Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury.

Spinal cord injury (SCI) is an incurable disorder with an unmet need of an effective treatment. Recently, autologous human bone marrow-derived stem cells have shown to promote functional improvement, due to their anti-inflammatory and regenerative/apocrine properties. In this study, the primary objective was to test whether a single intrathecal injection with a 100 µL suspension of 400,000 fresh human bone marrow-derived CD34+ and an equal number of CD105+ stem cells (Neuro-Cells (NC)), one day after balloon-compression of the spinal cord, improves motor function and reduces secondary damage in immunodeficient rats. During the first 5 weeks after this intervention, NC significantly improved locomotor recovery and induced less injury-associated adverse events compared to vehicle-treated rats. Histological analysis showed that NC reduced astrogliosis, and apoptosis early after administration (day 4), but not at a later stage (day 56) after SCI. Proteomic studies (at day 56) pointed to the release of paracrine factors and identified proteins involved in regenerative processes. As stem cells seem to reach their effects in acute lesions by mainly suppressing (secondary) inflammation, it is thus realistic to expect a lower magnitude of their eventual beneficial effect in T-cell deficient rats, a fact reinforcing the robustness of Neuro-Cells efficacy. Taken together, this study indicates that an intrathecal instillation of Neuro-Cells holds great promise as a neuro-regenerative intervention in a clinical setting with acute SCI patients.

CBCT-based predictability of attachment of the neurovascular bundle to the proximal segment of the mandible during sagittal split osteotomy.

Injury to the inferior alveolar nerve (IAN) during surgery is an important complication of bilateral sagittal split osteotomy. With cone beam computed tomography, the course of the nerve and its relationship to the surrounding structures can be assessed in three dimensions. This study aims to determine whether tomography can predict attachment of the neurovascular bundle to the proximal segment of the mandible during sagittal split osteotomy (SSO). Bilateral linear measurements were taken on cross-sectional tomography images. During osteotomy, it was noted for each patient whether the neurovascular bundle was attached to the proximal segment during the split. If attached, a bone-cutting instrument or a blunt instrument was needed to free the nerve. The nerve was attached at more than one-third of operation sites (170 sites). Of these, over 65% of attached nerves (108 sites) required a bone-cutting intervention to free them from the mandible. After correcting for confounding factors, the linear distances from the buccal cortical margin of the IAN canal to the inner and outer buccal cortical margins of the mandible were important predictors of whether the IAN will be attached to the proximal segment of the mandible during SSO.

Heritability analysis of lipids and three gene loci in twins link the macrophage scavenger receptor to HDL cholesterol concentrations.

We studied 100 healthy monozygotic and 72 dizygotic twin pairs (mean age, 34 +/- 14 years) to test for genetic influences on blood lipids and to examine relevant gene loci. Total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglyceride (TG) levels were determined after a 12-hour fast. Zygosity was determined with the use of microsatellite markers. Heritability estimates were conducted by using the lisrel 8 program; a sib-pair analysis was conducted by using the sibpal program. Linear regression analyses were carried out between identical-by-descent status and squared within-pair differences of TC, LDL-C, HDL-C, and TG values. Heritability estimates of the lipid serum concentrations ranged from .58 to .66. A significant linkage relationship was found for HDL-C (P = .008) and TGs (P = .05) with D8S261 on chromosome 8p. However, no linkage was found between any of the lipid variables and the lipoprotein lipase gene locus (LPL GZ14/15 and D8S282). Because D8S261 is located approximately halfway between the LPL and macrophage scavenger receptor genes, we examined the nearby markers D8S549 and D8S1731. Linkage was found for HDL-C and D8S549 (P = .001) and for HDL-C and D8S1731 (P = .04). On the other hand, we found no linkage between the LDL receptor gene locus and LDL-C serum concentrations nor between the LPL gene locus and the various other lipid fractions. Our data suggest a significant influence of the macrophage scavenger receptor gene locus on HDL-C and weak influence on TG levels. We suggest that inherited variability in the macrophage scavenger receptor gene has an influence on serum lipid concentrations.