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1.
Allergol Immunopathol (Madr) ; 47(6): 535-543, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31196774

RESUMO

INTRODUCTION: Food allergies are inflammatory conditions mediated by Th2 and probably STAT-6 dependent immune responses. OBJECTIVE AND DESIGN: Here we investigated the role of Signal Transducer and Activator of Transcription 6 (STAT-6) in development of inflammation in peanut allergy. METHODS: To induce food allergy, wild-type (WT) and mice deficient for STAT-6 (Stat6-/-) were sensitized with peanut proteins and challenged with peanut seeds. RESULTS: WT animals lost weight and refused the peanut diet, in contrast to Stat6-/- mice, which had a better maintenance of body weight and more regular seeds' consumption. The augmented peanut-specific IgG, IgG1 and IgE in the allergic WT was abolished in Stat6-/- animals that also presented increased IgG2a. There was an overall reduction in the gut mediators in the absence of STAT-6, including those related to inflammatory and Th2 responses, in contrast to a rising counter regulatory and Th1 reaction in Stat-6-/- mice. These animals had IFN-γ and IL-10 similar to WT after the four-week challenge. Most interestingly, Stat-6-/- mice had no intestinal damage, in contrast to WT animals, which had inflammatory infiltrate, tissue destruction, epithelial exulceration, edema, congestion and loss of villous architecture in the small gut segments. CONCLUSIONS: STAT-6 plays an important role in the establishment of the Th2 inflammatory responses and intestinal damage in peanut allergy.


Assuntos
Inflamação/imunologia , Intestinos/patologia , Hipersensibilidade a Amendoim/imunologia , Fator de Transcrição STAT6/imunologia , Células Th2/imunologia , Alérgenos/imunologia , Animais , Arachis/imunologia , Modelos Animais de Doenças , Humanos , Imunoglobulina E/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais
2.
Cardiovasc Diabetol ; 17(1): 33, 2018 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-29477146

RESUMO

BACKGROUND: Long-term visit-to-visit glycemic variability is an additional measure of glycemic control. We aimed to evaluate the prognostic value of several measures of glycemic variability for the occurrence of micro- and macrovascular complications, and all-cause mortality in patients with type 2 diabetes. METHODS: 654 individuals were followed-up over a median of 9.3 years. Glycemic variability (SDs and coefficients of variation of HbA1c and fasting glycaemia) was measured during the first 12- and 24-months. Multivariate Cox analysis, adjusted for risk factors and mean HbA1c and fasting glycaemia levels, examined the associations between glycemic variability and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications [total cardiovascular events (CVE), major adverse CVEs (MACE) and cardiovascular mortality], and of all-cause mortality. RESULTS: During follow-up, 128 patients had a CVE (96 MACE), and 158 patients died (67 from cardiovascular diseases); 152 newly-developed or worsened diabetic retinopathy, 183 achieved the renal composite outcome (89 newly developed microalbuminuria and 91 deteriorated renal function), and 96 newly-developed or worsened peripheral neuropathy. Glycemic variability, particularly the 24-month parameters either estimated by HbA1c or by fasting glycemia, predicted all endpoints, except for retinopathy and peripheral neuropathy development/progression, and was a better predictor than mean HbA1c. Glycemic variability predicted retinopathy development/progression in patients with good glycemic control (HbA1c ≤ 7.5%, 58 mmol/mol) and predicted new-incident peripheral neuropathy. CONCLUSIONS: Long-term visit-to-visit glycemic variability is an additional and frequently a better glycemic parameter than mean HbA1c levels for assessing the risk of future development of micro- and macrovascular complications in patients with type 2 diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/epidemiologia , Hemoglobinas Glicadas/metabolismo , Idoso , Albuminúria/sangue , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Biomarcadores/sangue , Brasil/epidemiologia , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/mortalidade , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Retinopatia Diabética/sangue , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
3.
Braz. j. med. biol. res ; 48(2): 96-107, 02/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-735857

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Escalas de Graduação Psiquiátrica , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Comparação Transcultural , Análise Fatorial , Hipercinese/psicologia , Comportamento Impulsivo/fisiologia , Psicometria , Reprodutibilidade dos Testes , Autorrelato , Espanha
4.
Braz J Med Biol Res ; 48(2): 96-107, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25466162

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Imunossupressores/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos/métodos , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Humanos , Doenças Inflamatórias Intestinais/terapia , Metotrexato/uso terapêutico , Microbiota/efeitos dos fármacos , Probióticos/uso terapêutico , Purinas/uso terapêutico , Qualidade de Vida , Fator de Necrose Tumoral alfa/antagonistas & inibidores
5.
Braz. j. med. biol. res ; 47(9): 727-737, 09/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-719316

RESUMO

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.


Assuntos
Animais , Humanos , Trato Gastrointestinal/microbiologia , Predisposição Genética para Doença/etiologia , Interações Hospedeiro-Patógeno/imunologia , Doenças Inflamatórias Intestinais/etiologia , Microbiota/imunologia , Interação Gene-Ambiente , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Microbiota/genética , Polimorfismo Genético
6.
Braz J Med Biol Res ; 47(9): 727-37, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25075576

RESUMO

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.


Assuntos
Trato Gastrointestinal/microbiologia , Predisposição Genética para Doença/etiologia , Interações Hospedeiro-Patógeno/imunologia , Doenças Inflamatórias Intestinais/etiologia , Microbiota/imunologia , Animais , Interação Gene-Ambiente , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Microbiota/genética , Polimorfismo Genético
7.
Immunobiology ; 216(3): 409-15, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20655616

RESUMO

Injury triggers inflammatory responses and tissue repair. Several treatments are currently in use to accelerate healing; however, more efficient formulations are still needed for specific injuries. Since unsaturated fatty acids modulate immune responses, we aimed to evaluate their therapeutic effects on wound healing. Skin wounds were induced in BALB/c mice and treated for 5 days with n-3, n-9 fatty acids or vehicle (control). n-9 treated mice presented smaller wounds than control and n-3 at 120 h post-surgery (p.s.). Collagen III mRNA, TIMP1 and MMP9 were significantly elevated in n-9 group compared to n-3 or vehicle at 120 h p.s. Among the inflammatory mediators studied we found that IL-10, TNF-α and IL-17 were also higher in n-9 treated group compared to n-3 or vehicle at 120 h p.s. Interestingly, COX2 had decreased expression on wound tissue treated with n-9. Inflammatory infiltrate analysis revealed diminished frequency of CD4(+), CD8(+) and CD11b(+) cells in n-9 wounds at 24 and 120 h p.s., which was not related to cell death, since in vitro apoptosis experiments did not show any cell damage after fatty acids administration. These results suggested that unsaturated fatty acids, specifically n-9, modulate the inflammation in the wound and enhance reparative response in vivo. n-9 may be a useful tool in the treatment of cutaneous wounds.


Assuntos
Ácidos Linolênicos/farmacologia , Ácido Oleico/farmacologia , Pele/imunologia , Pele/lesões , Cicatrização/efeitos dos fármacos , Cicatrização/imunologia , Animais , Apoptose , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Colágeno/genética , Ciclo-Oxigenase 2/genética , Citometria de Fluxo , Expressão Gênica , Inflamação , Interleucina-10/sangue , Interleucina-17/sangue , Ácidos Linolênicos/uso terapêutico , Macrófagos/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ácido Oleico/uso terapêutico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Pele/crescimento & desenvolvimento , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/sangue
8.
J. venom. anim. toxins incl. trop. dis ; 17(2): 190-198, 2011. graf, tab
Artigo em Inglês | LILACS | ID: lil-587779

RESUMO

Plathymenia reticulata Benth has an anti-inflammatory effect and is capable of neutralizing the neuromuscular blockade induced by Bothrops jararacussu or Crotalus durissus terrificus venoms, probably by precipitating venom proteins (an effect caused by plant tannins). The present study aimed to evaluate the mutagenic activity of P. reticulata by using the Salmonella mutagenicity assay (Ames test) and the micronucleus test in CHO-K1 cells. P. reticulata extract concentrations of 2.84, 5.68, 11.37, and 19.90 mg/plate were assayed by the Ames test using TA97a, TA98, TA100 and TA102 bacterial strains, with (+S9) and without (-S9) metabolic activation. Concentrations of 5, 1.6 and 0.5 ìg/mL of P. reticulata extract were used for the micronucleus test. P. reticulata extract was mutagenic to TA98 (-S9) and showed signs of mutagenic activity in TA97a and TA102 (both -S9) strains. Micronucleus test CBPI values showed that the endogenous metabolic system increased the number of viable cells when compared to the non-activated samples and the micronucleus frequency increased when the cells were treated in the absence of S9. We concluded that P. reticulata extract may present direct mutagenic properties.


Assuntos
Anti-Inflamatórios , Bothrops , Venenos de Crotalídeos , Crotalus cascavella , Solução Hidroalcoólica , Bloqueadores Neuromusculares , Plantas Medicinais , Testes de Mutagenicidade/métodos
9.
Rev Alerg Mex ; 57(1): 26-32, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20857626

RESUMO

OBJECTIVE: To determine whether camel's milk can be consumed by patients intolerant to lactose without undesirable reactions. PATIENTS AND METHOD: Twenty-five patients with clinical and laboratorial diagnosis of lactose intolerance underwent provocation tests with growing amounts of cow's milk and subsequently with camel's milk. RESULTS: Except for two patients, who had mild reactions to the maximum dosage of camel's milk (250 mL), the acceptance was excellent. Pasteurization of camel's milk did not affect tolerance. Also, most of the patients showed significant clinical reactions when drinking very low amounts of cow's milk. CONCLUSION: Camel's milk can be considered an option for the individuals intolerant to lactose who present symptoms when ingesting cow's milk.


Assuntos
Intolerância à Lactose , Leite , Adolescente , Adulto , Idoso , Animais , Camelus , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Bone Marrow Transplant ; 45(10): 1562-71, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20228850

RESUMO

Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4(+) leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8(+) cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Terapia de Imunossupressão/métodos , Doenças Inflamatórias Intestinais/terapia , Animais , Transplante de Medula Óssea , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Colite/tratamento farmacológico , Colite/imunologia , Colite/patologia , Colite/terapia , Terapia Combinada , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Citocinas/metabolismo , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Índice de Gravidade de Doença , Análise de Sobrevida , Ácido Trinitrobenzenossulfônico/toxicidade
11.
Oral Microbiol Immunol ; 24(1): 1-6, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19121062

RESUMO

INTRODUCTION: Periodontal disease is a chronic inflammation of the attachment structures of the teeth, triggered by potentially hazardous microorganisms and the consequent immune-inflammatory responses. In humans, the T helper type 17 (Th17) lineage, characterized by interleukin-17 (IL-17) production, develops under transforming growth factor-beta (TGF-beta), IL-1beta, and IL-6 signaling, while its pool is maintained by IL-23. Although this subset of cells has been implicated in various autoimmune, inflammatory, and bone-destructive conditions, the exact role of T lymphocytes in chronic periodontitis is still controversial. Therefore, in this study we investigated the presence of Th17 cells in human periodontal disease. METHODS: Gingival and alveolar bone samples from healthy patients and patients with chronic periodontitis were collected and used for the subsequent assays. The messenger RNA expression for the cytokines IL-17, TGF-beta, IL-1beta, IL-6, and IL-23 in gingiva or IL-17 and receptor activator for nuclear factor-kappaB ligand in alveolar bone was evaluated by real-time polymerase chain reaction. The production of IL-17, TGF-beta, IL-1beta, IL-6, and IL-23 proteins was evaluated by immunohistochemistry and the presence of Th17 cells in the inflamed gingiva was confirmed by immunofluorescence confocal microscopy for CD4 and IL-17 colocalization. RESULTS: Our data demonstrated elevated levels of IL-17, TGF-beta, IL-1beta, IL-6, and IL-23 messenger RNA and protein in diseased tissues as well as the presence of Th17 cells in gingiva from patients with periodontitis. Moreover, IL-17 and the bone resorption factor RANKL were abundantly expressed in the alveolar bone of diseased patients, in contrast to low detection in controls. CONCLUSION: These results provided strong evidence for the presence of Th17 cells in the sites of chronic inflammation in human periodontal disease.


Assuntos
Perda do Osso Alveolar/imunologia , Periodontite Crônica/imunologia , Interleucina-17/biossíntese , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Perda do Osso Alveolar/metabolismo , Estudos de Casos e Controles , Feminino , Imunofluorescência , Expressão Gênica , Humanos , Imuno-Histoquímica , Interleucina-1beta/biossíntese , Interleucina-23/biossíntese , Interleucina-6/biossíntese , Masculino , Microscopia Confocal , Ligante RANK/biossíntese , RNA Mensageiro/biossíntese , Linfócitos T Auxiliares-Indutores/metabolismo , Fator de Crescimento Transformador beta/biossíntese
12.
J Periodontal Res ; 44(5): 598-608, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19076989

RESUMO

BACKGROUND AND OBJECTIVE: Inflammatory cytokines such as tumor necrosis factor-alpha are involved in the pathogenesis of periodontal diseases. A high between-subject variation in the level of tumor necrosis factor-alpha mRNA has been verified, which may be a result of genetic polymorphisms and/or the presence of periodontopathogens such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola (called the red complex) and Aggregatibacter actinomycetemcomitans. In this study, we investigated the effect of the tumor necrosis factor-alpha (TNFA) -308G/A gene polymorphism and of periodontopathogens on the tumor necrosis factor-alpha levels in the periodontal tissues of nonsmoking patients with chronic periodontitis (n = 127) and in control subjects (n = 177). MATERIAL AND METHODS: The TNFA -308G/A single nucleotide polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism analysis, whereas the tumor necrosis factor-alpha levels and the periodontopathogen load were determined using real-time polymerase chain reaction. RESULTS: No statistically significant differences were found in the frequency of the TNFA -308 single nucleotide polymorphism in control and chronic periodontitis groups, in spite of the higher frequency of the A allele in the chronic periodontitis group. The concomitant analyses of genotypes and periodontopathogens demonstrated that TNFA -308 GA/AA genotypes and the red-complex periodontopathogens were independently associated with increased levels of tumor necrosis factor-alpha in periodontal tissues, and no additive effect was seen when both factors were present. P. gingivalis, T. forsythia and T. denticola counts were positively correlated with the level of tumor necrosis factor-alpha. TNFA -308 genotypes were not associated with the periodontopathogen detection odds or with the bacterial load. CONCLUSION: Our results demonstrate that the TNFA -308 A allele and red-complex periodontopathogens are independently associated with increased levels of tumor necrosis factor-alpha in diseased tissues of nonsmoking chronic periodontitis patients and consequently are potentially involved in determining the disease outcome.


Assuntos
Adenina , Bacteroides/fisiologia , Periodontite Crônica/imunologia , Guanina , Polimorfismo de Nucleotídeo Único/genética , Porphyromonas gingivalis/fisiologia , Treponema denticola/fisiologia , Fator de Necrose Tumoral alfa/genética , Adulto , Aggregatibacter actinomycetemcomitans/fisiologia , Periodontite Crônica/microbiologia , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/imunologia , Perda da Inserção Periodontal/microbiologia , Bolsa Periodontal/imunologia , Bolsa Periodontal/microbiologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Vet Parasitol ; 158(4): 319-28, 2008 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-18977600

RESUMO

The present study, investigated the mechanisms involved in the immune responses of Major Histocompatibility Complex class I or class II knockout mice, following Strongyloides venezuelensis infection. Wild-type C57BL/6 (WT), MHC II(-/-) and MHC I(-/-) mice were individually inoculated with 3000 larvae (L3) of S. venezuelensis and sacrificed on days 1, 3, 5, 8, 13 and 21 post-infection (p.i.). Samples of blood, lungs and small intestines were collected. The tissue samples were stained with hematoxylin-eosin for the pathological analysis. The presence of the parasite was demonstrated by immunoperoxidase analysis. MHC II(-/-) mice presented a significantly higher number of adult worms recovered from the small intestine on day 5p.i. and presented elevated numbers of eggs in the feces. The infection by S. venezuelensis was completely eliminated 13 days after infection in WT as well as in MHC I(-/-) mice. In MHC II(-/-) mice, eggs and adult worms were still found on day 21 p.i., however, there was a significant reduction in their numbers. In the lung, the parasite was observed in MHC I(-/-) on day 1 p.i. and in MHC II(-/-) mice on days 1 and 5 p.i. In the small intestine of WT mice, a larger number of parasites were observed on day 8 p.i. and their absence was observed after day 13 p.i. Through immunohistochemistry analysis, the parasite was detected in the duodenum of WT on days 5 and 8 p.i., and in knockout mice on days 5, 8 and 13 p.i.; as well as in posterior portions of the small intestine in MHC I(-/-) and MHC II(-/-) on day 13 p.i., a finding which was not observed in WT mice. We concluded that immunohistochemistry analysis contributed to a more adequate understanding of the parasite localization in immunodeficient hosts and that the findings aid in the interpretation of immunopathogenesis in Strongyloides infection.


Assuntos
Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Enteropatias Parasitárias/imunologia , Pneumopatias Parasitárias/imunologia , Estrongiloidíase/imunologia , Animais , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/patologia , Intestinos/patologia , Pulmão/patologia , Pneumopatias Parasitárias/parasitologia , Pneumopatias Parasitárias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Strongyloides , Estrongiloidíase/parasitologia , Estrongiloidíase/patologia
14.
Lupus ; 17(11): 1042-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18852231

RESUMO

The aim of this study was to investigate whether initial and accrued organ damage measured by Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) predicts mortality in cohort of Brazilian patients with systemic lupus erythematosus (SLE). One hundred and five outpatients with SLE were enrolled from July 2000 to March 2001; their demographics, disease manifestations, interventions and quantified disease activity (SLEDAI) were obtained. SDI was measured at baseline and at the end of follow-up. Initial and accrued SDI prognostic values for mortality were investigated by multivariate Cox survival analysis and Kaplan-Meyer survival curves. After a median follow-up of 6.3 years, 19 patients died due to disease activity, end-organ failure, cardiovascular events, cancer and infection. Deceased patients had longer disease duration and greater initial and final SDI than survivors had. After adjustment for age, sex and disease duration, both initial and final SDI >/= 3 points were independent predictors of mortality, with hazard ratios (HRs) of 3.0 (1.1-8.2) and 4.7 (1.6-14.5), respectively. Damage accrual during follow-up was the strongest predictor of death (HR: 5.1, 2.0-13.0). Renal and pulmonary damages were the main predictors of increased mortality risk. In conclusion, baseline and accrued damage increase mortality risk in Brazilian patients with SLE. Measures to prevent damage development and progression are urgent to reduce the mortality of patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico/mortalidade , Adulto , Brasil/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
15.
Braz J Med Biol Res ; 41(8): 674-80, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18797700

RESUMO

Increased proteinuria is recognized as a risk predictor for all-cause and cardiovascular mortality in diabetic patients; however, no study has evaluated these relationships in Brazilian patients. The aim of this study was to investigate the prognostic value of gross proteinuria for all-cause and cardiovascular mortalities and for cardiovascular morbidity in a cohort study of 471 type 2 diabetic individuals followed for up to 7 years. Several clinical, laboratory and electrocardiographic variables were obtained at baseline. The relative risks for all-cause, cardiovascular and cardiac mortalities and for cardiovascular and cardiac events associated with the presence of overt proteinuria (>0.5 g/24 h) were assessed by Kaplan-Meier survival curves and by multivariate Cox regression model. During a median follow-up of 57 months (range 2-84 months), 121 patients (25.7%) died, 44 from cardiovascular and 30 from cardiac causes, and 106 fatal or non-fatal cardiovascular events occurred. Gross proteinuria was an independent risk predictor of all-cause, cardiovascular and cardiac mortalities and of cardiovascular morbidity with adjusted relative risks ranging from 1.96 to 4.38 for the different endpoints. This increased risk remained significant after exclusion of patients with prior cardiovascular disease at baseline from the multivariate analysis. In conclusion, gross proteinuria was a strong predictor of all-cause, cardiovascular and cardiac mortalities and also of cardiovascular morbidity in a Brazilian cohort of type 2 diabetic patients. Intervention studies are necessary to determine whether the reduction of proteinuria can decrease morbidity and mortality of type 2 diabetes in Brazil.


Assuntos
Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Proteinúria/complicações , Brasil/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/urina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Eletrocardiografia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
16.
Clin Exp Immunol ; 154(2): 153-61, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18778361

RESUMO

Food enteropathies involve uncontrolled or hypersensitivity reactions to ingested nutrients and may result in IgE and T-helper type 2 (Th2) responses as in food allergy. However, the precise role of B cells in the development of food enteropathies remains uncertain. In this work, we used B cell-deficient mice (B KO) and a model of peanut sensitization to examine the involvement of B lymphocytes in the pathogenesis of food allergy. Results showed that priming of wild-type (WT) mice with peanut proteins induced specific IgG1 and IgE responses in serum, with edema, tissue destruction, epithelial exulceration and inflammatory infiltrate in the gut of sensitized and challenged (S + Peanut) WT animals. In contrast, there was no sera immunoglobulin detection and absence of tissue destruction in the gut of B KO mice, which presented moderate inflammatory infiltrate and villous enlargement after peanut challenge. These animals presented marked decrease in IL-4 and TNF-alpha and high levels of IL-10, TGF-beta, IL-12p40 and IFN-gamma mRNA in the gut. Moreover, the expression of CCL5, CCL11 and CXCL1 was reduced in the gut of B KO mice, in contrast to elevated messages of CCL2 or similar detection of Th1-related chemokines in S + Peanut WT mice. Finally, we provided evidence that B cells are necessary to the development of food-related enteropathies and induction of gut inflammation during allergic reactions to food.


Assuntos
Linfócitos B/imunologia , Enterite/imunologia , Hipersensibilidade a Amendoim/imunologia , Alérgenos/imunologia , Animais , Arachis/imunologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Enterite/patologia , Imunoglobulinas/biossíntese , Jejuno/imunologia , Jejuno/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hipersensibilidade a Amendoim/patologia , Proteínas de Vegetais Comestíveis/imunologia , Células Th2/imunologia
17.
Braz. j. med. biol. res ; 41(8): 674-680, Aug. 2008. graf, tab
Artigo em Inglês | LILACS | ID: lil-491923

RESUMO

Increased proteinuria is recognized as a risk predictor for all-cause and cardiovascular mortality in diabetic patients; however, no study has evaluated these relationships in Brazilian patients. The aim of this study was to investigate the prognostic value of gross proteinuria for all-cause and cardiovascular mortalities and for cardiovascular morbidity in a cohort study of 471 type 2 diabetic individuals followed for up to 7 years. Several clinical, laboratory and electrocardiographic variables were obtained at baseline. The relative risks for all-cause, cardiovascular and cardiac mortalities and for cardiovascular and cardiac events associated with the presence of overt proteinuria (>0.5 g/24 h) were assessed by Kaplan-Meier survival curves and by multivariate Cox regression model. During a median follow-up of 57 months (range 2-84 months), 121 patients (25.7 percent) died, 44 from cardiovascular and 30 from cardiac causes, and 106 fatal or non-fatal cardiovascular events occurred. Gross proteinuria was an independent risk predictor of all-cause, cardiovascular and cardiac mortalities and of cardiovascular morbidity with adjusted relative risks ranging from 1.96 to 4.38 for the different endpoints. This increased risk remained significant after exclusion of patients with prior cardiovascular disease at baseline from the multivariate analysis. In conclusion, gross proteinuria was a strong predictor of all-cause, cardiovascular and cardiac mortalities and also of cardiovascular morbidity in a Brazilian cohort of type 2 diabetic patients. Intervention studies are necessary to determine whether the reduction of proteinuria can decrease morbidity and mortality of type 2 diabetes in Brazil.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , /mortalidade , Proteinúria/complicações , Brasil/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/urina , /complicações , /urina , Eletrocardiografia , Métodos Epidemiológicos , Valor Preditivo dos Testes , Prognóstico
18.
Clin Exp Allergy ; 38(2): 338-49, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18005184

RESUMO

BACKGROUND: Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. OBJECTIVE: To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. METHODS: C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. RESULTS: Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gammadelta+ and CD4+CD25+Foxp3+ cells in Peyer's patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. CONCLUSION: A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.


Assuntos
Colite/imunologia , Mucosa Intestinal/imunologia , Hipersensibilidade a Amendoim/complicações , Animais , Arachis/química , Arachis/imunologia , Colite/genética , Colite/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Fator de Transcrição GATA3/metabolismo , Expressão Gênica , Imunidade nas Mucosas , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulinas/metabolismo , Mucosa Intestinal/patologia , Leucócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Nódulos Linfáticos Agregados/imunologia , Extratos Vegetais/química , Extratos Vegetais/imunologia , Células Th2/imunologia , Redução de Peso
19.
Clin Exp Immunol ; 147(1): 128-38, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17177972

RESUMO

Inflammatory immune reactions in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. Thus, we examined the mechanisms by which the proinflammatory cytokine tumour necrosis factor (TNF)-alpha modulates the outcome of Actinobacillus actinomycetemcomitans-induced periodontal disease in mice. Our results showed that TNF-alpha receptor p55-deficient mice [p55TNF-knock-out (KO)] developed a less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significantly less alveolar bone loss and inflammatory reaction. Real-time polymerase chain reaction (PCR) demonstrated that levels of chemokines (CXCL1, 3 and 10; CCL3 and 5) and their receptors (CXCR2 and 3, CCR5) were lower in p55TNF-KO mice, as were matrix metalloproteinase (MMP)-1, 2 and 9 and receptor activator of nuclear factor kB ligand (RANKL) mRNA levels. However, the absence of the TNF-alpha p55 results in an impairment of protective immunity to A. actinomycetemcomitans infection, characterized by increased bacterial load and higher levels of C-reactive protein during the course of disease. Such impaired host response may be the result of the reduced chemoattraction of lymphocytes, neutrophils and macrophages, and reduced inducible nitric oxide synthase expression (iNOS) and myeloperoxidase (MPO) production in periodontal tissues of p55 TNF-KO mice. Our results demonstrate the mechanisms involved determining periodontal disease severity by TNF-alpha receptor p55, and its role in providing immune protection to A. actinomycetemcomitans periodontal infection.


Assuntos
Infecções por Actinobacillus/imunologia , Aggregatibacter actinomycetemcomitans , Periodontite/imunologia , Periodonto/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Chamariz do Fator de Necrose Tumoral/metabolismo , Infecções por Actinobacillus/patologia , Aggregatibacter actinomycetemcomitans/imunologia , Perda do Osso Alveolar , Animais , Anticorpos Antibacterianos/sangue , Proteína C-Reativa/análise , Quimiocina CCL5 , Quimiocina CXCL1 , Quimiocina CXCL10 , Quimiocinas CC/análise , Quimiocinas CC/genética , Quimiocinas CXC/análise , Quimiocinas CXC/genética , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática/métodos , Citometria de Fluxo , Interferon gama/análise , Interferon gama/genética , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-1beta/análise , Interleucina-1beta/genética , Metaloproteinases da Matriz/análise , Metaloproteinases da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Periodontite/patologia , Periodonto/patologia , Peroxidase/análise , Ligante RANK/análise , Ligante RANK/genética , Receptores CCR5/análise , Receptores CCR5/genética , Receptores CXCR3 , Receptores de Quimiocinas/análise , Receptores de Quimiocinas/genética , Receptores de Interleucina-8B/análise , Receptores de Interleucina-8B/genética , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptores Chamariz do Fator de Necrose Tumoral/imunologia , Fator de Necrose Tumoral alfa/imunologia
20.
J Periodontal Res ; 41(6): 580-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17076785

RESUMO

BACKGROUND AND OBJECTIVE: Inflammatory cytokines are thought to trigger periodontal tissue destruction. In addition to being regulated by anti-inflammatory mediators, their activity is under the control of suppressors of cytokine signaling (SOCS), which down-regulate the signal transduction as part of an inhibitory feedback loop. We therefore investigated the expression of SOCS-1, -2 and -3, and the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-10, in different forms of human periodontal diseases. MATERIAL AND METHODS: Quantitative polymerase chain reaction (RealTime-PCR) was performed with mRNA from gingival biopsies of control subjects and from that of patients with chronic gingivitis and chronic periodontitis. RESULTS: Our results show that patients with chronic gingivitis and chronic periodontitis exhibit significantly higher SOCS-1, -2 and -3, TNF-alpha and interleukin-10 mRNA expression when compared with healthy controls. The data also demonstrate that SOCS-1 and -3 mRNA expression was higher in tissue from patients with chronic gingivitis than chronic periodontitis, while the levels of SOCS-2, TNF-alpha and interleukin-10 mRNA were similar in these groups. CONCLUSION: The increased expression of SOCS-1, -2 and -3 mRNA in diseased periodontal tissues is believed to be involved in the down-regulation of inflammatory cytokine and Toll-like receptor signaling, and therefore in the attenuation of both the inflammatory reaction and disease severity. Furthermore, it is possible that variation in the levels of SOCS mRNA expressed in different forms of periodontal diseases may determine the stable or progressive nature of the lesions.


Assuntos
Interleucina-10/análise , Periodontite/metabolismo , RNA Mensageiro/análise , Proteínas Supressoras da Sinalização de Citocina/análise , Fator de Necrose Tumoral alfa/análise , Adulto , Estudos de Casos e Controles , Progressão da Doença , Feminino , Gengivite/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
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