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1.
J Mech Behav Biomed Mater ; 103: 103572, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090961

RESUMO

Bioabsorbable polymeric fixation devices have been used as an alternative to metallic implants in orthopedics, preventing the stress shielding effect and avoiding a second surgery for implant removal. However, several problems are still associated with current bioabsorbable implants, including the limited mechanical stiffness and strength, and the adverse tissue reactions generated. To minimize or even eliminate the problems associated with these implants, strategies have been developed to synthesize new implant materials based on chitosan. To overcome the brittle behavior of most 3D chitosan-based structures, glycerol and sorbitol were blended to chitosan and the effect of these plasticizers in the produced specimens was analyzed by flexural tests, Berkovich tests, scanning electron microscopy (SEM) and micro-CT analyzes. The improvement of the mechanical properties was also tested by adding ceramics, namely hydroxyapatite powder and biphasic mixtures of hydroxyapatite (HA) and beta-tricalcium phosphate (ß-TCP). In the plasticizers group, the best combination of the measured properties was obtained for chitosan with 10% glycerol (flexural strength of 53.8 MPa and indentation hardness of 19.4 kgf/mm2), while in the ceramics group the best mechanical behavior was obtained for chitosan with 10% HA+ß-TCP powder (flexural strength of 67.5 MPa and indentation hardness 28.2 kgf/mm2). All the tested material compositions were dense and homogeneous, fundamental condition for a good implant performance. These are encouraging results, which support the continued development of chitosan-based materials for orthopedic fixation applications.


Assuntos
Implantes Absorvíveis , Quitosana , Ortopedia , Cerâmica , Teste de Materiais , Microscopia Eletrônica de Varredura
2.
Mar Drugs ; 17(4)2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31013628

RESUMO

Chitin was extracted from Polybius henslowii, a swimming crab, captured in large quantities throughout the Portuguese coast by purse seine vessels as bycatch. After standard chitin extraction procedures, water-soluble chitosan products were obtained via two different methods: (1) N-acetylation with the addition of acetic anhydride and (2) a reaction with hydrogen peroxide. The chemical structure and molecular weight of chitosan derivatives, water-soluble chitosan (WSC) and chitooligosaccharides (COS), were confirmed by Fourier Transform Infrared Spectroscopy (FT-IR) and gel permeation chromatography (GPC). Antioxidant and metal chelation activities were evaluated, and the growth inhibition capacity was tested on four phytopatogens. The chitooligosaccharides from pereopods (pCOS) and shell body parts (sCOS) inhibited all fungal species tested, particularly Cryphonectria parasitica with 84.7% and 85.5%, respectively. Both radical scavenging and antifungal activities proved to be dose-dependent. Chitooligosaccharides with a low molecular weight (2.7, 7.4, and 10.4 Kg·mol-1) showed the highest activity among all properties tested. These results suggested that chitosan derivatives from P. henslowii raw material could potentially be used against phytopathogens or as ingredient in cosmetics and other products related to oxidative stress.


Assuntos
Antifúngicos/farmacologia , Antioxidantes/farmacologia , Braquiúros/química , Quitosana/farmacologia , Animais , Antifúngicos/química , Antioxidantes/química , Quitina/análogos & derivados , Quitina/química , Quitina/farmacologia , Quitosana/química , Fungos/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Peso Molecular , Oligossacarídeos , Polímeros/química , Polímeros/farmacologia , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Água
3.
Mol Cell Biol ; 39(9)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30782775

RESUMO

Intracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H-rasV12 showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells. PLIN2 gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis that PLIN2 is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in human colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a process that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.


Assuntos
Adenocarcinoma/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias do Colo/metabolismo , Gotículas Lipídicas/metabolismo , Perilipina-2/metabolismo , Adenocarcinoma/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ciclo Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Neoplasias do Colo/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Células NIH 3T3 , Perilipina-2/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Regulação para Cima
5.
J Food Sci ; 83(5): 1366-1372, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29660800

RESUMO

This study was conducted to test the effect of dietary tannin on the fatty acid profile and sensory attributes of meat from Nellore steers. Thirty-two Nellore bull male were distributed in a completely randomized design and fed diets with condensed tannin extract as follows: 0, 10, 30, and 50 g/kg total DM basis. The physicochemical composition of the meat, lipid oxidation, fatty acid profile, flavor, tenderness, and overall acceptance were evaluated. There was a linear decrease (P ≤ 0.05) on lipid content, tenderness, cooking weight loss, myristic, palmitic, and oleic acids in meat as tannin increased in the diets. The total saturated and monounsaturated fatty acids, the atherogenicity index decreased. However, a linear increase (P ≤ 0.05) was observed for linoleic, linolenic, arachidonic, eicosapentaenoic, and docosapentaenoic acids. The physicochemical characteristic of the meat, such as moisture, ash, and protein contents, water retention capacity, final pH, Warner-Bratzler shear force, collagen, and color indexes (lightness, redness, yellowness, and chrome) did not change with dietary tannin. Also, CLA, n-6:n-3 ratio, Δ9 -desaturase, and elongase activity were not different among diets. In conclusion, condensed tannin linearly increases unsaturated fatty acids and decreases the atherogenicity index of meat; thus, it can be recommended at the highest level (50 g/kg DM) in the diet of Nellore steers. PRACTICAL APPLICATION: Agriculture byproducts plays an important part in the diet of ruminant animals and consequently on food chain and has implications for the composition and quality of the livestock products (milk, meat, and eggs) that people consume. Feeding tannin to steers increases the amount of unsaturated fatty acids and meat tenderness, with a concomitant reduction on saturated fatty acids and the atherogenicity index in meat. Thus, we recommend adding tannin to steer diets to reduce the risk factors for cardiovascular diseases in red meat for human consumption.


Assuntos
Fenômenos Químicos , Ácidos Graxos/análise , Proantocianidinas/administração & dosagem , Carne Vermelha/análise , Adulto , Ração Animal/análise , Animais , Bovinos , Cor , Comportamento do Consumidor , Laticínios/análise , Dieta/veterinária , Feminino , Análise de Alimentos , Qualidade dos Alimentos , Inocuidade dos Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proantocianidinas/análise , Fatores de Risco , Paladar , Adulto Jovem
6.
Glob Chang Biol ; 24(5): 2129-2142, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29215789

RESUMO

Brazil is one of the major contributors to land-use change emissions, mostly driven by agricultural expansion for food, feed, and bioenergy feedstock. Policies to avoid deforestation related to private commitments, economic incentives, and other support schemes are expected to improve the effectiveness of current command and control mechanisms increasingly. However, until recently, land tenure was unknown for much of the Brazilian territory, which has undermined the governance of native vegetation and challenged support and incentive mechanisms for avoiding deforestation. We assess the total extent of public governance mechanisms protecting aboveground carbon (AGC) stocks. We constructed a land tenure dataset for the entire nation and modeled the effects and uncertainties of major land-use acts on protecting AGC stocks. Roughly 70% of the AGC stock in Brazil is estimated to be under legal protection, and an additional 20% is expected to be protected after areas in the Amazon with currently undesignated land undergo a tenure regularization. About 30% of the AGC stock is on private land, of which roughly two-thirds are protected. The Cerrado, Amazon, and Caatinga biomes hold about 40%, 30%, and 20% of the unprotected AGC, respectively. Effective conservation of protected and unprotected carbon will depend on successful implementation of the Forest Act, and regularization of land tenure in the Amazon. Policy development that prioritizes unprotected AGC stocks is warranted to promote conservation of native vegetation beyond the legal requirements. However, different biomes and land tenure structures may require different policy settings considering local and regional specifics. Finally, the fate of current AGC stocks relies upon effective implementation of command and control mechanisms, considering that unprotected AGC in native vegetation on private land only accounts for 6.5% of the total AGC stock.


Assuntos
Sequestro de Carbono , Carbono/química , Conservação dos Recursos Naturais/legislação & jurisprudência , Florestas , Agricultura , Brasil , Ecossistema , Propriedade
7.
Curr Rheumatol Rep ; 19(6): 36, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28612332

RESUMO

PURPOSE OF REVIEW: To understand the clinical spectrum of cocaine-levamisole-induced vasculitis. Worldwide recreational drug consumption is high among the adult population from various social strata. The use of cocaine with levamisole, a frequently added antiparasitic diluent, favors the manifestations of vasculitic lesions, especially in the skin. RECENT FINDINGS: New insights into immunological mechanisms involved in the pathogenesis of the disease. There are still many unknown aspects in the pathogenesis of this disease, such as the immune system interaction with p-ANCAs and the release of inflammatory NETs (neutrophil extracellular traps), which are the origin of auto-antigens and tissue damage, manifesting as vasculitic purpura on the skin. The clinical presentation constitutes a challenge for the clinician to be able to distinguish it from small-vessel vasculitides. This paper intends to improve the understanding of this condition, exhibiting the broad clinical spectrum of local and systemic manifestations of cocaine-levamisole-induced vasculitis, to facilitate a timely diagnosis, in order to take corrective measures and avoid sequelae, along with tissue damage and the consequent deformities and permanent scars.


Assuntos
Cocaína/efeitos adversos , Drogas Ilícitas/efeitos adversos , Levamisol/efeitos adversos , Vasculite/induzido quimicamente , Anticorpos Anticitoplasma de Neutrófilos , Armadilhas Extracelulares , Humanos , Vasculite/imunologia
8.
Colloids Surf B Biointerfaces ; 147: 81-89, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27494772

RESUMO

In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate - CaCl2)/(chitosan+glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle≈0) and biocompatibility, it should avoid the use of further surface treatments to enhance the users comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug.


Assuntos
Alginatos/química , Materiais Biocompatíveis/química , Quitosana/química , Lentes de Contato Hidrofílicas , Liberação Controlada de Fármacos , Lentes Intraoculares , Silicones/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Interações Hidrofóbicas e Hidrofílicas , Propriedades de Superfície
9.
J Mech Behav Biomed Mater ; 40: 413-425, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25305635

RESUMO

Chitosan biocompatibility and biodegradability properties make this biopolymer promising for the development of advanced internal fixation devices for orthopedic applications. This work presents a detailed study on the production and characterization of three dimensional (3D) dense, non-porous, chitosan-based structures, with the ability to be processed in different shapes, and also with high strength and stiffness. Such features are crucial for the application of such 3D structures as bioabsorbable implantable devices. The influence of chitosan's molecular weight and the addition of one plasticizer (glycerol) on 3D dense chitosan-based products' biomechanical properties were explored. Several specimens were produced and in vitro studies were performed in order to assess the cytotoxicity of these specimens and their physical behavior throughout the enzymatic degradation experiments. The results point out that glycerol does not impact on cytotoxicity and has a high impact in improving mechanical properties, both elasticity and compressive strength. In addition, human mesenchymal stem/stromal cells (MSC) were used as an ex-vivo model to study cell adhesion and proliferation on these structures, showing promising results with fold increase values in total cell number similar to the ones obtained in standard cell culture flasks.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis/química , Quitosana/química , Células-Tronco Mesenquimais/citologia , Adesão Celular , Proliferação de Células , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Engenharia Tecidual
10.
Ann N Y Acad Sci ; 1325: 69-76, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25266016

RESUMO

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on comparative genomic analysis of esophageal cancers: genomic polymorphisms, the genetic and epigenetic drivers in esophageal cancers, and the collection of data in the UK Barrett's Oesophagus Registry.


Assuntos
Epigênese Genética/genética , Neoplasias Esofágicas/genética , Genômica/tendências , Polimorfismo Genético/genética , Animais , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/prevenção & controle , Genômica/métodos , Humanos , Paris
11.
Biomaterials ; 34(38): 9886-904, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24050875

RESUMO

Biosynthetic nerve grafts are desired as alternative to autologous nerve grafts in peripheral nerve reconstruction. Artificial nerve conduits still have their limitations and are not widely accepted in the clinical setting. Here we report an analysis of fine-tuned chitosan tubes used to reconstruct 10 mm nerve defects in the adult rat. The chitosan tubes displayed low, medium and high degrees of acetylation (DAI: ≈ 2%, DA: ≈ 5%, DAIII: ≈ 20%) and therefore different degradability and microenvironments for the regenerating nerve tissue. Short and long term investigations were performed demonstrating that the chitosan tubes allowed functional and morphological nerve regeneration similar to autologous nerve grafts. Irrespective of the DA growth factor regulation demonstrated to be the same as in controls. Analyses of stereological parameters as well as the immunological tissue response at the implantation site and in the regenerated nerves, revealed that DAI and DAIII chitosan tubes displayed some limitations in the support of axonal regeneration and a high speed of degradation accompanied with low mechanical stability, respectively. The chitosan tubes combine several pre-requisites for a clinical acceptance and DAII chitosan tubes have to be judged as the most supportive for peripheral nerve regeneration.


Assuntos
Quitosana/química , Acetilação , Animais , Western Blotting , Cromatografia em Gel , Eletrofisiologia , Feminino , Regeneração Tecidual Guiada/métodos , Imuno-Histoquímica , Espectroscopia de Ressonância Magnética , Regeneração Nervosa/fisiologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Exp Mol Pathol ; 91(2): 584-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21777580

RESUMO

Esophageal squamous cell carcinoma (ESCC) is highly fatal due to late diagnosis and inefficient treatment. Early disease detection could improve diagnosis and patient survival. Esophageal squamous epithelial cells express SPRR3, a member of the small proline-rich protein family, which is downregulated in ESCC. Therefore, SPRR3 expression may be used as a biomarker to follow the transition from healthy mucosa to ESCC. Both SPRR3 mRNA splice variants, v1 and v2, were evaluated by real time PCR in tumor and histologically normal adjacent tissue biopsies from 84 ESCC patients and 18 healthy controls. SPRR3-v1 was most highly expressed in the esophageal mucosa of healthy subjects, with an increasingly lower expression in the adjacent mucosa of ESCC patients and in tumors, respectively. SPRR3-v2 expression was low in normal mucosa and in tumors but it was higher in the adjacent mucosa of ESCC patients. In addition, we found a significant correlation between a lower SPRR3-v1 and SPRR3-v2 expression and age and alcohol consumption, respectively. SPRR3 protein expression presented a good correlation with SPRR3 mRNA expression. Cut-off points to discriminate between healthy mucosa, tumor and adjacent mucosa were determined with receiver operating characteristic (ROC) curves. This analysis showed that SPRR3-v1 expression discriminates the esophageal mucosa of healthy subjects from the adjacent mucosa and the tumor of ESCC patients with high sensitivity and specificity. Our data shows that the quantitative analysis of SPRR3 mRNA is a robust and reliable method to monitor the malignant transformation of the healthy esophageal mucosa into ESCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Neoplasias Esofágicas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Demografia , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Sensibilidade e Especificidade
14.
Rev. colomb. reumatol ; 17(2): 80-85, Apr.-June 2010. tab
Artigo em Espanhol | LILACS | ID: lil-636824

RESUMO

Las espondiloartritis comparten un contexto ambiental, genético y clínico. Objetivo. Conocer y describir el comportamiento demográfico, clínico y radiológico de pacientes con espondiloartritis en el Hospital Pablo Tobón desde el 1 de enero de 2005 hasta el 31 de diciembre de 2008. Materiales y métodos. Este es un estudio descriptivo, observacional, de corte transversal. Se empleó estadística descriptiva para las variables demográficas, clínicas, radiológicas y los diversos tipos de tratamiento. Resultados. 71 pacientes fueron identificados. Las características clínicas más importantes fueron: dolor lumbar inflamatorio en el 84% de los pacientes, entesopatía, 67%; artritis periférica, 64% y dolor glúteo alternante, 57%. Las articulaciones comprometidas con mayor frecuencia fueron: sacroilíacas, 62%; tobillos, 32%; rodillas, 30%; tarso, 14%. El 64% presentó sacroilitis radiológica. Las manifestaciones extraarticulares más frecuentes fueron: dactilitis, 22%; uveítis, 19%; compromiso renal, 5% y fibrosis pulmonar, 1%. Los índices de actividad (BASDAI) fueron de 4.82 y la función (BASFI) de 4. 54% y 34% de los pacientes tenían eritrosedimentación y PCR elevada, respectivamente. El HLA B27 + en el 52%. Los DMARDs (sulfasalazina y metotrexate) fueron los medicamentos más usados en el 68% de los casos. Le siguieron los AINES en el 52% y los medicamentos anti-TNF en el 42% de los pacientes (Infliximab 20%, adalimumab 16% y etanercept 6%). Conclusión. Nuestros pacientes tenían una enfermedad activa y con limitación funcional. Se encontró un alto porcentaje de pacientes con espondiloartritis indiferenciada. La dactilitis fue la manifestación extraarticular más frecuente y el compromiso radiológico fue similar al descrito en la literatura. Palabras clave: espondiloartritis, índices de actividad, dactilitis, entesitis.


Spondyloartropahties share a genetic, clinical and environmental context. Objective. To describe demographic, clinical and radiological characteristics of spondyloarthropathies in a tertiary hospital. Methods. Descriptive analysis of a 71 patients. Demographics, clinical, radiological and treatment modalities are shown. Results. A total of 71 patients were identified. Low back pain 84%, entesopathye 67%, peripheral arthritis 64% and alternant buttock pain were often seen. The most common joint involved were sacroiliac joints 62%, ankles 32%, knees 30%, tarsal joints 14%. Radiological sacroiliacs involvement 64%. Dactilytis 22%, uveitis 19%, renal and pulmonary involvement were seen 5% and 1% respectively. Activity and functional indexes were (BASDAI) 4.82 and (BASFI) 4. High ESR and PCR were seen 54% and 34%, while HLA B27+52%. DMARDs (sulfasalazine and methotrexate) were used 68%. NSAIDs 52%. Anti-TNF blockers 42% (Infliximab 20%, adalimumab 16% and etanercept 6%). Conclusion. Our patients shown an active disease. A high incidence of undifferentiated spondyloarthropahies was found. Dactylitis was the most common extraarticular manifestation and radiological findings were similar to previously reported in the literature.


Assuntos
Humanos , Estudos de Coortes , Espondilartrite , Radioterapia , Comportamento , Técnicas de Laboratório Clínico , Indicadores Demográficos , Hospitais
15.
Acta Trop ; 95(1): 58-66, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15862583

RESUMO

Schistosoma mansoni has been reported to cause a downregulation of hepatic cytochrome P450 activities after granulomas are formed around worm eggs harbored in the mouse liver. Only a few studies, however, provided data on the activity of xenobiotic-biotransaformation enzymes in the early phase of S. mansoni infection. In this study, we evaluated the alterations of liver microsomal enzymes during early infection (post-infection days, PIDs, 15 and 30) when granulomas are not found in the mouse liver yet. Swiss Webster (SW) and DBA/2 mice of either sex were infected with 100 S. mansoni cercariae on postnatal day 10. Levels of total-CYPs and activities of alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD), N-nitrosodimethylamine-N-demethylase (NDMA-d), coumarin 7-hydroxylase (COH, DBA/2 only) and UDP-glucuronosyltransferase (UGT) were measured in liver microsomes from mice killed on PIDs 15 and 30. Age-matched (sham-infected) mice of the same sex and strain were used as controls. Neither total-CYP levels nor microsomal enzyme activities were altered in SW and DBA/2 mice on PID 15. On PID 30, total-CYP levels, and COH, PROD and UGT activities remained unaltered, while gender- and strain-specific minor changes of EROD, MROD, BROD and NDMA-d (i.e., increase in SW and reduction in DBA/2) were found. In conclusion, our results suggest that, contrasting to a consistent and almost generalized downregulation of CYPs in chronic schistosomiasis, alterations of hepatic CYPs in early (acute) infection are isoform and mouse's gender and strain specific.


Assuntos
Microssomos Hepáticos/enzimologia , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/fisiopatologia , Doença Aguda , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Glucuronosiltransferase/metabolismo , Isoenzimas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , Microssomos Hepáticos/patologia , Esquistossomose mansoni/parasitologia , Fatores de Tempo
16.
Cancer Epidemiol Biomarkers Prev ; 13(9): 1473-9, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15342448

RESUMO

The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile-->Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86-1.12) with the GSTM1 null, 1.11 (0.87-1.41) with the GSTT1 null, 1.01 (0.79-1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62-1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.


Assuntos
Aciltransferases/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Glutationa Transferase/genética , Sequência de Bases , Carcinógenos Ambientais/farmacocinética , Carcinógenos Ambientais/toxicidade , Estudos de Casos e Controles , Deleção Cromossômica , Códon , Análise Mutacional de DNA , Feminino , Triagem de Portadores Genéticos , Predisposição Genética para Doença/genética , Genótipo , Humanos , Metanálise como Assunto , Polimorfismo Genético/genética , Fatores de Risco
17.
Biomedica ; 23(3): 293-300, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14582332

RESUMO

A cross-sectional and multicenter study was undertaken to analyze the clinical and immunological characteristics at diagnosis associated with nephritis in northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty-nine patients with lupus nephritis were included and were compared to 100 SLE patients without nephritis. A multivariate analysis was performed. The patients who developed nephritis had a higher frequency of oral ulcers (41% vs. 21%, OR = 3.1, 95% CI: 1.3-7.5 p = 0.01) and malar erythema (77% vs. 45%, OR = 4.4, 95% CI: 1.8-10.8 p = 0.001). Lupus nephritis was observed in 77% of cases during the first year of the disease. The frequency of anti-DNA antibodies was higher in patients with nephritis, however, differences were not statistically significant (83% vs 64%, OR = 2.6, 95% CI: 1.03-6.41, p = 0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remained unchanged throughout the evolution of the disease. Patients with lupus nephritis had a higher prevalence of arterial hypertension (60% vs 10%, OR = 13.7, 95% IC: 5-37, p = 0.00001) and hyperlipidemia (30% vs 7%, OR = 8.1, 95% IC: 2.5-27, p = 0.0006) at onset. Finally, patients with lupus nephritis required more hospitalizations (> 1) over the course of disease (89% vs 60%, OR = 7.8, 95% CI: 2.1-29, p = 0.002). In conclusion, lupus nephritis appears early during the course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of disease are associated factors. Lupus nephritis is a major risk factor leading to repeated hospitalizations. This study may help to assist in public health policies in our population in order to improve patient outcomes while simultaneously reducing disease costs.


Assuntos
Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Adulto , Colômbia , Estudos Transversais , Feminino , Humanos , Nefrite Lúpica/complicações , Masculino
18.
Biomédica (Bogotá) ; 23(3): 293-300, sept. 2003. tab
Artigo em Espanhol | LILACS | ID: lil-356779

RESUMO

A cross-sectional and multicenter study was undertaken to analyze the clinical and immunological characteristics at diagnosis associated with nephritis in northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty nine patients with lupus nephritis were included and were compared to 100 SLE patients without nephritis. A multivariate analysis was performed. The patients who developed nephritis had a higher frequency of oral ulcers (41 percent vs. 21 percent, OR3.1, 95 percent CI: 1.3-7.5 p 0.01) and malar erythema (77 percent vs. 45 percent, OR4.4, 95 percent CI: 1.8-10.8 p0.001). Lupus nephritis was observed in 77 percent of cases during the first year of the disease. The frequency of anti-DNA antibodies was higher in patients with nephritis, however, differences were not statistically significant (83 percent vs 64 percent, OR2.6, 95 percent CI: 1.03-6.41, p0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remained unchanged throughout the evolution of the disease. Patients with lupus nephritis had a higher prevalence of arterial hypertension (60 percent vs 10 percent, OR13.7, 95 percent IC: 5-37, 0.00001) and hyperlipidemia (30 percent vs 7 percent, OR8.1, 95 percent IC: 2.5-27, p0.0006) at onset. Finally, patients with lupus nephritis required more hospitalizations (1) over the course of disease (89 percent vs 60 percent, OR7.8, 95 percent IC: 2.1-29, p0.002). In conclusion, lupus nephritis appears early during the course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of disease are associated factors. Lupus nephritis is a major risk factor leading to repeated hospitalizations. This study may help to assist in public health policies in our population in order to improve patient outcomes while simultaneously reducing disease costs.


Assuntos
Humanos , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Anticorpos , Colômbia , Hiperlipidemias , Hipertensão , Fatores de Risco
20.
Rev. colomb. reumatol ; 10(1): 9-18, mar. 2003. tab, graf
Artigo em Espanhol | LILACS | ID: lil-359023

RESUMO

Objetivos: Caracterizar la presentación clínica de los pacientes con polimiositis y dermatomiositis en el Servicio de Reumatología del Instituto de Seguros Sociales de Medellín, evaluar su presentación clínica, las manifestaciones sistémicas, su asociación a neoplasias y la respuesta a corticosteroides. Métodos: Se diseñó un estudio descriptivo transversal incluyendo todos los pacientes seguidos entre enero de 1992 y febrero de 2000, con un tiempo de seguimiento mínimo de 6 meses y que cumplieran los criterios definitivos para polimiositis y dermatomiositis, según Bohan y Peter. Resultados: Se incluyen 29 pacientes, 17 con dermatomiositis y 12 con polimiositis, con mayor representación del sexo femenino (4.1/1) y con una edad promedio al momento del diagnóstico de 34,5 años (rango de 4 a 69 años). Las manifestaciones sistémicas más frecuentes fueron la disfagia (69 por ciento) y artralgias/artritis (62 por ciento); la manifestación pulmonar más frecuente fue la EPID (17,2 por ciento) y se documentó neoplasia durante el seguimiento en el 17,2 por ciento de los pacientes siendo más frecuentes en el grupo de mayores de 50 años (55 por ciento). La mortalidad fue del 13,7 por ciento y las causas de muerte fueron EPID y neoplasias (2 casos cada una). El 29,5 por ciento de los pacientes respondieron al tratamiento esteroideo y el 44,5 por ciento mejoraron al combinar un segundo inmunosupresor; en el 26 por ciento de los casos, la gravedad de los pacientes justificó la combinación de esteroides con otro inmunosupresor desde el comienzo del tratamiento. Conclusiones: Encontramos menor frecuencia de EPID y broncoaspiración que lo descrito en la literatura mundial. Las neoplasias fueron más frecuentes en los pacientes diagnosticados después de 50 años de edad. La tercera parte de los pacientes respondió satisfactoriamente a esteroides como única terapia. Los restantes pacientes requirieron uno o más inmunosupresores adicionales por resistencia a esferoides o por la gravedad de su presentación. Se propone seleccionar tempranamente a los pacientes con mayor severidad para utilizar, desde el principio del tratamiento, la combinación de esferoides e inmunosupresores para evitar las complicaciones inherentes al tratamiento esteroideo y prevenir la atrofia muscular como secuela de las miopatías inflamatorias.


Assuntos
Dermatomiosite , Polimiosite
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