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1.
Open Biol ; 10(4): 190258, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32228398

RESUMO

Haemocyanins (Hcs) are copper-containing, respiratory proteins that occur in the haemolymph of many arthropod species. Here, we report the presence of Hcs in the chilopode Myriapoda, demonstrating that these proteins are more widespread among the Arthropoda than previously thought. The analysis of transcriptome of S. subspinipes subpinipes reveals the presence of two distinct subunits of Hc, where the signal peptide is present, and six of prophenoloxidase (PPO), where the signal peptide is absent, in the 75 kDa range. Size exclusion chromatography profiles indicate different quaternary organization for Hc of both species, which was corroborated by TEM analysis: S. viridicornis Hc is a 6 × 6-mer and S. subspinipes Hc is a 3 × 6-mer, which resembles the half-structure of the 6 × 6-mer but also includes the presence of phenoloxidases, since the 1 × 6-mer quaternary organization is commonly associated with hexamers of PPO. Studies with Chelicerata showed that PPO activity are exclusively associated with the Hcs. This study indicates that Scolopendra may have different proteins playing oxygen transport (Hc) and PO function, both following the hexameric oligomerization observed in Hcs.


Assuntos
Catecol Oxidase/metabolismo , Quilópodes/metabolismo , Precursores Enzimáticos/metabolismo , Hemocianinas/química , Hemocianinas/metabolismo , Análise de Sequência de DNA/métodos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Catecol Oxidase/química , Quilópodes/genética , Cromatografia em Gel , Precursores Enzimáticos/química , Regulação da Expressão Gênica , Hemocianinas/genética , Hemolinfa/metabolismo , Modelos Moleculares , Peso Molecular , Filogenia , Conformação Proteica , Multimerização Proteica
2.
Pulmonology ; 25(3): 154-161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29898876

RESUMO

BACKGROUND: Recent studies show contradictory data on the incidence of hospitalizations for acute bronchiolitis (AB) and an escalating increase in public health burden. AIMS AND OBJECTIVES: We aimed to analyze the population-based admission rate for AB in children under 2 years of age, in Portuguese public hospitals, from 2000 to 2015, to assess trends and regional variations in admission rate; outcomes; associated direct health-care costs; and changes in management after the implementation of national guidelines. METHODS: Retrospective observational study, conducted using a Portuguese administrative database, which contains all registered public hospitalizations in mainland Portugal, and demographic data from the National Statistics Institute. RESULTS: Over the study period, we recorded 80,491 admissions for AB. The mean admission rate was 26.28 and was higher in the northernmost regions of the country. Along the time, the admission rate rose by an average of 1.6% per year (3.8% in children younger than 3 months) and the average length of stay (LOS) was 6.1 days and decreased, to a minimum of 5.5 days in 2014. The in-hospital mortality rate (0.1%) and the use of invasive ventilation remained stable, but non-invasive ventilation use increased from 0.4% in 2000 to 4% in 2015. The direct estimated total costs were of 72,420,732€. In recent years, there was a decrease in the reported tests and procedures. CONCLUSIONS: AB remains a major burden in the healthcare system. The admission rate increased but does not seem to be due to an increase in severity, as LOS decreased, and the use of invasive ventilation and mortality remained unchanged.


Assuntos
Bronquiolite/epidemiologia , Hospitalização/tendências , Bronquiolite/economia , Bronquiolite/terapia , Efeitos Psicossociais da Doença , Feminino , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Portugal/epidemiologia , Respiração Artificial/economia , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos
3.
Transplant Proc ; 50(3): 819-823, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661445

RESUMO

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) consists of the intravenous infusion of healthy hematopoietic stem cells to restore the medullary and immunologic function of patients affected by a series of hematologic, oncologic, immunologic, malignant and nonmalignant inherited or acquired diseases, with the possibility of cure or increase of disease-free survival. OBJECTIVE: To characterize the epidemiologic profile and the cases of death of patients who underwent HSCT. METHODS: This is a cohort quantitative study, nested with a retrospective, descriptive, and analytical study of a hospital-based cohort that included the patients who underwent HSCT at a referral service in the state of Rio Grande do Norte, a region of northeastern Brazil. RESULTS: There was a slight male prevalence (52.94%), the age of the patients ranged from 2 to 73 years old, 18.38% were brown, 47.06% were married, 15.07% were students, 78.31% had a diagnosis of multiple myeloma, 93.38% developed gastrointestinal toxicities, all patients received chemotherapeutic treatment, 54.78% had allogeneic HSCT, and the cause of the most recorded deaths was septic shock (48.19%). CONCLUSIONS: This study showed relevant scientific evidence on the clinical and epidemiologic profile of patients who underwent HSCT. In general, sociodemographic data are similar to national and international research results.


Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Mieloma Múltiplo/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Transplant Proc ; 50(3): 827-830, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661447

RESUMO

INTRODUCTION: The quality of corneal tissue is influenced by several factors inherent to the recipient, donor, donation process, and transplantation that may primarily or secondarily interfere in the survival of a corneal graft. OBJECTIVE: The objective of this study was to identify the factors inherent to the donation process, specifically related to the harvesting and processing of tissue and to the donor, that may interfere with the quality of corneal tissue. MATERIALS AND METHODS: This was a cross-sectional, descriptive, and analytical study carried out from January to April 2015 at the Onofre Lopes University Hospital, Natal/RN, Brazil. A survey of the keratoplasties performed between the years 2010 and 2014 was carried out, totaling 258 donated corneas. RESULTS: The mean age of donors was 42.08 years, ranging from 2-80 years. As for quality, 64.45% of the corneas were classified as good, 23.05% as regular, 11.33% as poor, and 1.17% as excellent. The mean time between death and preservation was approximately 7 hours and 15 minutes, and the mean time elapsed until use was 10 days after immersion in preservation medium. DISCUSSION AND CONCLUSIONS: Factors inherent in the donation process that may interfere with the quality of the corneal graft correspond to factors of a chronological nature: donor age and time elapsed between death and preservation of the graft.


Assuntos
Transplante de Córnea , Preservação de Órgãos/estatística & dados numéricos , Fatores de Tempo , Coleta de Tecidos e Órgãos/estatística & dados numéricos , Transplantes/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Córnea/patologia , Córnea/cirurgia , Estudos Transversais , Bancos de Olhos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Inquéritos e Questionários , Doadores de Tecidos/estatística & dados numéricos , Coleta de Tecidos e Órgãos/métodos , Transplantes/patologia , Transplantes/cirurgia , Adulto Jovem
5.
Genet Mol Res ; 16(2)2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28437552

RESUMO

In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.


Assuntos
Biomarcadores Tumorais/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mieloide de Fase Crônica/genética , RNA Mensageiro/genética , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Feminino , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/sangue , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , RNA Mensageiro/metabolismo
7.
Lymphology ; 50(4): 188-196, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30248723

RESUMO

Congenital pulmonary lymphangiectasia (CPL) and chylothorax (CC) are rare lymphatic developmental disorders. We report six clinical cases of CPL and CC that were admitted to our level III neonatal intensive care unit over the last 20 years. One case of unilateral CC was successfully treated with pleuro-amniotic shunt; three cases of bilateral CC were associated to lung hypoplasia, hydrops fetalis, and generalized lymphangiectasias; one case of CPL was associated with obstructive congenital heart defect; one case of unilateral CC was successfully treated with thoracocentesis and medium-chain triglyceride diet. Mortality was high (66.6%).

8.
Transplant Proc ; 48(7): 2366-2370, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27742299

RESUMO

BACKGROUND: The purpose of the study was to characterize the epidemiological profile and average time on the waiting list of patients undergoing an urgent corneal transplantation (CT) in a referral center in the state of Rio Grande do Norte, northeastern Brazil. METHODS: This cross-sectional study included cases of urgent corneal transplants performed in a referral center from January 2010 to December 2014. Data were collected between January and March 2015. RESULTS: Seventy-four cases of emergency CT were analyzed. Of these, 69.4% were male, over the age range from 8 to 92 years. There were 38 transplants occurring in the right eye, 55.4% with tectonic purpose, 25.7% with optical purpose, and 18.9% therapy purpose. The main indications for patient inclusion in an emergency were the perforation (52.7%) and corneal ulcer unresponsive to medical treatment (33.8%). Interstitial keratitis was the most common diagnosis (74.3%), responsible for all prioritized cases in line for corneal ulcer unresponsive to treatment. The average length of the waiting line to perform the urgent CT was 9.03 days. CONCLUSIONS: In this study, there was a predominance of male patients and patients >50 years old, which corroborates the results of other studies with similar results. Perforation was the main indication to include the patient on the urgency list (52.7%). There is a need for further research to improve public health policies on the process of corneal transplantation as well as raising awareness of the importance of organ donation.


Assuntos
Transplante de Córnea/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Doenças da Córnea/cirurgia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
Enferm. univ ; 13(2): 90-98, abr.-jun. 2016. graf
Artigo em Espanhol | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-828736

RESUMO

Objetivo Analizar la percepción de los estudiantes en relación con las contribuciones de su inserción en actividades artístico-culturales en el espacio universitario para la formación en enfermería. Método Investigación cualitativa, guiada por la epistemología de Fleck. Participaron 17 estudiantes de enfermería integrantes de movimientos artístico-culturales existentes en una institución de enseñanza superior, a saber: Grupo teatral, grupo musical y grupo de Maracatú. Los datos fueron recolectados por medio de entrevista semiestructurada y organizados por la técnica del discurso del sujeto colectivo. Resultados: Los estudiantes destacaron entre las ventajas de las actividades artístico-culturales el estímulo para estudiar, sentirse relajado y más preparado para las actividades académicas, así como propiciar el desarrollo de sensibilidad y competencias que puedan transformar los escenarios de la práctica clínica de enfermería. Fueron indicadas como dificultades, la credibilidad de estas actividades en la academia, frente a la lógica de la formación curativa. Conclusiones: Integrar actividades artísticas y culturales con la formación académica permite al alumno protagonizar modos renovados de pensar en el cuidado de enfermería y fortalecer conexiones con los diferentes conocimientos necesarios para la práctica del cuidado holístico.


Objective To analyze the students' perceptions of the impact which their participation in artistic-cultural activities within the university space has on their nursing-formation process. Method: This is a qualitative research guided by the epistemology of Fleck. Seventeen nursing students from a high level school, and also members of artistic-cultural movements such as theater, music and Maracatu groups, participated in this study. Data were collected through semi-structured interviews and then organized following the collective subject discourse technique. Results: Related to the positive influence of their artistic-cultural activities, the students highlighted their stimulus to study, feeling relaxed, and being more prepared for the academic activities including those which can help them develop competences and sensibilities to improve the clinical nursing practice scenarios. A remark on the academia who doubts the credibility of these activities and who follows a model in which health is only viewed as the absence of illness was also highlighted. Conclusions: The integration of artistic and cultural activities into the nursing formation process allows the students to develop renewed modes of thinking which can strengthen the links among their knowledge areas, and thus prepare them better for a holistic care practice


Objetivo Analisar a percepção dos estudantes em relação às contribuições da sua inserção em atividades artístico-culturais no espaço universitário para a formação em enfermagem. Método: Investigação qualitativa, guiada pela epistemologia de Fleck. Participaram 17 estudantes de enfermagem, integrantes de movimentos artístico-culturais existentes em uma instituição de ensino superior, a saber: Grupo teatral, grupo musical e grupo de Maracatú. Os dados foram coletados por médio da entrevista semiestruturada e organizados pela técnica de discurso do sujeito coletivo. Resultados Os estudantes destacaram de entre as vantagens das atividades artístico-culturais, o estímulo para estudar, sentir-se relaxado e mais preparado para as atividades acadêmicas, bem como propiciar o desenvolvimento de sensibilidade e competências que pudessem transformar os cenários da prática clínica de enfermagem. Foram indicadas como dificuldades, a credibilidade destas atividades na escola, perante à lógica da formação curativista. Conclusões Integrar atividades artísticas e culturais na formação acadêmica, permite ao aluno protagonizar modos renovados de pensar no cuidado de enfermagem e fortalecer conexões com os diferentes conhecimentos necessários para a prática do cuidado holístico.


Assuntos
Humanos , Masculino , Feminino , Estudantes de Enfermagem , Enfermagem , Capacitação Profissional
10.
Rev Port Pneumol (2006) ; 22(3): 157-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26804664

RESUMO

INTRODUCTION: Thoracoscopy is increasingly being used in the treatment of empyema. This study assesses feasibility, efficacy and safety in children. MATERIAL AND METHODS: Clinical files of patients who underwent primary thoracoscopy for empyema between 2006 and 2014 were reviewed. Demographic, clinical and surgical data were analyzed and a comparison between the period before (period1) and after (period2) the learning curve was performed. RESULTS: Ninety-one patients (53 males, 58%) were submitted to thoracoscopy at a median age of 4 years. There were 19 conversions to thoracotomy with a steady decrease of conversion rate until 2009 (period1) and no conversions thereafter (period2). There was no difference in any of the analyzed parameters between patients submitted to thoracoscopy alone and those requiring conversion in period1. Six cases (6.6%) needed redo-operation (five in period2) and thoracotomy was the elected approach in four. Necrotizing pneumonia was present in 60% of the reoperated cases; in other words, in period2 3 out of 9 cases with necrotizing pneumonia required reintervention (p=0.07). Thoracotomy was avoided in sixty-eight (75%) patients (62% in period1 versus 92% in period2, p=0.001). DISCUSSION AND CONCLUSIONS: Thoracoscopic approach for empyema is feasible and safe avoiding a significant number of thoracotomies after a short learning curve. An increase of reintervention rate should be expected, but throracoscopy alone is effective in the great majority of the cases. Necrotizing pneumonia may be associated with a higher risk of reintervention, as it is a contra-indication to thoracoscopy and probably surgery.


Assuntos
Empiema Pleural/cirurgia , Toracoscopia , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
11.
Biochimie ; 118: 60-70, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26276061

RESUMO

Comparisons between venoms from snakes kept under captivity or collected at the natural environment are of fundamental importance in order to obtain effective antivenoms to treat human victims of snakebites. In this study, we compared composition and biological activities of Bothrops atrox venom from snakes collected at Tapajós National Forest (Pará State, Brazil) or maintained for more than 10 years under captivity at Instituto Butantan herpetarium after have been collected mostly at Maranhão State, Brazil. Venoms from captive or wild snakes were similar except for small quantitative differences detected in peaks correspondent to phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP) class PI and serine proteinases (SVSP), which did not correlate with fibrinolytic and coagulant activities (induced by PI-SVMPs and SVSPs). In both pools, the major toxic component corresponded to PIII-SVMPs, which were isolated and characterized. The characterization by mass spectrometry of both samples identified peptides that matched with a single PIII-SVMP cDNA characterized by transcriptomics, named Batroxrhagin. Sequence alignments show a strong similarity between Batroxrhagin and Jararhagin (96%). Batroxrhagin samples isolated from venoms of wild or captive snakes were not pro-coagulant, but inhibited collagen-induced platelet-aggregation, and induced hemorrhage and fibrin lysis with similar doses. Results suggest that in spite of environmental differences, venom variability was detected only among the less abundant components. In opposition, the most abundant toxin, which is a PIII-SVMP related to the key effects of the venom, is structurally conserved in the venoms. This observation is relevant for explaining the efficacy of antivenoms produced with venoms from captive snakes in human accidents inflicted at distinct natural environments.


Assuntos
Bothrops/fisiologia , Venenos de Crotalídeos/química , Metaloproteases/química , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Venenos de Crotalídeos/metabolismo , Feminino , Masculino , Metaloproteases/metabolismo , Dados de Sequência Molecular , RNA Mensageiro/análise , Espectrometria de Massas em Tandem
13.
Arq. bras. med. vet. zootec ; 67(3): 940-944, May-Jun/2015. ilus
Artigo em Português | LILACS | ID: lil-779233

RESUMO

The aim of this study was to evaluate the antimicrobial activity of essential oils on enterobacteria Escherichia coli and Staphylococcus aureus isolated from poultry fecal samples in the cloaca from 49 laying hens. To analyze the antimicrobial sensibility an agar diffusion susceptibility test was performed and the Minimum Inhibitory Concentration (MIC) and the Minimum Bactericida Concentration (MBC) of Lippia origanoides and Lippia rotundifolia essential oils was determined. The concentrations used were 160, 80 and 40 L/mL. The L. origanoides essential oil showed antimicrobial effect from 40 L/mL dose against both microorganisms, with larger efficiency in E. coli. The L.rotundifolia essential oil was more efficient at the concentration of 160L/mL. Its effect was observed in all microorganisms. These results suggest that L. origanoides oil is more effective than L. rotundifolia oil in inhibiting the growth of microorganism isolated from poultry, although it also has a satisfactory antimicrobial effect. Results indicate the potential use of these plant's essential oils in poultry feed as an alternative to conventional antimicrobial products.


Assuntos
Animais , Anti-Infecciosos/uso terapêutico , Aves Domésticas/microbiologia , Lippia/microbiologia , Escherichia coli , Óleos Voláteis/uso terapêutico , Staphylococcus aureus
14.
Artigo em Inglês | MEDLINE | ID: mdl-25966653

RESUMO

The organic sulfur compound 3-mercaptopropionic acid (3-MPA) is an important thiol intermediate in organic sulfur metabolism in natural environments. It is generated during degradation of sulfur-containing amino acids (e.g. methionine) and from demethylation of dimethylsulfoniopropionate (DMSP). This pathway is an alternative enzymatic process in the DMSP catabolism that routes sulfur away from the climatically-active dimethyl sulfide (DMS). 3-MPA detection and subsequent quantification in different matrices is difficult due to its extreme reactivity. We therefore developed a sensitive method for determination of 3-MPA based on pre-column derivatization with monobromobimane and analysis by high-performance liquid chromatography (HPLC) with fluorescence detection. This methodology was first tested with 3-MPA standards under low (0.005-0.2µmolL(-1)) and high (1-25µmolL(-1)) concentrations. For the optimization of the reaction, CHES and, alternatively, Tris-HCl buffers were evaluated in the derivatization step, with Tris-HCl showing more effective separation of thiol derivatives and a better 3-MPA peak shape. The detection limit was 4.3nmolL(-1) with a 10µL sample injection, and mean recoveries of 3-MPA ranged from 97 to 105% in estuarine waters with different salinities (0.17 and 35.9ppt). The linearity (r>0.99) and repeatability of detector response, with intra- and inter-day precision (% CV) of 2.68-7.01% and 4.86-12.5%, respectively, confirmed the reliability of the method. Previous 3-MPA analytical methods required immediate analysis due to unstable derivatives, but in this method we achieved high stability of the derivatized samples when stored at 4°C, with only a 3-5% loss after more than one year of storage. This method was successfully applied to measure 3-MPA concentrations and rates of 3-MPA production in a variety of intertidal estuarine sediment slurries. Dissolved 3-MPA concentrations in these sediment slurries varied between 2 and 237µmolL(-1) and, 3-MPA net fluxes ranged in wet sediments between -3.6±1.7 and 30±5µmolL(-1)g(-1)h(-1). Thus, the application of this optimized methodology showed an efficient performance for measuring 3-MPA in environmental samples, with a straightforward sample derivatization and a simple analysis of stable 3-MPA derivatives.


Assuntos
Ácido 3-Mercaptopropiônico/análise , Cromatografia Líquida de Alta Pressão/métodos , Ácido 3-Mercaptopropiônico/química , Ecologia , Estuários , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Genome Announc ; 3(1)2015 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-25700409

RESUMO

Despite the reduction in incidence after vaccination, pertussis disease is still considered a public health problem worldwide, mainly due to recent and potential new outbreaks. We report here the complete genome of the Bordetella pertussis Butantan strain used in the Brazilian National Immunization Program as a whole-cell pertussis antigen to compose vaccines such as DTwP (diphtheria, tetanus, and whole-cell pertussis).

17.
Diabetes Obes Metab ; 14(10): 869-81, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22321826

RESUMO

Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11ß-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre-receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11ß-HSD1) or inactivate cortisol to cortisone (11ß-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11ß-HSD1 as a possible pharmacological target and into the role of dietary habits on the establishment or the prevention of the metabolic syndrome, obesity and T2DM through 11ß-HSD1 modulation. We intend to review and discuss 11ß-HSD1 and obesity, the metabolic syndrome and T2DM and to highlight the potential of its inhibition for therapeutic or prophylactic approaches in those metabolic diseases.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/farmacologia , Aterosclerose/enzimologia , Síndrome de Cushing/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Glucocorticoides/sangue , Síndrome Metabólica/enzimologia , Obesidade/enzimologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Tecido Adiposo/enzimologia , Animais , Anti-Inflamatórios , Aterosclerose/tratamento farmacológico , Corticosterona/sangue , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Fígado/enzimologia , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/tratamento farmacológico , Camundongos , Camundongos Transgênicos , Obesidade/tratamento farmacológico , Ratos , Ratos Transgênicos
18.
Allergol Immunopathol (Madr) ; 40(2): 129-31, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21549496
20.
Curr Drug Targets ; 12(10): 1454-61, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21466487

RESUMO

It is estimated that 50% of patients who have undergone ileal pouch-anal anastomosis (IPAA) surgery for UC will develop at least one episode of pouchitis. The risk of developing pouchitis is much higher in patients with preoperative extraintestinal manifestations and primary sclerosing cholangitis. In acute pouchtis metronidazole or ciprofloxacin have shown efficacy, however there is some evidence that ciprofloxacin may have better and has less toxic. In patients with chronic pouchitis antibiotics are less effective, and maintenance therapy may be required. In cases of refractoriness to conventional therapy a combination of two antibiotics for a prolonged period or infliximab may be effective. Starting maintenance treatment with highly concentrated probiotics is recommended as primary and secondary prophylaxis.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Pouchite/tratamento farmacológico , Pouchite/etiologia , Proctocolectomia Restauradora/efeitos adversos , Animais , Colite Ulcerativa/tratamento farmacológico , Humanos , Fatores de Risco
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