Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

Terapêutica Anti-Retroviral na Infecção a VIH (1ª Parte)

Faz-se uma breve revisão sobre a imunofisiopatologia da infecção pelo VIH. Abordam-se os fármacos que se encontram em investigação clínica mais avançada e alguns que poderão ter interesse futuro. Destacam-se os compostos actualmente disponíveis para uso clínico, tentando abordar os aspectos que na prática clínica são mais importantes. Referenciam-se ensaios clínicos quanto à eficácia nestas drogas em monoterapia ou combinação.

Padronização do Uso de Imunoglobulina Anti-D na Profilaxia da Isoimunização Rh

A isoimunização RhD durante a gravidez tem graves repercussões fetais e neonatais. Apesar da imunoprofilaxia com imunoglobulina anti-D ter diminuído drasticamente a mortalidade e morbilidade perinatais, continuam a existir casos de isoimunização que se devem a uma administração inadequada. No âmbito de um projecto de padronização da administração de imunoglobulina anti-D, foram levados a cabo um inquérito aos obstetras da MAC e uma análise retrospectiva de processos de mulheres RhD negativas. Neste artigo são apresentados os resultados destes dois trabalhos. É também apresentada uma proposta de protocolo de imunoprofilaxia.

Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

BACKGROUND: Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking. MATERIALS AND METHODS: Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed simultaneously. RESULTS: We evaluated 132 sets of biopsies and simultaneous serum samples. PTC C4d deposition was demonstrated in 15.9% (21/132) of biopsies. Circulating anti-HLA I/II AlloAb were detected in 25% (33/132) of serum samples. Employing receiver-operator characteristic (ROC) curves for all C4d-positive biopsies, screening for AlloAb showed a global specificity of 82% and sensitivity of 61.9%. When this analysis was restricted to biopsies obtained in the first month posttransplantation, the sensitivity increased to 81.8%, but the specificity decreased to 76.9%. After the first month posttransplantation, we observed sensitivity of 40.0% and a specificity of 86.4%. In the first month posttransplantation, all patients with a diagnosis of acute antibody-mediated rejection displayed circulating anti-HLA class I/II, but not always at the same time as the C4d-positive biopsy. CONCLUSIONS: In the first month posttransplantation, prospective monitoring of anti-HLA antibodies may be useful. The high sensitivity allows the identification of patients at risk, affording an earlier diagnosis of antibody-mediated rejection. After the first month, the test can be used to evaluate allograft dysfunction episodes, since positivity is highly suggestive of an antibody-mediated process.

Associação entre Pré-Eclâmpsia Grave e Anticorpos Anti-Fosfolípidos

Um número clinicamente importante de mulheres com pré-eclâmpsia grave de início precoce tem níveis significativos de anticorpos (Ac) anti-fosfolípidos. A sua detecção precoce pode ajudar a definir o risco de complicações no peri-parto levando ao estabelecimento de medidas de prevenção de episódios trombóticos nestas doentes.

Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance

Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction. Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies. Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ≥ 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating alloantibodies were absent in 92.5% of the C4d negative biopsies. Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies. The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%).

Tromboembolias Múltiplas Associadas a Défice de Anti-Trombina III

A deficiência congénita de anti-trombina III é considerada como um estado de hipercoagulabilidade primária. Os autores apresentam um caso de deficiência de anti-trombina III num jovem do sexo masculino, de 28 anos de idade, com doença valvular aórtica e múltiplos episódios de fenómenos tromboembólicos. Ao discutirem os seus aspectos diagnósticos e terapêuticos, procuram sensibilizar para a necessidade de se rastrear situações de trombofilia em doentes com fenómenos trombóticos recorrentes.

Anti-Tumor Necrosis Factor Alpha-Induced Drug Eruptions: One Patient, More Than a Pattern

Background: Tumor necrosis factor alpha (TNFα) antagonists are effective in treating several immune-inflammatory diseases, including psoriasis and inflammatory bowel disease. The paradoxical and unpredictable induction of psoriasis and psoriasiform skin lesions is a recognized adverse event, although of unclear aetiology. However, histological analysis of these eruptions remains insufficient, yet suggesting that some might constitute a new pattern of adverse drug reaction, rather than true psoriasis. Case report: The authors report the case of a 43-year-old woman with severe recalcitrant Crohn disease who started treatment with infliximab. There was also a personal history of mild plaque psoriasis without clinical expression for the past eight years. She developed a heterogeneous cutaneous eruption of psoriasiform morphology with pustules and crusts after the third infliximab infusion. The histopathological diagnosis was of a Sweet-like dermatosis. The patient was successfully treated with cyclosporine in association with both topical corticosteroid and vitamin D3 analogue. Three weeks after switching to adalimumab a new psoriasiform eruption was observed, histologically compatible with a psoriasiform drug eruption. Despite this, and considering the beneficial effect on the inflammatory bowel disease, it was decided to maintain treatment with adalimumab and to treat through with topicals, with progressive control of skin disease. Discussion: Not much is known about the pathogenesis of psoriasiform eruptions induced by biological therapies, but genetic predisposition and Koebner phenomenon may contribute to it. Histopathology can add new facets to the comprehension of psoriasiform reactions. In fact, histopathologic patterns of such skin lesions appear to be varied, in a clear asymmetry with clinical findings. Conclusion: The sequential identification in the same patient of two clinical and histopathologic patterns of drug reaction to TNFα antagonists is rare. Additionally, to the authors’ knowledge, there is only one other description in literature of a TNFα antagonist-induced Sweet-like dermatosis, emphasizing the singularity of this case report.

Hyper-IgD and Periodic Fever Syndrome: a New MVK Mutation (p.R277G) Associated with a Severe Phenotype

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM#260920) is a rare recessively-inherited autoinflammatory condition caused bymutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Herewe report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, where as anakinra showed positive responses only at high doses. The p.R277Gmutation here described is a novel missense MVK mutation, and it has been detected in this casewith a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.

Anticorpos Anti-Receptor da TSH na Doença de Graves

Neste trabalho os AA avaliam a sensibilidade, especificidade e valor predictivo do doseamen to dos anticorpos anti-receptor da TSH (TRAb) no diagnóstico da doença de Graves. A população estudada incluiu 80 doentes com doença de Graves recentemente diagnosticada e sem tratamento prévio (grupo 1), 63 doentes com outras patologias tiroideias (grupo II) e 60 indivíduos sem patologia tiroideia (grupo III). Utilizaram uma técnica de radioreceptor, o kit TRAK Henning, que considera positividade> 14 U TRAb L, negatividade 9 e zona cinzenta entre estes 2 valores. No grupo 1, 11 doentes tinham TRAb negativo e 7 situavam-se na zona cinzenta. No grupo II apenas 2 doentes tinham TRAb de 9 e todos os indivíduos do grupo controlo tinham TRAb negativo. Para efeito estatístico foram excluidos os doentes com valores na zona cinzenta. Os valores de sensibilidade e especificidade para o método ensaiado foram respectivamente de 84,5° o e 10000. O valor predictivo foi de 1000 o, o que permite afirmar com segurança que um doente com hipertiroidismo e TRAb positivo tem doença de Graves.

The Effect of Statins on Mortality in Septic Patients: a Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay. DATA SOURCES AND STUDY SELECTION: Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients. DATA EXTRACTION AND SYNTHESIS: Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found. CONCLUSIONS: Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.

Hipersensibilidade a Anti-inflamatórios Não Esteróides em Doentes Asmáticos com Idade Pediátrica

Introdução: Os dados publicados sobre a frequência de hipersensibilidade (HS) a anti-inflamatórios não esteróides (AINEs) em doentes asmáticos são discrepantes, sendo escassos na população pediátrica. O objectivo deste estudo foi avaliar a frequência de HS a AINEs, reportada por inquérito telefónico em doentes asmáticos com idade pediátrica. Métodos: Incluíram -se os doentes com idades entre 6 e 17 anos com clínica de asma confirmada por prova de broncodilatação positiva, realizada no período entre 1 de Agosto de 2008 e 30 de Novembro de 2010. Aplicou-se um inquérito telefónico para questionar sobre alguma reacção adversa a fármacos, nomeadamente a AINEs. Perante o reportar de reacção adversa a AINEs, detalhava-se fármaco envolvido, idade na primeira reacção, manifestações clínicas, intervalo entre a toma e o início da reacção, reprodutibilidade, evicção do fármaco implicado e tolerância de fármacos alternativos. Resultados: Foram selecionados, por prova de broncodilatação positiva, 184 doentes. Foi possível aplicar o inquérito a 111/184 (60,3%). A maioria (59,4%) era do género masculino, com 11 ± 3,1 anos. Nove doentes (8,1%) reportaram reacção de HS a AINEs, reprodutível em três. A primeira reacção ocorreu com uma idade mediana de 2 anos (P25:1,8; P75:5,75), abaixo dos 10 anos em todos os doentes. O ibuprofeno foi o fármaco implicado em todos os casos, sendo o paracetamol usado em alternativa. Todos descreveram reacções imediatas, com as seguintes manifestações: respiratória (7), cutânea (3), gastrintestinal (1). A frequência reportada de sintomas respiratórios como manifestação de reacção de HS a AINEs nesta amostra de doentes asmáticos foi de 6,3% (7/111). Quatro doentes (3,6%) estavam sob evicção de AINEs apesar de negarem qualquer reacção de HS prévia. Conclusões: A frequência reportada de HS a AINEs contraria os dados que descrevem estas reacções como infrequentes abaixo dos 10 anos de idade. O paracetamol parece ser uma alternativa segura.

Anti-Phospholipase A2 Receptor Antibodies in the Diagnosis of Idiopathic Membranous Nephropathy

Circulating anti-phospholipase A2 receptor antibodies (anti-PLA2R) have been described in 70% to 80% of the patients with idiopathic membranous nephropathy (iMN), but not in patients with secondary membranous nephropathy or other glomerular diseases. The goal of this study was to evaluate the sensitivity and specificity of the assay for anti-PLA2R in the diagnosis of iMN. Anti-PLA2R IgG, Elisa and immunofluorescence tests were used to detect circulating anti-PLA2R. These tests were applied in 53 patients who had a kidney biopsy. Of these, 38 had histological diagnosis of membranous nephropathy (MN) and the remaining had other glomerular diseases. The MN was classified as idiopathic in 33 patients after clinical exclusion of secondary causes. Anti-PLA2R were positive in 57.6% of the patients with iMN. All patients with secondary membranous nephropathy or other glomerular diseases did not show circulating anti-PLA2R. The sensitivity was 57.6% (CI 39.2-74.5) and specificity 100% (CI 47.8-100), AUC 0.788; p < 0.0001 for the detection of iMN. 71.4% of the iMN patients that tested negative for anti-PLA2R were in partial or complete remission. The detection of anti-PLA2R in the studied population had a specificity of 100% for the iMN diagnosis. Prior treatments seem to make the test negative and contribute to a lower sensitivity.