ABSTRACT
BACKGROUND: Pentavalent antimonial-based chemotherapy is the first-line approach for leishmaniasis treatment and disease control. Nevertheless antimony-resistant parasites have been reported in some endemic regions. Treatment refractoriness is complex and is associated with patient- and parasite-related variables. Although amastigotes are the parasite stage in the vertebrate host and, thus, exposed to the drug, the stress caused by trivalent antimony in promastigotes has been shown to promote significant modification in expression of several genes involved in various biological processes, which will ultimately affect parasite behavior. Leishmania (Viannia) guyanensis is one of the main etiological agents in the Amazon Basin region, with a high relapse rate (approximately 25%). METHODS: Herein, we conducted several in vitro analyses with L. (V.) guyanensis strains derived from cured and refractory patients after treatment with standardized antimonial therapeutic schemes, in addition to a drug-resistant in vitro-selected strain. Drug sensitivity assessed through Sb(III) half-maximal inhibitory concentration (IC50) assays, growth patterns (with and without drug pressure) and metacyclic-like percentages were determined for all strains and compared to treatment outcomes. Finally, co-cultivation without intercellular contact was followed by parasitic density and Sb(III) IC50 measurements. RESULTS: Poor treatment response was correlated with increased Sb(III) IC50 values. The decrease in drug sensitivity was associated with a reduced cell replication rate, increased in vitro growth ability, and higher metacyclic-like proportion. Additionally, in vitro co-cultivation assays demonstrated that intercellular communication enabled lower drug sensitivity and enhanced in vitro growth ability, regardless of direct cell contact. CONCLUSIONS: Data concerning drug sensitivity in the Viannia subgenus are emerging, and L. (V.) guyanensis plays a pivotal epidemiological role in Latin America. Therefore, investigating the parasitic features potentially related to relapses is urgent. Altogether, the data presented here indicate that all tested strains of L. (V.) guyanensis displayed an association between treatment outcome and in vitro parameters, especially the drug sensitivity. Remarkably, sharing enhanced growth ability and decreased drug sensitivity, without intercellular communication, were demonstrated.
Subject(s)
Cell Communication , Leishmania guyanensis/growth & development , Leishmania guyanensis/physiology , Antiprotozoal Agents/pharmacology , Drug Resistance , Humans , Inhibitory Concentration 50 , Latin America , Leishmania guyanensis/drug effects , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitologyABSTRACT
INTRODUCTION: A proliferation-inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. The aim of this study was to investigate whether APRIL and BAFF plasma concentrations could be part of inflammatory responses associated with P. vivax and P. falciparum malaria in patients from the Brazilian Amazon. METHODS: Blood samples were obtained from P. vivax and P. falciparum malaria patients (n = 52) resident in Porto Velho before and 15 days after the beginning of treatment and from uninfected individuals (n = 12). We investigated APRIL and BAFF circulating levels and their association with parasitaemia, WBC counts, and cytokine/chemokine plasma levels. The expression levels of transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) on PBMC from a subset of 5 P. vivax-infected patients were analyzed by flow cytometry. RESULTS: APRIL plasma levels were transiently increased during acute P. vivax and P. falciparum infections whereas BAFF levels were only increased during acute P. falciparum malaria. Although P. vivax and P. falciparum malaria patients have similar cytokine profiles during infection, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL-1, IL-2, IL-4, IL-6, and IL-13 levels. We did not find any association between P. vivax parasitaemia and APRIL levels, while an inverse correlation was found between P. falciparum parasitaemia and APRIL levels. The percentage of TACI positive CD4+ and CD8+ T cells were increased in the acute phase P. vivax malaria. CONCLUSION: These findings suggest that the APRIL and BAFF inductions reflect different host strategies for controlling infection with each malaria species.
Subject(s)
B-Cell Activating Factor/blood , Malaria, Falciparum/blood , Malaria, Vivax/blood , Malaria/blood , Tumor Necrosis Factor Ligand Superfamily Member 13/blood , Adult , Antimalarials/therapeutic use , B-Cell Activating Factor/immunology , Brazil , Case-Control Studies , Drug Therapy, Combination/methods , Female , Healthy Volunteers , Host-Parasite Interactions/immunology , Humans , Interleukins/blood , Interleukins/immunology , Leukocyte Count , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Malaria/drug therapy , Malaria/parasitology , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Malaria, Vivax/drug therapy , Malaria, Vivax/parasitology , Male , Parasitemia/immunology , Parasitemia/parasitology , Plasmodium falciparum/immunology , Plasmodium vivax/immunology , Transmembrane Activator and CAML Interactor Protein/immunology , Transmembrane Activator and CAML Interactor Protein/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 13/immunology , Young AdultABSTRACT
The enzyme cyclooxygenase 2 (COX-2) is known to be involved in tumorigenesis and metastasis in certain types of cancer. Nevertheless, the prognostic value of COX-2 overexpression and its polymorphisms in patients with non-small cell lung cancer (NSCLC) have yet to be fully elucidated. The aim of the present study was to investigate the association between the three most commonly studied COX-2 gene polymorphisms (-1195 G/A, -765 G/C and 8473 T/C) with COX-2 expression and lung cancer risk in a Brazilian cohort. In the present hospital based, case-control retrospective study, 104 patients with NSCLC and 202 cancer free control subjects were genotyped for -1195 G/A, -765 G/C and 8473 T/C polymorphisms using allelic discrimination with a reverse transcription quantitative polymerase chain reaction method. COX-2 mRNA expression was analyzed in surgically resected tumors from 34 patients with NSCLC. The results revealed that COX-2 expression levels were higher in tumor tissue compared with normal lung tissue. However, this overexpression of COX-2 was not associated with the patient outcome, and furthermore, none of the analyzed polymorphisms were associated with the risk of developing lung cancer, COX-2 overexpression, or the overall survival of the patients with NSCLC. Taken together, the findings described in the present study do not support a major role for COX-2 polymorphisms and COX-2 overexpression in lung carcinogenesis within the Brazilian population.
ABSTRACT
Na infäncia a mais frequente neoplasia ovariana é o teratoma maduro, o qual pode apresentar torçäo do seu pedículo configurando um quadro de abdome agudo. Apresentamos o relato de caso de uma menina de 10 anos de idade com diagnóstico de abdome agudo por torçäo de teratoma cístico maduro de ovário confirmado por ultrassonografia abdominal e submetida a cirurgia para salpingo-ooforectomia, fartamente documentado por imagens que säo apresentadas no artigo
Subject(s)
Humans , Female , Child , Ovarian Neoplasms/complications , Teratoma/complications , Abdomen, Acute/etiology , Ovarian Neoplasms/surgery , Ovarian Neoplasms , Teratoma/surgery , Teratoma , Abdomen, Acute/surgery , Abdomen, AcuteABSTRACT
Foram estudados 316 pacientes portadores de hérnia inguinal, no período de junho de 1997 a junho de 1998, atendidos nos Serviços de Cirurgia Pediátrica do Hospital de Clínicas da Universidade Federal do Paraná e Hospital Infantil Pequeno Príncipe, em Curitiba. Destes, 237 (75 por cento) eram do sexo masculino e 79 (25por cento) eram do sexo feminino. A idade variou de 3 dias a 11 anos e meio com predomínio na faixa etária de 0 a um ano de idade em ambos os sexos. Foram descartados do estudo todos os pacientes prematuros e os casos de testículo näo descido manifestado como uma hérnia. O propósito deste trabalho foi observar alguns aspectos da afecçäo nas diversas faixas etárias analisando a incidência sobre o lado mais comum, episódios de encarceramento, número de procedimentos realizados, confirmaçäo diagnóstica pós-operatória, conteúdo do saco herniário, achados transoperatórios e complicaçöes ocorridas nos pacientes estudados nos serviços citados e discutior nossos resultados com os dados publicados na literatura
Subject(s)
Humans , Female , Male , Infant, Newborn , Infant , Child, Preschool , Child , Hernia, Inguinal/genetics , Prospective StudiesABSTRACT
Dois casos de estenose hipertrófica de piloro associado com malrotaçäo intestinal säo apresentados. Em nenhum deles o diagnóstico foi feito sincronicamente. A partir do 3§/4§ dias pós operatório de pilomiotomia ambos reiniciaram o quadro com vômitos biliosos e distensäo abdominal. Na investigaçäo o diagnóstico de malrotaçäo intestinal e um segundo procedimento foi justificado pelo resultado do estudo radiológico. No caso 1, o RX simples com imagem de pneumoperitônio sugestiva de perfuraçäo de viscera oca indicou a laparotomia. Alèm da enterorrafia obrigatória, uma exploraçäo da cavidade abdominal mostrava a presença de brida de Ladd, rotaçäo parcial do colon e um divertículo de Meckel há mais ou menos 30cm da válvula íleo cecal. No caso 2, o RX contrastado (trânsito) mostrava um desvio de alças intestinais com dificuldade de passagem do contraste além do duodeno e igualmente indicou a laparotomia, durante a qual foi liberada a brida de Ladd e melhorada a reposiçäo das alças. A recuperaçäo pós operatória foi rápida e sem intercorrências com estabilizaçäo e ganho de peso no seguimento ambulatorial, em ambas as crianças