Andiroba oil (Carapa guianensis Aubl) shows cytotoxicity but no mutagenicity in the ACPP02 gastric cancer cell line.

Andiroba (Carapa guianensis Aubl) is an Amazonian plant whose oil has been widely used in traditional medicine for various purposes, including anti-inflammation. Research reports indicate that the oil can confer antitumor activity due to the presence of fatty acids, which can directly influence cell death mechanisms. Thus, andiroba oil (AO) has gained interest for its potential to be used in antineoplastic therapies. Here, we report an in vitro analysis of the cytotoxic and mutagenic potential of AO in the gastric cancer cell line, ACP02. Cell survival was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, differential staining with ethidium bromide and acridine orange assessed apoptosis-necrosis, and mutagenesis was assessed by the micronucleus test. The apolar oil was first diluted in 0.1% dimethyl sulfoxide (DMSO) and then further diluted to six concentrations (0.01, 0.1, 1, 10 and 100 µg/mL and 1 mg/mL) in RPMI medium. Controls included RPMI alone (negative control) and 0.1% DMSO diluted in medium (vehicle control). The MTT test showed that AO significantly reduced cell viability (P < .05) only when the highest tested concentration was applied for 48 hours. The apoptosis/necrosis test showed that the highest concentration of AO induced cell death by apoptosis at 24 and 48 hours. There was no statistically significant increase in the frequency of micronuclei. The ability of the AO to decrease the viability of ACP02 cells via apoptosis, without exerting mutagenic effects, suggests that the oil could be useful as an alternative therapeutic agent for primary tumors of stomach cancer.

FISH in micronucleus test demonstrates aneugenic action of rotenone in a common freshwater fish species, Nile tilapia (Oreochromis niloticus).

Aneuploidies are numerical genetic alterations that lead to changes in the normal number of chromosomes due to abnormal segregation during cell division. This type of alteration can occur spontaneously or as a result of exposure to mutagenic agents. The presence of these agents in the environment has increased concern about potential damage to human health. Rotenone, derived from plants of the genera Derris and Lonchocarpus, is a product that is used all over the world as a pesticide and piscicide. Before establishing its potential and efficiency for these purposes, it is essential to know more about the possible adverse effects that it may cause. The current work aimed to evaluate the mutagenic potential of rotenone using fish from the species Oreochromis niloticus, as well as to help in understanding its action mechanism. Our results showed the mutagenic potential of rotenone evidenced by increased formation of micronuclei and nuclear buds at low doses of exposure. The use of fluorescence in situ hybridisation technique made it possible to measure the aneugenic potential of the substance, probably due to its impairment of mitotic spindle formation.

Impacto do tratamento com imunoglobulina humana intravenosa no número de pneumonias em pacientes com deficiência de anticorpo / Efficacy of immunoglobulin therapy in reducing pneumonia

A imunodeficiência comum variável (ICV) e a agamaglobulinemia ligada ao X (ALX) são imunodeficiências primárias caracterizadas por deficiência de anticorpos e susceptibilidade aumentada a infecções, sendo a pneumonia a infecção mais frequente. Esses pacientes são tratados com infusões regulares de imunoglobulina intravenosa (IGIV). Objetivo: Avaliar a frequência de pneumonias e o impacto do tratamento com IGIV em 25 pacientes com ICV ou ALX. Métodos: Análise retrospectiva dos prontuários médicos de pacientes com diagnóstico confirmado de ICV ou ALX, em tratamento regular com IGIV. Resultados: Analisamos 25 pacientes (18 com ICV e 7 com ALX; 14 homens e 11 mulheres; média de idade atual de 18 anos). A média de idade ao início dos sintomas foi de 5,7 anos e a média de idade ao diagnóstico foi de 11,5 anos. Treze pacientes (52%) apresentaram pneumonia como primeira manifestação da imunodeficiência. A pneumonia foi a infecção mais frequente nesses pacientes antes do diagnóstico – 22 pacientes (88%) tiveram pelo menos um episódio de pneumonia antes do diagnóstico e, desses, 59% tiveram mais do que 5 episódios – antes do diagnóstico houve uma média de 6,2 episódios de pneumonia por paciente. Após início do tratamento com IGIV, 10 pacientes (40%) tiveram algum episódio de pneumonia, com uma média de 1,5 episódio por paciente. Nove pacientes (36%) apresentavam algum tipo de sequela pulmonar antes do diagnóstico da imunodeficiência. Conclusão: O tratamento com IGIV é eficaz na redução dos episódios de pneumonia nesses pacientes. O diagnóstico e tratamento precoces são de extrema importância.

Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are primary immune disorders characterized by antibody deficiency and increased susceptibility to infections, especially pneumonia. Replacement therapy with intravenous immunoglobulin (IVIG) is the standard treatment. Objective: To assess the frequency of pneumonia in 25 patients with CVID or XLA and the effectiveness of intravenous immunoglobulin replacement therapy in these patients. Methods: a descriptive study, based on a retrospective analysis of medical records from 25 patients with diagnosis of CVID or XLA treated with IVIG. Results: A total of 25 patients were studied (18 with CVID and 7 with XLA; 14 male and 11 female; mean current age, 18 years). The mean age of onset of symptoms was 5.7 years and the mean age of diagnosis was 11.5 years. Pneumonia was the most common primary clinical presentation (13 patients – 52%). Twenty-two (88%) of the 25 patients had pneumonia at least once before diagnosis and 13 out of 22 of these patients had more than 5 episodes. Pre-diagnosis patients had an average of 6.2 episodes of pneumonia. After treatment with IVIG, ten patients (40%) had pneumonia – with an average of 1.5 episode of pneumonia per patient. Conclusion: IVIG treatment provides a remarkable reduction in pneumonia in these patients. Early diagnosis and treatment is mandatory for a positive prognosis.

Skewed distribution of circulating activated natural killer T (NKT) cells in patients with common variable immunodeficiency disorders (CVID).

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action.

A decreased frequency of regulatory T cells in patients with common variable immunodeficiency.

INTRODUCTION: Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4(+)CD25(high) regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens. OBJECTIVE: In this study we set out to investigate the frequency of Treg cells in CVID patients and correlate with their immune activation status. MATERIALS AND METHODS: Sixteen patients (6 males and 10 females) with CVID who had been treated with regular intravenous immunoglobulin and 14 controls were enrolled. Quantitative analyses of peripheral blood mononuclear cells (PBMC) were performed by multiparametric flow cytometry using the following cell markers: CD38, HLA-DR, CCR5 (immune activation); CD4, CD25, FOXP3, CD127, and OX40 (Treg cells); Ki-67 and IFN-gamma (intracellular cytokine). RESULTS: A significantly lower proportion of CD4(+)CD25(high)FOXP3 T cells was observed in CVID patients compared with healthy controls (P<0.05). In addition to a higher proportion of CD8(+) T cells from CVID patients expressing the activation markers, CD38(+) and HLA-DR(+) (P<0.05), we observed no significant correlation between Tregs and immune activation. CONCLUSION: Our results demonstrate that a reduction in Treg cells could have impaired immune function in CVID patients.

Síndrome de DiGeorge: Aspectos clínico-imunológicos e manejo / DiGeorge Syndrome: Clinical-immunologic aspects and management

Objetivo: revisar a literatura sobre a Síndrome de DiGeorge (SDG) com ênfase para as principais manifestações clínicas e abordagens diagnóstica e terapêutica. Fonte de dados: Literatura médica publicada sobre o assunto nos últimos dez anos utilizando PubMed, MEDLINE e livros médicos especializados. Palavras chave usadas na pesquisa: Síndrome de DiGeorge, FISH, síndrome Velo-cárdio-facial, imunodeficiência primária, infecções recorrentes. Síntese de dados: A SDG é distúrbio congênito resultante da migração anormal das células embrionárias da terceira e quarta bolsas faríngeas, levando a hipo ou aplasia do ti mo, defeitos da paratireóide, arco aórtico e imunodeficiência celular. Além de hipocalcemia neonatal e dismorfismos faciais tipicos, as alterações observadas ocorrem principalmente nos sistemas imunológico e cardiovascular. Os principais defeitos cardíacos relatados são: Anomalia conotruncal, interrupção do arco aórtico e Tetralogia de Fallot. Quanto às anormalidades do sistema imunológico, os pacientes podem ser assintomáticos ou cursar com defeitos graves de células T, dependendo do grau de comprometimento tímico. Conclusões: O diagnóstico, após suspeição clínica deve ser confirmado pelo teste FISH. O manejo destes pacientes visa principalmente o controle das infecções de repetição, correção dos distúrbios cardíacos e controle de co-morbidades. O tratamento definitivo nos casos mais graves é o transplante tímico, com resultados promissores