RESUMO
Objectives To better characterize the role of endoscopic cubital tunnel release in leprosy neuritis and determine whether there is an improvement in pain, sensitivity, and strength with the use of this minimally invasive technique. Methods A total of 44 endoscopic procedures for ulnar nerve decompression at the elbow were performed in patients who were previously diagnosed with leprosy neuritis. The inclusion criteria were surgical indication for ulnar nerve release and clinical treatment failure for 4 weeks in patients with cubital tunnel syndrome who had their ulnar nerve function, whether motor or sensitive, deteriorated progressively despite the treatment with prednisone 1 mg/kg/day and physiotherapy. For endoscopic release, the CTS Relief Kit (Linvatec. Largo, FL, USA) and a standard 4mm 30° arthroscope were used. Results The study included 39 patients, 29 (74.4%) males and 10 (25.6%) females. The age of the patients ranged from 12 to 64 years (33 ± 14.97). Five patients underwent bilateral release. The release demonstrated a statistically significant improvement in pain ( p 0.002), in sensitivity ( p < 0.001), and in strength ( p < 0.001). The best results were obtained when ulnar release was performed less than 6 months after surgery indication. None of the procedures were converted from endoscopic to open. No major complications (infection, vascular injury, and nervous injury) were reported. One patient had ulnar nerve subluxation. Conclusion The endoscopic release of the ulnar nerve at the elbow in leprosy neuritis entails true and safe benefits for the patient, such as improvement in pain, sensitivity and strength.
RESUMO
Abstract Objectives To better characterize the role of endoscopic cubital tunnel release in leprosy neuritis and determine whether there is an improvement in pain, sensitivity, and strength with the use of this minimally invasive technique. Methods A total of 44 endoscopic procedures for ulnar nerve decompression at the elbow were performed in patients who were previously diagnosed with leprosy neuritis. The inclusion criteria were surgical indication for ulnar nerve release and clinical treatment failure for 4 weeks in patients with cubital tunnel syndrome who had their ulnar nerve function, whether motor or sensitive, deteriorated progressively despite the treatment with prednisone 1 mg/kg/day and physiotherapy. For endoscopic release, the CTS Relief Kit (Linvatec. Largo, FL, USA) and a standard 4mm 30° arthroscope were used. Results The study included 39 patients, 29 (74.4%) males and 10 (25.6%) females. The age of the patients ranged from 12 to 64 years (33 ± 14.97). Five patients underwent bilateral release. The release demonstrated a statistically significant improvement in pain (p 0.002), in sensitivity (p< 0.001), and in strength (p< 0.001). The best results were obtained when ulnar release was performed less than 6 months after surgery indication. None of the procedures were converted from endoscopic to open. No major complications (infection, vascular injury, and nervous injury) were reported. One patient had ulnar nerve subluxation. Conclusion The endoscopic release of the ulnar nerve at the elbow in leprosy neuritis entails true and safe benefits for the patient, such as improvement in pain, sensitivity and strength.
Resumo Objetivos Os objetivos deste estudo foram caracterizar melhor o papel da liberação endoscópica do túnel cubital na neurite hansênica e determinar se há melhora da dor, sensibilidade e força com esta técnica minimamente invasiva. Métodos Um total de 44 procedimentos endoscópicos para descompressão do nervo ulnar no cotovelo foram realizados em pacientes previamente diagnosticados com neurite por hanseníase. Os critérios de inclusão foram indicação cirúrgica para liberação do nervo ulnar e insucesso do tratamento clínico por 4 semanas em pacientes com síndrome do túnel cubital que sofreram deterioração progressiva da função motora ou sensitiva do nervo ulnar apesar do tratamento de 1 mg/kg/dia de prednisona e fisioterapia. A liberação endoscópica foi realizada com CTS Relief Kit (Linvatec. Largo, FL, EUA) e um artroscópio padrão de 4 mm e 30°. Resultados O estudo incluiu 39 pacientes, sendo 29 (74,4%) homens e 10 (25,6%) mulheres. A idade dos pacientes variou de 12 a 64 anos (33 ± 14,97). Cinco pacientes foram submetidos à liberação bilateral. A liberação provocou melhora estatisticamente significativa de dor (p= 0,002), sensibilidade (p <0,001) e força (p <0,001). Os melhores resultados foram obtidos quando a liberação ulnar foi realizada em menos de 6 meses após a indicação da cirurgia. Nenhum procedimento foi convertido de endoscópico para aberto. Não foram relatadas complicações maiores (infecção, lesão vascular e lesão nervosa). Um paciente apresentou subluxação do nervo ulnar. Conclusão A liberação endoscópica do nervo ulnar no cotovelo na neurite hansênica traz benefícios verdadeiros e seguros para o paciente, como melhora da dor, sensibilidade e força.
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Humanos , Neuropatias Ulnares , Síndrome do Túnel Ulnar/terapia , EndoscopiaRESUMO
O objetivo desse manual é servir como um guia para os discentes, docentes e funcionários da Faculdade de Odontologia de Piracicaba em relação às medidas a serem adotadas para que se promovam boas práticas de biossegurança durante os procedimentos de prestação de serviços de saúde
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Medidas de Segurança , Contenção de Riscos Biológicos , Clínicas OdontológicasRESUMO
OBJECTIVE: Describe a reliable anatomical landmark that can be used to locate the maxillary sinus natural ostium (MSNO) during endoscopic surgery, even if the uncinate process is preserved. DESIGN: Descriptive anatomical. SETTING: An anatomical and radiological study was performed to evaluate the consistency of the landmark, denominated "M" line. SUBJECTS AND METHODS: Dissections were performed in 57 cadaver heads (114 sides). In addition, 73 computerised tomography (CT) scans (146 sides) of patients with chronic inflammatory sinonasal disease were analysed using a three-dimensional (3D) reconstruction computer program. RESULTS: The "M" line crossed the MSNO in 112 dissected sides (98.2%) and 140 sides at CT 3D reconstruction (95.9%). CONCLUSION: The "M" line is a reliable anatomical landmark for predicting MSNO location. As such, it could improve and facilitate endoscopic sinus surgery, using traditional, minimally invasive or uncinate preserving techniques.
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Endoscopia/métodos , Seio Etmoidal/diagnóstico por imagem , Seio Maxilar/cirurgia , Tomografia Computadorizada por Raios X/métodos , Adulto , Cadáver , Feminino , Humanos , Masculino , Seio Maxilar/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Many Escherichia coli strains harbour astA, which is the gene encoding the enteroaggregative E. coli heat-stable enterotoxin (EAST1). This gene is embedded in a putative transposase (ORF1) and presents polymorphism in diarrheagenic strains. Although astA and orf1 are detected in extraintestinal strains, little is known about polymorphism and differential gene transcription in this pathotype. In the present work, extraintestinal E. coli from humans (ExPEC - Extraintestinal Pathogenic E. coli) and poultry (APEC - Avian Pathogenic E. coli) were assayed to verify the presence of astA/orf1 and possible polymorphisms in these genes. Three astA/orf1 patterns were detected via Sanger sequencing. Pattern 1 was novel and represented an astA pseudogene. Pattern 2 and pattern 3 presented distinct amino acids within the reading frame encoding astA and were identical to the sequences found in EAEC 17-2 and EAEC 042, respectively. Regarding the frame encoding ORF1, all mutations detected in the three patterns were neutral. The transcripts of astA/orf1 in vitro were underregulated in strains possessing the pattern 1 sequence. The results demonstrate that the same astA sequences may be detected in diarrheagenic and extra-intestinal E. coli. However, extraintestinal isolates may also present an astA pseudogene that has not been reported in diarrheagenic E. coli.
Assuntos
Toxinas Bacterianas/genética , Enterotoxinas/genética , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Variação Genética , Sequência de Aminoácidos , Animais , Toxinas Bacterianas/química , Sequência de Bases , Enterotoxinas/química , Escherichia coli/classificação , Proteínas de Escherichia coli/química , Genes Bacterianos , Humanos , Modelos Moleculares , Conformação Proteica , Análise de Sequência de DNA , Sorogrupo , Virulência/genéticaRESUMO
BACKGROUND: Avian pathogenic Escherichia coli strains cause extraintestinal diseases in birds, leading to substantial economic losses to the poultry industry worldwide. Bacteria that invade cells can overcome the host humoral immune response, resulting in a higher pathogenicity potential. Invasins are members of a large family of outer membrane proteins that allow pathogen invasion into host cells by interacting with specific receptors on the cell surface. RESULTS: An in silico analysis of the genome of a septicemic APEC strain (SEPT362) demonstrated the presence of a putative invasin homologous to the ychO gene from E. coli str. K-12 substr. MG1655. In vitro and in vivo assays comparing a mutant strain carrying a null mutation of this gene, a complemented strain, and its counterpart wild-type strain showed that ychO plays a role in the pathogenicity of APEC strain SEPT362. In vitro assays demonstrated that the mutant strain exhibited significant decreases in bacterial adhesiveness and invasiveness in chicken cells and biofilm formation. In vivo assay indicated a decrease in pathogenicity of the mutant strain. Moreover, transcriptome analysis demonstrated that the ychO deletion affected the expression of 426 genes. Among the altered genes, 93.66% were downregulated in the mutant, including membrane proteins and metabolism genes. CONCLUSION: The results led us to propose that gene ychO contributes to the pathogenicity of APEC strain SEPT362 influencing, in a pleiotropic manner, many biological characteristics, such as adhesion and invasion of in vitro cultured cells, biofilm formation and motility, which could be due to the possible membrane location of this protein. All of these results suggest that the absence of gene ychO would influence the virulence of the APEC strain herein studied.
Assuntos
Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Doenças das Aves Domésticas/microbiologia , Fatores de Virulência/metabolismo , Animais , Galinhas , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Mutação , Virulência , Fatores de Virulência/genéticaRESUMO
OBJECTIVES: To investigate intra- and postoperative outcomes of endoscopic stapes surgery. STUDY DESIGN: Case series with chart review. SETTING: Four tertiary care otologic centers. SUBJECTS AND METHODS: Sixty-five subjects 18 years and older who underwent endoscopic stapes surgeries were analyzed. Variables analyzed included surgical techniques and intraoperative findings. Outcomes measured included postoperative hearing and complications to date. RESULTS: Fifty-one patients met inclusion and exclusion criteria. The average patient age was 48.1 years (range, 26-87 years), with 60.0% female patients. Patients had a median follow-up of 5.13 months (range, 0.8-57.4 months). Of the subjects, 71.7% required scutum removal. The chorda tympani nerve was manipulated in 94.0% of subjects and transected in 12.0%. At last follow-up visit, the median air-bone gap decreased from 34.5 dB hearing level (HL) preoperatively to 9.0 dB HL postoperatively (P < .0001). Ninety percent of subjects had closure of their air-bone gap ≤20 dB HL. Intraoperative complications included tympanic membrane tears in 8.0% of subjects, all of which resolved at first follow-up. Postoperatively, 10.0% of subjects complained of altered taste. CONCLUSIONS: The present multicentered study of endoscopic stapes surgery demonstrates similar audiometric and postoperative outcomes previously published in the literature, with a median postoperative air-bone gap of 9.0 dB HL. Future prospective endoscopic stapes surgery studies, addressing the need for scutum removal, postoperative taste changes, and pain scores, are merited.
Assuntos
Endoscopia/métodos , Cirurgia do Estribo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Audiometria , Brasil , Colômbia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento , Estados UnidosRESUMO
CONTEXT AND OBJECTIVE: The prevalence of post-renal transplant anemia (PTA) reported in the literature is variable and several factors contribute towards its pathophysiology. This study aimed to investigate the prevalence of PTA, its associated risk factors and the impact of therapy without steroids. DESIGN AND SETTING: Retrospective cohort study in a renal transplantation unit at a tertiary hospital. METHODS: Anemia was defined as hemoglobin (Hb) < 12 g/dl in female adult recipients and < 13 g/dl in males. Donor and recipient age and gender, type of donor, creatinine, delayed graft function, acute rejection, use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) and therapy without steroids were investigated as risk factors for PTA through multivariate logistical regression analysis. RESULTS: Evaluations were performed on 258 recipients (mean age: 38.8 years; 60.5% males; 35.7% did not receive steroids). Anemia was diagnosed in 38% of the patients (at the sixth month, M6), 28% (M12), 32% (M24) and 45% (at last follow up). Donor age > 50 years was associated with greater risks of PTA at M6 (odds ratio (OR) = 4.68) and M24 (OR = 6.57), as well as with therapy without steroids at M6 (OR = 2.96). Delayed graft function was independently associated with PTA at M6 (OR = 3.66) and M12 (OR = 2.85). CONCLUSION: The lowest prevalence of PTA was observed between M9 and M24 after renal transplantation. Delayed graft function, donor age and therapy without steroids were the most important factors associated with PTA.
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Anemia/epidemiologia , Anemia/etiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Fatores Etários , Brasil/epidemiologia , Creatinina/sangue , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Doadores de TecidosRESUMO
CONTEXT AND OBJECTIVE: The prevalence of post-renal transplant anemia (PTA) reported in the literature is variable and several factors contribute towards its pathophysiology. This study aimed to investigate the prevalence of PTA, its associated risk factors and the impact of therapy without steroids. DESIGN AND SETTING: Retrospective cohort study in a renal transplantation unit at a tertiary hospital. METHODS: Anemia was defined as hemoglobin (Hb) < 12 g/dl in female adult recipients and < 13 g/dl in males. Donor and recipient age and gender, type of donor, creatinine, delayed graft function, acute rejection, use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) and therapy without steroids were investigated as risk factors for PTA through multivariate logistical regression analysis. RESULTS: Evaluations were performed on 258 recipients (mean age: 38.8 years; 60.5% males; 35.7% did not receive steroids). Anemia was diagnosed in 38% of the patients (at the sixth month, M6), 28% (M12), 32% (M24) and 45% (at last follow up). Donor age > 50 years was associated with greater risks of PTA at M6 (odds ratio (OR) = 4.68) and M24 (OR = 6.57), as well as with therapy without steroids at M6 (OR = 2.96). Delayed graft function was independently associated with PTA at M6 (OR = 3.66) and M12 (OR = 2.85). CONCLUSION: The lowest prevalence of PTA was observed between M9 and M24 after renal transplantation. Delayed graft function, donor age and therapy without steroids were the most important factors associated with PTA. .
CONTEXTO E OBJETIVO: A prevalência de anemia pós-transplante renal (APR) relatada na literatura é variável e vários fatores contribuem para sua fisiopatologia. Este estudo objetivou investigar a prevalência de APR, os fatores de risco associados e o impacto da terapia sem esteroides. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo em unidade de transplante renal em hospital terciário. MÉTODOS: Anemia foi definida como hemoglobina (Hb) < 12 g/dl em receptores adultos do sexo feminino e < 13 g/dl no masculino. Idade e gênero do doador e do receptor, tipo de doador, creatinina, função retardada do enxerto (FRE), rejeição aguda, uso de inibidores da enzima conversora da angiotensina (IECA)/bloqueadores dos receptores da angiotensina (BRA) e terapia sem esteroides foram investigados como fatores de risco para APR em análise de regressão logística multivariada. RESULTADOS: Duzentos e cinquenta e oito receptores foram avaliados (idade média: 38,8 anos; 60,5% homens; 35,7% em terapia sem esteroides). Anemia foi diagnosticada em 38% no sexto mês (M6), 28% (M12), 32% (M24) e em 45% dos pacientes na última data de acompanhamento. Idade do doador > 50 anos associou-se a maior risco de APR aos 6 (odds ratio, OR = 4,68) e 24 meses (OR = 6,57), bem como terapia sem esteroides aos 6 meses (OR = 2,96). FRE associou-se independentemente com APR aos 6 (OR = 3,66) e 12 meses (OR = 2,85). CONCLUSÃO: A menor prevalência de APR foi observada entre 9 e 24 meses pós-transplante renal. FRE, idade do doador e terapia sem esteroides foram os principais fatores associados à APR. .
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anemia/epidemiologia , Anemia/etiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores Etários , Brasil/epidemiologia , Creatinina/sangue , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto , Terapia de Imunossupressão , Análise Multivariada , Prevalência , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Doadores de TecidosAssuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Integrons/genética , Shigella sonnei/efeitos dos fármacos , Adolescente , Adulto , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Diarreia/microbiologia , Disenteria Bacilar/genética , Humanos , Lactente , Prevalência , Shigella sonnei/genética , Shigella sonnei/isolamento & purificação , Adulto JovemRESUMO
BACKGROUND: Burns can result in substantial morbidity through fibroblast proliferation and contracture. Imiquimod (IMQ), an immune response modifier and upregulator of endogenous cytokine expression, has been shown to suppress fibroblast proliferation. It is widely used in the treatment of viral, neoplastic and non-neoplastic skin conditions and has recently been tested in the reduction of hypertrophic scarring and keloids. To our knowledge, no other study has so far evaluated the effect of IMQ on cutaneous burns. METHODS: Partial-thickness burns were produced on the dorsum of 32 Wistar rats. Right-sided wounds received saline and left-sided wounds received 5% IMQ cream three times/week following injury. Photographs taken on post-burn days (PBD) 4, 7, 14 and 21 were evaluated for wound appearance using a clinical assessment scale and a visual analog scale. Scars were measured by digital planimetry. Samples stained with hematoxylin-eosin were submitted to conventional histological analysis. Samples stained with Sirius Red were analyzed under polarized light for collagen morphometry. RESULTS: Visual scores were higher in the saline group on PBD 21 (p<0.05). Wound edge migration rates were lower (p<0.05) and conventional histology showed accentuated inflammation and delayed reepithelialization in the IMQ group. Type-I and type-III collagen deposition increased in the saline group and decreased in the IMQ group. Conversely, the proportion between type-I and type-III collagen differed significantly between treatments on PBD 4 and 21 (p<0.05 in both cases). CONCLUSIONS: Short-term topical imiquimod treatment of partial-thickness burns in rats did not improve clinical appearance and scarring but rather decreased fibrosis. Significant differences in collagen deposition were observed between the treatments.
Assuntos
Aminoquinolinas/uso terapêutico , Queimaduras/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Administração Cutânea , Animais , Índice de Massa Corporal , Queimaduras/complicações , Queimaduras/metabolismo , Queimaduras/patologia , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz/prevenção & controle , Colágeno/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Imiquimode , Masculino , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Pele/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: An inherited profile of genes related to the response to aggressive environmental factors such as viruses and chemicals may be related to an increased susceptibility to Graves' disease (GD). DESIGN AND METHODS: This prospective case-control study was designed to examine the relationship between human herpesviruses (HHV) infection, determined by circulating DNA; tumour protein p53 (TP53) apoptotic ability; and detoxification system genes, and GD. We studied 280 confirmed GD patients paired to 284 controls with respect to environmental exposure. Exclusion criteria included medications that could interfere with thyroid function evaluation and a recent history of viral and bacterial infections. RESULTS: A stepwise regression analysis adjusted for age, gender, and ethnicity established the inheritance of glutathione S-transferase pi 1 (GSTP1) (odds ratio (OR)=3.423; 95% confidence interval (CI)=2.120-5.527; P<0.001) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) variants (OR=1.649; 95% CI=1.012-2.686; P=0.0445) as significant risk factors for the disease. HHV-7 infection was much more common in GD patients (64.64%) than in controls (38.73%; chi(2), P<0.0001), and it increased the risk for GD more than three times (OR=3.133; 95% CI=1.959-5.011; P<0.0001). The inheritance of less efficient Pro/Pro TP53 gene variants significantly increased the risk of GD development (OR=5.196; 95% CI=2.112-12.783; P<0.0001) and also favored HHV-7 infection (OR=2.835; 95% CI=1.100-7.310; P=0.0275). In addition, 72TP53 variants augmented the risk of GD relapse (OR=1.860; 95% CI=1.015-3.410; P=0.0446). CONCLUSIONS: We suggest that an inherited genetic profile involving TP53 may favor HHV-7 infection and maintenance, which, in turn, may initiate and perpetuate GD autoimmune process.
Assuntos
Doença de Graves/epidemiologia , Doença de Graves/genética , Herpesvirus Humano 7 , Infecções por Roseolovirus/epidemiologia , Proteína Supressora de Tumor p53/genética , Adulto , Autoimunidade , Estudos de Casos e Controles , Ciclofosfamida/análogos & derivados , Citocromo P-450 CYP1A1/genética , Feminino , Predisposição Genética para Doença/epidemiologia , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Doença de Graves/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Regressão Psicológica , Fatores de Risco , Infecções por Roseolovirus/imunologia , Adulto JovemRESUMO
Os herpesvírus tÛm sido vistos como potenciais agentes carcinogÛnicos e identificados em diversas malignidades. Acometem indivíduos imunossuprimidos e também indivíduos saudáveis e possuem elevada prevalÛncia. A capacidade de permanecerem latentes nas células do hospedeiro garante aos vírus sua sobrevivÛncia até serem reativados. Células infectadas por herpes supostamente nÒo seriam destruídas por apoptose em portadores de alteraþ§es no gene TP53. Nossos estudos comprovam uma maior prevalÛncia de herpesvírus tipo 6 em pacientes transplantados renais do que numa populaþÒo controle e mostram que polimorfismos no gene TP53 poderiam influenciar na suscetibilidade O infecþÒo por este vírus. Observamos que os herpesvírus também podem aumentar o risco para o desenvolvimento de carcinomas da pele e isso se associa ao perfil genotípico GSTM1-GSTT1+. Mais recentemente, estudando doenþas auto-imunes, observamos que a infecþÒo pelo herpesvírus 6 aumentou a susceptibilidade para o desenvolvimento da doenþa de Graves. Estes estudos poderÒo ter utilidade na prevenþÒo de doenþas. Por exemplo, pacientes em imunodepressÒo que tenham infecþÒo por herpesvírus devem ser particularmente mais cuidadosos em relaþÒo O exposiþÒo solar.(AU)
Assuntos
Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/epidemiologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Neoplasias/etiologiaRESUMO
Os herpesvírus têm sido vistos como potenciais agentes carcinogênicos e identificados em diversas malignidades. Acometem indivíduos imunossuprimidos e também indivíduos saudáveis e possuem elevada prevalência. A capacidade de permanecerem latentes nas células do hospedeiro garante aos vírus sua sobrevivência até serem reativados. Células infectadas por herpes supostamente não seriam destruídas por apoptose em portadores de alterações no gene TP53. Nossos estudos comprovam uma maior prevalência de herpesvírus tipo 6 em pacientes transplantados renais do que numa população controle e mostram que polimorfismos no gene TP53 poderiam influenciar na suscetibilidade à infecção por este vírus. Observamos que os herpesvírus também podem aumentar o risco para o desenvolvimento de carcinomas da pele e isso se associa ao perfil genotípico GSTM1-GSTT1+. Mais recentemente, estudando doenças auto-imunes, observamos que a infecção pelo herpesvírus 6 aumentou a susceptibilidade para o desenvolvimento da doença de Graves. Estes estudos poderão ter utilidade na prevenção de doenças. Por exemplo, pacientes em imunodepressão que tenham infecção por herpesvírus devem ser particularmente mais cuidadosos em relação à exposição solar.
Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/epidemiologia , Neoplasias/etiologiaRESUMO
PURPOSE: Genetic polymorphisms in genes encoding for enzymes involved in the biotransformation of carcinogens have been shown to be relevant as risk for cancer and may be of considerable importance from a public health point of view. Considering that N-acetyltransferase 2 (NAT2) polymorphisms modulate the response to ionizing radiation, the strongest risk factor recognized to cause differentiated thyroid cancer (DTC) thus far, we sought to determine the influence of NAT2 detoxification system on thyroid cancer susceptibility. EXPERIMENTAL DESIGN: We conducted a prospective case-control study, comparing 195 patients presenting with DTC that were previously genotyped for GSTT1, GSTM1, GSTP1, and CYP1A1, comprising 164 papillary carcinomas and 31 follicular carcinomas, with 196 control individuals paired for gender, age, ethnicity, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. We used PCR-RFLP assays and the combination of 6 variant alleles to define 18 NAT2 haplotypes that characterized slow, intermediate, or rapid phenotypes. RESULTS: A multivariate logistic regression analysis identified the presence of *12A and the absence of *12B, *13, *14B, *14D, *6A, and *7A NAT2 haplotypes as risk factors for DTC. The inheritance of a rapid acetylation phenotype doubled the risk for a papillary carcinoma (odds ratio, 2.024; 95% confidence interval, 1.252-3.272). We found no relationship between genotypes and clinical, pathologic, or laboratory features of patients or between genotypes and outcome. CONCLUSIONS: We showed that NAT2 genotypes and the NAT2 rapid acetylation phenotype are important susceptibility factors for DTC, suggesting that NAT2 detoxification system is involved in this tumor pathogenesis.
Assuntos
Arilamina N-Acetiltransferase/genética , Neoplasias da Glândula Tireoide/genética , Brasil , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Inativação Metabólica , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimialgia Reumática , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: The glutathione-S-transferase (GST) gene family has an important role in the biotransformation and detoxification of different xenobiotics and endogenous carcinogens. GST profile has been associated to an increased risk for several types of tumors in different populations, but ethnic stratification makes data interpretation difficult. The Brazilian population represents a unique model in which the types and frequencies of GST gene polymorphisms are less influenced by ethnicity. MATERIAL/METHODS: To evaluate the influence of GST profile in different age and gender groups regarding the risk of developing cancer and its relationship to smoking habit, the GSTT1, GSTM1, and GSTP1 genotypes of 785 Brazilian patients with cancer and 873 cancer-free controls paired on the basis of sex, age, ethnicity, diet and exercise routine, lifetime occupational history, smoking history, general health conditions, and previous diseases were compared. RESULTS: A univariate logistic regression analysis demonstrated that age over 45 years (p=0.0417) and smoking (p=0.0015) were related to cancer. Multivariate analysis confirmed the importance of advanced age in susceptibility to cancer (p=0.0001). It was also observed that smoking significantly increased the risk of cancer among individuals over 45 years old (OR: 1.825, 95%CI: 1.241-2.682). However, no correlation between risk of cancer, smoking habit, age, or gender and any of the studied GST polymorphisms was found. CONCLUSIONS: It is suggested that GST profile does not exert an important impact on the influence of tobacco smoking on cancer risk.
Assuntos
Glutationa Transferase/genética , Neoplasias/genética , Polimorfismo Genético , Fumar/efeitos adversos , Fatores Etários , Brasil , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Neoplasias/induzido quimicamente , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVE: Cigarette smoking is a well-recognized risk factor of Graves' disease and, particularly, Graves' ophthalmopathy. Hence, germline polymorphisms of detoxification genes and genes belonging to the major DNA repair-apoptosis pathways might have an important role in disease susceptibility. In addition, as some of these genes are regulated by thyroid hormones, they may affect the patients' outcomes. We aimed to assess the influence of the GST, CYP and TP53 gene polymorphisms in the risk of Graves' disease and its outcome. DESIGN: Prospective case-control study. PATIENTS: A PCR-based strategy was used for GSTT1, GSTM1, GSTP1, CYP1A1 and TP53 codon 72 genotypes in a group of 400 Graves' disease patients, and to compare them to 574 control individuals with similar environmental exposure features. RESULTS: GSTM1 and GSTT1 genotypes were equally distributed in cases and controls, respectively. However, GSTP1 (P < 0.0001), CYP1A1 (P < 0.0033) and Pro/ProTP53 (P < 0.0035) variants appeared more frequently in Graves' disease patients than in controls. A multivariate analysis indicated that cigarette smoking and inheritance of GSTP1, CYP1A1 and Pro/ProTP53 variants were important risk factors for Graves' disease, but only smoking appeared as an independent risk factor for Graves' ophthalmopathy. There was no association between clinical features, including ophthalmopathy or treatment outcome, and the studied genotypes. CONCLUSION: We concluded that GSTP1, CYP1A1 and TP53, but not GSTT1 and GSTM1 germline polymorphisms, may be associated with smoking-related Graves' disease susceptibility and configure a risk profile for the disease. However, these polymorphisms do not influence the patients' response to treatment.
Assuntos
Doença de Graves/genética , Polimorfismo Genético , Fumar/genética , Adulto , Antitireóideos/uso terapêutico , Estudos de Casos e Controles , Citocromo P-450 CYP1A1/genética , Feminino , Genótipo , Glutationa Transferase/genética , Doença de Graves/tratamento farmacológico , Doença de Graves/radioterapia , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína Supressora de Tumor p53/genética , Adulto JovemRESUMO
Objective: The association among IRS-IG972R and PPAR-gama2Pro1l5Gln gene variants and insulin resistance is controversial. This study aimed to investigate the relationship between PPAR-gama2Pro115Gln and IRS-IG972R variants to insulin resistance. Design and Setting: This prospective study was developed in the University Hospital of Unicamp. Methods: We studied the prevalence of these mutations in 67 lean and 64 obese subjects (91 women and 40 men, 18 to 67 years old) evaluating metabolic and obesity parameters. Both genetic variants were detected by restriction fragment length polymorphism assays. Insulin sensitivity was estimated through the insulin resistance index; Body Mass Index (BMI), waist, fat and fat-free mass, indirect calorimetry, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, insulin and serum uric acid were also measured. Results: Genetic analysis showed that 5 (3.8%) individuals presented mutations in the PPAR-gama2 gene, all of them homozygotes, whereas polymorphism of the IRS-l gene was found in 12 (9.1 %) cases, all in heterozygosis. There was no correlation between the genetic profile and insulin resistance or any ofthe anthropometric, hemodynamic and biochemical parameters measured in the obese group. The rate of PPAR-gama2 and IRS-l variants was similar in lean and obese subjects. Among the PPAR-gama2Pro1l5Gln carriers, 3 were insulin resistant (p equal 0.05 HOMA-IR greater that 75th). Conclusion: We suggest that there is a trend to the association between the PPAR -gama2Pro 115, but not the IRS-l G972R gene mutation to insulin resistance in the Brazilian population, that needs to be confirmed in larger samples.
Assuntos
Humanos , Masculino , Feminino , Adulto , Obesidade , Receptores Ativados por Proliferador de Peroxissomo , Receptor de Insulina , Resistência à Insulina/genéticaRESUMO
The large use of simple and effective diagnostic tools has significantly contributed to the increase in diagnosis of thyroid cancer over the past years. However, there is compelling evidence that most micropapillary carcinomas have an indolent behavior and may never evolve into clinical cancers. Therefore, there is an urgent need for new tools able to predict which thyroid cancers will remain silent, and which thyroid cancers will present an aggressive behavior. There are a number of well-established clinical predictors of malignancy and recent studies have suggested that some of the patients laboratory data and image methods may be useful. Molecular markers have also been increasingly tested and some of them appear to be very promising, such as BRAF, a few GST genes and p53 polymorphisms. In addition, modern tools, such as immunocytochemical markers, and the measure of the fractal nature of chromatin organization may increase the specificity of the pathological diagnosis of malignancy and help ascertain the prognosis. Guidelines designed to select nodules for further evaluation, as well as new methods aimed at distinguishing carcinomas of higher aggressiveness among the usually indolent thyroid tumors are an utmost necessity.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Fatores Etários , Carcinoma Papilar/etiologia , Carcinoma Papilar/metabolismo , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Masculino , Mucina-1 , Mucinas/genética , Mucinas/metabolismo , Fragmentos de Peptídeos/genética , Proteínas Proto-Oncogênicas B-raf/genética , Lesões por Radiação/mortalidade , Fatores de Risco , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/metabolismo , Tireotropina/sangue , Fatores de Tempo , UltrassonografiaRESUMO
The large use of simple and effective diagnostic tools has significantly contributed to the increase in diagnosis of thyroid cancer over the past years. However, there is compelling evidence that most micropapillary carcinomas have an indolent behavior and may never evolve into clinical cancers. Therefore, there is an urgent need for new tools able to predict which thyroid cancers will remain silent, and which thyroid cancers will present an aggressive behavior. There are a number of well-established clinical predictors of malignancy and recent studies have suggested that some of the patientÆs laboratory data and image methods may be useful. Molecular markers have also been increasingly tested and some of them appear to be very promising, such as BRAF, a few GST genes and p53 polymorphisms. In addition, modern tools, such as immunocytochemical markers, and the measure of the fractal nature of chromatin organization may increase the specificity of the pathological diagnosis of malignancy and help ascertain the prognosis. Guidelines designed to select nodules for further evaluation, as well as new methods aimed at distinguishing carcinomas of higher aggressiveness among the usually indolent thyroid tumors are an utmost necessity.
O uso cada vez mais freqüente de métodos diagnósticos simples e efetivos tem contribuído significativamente para um aumento no diagnóstico de câncer da tiróide nos últimos anos. Entretanto, existem importantes evidências de que muitos dos microcarcinomas papilíferos têm um comportamento indolente e podem nunca evoluir para cânceres clínicos. Existe, portanto, uma necessidade urgente de desenvolver novas ferramentas capazes de predizer quais os tumores tiroidianos que permanecerão silenciosos e quais desenvolverão comportamento agressivo. Há uma série de marcadores clínicos de evolução bem estabelecidos e alguns estudos recentes sugerem que dados laboratoriais e métodos de imagem podem ser úteis. Marcadores moleculares também vêm sendo ativamente investigados e alguns, como BRAF, os genes GST e polimorfismos de p53, parecem promissores. Além disso, marcadores imunocitoquímicos e a medida da natureza fractal da cromatina podem aumentar a especificidade do diagnóstico anatomopatológico e ajudar a predizer o prognóstico. Existe uma necessidade imperiosa de elaborarmos diretrizes destinadas a selecionar os nódulos que merecem prosseguimento em sua avaliação, assim como novos métodos capazes de identificar lesões mais agressivas entre os geralmente indolentes tumores tiroidianos.