Objective
The objective of this study was to test the hypothesis that a compression‐resistant bone graft augmented with recombinant human morphogenetic protein‐2 (rhBMP‐2) will promote lateral ridge ...augmentation without the use of protective mesh in a canine model.
Materials & Methods
Compression‐resistant (CR) bone grafts were evaluated in a canine model of lateral ridge augmentation. Bilateral, right trapezoidal prism‐shaped defects (13–14 mm long × 8–9 mm wide × 3–4 mm deep at the base) in 13 hounds (two defects per hound) were treated with one of four groups: (i) absorbable collagen sponge + 400 μg rhBMP‐2/ml (ACS, clinical control) protected by titanium mesh, (ii) CR without rhBMP‐2 (CR, negative control), (iii) CR + 200 μg rhBMP‐2 (CR‐L), or (iv) CR + 400 μg rhBMP‐2 (CR‐H). All animals were euthanized after 16 weeks. Ridge height and width and new bone formation were assessed by μCT, histology, and histomorphometry. The release kinetics of rhBMP‐2 from CR bone grafts in vitro and in vivo in a femoral condyle defect model in rabbits was also evaluated.
Results
All four bone grafts promoted new bone formation (11–31.6 volume%) in the lateral ridge defects. For CR grafts, ridge height and width increased in a dose‐responsive manner with increasing rhBMP‐2 concentration. Ridge height and width measured for CR‐H without the use of protective mesh was comparable to that measured for ACS with a protective mesh.
Conclusions
At the same dose of rhBMP‐2, an injectable, compression‐resistant bone graft resulted in a comparable volume of new bone formation with the clinical control (ACS). These findings highlight the potential of compression‐resistant bone grafts without the use of protective mesh for lateral ridge augmentation.
Autograft (AG) is the gold standard for bone grafts, but limited quantities and patient morbidity are associated with its use. AG extenders have been proposed to minimize the volume of AG while ...maintaining the osteoinductive properties of the implant. In this study, poly(ester urethane) (PEUR) and poly(thioketal urethane) (PTKUR) AG extenders were implanted in a 20-mm rabbit radius defect model to evaluate new bone formation and graft remodeling. Outcomes including µCT and histomorphometry were measured at 12 weeks and compared to an AG (no polymer) control. AG control examples exhibited new bone formation, but inconsistent healing was observed. The implanted AG control was resorbed by 12 weeks, while AG extenders maintained implanted AG throughout the study. Bone growth from the defect interfaces was observed in both AG extenders, but residual polymer inhibited cellular infiltration and subsequent bone formation within the center of the implant. PEUR-AG extenders degraded more rapidly than PTKUR-AG extenders. These observations demonstrated that AG extenders supported new bone formation and that polymer composition did not have an effect on overall bone formation. Furthermore, the results indicated that early cellular infiltration is necessary for harnessing the osteoinductive capabilities of AG.
The cosmopolitan, bloom‐forming diatom, Skeletonema costatum, is a prominent primary producer in coastal oceans, fixing CO2 with ribulose 1,5‐bisphosphate carboxylase/oxygenase (RubisCO) that is ...phylogenetically distinct from terrestrial plant RubisCO. RubisCOs are subdivided into groups based on sequence similarity of their large subunits (IA–ID, II, and III). ID is present in several major oceanic primary producers, including diatoms such as S. costatum, coccolithophores, and some dinoflagellates, and differs substantially in amino acid sequence from the well‐studied IB enzymes present in most cyanobacteria and in green algae and plants. Despite this sequence divergence, and differences in isotopic discrimination apparent in other RubisCO enzymes, stable carbon isotope compositions of diatoms and other marine phytoplankton are generally interpreted assuming enzymatic isotopic discrimination similar to spinach RubisCO (IB). To interpret phytoplankton δ13C values, S. costatum RubisCO was characterized via sequence analysis, and measurement of its KCO2 and Vmax, and degree of isotopic discrimination. The sequence of this enzyme placed it among other diatom ID RubisCOs. Michaelis‐Menten parameters were similar to other ID enzymes (KCO2 = 48.9 ± 2.8 μm; Vmax = 165.1 ± 6.3 nmol min−1 mg−1). However, isotopic discrimination (ε = 12k/13k − 1 × 1000) was low (18.5‰; 17.0–19.9, 95% CI) when compared to IA and IB RubisCOs (22–29‰), though not as low as ID from coccolithophore, Emiliania huxleyi (11.1‰). Variability in ε‐values among RubisCOs from primary producers is likely reflected in δ13C values of oceanic biomass. Currently, δ13C variability is ascribed to physical or chemical factors (e.g. illumination, nutrient availability) and physiological responses to these factors (e.g. carbon‐concentrating mechanisms). Estimating the importance of these factors from δ13C measurements requires an accurate ε‐value, and a mass‐balance model using the ε‐value for S. costatum RubisCO is presented. Clearly, appropriate ε‐values must be included in interpreting δ13C values of environmental samples.
Species of the genus
Bothrops induce the vast majority of snakebite envenomings in Latin America. A preclinical study was performed in the context of a regional network of public laboratories ...involved in the production, quality control and development of antivenoms in Latin America. The ability of seven polyspecific antivenoms, produced in Argentina, Brazil, Peru, Bolivia, Colombia and Costa Rica, to neutralize lethal, hemorrhagic, coagulant, defibrinogenating and myotoxic activities of the venoms of
Bothrops neuwiedi (
diporus) (Argentina),
Bothrops jararaca (Brazil),
B. neuwiedi (
mattogrossensis) (Bolivia),
Bothrops atrox (Peru and Colombia) and
Bothrops asper (Costa Rica) was assessed using standard laboratory tests. Despite differences in the venom mixtures used in the immunization of animals for the production of these antivenoms, a pattern of extensive cross-neutralization was observed between these antivenoms and all the venoms tested, with quantitative differences in the values of effective doses. This study reveals the capacity of these antivenoms to neutralize, in preclinical tests, homologous and heterologous
Bothrops venoms in Central and South America, and also highlight quantitative differences in the values of Median Effective Doses (ED50s) between the various antivenoms.
To evaluate the distribution of white matter (WM) disease in frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) and to evaluate the relative usefulness of WM and gray matter (GM) for ...distinguishing these conditions in vivo.
Patients were classified as having FTLD (n = 50) or AD (n = 42) using autopsy-validated CSF values of total-tau:β-amyloid (t-tau:Aβ(1-42)) ratios. Patients underwent WM diffusion tensor imaging (DTI) and volumetric MRI of GM. We employed tract-specific analyses of WM fractional anisotropy (FA) and whole-brain GM density analyses. Individual patient classification was performed using receiver operator characteristic (ROC) curves with FA, GM, and a combination of the 2 modalities.
Regional FA and GM were significantly reduced in FTLD and AD relative to healthy seniors. Direct comparisons revealed significantly reduced FA in the corpus callosum in FTLD relative to AD. GM analyses revealed reductions in anterior temporal cortex for FTLD relative to AD, and in posterior cingulate and precuneus for AD relative to FTLD. ROC curves revealed that a multimodal combination of WM and GM provide optimal classification (area under the curve = 0.938), with 87% sensitivity and 83% specificity.
FTLD and AD have significant WM and GM defects. A combination of DTI and volumetric MRI modalities provides a quantitative method for distinguishing FTLD and AD in vivo.
Envenoming from snakebites is an important public health issue in Brazil. In 2005, 28,597 cases were notified (15 cases/100,000 inhabitants), 87.5% due to
Bothrops and 9.2% to
Crotalus genus. ...Antivenoms available in Brazil are liquid preparations containing purified equine Fab′2. Since 1987, the National Institute for Quality Control in Health (INCQS/FIOCRUZ) has been testing all lots prior to batch release. Between 2000 and 2006, 619 lots of antivenoms were tested, comprising 2,513,690 ampoules. The potency assay was performed only for bothropic and crotalic antivenoms (485 lots corresponding to 1,866,726 ampoules) due to the unavailability of the other reference venoms. This paper aims to report the last 7-year activities of INCQS on the quality control, batch release and potency evaluation of antivenoms.
Heat capacity of poly(trimethylene terephthalate) Pyda, M.; Boller, A.; Grebowicz, J. ...
Journal of polymer science. Part B, Polymer physics,
October 1998, Letnik:
36, Številka:
14
Journal Article
Most fractures heal by a combination of endochondral and intramembranous ossification dependent upon strain and vascularity at the fracture site. Many biomaterials-based bone regeneration strategies ...rely on the use of calcium phosphates such as nano-crystalline hydroxyapatite (nHA) to create bone-like scaffolds. In this study, nHA was dispersed in reactive polymers to form composite scaffolds that were evaluated both in vitro and in vivo. Matrix assays, immunofluorescent staining, and Western blots demonstrated that nHA influenced mineralization and subsequent osteogenesis in a dose-dependent manner in vitro. Furthermore, nHA dispersed in polymeric composites promoted osteogenesis by a similar mechanism as particulated nHA. Scaffolds were implanted into a 2-mm defect in the femoral diaphysis or metaphysis of Sprague-Dawley rats to evaluate new bone formation at 4 and 8 weeks. Two formulations were tested: a poly(thioketal urethane) scaffold without nHA (PTKUR) and a PTKUR scaffold augmented with 22 wt% nHA (22nHA). The scaffolds supported new bone formation in both anatomic sites. In the metaphysis, augmentation of scaffolds with nHA promoted an intramembranous healing response. Within the diaphysis, nHA inhibited endochondral ossification. Immunohistochemistry was performed on cryo-sections of the bone/scaffold interface in which CD146, CD31, Endomucin, CD68, and Myeloperoxidase were evaluated. No significant differences in the infiltrating cell populations were observed. These findings suggest that nHA dispersed in polymeric composites induces osteogenic differentiation of adherent endogenous cells, which has skeletal site-specific effects on fracture healing.
Understanding the mechanism by which synthetic scaffolds promote new bone formation in preclinical models is crucial for bone regeneration applications in the clinic where complex fracture cases are seen. In this study, we found that dispersion of nHA in polymeric scaffolds promoted in vitro osteogenesis in a dose-dependent manner through activation of the PiT1 receptor and subsequent downstream Erk1/2 signaling. While augmentation of polymeric scaffolds with nHA enhanced intramembranous ossification in metaphyseal defects, it inhibited endochondral ossification in diaphyseal defects. Thus, our findings provide new insights into designing synthetic bone grafts that complement the skeletal site-specific fracture healing response.
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This study was designed to test the hypothesis that compression-resistant (CR) scaffolds augmented with recombinant human bone morphogenetic protein-2 (rhBMP-2) at clinically relevant doses in a ...nonhuman primate lateral ridge augmentation model enhances bone formation in a dose-responsive manner without additional protective membranes.
Defects (15 mm long × 8 mm wide × 5 mm deep) were created bilaterally in the mandibles of nine hamadryas baboons. The defect sites were implanted with poly(ester urethane) (PEUR)/ceramic CR scaffolds augmented with 0 mg/mL rhBMP-2 (CR control), 0.75 mg/mL rhBMP-2 (CR-L), or 1.5 mg/mL rhBMP-2 (CR-H). The primary outcome of ridge width and secondary outcomes of new bone formation, cellular infiltration, and integration with host bone were evaluated using histology, histomorphometry, and microcomputed tomography (micro-CT) at 16 weeks following implantation.
New bone formation in the mandible was observed in a dose-responsive manner. CR-H promoted significantly greater new bone formation compared with the CR control group. In all groups, ridge width was maintained without an additional protective membrane.
CR scaffolds augmented with a clinically relevant dose of rhBMP-2 (1.5 mg/mL) promoted significant new bone formation. These results suggest that a CR PEUR/ceramic composite scaffold without a protective membrane may be a potential new rhBMP-2 carrier for clinical use.
In September 2004, an outbreak of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI) was reported among members of a religious community. ...We conducted a retrospective cohort study on all 175 community members; performed a nasal carriage survey, and environmental swab testing. We identified 24 MRSA cases (attack rate 14%). In multivariate analysis, sauna use odds ratio (OR) 19·1, 95% confidence interval (CI) 2·7–206·1 and antimicrobial use within 12 months before infection (OR 11·7, 95% CI 2·9–47·6) were risk factors for infection. MRSA nasal carriage rate was 0·6% (1/174). Nine of 10 clinical isolates and an isolate from an administrative office within the community had the pulsed-field gel electrophoresis type USA300. Targeted hygiene improvement, wound care, and environmental cleaning were implemented. We describe the first reported outbreak of MRSA SSTI in a religious community. Adherence to appropriate personal and environmental hygiene might be critical factors in controlling transmission.
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