HIV infection and antiretroviral therapy (ART) are now established independent risk factors for osteoporosis. With a spate of recent studies reporting significant elevations in fracture prevalence in HIV patients, and a rapidly aging demographic, defining the mechanisms underlying HIV/ART-induced skeletal decline has become imperative. The recent emergence of the field of “osteoimmunology” has provided a conceptual framework to explain how the immune and skeletal systems interact. Furthermore, it is becoming clear that inflammatory states leading to perturbations in the immuno-skeletal interface, a convergence of common cells and cytokine mediators that regulate both immune and skeletal systems, conspire to imbalance bone turnover and induce osteoporosis. In this review we examine the role of inflammation in the bone loss associated with diverse inflammatory conditions and new concepts into how the underlying mechanisms by which inflammation and immune dysregulation impact bone turnover may be pertinent to the mechanisms involved in HIV/ART-induced bone loss.
This paper uses the Cost of Illness (COI) framework to estimate the cost of rheumatoid arthritis (RA) to society in the year 1992-93. By doing so, a clear insight is given into the many cost elements of RA treatment and monitoring. This paper estimates point prevalence rates of 2.06 and 6.94 1000 persons at risk for men and women, respectively, showing that prevalence is three times higher amongst women than men. Further to this, prevalence increases with age in both sexes, resulting in very high prevalence rates for RA amongst the elderly. The total economic impact of RA in England was estimated to be pounds 1.256 billion in 1992, of which 52% was a result of production loss caused by RA disability.
The activity of three new, 8-methoxy-nonfluorinated quinolones (NFQs) against multiple-drug-resistant staphylococci was investigated. First, using Staphylococcus aureus strains containing point mutations in the serine 84-80 hot spots of the target genes (gyrA and grlA), cell growth inhibition potencies of the NFQs as a result of DNA gyrase and topoisomerase IV inhibition were estimated and compared with those of known fluoroquinolones. The NFQs and clinafloxacin showed higher affinities toward both the targets than ciprofloxacin, trovafloxacin and gatifloxacin. Furthermore, the ratio of the calculated affinity parameter for DNA gyrase to that for topoisomerase IV was lower in the case of the NFQs, clinafloxacin, and gatifloxacin than in the case of ciprofloxacin and trovafloxacin. These results suggest that the former group of quinolones is better able to exploit both the targets. Next, using clinical isolates of methicillin-resistant S. aureus (MRSA; n ؍ 34) and coagulasenegative staphylococci (CoNS; n ؍ 24), the NFQs and clinafloxacin were shown to be more potent (MIC at which 90% of the isolates are inhibited [MIC 90 ] ؍ 2 g/ml for MRSA and 0.5 g/ml for CoNS) than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC 90 ؍ 16 to >64 g/ml for MRSA and 4 to >32 g/ml for CoNS). Bactericidal kinetics experiments, using two MRSA isolates, showed that exposure to the NFQs at four times the MIC reduced the bacterial counts (measured in CFU per milliliter) by >3 log units in 2 to 4 h. Overall, the NFQs and clinafloxacin were less susceptible than the other quinolones to existing mechanisms of quinolone resistance in staphylococci.
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