Vivosorb as a barrier membrane in rat mandibular defects. An evaluation with transversal microradiography

Vivosorb^® is a new degradable membrane composed of poly(DL-lactide--caprolactone) (PDLLCL). The aim of this study was to appraise its performance in guided bone regeneration procedures. In 192 rats a 5.0 mm defect was drilled in the mandibular angle. The defects were covered with a membrane (PDLLCL, collagen, or expanded polytetrafluoroethylene (ePTFE)) or left uncovered (control). Defect closure, mineralization and thickness of the new bone were assessed by means of transversal microradiography at three different time intervals (2, 4 and 12 weeks). The data were analysed using multiple regression analyses. The regression analyses showed significant effect modification between time and collagen and time and ePTFE for mineralization of the newly formed bone. For defect closure and bone thickness all membrane-treated groups showed effect modification between time and membrane; these effects were more significant and larger in the collagen and ePTFE groups. In the non-treated controls no effect modification was observed. The membrane groups showed significantly better results than the control groups. The ePTFE and collagen membranes performed equally well and better than the PDLLCL membrane during this experiment. It was concluded that a PDLLCL membrane is not suitable for clinical application in its current form.     

Azacitidine differentially affects CD4(pos) T-cell polarization in vitro and in vivo in high risk myelodysplastic syndromes

CD4(pos) T-cell subsets play a role in myelodysplastic syndromes (MDS) pathogenesis and may be affected upon 5-azacitidine (Aza) treatment. Aza enhanced human T(H)1 frequencies in vitro but not in vivo. The proportion of functional FoxP3(pos) regulatory T cells (Treg) was enhanced by Aza in vitro (p < 0.0002), and a modest, temporary increase was observed in vivo (p = 0.08). The overall number of T(H)17 was reduced both in vitro (p < 0.03) and in vivo (p < 0.006), indicating that Aza directly affects CD4(pos) polarization during activation in vitro. Upon in vivo treatment in high risk MDS patients, particularly the T(H)17-Treg axis is affected.     

Vivosorb, Bio-Gide, and Gore-Tex as barrier membranes in rat mandibular defects: an evaluation by microradiography and micro-CT

Objectives: The objectives of this study were to determine whether a new degradable synthetic barrier membrane (Vivosorb^®) composed of poly(dl ‐lactide‐?‐caprolactone) (PDLLCL) can be useful in implant dentistry and to compare it with collagen and expanded polytetrafluoroethylene (ePTFE) membranes. Material and methods: In 192 male Sprague–Dawley rats, a standardized 5 mm circular defect was created through the right angle of the mandible. New bone formation was evaluated by post‐mortem microradiography and micro‐CT (μCT) imaging. Four groups (control, PDLLCL, collagen, ePTFE) were evaluated at three time intervals (2, 4, and 12 weeks). In the membrane groups the defects were covered; in the control group the defects were left uncovered. Data were analysed using a multiple regression model. Results: New bone formation could be detected by post‐mortem microradiography in 130 samples and by μCT imaging in 112 samples. Bone formation was progressive in 12 weeks, when the mandibular defect was covered with a membrane. Overall, more bone formation was observed underneath the collagen and ePTFE membranes than the PDLLCL membranes. Conclusions: In contrast to uncovered mandibular defects, substantial bone healing was observed in defects covered with a PDLLCL membrane. However, bone formation in PDLLCL‐covered defects tended to be less than in the defects covered with collagen or ePTFE. The high variation in the PDLLCL samples at 12 weeks may be caused by the moderate adherence of this membrane to bone compared with collagen. These results indicate that further study is needed to optimize the properties of PDLLCL membranes.     

Individual and combined roles of CYP3A, P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) in the pharmacokinetics of docetaxel

Docetaxel is one of the most widely used anticancer drugs. A major problem with docetaxel treatment, however, is the considerable interpatient variability in docetaxel exposure. Another disadvantage of the drug is that it has a very low oral bioavailability and can, therefore, only be administered intravenously. The drug-metabolizing enzyme CYP3A and the drug transporter MDR1 (P-glycoprotein) are major determinants of docetaxel pharmacokinetics. In vitro studies have indicated that docetaxel is also a substrate for the drug transporter MRP2, but the in vivo importance of MRP2 for docetaxel is currently unknown. We, therefore, investigated the role of MRP2 in the pharmacokinetics of docetaxel by utilizing Mrp2(-/-) mice. We also generated and characterized Cyp3a/Mdr1a/b/Mrp2(-/-) combination knockout mice to get more insight into how these drug-handling systems work together in determining docetaxel pharmacokinetics. The systemic exposure in Mrp2(-/-) mice was not significantly different from wild-type, after either oral or intravenous administration. Strikingly, however, in Cyp3a/Mdr1a/b/Mrp2(-/-) mice, systemic docetaxel exposure was increased 166-fold after oral administration when compared with wild-type mice, and 2.3-fold when compared with Cyp3a/Mdr1a/b(-/-) mice. Interestingly, this 166-fold increase was disproportionate compared with that for the separate Cyp3a (12-fold) or Mdr1a/b/Mrp2 (4-fold) knockouts. The oral bioavailability was increased to 73% in the Cyp3a/Mdr1a/b/Mrp2(-/-) strain, versus only 10% in wild-type mice. Our data thus indicate that in the absence of CYP3A and Mdr1a/b activity, Mrp2 has a marked impact on docetaxel pharmacokinetics. These findings could have important implications for improving the oral bioavailability and reducing the variability in docetaxel exposure.     

Immediate dental implant placement in calvarial bone grafts to rehabilitate the severely resorbed edentulous maxilla: A prospective pilot study

Purpose

The aim of this study was to describe the surgical technique of immediate dental implant placement in calvarial grafts for augmentation of the severely resorbed maxilla and to assess the treatment results.

Intraoral myxoid nerve sheath tumour

A case of an intraoral myxoid nerve sheath tumour of the dorsum of the tongue in a 73-year-old Caucasian male is reported. This case describes the oldest patient with this pathology to date. Immunoperoxidase staining for neuron-specific enolase (NSE) and epithelial membrane antigen (EMA) expression demonstrated the perineural origin of the lesion.     

Muscle ultrasound analysis: normal values and differentiation between myopathies and neuropathies

In this study, 145 healthy adults (20 to 94 years old, 69 women) were examined using ultrasound (US) imaging to obtain reference values of muscle parameters that were previously not available. We measured biceps and quadriceps sizes and subcutaneous fat thickness. To quantify muscle aspect, we defined and calculated the muscle aspect parameters muscle density, inhomogeneity and white-area index by digital image analysis. All muscle aspect parameters were found to increase with age, which may be due to age-related muscle replacement by fatty tissue and collagen. Other age-, weight- and gender-dependencies are also discussed. The complete set of muscle parameters was used to differentiate between typical myopathies and neuropathies in a group of 32 patients (24 to 79 years old, 18 women). We were successful in almost completely separating the two types of disorders based on abnormality of muscle aspect parameters alone. These preliminary results show that this set of normal muscle parameters can be used to help diagnose neuromuscular disorders. It will also facilitate follow-up in disease progression and therapy.