Clinical Analysis and Toxicology

Nosso grupo de pesquisa tem desenvolvido experiências de monitoramento de reações adversas em pacientes chagásicos em tratamento com benznidazol. A proposta de produção deste artigo nasceu da constatação da escassez de artigos de revisão que reunissem vários aspectos relacionados ao tratamento etiológico da doença de Chagas. Portanto, foram realizadas buscas de artigos originais e revisões indexadas, nas bases do Medline e Lilacs, de publicações relativas ao tratamento etiológico da doença de Chagas desde os primeiros ensaios terapêuticos até o momento, incluindo mecanismo de ação, reações adversas, critérios de cura e indicações de tratamento do consenso brasileiro. Os medicamentos nifurtimox e benznidazol, utilizados atualmente no tratamento da doença de Chagas, apresentam eficácia acima de 80% na fase aguda e de 8% a 30% na fase crônica. O sucesso da terapêutica esbarra em alguns pontos tais como: esquema terapêutico prolongado, reações adversas, variabilidade genética dos parasitos e cepas naturalmente resistentes aos fármacos. Os resultados desta atualização revelam a necessidade do desenvolvimento de novos

The present work proposed to correlate serum antibody avidity and salivary antibody titers as parameters for time of infection and antigen exposure in a co-hort study evaluating leprosy patients in different periods of treatment. Colorimetric enzyme-immunoassays for salivary antibodies, serum antibody IgG titers and avidities were performed in the samples. Anti-PGL-1 IgA and IgM salivary antibodies were significantly higher in multibacillar (MB-L) patients compared to normal controls (p<0.05), but not when compared to borderline tuberculoid (BT) or to paucibacillar (PB-L) patients (p>0.05). A good correlation was found between salivary anti-PGL-1 IgA and IgM levels in MB-L patients (r=0.41, p<0.01). Two out of 33 tested saliva samples from patients who had completed the drug regimen treatment presented positive salivary antibodies. Among non-treated patients, samples with low, medium or high serum IgG antibody avidity were found in similar frequencies. In patients under treatment, most of the serum samples showed low or medium IgG antibody avidity. The treated MB-L patients showed medium or high antibody avidity, except for two, who showed very low antibody avidity results. We suggest that salivary anti-PGL antibodies and serum IgG avidity could be useful for the indication of recent exposure or re-exposure to bacteria after chemotherapy.

Coccidioidal pericarditis is a condition found in approximately 1-5 % of patients infected by Coccidioides species. It is associated with widely diverse clinical symptoms. This paper reports a case of coccidioidal pericarditis diagnosed by an in-house Coccidioides posadasii antigen and confirmed with mycological and molecular methods. From February to September 2005, the patient suffered from fever, weight loss, a non-productive cough, thoracic pain and tachycardia. He received a positive diagnosis of coccidioidal pericarditis only in October 2005. The macromorphological examination of the culture showed a whitish felt-like colony, which became brownish with age. Preparations in lactophenol cotton blue stain showed hyaline septate hyphae with fragmentation and thin arthroconidia-like structures. Pericardial fluid and sera samples were positive for Coccidioides antibodies by immunodiffusion and ELISA with a C. posadasii inhouse antigen preparation. The C. posadasii identification was confirmed by nested PCR of the antigen 2/proline-rich antigen (Ag2/PRA) encoding gene.

INTRODUCTION: Chagas disease is caused by Trypanosoma cruzi and treated with benznidazole (BNZ). This drug has the troublesome features of presenting partial effectiveness and high toxicity ranging from hypersensitivity reactions to medullary aplasia. The objective here was to describe and evaluate the occurrence of adverse reactions in Chagas disease patients treated with benznidazole in Fortaleza, Ceará. METHODS: This was a prospective descriptive study involving 32 chronic Chagas patients treated with benznidazole between January 2005 and April 2006. Sociodemographic and clinical data were collected through questionnaires, interviews and laboratory tests. Blood samples were collected before treatment and after 30 and 60 days of treatment. RESULTS: Adverse reactions were reported in 28 patients (87.5%) patients and the most frequent of these were pruritus (50%), prickling (43.8%), muscle weakness (37.5%) and skin rash (31.3%). Out of the 28 patients with adverse reactions, eight (28.57%) discontinued their treatment. The adverse reactions that culminated with discontinuation of the treatment were prickling (7; 87.5%) or skin eruptions (5; 62.5%). There was a slight increase in aminotransferase levels during the treatment in 9.4% of the patients. CONCLUSIONS: Following up the drug therapy administered to Chagas patients is of great importance for prevention and early detection of adverse reactions to drugs.

OBJETIVO: Estudar a produção de anticorpos a antígenos polissacarídicos em pacientes com ataxia-telangiectasia CASUÍSTICA E MÉTODO: Utilizando a técnica de ELISA, determinamos os níveis de IgG aos sorotipos 1, 3, 5, 6B, 9V e 14 do pneumococo em 14 pacientes com ataxia-telangiectasia, antes e após a imunização com a vacina pneumocócica 23-valente. Resposta adequada a cada sorotipo foi definida como IgG > 1,3 µg/ml ou o incremento de quatro vezes dos níveis pós em relação aos pré-imunização. RESULTADOS: Seis pacientes (43%) não responderam a todos os sorotipos analisados, quatro a apenas um sorotipo, um paciente a dois, dois a três e apenas um paciente a quatro dos seis sorotipos analisados. Nenhum paciente apresentou resposta adequada a todos os sorotipos testados. Os níveis de IgG ao pneumococo pós-imunização foram superiores aos pré-imunização para todos os sorotipos testados, exceto o 3. Apesar disso, os valores médios pós-imunização foram inferiores a 1,3 µg/ml para todos os sorotipos analisados, exceto o 14. A média de incremento da resposta foi inferior a quatro para todos os sorotipos analisados. CONCLUSÃO: Nossos resultados sugerem que pacientes com ataxia-telangiectasia têm grande risco de apresentar resposta inadequada ao pneumococo, o que pode ser uma das causas das infecções sinopulmonares de repetição.

OBJETIVO: Rever as publicações recentes mais relevantes sobre alergia medicamentosa e oferecer ao clínico subsídios para uma maior compreensão dessa problemática de grande relevância para a saúde pública. FONTES DOS DADOS: Busca de artigos originais e revisões indexados nas bases MEDLINE, Pubmed e Lilacs, publicados na última década, relacionando o tema de alergia a medicamentos com mecanismos imunológicos, epidemiologia, diagnóstico laboratorial, lesões cutâneas, manejo clínico e reexposição ao fármaco. SÍNTESE DOS DADOS: As reações alérgicas representam um terço das reações adversas a medicamentos. São consideradas eventos raros, mas com elevada morbimortalidade. Apesar da descrição de Gell & Coombs, útil para classificar reações alérgicas a fármacos, algumas permanecem sem classificação devido ao desconhecimento dos mecanismos imunológicos envolvidos. A existência de subpopulações de células T com características diversas daquelas comumente descritas revela a complexidade do tema e, ao mesmo tempo, elucida inúmeras questões inerentes ao mesmo. Recentemente, um novo conceito de apresentação de fármaco a linfócitos T surgiu, diante de evidências crescentes do seu envolvimento nas lesões cutâneas decorrentes de reações alérgicas a medicamentos. Na prática clínica, é muito difícil a correlação de sinais e sintomas das reações alérgicas a medicamentos com o mecanismo imunológico envolvido sem o auxílio de testes laboratoriais. Testes cutâneos in vivo e testes in vitro têm sido empregados nas suspeitas de reações alérgicas a medicamentos. No entanto, há poucos produtos comerciais adequados para sua execução. CONCLUSÕES: As reações alérgicas a fármacos constituem uma fração importante dos eventos adversos a medicamentos. É importante enfatizar a necessidade de notificação dessas reações pelos profissionais envolvidos no tratamento do paciente de forma sistematizada, por meio de ações de farmacovigilância, bem como a identificação dos possíveis mecanismos imunológicos envolvidos através de testes laboratoriais, história e avaliação clínica detalhadas.

Introdução: A doença de Chagas, causada pelo Trypanosoma cruzi, é tratada com benzonidazol, tendo o inconveniente de apresentar efetividade parcial e alta toxicidade, que varia desde reações de hipersensibilidade a aplasia medular. O objetivo foi descrever e avaliar a ocorrência de reações adversas em pacientes chagásicos em tratamento com benzonidazol em Fortaleza, Ceará. Métodos: Estudo descritivo prospectivo envolvendo 32 pacientes chagásicos crônicos tratados com benzonidazol entre janeiro de 2005 e abril de 2006. Dados sociodemográficos e clínicos foram coletados de questionários, entrevistas e exames laboratoriais. As amostras de sangue foram coletadas antes, com 30 e 60 dias de tratamento. Resultados: Reações adversas foram relatadas em 28 (87,5%) pacientes tratados, tendo sido as mais frequentes: prurido (50%), formigamento (43,8%), fraqueza muscular (37,5%) e rash cutânea (31,3%). Dos 28 pacientes com reações adversas, oito (28,57%) interromperam o tratamento. Reações adversas que culminaram com a suspensão do tratamento foram formigamento sete (87,5%) ou erupção cutânea cinco (62,5%). Observou-se aumento discreto dos níveis de aminotransferases durante o tratamento em (9,4%) pacientes. Conclusões: Concluindo, o acompanhamento farmacoterapêutico dos pacientes chagásicos é de grande relevância na prevenção e detecção precoce das reações adversas a medicamentos. Palavras-chaves: Doença de Chagas. Trypanosoma cruzi. Benzonidazol. Reação adversa a medicamento.

Objective: To study the relationship between parity and immunoglobulin concentrations in human colostrum. Methods: 82 puerperas aged 21-41 years were selected, with gestational age ≥ 37 weeks, up to the fourth parity, good nutritional status and no gestational or puerperal diseases. The inclusion criteria for the newborn were: weight > 2,500 g, Apgar score > 7 in the first minute and exclusive maternal breastfeeding until discharge from the nursery. The mothers were divided into 2 groups: Aprimiparous, B -multiparous. Colostrum was collected manually from 48 to 72 hours after delivery and the immunoglobulins were measured by ELISA technique. Results: No differences were observed regarding timing to collect colostrum; the earlier colostrum was collected, the higher the concentration of immunoglobulin A; primiparous women showed higher concentrations of IgA and IgM in their colostrum than multiparous women; there were no differences regarding IgG concentrations in the two groups. Conclusion: Primiparous women presented higher concentrations of IgA and IgM in their colostrum than multiparous women.

The penicillin allergy skin testing is the only accurate and reliable test for penicillin hypersensitivity mediated by IgE. It is useful for identifying patients with doubtful history of allergy. Positive test for major and minor determinants presents a positive predictive value ...

Objective: To investigate the association between type of delivery and immunoglobulin concentration in maternal colostrum. Methods: We studied 82 women who were giving birth. Age was between 21 and 41 years, gestational age was 37 or more weeks and parity up to IV pregnancies. The women were in good nutritional condition and did not have any pregnancy or puerperium-associated diseases. The following aspects were also considered as inclusion criteria for the newborn: weight > 2,500 g, Apgar score > 7 in the first minute and exclusive breastfeeding until discharge from the nursery. The women were divided into three groups: A-vaginal delivery, Bcaesarean section with labor and C-elective caesarean section. Colostrum was collected manually between 48 and 72h after delivery. Immunoglobulins were dosed using the ELISA technique. Results: There were no differences between the three groups in terms of time of colostrum collection. The shorter the time of colostrum collection, the greater the concentration of immunoglobulin A. Primiparous women had higher concentrations of IgA and IgM in maternal colostrum than did multiparous women. The group submitted to caesarean section with labor had higher concentrations of IgA in maternal colostrum than did the normal delivery group. IgM and IgG concentrations in colostrum were not influenced by type of delivery. Conclusion: The occurrence of labor together with surgical stress induce higher IgA concentrations in the colostrum of women submitted to caesarean section with labor.

Objectives: Leprosy household contacts represent a group at high risk of developing the disease. The aim of this study was to detect Mycobacterium leprae subclinical infection in this group through serological and molecular parameters. Methods: Serum anti-PGL1 IgG/IgM and salivary anti-PGL1 IgA/IgM was investigated using an ELISA, and nasal carriage of M. leprae DNA was detected by PCR, in leprosy household contacts of paucibacillary (PB) and multibacillary (MB) household leprosy patients (n = 135), their index cases (n = 30), and in persons living in a low endemic city (n = 17). Results: Salivary anti-PGL1 IgA and IgM and serum anti-PGL1 IgG showed good correlation comparing contacts and index cases (p < 0.01, p < 0.005, and p < 0.0001, respectively). This was not observed for serum anti-PGL1 IgM (p > 0.05). A high frequency of anti-PGL1 IgM positivity was found in IgG-negative samples (p < 0.0001). For IgG-positive samples, IgM antibodies were also positive in most of the samples. None of the 17 volunteers living in a low endemic city presented seropositivity for IgG; however, two of them showed positivity for anti-PGL1 IgM. M. leprae DNA was found in the nasal swabs of nine out of the 85 MB household leprosy contacts (10.6%) and in three out of the 50 PB household leprosy contacts (6.0%). Conclusion: We strongly suggest that serum IgG/IgM and salivary anti-PGL1 IgA/IgM measurements are used to follow leprosy household contacts.

We evaluated the antimicrobial activity and some mechanisms used by subinhibitory and inhibitory concentrations of the essential oil, obtained from leaves of Plectranthus amboinicus, against a standard strain of Klebsiella pneumoniae and 5 multiresistant clinical isolates of the bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the rate of kill and the pH sensitivity of the essential oil were determined by microdilution tests performed in 96-well plates. Subinhibitory and inhibitory concentrations of the essential oil were tested in order to check its action on K. pneumoniae membrane permeability, capsule expression, urease activity and cell morphology. The MIC and MBC of the essential oil were 0.09 ± 0.01%. A complete inhibition of the bacterial growth was observed after 2 h of incubation with twice the MIC of the essential oil. A better MIC was found when neutral or alkaline pH broth was used. Alteration in membrane permeability was found by the increase of crystal violet uptake when the bacteria were incubated with twice the MIC levels of the essential oil. The urease activity could be prevented when all the subinhibitory concentrations were tested in comparison to the untreated group (p < 0.001). Alteration of the bacterial morphology besides inhibition of the capsule expression was verified by atomic force microscopy, and Anthony's stain method, respectively. Our data allow us to conclude that the essential oil of P. amboinicus can be a good candidate for future research.

Objective: To study the relationship between parity and immunoglobulin concentrations in human colostrum. Methods: 82 puerperas aged 21-41 years were selected, with gestational age ≥ 37 weeks, up to the fourth parity, good nutritional status and no gestational or puerperal diseases. The inclusion criteria for the newborn were: weight &gt; 2,500 g, Apgar score &gt; 7 in the first minute

Objective: To investigate the association between type of delivery and immunoglobulin concentration in maternal colostrum. Methods: We studied 82 women who were giving birth. Age was between 21 and 41 years, gestational age was 37 or more weeks and parity up to IV pregnancies. The women were in good nutritional condition and did not have any pregnancy or puerperium-associated diseases. The following aspects were also considered as inclusion criteria for the newborn: weight > 2,500 g, Apgar score > 7 in the first minute and exclusive breastfeeding until discharge from the nursery. The women were divided into three groups: A-vaginal delivery, Bcaesarean section with labor and C-elective caesarean section. Colostrum was collected manually between 48 and 72h after delivery. Immunoglobulins were dosed using the ELISA technique. Results: There were no differences between the three groups in terms of time of colostrum collection. The shorter the time of colostrum collection, the greater the concentration of immunoglobulin A. Primiparous women had higher concentrations of IgA and IgM in maternal colostrum than did multiparous women. The group submitted to caesarean section with labor had higher concentrations of IgA in maternal colostrum than did the normal delivery group. IgM and IgG concentrations in colostrum were not influenced by type of delivery. Conclusion: The occurrence of labor together with surgical stress induce higher IgA concentrations in the colostrum of women submitted to caesarean section with labor.

Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G&gt;A), IL4 (-589 C&gt;T), CTLA4 (+49A&gt;G), and DAO (+8956 C&gt;G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). ...

Considering that the main route of Mycobacterium leprae transmission is the upper respiratory tract, detection of salivary antibodies can be a useful tool for diagnosing early infection. The study aimed to analyze salivary anti-PGL-1 IgA and IgM antibodies in 169 children aged 4-16 years old, who lived nearby or inside the house of multibacillary or paucibacillary leprosy patients in two endemic cities in Alagoas State - Brazil. Salivary anti-PGL-1 antibodies were quantified by modified ELISA method. The frequency of contact and clinical form of the index case were significantly associated with salivary antibodies levels. High frequency of IgM positivity strongly suggests active transmission of M. leprae in these communities. We suggest in the present work that salivary anti-PGL IgA and IgM are important biomarkers to be used for identifying communities with probable active transmission of M. leprae.

Summary: Patients with chronic kidney disease (CKD) or on dialysis are at greater risk of infection, which might be due to a defective immune function. While there are controversial reports on efficacy of vaccination in this group of patients, the aim of this study was to evaluate the antibody response to pneumococcal capsular polysaccharide vaccine (PPV23) in CKD patients. Sixty-six patients with CKD and 40 healthy individuals were vaccinated with PPV23. Blood samples were taken before and four weeks after vaccination. Specific ...