correlated with increased counts of microorganisms. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2012.

Induction or exacerbation of psoriatic lesions during anti-TNF-α therapy for inflammatory bowel disease: A systematic literature review based on 222 cases

Background: Paradoxical cases of psoriatic lesions induced or exacerbated by anti-tumor necrosis factor (TNF)-α therapy have been reported more frequently in recent years, but data related to inflammatory bowel disease (IBD) are rare. A systematic literature review was performed to provide information about this adverse effect in patients with IBD who receive anti-TNF therapy. Methods: Published studies were identified by a search of Medline, Embase, Cochrane, SciELO, and LILACS databases. Results: A total of 47 studies (222 patients) fulfilled the inclusion criteria and were selected for analysis. Clinical and therapeutic aspects varied considerably among these reports. Of the 222 patients, 78.38% were diagnosed with Crohn's disease, and 48.20% were female. The mean patient age was 26.50. years, and 70.72% of patients had no history of psoriasis. Patients developed psoriasiform lesions (55.86%) more often than other types of psoriatic lesions, and infliximab was the anti-TNF-α therapy that caused the cutaneous reaction in most patients (69.37%). Complete remission of cutaneous lesions was observed in 63.96% of the cases. Conclusions: We found that psoriatic lesions occurred predominantly in adult patients with Crohn's disease who received infliximab and had no previous history of psoriasis. Most patients can be managed conservatively without discontinuing anti-TNF-α therapy. © 2012 European Crohn's and Colitis Organisation.

Photoprotective and antioxidant effects of Rhubarb: Inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes

Background: Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes.Methods: The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method.Results: Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation.Conclusions: These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage. © 2013 Silveira et al; licensee BioMed Central Ltd.

IL-4 and IL-13 inhibit IL-1β and TNF-α induced kinin B 1 and B2 receptors through a STAT6-dependent mechanism

Background and Purpose Bone resorption induced by interleukin-1β (IL-1β) and tumour necrosis factor (TNF-α) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation-induced bone resorption can be impaired by IL-4 and IL-13. The aim was to investigate if expression of B1 and B2 kinin receptors can be affected by IL-4 and IL-13. Experimental Approach We examined effects in a human osteoblastic cell line (MG-63), primary human gingival fibroblasts and mouse bones by IL-4 and IL-13 on mRNA and protein expression of the B1 and B2 kinin receptors. We also examined the role of STAT6 by RNA interference and using Stat6-/- mice. Key Results IL-4 and IL-13 decreased the mRNA expression of B1 and B2 kinin receptors induced by either IL-1β or TNF-α in MG-63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. The burst of intracellular calcium induced by either bradykinin (B2 agonist) or des-Arg10-Lys-bradykinin (B1 agonist) in gingival fibroblasts pretreated with IL-1β was impaired by IL-4. Similarly, the increased binding of B1 and B2 ligands induced by IL-1β was decreased by IL-4. In calvarial bones from Stat6-deficient mice, and in fibroblasts in which STAT6 was knocked down by siRNA, the effect of IL-4 was decreased. Conclusions and Implications These data show, for the first time, that IL-4 and IL-13 decrease kinin receptors in a STAT6-dependent mechanism, which can be one important mechanism by which these cytokines exert their anti-inflammatory effects and impair bone resorption. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

Atividade mutagênica e ativadora da resposta imune celular induzidas por Byrsonima crassa Niedenzu e Byrsonima intermedia A.Juss. (Malpighiaceae)

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Efeito de treinamentos resistidos sobre marcadores inflamatórios, força e massa magra corporal de pacientes com doença pulmonar obstrutiva crônica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da silibinina sobre o metabolismo oxidativo e produção de citocinas por monócitos em gestantes portadores de pré-eclâmpsia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)