Current pharmaceutical design
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Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol is an oil at room temperature and insoluble in aqueous solution. Present formulations consists of 1% or 2% (w/v) propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg phosphatide. ⋯ In addition, this formulation has been demonstrated to result in the generation of oxygen free radicals. High dose propofol infusions have been associated with the "propofol syndrome"; this is a potentially fatal complication characterized by severe metabolic acidosis and circulatory collapse. This is a rare complication first reported in pediatric patients and believed to be due to decreased transmembrane electrical potential and alteration of electron transport across the inner mitochondrial membrane.
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The HIV/AIDS pandemic continues its spread at a rate of over 15,000 new infections every day. Sexual transmission of HIV-1 is the dominant mode of this pandemic spread. For the first time since the disease emerged in the early 1980s, about half the 42 million people now living with HIV/AIDS worldwide are women. ⋯ It is now apparent that sexually transmitted R5 HIV-1 viruses have less positive charge on their surface compared with the R4 HIV-1 viruses, which may limit the anionic polymers as topical microbicides despite extensive clinical trials. Nevertheless, their ongoing clinical trials, reviewed here, using optimized formulations, and special populations in various geographic locations are paving the way for future rigorous clinical testing of "mechanism-based" broad-spectrum anti-HIV microbicides that are currently under intense development. It is anticipated that future microbicide trials will focus on combination of products capable of attacking HIV life cycle at multiple steps intended to increase efficacy, limit cross-resistance as well as minimize microbicide-induced host toxicity.
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Review Comparative Study
Arterial hyperoxia in severe head injury: a useful or harmful option?
There is mounting evidence both from experimental and clinical studies that traumatic brain injury (TBI) is associated with a reduction of aerobic metabolism. This results from a variable combination of impaired substrate delivery and mitochondrial failure. Mitochondria, which are responsible for the production of 95% of cell adenosine triphosphate (ATP), may become compromised after TBI. ⋯ Several experimental and clinical studies, using normobaric hyperoxia, demonstrated an increase in brain tissue oxygen tension and a reduction of brain extracellular lactate levels, but there is no consensus about the biological meaning of these findings. For some authors, they translate an improvement of brain oxidative metabolism, while for others they represent only biological epiphenomena. The current review addresses the rational behind normobaric hyperoxia as a therapeutic application and discusses the experimental and clinical results achieved so far.
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Ginkgo biloba extracts (EGb) are well-defined plant extracts. It has several indications as dementia, macula degeneration, tinnitus and winter depression. A review of the current and past literature about older people with Alzheimer's dementia or vascular dementia or age-associated memory impairment treated with Ginkgo biloba extract, reveals that EGb has reproducible effects on cognitive functions in Alzheimer's disease. The drug is well tolerated.
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The DNA mismatch repair system maintains genomic stability by correcting DNA sequence errors generated during DNA replication, during genetic exchanges between chromosomes i.e., recombination, and by correcting DNA lesions caused by mutagenic agents such as cis-platinum. Post-synthesis mismatch repair improves almost 1000-fold the fidelity of DNA replication; however, the functions of mismatch repair proteins extend well beyond DNA repair. ⋯ Hence, mismatch repair proteins regulate the survival threshold to DNA damage, and this function provides a novel platform for understanding the role of mismatch repair in B cells, in tumor formation, as well as in resistance to chemotherapy. In this communication, we review how mismatch repair may contribute to the physiology of cells and may be regulated by the intracellular trafficking of mismatch repair proteins.