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Gonzaga H.F.S.,Discipline of Dermatology | Marcos E.V.C.,Instituto Lauro Of Souza Lima | Santana F.C.S.,Instituto Lauro Of Souza Lima | Tomimori J.,Federal University of São Paulo
Journal of the European Academy of Dermatology and Venereology | Year: 2013

Background Fissured tongue (FT) is a clinical condition manifested by numerous little furrows on the tongue's surface. Previously, the authors observed an association with HLA-C×06 in psoriasis (PS) and benign migratory glossitis (BMG); however, HLA-C was not surveyed in FT. Objective This study investigated the association between HLA alleles and FT. Methods Thirty-three FT bearers were studied, after evaluation of criteria for inclusion. These patients did not present PS, BMG or any other conditions associated with FT. The control group (CG) was composed of 561 individuals with HLA-A, 560 individuals with HLA-B, 168 individuals with HLA-C, 564 individuals with HLA-DRB1 and 390 individuals with HLA-DQB1. Samples from these individuals were processed to extract DNA. The HLA classes I and II were determined using the reverse line blot technique. The frequencies of HLA antigens found in patients were compared with the CG using Fisher's exact test. Results The comparison of the frequencies of HLA antigens found in the patient groups and in CG revealed no association with any of the alleles studied, except for HLA-A*01, which exhibited a decreased frequency in patient groups. HLA-C*06 was detected in 7.57% of FT patients and 10.42% of the CG (not significant). Conclusion The lack of association of FT with HLA-C*06 reinforces the proposal that this disease does not have a common genetic factor in the triad of BMG, FT and PS. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.


Casaroto A.R.,University of Sao Paulo | Toledo G.L.,University of Sao Paulo | Toledo Filho J.L.,University of Sao Paulo | Soares C.T.,Instituto Lauro of Souza Lima | Lara V.S.,University of Sao Paulo
Anticancer Research | Year: 2012

Ameloblastic carcinoma (AC) is a rare malignant odontogenic neoplasm with scarce reported cases in the literature and it can be confused with benign ameloblastoma (AM). This study reports a case of AC, and presents a literature review of AC classified into primary type (ACPt) or secondary type (ACSt) by the World Health Organization (WHO). The review addressed 31 cases published in the English literature between the years 2005 and 2011. The majority of cases were ACSt. The mandible was the most common site of occurrence for both AC types. All patients who died of their disease had ACSt. Tumors with plexiform pattern, hyperchromatism, mitosis and necrosis were associated with a higher ratio of histories of recurrence and death by disease, as well as the tumors with clear cells, especially in the ACSt. ACSt appeared to correlate with recurrence and mortality. The histological features may have different prognostic importance depending on the AC type.


Das P.K.,University of Birmingham | Das P.K.,Instituto Lauro Of Souza Lima | Rosa P.S.,Instituto Lauro Of Souza Lima | Morgan B.P.,University of Cardiff
Acta Neuropathologica | Year: 2015

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients. © 2015, The Author(s).


Pontillo A.,University of Sao Paulo | Laurentino W.,Instituto Lauro Of Souza Lima | Crovella S.,Federal University of Pernambuco | Pereira A.C.,Instituto Lauro Of Souza Lima
Infection, Genetics and Evolution | Year: 2013

Polymorphisms in innate immunity genes are known to be involved in the multifactorial susceptibility to Mycobacterium leprae infection. M. leprae can downregulate IL-1β secretion escaping monocyte digestion. The intracellular receptors NLRPs (NACHT, LRR and PYD domains-containing proteins) sense pathogen associated molecular patterns (PAMPs) activating caspase-1 and IL-1β secretion in the context of inflammasome. Considering the possible role of inflammasome in the immune response against M. leprae, known single nucleotide polymorphisms (SNPs) in two NLRP genes, NLRP1 and NLRP3, were analyzed in Brazilian leprosy patients.Disease-associated SNPs (5 in NLRP1 and 2 in NLRP3), previously associated to infections and to immunologic disorders, were genotyped in 467 leprosy patients (327 multibacillary, MB; 96 paucibacillary, PB) and in 380 healthy controls (HC) from the state of Sao Paulo (Brazil), and in 183 patients (147. MB; 64. PB) and 186 HC from Mato Grosso (Brazil). Logistic regression analysis was performed considering susceptibility to leprosy di per se (leprosy versus HC) and clinical form (MB versus PB), adjusting for gender and ethnicity.Whereas none of the considered SNPs were statistically associated with leprosy, the NLRP1 combined haplotype rs2137722/G-rs12150220/T-rs2670660/G resulted significantly more frequent in patients than in HC as well as in PB than in MB. While both associations were lost after correction for gender and ethnicity, the NLRP1 combined haplotype rs2137722/G-rs12150220/A-rs2670660/G resulted strongly associated to PB.NLRP1 might be involved in the susceptibility to leprosy with particular emphasis for PB clinical form. Although preliminary, this is the first report linking NLRPs and inflammasome with leprosy: replication studies as well as functional assays are envisaged to deeper investigate the role of NLRP1 in M. leprae infection. Interestingly, NLRP1 SNPs were previously associated to susceptibility to Crohn disease, suggesting that NLRP1 could be a new modifier gene in common between leprosy and Crohn disease. © 2013 Elsevier B.V.


Garbino J.A.,Instituto Lauro Of Souza Lima | Heise C.O.,Fleury Institute | Marques W.,University of Sao Paulo
Clinics in Dermatology | Year: 2016

Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation. © 2016 Elsevier Inc.


Vilani-Moreno F.R.,Instituto Lauro Of Souza Lima | De Faria Fernandes Belone A.,Instituto Lauro Of Souza Lima | Lara V.S.,University of Sao Paulo | Venturini J.,São Paulo State University | And 2 more authors.
Medical Mycology | Year: 2011

Studies investigating the immunopathological aspects of Jorge Lobo's disease have shown that the inflammatory infiltrate consists mainly of histiocytes and multinucleated giant cells involving numerous yeast-like cells of Lacazia loboi, with the T lymphocytes more common than B lymphocytes and plasma cells. The quantification of cytokines in peripheral blood mononuclear cells culture supernatant has revealed alterations in the cytokines profile, characterized by predominance of a Th2 profile. In view of these findings and of the role of cytokines in cell interactions, the objective of the present study was to investigate the presence of the cytokines IL-10, TGF-β1 and TNF-α, as well as iNOS enzyme in granulomas induced by L. loboi. Histological sections obtained from skin lesions of 16 patients were analyzed by immunohistochemistry for the presence of these cytokines and iNOS. The results showed that TGF-β1 was the cytokine most frequently expressed by cells present in the inflammatory infiltrate, followed by IL-10. There was a minimum to discrete positivity of cells expressing TNF-α and iNOS. The results suggest that the presence of immunosuppressive cytokines in skin lesions of patients with the mycosis might be responsible for the lack of containment of the pathogen as demonstrated by the presence of numerous fungi in the granuloma. © 2011 ISHAM.


Barreto J.G.,Federal University of Pará | Guimaraes L.S.,Federal University of Pará | Frade M.A.C.,University of Sao Paulo | Rosa P.S.,Instituto Lauro Of Souza Lima | Salgado C.G.,Federal University of Pará
Memorias do Instituto Oswaldo Cruz | Year: 2012

Leprosy in children is correlated with community-level factors, including the recent presence of disease and active foci of transmission in the community. We performed clinical and serological examinations of 1,592 randomly selected school children (SC) in a cross-sectional study of eight hyperendemic municipalities in the Brazilian Amazon Region. Sixty-three (4%) SC, with a mean age of 13.3 years (standard deviation = 2.6), were diagnosed with leprosy and 777 (48.8%) were seropositive for anti-phenolic glycolipid-I (PGL-I). Additionally, we evaluated 256 house-hold contacts (HHCs) of the students diagnosed with leprosy; 24 (9.4%) HHC were also diagnosed with leprosy and 107 (41.8%) were seropositive. The seroprevalence of anti-PGL-I was significantly higher amongst girls, students from urban areas and students from public schools (p < 0.0001). Forty-five (71.4%) new cases detected amongst SC were classified as paucibacillary and 59 (93.6%) patients did not demonstrate any degree of physical disability at diagnosis. The results of this study suggest that there is a high rate of undiagnosed leprosy and subclinical infection amongst children in the Amazon Region. The advantages of school surveys in hyperendemic areas include identifying leprosy patients at an early stage when they show no physical disabilities, preventing the spread of the infection in the community and breaking the chain of transmission.


Virmond M.,Instituto Lauro Of Souza Lima | Grzybowski A.,Poznan City Hospital | Grzybowski A.,University of Warmia and Mazury | Virmond L.,Pontifical Catholic University of Parana
Clinics in Dermatology | Year: 2015

Leprosy continues to afflict residents from a number of countries in Africa, South America, and southeast Asia, despite the marked reduction in the number of cases of leprosy worldwide, after the introduction of the multidrug regimens as recommended by the World Health Organization (WHO-MDT). With the increasing immigration of individuals from risk areas to Europe and the United States, knowledge of the basic concepts of leprosy would be helpful to clinicians caring for immigrants in nonendemic areas. We present a comprehensive, updated, and critical glossary of the most relevant terms related to leprosy. © 2015.


Woods W.J.,Avenida Nacoes Unidas 700 | Belone A.F.F.,Instituto Lauro Of Souza Lima | Carneiro L.B.,Avenida Nacoes Unidas 700 | Rosa P.S.,Instituto Lauro Of Souza Lima
Revista do Instituto de Medicina Tropical de Sao Paulo | Year: 2010

Jorge Lobo's disease is a cutaneous and subcutaneous mycosis that affects patients in the Amazon region. The number of patients is relatively small, but the real situation of the disease as public health problem is not known, because Jorge Lobo's disease is not a notifiable disease. This study aims to report the clinical evolution in patients affected and to determine the prevalence and areas of occurrence of the disease. A retrospective study was carried out based on the analysis of the clinical records, which included a collection of photographs of patients in the Department of Sanitary Dermatology, in Rio Branco, and patients seen in the interior of the state. In a decade, in Rio Branco, 249 cases of the disease were reported, 30 were females and 219 males. Of these patients, 153 had localized lesions, 94 of them were on one ear, 55 had multifocal lesions and 41 had disseminated lesions. The average time between the onset of symptoms and diagnosis was 19 years. The average age at the time of diagnosis was 53 years, and ages ranged from 14 to 96 years.


Cardoso C.C.,Instituto Oswaldo Cruz | Pereira A.C.,Instituto Lauro Of Souza Lima | De Sales Marques C.,Instituto Oswaldo Cruz | Moraes M.O.,Instituto Oswaldo Cruz
Future Microbiology | Year: 2011

The past few years have been very productive concerning the identification of genes associated with leprosy. Candidate gene strategies using both case-control and family-based designs, as well as large-scale approaches such as linkage and gene-expression genomic scans and, more recently, genome-wide association studies, have refined and enriched the list of genes highlighting the most important innate and adaptive immune pathways associated with leprosy susceptibility or resistance. During the early events of host-pathogen interaction identified genes are involved in pattern recognition receptors, and mycobacterial uptake (TLRs, NOD2 and MRC1), which modulate autophagy. Another gene, LTA4H, which regulates the levels of lipoxin A4 and possibly interacts with lipid droplet-related events, also plays a role in the early immune responses to Mycobacterium leprae. Together, the activation of these pathways regulates cellular metabolism upon infection, activating cytokine production through NF-κB and vitamin D-vitamin D receptor pathways, while PARK2 and LRRK2 participate in the regulation of host-cell apoptosis. Concomitantly, genes triggered to form and maintain granulomas (TNF, LTA and IFNG) and genes involved in activating and differentiating T-helper cells (HLA, IL10, as well as the TNF/LTA axis and the IFNG/IL12 axis) bridge immunological regulation towards adaptive immunity. Subtle variations in these genes, mostly single nucleotide polymorphisms, alter the risk of developing the disease or the severity of leprosy. Knowing these genes and their role will ultimately lead to better strategies for leprosy prevention, treatment and early diagnosis. Finally, the same genes associated with leprosy were also associated with autoimmune (Crohn's disease, rheumathoid arthritis, psoriasis) or neurodegenerative diseases (Parkinson's and Alzheimer's). Thus, information retrieved using leprosy as a model could be valuable to understanding the pathogenesis of other complex diseases. © 2011 Future Medicine Ltd.

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