Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model

Osteoporosis (OP) is one of the most prevalent bone diseases worldwide with bone fracture the major clinical consequence. The effect of OP on fracture repair is disputed and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer to this question still eludes us. The aim of this study was to clarify the effect of osteoporosis in a rodent fracture model. OP was induced in 3-month-old rats (n = 53) by ovariectomy (OVX) followed by an externally fixated, mid-diaphyseal femoral osteotomy at 6 months (OVX group). A further 40 animals underwent a fracture at 6 months (control group). Animals were sacrificed at 1, 2, 4, 6, and 8 weeks postfracture with outcome measures of histology, biomechanical strength testing, pQCT, relative BMD, and motion detection. OVX animals had significantly lower BMD, slower fracture repair (histologically), reduced stiffness in the fractured femora (8 weeks) and strength in the contralateral femora (6 and 8 weeks), increased body weight, and decreased motion. This study has demonstrated that OVX is associated with decrease in BMD (particularly in trabecular bone) and a reduction in the mechanical properties of intact bone and healing fractures. The histological, biomechanical, and radiological measures of union suggest that OVX delayed fracture healing. (C) 2007 Orthopaedic Research Society. Published by Wiley Periodicals.

A tentative determination of upwelling influence on the paleo-surficial marine water reservoir effect in southeastern Brazil.

Previous work has suggested that seasonal and inter-annual upwelling of deep, cold, radiocarbon depleted waters from the South Atlantic has caused variations in the reservoir effect (R) through time along the southern coast of Brazil. This work aims to examine the possible upwelling influence on the paleo-reservoir age of Brazilian surficial coastal waters based on paired terrestrial/marine samples obtained from archaeological remains. On the Brazilian coast there are hundreds of shell-middens built up by an ancient culture that lived between 6500 to 1500 years ago, but there are few located on open coast with a known upwelling influence. Three archaeological sites located in a large headland in Arraial do Cabo and Ilha de Cabo Frio, southeastern coast of Brazil with open ocean conditions and a well-known strong and large upwelling of the Malvinas/Falkland current were chosen for this study. The 14C age differences between carbonized seed and marine samples varied from 281 ± 44 to 1083 ± 51 14C yr. There are also significant age differences between carbonized seed samples (977 14C yr) and marine samples (200 and 228 14C yr) from the same archaeological layer that cannot be explained by a reservoir effect or an old-wood effect for charcoal. Therefore the present data from the southeastern Brazilian coast are inconclusive for identifying an upwelling effect on R. To do so it would be necessary to more precisely define the present-pre-bomb R in upwelling regions and to analyze paired marine/terrestrial samples that are contemporaneous beyond doubt.

Safety and Pharmacokinetics of Dapivirine Delivery From Matrix and Reservoir Intravaginal Rings to HIV-Negative Women

Vaginal microbicides for the prevention of HIV transmission may be an important option for protecting women from infection. Incorporation of dapivirine, a lead candidate nonnucleoside reverse transcriptase inhibitor, into intravaginal rings (IVRs) for sustained mucosal delivery may increase microbicide product adherence and efficacy compared with conventional vaginal formulations. Twentyfour
healthy HIV-negative women 18–35 years of age were randomly assigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR, or placebo IVR. Dapivirine concentrations were measured in plasma
and vaginal fluid samples collected at sequential time points over the 33-day study period (28 days of IVR use, 5 days of follow-up). Safety was assessed by pelvic/colposcopic examinations, clinical laboratory tests, and adverse events. Both IVR types were safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Dapivirine from both IVR types was successfully distributed throughout the lower genital tract at concentrations over 4 logs greater than the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) values were significantly higher with the matrix than reservoir IVR. Mean plasma concentrations of dapivirine were ,2 ng/mL. These findings suggest that IVR delivery of microbicides is a viable option meriting further study.