Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine.

Cancellous bone morphometry was investigated in the sagittal plane of lumbar vertebrae using histoquantitation. The aim of this study was to identify variations in cancellous bone architecture at increasing states of intervertebral disc (IVD) disorganization after age adjustment and to investigate regional variations within the whole vertebral body. Measurements were taken of the ratio of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12-L5) of 19 men and 8 women were removed at autopsy from an adult sample with no clinical history of bone-related disease or histologically identifiable bone disease. It was found that degeneration of the IVD becomes more common with increasing age. After age-adjustment, significant increases in the proportion of BV/TV were observed in the presence of advancing IVD disorganization. Significant architectural changes were observed in the anterior regions of the vertebral body with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were found at posterior regions. Bone loss was observed in central regions (most distant from the cortex) as IVD disorganization increased through reduction in both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a response to a redistribution of load to the vertebral body periphery as a result of IVD disorganization. It appears that trabecular morphology is related to the condition of the associated IVD, rather than being the sole consequence of a loss of BV/TV with age. This relationship could influence the occurrence of vertebral body crush fracture.     

EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair

Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts. In the present study, we examined the role of EphB4 during bone repair after traumatic injury. We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1‐EphB4) and investigated the bone repair process up to 12 weeks postfracture. The data indicated that Col1‐EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild‐type mice. The fractured bones of Col1‐EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild‐type mice. These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively. Interestingly, Col1‐EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU‐F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild‐type control mice. Furthermore, Col1‐EphB4 mice had significantly lower numbers of TRAP‐positive multinucleated osteoclasts within the callus site. Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones. © 2013 American Society for Bone and Mineral Research.     

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

The effect of captopril treatment on potassium-induced stimulation of aldosterone production in vitro

Potassium and angiotensin (AII) show interdependence as stimuli of aldosterone production. However, potassium stimulates in vitro in the absence of AII. In the present study we examined for a contribution by AII to the in vitro stimulatory potential of potassium, an AII effect mediated on the adrenal before killing of the animal. Captopril, an angiotensin converting-enzyme inhibitor, was administered orally and by sc injection for 3 days so as to decrease levels of AII. Aldosterone secretory responses by adrenal capsules to graded increments in potassium were measured subsequently using a perifusion system. It was found that captopril pretreatment significantly reduced the magnitude of aldosterone secretory response to increments in potassium of 0.5 to 6.0 mM, from a baseline potassium concentration of 3.5 mM. Responses to the lowest increment in potassium, 0.5 and 1.0 mM, were virtually abolished by captopril treatment. The results suggest that AII sensitizes the adrenal glomerulosa such that very small changes in potassium concentration can affect aldosterone production.