Performance of an Ultra-Sensitive Assay Targeting the Circulating Anodic Antigen (CAA) for Detection of Schistosoma mansoni Infection in a Low Endemic Area in Brazil

Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings, where the conventional parasitological methods are insensitive. We determined the accuracy of an up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay in urine and serum for Schistosoma mansoni diagnosis in low-prevalence settings in Ceará, Brazil, before and after praziquantel treatment. Clinical samples of a total of 258 individuals were investigated by UCP-LF CAA, point-of-care—circulating cathodic antigen (POC-CCA), soluble worm antigen preparation (SWAP)-ELISA and Kato-Katz (KK); a selection of 128 stools by real-time PCR technique. Three and 6-weeks after treatment, samples were collected and evaluated by detection Schistosoma circulating antigens (CAA and CCA). The UCP-LF CAA assays detected 80 positives (31%) with urine and 82 positives (31.8%) with serum. The urine POC-CCA and serum SWAP-ELISA assays detected 30 (11.6%) and 107 (40.7%) positives, respectively. The Kato-Katz technique revealed only 4 positive stool samples (1.6%). Among the 128 individuals with complete data records, 19 cases were identified by PCR (14.8%); Sensitivities and specificities of the UCP-LF CAA assays, determined versus a combined reference standard based on CCA/KK/PCR positivity, ranged from 60–68% to 68–77%, respectively. In addition only for comparative purposes, sensitivities of the different assays were determined vs. a comparative reference based on CAA/KK/PCR positivity, showing the highest sensitivity for the urine CAA assay (80%), followed by the serum CAA (70.9%), SWAP-ELISA (43.6%), PCR (34.5%), POC-CCA (29.1%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (3.6%). CAA concentrations were higher in serum than in urine and were significantly correlated. There was a significant decrease in urine and serum CAA levels 3 and 6-weeks after treatment. The UCP-LF CAA assays revealed 33 and 28 S. mansoni-infected patients at the 3- and 6-week post-treatment follow-up, respectively. The UCP-LF CAA assays show high sensitivity for the diagnosis of S. mansoni in low-endemicity settings. It detects a considerably higher number of infections than microscopy, POC-CCA or PCR. Also it shows to be very useful for evaluating cure rates after treatment. Hence, the UCP-LF CAA assay is a robust and promising diagnostic approach in low-transmission settings

Nasal polyposis : more than a chronic inflammatory disorder : a disease of mechanical dysfunction : the São Paulo position

Introduction The importance of our study lies in the fact that we have demonstrated the occurrence of mechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity. Objective To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked. Data Synthesis We propose a fundamentally new approach to intervening in the pathological process of NP, addressing biomechanical properties, fluid dynamics, and the concept of surface tension. Conclusion The incorporation of biomechanical knowledge into our understanding of NP provides a new perspective to help elucidate the physiology and the pathology of nasal polyps, and new avenues for the treatment and cure of NP

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.Univ Sao Paulo, Inst Canc Estado Sao Paulo, BR-01246000 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Radiol & Oncol, BR-01246903 Sao Paulo, BrazilHosp Sirio Libanes, BR-01308050 Sao Paulo, BrazilHosp Moinhos de Vento Porto Alegre, BR-90035000 Porto Alegre, RS, BrazilOncoctr, BR-30360680 Belo Horizonte, MG, BrazilUniv Fed Rio Grande do Sul, Dept Cirurgia, BR-90040060 Porto Alegre, RS, BrazilHosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Ceara, Fac Med, Dept Fisiol & Farmacol, BR-60020180 Fortaleza, Ceara, BrazilHosp Univ Walter Cantidio, BR-60430370 Fortaleza, Ceara, BrazilInst Nacl Canc, BR-20230240 Rio De Janeiro, BrazilUniv Sao Paulo, Fac Med, Disciplina Endocrinol & Metabol, BR-01246903 Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Surg, BR-01509010 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol, Sao Paulo, BrazilUniv Fed Ciencias Saude Porto Alegre, BR-90050170 Porto Alegre, RS, BrazilHosp Albert Einstein, BR-05652900 Sao Paulo, BrazilHosp Base, Fac Med Sao Jose do Rio Preto, BR-15090000 Sao Paulo, BrazilSanta Casa Sao Jose do Rio Preto, BR-15025500 Sao Jose Do Rio Preto, BrazilPontificia Univ Catolica Parana, Hosp Erasto Gaertner, BR-81520060 Curitiba, Parana, BrazilUniv Fed Rio Grande do Norte, BR-59300000 Natal, RN, BrazilUniv Sao Paulo, Inst Coracao, BR-05403900 Sao Paulo, BrazilAC Camargo Canc Ctr, Med Oncol, BR-01509010 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilHosp Sao Rafael, BR-41253190 Salvador, BA, BrazilHosp Canc Barretos, Dept Cirurgia Aparelho Digest Alto & Hepatobiliop, BR-14784400 Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Dept Patol, BR-01246903 Sao Paulo, BrazilClin AMO, BR-1950640 Salvador, BA, BrazilHosp Sao Jose, BR-01323001 Sao Paulo, BrazilUniv Nove de Julho, BR-02111030 Sao Paulo, BrazilUniv Fed Sao Paulo, Disciplina Gastroenterol, BR-04021001 Sao Paulo, BrazilWeb of Scienc

Clofazimine Inhibits Human Kv1.3 Potassium Channel by Perturbing Calcium Oscillation in T Lymphocytes

The Kv1.3 potassium channel plays an essential role in effector memory T cells and has been implicated in several important autoimmune diseases including multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small molecule inhibitors of Kv1.3 channel have been reported, some of which were found to be effective in various animal models of autoimmune diseases. We report herein the identification of clofazimine, a known anti-mycobacterial drug, as a novel inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway. These effects of clofazimine provide the first line of experimental evidence in support of a causal relationship between Kv1.3 and calcium oscillation in human T cells. Furthermore, clofazimine was found to be effective in blocking human T cell-mediated skin graft rejection in an animal model in vivo. Together, these results suggest that clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders