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Abstract: Highly active antiretroviral therapies have decreased human immunodeficiency virus-associated mortality explaining the greater number of older adults living with HIV infection. Low bone mineral density is more prevalent in HIV-infected patients compared to controls. Data about fracture risk in HIV patients are more conflicting. Pathogenesis of this reduced bone mineral density appear to be multifactorial with interaction of high rates of osteoporosis risk factors like tobacco and alcohol use, low vitamin D levels, direct HIV infection and antiretroviral therapy use. Among antiretroviral drugs, protease inhibitors and some nucleotide reverse transcriptase inhibitors, like tenofovir, are more associated with bone loss. Some protease inhibitors are potent inhibitors of cytochrome interacting with metabolism of vitamin D and affect bone metabolism inhibiting osteoblast and osteoclast differentiation. These data suggest that detection of osteoporosis is important for HIV patients before any treatment with subsequent BMD monitoring. [Copyright &y& Elsevier]

Abstract: Antiepileptic drugs are more used today for the treatment of epilepsy and other diseases as psychiatric disorders and chronic pain. An increased risk of fracture has been reported in cross-sectional and longitudinal studies in epileptic patients treated with antiepileptic drugs. Longitudinal studies in subjects older than 65 years show that antiepileptic drugs are associated with an increase risk of bone loss. Although many studies have been adjusted for a number of confounders, none have addressed whether the disease or condition for which the treatment was prescribed is responsible for the fracture. A potential mechanism is the increase catabolism of vitamin D due to hepatic induction of the P-450 cytochrome (CYP 450). However, the mechanisms of antiepileptic drugs-induced bone loss appears to be multiple, and all types of antiepileptic drugs are potentially implicated. There is limited data regarding the newer antiepileptic drugs. Although there are no consensus guidelines, adult patients receiving long-term antiepileptic drugs require a screening for osteoporosis and measurements of serum calcium, phosphate, alkaline phosphatase, and vitamin D. [Copyright &y& Elsevier]

Centipeda minima is a medicinal plant reputed in China as a remedy for nasopharyngeal carcinoma (NPC). In this study, bioactivity-guided fractionation of the anti-NPC compound(s) from C. minima led to the isolation of 2β- (isobutyryloxy)florilenalin (IF), a sesquiterpene lactone. IF showed significant dose- and time- dependent inhibition on the growth of the human nasopharyngeal carcinoma epithelia cells (CNE). It induced apoptosis in CNE cells, as shown by the accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation, caspase-3 activation and PARP cleavage. Such induction was associated with the depletion of mitochondrial membrane potential (ΔΨm) and the release of cytochrome c to cytosol to regulate the expression of Bcl-2 family proteins. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, IF in C. minima showed potent antiproliferative effect of C. minima on NPC cells, suggesting that the plant deserves more extensive investigation for its potential medicinal application. [ABSTRACT FROM AUTHOR]

Abstract: Over the past 50 years, significant clinical information has been obtained on numerous aspects of benzodiazepines, notably on their pharmacokinetics and pharmacodynamic properties, drug interactions and therapeutic usage. The main objective of this review is to determine which of these aspects a clinician should consider when choosing a benzodiazepine. Benzodiazepines can be distinguished by their half-lives and those with an intermediate half-life (6–12h) are indicated for punctual usage and for initial insomnia while those with a longer half-life (over 12h) are indicated for clinical situations requiring sustained therapeutic treatment. Benzodiazepines with longer half-lives are more at risk of causing side effects due to accumulation of the drug. Most, but not all, benzodiazepines are metabolized by the liver and should be used carefully in patients known to have a hepatic disease, in geriatric patients or in patients taking other medication modifying hepatic metabolism. In these cases, lorazepam, oxazepam or temazepam should be chosen because they are less dependant on hepatic metabolism. Most but not all benzodiazepines are metabolized by the intestinal and hepatic cytochrome P-450 3A4 system. A number of medication namely ketoconazole, erythromycin, corticosteroids, fluoxetine, fluvoxamine, sertraline, calcium channel blockers and grapefruit juice may increase plasma concentrations of some benzodiazepines by inhibiting P-450 3A4 cytochrome activity. Cigarette smoking has been reported to significantly increase the clearance of alprazolam. The mechanism of action of benzodiazepines consists in increasing the inhibitory effect of gamma-aminobutyrique acid (GABA) in the central nervous system. GABA receptor contains five sub-units organised in the form of a rosette. The canal in the centre of the rosette permits the entrance of chloride ions and the opening of the channel is modulated by GABA through changing the configuration of the proteins constituting the rosette. Benzodiazepines alone have no inhibitory activity on neurones but will potentiate the effect of GABA by binding to the sub-units α, β and γ of the rosette. Binding to the sub-unit α1 localised mainly in the brain stem will increase sedation while binding to the sub-unit α2 in the limbic system will confer anxiolytic properties to benzodiazepines. No differences among benzodiazepines have been reported concerning their binding to different sub-units. However, clonazepam does appear to modify serotoninergic transmission and this pharmacodynamic characteristic may increase clonazepam inhibitory properties and also stabilise mood in patient with unipolar depression. Benzodiazepines prolonged usage will modify the DNA expression and decrease synthesis m-RNA coding for sub-units α1, α2, α3 and possibly β. These modifications in the composition of GABA receptors are thought to be a mechanism of autoregulation of the receptor and could explain tolerance which is observed in prolonged usage of benzodiazepines. Overall, pharmacokinetics properties and drug interaction remain the most important characteristics when choosing a benzodiazepine while pharmacodynamic properties have little relevance because differences are not significant within this class of medication. [Copyright &y& Elsevier]