Oxysterols selectively promote short-term apoptosis in tumor cell lines.

Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of several oxysterols to induce short-term death in cancerous (human breast cancer and mouse skin melanoma cells) and non-cancerous (human endothelial cells and lung fibroblasts) cell lines. We determined cell viability, Ki67 expression, cell cycle regulation, and apoptosis after 24-h incubations with oxysterols. We found that different oxysterols had different effects on the studied parameters. Moreover, the effects depended on cell type and oxysterol concentration. Three cytotoxic oxysterols (7-ketocholesterol, cholestane-3ß-5α-6ß-triol, and 5α-cholestane-3ß,6ß-diol) inhibited the S phase and stimulated the G0/G1 or G2/M phases. These oxysterols promoted apoptosis, determined with Annexin V and propidium iodide assays. These results showed that different oxysterols have cytotoxic effects depending on the cell line. The findings suggest a potential pharmacological utility of cytotoxic oxysterols.

CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction.

Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg2+ in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg2+ on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg2+ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg2+ -toxicity by preserving their ability to retain matrix content, such as accumulated Ca2+ . This nucleotide also protected mitochondria from Hg2+ -induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP-choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL-1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg2+ and CDP, CDP-choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine.

Oxysterols and mesenchymal stem cell biology.

Oxysterols are oxidized products of cholesterol that play several roles in various pathophysiological processes, including the control of lipid metabolism, immunological processes, and cytotoxicity. Mesenchymal stem cells are multipotent cells with properties of self-renewal and the ability to differentiate into other cell types, including osteoblasts and adipocytes. Here, we review the literature regarding the effects of oxysterols on mesenchymal stem cell differentiation and the main signaling pathways involved in this process.

Organochlorine pesticide distribution in an organic production system for cow's milk in Chiapas, Mexico.

The objective of this study was to evaluate the presence of organochlorine pesticides in samples of forage, soil, water, and milk in four units of an organic production system for cow´s milk (samples of forage, milk, soil, and water) in Tecpatan, Chiapas, Mexico. The organochlorine pesticides were extracted from forage, soil and water based on the USEPA (2005) guideline and from milk based on the IDF 1991 guideline. The pesticides were identified and quantified by gas chromatography with electron capture detector (CG-ECD). In general, the highest average concentration of total pesticides was found in the samples of milk and forage (311 ± 328 and 116.5 ±77 ng g(-1) respectively). Although, the production systems analyzed are organic, organochlorine pesticides were detected in all environmental samples (forage, soil, water, and organic milk). Although no values surpassed the defined limits of Mexican and International regulation it is advisable that a monitoring program of contaminants in these production systems is continued.

Interrelationship between ATP-binding cassette transporters and oxysterols.

ATP-binding cassette (ABC) transporters constitute a ubiquitous superfamily of membrane proteins responsible for the translocation of several substances across membranes using the chemical energy provided by ATP hydrolysis. ABC transporters participate in many physiological and pathophysiological processes, including cholesterol and lipid transportation and multidrug resistance. Oxysterols are the products of cholesterol oxidation, formed by both enzymatic and non-enzymatic mechanisms. The role of oxysterols in cholesterol metabolism and several diseases has been widely investigated, but many questions remain to be answered. Several lines of evidence link ABC transporter functions with cholesterol and oxysterol metabolism. This review discusses ABC transporters, oxysterols, and how they interact with each other.

Azidothymidine is effective against human multiple myeloma: a new use for an old drug?

Azidothymidine (AZT) is an antiretroviral drug that affects cell proliferation, apoptosis, and the NF-κB pathway. As multiple myeloma (MM) presents with constitutive activation of NF-κB, we analyzed the effect of AZT on human MM cell lines. We evaluated the cytotoxic effect of AZT in human MM cell lines sensitive (8226/S) or resistant to doxorubicin (8226/DX5) and human T cell lymphoblast-like cells, uterine sarcoma cells, and HUVEC using MTT assay. Cytotoxicity was also evaluated in vivo in nude mice xenografted with 8226/S tumor. The effect of AZT on the expression of genes involved in cell proliferation, apoptosis, angiogenesis, and the NF-κB pathway was analyzed in the xenografts using real-time polymerase chain reaction. AZT was effective against both 8226/S and 8226/DX5 cells in a dose and time-dependent manner (p = 0.02) in vitro and promoted cell cycle arrest in S phase in these cells. The tumor volume was lower in mice treated with AZT compared to untreated mice (p = 0.0003). AZT down-regulated the pro-proliferative genes encoding AKT1, MYC, STAT1, MAPK8, MAPK9, CCL-3, Bcl-3, and cyclin D2; pro-angiogenenic genes encoding VEGF and IL8; and genes involved in cell adhesion (ICAM1 and FN1) and the NF-κB pathway. AZT up-regulated the expression of tumor suppressor gene FOXP1 and the pro-apoptotic genes encoding BID, Bcl-10, and caspase-8. Thus, we demonstrated the cytotoxic effect of AZT in human MM cell lines for the first time. Our data may provide the rationale for future clinical trials of AZT for treating MM.

Cáncer de mama y biopsia con aguja fina

Entre enero de 1992 y enero de 1997 recibieron tratamiento 146 pacientes con cáncer de mama en el Hospital Provincial Docente Clinico-quirúrgico "Arnaldo Milián Castro" de Villa Clara. Se utilizó la biopsia por aspiración con aguja fina como procedimiento de diágnostico de preoperatorio en el 69,86 por ciento de los pacientes, y mediante la misma se realizó el diagnóstico de corteza en el 71,56 por ciento. El carcinoma ductal infiltrante fue la variedad hística más fercuente encontrada en nuestro estudio

Biopsia aspirativa con aguja fina guiada por ultrasonido en lesiones hepáticas localizadas

Se realizaron 53 aspiraciones a 48 pacientes, con una edad promedio de 54 años que presentaban lesiones hepática localizadas, en el servicio de Ultrasonografía del Hospital Provincial Docente Clínico-quirúrgico "Arnaldo Milián Castro" de Cilla Clara, desde agosto de 1991 a mayo del 1995, con el propósito de procesar los patrones ultrasonográficos que permitieran reconocer las lesiones antes de realizar la biopsia, y dirigir la aguja de punción hacia el área más sospechosa. Se evaluó la utilidad del valor diagnóstico de la técnica. La biopsia aspirativa con aguja fina guiada por ultrasonido, resultó ser una técnica muy útil en la toma de muestra, pues los porcentajes de específicidad fueron más alto que los de sensibilidad, dada la insuficiencia del material obtenido mediante el procedimiento. Existió una relación muy positiva entre la ultrasonografía y el citodiagnóstico, y predominó la lesión benigna sobre la maligna. No hubo complicaciones de trascendencia clínica