Apoptosis induced by Aß25-35 peptide is Ca(2+) -IP3 signaling-dependent in murine astrocytes.

Although the accumulation of the neurotoxic peptide ß-amyloid (Aß) in the central nervous system is a hallmark of Alzheimer's disease, whether Aß acts in astrocytes is unclear, and downstream functional consequences have yet to be defined. Here, we show that cytosolic Ca(2+) dysregulation, induced by a neurotoxic fragment (Aß25-35), caused apoptosis in a concentration-dependent manner, leading to cytoplasmic Ca(2+) mobilization from extra- and intracellular sources, mainly from the endoplasmic reticulum (ER) via IP3 receptor activation. This mechanism was related to Aß-mediated apoptosis by the intrinsic pathway because the expression of pro-apoptotic Bax was accompanied by its translocation in cells transfected with GFP-Bax. Aß-mediated apoptosis was reduced by BAPTA-AM, a fast Ca(2+) chelator, indicating that an increase in intracellular Ca(2+) was involved in cell death. Interestingly, the Bax translocation was dependent on Ca(2+) mobilization from IP3 receptors because pre-incubation with xestospongin C, a selective IP3 receptor inhibitor, abolished this response. Taken together, these results provide evidence that Aß dysregulation of Ca(2+) homeostasis induces ER depletion of Ca(2+) stores and leads to apoptosis; this mechanism plays a significant role in Aß apoptotic cell death and might be a new target for neurodegeneration treatments.

Interplay between apoptosis and autophagy, a challenging puzzle: new perspectives on antitumor chemotherapies.

Autophagy is a mechanism of protection against various forms of human diseases, such as cancer, in which autophagy seems to have an extremely complex role. In cancer, there is evidence that autophagy may be oncogenic in some contexts, whereas in others it clearly contributes to tumor suppression. In addition, studies have demonstrated the existence of a complex relationship between autophagy and cell death, determining whether a cell will live or die in response to anticancer therapies. Nevertheless, we still need to complete the autophagy-apoptosis puzzle in the tumor context to better address appropriate chemotherapy protocols with autophagy modulators. Generally, tumor cell resistance to anticancer induced-apoptosis can be overcome by autophagy inhibition. However, when an extensive autophagic stimulus is activated, autophagic cell death is observed. In this review, we discuss some details of autophagy and its relationship with tumor progression or suppression, as well as role of autophagy-apoptosis in cancer treatments.

The role of calcium stores in apoptosis and autophagy.

The mechanisms that regulate programmed cell death, such as apoptosis, and the cellular "self-eating" phenomenon of autophagy, share many regulatory systems and common pathways. These mechanisms have been extensively investigated over the last few years. Some intracellular structures may determine and control the autophagic fate of the cell such as the endoplasmic reticulum, mitochondria, and lysosomes. The coordination and interrelation of these organelles are crucial in maintaining calcium levels and general cellular homeostasis, as well as in regulating cell life and death under physiological and pathological conditions, including cancer, neurodegeneration, and aging. In this review, we discuss the crosstalk between the aforementioned organelles and their influence in apoptotic and autophagic processes.

Avaliação da utilização de medicamentos na prática clínica em um hospital público / Assessment of drugs prescribed to medical in-patients in a public hospital

Através desta pesquisa, objetivou-se estudar o consumo dos medicamentos em pacientes hospitalizados na clínica médica de um hospital público na cidade de Campina Grande (PB). O estudo caracterizou-se como descritivo e exploratório, de caráter transversal, com abordagens quali-quantitativas, e foi constituído por uma amostra de 107 pacientes que iniciaram internação na clínica médica no período de agosto de 2007 a julho de 2008. Os 107 pacientes apresentavam 270 diagnósticos ativos, sendo as doenças do aparelho circulatório as de maior ocorrência. Dos pacientes, 65,4% eram idosos e 3,33% dos medicamentos prescritos foram considerados impróprios para eles. Os pacientes que apresentaram possíveis 107 RAMs totalizaram 43%, com média de 2,32 por paciente; as que afetaram o sistema gastrintestinal dos pacientes foram as identificadas com maior frequência. Houve 42 interações distintas, envolvendo 26 tipos de fármacos. Dessa forma, os resultados podem ser úteis no estímulo ao desenvolvimento de mecanismos de avaliação de processos que visem reduzir esses riscos, aumentando a chance de resultados terapêuticos positivos e benefícios para os pacientes.

We studied the consumption of drugs by in-patients in the medical ward of a public hospital in the city of Campina Grande, PB, Brazil. This paper describes a descriptive / exploratory cross-sectional quali-quantitative study of a sample of 107 patients who were admitted to the general medical ward, from August 2007 to July 2008. The 107 patients were diagnosed with 270 active complaints, mainly diseases of the circulatory system. Most of the patients (65.4%) were elderly and 3.33% of drugs prescribed for them are considered unfit for use in the elderly. Many patients (43%) presented 107 possible Adverse Drug Reactions, with an average of 2.32 per patient, those affecting the gastrointestinal system of the patients being identified most frequently. There were 42 different drug interactions, involving 26 types of drug. We hope these results may be useful in stimulating the development of means to assess drug treatment in hospital, so as to reduce these risks and increase the chance of positive outcomes and therapeutic benefits for the patients.