Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma.

Cannabis has been used for decades as a palliative therapy in the treatment of cancer. This is because of its beneficial effects on the pain and nausea that patients can experience as a result of chemo/radiotherapy. Tetrahydrocannabinol and cannabidiol are the main compounds present in Cannabis sativa, and both exert their actions through a receptor-mediated mechanism and through a non-receptor-mediated mechanism, which modulates the formation of reactive oxygen species. These oxidative stress conditions might trigger lipidic changes, which would compromise cell membrane stability and viability. In this sense, numerous pieces of evidence describe a potential antitumor effect of cannabinoid compounds in different types of cancer, although controversial results limit their implementation. In order to further investigate the possible mechanism involved in the antitumoral effects of cannabinoids, three extracts isolated from Cannabis sativa strains with high cannabidiol content were analyzed. Cell mortality, cytochrome c oxidase activity and the lipid composition of SH-SY5Y cells were determined in the absence and presence of specific cannabinoid ligands, with and without antioxidant pre-treatment. The cell mortality induced by the extracts in this study appeared to be related to the inhibition of the cytochrome c oxidase activity and to the THC concentration. This effect on cell viability was similar to that observed with the cannabinoid agonist WIN55,212-2. The effect was partially blocked by the selective CB1 antagonist AM281, and the antioxidant α-tocopherol. Moreover, certain membrane lipids were affected by the extracts, which demonstrated the importance of oxidative stress in the potential antitumoral effects of cannabinoids.

Vaccine strategies: Optimising outcomes.

Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the factors that encourage success, which often include strong support from government and healthcare organisations, as well as tailored, culturally-appropriate local approaches to optimise outcomes.

Vitamin A supplementation modifies the association between mucosal innate and adaptive immune responses and resolution of enteric pathogen infections.

BACKGROUND: The efficacy of vitamin A supplementation on diarrheal disease morbidity may reflect the divergent effects that supplementation has on pathogen-specific immune responses and pathogen-specific outcomes. OBJECTIVE: We examined how vitamin A supplementation modified associations between gut-cytokine immune responses and the resolution of different diarrheal pathogen infections. DESIGN: Stools collected from 127 Mexican children who were 5-15 mo old and enrolled in a randomized, placebo-controlled vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of interleukin (IL)-6, IL-8, IL-4, IL-5, IL-10, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by using an enzyme-linked immunosorbent assay. Hazard models that incorporated categorized cytokine variables (ie, nondetectable, less than the median of detectable concentrations, and at least the median of detectable concentrations) were fit to the length of pathogen infections stratified by treatment group. RESULTS: Vitamin A-supplemented children with fecal MCP-1 or IL-8 concentrations less than the median of detectable concentrations and IL-10 concentrations of at least median concentrations had longer durations of EPEC infection than did children in the placebo group. In supplemented children, detectable fecal TNF-α or IL-6 concentrations were associated with shorter ETEC infection durations, whereas MCP-1 concentrations of at least the median were associated with longer infection durations. Children in this group who had IL-4, IL-5, or IFN-γ concentrations of at least median detectable concentrations had shorter durations of G. lamblia infection. CONCLUSION: The effect of supplementation on associations between fecal cytokine concentrations and pathogen infection resolution depends on the role of inflammatory immune responses in resolving specific pathogen infections.

Associations between mucosal innate and adaptive immune responses and resolution of diarrheal pathogen infections.

The identification of immune response mechanisms that contribute to the control of diarrheal disease in developing countries remains an important priority. We addressed the role of fecal chemokines and cytokines in the resolution of diarrheal Escherichia coli and Giardia lamblia infections. Stools collected from 127 Mexican children 5 to 15 months of age enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and Giardia lamblia. Fecal concentrations of tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), interleukin-4 (IL-4), IL-5, IL-6, IL-8, IL-10, and interferon-gamma (IFN-gamma) were determined. Hazard models incorporating cytokine variables were fit to durations of asymptomatic and symptomatic pathogen infections, controlling for treatment group. Increased levels of TNF-alpha and IL-6 were associated with decreased durations of EPEC infection and increased ETEC durations. Increased IL-4 and IFN-gamma levels were associated with decreased and increased durations, respectively, of both EPEC and ETEC infections. Increased IL-10 levels were associated with increased and decreased durations of asymptomatic and symptomatic EPEC infections, respectively, and increased durations of both asymptomatic and symptomatic ETEC infections. Increased levels of MCP-1, IFN-gamma, IL-4, and IL-5 were associated with increased G. lamblia infection duration, while increased IL-8 levels were associated with decreased durations. Differences in proinflammatory and Treg cytokine levels are associated with differences in the resolution of inflammatory and noninflammatory pathogen infections.

Defective in vitro growth of primitive hematopoietic cells from pediatric patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a neoplastic hematologic disorder that arises at the level of a primitive stem/progenitor cell. Most studies on the biology of the hematopoietic system in AML have focused on cells from adult patients; much less is known about hematopoietic cells from childhood AML. PROCEDURE: By using a negative immunoselection system, we have obtained a primitive cell population (enriched for CD34(+) Lin(-) cells) from the bone marrow (BM) of 17 pediatric AML patients and characterized its proliferation, expansion, and differentiation potentials in liquid cultures supplemented with a mixture of 8 different recombinant stimulatory cytokines. RESULTS: The proportion of CD34(+) cells in AML patients was extremely heterogeneous, ranging from 0% to 74%. Regardless of their CD34(+) cell content, and in contrast to normal cells, AML cells showed a deficient capacity to proliferate even in the presence of the stimulatory cytokines. AML progenitors were unable to generate new progenitor cells, indicating their inability to expand. Interestingly, AML cells were able to differentiate in culture, giving rise to morphologically recognizable precursors. A major difference, however, as compared to hematopoietic progenitors from normal subjects, was the fact that whereas in cultures of normal cells both myeloid and erythroid precursors were produced, in AML cultures the vast majority of the cells generated corresponded to myeloid cells, mostly mature macrophages. CONCLUSION: As compared to their normal counterparts, primitive hematopoietic cells from pediatric patients with AML possess impaired proliferation, expansion, and differentiation potentials in vitro.

Cardiac manifestations of parasitic infections part 3: pericardial and miscellaneous cardiopulmonary manifestations.

This is part three of a three-part series discussing parasites of the heart. In this section, we present an overview on parasitic diseases involving predominantly the pericardium and other miscellaneous cardiopulmonary manifestations such as some pulmonary hypertension syndromes and endomyocardial fibrosis.

The solution conformation of C-glycosyl analogues of the sialyl-Tn antigen.

The conformational behavior of two C-glycosyl analogues of the sialyl-Tn antigen has been determined by a combination of NMR methods and molecular mechanics calculations. Both compounds show a major solution conformation that is drastically different from the major one of the natural compound.

Susceptibilidad de cepas de Haemophilus influenzae no tipificable a laracarbef (LY163892) y antimicrobianos de uso común / The susceptibility of strains of non-typable H. influenzae a loracarbef(LY163892) or antimicrobials

La participación de cepas de Haemophilus influenzae no tipificable en infecciones de vías respiratorias superiores es frecuente. En las últimas dos décadas un aumento gradual de resistencia mediada por beta lactamasa de H. infuenzae no tipificable se ha observado. Nosotros evaluamos el patrón de susceptbilidad mediante la técnica de kirby.Bauer, de 150 cepas de H. influenzae no tipificable de niños portadores sanos a cuatro antibióticos de uso común y determinamos la producción de ß-lactamasa por la técnica de cefinasa. Encontramos que 129/150 (86 por ciento) fueron susceptibles y 17 (11 por ciento) resistentes a ampicilina; de estas 17, sólo 7 fueron productoras de ß-lactamasas. La susceptibilidad para cefaclor fue 140/150 (95 por ciento); para trimetroprim/sulfametoxazol 97 por ciento, y para loracarbef el 93 por ciento. En este estudio encontramos que la resistencia de H. influenzae no tipificable a ampicilina fue inferior a lo reportado en Estados Unidos y que de las cepas resistentes menos de la mitad fueron productoras de beta lactamasas. La actividad in vitro de loracarbef contra cepas de H. Influenzae no tipificable mostró ser similar a cefaclor pero inferior trimetropim/sulfametozaxol, aunque con la ventaja de tner adecuada cobertura contra estreptococos

Comparative analisis plasmids from nosocomial Klebsiella pneumoniae strains isolated from two hospitals

A total of 46 clinical isolates of Klebsiella pneumoniae were studied. Of these, 33 were from "Hospital Infantil de Mexico" (HIM) and 13 from "Hospital General de Mexico" (HGM). The susceptibility of these strains to five antibiotics, as well as the plasmid DNA profiles, were determined for each group. Antibiotic susceptibility profiles were very similar in strains from both hospitals; however, most of the strains analyzed exhibited heterogeneous plasmid DNA profiles. Results showed that strains isolated in the two hospitals did not differ regarding morphology, biochemical profiles, antibiotic susceptibility or plasmid populations, and these characteristics may not be used as markers to differentiate Klebsiella pneumoniae strains from different hospitals

Infección respiratoria recurrente en el niño: evaluación clínica y de laboratorio / Recurrent respiratory infections in children: a clinical and laboratory

Las infecciones respiratorias constituyen la principal causa de consulta médica, y una de las dos primeras causas de morbimortalidad en menores de cinco años en los países en desarrollo. Estudios epidemiológicos han demostrado que niños preescolares contraen entre cuatro y seis infecciones respiratorias en el transcurso de un año sin que esto necesariamente implique desviación de la "normalidad". Sin embargo, el médico general y el pediatra frecuentemente se enfrentan ante el dilema de decidir si el niño que esta "siempre enfermo" por cursar una infección respiratoria recurrente (IRR), en un niño normal o tiene alguna condición predisponente. Dentro de las condiciones predisponentes de IRR en el niño se encuentran factores del hospedero (mecanismos de defensa inmenes y no inmunes), del agente infectante y/o del medio ambiente. En esta revisión se presenta un panorama general de la evaluación clínica y de laboratorio del paciente pediátrico con IRR, lo cual está al alcance y dentro de la capacidad de todo médico

Las citocinas y su papel como mediadores de salud y enfermedad: nuevos enfoques para viejos problemas / Cytokiens and theirrole in health and diseases new approaches to old problems

Las citocinas son hormonas polipeptídicas multifuncionales, sintetizadas por una variedad de células del organismo que intervienen en la regulación de numerosos procesos biológicos. Como mensajeros esenciales de la comunicación intercelular, colaboran en la mantención de la homeostasis en los tejidos normales. Dada su función primordial como mediadores de la respuesta inmuno-inflamatoria tanto a nivel local como sistémico, alteraciones en su secreción, respuesta y/o regulación han sido implicados en la fisiopatología de diversas enfermedades caracterizadas por un componente autoinmune. Asimismo, la aumentada susceptibilidad a las infecciones microbianas observada, por ejemplo en el neonato o en la desnutrición, podría estar dada, en parte por déficit en la producción o en la respuesta de las células inmunes a las citocinas. En este artículo se revisan los aspectos más sobresalientes de la biología de las citocinas, su influencia en diversos estados de enfermedad así como las aplicaciones clínicas de estos noveles agentes inmunomoduladoeres.

Programa educacional y de investigación sobre diagnóstico y tratamiento de otitis media en latinoamérica / Latin americana otitis media research and trining program

La otitis media en Latinoamérica es a causa más importante de deterioro de la audición en la población infantil, originando además repercusiones en el lenguaje y aprendizaje. Sus complicaciones infecciosas intra y extratemporales son además padecimientos que ponen en peligro la vida del paciente. Todo esto puede ser prevenido de manera simple y económica. El programa educacional y de investigación sobre la otitis media en Latinoamérica es un proyecto internacional multidisciplinario, diseñado para mejorar su diagnóstico y tratamiento; más de 200 profesionistas al cuidado de la salud han participado en los seminarios piloto presentados en Brasil, Costa Rica y México. Los cursos teórico-prácticos con apoyo audiovisual destacan el papel de la otoscopia neumática y se concluye que este programa de educación médica continua contribuye significativamente a la atención primaria y mejora el nivel de la salud infantil