Predicting kidney allograft survival with explainable machine learning.

INTRODUCTION: Despite significant progress over the last decades in the survival of kidney allografts, several risk factors remain contributing to worsening kidney function or even loss of transplants. We aimed to evaluate a new machine learning method to identify these variables which may predict the early graft loss in kidney transplant patients and to assess their usefulness for improving clinical decisions. MATERIAL AND METHODS: A retrospective cohort study was carried out with 627 kidney transplant patients followed at least three months. All these data were pre-processed, and their selected features were used to develop an automatically working a machine learning algorithm; this algorithm was then applied for training and parameterization of the model; and finally, the tested model was then used for the analysis of patients' features that were the most impactful for the prediction of clinical outcomes. Our models were evaluated using the Area Under the Curve (AUC), and the SHapley Additive exPlanations (SHAP) algorithm was used to interpret its predictions. RESULTS: The final selected model achieved a precision of 0.81, a sensitivity of 0.61, a specificity of 0.89, and an AUC value of 0.84. In our model, serum creatinine levels of kidney transplant patients, evaluated at the hospital discharge, proved to be the most important factor in the decision-making for the allograft loss. Patients with a weight equivalent to a BMI closer to the normal range prior to a kidney transplant are less likely to experience graft loss compared to patients with a BMI below the normal range. The age of patients at transplantation and Polyomavirus (BKPyV) infection had significant impact on clinical outcomes in our model. CONCLUSIONS: Our algorithm suggests that the main characteristics that impacted early allograft loss were serum creatinine levels at the hospital discharge, as well as the pre-transplant values such as body weight, age of patients, and their BKPyV infection. We propose that machine learning tools can be developed to effectively assist medical decision-making in kidney transplantation.

Interlocus gene conversion: Identification of HLA-A*23:128 in a Brazilian bone marrow donor.

Identification of novel HLA-A*23:128 allele generated by interlocus gene conversion in Brazilian bone marrow donor.

Impact of pretransplantation malnutrition risk on the clinical outcome and graft survival of kidney transplant patients / Impacto do risco de desnutrição pré-transplante no desfecho clínico e na sobrevida do enxerto de pacientes transplantados renais

ABSTRACT Background: The prevalence of malnourished patients before transplantation and the influence of malnutrition on graft and patient outcomes remain underestimated, despite being associated with higher postoperative morbidity and mortality. This study aimed to develop an easy nutritional screening tool and evaluate the impact of nutritional status on clinical outcome, graft survival (GS) and mortality risk in kidney transplant patients (KTP). Methods: In this retrospective cohort study including 451 KTP, we developed a score by using anthropometric, clinical, and laboratory measures performed in the pretransplant evaluation. The patients were stratified into 3 groups according to the final score: G1 (0 or 1 point)=low risk, G2 (2 to 4 points)=moderate risk, and G3 (>5 points)=high risk of malnutrition. The patients were monitored after transplantation at least 1 to 10 years. Results: Stratifying the 451 patients based on the pretransplant risk score, G1, G2, and G3 were composed of 90, 292, and 69 patients, respectively. Patients from G1 maintained the lowest serum creatinine levels at hospital discharge when compared with others (p = 0.012). The incidence of infection in the patients from G3 was higher than patients from G1 and G2 (p = 0.030). G3 recipients showed worse GS than G1 patients (p = 0.044). G3 patients showed almost threefold higher risk for graft loss (HR 2.94, 95% CI 1.084-7.996). Conclusions: KTP with higher malnutrition risk score were associated with worse outcomes and GS. The nutritional screening tool is easy to be used in clinical practice to evaluate the patient in preparation for kidney transplant.

RESUMO Antecedentes: A prevalência de pacientes desnutridos antes do transplante e a influência da desnutrição nos desfechos do enxerto e do paciente permanecem subestimadas, embora estejam associadas a maior morbimortalidade pós-operatória. Este estudo buscou desenvolver uma ferramenta simples de triagem nutricional e avaliar o impacto do estado nutricional no desfecho clínico, sobrevida do enxerto (SE) e risco de mortalidade em pacientes transplantados renais (PTR). Métodos: Neste estudo de coorte retrospectivo incluindo 451 PTR, desenvolvemos um escore usando medidas antropométricas, clínicas e laboratoriais tomadas na avaliação pré-transplante. Os pacientes foram estratificados em 3 grupos segundo a pontuação final: G1 (0-1 ponto) = baixo risco, G2 (2-4 pontos) = risco moderado e G3 (>5 pontos) = alto risco de desnutrição. Eles foram monitorados por pelo menos 1 a 10 anos após o transplante. Resultados: Os 451 pacientes foram estratificados em G1, G2 e G3, que consistiram em 90, 292 e 69 pacientes, respectivamente. Os pacientes do G1 mantiveram os menores níveis de creatinina sérica na alta hospitalar em relação aos demais (p = 0,012). A incidência de infecção nos pacientes do G3 foi maior que nos pacientes do G1 e G2 (p = 0,030). Os pacientes do G3 apresentaram SE pior do que os pacientes do G1 (p = 0,044) e um risco quase três vezes maior de perda do enxerto (HR 2,94; IC 95% 1,084-7,996). Conclusões: PTR com maior escore de risco de desnutrição foram associados a piores desfechos e menor SE. A ferramenta de triagem nutricional é fácil de usar na prática clínica para avaliar pacientes em preparação para transplante renal.

Remarkable 107-year-old kidney with a 49-year of long-term allograph survival through continuous azathioprine monotherapy.

BACKGROUND: The main goal of kidney allograft transplantation is to improve survival in patients with end-stage kidney failure. Herein, we report a 49-year long-term allograft survival with non-identical human leukocyte antigens (HLA). The purpose of this study was to report the successful clinical outcome of 49 years of transplant survival in a 79-year-old patient with a 107-year-old kidney undergoing continued immunosuppressive monotherapy. MATERIAL AND METHODS: The patient was evaluated clinically and immunologically with HLA typing and anti-HLA antibodies before transplantation. Post-transplant, the patient's clinical and immunological survival were monitored for 49 years. The state of the chimerism was assessed using the polymerase chain reaction to amplify 24 short tandem repeats using a DNA thermocycler and DNA analyzer. RESULTS: The patient and donor were haploidentical and the patient was treated with azathioprine monotherapy. Donor-specific antibodies were detected only for the HLA-DPB1* 03:01 mismatch. This patient developed multiple skin tumors 26 years after transplant, which were successfully treated with topical therapy or surgical removal. The patient developed an intestinal adenocarcinoma 43 years after kidney transplantation, which was surgically removal; six years later, adenocarcinoma was diagnosed in a finger, followed by axillar and hepatic metastases. After 49 years of graft survival of a kidney of 107 years old in a patient with 79 years of age, the patient's health worsened with severe dehydration, anemia, and bacterial infection. The patient was hospitalized with a serum creatinine level of 3.45 mg/dL, urea level of 188 mg/dL, and estimated glomerular filtration rate of 22 mL/1.72 m2; septicemia developed and was treated with antibiotics. The patient had poor clinical progress, was intubated, and later died due to septic shock. CONCLUSIONS: To the best of our knowledge, this is the first case of a 107-year-old kidney, transplanted into a recipient who was treated with azathioprine monotherapy for 49 years.

Malignancy Diseases in Kidney Transplantation, Clinical Outcomes, Patient, and Allograft Survival: A Case-Control Study.

BACKGROUND: Malignancy is a well-known complication in patients after kidney transplantation (KT), but its effect on posttransplant outcomes, allograft, and patient survival remains unexplored. The aim of this study is to report the impact of the comorbidity on clinical outcome, function, and failure of an allograft kidney. METHODS: This case-control study included 101 KT patients. Twenty-six patients who developed cancer (CA) were assigned to the case group and 75 to the control group. Statistical analysis was performed using logistic regression models, and graft survival was analyzed using the Kaplan-Meier curve. RESULTS: Non-melanoma skin CA was the most common malignancy, accounting for almost 60% of cases, followed by stomach CA, prostate CA, and lymphoproliferative diseases (7.70% each). Difference in graft and patient survival was not significant between the two groups (P > .05). A tumor in nonfunctioning in the first nonfunctioning KT was identified in 1 KT patient with a second allograft and by anatomopathological was detect Fuhrman grade II renal cell carcinoma. This KT patient was in good clinical condition with serum creatinine level of 1.5 mg/dL. CONCLUSIONS: No association was observed between CA development and risk factors, including family history and smoking habit, and no differences in allograft and patient survival were found. Nevertheless, in our data, CA in KT patients occurred early after transplantation. Renal cell carcinoma in allograft failure was identified in a patient; that suggested that nephrectomy of kidney failure must be performed to avoid patient allosensitization and neoplasia. Thus, we suggest continuous screening of malignancy diseases for KT patients.

Estudo prospectivo para avaliar clínica e imunologicamente receptores em baixo, médio, alto e muito alto risco de rejeição humoral com rins de doadores falecidos / Prospective study to clinical and immunological evaluation of recipients in low, medium, high and strong risk of humoral rejection with kidney of deceased donors

Introdução: Os anticorpos específicos contra o doador (DSA) representam uma das principais barreiras para o sucesso do transplante renal. Material e métodos: Os cem receptores, classificados em baixo risco (BR), médio risco (MR), alto risco (AR) e muito alto risco (MAR) de terem rejeição mediada por anticorpos (RMA) foram transplantados com rins de doadores falecidos (DF). A sobrevida dos enxertos foi avaliada após um ano. Resultados: Dos 100 receptores que receberam rins de DF, 54 (54,0%) foram classificados como BR. Destes, oito rejeitaram (14,8%), três perderam os enxertos, sendo duas perdas por RMA (DSA MFI 1223 a 2341) e uma por causa não imunológica (CNI). Entre os 30 (30,0%) classificados em MR, 10 (33,3%) rejeitaram, desses quatro perderam os enxertos, sendo duas perdas por RMA (DSA MFI 530 e 870), uma por rejeição celular (RC) e uma por CNI. Entre os 10 (10,0%) classificados em AR, três rejeitaram, sendo observadas três perdas por RMA (DSA MFI de 3493 a 6068). Entre os 6 (6,0%) classificados como MAR, cinco tiveram episódios de rejeições, quatro perderam os enxertos, sendo três perdas por RMA (DSA MFI 7226 a 12591) e uma por RC. A sobrevida dos enxertos no primeiro ano para os pacientes em BR, MR, AR+MAR foi de 91,22%, 78,75% e 80,28%, respectivamente. Conclusão: Esse protocolo demonstrou ser eficiente e permitiu uma avaliação imunológica precisa de receptores classificados de acordo com o risco de RMA. Do total de pacientes, 26 (26%) tiveram episódios de rejeições, 12 (46%) pacientes perderam os enxertos devido a causas imunológicas, sendo duas perdas por RC e 10 por RMA, o que evidencia a gravidade das rejeições. Além disso, tivemos duas perdas por CNI. Após um ano, 87 (87%) dos pacientes mantiveram boa função renal, com creatinina variando de 0,9 a 1,6 mg/dL...

Identification of candidate antigens from adult stages of Toxocara canis for the serodiagnosis of human toxocariasis

In the present work, we identified adult Toxocara canis antigens through sodium dodecyl sulfate-polyacrylamide gel electrophoresis for potential use in human toxocariasis immunodiagnosis. The sensitivity and specificity of several semi-purified antigens, as well as their cross-reactivity with other parasitic infections, were assessed by IgM and IgG-enzime linked immunosorbent assay. Whilst we found that the crude extract of the parasite presented limited sensitivity, specificity and high cross-reactivity against other parasites, we identified 42, 58, 68 and 97-kDa semi-purified antigens as the most promising candidates for immunodiagnosis. Moreover, the 58 and 68-kDa antigens presented the lowest IgM cross-reactivity. When tested as a combination, a mixture of the 58 and 68-kDa antigens presented 100 percent sensitivity and specificity, as well as minor cross-reactivity. Although the combination of the 42, 58, 68 and 97-kDa antigens presented 100 percent sensitivity at a dilution of 1:40, the low specificity and high cross-reactivity observed suggested a limited use for diagnostic purposes. Our data suggested that the 58 and 68-kDa antigens might be most suitable for the immunodiagnosis of human toxocariasis.

A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with meglumine antimoniate for the treatment of cutaneous leishmaniasis.

Forty-four adult patients with cutaneous leishmaniasis (CL) were enrolled in a randomized, double-blind, controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1+MPL-SE vaccine (consisting of 5, 10, or 20 µg recombinant Leishmania polyprotein LEISH-F1 antigen+25 µg MPL-SE adjuvant) (n=27), adjuvant alone (n=8), or saline placebo (n=9). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received chemotherapy with meglumine antimoniate starting on Day 0. The vaccine was safe and well tolerated. Nearly all vaccine recipients and no adjuvant-alone or placebo recipients demonstrated an IgG antibody response to LEISH-F1 at Day 84. Also at Day 84, 80% of vaccine recipients were clinically cured, compared to 50% and 38% of adjuvant-alone and placebo recipients. The LEISH-F1+MPL-SE vaccine was safe and immunogenic in CL patients and appeared to shorten their time to cure when used in combination with meglumine antimoniate chemotherapy.

Avaliação de atividades de controle para enteroparasitos em uma aldeia Kaingáng do Paraná / Evaluation of enteroparasite control activities in a Kaingáng community of Southern Brazil

OBJETIVO: Analisar o estado parasitológico de famílias de comunidade indígena após instituição de medidas de controle para enteroparasitos. MÉTODOS: Estudo longitudinal realizado entre 2004 e 2006 com 447 pessoas da etnia Kaingáng, no município de Cândido de Abreu, PR. As medidas de controle de enteroparasitos foram: melhorias sanitárias em 2003, tratamentos antiparasitários realizados durante o período de estudo e atividades de educação em saúde iniciadas em 2005. Foram obtidos indicadores parasitológicos de saúde em três inquéritos coproparasitológicos em 2004, 2005 e 2006 quando foram coletadas 250, 147 e 126 amostras de fezes, respectivamente. Foram utilizados os métodos de sedimentação espontânea, centrífugo-flutuação e Kato/Katz. As condições de moradia e higiene foram determinadas utilizando-se questionário aplicado a 69 (2004), 57 (2005) e 38 (2006) das 90 famílias. RESULTADOS: As prevalências totais de enteroparasitos de 2004-06 foram, respectivamente: 91,6 por cento, 94,6 por cento e 87,3 por cento, sem redução significativa. A prevalência de algumas espécies reduziu enquanto que a de outras aumentou significativamente. As infecções de alta intensidade por geoelmintos apresentaram taxas menores de 2 por cento no período do estudo. Houve aumento nas taxas de entrevistados que relataram usar o banheiro (p<0,005) de 38,8 por cento para 71,1 por cento e ter tomado antiparasitário (p=0,001) de 70,2 por cento para 100,0 por cento. CONCLUSÕES: Houve melhora significativa de indicadores parasitológicos de saúde da população como a redução na prevalência de algumas espécies de enteroparasitos, além da manutenção de baixa carga parasitária, mostrando a importância de se associar o tratamento antiparasitário às melhorias sanitárias.

OBJECTIVE: To analyze the parasitological state of families in an indigenous community after institution of enteroparasite control measures. METHODS: A longitudinal study was conducted between 2004 and 2006 among 447 individuals of the Kaingáng ethnic group, in the municipality of Cândido de Abreu, Southern Brazil. The enteroparasite control measures were: sanitation improvements in 2003, antiparasite treatments that were administered during the study period, and health education activities that were started in 2005. Parasitological health indicators were obtained through three coproparasitological surveys (in 2004, 2005 and 2006), in which 250, 147 and 126 stool samples, respectively, were collected. These were evaluated using the spontaneous sedimentation, centrifugation-flotation and Kato-Katz methods. Housing and hygiene conditions were assessed by means of a questionnaire applied to 69 (2004), 57 (2005) and 38 (2006) of the 90 families. RESULTS: The overall prevalences of enteroparasites were 91.6 percent (2004), 94.6 percent (2005) and 87.3 percent (2006) and did not show any significant reduction. The prevalence of some species decreased, while the prevalence of others increased significantly. High-intensity infections due to geohelminths presented rates of less than 2 percent over the study period. The proportion of the interviewees who reported using a toilet increased from 38.8 percent to 71.1 percent (p< 0.005) and the proportion taking antiparasite agents increased from 70.2 percent to 100 percent (p= 0.001). CONCLUSIONS: There were significant improvements in the parasitological health indicators, such as reductions in the prevalence of some species of enteroparasites and maintenance of a low parasite load, thus showing the importance of combining antiparasite treatment with sanitation improvements.

Análise de citocinas pela RT-PCR em pacientes com rinite alérgica / RT-PCR cytokine study in patients with allergic rhinitis

Rinite alérgica é uma doença que decorre de um processo inflamatório da mucosa nasal conseqüente à reação de hipersensibilidade a alérgenos inalatórios e, eventualmente, alimentares. É mediada por IgE, envolvendo diferentes células, mediadores e citocinas. OBJETIVO: Avaliar as transcrições para as seguintes citocinas: IL-4, IL-5, IL-8 e IFN-gama, particularmente importantes no processo alérgico nasal, principalmente IL-4 e IL-5. Neste estudo, optou-se por avaliar os pacientes atópicos fora das crises alérgicas, com a finalidade de se conhecer as expressões das citocinas neste período. MATERIAL E MÉTODO: Realizou-se um estudo transversal e prospectivo, selecionando-se 30 pacientes, sendo 13 pacientes portadores de rinite alérgica paucissintomáticos e 17 pacientes não-atópicos. Os grupos foram selecionados através da história, do exame clínico otorrinolaringológico e do teste alérgico cutâneo - Prick Test. O perfil das citocinas foi pesquisado nos fragmentos de mucosa nasal, através da RT-PCR semiquantitativa, escolhida por apresentar boa reprodutibilidade e especificidade, utilizando-se como referência o gene da Beta-actina. RESULTADOS: Os valores de IL-5, IL-8, IFN-gama mantiveram-se homogêneos em relação ao grupo controle. A IL-4 apresentou diferença com significância estatística. CONCLUSÃO: Os pacientes alérgicos paucissintomáticos apresentaram normalização da expressão das citocinas na mucosa nasal à exceção de IL-4.

Allergic rhinitis is an inflammatory reaction of the nasal mucosa, in consequence of an IgE mediated hypersensitive reaction to inhaling allergens, involving different mediators and cytokine cells. AIM: The purpose of this study was to evaluate the transcriptions for IL-4, IL-5, IL-8 and IFN-gama, particularly important in the nasal allergy process, especially IL-4 and IL-5. For this study we decided to evaluate atopic patients who were free from allergic crises, with the purpose of knowing the cytokine expressions during this period. MATERIALS AND METHODS: Another prospective and transversal study was carried out, selecting 30 patients, 13 of these patients were pauci-symptomatic and 17 were non atopic. The groups were selected by means of a medical interview, an otolaryngologic clinical exam and allergy skin tests - Prick Test. The cytokines were investigated in fragments of the nasal mucosa, using RT-PCR - chosen because it has good reproducibility and specificity. RESULTS: IL-5, IL-8, IFN-gama cytokine values were kept homogeneous in relation to the control group. Only IL-4 presented significant statistic differences. CONCLUSION: Asymptomatic patients with allergic rhinitis presented with normalization of cytokine expression in the nasal mucosa, with exception of IL-4.

Evaluation of an immunochemotherapeutic protocol constituted of N-methyl meglumine antimoniate (Glucantime) and the recombinant Leish-110f + MPL-SE vaccine to treat canine visceral leishmaniasis.

The evaluation of the efficacy of an immunochemotherapy protocol to treat symptomatic dogs naturally infected with Leishmania chagasi was studied. This clinical trial had the purpose to test the combination of N-methyl meglumine antimoniate (Glucantime and the second generation recombinant vaccine Leish-110f plus the adjuvant MPL-SE to treat the canine leishmaniasis (CanL). Thirty symptomatic naturally infected mongrel dogs were divided into five groups. Animals received standard treatment with Glucantime or treatment with Glucantime Leish-110f + MPL-SEas immunochemotherapy protocol. Additional groups received Leish-110f + MPL-SE only, MPL-SE only, or placebo. Evaluation of haematological, biochemical (renal and hepatic function) and plasmatic proteins, immunological (humoral and cellular immune response) and the parasitological test revealed improvement of the clinical parameters and parasitological cure in dogs in both chemotherapy alone and immunochemotherapy cohorts. However, the immunotherapy and immunochemotherapy cohorts had reduced number of deaths, higher survival probability, and specific cellular reactivity to leishmanial antigens, in comparison with chemotherapy cohort only and control groups (adjuvant alone and placebo). These results support the notion of using well-characterized recombinant vaccine as an adjunct to improve the current chemotherapy of CanL.

A cross-sectional study of 130 Brazilian patients with Crohn's disease and ulcerative colitis: analysis of articular and ophthalmologic manifestations.

This is a cross-sectional study that analyzed the pattern and frequency of articular and ophthalmologic manifestations in patients with Crohn's disease (CD) and ulcerative colitis (UC), with or without signs of active bowel inflammation. One hundred and thirty consecutive patients with CD (n = 71) and UC (n = 59) were examined. Simple X-rays of lumbar spine, sacroiliac joints, and calcaneal bone were performed and human leukocyte antigen (HLA)-B27 was typed. Joint manifestations occurred in 41 (31.5%) patients, 27 (38%) with CD and 14 (23.7%) with UC. Peripheral involvement occurred in 22 patients, axial involvement in five, and mixed involvement in 14. The most frequently involved joints were knees (56.1%), ankles (29.3%), and hips (29.3%), while the predominant pattern was oligoarticular (84.6%) and asymmetrical (65.6%). Enthesitis was identified in seven (5.4%) patients and inflammatory lumbar pain in 13 (10%). Eight of these patients fulfilled the diagnostic criteria for ankylosing spondylitis (6.2%). Radiographic sacroiliitis occurred in 12 patients (9.2%). Ocular abnormalities were present in six patients (6.2%), and HLA-B27 was positive in five (5.8%). In conclusion, the articular manifestations in the present study were predominantly oligoarticular and asymmetric, with a low frequency of ophthalmologic involvement and positive HLA-B27.

Immunodiagnosis of human neurocysticercosis by using semi-purified scolex antigens from Taenia solium cysticerci.

Crude antigen and semi-purified proteins from scolices of Taenia solium cysticerci were evaluated for the immunodiagnosis of human neurocysticercosis neurocysticercosis. Semi-purified proteins obtained by electrophoresis on polyacrylamide gel and by electroelution were tested by means of the immunoenzymatic reaction against sera from normal individuals and from patients with neurocysticercosis or other parasitic diseases. The 100 kDa protein provided 100% sensitivity and specificity in the immunodiagnosis. When 95 or 26 kDa proteins were used, 95 and 100% sensitivity and specificity were obtained, respectively. The assays involving crude antigen and sera from normal individuals or from patients with neurocysticercosis, diluted to 1:256, gave excellent agreement with those in which 100, 95 or 26 kDa proteins were tested against the same serum samples diluted to 1:64. (Kappa: 0.95 to 1.00). Crude scolex antigen may be useful for serological screening, while 100, 95 or 26 kDa protein can be used in confirmatory tests on neurocysticercosis-positive cases.

Immunodiagnosis of human neurocysticercosis by using semi-purified scolex antigens from Taenia solium cysticerci

Crude antigen and semi-purified proteins from scolices of Taenia solium cysticerci were evaluated for the immunodiagnosis of human neurocysticercosis neurocysticercosis. Semi-purified proteins obtained by electrophoresis on polyacrylamide gel and by electroelution were tested by means of the immunoenzymatic reaction against sera from normal individuals and from patients with neurocysticercosis or other parasitic diseases. The 100kDa protein provided 100 percent sensitivity and specificity in the immunodiagnosis. When 95 or 26kDa proteins were used, 95 and 100 percent sensitivity and specificity were obtained, respectively. The assays involving crude antigen and sera from normal individuals or from patients with neurocysticercosis, diluted to 1:256, gave excellent agreement with those in which 100, 95 or 26kDa proteins were tested against the same serum samples diluted to 1:64. (Kappa: 0.95 to 1.00). Crude scolex antigen may be useful for serological screening, while 100, 95 or 26kDa protein can be used in confirmatory tests on neurocysticercosis-positive cases.

Antígeno bruto e proteínas semipurificadas de escóleces de cisticercos de Taenia solium foram avaliados para o imunodiagnóstico da neurocisticercose humana neurocisticercose. As proteínas semipurificadas, obtidas por eletroforese em gel de poliacrilamida e eletroeluição, foram testadas na reação imunoenzimática contra soros de indivíduos normais e de pacientes com neurocisticercose ou outras parasitoses. A proteína de 100kDa proporcionou 100 por cento de sensibilidade e especificidade no imunodiagnóstico. Quando a proteína de 95 ou 26kDa foi empregada, foram obtidos 95 e 100 por cento de sensibilidade e especificidade, respectivamente. Os ensaios envolvendo antígeno bruto e soros de indivíduos normais ou de pacientes com neurocisticercose, diluídos a 1:256, tiveram ótima concordância com aqueles onde a proteína de 100, 95 ou 25kDa foi testada contra os mesmas amostras de soro diluídas a 1:64 (Kappa: 0,95 a 1,00). O antígeno bruto de escolex poderá ser empregado na triagem sorológica enquanto a proteína de 100, 95 ou 26kDa nos testes confirmatórios dos casos positivos de NC.

Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment.

The first choice of treatment for American cutaneous leishmaniasis is the pentavalent antimonial drug. Although it has been shown that this treatment is mostly effective and indicated, some disadvantages should be taken into account such as side effects, long term treatment inconveniences and counter-indication for patients suffering from cardiopathy, nephropathy; yet, aging, pregnancy and other conditions. With the advent of the vaccine anti-American cutaneous leishmaniasis as a prophylactic measure, studies on therapy using the vaccine associated or not with other drugs have been performed by many investigators and it is currently among the alternative treatments and prevention measures for American cutaneous leishmaniasis. In conclusion, the association between antimony and vaccine (immunochemotherapy) showed the same cure rate when compared with the standard treatment (100%) and it was also able to reduce the salt volume in 17.9% and treatment length from 87 to 62 days, decreasing side effects.

Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment

O tratamento de primeira escolha para leishmaniose tegumentar americana é o antimonial pentavalente. Embora este tratamento seja na maioria das vezes efetivo e indicado, devem ser consideradas as desvantagens tais como efeitos colaterais, longa duracão do tratamento e contra-indicacão para cardiopatas, nefropatas, idosos, grávidas e outras condicões. Com o advento da vacina antileishmaniose tegumentar americana para fins profiláticos e terapêuticos, associando-a ou não a outros fármacos, muitas pesquisas têm sido desenvolvidas, sendo a vacina a principal entre os atuais recursos no tratamento e prevencão da leishmaniose tegumentar americana. Em conclusão, a associacão do antimônio com a vacina (imunoquimioterapia) apresentou o mesmo índice de cura em relacão ao tratamento padrão (100%), e ainda reduziu o volume do sal em 17,9% e o tempo de cura significativamente, de 87 para 62 dias; conseqüentemente, reduzindo os efeitos colaterais.

Efeito da mitomicina C na secreção de fator estimulador de granulócitos macrófagos e interleucina-5 em cultura de estroma de pólipos nasais eosinofílicos / Effect of mitomycin C on the secretion of granulocyte macrophages colonies stimulating factor and interleukin-5 in eosinophilic nasal polyps stromal culture

O estudo de fatores teciduais, como a concentração de fator estimulador de colônias de macrófagos (GM-CSF) e interleucina 5 (IL-5), aponta para os mecanismos envolvidos na manutenção da eosinofilia em pólipos nasossinusais eosinofílicos. A mitomicina C (MMC) tem sido utilizada com bons resultados em otorrinolaringologia. OBJETIVO: Este estudo teve como objetivo avaliar a ação da Mitomicina C sobre a secreção de GM-CSF e IL-5 em pólipos eosinofílicos. FORMA DE ESTUDO: caso-controle. MATERIAL E MÉTODO: O estudo foi comparativo experimental autopareado, com amostras de pólipos biopsiados de pacientes portadores de polipose nasossinusal eosinofílica. Os fragmentos semeados como grupo experimental receberam mitomicina C por 5 minutos na dosagem de 400microg/ml e então lavadas em meio RPMI. Nos tempos zero, 12 e 24 horas, o sobrenadante foi retirado para determinação dos níveis de GM-CSF em 22 pacientes e IL-5, em 19 pacientes, utilizando o método de ELISA. RESULTO: Diminuição de secreção de GM-CSF nos grupos tratados com mitomicina C no tempo 24h (p<= 0,05); no grupo tratado houve expressão significativa de GM-CSF entre zero e 12 horas (p=0,013) demonstrando a viabilidade da cultura igualmente ao grupo não tratado; tendência à queda dos níveis de IL-5 no grupo tratado em 24h. CONCLUSÃO: O estudo demonstrou que a mitomicina C foi capaz de inibir a síntese de GM-CSF em culturas de pólipos nasais eosinofílicos e com provável ação sobre a secreção de IL-5, necessitando de estudos complementares.

Effect of mitomycin C on the secretion of granulocyte macrophages colonies stimulating factor and interleukin-5 in eosinophilic nasal polyps stromal culture.

UNLABELLED: The research involving tissue factors, such as granulocyte macrophage colonies stimulating factor (GM-CSF) and interleukin 5 (IL-5), leads to the mechanisms involved in the maintenance of eosinophilia, which is essential for the pathogenesis on eosinophilic nasal polyps. Mitomycin C has been successfully used in otolaryngology. AIM: The objective of this study was to evaluate the effect of mitomycin C in secretion of GM-CSF and IL-5 on eosinophilic nasal polyps. STUDY DESIGN: Case-control. MATERIAL AND METHOD: This is a comparative and auto-matched experimental study, performed with fragments of polyps which had been obtained from biopsy of patients with eosinophilic nasosinusal polyposis. The fragments of the experimental group were treated with mitomycin C (400 microg/ml) for 5 minutes and then washed in RPMI substrate. At time zero, 12 and 24 hours, the surface material was taken to determination of its GM-CSF levels in 22 patients and of IL-5 levels in 19 patients, by ELISA method. RESULTS: Reduction in GM-CSF expression on the experimental group at time 24 h (p< or = 0.05). The treated group presented significant GM-CSF expression between zero time and 12 h time (p= 0.013) showing the culture viability such as in the non-treated group. Tendency to decreasing IL-5 levels on the treated groups at 24 hours. CONCLUSION: This study showed that mitomycin C was efficient in inhibiting GM-CSF synthesis with reduction of IL-5 secretion, but this fact needs complementary studies.

Efeito da mitomicina C em cultura de estroma de pólipos nasais eosinofílicos: indução de apoptose em eosinófilos / Effect of mitomicin C in eosinofilic nasal polyps estromal culture: induction of apoptosis in eosinophil

A polipose nasossinusal eosinofílica é uma afecção comum a várias doenças, determina acometimento extenso dos seios paranasais e possui grande tendência à recidiva após tratamento. Os eosinófilos exercem papel essencial na patogênese, relacionada a baixo índice de apoptose e a longa permanência destas células ativas nos tecidos. OBJETIVO: Este estudo teve por objetivo avaliar o efeito da mitomicina C na indução de apoptose em eosinófilos presentes no estroma de pólipos nasais eosinofílicos. FORMA DE ESTUDO: Caso controle. MATERIAL E MÉTODO: O estudo foi auto-pareado, com 9 amostras cultivadas em meio RPMI 1640 e avaliadas em zero, 12 e 24 horas. O grupo estudo recebeu mitomicina C numa concentração de 400æg/ml durante 5 minutos. Em cada tempo as duas culturas, controle e estudo, foram submetidas a estudo histopatológico para determinação do índice apoptótico. Utilizou-se a coloração hematoxilina-eosina com aumento microscópico de 1000x. RESULTADO: Pela análise de 674 campos digitalizados observou-se que as culturas tratadas com mitomicina C apresentaram índice apoptótico em 12 horas significativamente maior em relação ao grupo controle (p< 0,001). CONCLUSÃO: Concluiu-se que a mitomicina C é eficaz na indução de apoptose em eosinófilos presentes em estroma de pólipos nasais eosinofílicos.

Perfil de citocinas e tipificação de HLA em pacientes com polipose nasossinusal tolerantes e intolerantes a aspirina / Cytokines profile and HLA typing in tolerant and non-tolerant patients to aspirin with nasossinusal polyposis

A infiltraçäo eosinofílica do pólipo nasossinusal (PNS) associado à intolerância aspirínica (IA) é característica relevante. Diversos mediadores participam da migraçäo dos eosinófilos para os tecidos. A IA decorre do aumento da síntese de leucotrienos em indivíduos geneticamente susceptíveis. OBJETIVO: Analisar o perfil de citocinas e a tipificaçäo de HLA-A, B e DR em pacientes com PNS tolerantes e intolerantes à aspirina. FORMA DE ESTUDO: Estudo de coorte transversal. MATERIAL E MÉTODO: selecionando-se 45 pacientes: 15 portadores de PNS eosinofílica tolerantes à aspirina (grupo TA); 15 de PNS eosinofílica associada à intolerância aspirínica, manifestada por broncoespasmo (grupo IA) e 15 sem PNS, que apresentavam desvio de septo nasal (grupo controle). O perfil de citocinas (IL-2; IL-4; IL-5; IL-6; IL-8; IL-10; IFN-gama e TNF-alfa) foi pesquisado nos fragmentos de pólipo nasal ou de mucosa de concha média (grupo controle) através da reaçäo reversa da cadeia de polimerase (RT-PCR). A tipificaçäo de HLA-A, B e DR foi realizada através de teste sorológico de microcitotoxicidade ou por amplificaçäo de DNA pela reaçäo em cadeia da polimerase (PCR). RESULTADOS: A expressäo de RNAm para as interleucinas 4, 5, 6, 8, 10, IFN-gama e TNF-alfa foi semelhante nos três grupos. A expressäo de RNAm para IL-2 associou-se com a IA. Os pacientes portadores dos antígenos A11, B49, DR15 e DR13 apresentaram uma maior probabilidade de desenvolver polipose nasossinusal näo relacionada à IA, enquanto os portadores de DR17 apresentaram uma maior probabilidade de desenvolver polipose nasossinusal associada à intolerância aspirínica (Tríade Aspirínica). CONCLUSÄO: A polipose nasossinusal associada à intolerância aspirínica (Tríade Aspirínica) mostrou associaçäo significante com HLA- DR17 e IL-2, sugerindo um perfil de citocinas TH1