Search

Non-aggressive basal cell carcinoma (BCC) growth is slow and might be mediated by the immune system. This study analysed the human leukocyte antigen (HLA)-G expression and cytokine profile in non-aggressive BCC subtypes from distinct locations. HLA-G was evaluated via immunohistochemistry and cytokine expression was analysed by a quantitative real-time polymerase chain reaction in 26 primary BCC samples, including nodular BCC (nBCC, n = 16) and superficial BCC (n = 10) from cephalic (ceBCC, n = 12) and non-cephalic (n = 14) locations, and by bioinformatics analysis of public GEO databases. Inflammatory infiltrate was concentrated around the tumour nests. HLA-G-positive inflammatory cells (53.85%) were more abundant than HLA-G-positive tumour cells (21.54%, p

Mentha piperita L. has been studied by our group as a possible phytopharmacological drug for treatment of diseases that promote intense inflammatory responses mediated by eosinophils and neutrophils. Thus, the analysis of antioxidant effects and cytokine production by these cells is important to understand the effect of these compounds on the innate and effector phase of adaptive immune response. In this way, an essential oil from M. piperita (Mentaliv®) was used and the myeloperodase enzyme activity (MPO) in neutrophils was evaluated by luminol-dependent chemiluminescence assay (QLDLum) and lucigenin (QLDLuc). The levels of IL-4, IL-6 and TNF-α and QLDLum in eosinophils were also evaluated. Our results showed an inhibition of the production of superoxide anionic radicals and NADPH oxidase in neutrophils after the essential M. piperita oil treatment. However, IL-4 levels were increased after treatment. These data suggest that this phytopharmaceutical has anti-inflammatory activity, by controlling the secreted products during the inflammatory responses, mainly as can occur during infections and chronic inflammatory processes of several diseases, which present a strong tissue eosinophilia with significant presence of PMN in blood and tissue.

Schistosomiasis, caused by Schistosoma mansoni trematode worm, affects more than 1.5 million people in Brazil. The current treatment consists in the administration of Praziquantel, the only medicine used for treatment for more than 40 years. Some of the limitations of this drug consist in its inactivity against schistosomula and parasite eggs, the appearance of resistant strains and non-prevention against reinfection. Thus, the objective of this study was to evaluate the effect of immunization with recombinant functional enzymes of the purine salvage pathway of S. mansoni, Nucleoside Diphosphate Kinase (NDPK) and Adenylosuccinate Lyase (ADSL), to evaluate the host immune response, as well as the parasite load after vaccination. For this, Balb/c mice were divided into 5 groups: control (uninfected and untreated), non-immunized/infected, NDPK infected, ADSL infected, and NDPK + ADSL infected. Immunized groups received three enzyme dosages, with a 15-day interval between each dose, and after 15 days of the last application the animals were infected with 80 cercariae of S. mansoni. On the 47th day after the infection, fecal eggs were counted and, on the 48th day after the infection, the evaluation of leukocyte response, parasite load, antibody production, cytokines quantification, and histopathological analysis were performed. The results showed that immunizations with NDPK, ADSL or NDPK + ADSL promoted a discreet reduction in eosinophil counts in lavage of peritoneal cavity. All immunized animals showed increased production and secretion of IgG1, IgG2a, and IgE antibodies. Increased production of IL-4 was observed in the group immunized with the combination of both enzymes (NDPK + ADSL). In addition, in all immunized groups there were reductions in egg counts in the liver and intestine, such as reductions in liver granulomas. Thus, we suggest that immunizations with these enzymes could contribute to the reduction of schistosomiasis transmission, besides being important in immunopathogenesis control of the disease.

Objetivo: Analisar os registros de amostras biológicas coletadas para exame histopatológico nos laudos necroscópicos do Serviço de Verificação de Óbitos de Ribeirão Preto (SVOI-RP) e correlacionar registros de resultados histopatológicos com os registros de causas de mortalidade e de morbidade. Metodologia: Estudo analítico observacional transversal em dados coletados nos laudos necroscópicos, concluídos pelos médicos patologistas e arquivados do SVOI-SP, entre 2014 e 2016. Resultados: Foram estudados 702 laudos necroscópicos, com 1652 registros de causas de mortalidade, 625 causas de morbidade e de 291 amostras coletadas para histopatologia. Discussão: Foram utilizados 28 registros de amostras coletadas para histopatologia com autólise, não havendo correlação significativa com quantidade e qualidade das causas de morbidade e mortalidade. Houve um maior registro de causa de mortalidade naqueles laudos sem registros de amostras coletadas. Laudos com registros superiores a sete amostras apresentaram menor quantidade de morbidades. Conclusão: Não houve necessidade de análise histopatológica para a definição de diagnósticos de mortalidade e morbidade. Padronizar a coleta de amostras poderá dirimir custos, mesmo sem o impacto da autólise na quantidade e qualidade das causas de mortalidade e morbidade no SVOI de Ribeirão Preto, São Paulo.

Introducao: No Brasil, em 2003, 13,3% das causas basicas de obito foram identificadas como mal definidas, cujas maiores proporcoes ocorreram nas regioes Nordeste e Norte do Brasil. Metodologia: Trata-se de um estudo descritivo epidemiologico, das principais causas de obitos por doencas infectocontagiosas e neoplasicas. Os dados sobre os obitos provieram do banco de dados do Departamento de Informatica do Sistema Unico de Saude e Sistema de Informacao de Mortalidade DATASUS/SIM do Ministerio da Saude do Brasil. Resultados: Para as doencas infectocontagiosas e neoplasias foram registrados 3591 obitos, sendo que, dentre as cinco principais doencas que se enquadram em doencas infectocontagiosas tiveram 360 registros de obitos e para as cinco principais neoplasias o registro foi de 925 obitos. Discussao: As doencas infectocontagiosas tiveram um decrescimo na sua importância ao longo da decada de 80, tanto para o sexo masculino quanto para o feminino. No entanto, a mortalidade por essas doencas permanece elevada principalmente nos homens. A incidencia de câncer e maior nas idades mais avancadas. Conclusao: A producao de informacoes mais precisas quanto a mortalidade reflete a situacao de saude e contribui para gestao eficaz em saude, objetivando a reducao da morbimortalidade no Estado do Tocantins. A analise de dados epidemiologicos oriundos do SVO e relevante para verificar a causa base de doencas mal definidas que levam ao obito. Tem-se com isto contribuicoes para melhorar a qualificacao das informacoes dos agravos que mais tem acometido a populacao brasileira, inclusive na regiao Norte, Estado do Tocantins.

Este artigo analisa a formação de professores universitários, no contexto da pesquisa Curso Pedagogia Universitária: os professores e sua prática pedagógica desenvolvida pelo Grupo de Apoio Pedagógico do Campus USP-Ribeirão Preto/Universidade de São Paulo – Brasil – (GAPRP). Trata de pesquisa descritivo-exploratória, de natureza qualitativa que se propõe a analisar as reflexões de professores, participantes do I e II Curso de Pedagogia Universitária realizado em Ribeirão Preto em 2008 e 2009, acerca de sua prática pedagógica. Os dados revelam que as reflexões desses professores contemplam a revisitação de suas práticas pedagógicas, os limites contextuais e administrativos e a gestão do projeto político pedagógico com possibilidades de mudanças. Evidenciam-se também alguns pontos de tensão que necessitam ser trabalhados: aprendizagem da docência como perspectiva individual versus docência como perspectiva coletiva; formação pedagógica como prática sócio-política versus prática instrumental e valorização da pesquisa em detrimento do ensino.

Previous studies have indicated that cancer may be promoted and/or exacerbated by inflammation and infection. The cytokines produced by activated innate immune cells that stimulate tumor growth and progression are considered as important components in this process. The interleukin (IL)-23/T helper (Th)17 axis, which exerts marked pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. Increasing clinical evidence indicates that Th17 may promote or inhibit tumor progression, however, the function of Th17 in the pathogenesis of benign and malignant thyroid neoplasms remains unclear. The present study investigated the association between the IL-23/Th17 axis and neoplastic and non-neoplastic thyroid lesions using immunohistochemistry. A total of 131 thyroid biopsy specimens were analyzed, which revealed high IL-17 and IL-23 expression in differentiated thyroid cancer and medullary thyroid cancer tissues when compared with benign lesions, including follicular thyroid adenoma and goiter tissues. Furthermore, high IL-17 expression was associated with recurrence and mortality. These results indicate that the IL-23/Th17 axis exhibits a pivotal function in the development of thyroid neoplasms.

Cobalt is the standard binder in tungsten carbide (WC) hardmetals due to its compatibility with the WC phase, resulting in composites with exceptional hardness and wear resistance. However, their corrosion resistance is not satisfactory in many applications, leading to the early deterioration and failure of tools and equipment. In this work, the corrosion of WC hardmetals with three alternative binders (FeCoNi, NiCrCoMo and NiCrMo) is compared with a benchmark WC-Co composite, using electrochemical techniques such as open circuit potential (OCP) monitoring, polarisation curves and electrochemical impedance spectroscopy (EIS), assisted by scanning electron microscopy (SEM).

Analyze, in the necroscopic reports of the Death Verification Service of the State of Tocantins (SVO-TO), the records of biological samples collected for histopathological examination and records of autolysis in histopathological results and correlate them with records of causes of mortality and morbidity. Cross-sectional observational analytical study conducted in 494 autopsy reports completed and filed in SVO-TO, Brazil, between 2012 and 2016. Records of the number of biological samples collected for histopathology, number of autolysis, number of causes of mortality and number of causes of morbidity were extracted and identified. For the analysis of the relationship between the variables, descriptive and analytical statistics were used in SAS SYSTEM software. The mean number of mortality records was 5.72 ± 2.42 (CV 42.32%), causes of morbidity: 0.2 ± 0.5 (CV 251.46%), number of biological samples collected: 2.66 ± 1.13 (CV 42.59%), number of autolysis: 1.74 ± 1.05 (CV 60.06%). The number of mortality and morbidity diagnoses recorded in SVO reports increases the higher the number of samples collected by necropsies physicians. The number of biological samples collected by necropsy positively impacts the number of causes of mortality and morbidity. Collecting more than seven tissue samples by necropsy does not impact the number of causes of mortality and morbidity. The low numbers of autolysis records suggest efficacy in the collection of biological samples in SVO-TO.

Objective: to investigate the presence of eosinophils in oral intraepithelial neoplasia (OIN) and oral squamous cell carcinoma (OSCC) lesions and its relation to invasion. Subjects and methods: ninety‐nine oral biopsies were selected and subdivided into the following: OIN‐1(16 cases), OIN‐2 (18 cases), OIN‐3 (17 cases), microinvasive OSCC (10 cases), non‐metastatic OSCC (22 cases) and metastatic OSCC (16 cases). The tissue eosinophilia was evaluated histologically in slices stained with haematoxylin and eosin. Results: Eosinophil distribution was associated with diagnosis severity (p < .01). A significant difference was found between OIN‐3 or microinvasive OSCC and non‐metastatic or metastatic OSCC. Stromal invasion threshold was 7 eos/10 high power field (hpf) (96.1% specificity and 62.5% sensitivity). Eosinophils were absent in OIN‐1; in OIN‐2, two cases were positive. In OIN‐3, five cases showed tissue eosinophilia, four of which had ≥3 eos/hpf or ≥7 eos/10 hpf. Three cases were suspected of invasion; two had a previous history of OSCC with elevated eosinophil infiltrate. In microinvasive OSCC, the four positive cases presented ≥3 eos/hpf and ≥7 eos/10 hpf. Although not significantly different, non‐metastatic invasive OSCC had a higher number of cases (68.2%) with ≥22 eos/10 hpf contrasting with 50% in metastatic OSCC. Conclusion: our results suggest that eosinophils can be considered an indicator of invasion in OIN, helping in cases of difficult diagnosis. info:eu-repo/semantics/publishedVersion

University pedagogy has been promoted in the context of the policy for valuing undergraduate training at the University of São Paulo (USP). In this regard, one action of the Undergraduate Pro-Rectory was the creation of pedagogic support groups. The objective of this study is to report and analyze the strategies for university teacher training developed by the Pedagogic Support Group at the Ribeirão Preto Campus (GAPRP/USP–Grupo de Apoio Pedagógico do Campus de Ribeirão Preto), during the period from 2002 to 2015. The group takes on a conception of teacher training that extrapolates the technical dimension, considering political-social and historical determinants that have shaped the university, undergraduate teaching, and the faculty, as well as the valorization of strategies promoting reflection, theoretical-practical articulation, and collective learning. During the day-to-day monitoring of these education strategies, a few aspects are highlighted and analyzed: identification of the need for pedagogic training as an individual initiative of the teaching staff, despite the policies for valuing undergraduate training; investment in continuous educational strategies and the education undergone by the faculty that compose GAPRP/USP. To conclude, teacher training means to value the construction of a political project so as to qualify university teachers.

Vitamin B complex can modulate the inflammatory response and activate wound healing. However, the action mechanisms involved in this process are still unclear. The aim of this study was to evaluate the effects of vitamin B complex on the modulation of monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-β1, and α-smooth muscle actin (α-SMA) in granulation tissue growth. Cutaneous ulcers on Wistar rats were topically treated with vitamin B complex. MCP-1, TGF-β1, and α-SMA expressions were evaluated 24, 72, and 168 h after the treatment. Inflammatory cells were counted and collagen fibril staining was performed. After 24 h, more mononuclear cells (p ≤ 0.01) and a higher MCP-1 (p ≤ 0.05) and TGF-β1 (p ≤ 0.01) expression were observed. After 72 h, the number of fibroblasts and mononuclear cells (p ≤ 0.05) was elevated. After 168 h, an increased number of fibroblasts, myofibroblasts, and blood vessels (p ≤ 0.01) as well as a strong intensity of collagen fibril staining were seen. At that point, the cells presented a higher TGF-β1 expression (p ≤ 0.05), and the size of the ulcer area was decreased (p ≤ 0.01). We can conclude that vitamin B complex may stimulate a positive modulation of MCP-1, TGF-β1, and α-SMA expressions in granulation tissue of cutaneous ulcers. © 2014 S. Karger AG, Basel

The aim of this study was to investigate the immunomodulatory effects of glucocorticoids on the immune response to Strongyloides venezuelensis in mice. Balb/c mice were infected with S. venezuelensis and treated with Dexamethasone (Dexa) or vehicle. Dexa treatment increased circulating blood neutrophil numbers and inhibited eosinophil and mononuclear cell accumulation in the blood, bronchoalveolar, and peritoneal fluid compared with control animals. Moreover, Dexa decreased tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-3 (IL-3), IL-4, IL-5, IL-10, and IL-12 production in the lungs and circulating immunoglobulin G1 (IgG1), IgG2a, and IgE antibody levels while increasing the overall parasite burden in the feces and intestine. Dexa treatment enhanced the fertility of female nematodes relative to untreated and infected mice. In summary, the alterations in the immune response induced by Dexa resulted in a blunted, aberrant immune response associated with increased parasite burden. This phenomenon is similar to that observed in S. stercoralis-infected humans who are taking immunosuppressive or antiinflammatory drugs, including corticosteroids.

Since the role of human papillomavirus (HPV) infection in oral carcinogenesis is still unclear, the purpose of this study was to verify the association between the expression of p27, mdm2 and cathepsin B and by HPV-related oral lesions. Fifty-five oral biopsies were studied and HPV detection and typing (6/11, 16, 18, 31 and 33) were performed using polymerase chain reaction techniques. The distribution p27, mdm2 and cathepsin B was determined by immunohistochemistry. Twenty-one (38%) out of the 55 oral lesions tested positive for HPV, of which 6 (33%) were HPV 6/11, 1 (5%) was HPV 16, 14 (72%) were HPV 18 and none was HPV 33/31. Among the 55 biopsies, immunopositivity for p27, mdm2 and cathepsin B was observed in 17 (30.9%), 37 (67.2%) and 37 (67.2%), respectively. Among 21 HPV-positive oral lesions, immunopositivity of mdm2, p27 and cathepsin B was found, respectively, in 6 (33%) out of 18 benign lesions (BL), 4 (22%) out of 18 potential malignant epithelial lesions (PMEL) and 11 (57.9%) out of 19 malignant lesions (ML). High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B.

Summary Background The nonclassical human leucocyte antigen (HLA)-G molecule has been well recognized as a tolerogenic molecule and few studies have evaluated the role of the molecule in inflammatory cutaneous autoimmune diseases. Objectives To evaluate the expression of HLA-G in skin specimens of patients with psoriasis and to analyse its correlation with epidemiological and clinical variables. Methods Thirty untreated patients with psoriasis and 32 healthy individuals were enrolled. Immunohistochemistry was applied to identify HLA-G expression in formalin-fixed paraffin-embedded cutaneous skin biopsies. Results Soluble and membrane-bound HLA-G expression was detected in 30 (90%) of the skin specimens from patients presenting clinical and histopathological features of psoriasis. Although infiltrating lymphomononuclear cells of the dermis exhibited HLA-G expression, the epidermis was primarily targeted. HLA-G expression was also observed in 27% (three of 11) of the specimens that exhibited no clinical and histopathological features of psoriasis (nonaffected areas). In contrast, skin specimens obtained from healthy individuals exhibited no HLA-G expression (P

ABH and Lewis antigen expression has been associated with cancer development and prognosis, tumor differentiation, and metastasis. Considering that invasive ductal breast carcinoma (IDC) presents multiple molecular alterations, the aim of the present study was to determine whether the polymorphism of ABO, Lewis, and Secretor genes, as well as ABO phenotyping, could be associated with tumor differentiation and lymph nodes metastasis. Seventy-six women with IDC and 78 healthy female blood donors were submitted to ABO phenotyping/genotyping and Lewis and Secretor genotyping. Phenotyping was performed by hemagglutination and genotyping by the polymerase chain reaction with sequence-specific primers. ABO, Lewis, and Secretor genes were classified by individual single nucleotide polymorphism at sites 59, 1067, 202, and 314 of the Lewis gene, 428 of the Secretor gene, and 261 (O1 allele), 526 (O2 and B allele), and 703 (B allele). No association was found between breast cancer and ABO antigen expression (P = 0.9323) or genotype (P = 0.9356). Lewis-negative genotype was associated with IDC (P = 0.0126) but not with anatomoclinical parameters. Nonsecretor genotype was associated with axillary lymph node metastasis (P = 0.0149). In conclusion, Lewis and Secretor genotyping could be useful to predict respectively breast cancer susceptibility and axillary lymph nodes metastasis.

Histoplasmosis is a pulmonary disease characterised by chronic granulomatous and suppurative inflammatory reactions caused by Histoplasma capsulatum . Regarding new therapies to control fungal infections, the aim of this study was to investigate whether pulmonary administration of leukotriene B 4 (LTB 4 )-loaded microspheres (MS) could confer protection to 5-lipoxygenase knockout (5-LO −/− ) mice infected by H. capsulatum . In this study, MS containing LTB 4 were administered intranasally to mice infected by H. capsulatum . On Day 14 after the infection, fungal recovery from the lungs and histology were evaluated and inflammatory cytokines were measured. Pulmonary administration of LTB 4 -loaded MS was able to reduce fungal recovery from infected lungs. Production of important inflammatory cytokines related to host defence was augmented following MS administration to the lungs. Lung histology also showed that infected mice presented a clear reduction in the fungal burden following the pulmonary release of LTB 4 from MS. Our study provides evidence that the proposed biodegradable microparticulate system, which can release LTB 4 to the lungs, can be employed as therapy, enhancing the antimicrobial activity of host cells during histoplasmosis.

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICCw)] and absence [ICC without metastasis (ICCwt)] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICCwt ( n=52 patients) and ICCw ( n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.

Objective Eosinophils and cytokines are implicated in the pathogenesis of allergic diseases. In the present study, we investigate the anti-inflammatory effect of quercetin and isoquercitrin in a murine model of asthma. Methods BALB/c mice were immunized (ovalbumin/aluminum hydroxide, s. c.), followed by two intranasal ovalbumin challenges. From day 18 to day 22 after the first immunization, the mice received daily gavages of isoquercitrin (15 mg/kg) or quercetin (10 mg/kg). Dexamethasone (1 mg/kg, s. c.) was administered as a positive control. Leucocytes were analyzed in bronchoalveolar lavage fluid (BALF), blood and pulmonary parenchyma at 24 h after the last ovalbumin challenge. Interleukin-5 (IL-5) was analyzed in BALF and lung homogenates. Results In animals receiving isoquercitrin or quercetin, eosinophil counts were lower in the BALF, blood and lung parenchyma. Neutrophil counts in blood and IL-5 levels in lung homogenate were lower only in isoquercitrin-treated mice. No alterations in mononuclear cell numbers were observed. Conclusion Quercetin and isoquercitrin are effective eosinophilic inflammation suppressors, suggesting a potential for treating allergies.

The results of various animal model studies of tuberculosis (TB) suggest that culture filtrate proteins (CFPs), which are antigens secreted by Mycobacterium tuberculosis, are largely responsible for improvements in TB vaccines. The great obstacle to developing protein subunit vaccines is that adjuvants are required in order to stimulate relevant protective immune responses. Acting as immune adjuvants, CpG-oligodeoxynucleotides (CpG-ODNs) promote the activation of Th1 cells and of pro-inflammatory cytokines. To evaluate the adjuvant role of CpG-ODNs in conferring enhanced immunogenic capacity and protection against M. tuberculosis, we immunized mice with CFP antigen combined with synthetic CpG-ODNs (CFP/CpG) or with incomplete Freund's adjuvant (IFA) (CFP/IFA). Immunization with CFP/CpG induced a T helper 1 (Th1)-biased response accompanied by a higher immunoglobulin G2a (IgG2a) antibody/IgG1 antibody ratio, elevated production of interferon-gamma (IFN-gamma) by spleen cells and in lungs. However, CFP/IFA-immunized mice presented higher levels of IgG1 antibodies, as well as increased production of IFN-gamma, interleukin (IL)-5, and IL-10 by spleen cells, together with lower levels of IFN-gamma in the lungs. Despite the stronger Th1 response seen in both groups, believed to be necessary for protection against TB, only mice immunized with CFP/IFA were protected after M. tuberculosis infection. Lung histology revealed that lung parenchyma were better preserved in CFP/IFA-immunized mice, which also presented intense lymphocyte recruitment to the lesion, whereas CFP/CpG-immunized mice presented severe pulmonary injury accompanied by necrosis. Based on the data presented, we discuss the widely accepted paradigm that high levels of IFN-gamma are directly correlated with protection against experimental TB.

Extracts from the plant Synadenium carinatum latex are widely and indiscriminately used in popular medicine to treat a great number of inflammatory disorders and although the mechanisms underlying these effects remain undefined, the lectin isolated from S. carinatum latex (ScLL) is thought to be in part responsible for these anti-inflammatory effects. In order to elucidate possible immunoregulatory activities of ScLL, we investigated the effects of ScLL administration in models of acute and chronic inflammation. Oral administration of ScLL significantly inhibited neutrophil and eosinophil extravasation in models of acute and chronic inflammation and reduced eosinophil and mononuclear blood counts during chronic inflammation. ScLL administration reduced IL(interleukin)-4 and IL-5 levels but increased interferon-gamma and IL-10 in an asthma inflammatory model, which suggested that it might induce a TH2 to TH1 shift in the adaptive immune response. ScLL also inhibited IkappaBalpha degradation, a negative regulator of proinflammatory NF-kappaB. Taken together, these results provide the first description of a single factor isolated from S. carinatum latex extract with immunoregulatory functions and suggest that ScLL may be useful in the treatment of allergic inflammatory disorders.

Experimental toxocariasis was used as a model of eosinophil migration. Mice inoculated with 200 Toxocara canis eggs were treated with the leukotriene inhibitor MK886 (1 mg/kg/day). Eosinophils were counted in peripheral blood (PB), peritoneal cavity (PC) and bronchoalveolar lavage fluid (BALF) samples on post-infection days 3, 6, 12, 18, 24 and 36. Eosinophil expression of Mac-1 and VLA-4 was analysed in PB and PC samples. We found that T. canis infection induced systemic eosinophilia from post-infection day 3, peaking on days 6, 12 and 24 in PB, PC and BALF samples respectively. Eosinophilia was more pronounced in PB and PC samples than in BALF samples, and MK886 downregulated eosinophilia to varying degrees in the different sample types. In PB and PC samples, T. canis infection caused early upregulation of Mac-1 with late changes in the VLA-4 profile, whereas MK886 had opposite effects. The distinct time-dependent eosinophilia peaks and differential involvement of leukotrienes in integrin expression demonstrate that, despite the systemic eosinophilia triggered by T. canis infection, inflammatory responses vary by compartment.

The protective effect of infectious agents against allergic reactions has been thoroughly investigated. Current studies have demonstrated the ability of some helminths to modulate the immune response of infected hosts. The objective of the present study was to investigate the relationship between Toxocara canis infection and the development of an allergic response in mice immunised with ovalbumin (OVA). We determined the total and differential blood and bronchoalveolar lavage fluid cells using BALB/c mice as a model. To this end, the levels of interleukin (IL)-4, IL-5 and IL-10 and anti-OVA-IgE were measured using an ELISA. The inflammatory process in the lungs was observed using histology slides stained with haematoxylin and eosin. The results showed an increase in the total number of leukocytes and eosinophils in the blood of infected and immunised animals at 18 days after infection. We observed a slight lymphocytic inflammatory infiltrate in the portal space in all infected mice. Anti-OVA-IgE levels were detected in smaller proportions in the plasma of immunised and infected mice compared with mice that were only infected. Therefore, we concluded that T. canis potentiates inflammation in the lungs in response to OVA, although anti-OVA-IgE levels suggest a potential reduction of the inflammatory process through this mechanism.

Summary Objective The aim of this study is to evaluate the articular cartilage alterations of rat ankles, after applying unilateral cyclic passive muscle stretching protocol in previously immobilized rats. Methods Twenty-two male albino rats divided into four groups, I – immobilized; IS – immobilized and stretched; S – stretched and C – control, were used in this experiment. The I and IS groups were immobilized for 4 weeks. In the muscle stretching protocol the treated ankle joint (groups IS and S) was manually full dorsal flexed 10 times for 60s with a 30s interval between each 60s period, 7 days a week for 3 weeks, to stretch the ankle plantar flexors muscle group. The right hind limb was free to move. At the end of the experiment, the ankles were removed, processed in paraffin and stained with hematoxylin–eosin and Safranin-O. Two blinded observers evaluated cellularity, chondrocyte cloning and Safranin-O staining through light microscopy. And a morphometric study was carried out using a hand count of chondrocyte cells and cartilage thickness measurement. Results No significant effect of solely muscle stretching concerning cellularity, chondrocyte cloning and Safranin-O staining parameters was detected. However, IS group presented a significantly higher reduction of proteoglycans content than the solely stretched and solely immobilized groups and the morphometric analysis showed significant cellularity increase without thickness alteration compared to control. Conclusions These findings suggest that the stretching protocol used was harmful to the previously immobilized articular cartilage. However, the same stretching protocol did not harm the cartilage of non-immobilized groups.

It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B4 production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase−/− mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid of Swiss mice treated with MK886. In the lung parenchyma of infected animals, MK886 significantly inhibited synthesis of IL-5 at the beginning of infection, whereas levels of IL-12 increased progressively throughout the postinfection period. However, levels of leukotriene C4, PGE2, TNF-α, IL-3, IL-4, IFN-γ, and IL-10 were comparable between the treated and untreated groups. Nevertheless, IgE and IgG1 (but not IgG2a) synthesis was also significantly inhibited by MK886 administration. Therefore, in S. venezuelensis-infected mice, adult worm and egg burdens are leukotriene dependent. These findings indicate potential immunostimulatory strategies involving leukotriene administration, and may serve as an alert to physicians treating Strongyloides stercoralis-infected patients presenting asthma-like symptoms because use of 5-lipoxygenase inhibitors may worsen the infection.

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent cytokine that plays an important role in inhibiting the action of microbial agents, andTNFmicrosatellite polymorphisms have been associated with several diseases, including cancer and viral infections. This study analyzed the associations betweenTNFato -emicrosatellite polymorphisms and the severity of squamous intraepithelial lesions (SIL), according to the presence of the oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low-grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women were studied.TNFmicrosatellite polymorphism typing and HPV detection and typing were performed using PCR-amplified DNA hybridized with sequence-specific primers. Data were analyzed by Fisher's exact test using the GENEPOP software. Significant associations were observed between LSIL and theTNFa-8allele (4/166;P= 0.04), as well as betweenTNFa-2with HPV18 only (16/44;P= 0.002) andTNFa-2with HPV18 coinfection with HPV16 (16/44;P= 0.001). Patients exhibiting theTNFa-2allele and harboring HPV18, in the presence or absence of coinfection with HPV16, had an increased risk of HSIL occurrence (13/38;P= 0.04; 5/10;P= 0.04) compared to patients with other HPV types. These results suggest that theTNFa-8allele is associated with increased susceptibility to the occurrence of LSIL and that despite the presence of a high TNF-α production allele, the ability of HPV18 to resist the inhibitory effects of TNF-α may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.

Made available in DSpace on 2022-04-29T08:42:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-04-01 Inactivation of the cell cycle inhibitor gene p16MTS1 seems to be involved in human papillomavirus (HPV)-related carcinogenesis because E6 and E7 oncoproteins may impair p16INK4a and, indirectly, bcl-2 functions. In this study, we analyzed the role of immunohistochemical expression of p16 INK4a and bcl-2 in HPV-infected cervical biopsies as prognostic markers of the progression of squamous intraepithelial lesion (SIL). Sixty-five cervical biopsies were stratified into two subgroups according to the second biopsy: 27 of them maintained a low-grade (LG)-SIL diagnosis, and 38 progressed from LG-SIL to high-grade (HG)-SIL. p16INK4a and bcl-2 quantitative expression levels were measured by the immunoperoxidase method. PCR-DNA techniques were used to detect and type HPV. The Wilcoxon and Fisher exact tests were employed for the statistical analysis. In the group with an LG-SIL diagnosis at the second biopsy, no significant associations were found between p16INK4a and bcl-2 expression and presence of HPV16/18. In the group that progressed to HG-SIL, a significant association was observed between p16INK4a overexpression and HPV16/18 presence (p = 0.021), but none with bcl-2 levels. It is concluded that immunohistochemical bcl-2 expression may not be useful for predicting the progression of HPV-related SIL. In contrast, p16INK4a overexpression seemed to be associated with HPV 16 and 18, suggesting that it may be a good marker for predicting SIL progression. Department of Pathology School of Medicine of Ribeirao Preto University of São Paulo, São Paulo Division of Clinical Immunology School of Medicine of Ribeirao Preto University of São Paulo, São Paulo Department of Clinical Analyses Sch. Pharmaceutical Sci. Araraquara University of São Paulo State, Araraquara Department of Pathology School of Medicine of Ribeirao Preto University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP

PURPOSE: Develop an experimental model to study esophageal preneoplastic lesions induced by diethylnitrosamine in rats with achalasia. METHODS: Male Wistar rats were divided into four groups: control - C (n=8); rats with megaesophagus - B (n=8); rats treated with DEN - D (n=15) and rats with megaesophagus plus DEN - BD (n=15). Megaesophagus can be experimentally obtained in rats by topical application of benzalkonium choride. The morphology and PCNA labeling index of the epithelium were evaluated. RESULTS: The morphometric analysis showed an increase in epithelial thickness in the animals of group BD (2166±1012mm²) when compared to the other groups (C = 878±278mm²; B = 1746±144mm² and D = 1691±697mm²), mainly due to basal layer hyperplasia, besides an increase in the keratin of the superficial layer. The PCNA labeling index in the basal layer was significantly higher in the group BD (0,695±0,111) when compared to the other groups (C = 0,490±0,132; B = 0,512±0,215 and D = 0,477±0,198). CONCLUSIONS: Our data confirm in an experimental model the previous observation in humans of increased epithelial cell proliferation during the esophageal carcinogenic process in achalasia and may be useful to further studies on the mechanisms of the esophageal carcinogenesis and the the design of follow-up endoscopic studies for patients with achalasia. OBJETIVO: Desenvolver um modelo experimental que permitisse o estudo de lesões preneoplásicas induzidas por diethylnitrosamina em ratos com acalasia. MÉTODOS: Ratos Wistar machos foram distribuídos em quatro grupos: controle - C (n=8); ratos com megaesôfago - B (n=8); ratos tratados com DEN - D (n=15) e ratos com megaesôfago mais DEN - BD (n=15). O megaesôfago pode ser obtido experimentalmente através da aplicação tópica de cloreto de benzalcônio. Foi avaliada a morfologia do epitélio e a proliferação celular do epitélio pelo método do PCNA. RESULTADOS: A análise morfométrica mostrou aumento da espessura epitelial no grupo BD (2166±1012mm²) em relação aos outros grupos (C = 878±278mm²; B = 1746±144mm² e D = 1691±697mm²), principalmente devido a uma hiperplasia da camada basal e um aumento na queratina da camada superficial. O índice de marcação pelo PCNA na camada basal foi significantemente maior neste mesmo grupo (0,695±0,111) quando comparado com os outros (C-0,490±0,132; B-0,512±0,215 e D-0,477±0,198). CONCLUSÕES: Estes dados confirmam através de um modelo experimental o aumento proliferativo celular durante o processo de carcinogênese na acalasia do esôfago e podem ser úteis durante estudos de endoscopia realizados em pacientes que possuem acalasia.

Medullary thyroid carcinoma (MTC) occurs in a sporadic or as an autosomal dominant hereditary form. Inherited forms of MTC are related to mutations in the RET proto-oncogene. We screened genomic DNA from 11 patients with MTC for mutations in exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene. Subsequently, we also evaluated a family of 1 patient with presumed diagnosis of sporadic MTC. Three patients with MEN2A from two unrelated families presented mutations in exon 11 (C634Y and C634R). A heterozygous mutation in exon 14 (V804M) was identified in the patient with the presumed sporadic MTC. We also observed two different polymorphisms: S904S in exon 15 (2 patients) and L769L in exon 13 (4 patients). The L769L polymorphism has been associated with earlier onset of sporadic MTC. On the other hand, mutations in exon 14 are associated with MTC of later onset and lower aggressiveness. Indeed, the carrier of the V804M mutation associated with L769L polymorphism presented MTC at 32 years of age, in contrast to her asymptomatic mother, who had only the V804M mutation and had MTC diagnosed by fine-needle aspiration biopsy at 60 years of age. In conclusion, the present study confirms the need for genetic screening to differentiate sporadic and hereditary forms of MTC. In addition, the genetic study allows the identification of asymptomatic carriers of hereditary forms of MTC. Finally, we speculated that the L769L polymorphism of the RET proto-oncogene may be related to earlier age of onset in the patient with the V804M mutation.

We evaluated the use of a vaccine formulation based on a mixture of two different PLGA microspheres, composed by faster and slower release profiles, containing DNA encoding hsp65 and the recombinant hsp65 protein, respectively, aiming to DNA priming and protein boost after a single dose vaccination. The combination of PLGA50:50 microspheres containing DNA-hsp65 and trehalose dimycolate (TDM) with PLGA75:25 microspheres containing recombinant hsp65 (prime-boost Me) was able to induce high levels of anti-hsp65 specific antibodies. The serum levels of these specific antibodies remained high during 90 days after vaccination, whereas the DNA Me formulation based only in DNA-hsp65 plus TDM-loaded microspheres was not able to sustain the high antibody levels during the same period. Production of IFN-gamma was significant in animals vaccinated with both formulations, while the prime-boost Me vaccinated mice sustained higher levels of this cytokine during all the evaluation period. Thus, prime-boost strategy by using biodegradable microspheres seems to be a promising strategy to stimulate long-lasting immune response.

Genetic susceptibility factors, parasite strain, and an adequate modulation of the immune system seem to be crucial for disease progression afterTrypanosoma cruziinfection. HLA-G and its murine functional homolog Qa2 have well-recognized immunomodulatory properties. We evaluated theHLA-G3′ untranslated region (3′UTR) polymorphic sites (associated with mRNA stability and target for microRNA binding) and HLA-G tissue expression (heart, colon, and esophagus) in patients presenting Chagas disease, stratified according to the major clinical variants. Further, we investigated the transcriptional levels of Qa2 and other pro- and anti-inflammatory genes in affected mouse tissues duringT. cruziexperimental acute and early chronic infection induced by the CL strain. Chagas disease patients exhibited differentialHLA-G3′UTR susceptibility allele/genotype/haplotype patterns, according to the major clinical variant (digestive/cardiac/mixed/indeterminate). HLA-G constitutive expression on cardiac muscle and colonic cells was decreased in Chagasic tissues; however, no difference was observed for Chagasic and non-Chagasic esophagus tissues. The transcriptional levels ofQa2and other anti and proinflammatory (CTLA-4, PDCD1, IL-10, INF-γ, andNOS-2) genes were induced only during the acuteT. cruziinfection in BALB/c and C57BL/6 mice. We present several lines of evidence indicating the role of immunomodulatory genes and molecules in human and experimentalT. cruziinfection.

HLA-G is a nonclassical major histocompatibility complex molecule that has well-recognized immunomodulatory properties. The expression of HLA-G in tumor cells has been considered to be detrimental, permitting tumor spreading and decreased survival. We evaluated the expression of HLA-G in histologically normal thyroid tissue, goiter, and benign and malignant thyroid tumors, and studied the relationship between HLA-G expression and patient clinical variables.The immunohistochemistry expression of HLA-G was performed on 72 specimens of papillary thyroid carcinoma (PTC), 19 follicular thyroid carcinomas (FTC), 22 follicular adenomas (FA), 22 colloid goiters (CG), and 14 histologically normal thyroid glands (NT). The percentage of HLA-G staining was graded from absent (-) to intense (+++).HLA-G was faintly expressed in areas of hyperplasia in NT and CG. In PTC, FTC, and FA, the percentage of cell staining was significantly higher than in NT and CG (p0.001 for each comparison). The tumor area with HLA-G expression was greater in FTC (p=0.0059) and PTC (p=0.0330) compared to FA. According to the magnitude of HLA-G staining, PTC tumors1 cm exhibited increased HLA-G staining when compared to smaller tumors (p=0.03). Aggressive histologic subtypes of PTC have a higher median stained tumor area. No association was found between HLA-G expression and tumoral staging or patient disease-free survival.The gradual increase of HLA-G expression from hyperplasia to carcinomas, and the association of strong HLA staining with some variables implicated in poor prognosis corroborate the unfavorable role of HLA-G in tumor thyroid cells, inhibiting cytotoxic immune system cells and facilitating tumor evasion and progression.

To correlate subclinical conjunctival inflammation and trabeculectomy results.Prospective case series of 28 patients with primary open-angle glaucoma (28 eyes) under topical anti-glaucoma medication who underwent trabeculectomy. During surgery, a sample from the inferior bulbar conjunctiva was collected and the expression of HLA-DR together with the presence of inflammatory cells was correlated with trabeculectomy outcomes after 24 months. Surgical success was defined as intraocular pressure between 6 and 20 mmHg irrespective of the use of anti-glaucoma medication.Five patients missed follow-up visits and were removed from the study. Ten eyes (43.5%) were HLA-DR(+), but no significant differences were observed between eyes with successful and failed surgeries (p = 0.214). There was no significant association between the number of neutrophils and surgical outcomes (p = 0.353).The presence of inflammatory cells and expression of the inflammation marker HLA-DR in the conjunctiva did not correlate with the prognosis of trabeculectomy in this study.

Cases of mixed medullary-papillary carcinoma are rare and have not been classified by WHO. We report a 32yo patient who had a diagnosis on cytological analysis by fine needle biopsy as Hurthle cell neoplasm with probable metastases to cervical nodules, due to the presence of numerous isolated cells of an oxyphilic pattern. After total thyroidectomy, on histology, a mixed medullary-papillary carcinoma with oxyphilic differentiation was diagnosed based on the papillary arrangement with fibrovascular septa containing cells showing a predominant oxyphilic pattern, both in the thyroid nodule and in regional cervical lymph nodes. Amorphous material of amyloidal aspect, which stained positively for Congo red, accompanied by focal calcification, was observed, both in the primary tumors and in the metastases. Thyroglobulin was not immunostained in the cells obtained by fine needle aspiration biopsy, but was immunostained in histology fields, both in the thyroid nodules and in the metastases. The immunoreaction for calcitonin was predominant on cytologic analysis and in the hystologic exam of the primary tumor and metastases. Dual differentiation in thyroid neoplasms has been interpreted as indicative of a common stem cell origin. It has been reported that the ultimobranchial body in man contributes both with C-cells and follicular cells to the thyroid. Thus, a common stem cell could give rise to such a mixed medullary-papillary neoplasm.

Human leukocyte antigen (HLA)—E is a non-classical molecule of the histocompatibility complex that functions as one of the main ligands of the Natural Killer (NK) cell inhibitory receptor CD94/NKG2A and inhibits its potent cytotoxic activity. Due to the important role of NK cells in combating neoplasm, we hypothesized that the differential expression of HLA-E could favor the progression of heterogeneous thyroid tumors. Using an immunohistochemistry technique in 143 biopsies of thyroid tumors, including benign and malignant neoplasms and goiters, we evaluated the expression of HLA-E among various tumor types and its association with the clinicopathological factors of diseases. We verified high HLA-E expression in all types of neoplastic tumors, although no significant differences between the groups were found. Low expression was observed in 95% of the goiter samples, showing significant differences between neoplastic and non-neoplastic lesions. Furthermore, a significant result was found with regard to the tumor size, with high HLA-E expression being related to smaller tumors. Therefore, our data suggest that an increase in HLA-E may be associated with the establishment of thyroid neoplasms, with either benign or malignant features.