RESUMO
Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with Plasmodium parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). P. berghei ANKA (PbA) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8+ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of Entamoeba hystolitica. Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8+ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8+ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.
Assuntos
Lesão Pulmonar Aguda , Modelos Animais de Doenças , Malária , Plasmodium berghei , Animais , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/etiologia , Camundongos , Malária/imunologia , Plasmodium berghei/imunologia , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/metabolismo , Pulmão/imunologia , Pulmão/patologia , Humanos , Feminino , OligopeptídeosRESUMO
Thiol reagents were shown to act as potent inhibitors of L5178-Y murine leukemia cell proliferation. A series of aryl maleimides (AMI) was synthesized and evaluated theoretically for global and local reactivity, showing their selectivity for thiol groups, due to a reaction of the vinyl moiety (a soft acid) with thiols (a soft base). Two AMI that are benzoic acid derivatives (1f and 1h) were tested with an in vitro and ex vivo model to evaluate their reactivity with thiols and their activity in L5178-Y cells. The in vitro reactions clearly showed a selective Michael type 1,4-addition reaction between thiols (glutathione and N-acetylcysteine, which are nucleophiles) and the AMI (1f and 1h, which are electrophiles). In cell cultures, the compounds induced a decreasing cellular viability and an apoptotic effect of up to 59.8% at 48 h. The ex vivo experimental model showed an important reduction of thiol levels in cells treated with 1h. Decreased cellular viability and increased apoptosis were confirmed by flow cytometry, DNA fragmentation and microscopy analysis (cytological studies). The increase in apoptosis on L5178-Y cells probably occurred, at least in part, by a decrease in glutathione levels and an increase in free radicals concentration. The decreased glutathione levels seem to make cancer cells more susceptible to death by apoptosis, and should certainly make them more vulnerable to a less aggressive treatment.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Leucemia/tratamento farmacológico , Maleimidas/farmacologia , Animais , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia/patologia , Maleimidas/química , Camundongos , Estrutura Molecular , Teoria Quântica , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
CONTEXT: Spirulina (Arthrospira) exerts a wide spectrum of pharmacological activities which are mainly attributed to its antioxidant effect. However, Spirulina has also been reported (both in preclinical and in clinical scenarios) to exhibit other bioactive effects, including an antitoxic potential. OBJECTIVE: We performed a systematic review of the literature, conducted in TOXNET, PubMed/MEDLINE, and Science Direct-Scopus; all available years were included. Searching criteria included the effects of Spirulina on experimental poisonings from arsenic, cadmium, carbon tetrachloride, deltamethrin, fluoride, hexachlorocyclohexane, iron, lead, lindane, and mercury. RESULTS: In all cases, it was established that the blue-green alga, and its isolated compounds, effectively counteracted these pollutants toxic effects on the exposed organisms. Some molecular mechanisms are proposed, although they have not been fully elucidated yet. CONCLUSION: Spirulina could be a useful coadjuvant agent within clinical practice for treatment of these or other pollutants poisonings.
Assuntos
Antídotos/farmacologia , Antioxidantes/farmacologia , Poluentes Ambientais/intoxicação , Intoxicação/tratamento farmacológico , Spirulina/metabolismo , Animais , Antídotos/isolamento & purificação , Antioxidantes/isolamento & purificação , Exposição Ambiental/efeitos adversos , Humanos , Exposição Ocupacional/efeitos adversos , Intoxicação/metabolismoRESUMO
Undernutrition constitutes a public health problem particularly in developing countries. The utilization of algae, particularly Spirulina, as a functional food was suggested decades ago due to the fact that it is not only a protein-dense food source, but because its amino acid profile is considered as of high biologic-value protein content. Spirulina provides essential fats (e.g., gamma-linolenic oleic acids), concomitant to low content nucleic acids. It also has an exceptionally high content of vitamin B12, is a good source of beta-carotene, iron, calcium and phosphorous. Moreover, Spirulina has also proven to have good acceptance as of its organoleptic properties (thus making it a possible prospect for food or a nutrition supplement) and it has not exhibited neither acute nor chronic toxicities, making it safe for human consumption.
La desnutrición constituye un problema de salud pública, fundamentalmente en los países en desarrollo. El uso de algas, particularmente Spirulina, como alimento funcional para combatir dicha patología se propuso desde hace algunas décadas debido a que estos alimentos no solo son fuentes alimentarias de alta densidad proteica, sino que también ofrecen un perfil de aminoácidos de alto valor biológico. Además, Spirulina provee ácidos grasos esenciales (p. ej., el gamma linolénico), concomitante con un bajo aporte de ácidos nucleicos. También tiene un contenido excepcionalmente alto de vitamina B12, es considerada una buena fuente de betacaroteno, hierro, calcio y fósforo. Más aún, se ha demostrado que Spirulina tiene una buena aceptación organoléptica, lo que le confiere un gran potencial para considerarse como suplemento nutricional y, finalmente, no se han reportado toxicidades crónicas ni agudas, haciéndola segura para el consumo humano.
Assuntos
Suplementos Nutricionais , Valor Nutritivo , Spirulina/química , Aminoácidos/química , Animais , Proteínas de Bactérias/química , Humanos , Micronutrientes/química , ToxicologiaRESUMO
BACKGROUND AND AIMS: In April 2009, a new strain of influenza A(H1N1) was identified in Mexico and in the U.S. In June 2009, WHO declared this a pandemic. Health care workers constituted a risk group for their close contact with infected individuals. The aim was to estimate seropositivity for A(H1N1)pdm09 in health staff at the Instituto Mexicano del Seguro Social. METHODS: A two-stage cross-sectional study, before and after vaccination in the same workers, was performed on a random sample of health-care workers. A socio-occupational questionnaire was applied and serum antibodies against influenza A(H1N1)pdm09 were determined through neutralization of retroviral pseudotypes; two logistic regression models for both were constructed. RESULTS: The average (median/mean) age of 1378 participants from 13 work centers was 41.7 years and 68.7% (947) were women. Seroprevalence for the first stage was 26.5% (365) (7.4-43%) vs. 20.8% (11) in a control group from the blood bank; for the second stage, the vaccinated group was 33% (215) (18.2-47%) and 27% (196) (11.6-50%) for the unvaccinated group. In regression models, seropositivity was associated with occupational exposure to suspected influenza infected patients, being physicians, and being vaccinated. CONCLUSIONS: Seropositivity against pandemic virus is similar to what was reported, both for vaccinated (2.8-40.9%) and unvaccinated (18.8-64.7%). Low seroprevalence in the vaccinated group indicates that between 67% and 73% were susceptible to infection. Given the relatively low vaccine-induced seropositivity, it is imperative to increase, hygiene and safety for health staff and at-risk populations, and strengthen epidemiological surveillance.