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The successful establishment of HIV-1 infection is related to inflammasome blocking or inactivation, which can result in the viral evasion of the immune responses and formation of reservoirs in several tissues. In this sense, we aimed to evaluate the viral and cellular mechanisms activated during HIV-1 infection in human primary macrophages that allow an effective viral replication in these cells. We found that resting HIV-1-infected macrophages, but not those activated in classical or alternative patterns, released IL-1β and other pro-inflammatory cytokines, and showed increased CXCL10 expression, without changes in the NLRP3, AIM2 or RIG-I inflammasome pathways. Also, similar levels of Casp-1, phosphorylated NF-κB (p65) and NLRP3 proteins were found in uninfected and HIV-1-infected macrophages. Likewise, no alterations were detected in ASC specks released in the culture supernatant after HIV-1 infection, suggesting that macrophages remain viable after infection. Using in silico prediction studies, we found that the HIV-1 proteins Gag and Vpr interact with several host proteins. Comparable levels of trans-LTB4 were found in the supernatants of uninfected and HIV-1-infected macrophages, whereas ROS production was impaired in infected cells, which was not reversed after the PMA stimulus. Immunofluorescence analysis showed structural alterations in the mitochondrial architecture and an increase of BIM in the cytoplasm of infected cells. Our data suggest that HIV-1 proteins Gag and Vpr, through interacting with cellular proteins in the early steps of infection, preclude the inflammasome activation and the development of effective immune responses, thus allowing the establishment of the infection.

The pilocarpine-induced (PILO) model has helped elucidate the electrophysiological and molecular aspects related to mesial temporal lobe epilepsy. It has been suggested that the extensive cell death and edema observed in the brains of these animals could be induced by increased inflammatory responses, such as the rapid release of the inflammatory cytokine interleukin 1 beta (Il1b). In this study, we investigate the role of endogenous Il1b in the acute phase of the PILO model. Our aim is twofold. First, we want to determine whether it is feasible to silence Il1b in the central nervous system using a non-invasive procedure. Second, we aim to investigate the effect of silencing endogenous Il1b and its antagonist, Il1rn.We used RNA interference applied non-invasively to knockdown Il1b and its endogenous antagonist Il1rn. We found that knocking down Il1b prior to pilocarpine injection increased the mortality rate of treated animals. Furthermore, we observed that, when exposing the animals to more Il1b by silencing its endogenous antagonist Il1rn, there was a better response to status epilepticus with decreased animal mortality in the acute phase of the PILO model. Thus, we show the feasibility of using a novel, less invasive approach to study genes involved in the inflammatory response in the central nervous system. Furthermore, our results provide suggestive evidence that modulating endogenous Il1b improves animal survival in the acute phase of the PILO model and may have effects that extend into the chronic phase.

Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.

Salmonella Heidelberg is a clinically-important serovar linked to food-borne illness, and commonly isolated from poultry products. Since 1962, Salmonella Heidelberg has been widely reported from poultry production systems in several countries, including Brazil. The emergence of multidrug-resistant (MDR) Salmonella Heidelberg strains in food animals underscores a significant food safety hazard. In our study, we performed antimicrobial susceptibility testing (AST) and Whole-genome sequencing (WGS) to identify the antimicrobial resistance (AMR) genes, pathogenicity mechanisms and virulence factors (VF) in Salmonella Heidelberg E2 strain recovered from a chicken carcass in Southern Brazil. Salmonella Heidelberg strain belonged to ST15 and showed to be susceptible to colistin (MIC ≤2 μg/mL) and multidrug-resistant to amoxicillin-clavulanic acid, gentamicin, ampicillin, cefaclor, cefazolin, ceftiofur, nalidixic acid, azithromycin, erythromycin, doxycycline, tetracycline and sulfonamide. We identified AMR genes mediating resistance to aminoglycosides (aac(6')-Iaa, aac(3)-VIa, aph(3')-Ia, aadA, 16S rrsD), β-lactams (blaCTX-M-2), quinolones (parC), macrolides (acrB), tetracyclines (tet(A)), fosfomycin (fosA7) and sulfonamide (sul1). Interestingly, the mutation in parC T255S has never been reported among Salmonella Heidelberg strains. To our knowledge, this is the first report of a Salmonella enterica strain harbouring 16S rrsD 471G A, acrB F28L and acrB L40P chromosomal point mutations. Three plasmid replicon types, ST2-IncHI2, ST2-IncHI2A and IncX1 were identified. Nine Salmonella Pathogenicity Islands and 98 virulence genes encoding virulence factors were identified associated with cell adhesion, invasion, intracellular survival and resistance to antimicrobial peptides. Although Salmonella Heidelberg E2 strain likely originated from poultry, cross-contamination during meat processing cannot be excluded. This study adds to our understanding of Salmonella Heidelberg transmission along the food-chain and informs ongoing regulatory discussions on Salmonella Heidelberg in poultry.

Background: Osteoarthritis (OA) is a progressive and multifactorial disease that is associated with aging. A number of changes occur in aged cartilage, such as increased oxidative stress, decreased markers of healthy cartilage, and alterations in the autophagy pathway. Propolis extracts contain a mixture of polyphenols and it has been proved that they have high antioxidant capacity and could regulate the autophagic pathway. Our objective was to evaluate the effect of ethanolic extract of propolis (EEP) on chondrocytes that were stimulated with IL-1&beta, Methods: Rabbit chondrocytes were isolated and stimulated with IL-1&beta, and treated with EEP. We evaluated cell viability, nitric oxide production, healthy cartilage, and OA markers, and the expression of three proteins associated with the autophagy pathway LC3, ATG5, and AKT1. Results: The EEP treatment reduces the expression of LC3, ATG5, and AKT1, reduces the production of nitric oxide, increases the expression of healthy markers, and reduces OA markers. Conclusions: These results suggest that treatment with EEP in chondrocytes that were stimulated with IL-1&beta, has beneficial effects, such as a decrease in the expression of proteins associated with autophagy, MMP13, and production of nitric oxide, and also increased collagen II.

Aim This double-blind, placebo-controlled clinical study compared multiple applications of the antimicrobial photodynamic therapy (aPDT) treatment protocol, to systemic doxycycline as adjuvant to scaling and root planing (SRP) on type 2 diabetic patients on clinical, systemic and immune-inflammatory outcomes. Materials and Methods Thirty patients with Hba1c >7% were allocated in two groups, SRP + Doxy (n = 15) using systemic doxycycline 100 mg/day (14 days) and SRP + aPDT (n = 15) with multiple applications (0, 3, 7 and 14 days). Primary outcome was glycated haemoglobin levels (HbA1c). Clinical parameters: plaque score (PS), bleeding on probe, probing depth, suppuration, gingival recession, and clinical attachment level, percentage of pockets with desired clinical endpoint were measured at baseline and 3 months after therapy. Cytokine profile was assessed at 0, 1 and 3 month to measure IL1-β, TNF-α and TGF-β on gingival crevicular fluid. Results No significant difference was detected on HbA1c, between treatments. The SRP + aPDT group showed advantage on reducing moderate pockets in single-rooted teeth at 3 months. SRP + aPDT presented better results at 3 months on IL1-β levels. There were no significant differences between TNF-α and TGF-β. Conclusions Both treatments improved clinical and systemic outcomes (Hba1c). SRP + aPDT performed better in moderate probing pocket depth on single-rooted teeth, reduced favourably inflammation in short term, and may be an alternative to systemic antibiotics. (Clinicaltrials.org ID NCT01595594).

Interleukin-1 beta (IL-1β) is a cytokine linking the neuroendocrine system and metabolic homeostasis. We have previously demonstrated the relevance of IL-1β for maintaining the pituitary ACTH-producing cells by immuno-blocking its effects in pituitary cultures. However, the morphological characteristics and the intimate relationship of the pituitary cells expressing IL-1β and ACTH remain unknown. For determining pituitary variations of immunoreactivity for IL-1β and its relation with ACTH-positive cells under stress situations, we performed an immunohistochemical analysis of the expression of IL-1β and ACTH in the pituitary gland of adult rats, in the absence or presence of corticosterone, by establishing different groups: untreated, sham-operated, and bilaterally adrenalectomized animals. In the rats subjected to surgery, the glucocorticoid was administered on the same day of the intervention and on the third day post-surgery. Interestingly, it was observed that IL-1β was located in the pituitary endothelial cells at the hypophyseal portal vessels, regardless of the treatment schedule. When comparing the pituitary immunoreactive surface to IL-1β expression without corticosterone, adrenalectomized animals displayed a significantly greater area than the sham-operated animals. Corticosterone significantly inhibited the effect of adrenalectomy depending on the time interval it was administered. By in situ hybridization, IL-1β mRNA expression was also correlated with immnunocytochemical expression of pituitary IL-1β. Our results demonstrate that IL-1β is a constitutive element in endothelial portal pituitary vessels and under stress experimental conditions IL-1β increases its expression and its relation with ACTH-positive cells, suggesting that IL-1β could participate in an autocrine-paracrine fashion thereby modulating the pituitary population of ACTH-positive cells.

Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries., Author summary Human paracoccidioidomycosis (PCM) represents a serious public health issue due to its disabling sequelae in working-age people and mortality rates (8th among chronic infectious parasitic diseases in endemic countries and first among mycoses in Brazil). Although antifungal drugs have been widely used and provide clinical improvement for patients, the long duration of treatments (commonly from 6 to 12 months) has contributed to non-compliance and worsening of the disease in many cases. Induction of protective immune responses (either prophylactic or immune-therapeutic) remains the most cost-effective approach against most infectious agents. Members of our group have previously reported the protective properties of P10, a peptide contained in Paracoccidioides brasiliensis gp43 antigen, against PCM. However, the magnitude of the CD4+ T-cell responses elicited lacked the capacity of completely protecting experimental animals. We demonstrate here that immunogenic virus-like particles (VLP) carrying multiple copies of P10 peptide substantially improve P10-related cellular immunity in mice. This was particularly true when an adenoviral immunization vector expressed the chimeric VLP. Moreover, VLP/P10 formulations were capable of controlling the host fungal burden and prevented fungal systemic dissemination. The efficacy of diverse VLP/P10 formulations in murine PCM showed at least one promising candidate vaccine against human PCM.

Objectives: This study aimed to evaluate the frequency of the different alleles of the VNTR IL1RN gene (86 by RP, intron 2), in a Portuguese Caucasian population with implant supported overdentures.Methods: Fifty-eight Caucasians rehabilitated with implant overdentures for at least 6 months, were randomly recruited from the Removable Prostheses Forms used in Faculty of Dental Medicine, University of Porto. After clinical examination, DNA was obtained through oral mucosa swab. PCR was used to identify the IL1RN gene alleles. The frequency estimates and the corresponding 95% CI for alleles and genotypes of the IL1RN gene were calculated using the exact binomial test.Results: The population included 44 females and 14 males. Only 2 subjects were smokers; 6 subjects had diabetes and 5 had chronic gastritis. The most frequent allele of IL1RN gene was allele 5, with an estimated frequency of 58.6%, followed by the allele 4 with a frequency of 48.3%. The alleles 1 and 2 were not detected. The most frequent genotype was allele 5/allele 5, followed by the allele 4/allele 4.Conclusions: Allele 5 was the most frequent IL1RN allele and allele 5/allele 5 was the most frequent genotype. Further studies are required in order to understand the role of alleles 5 and 4, as well as of the allelic combinations of the IL1RN gene polymorphism, on the development of biological complications with dental implants. (C) 2015 Sociedade Portuguesa de Estomatologia e Medicina Dentaria., info:eu-repo/semantics/publishedVersion

Journal Article; Review; Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium. Yes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Pecuaria e Abastecimento Instituto Nacional de Ciencia e Tecnologia de Vacinas Pathogens are detected by innate immune receptors that, upon activation, orchestrate an appropriate immune response. Recent studies revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella abortus infection. However, no report has elucidated the role of inflammasome receptors in Brucella recognition. Therefore, we decided to investigate the function of NLRC4, NLRP3, and AIM2 in sensing Brucella. in this study, we showed that NLRC4 is not required to induce caspase-1 activation and further secretion of IL-1 beta by B. abortus in macrophages. in contrast, we determined that AIM2, which senses Brucella DNA, and NLRP3 are partially required for caspase-1 activation and IL-1 beta secretion. Additionally, mitochondrial reactive oxygen species induced by Brucella were implicated in IL-1 beta production. Furthermore, AIM2, NLRP3, ASC, and caspase-1 knockout mice were more susceptible to B. abortus infection than were wild-type animals, suggesting that multiple ASC-dependent inflammasomes contribute to host protection against infection. This protective effect is due to the inflammatory response caused by IL-1 beta and IL-18 rather than pyroptosis, because we observed augmented bacterial burden in IL-1R and IL-18 knockout mice. Finally, we determined that bacterial type IV secretion system VirB and live, but not heat-killed, Brucella are required for full inflammasome activation in macrophages during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes that collectively orchestrate a robust caspase-1 activation and proinflammatory response. the Journal of Immunology, 2013, 190: 3629-3638. Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil Universidade Federal de São Paulo, Ctr Mol & Cellular Therapy, Dept Biol Sci, BR-04044010 São Paulo, Brazil Univ São Paulo, Sch Med Ribeirao Preto São Paulo, Dept Cell Biol, BR-14049900 Ribeirao Preto, Brazil Universidade Federal de São Paulo, Ctr Mol & Cellular Therapy, Dept Biol Sci, BR-04044010 São Paulo, Brazil Web of Science

In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ., Author Summary Ocular toxoplasmosis (OT), due to protozoan parasite Toxoplasma gondii, is a potential complication of both acquired and congenital infection, leading to visual impairment in numerous countries and being responsible for 30 to 50% of uveitis cases in immunocompetent individuals. In this study we confirmed the presence of more severe ocular toxoplasmosis in a tropical setting of Colombia, when compared to France. The main hypothesis for these clinical differences is based on the idea that severe disease in humans may result from poor host adaptation to neotropical zoonotic strains of T. gondii Indeed, our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the intraocular protective immune response.

The compound (5Z)-5-[(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione (LYSO-7) was synthesised in order to obtain a new type of anti-inflammatory drug, designed with hybrid features to inhibit cyclooxygenase (COX) and also to activate peroxisome proliferator-activated receptor (PPAR). Results obtained from docking (in silico) studies corroborated with experimental data, showing the potential affinity between the studied ligand and targets. The specificity of LYSO-7 for COX-enzymes was detected by the inhibition of COX-1 and COX-2 activities by 30% and 20%, respectively. In transactivation reporter gene assays LYSO-07 showed a pan partial agonist effect on the three PPAR subtypes (PPARγ, PPARα and PPARβ/δ). The agonist action on PPARγ was also observed by a pharmacological approach, as the reduction in the Escherichia coli lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1β) secretion and nitric oxide (NO) production by mouse neutrophils was blocked by GW9962, a specific PPARγ antagonist. Additionally, the in vivo effect was measured by reduced carrageenan-induced neutrophil influx into the subcutaneous tissue of mice. Taken together, these data show that LYSO-7 displays a potent in vivo anti-inflammatory effect during the innate acute response, which is dependent on its associated COX inhibitory activities and PPAR activation.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-07T14:55:48Z No. of bitstreams: 1 Magali Silveira Monteiro Ribeiro.pdf: 1146196 bytes, checksum: af6e9544b3c61c929f61136151e546dd (MD5) Made available in DSpace on 2021-01-07T14:55:48Z (GMT). No. of bitstreams: 1 Magali Silveira Monteiro Ribeiro.pdf: 1146196 bytes, checksum: af6e9544b3c61c929f61136151e546dd (MD5) Previous issue date: 2009-04-27 Periodontitis is a chronic inflammatory disease of bacterial origin mediated by cytokines, especially interleukin 1 (IL1) and tumor necrosis factor (TNFα). Genetic polymorphisms of IL1 and TNFα have been associated with expression variation of these proteins, what could justify interindividual differences in the disease forms. The aim of this study was to investigate possible associations between IL1B, IL1RN and TNFA genes and the susceptibility to aggressive periodontitis and severe chronic periodontitis. We selected 145 patients from Rio de Janeiro state, 43 with aggressive periodontitis (PAgr) (33.1 ± 4.8 years old), 52 with severe chronic periodontitis (PCr) (50.6 ± 5.8 years old), and 50 controls (40.1 ± 7.8 years old). Genomic DNAs of patients of PAgr, PCr and control groups were obtained through the collection of oral epithelial cells scraped from the inside cheek with a swab. The SNPs IL1B -511C>(pT, and TNFA -1031T>C were analyzed by PCR-RFLP technique using the restriction enzymes Ava I, Taq I and Bpi I, respectively. The polymorphism of variable number of tandem repeats (VNTR) in intron2 of the IL1RN gene was done by direct analysis of amplicons. All polymorphisms were analyzed by 8% polyacrylamide gel electrophoresis. Allelic and genotypic frequencies of the IL1B +3954C>T polymorphism in the PCr group were significantly different as compared to those observed in the control group (p=0.003 and p=0.041, respectively). The frequency of A2 allele of IL1RN intron 2 VNTR polymorphism in the PAgr group was significantly higher than in the control group (p=0.035). There was no association between the polymorphisms IL1B -511C>T and TNFA -1031T>C and aggressive and chronic periodontitis. The presence of alleles 2 in combined genotypes of IL1RN intron 2VNTR and IL1B +3954 C>T in the PCr group was significantly higher as compared to the control group (p=0.045). However no associations between the genotypic combinations IL1B -511C>T IL1B +3954C>T and IL1RN VNTR / IL1B -511C>T and predisposition to periodontal disease were observed. According to our results one can suggest that for the studied population the IL1B +3954C>T polymorphism interferes in the development of chronic periodontitis, whereas the presence of the A2 allele of IL1RN intron 2 VNTR polymorphism may be considered as an indicator of risk for aggressive periodontitis. The present study also allows us to suggest that the absence of homozygous for alleles 1 in the combined genotypes of IL1RN intron 2 VNTR and IL1B +3954C>T may increase the susceptibility to severe chronic periodontitis. A periodontite é um processo inflamatório crônico de origem bacteriana mediado por citocinas, em especial, interleucina-1 (IL1) e fator de necrose tumoral (TNFα). Polimorfismos genéticos de IL1 e TNFA têm sido associados com a variação de expressão dessas proteínas, o que poderia justificar as diferenças interindividuais de manifestação da doença. O objetivo do presente estudo foi investigar possíveis associações entre os genes IL1B, IL1RN e TNFA e a suscetibilidade à periodontite agressiva e à periodontite crônica severa. Foram selecionados 145 pacientes do Estado do Rio de Janeiro, 43 com periodontite agressiva (PAgr) (33,1 ± 4,8 anos), 52 com periodontite crônica severa (PCr) (50,6 ± 5,8 anos) e 50 controles (40,1 ± 7,8 anos). Os DNAs genômicos dos integrantes dos grupos PAgr, PCr e controle foram obtidos através da coleta de células epiteliais bucais raspadas da parte interna da bochecha com cotonete. Os SNPs IL1B -511C>T, IL1B +3954C>T e TNFA -1031T>C foram analisados pela técnica de PCR-RFLP, utilizando as enzimas de restrição Ava I Taq I e Bpi I, respectivamente. O polimorfismo de número variável de repetições in tandem (VNTR) no intron 2 do gene IL1RN foi feita pela análise direta dos amplicons. Todos os polimorfismos foram analisados por eletroforese em gel de poliacrilamida 8%. As frequências alélica e genotípica do polimorfismo IL1B +3954C>T no grupo PCr foram significativamente diferentes das observadas no grupo controle (p=0,003 e p=0,041, respectivamente). A freqüência do alelo A2 do polimorfismo IL1RN VNTR intron2 no grupo PAgr foi significativamente maior do que no grupo controle (p=0,035). Não houve associação entre os polimorfismos IL1B -511C>T e TNFA -1031T>C e as periodontites agressiva e crônica. A presença dos alelos 2 nos genótipos combinados de IL1RN VNTR intron2 e IL1B +3954C>T no grupo PCr foi significativamente maior quando comparada ao grupo controle (p=0,045). Entretanto, não se observou associação entre as combinações genotípicas IL1B -511C>T / IL1B +3954C>T e IL1RN VNTR / IL1B -511C>T e a predisposição à doença periodontal. De acordo com os nossos resultados podemos sugerir que, para a população estudada, o polimorfismo IL1B +3954C>T interfere no desenvolvimento da periodontite crônica, enquanto a presença do alelo A2 do polimorfismo IL1RN VNTR intron2 pode ser considerado como indicador de risco para a periodontite agressiva. O presente estudo também nos permite sugerir que a ausência de homozigose dos alelos 1 nos genótipos combinados de IL1RN VNTR intron2 e IL1B +3954C>T pode representar maior suscetibilidade à periodontite crônica severa.

Made available in DSpace on 2014-06-11T19:28:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-03-27Bitstream added on 2014-06-13T19:36:30Z : No. of bitstreams: 1 melo_rf_me_arafo.pdf: 805451 bytes, checksum: 73a6301db4198e271a504deca1228bda (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Universidade Estadual Paulista (UNESP) O objetivo deste estudo foi avaliar a concentração de interleucina-1 ß (IL-1ß) e o polimorfismo na posição +3954 do gene IL-1B em pacientes com a prótese sobre implante, em função, a pelo menos um ano. Vinte e cinco implantes, clinicamente satisfatórios, foram avaliados, em vinte pacientes saudáveis, sendo doze do gênero feminino e oito masculino. Exame clínico completo foi feito em todos os implantes e em um dente em condição de saúde de cada paciente. Amostra do sítio com maior profundidade de sondagem foi coletada para a quantificação da concentração de IL-1ß no fluido crevicular periimplantar/gengival. Células da mucosa bucal foram coletadas para extração do DNA genômico e análise do polimorfismo IL-1B +3954. Não foi detectada a presença da citocina IL-1ß nos sítios avaliados. Na população estudada houve uma predominância do genótipo homozigoto para o alelo C, o qual esteve presente em 75% dos pacientes avaliados. O genótipo homozigoto para o alelo T foi encontrado em apenas um (5%) paciente. Neste estudo não observamos uma relação entre a presença do alelo T e níveis aumentados de IL-1ß no fluido crevicular. The aim of the present study was to determine interleukin-1ß (IL-1ß) levels and the polymorphism IL-1B +3954 in patients with implant loaded at least for one year. Twenty five healthy implans from twelve patients, twenty female and eight male, were examined. Clinical parameters were recorded from all implants and one teeth from each patient. Gingival crevicular fluid from the highest pocket depth was collected, with PerioPaper, to evaluate the level of the IL-1ß. Cells from buccal mucosa were collected for genomic DNA extraction and analyze the polymorphism IL-1B +3954. IL-1ß was not detected in any sites collected. At the studied population we observed prevalence from negative genotype, present in 75% of patients. The positive genotype was observed only in one (5%) patient from the population. Negative genotype is associated with health implants, and are nor related to elevated levels of IL-1ß on the crevicular fluid.

Tomando como referencia los niveles de ingestión de proteínas y vitamina A informados en los estudios de la población cubana durante la epidemia de neuropatía de 1993, se ejecutó un biomodelo en ratas, con el objetivo de evaluar la incidencia de estos niveles sobre algunos indicadores del estado nutricional y de la respuesta inmune. Para ello se ensayaron 4 dietas: control, deficiente en proteínas, deficiente en vitamina A y deficiente en proteínas y vitamina A. La Interleucina 1 (IL-1) se evaluó a partir de su expresión en las placas de Peyer y los resultados obtenidos se relacionaron con indicadores del estado nutricional como peso, ingesta, recambio proteico, proteínas plasmáticas y vitamina A, con indicadores inmunológicos (conteo celular y complemento hemolítico total) y con el estudio histológico realizado en timo, bazo e hígado. La deficiencia de proteínas disminuyó la expresión génica de IL-1, la cual se asoció con lesiones degenerativas y de atrofia en los órganos estudiados. La deficiencia de proteínas y vitamina A provocó una estimulación de la expresión génica de IL-1, asociada además con indicadores sensibles del estado inflamatorio, que pudiera ser el resultado de una movilización deficiente de retinol hacia los tejidos. Los resultados obtenidos en el biomodelo abren la posibilidad de utilización de las citocinas en la detección de afectaciones subclínicas del sistema inmune provocadas por deficiencias nutricionales Gene expression of Interleukin 1 in vitamin A and protein deficiency. The influence of low levels of protein and vitamin A on indicators of the immune response was assayed in rats. The levels of protein and vitamin A intake of the Cuban population affected by epidemic neuropathy in 1993 was reproduced in 4 diets: control, protein deficiency (DP), vitamin A deficiency (DA), protein and vitamin A deficiency (DAP). The Peyer’s patches evaluated the Interleukin 1 expression gene and was related with corporal weight, food intake, serum protein, vitamin A, immunology indicators and histology evaluation (spleen, thymus and liver). Protein deficiency generated a significant decrease of the expression gene of Interleukin 1. Atrophy signs in lymphoid tissues and morphologic changes in the liver were associated with the dietary protein utilization. Protein and vitamin A deficiency generated significant stimulation of the Interleukin 1 expression gene with increase of the level of the inflammatory state indicators as serum a protein, total complement and neutrophils. This stimulation could be generated by a deficient retinol mobilization to tissues. These results support the hypothesis of the function of citokines as mediators of subclinical symthoms of the immune system during the nutritional affectations