Type 2 diabetes has minimal effect on osseointegration of titanium implants in Psammomys obesus.

OBJECTIVES: Dental implants are routinely used with high success rates in generally healthy individuals. In contrast, their use in patients with uncontrolled diabetes mellitus (DM) remains controversial as altered bone healing around implants has been reported. The majority of reports addressing the issue of osseointegration of implants in animals were performed in beta-cell cytotoxic-induced Type I diabetes. In this study, we assessed the osseointegration of implants in Gerbil Psammomys obesus, a model of nutritionally induced Type 2 DM. MATERIALS AND METHODS: Titanium implants were inserted into the tibial medullary space of 140 male diabetic and control animals. One, 2, 4, and 8 weeks after implantation the tibias were removed for histomorphometric evaluation, which included trabecular bone volumes (TBV) and osseointegration. RESULTS: Two weeks following implantation, diabetic animals had slightly less mature bone when compared with control animals. This distinction was not present 4 weeks after implantation. Interestingly, no correlation was found between ossetointegration or TBV and glucose and insulin levels. Furthermore, no difference in osseointegration and TBV values was seen between the groups. The heterogeneity of serum glucose and insulin levels in this model and the possible role of insulin in bone metabolism are discussed. CONCLUSIONS: No significant difference in osseointegration and TBV was seen between diabetic and control P. obesus, a model of nutritionally induced Type 2 DM.

Histomorphometric study of placental villi vascular volume in toxemia and diabetes.

The quantitative changes in the vascular tree in placentas from pregnancies complicated by diabetes mellitus and preeclampsia (PE) are not well defined. The purpose of this study was to quantify placental villi cross-sectional area of capillaries assessed by a computerized morphometry system in pregnancies complicated by PE (n = 23), well-controlled pregestational diabetes mellitus (PGDM; n = 10), and healthy controls (n = 13). Our aims were to test whether villous capillarization volume was changed in PE without intrauterine growth restriction or PGDM compared with the control group and to study these effects in 3 different areas of the placenta. Examination of placentas in women with PGDM and PE revealed limited pathological changes on light microscopic examination. However, the morphometric analysis revealed a more than 5-fold decrease of villous vascular volume in PGDM compared with controls (P = .003) and a 1.6-fold decrease in the PE group that did not reach statistical significance. These findings show quantitative changes in the villous vascular tree in PGDM that are not detectable by conventional light microscopy and suggest that morphometric analysis of the capillary tree may have diagnostic importance in this entity. The findings differ significantly from those previously reported in pregestational diabetes and do not differ significantly from those reported in PE without intrauterine growth restriction.

Osteogenic growth peptide modulates fracture callus structural and mechanical properties.

The osteogenic growth peptide (OGP) is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. Recent histologic studies have shown that OGP enhances fracture healing in experimental animals. To assess the effect of systemically administered OGP on the biomechanical and quantitative structural properties of the fracture callus, the present study used an integrated approach to evaluate the early stages (up to 4 weeks) of healing of unstable mid-femoral fractures in rats, which included biomechanical, micro-computed tomographic (microCT) and histomorphometric measurements. During the first 3 weeks after fracture, all the quantitative microCT parameters increased in the OGP- and vehicle-treated animals alike. After 4 weeks, the volume of total callus, bony callus, and newly formed bone was approximately 20% higher in animals administered with OGP, consequent to a decrease in the controls. The 4-week total connectivity was 46% higher in the OGP-treated animals. At this time, bridging between the fracture ends by newly formed bone was observed predominantly in the OGP-treated fractures. After 3 and 4 weeks, the OGP-treated animals showed higher biomechanical toughness of the fracture callus as compared to the PBS controls. Significant correlations between structural and biomechanical parameters were restricted to the OGP-treated rats. These data imply that the osteogenic effect of OGP results in enhanced bridging across the fracture gap and consequently improved function of the fracture callus. Therefore, OGP and/or its derivatives are suggested as a potential therapy for the acceleration of bone regeneration in instances of fracture repair and perhaps other bone injuries.

Characterization of nerve growth factors (NGFs) from snake venoms by use of a novel, quantitative bioassay utilizing pheochromocytoma (PC12) cells overexpressing human trkA receptors.

Snake venoms are a very abundant source of nerve growth factors (NGF). NGFs of Elapidae showing 65% sequence homology with mouse or human NGF, while the Viperidae NGF shows N-glycosylation (Asn-21) typical of these mammalian NGFs. Snake NGF-induced neurite outgrowth (neurotropic activity) was measured in the past by using PC12 cell or dorsal root ganglion bioassays. The present study was aimed at comparing, by dose-response experiments, the neurotropic activity of cobra and vipera versus mammalian NGFs, by using a novel bioassay involving PC12 cells genetically engineered to overexpress NGF-trkA receptors of human origin. These cells respond to NGF by differentiation (morphologically expressed as neurite outgrowth) by a process mediated by NGF-trkA receptors. This process was evaluated by two different criteria: (1) elongation of neurites (E), and (2) Percentage of responsive cells (PRC) determined by digital acquisition of data and computer analysis. We found that snake venom NGFs were less potent than mouse NGF, and that cobra NGF was more potent than vipera NGF. These data indicate the following order of NGF activity towards recombinant human trkA receptors: recombinant human NGF>mouse NGF>cobra NGF>vipera NGF. The neurotropic efficacy of these NGFs was found to be similar, reaching 80-90% of maximal activity obtained with all NGF forms. Interestingly, cobra (but not vipera) NGF demonstrated prolonged neurotropic activity compared with mouse NGF. The results of the present study indicate that cobra and vipera venom NGFs represent natural agonists of human trkA-receptor of a lower potency, but of similar efficacy, compared with mammalian NGFs. These compounds are important pharmacological tools to characterize the trkA receptor structure-function relationship, and to develop novel neurotropic drugs.

Principles of Bone Regeneration

Principles of Bone Regeneration is a timelypublication that addresses the modern aspects of bone healing andrepair.ÿThis exciting newÿvolume detailsÿtheconvergence of the different experimental and clinical approachesdesigned for the study and treatment of bone healing in its diverseforms and under varying conditions. Bone healing is affected by amultitude of genetic, environmental, mechanical, cellular andendocrine variables which eventually lead to changes in geneexpression that enhance the guided action of osteoblasts (andchondroblasts) to lay down bone that restores, or even improves,the skeletal load bearing capacity. Recent breakthroughs inunderstanding the regulatory aspects of bone formation andresorption, in both research and clinical arenas offer newmodalities to induce, enhances and guide repair processes in bonefor the benefit of millions of patients with conditions such asnonunion fractures, critical size defects, orthodontic toothmovement, periodontal bone loss, intraosseous implants and deformedbones.