Osseointegration of implants with dendrimers surface characteristics installed conventionally or with Piezosurgery®. A comparative study in the dog

Aim: The first aim of the present experiment was to compare bone healing at implants installed in recipient sites prepared with conventional drills or a piezoelectric device. The second aim was to compare implant osseointegration onto surfaces with and without dendrimers coatings. Material and Methods: Six Beagles dogs were used in this study. Five implants with two different surfaces, three with a ZirTi® surface (zirconia sand blasted, acid etched), and two with a ZirTi®-modified surface with dendrimers of phosphoserine and polylysine were installed in the right side of the mandible. In the most anterior region (P2, P3), two recipient sites were prepared with drills, and one implant ZirTi® surface and one coated with dendrimers implants were installed at random. In the posterior region (P4 and M1), three recipient sites were randomly prepared: two sites with a Piezosurgery® instrument and one site with drill and two ZirTi® surface and one coated with dendrimers implants installed. Three months after the surgery, the animals were sacrificed for histological analysis. Results: No complications occurred during the healing period. Three implants were found not integrated and were excluded from analysis. However, n = 6 was obtained. The distance IS-B at the buccal aspect was 2.2 ± 0.8 and 1.8 ± 0.5 mm, while IS-C was 1.5 ± 0.9 and 1.4 ± 0.6 mm at the Piezosurgery® and drill groups, respectively. Similar values were obtained between the dendrimers-coated and ZirTi® surface implants. The BIC% values were higher at the drill (72%) compared to the Piezosurgery® (67%) sites. The BIC% were also found to be higher at the ZirTi® (74%) compared to the dendrimers-coated (65%) implants, the difference being statistically significant. Conclusion: This study has revealed that oral implants may osseointegrate equally well irrespective of whether their bed was prepared utilizing conventional drills with abundant cooling or Piezosurgery®. Moreover, the surface coating of implants with dendrimers phosphoserine and polylysine did not improve osseointegration. © 2012 John Wiley & Sons A/S.

Five Percent 5-Fluorouracil in a Cream or for Superficial Peels in the Treatment of Advanced Photoaging of the Forearms: A Randomized Comparative Study

BACKGROUND The antimetabolite 5-fluorouracil (5-FU) is used for topical treatment of actinic keratosis. Overall improvement in the skin is also observed. Additionally, 5-FU was reported to be used for superficial peels.OBJECTIVES To evaluate the efficacy and safety of 5% 5-FU cream compared with peels for photodamaged forearms.METHODS This interventional, randomized, comparative, evaluator-blind study included 32 patients with severe photoaging of forearms. The regimens comprised either application of 5% 5-FU cream everyday for 4 weeks on 1 forearm and 4 weekly peels on the other. Efficacy assessment included: clinical photodamage scores, opinion of patients and investigators, and blind photographic evaluation by independent observers. Skin biopsies were performed for histologic and immunohistochemical analysis. Safety evaluation comprised observation of adverse events.RESULTS Clinical and histologic findings confirmed the benefits of topical 5% 5-FU, in cream or peels, which improved skin appearance and decreased the dermal elastotic material. Immunohistochemistry showed reduced levels of epidermal p53 and increase in the level of procollagen I. Results were maintained after 6 months. Predictable adverse events occurred, with no differences between treatments. Patients reported better tolerability to peels.CONCLUSION Five percent 5-FU cream or peels was safe and effective for the treatment of photodamaged forearms. Decreased epidermal p53 levels and new dermal collagen were confirmed.

Multiplicity of solutions for a biharmonic equation with subcritical or critical growth

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Deproteinized Bovine Bone Mineral or Autologous Bone at Dehiscence Type Defects at Implants Installed Immediately into Extraction Sockets: An Experimental Study in Dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Early loading of 6-mm-short implants with a moderately rough surface supporting single crowns: a prospective 5-year cohort study

AimTo evaluate prospectively the clinical and radiographic outcomes after 5years of early loading of 6-mm implants with a moderately rough (SLActive((R))) surface supporting single crowns in the posterior regions.Material and methodsThirty-five consecutive patients received 40 SLActive((R)) (Straumann) 6-mm implants with a diameter of 4.1mm (n=19) or 4.8mm (n=21). Insertion torque and resonance frequency analysis (RFA) were measured at implant installation. RFA was also measured at abutment connection. SynOcta abutments were tightened with 35Ncm after 6weeks of healing, and single porcelain fuse to metal crowns was cemented within 1week. Implant survival rate and marginal bone loss were evaluated at various time intervals until 5years after loading. The clinical crown/implant ratio was calculated as well.ResultsTwo of 40 implants were lost before loading (incorporation rate 95%), and no further implant loss or technical complications were encountered during the 5-year follow-up period. A mean marginal bone loss of 0.70.6mm was found after 5years of function. The clinical crown/implant ratio increased with time from 1.6 at the delivery of the prosthesis to 2 after 5years of loading.ConclusionSix millimeter implants with a SLActive((R)) moderately rough surface supporting single crowns in the posterior region and loaded after 6-7weeks maintained full function for at least 5year with low marginal bone resorption.

Cost-Effectiveness Analysis for Surgical, Angioplasty, or Medical Therapeutics for Coronary Artery Disease 5-Year Follow-Up of Medicine, Angioplasty, or Surgery Study (MASS) II Trial

Background-The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n = 203), percutaneous coronary intervention (PCI, n = 205), or medical treatment alone (MT, n = 203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies. Methods and Results-We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19 967.00 for PCI; and $18 263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI (P<0.01). The event-free plus angina-free costs were $16 553.00, $25 831.00, and $24 614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI (P>0.05). Conclusions-In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI.

Differential response of Human Bone Marrow Stromal Cells to either TGF-β1 or to rhGDF-5

Cell therapy along with growth factor injection is currently widely investigated to restore the intervertebral disc. However, there is increasing evidence that transplanted unconditioned bone marrow-derived stromal cells (BMSCs) cannot thrive in the intervertebral disc "niche". Moreover, uncertainty exists with respect to the cell phenotype that would be suitable to inject. The intervertebral disc cell phenotype only recently has been started to be characterised using transcriptomics profiling. Recent findings suggest that cytokeratin 19 (KRT-19) could be used as a potential candidate marker for the intervertebral disc, or more specifically the nucleus pulposus cell (NPC) phenotype. We present in vitro cell culture data using alginate bead culture of primary human BMSCs exposed to the standard chondrogenic stimulus, transforming growth factor beta-1 (TGF-β), the growth and differentiation factor 5 and/or bovine NPCs to induce a potential "discogenic" pathway. Chondrogenic induction via TGF-β pathway provoked down-regulation of KRT-19 gene expression in four out of five donors after 18 days of culture, whereas KRT-19 expression remained unchanged in the "discogenic" groups. In addition, the ratio of aggrecan/collagen II gene expression showed a remarkable difference (of at least 3 magnitudes) between the chondrogenic stimulus (low ratio) and the discogenic stimulus (high ratio). Therefore, KRT-19 and aggrecan/collagen II ratio may be potential markers to distinguish chondrogenic from "discogenic" differentiation.

Six-month clinical outcomes following implantation of the bioresorbable everolimus-eluting vascular scaffold in vessels smaller or larger than 2.5 mm

We investigated the 6-month clinical outcomes after implantation of second-generation 3.0-mm bioresorbable everolimus-eluting vascular scaffolds (BVS) in small coronary vessels (<2.5 mm).

Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3-5 weeks post partum, a randomized, double-blind clinical trial

BACKGROUND: Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. METHODS: 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21-35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. RESULTS: There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). CONCLUSION: The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge.

Differential response of porcine osteoblasts and chondrocytes in cell or tissue culture after 5-aminolevulinic acid-based photodynamic therapy

OBJECTIVE: Outcome in osteochondral allografting is limited by the immunological incompatibility of the grafted tissue. Based on a resistance of chondrocytes to photodynamic therapy in cell culture it is proposed that 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) might be used to inactivate bone while maintaining viability of chondrocytes and thus immunomodulate bone selectively. METHODS: Chondrocytes and osteoblasts from porcine humeral heads were either isolated (cell culture) or treated in situ (tissue culture). To quantify cytotoxic effects of 5-ALA-PDT (0-20J/cm(2), 100mW/cm(2)) an (3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide) (MTT)-assay was used in cell culture and in situ hybridization in tissue culture to assess metabolic active cells (functional osteoblasts: colalpha(1)(I) mRNA, functional chondrocytes: colalpha(1)(II) mRNA). RESULTS: In cell culture, survival after 5-ALA-PDT was significantly higher for chondrocytes (5J/cm(2): 87+/-12% compared to untreated cells) than for osteoblasts (5J/cm(2): 12+/-11%). In tissue culture, the percentage of functional chondrocytes in cartilage showed a decrease after 5-ALA-PDT (direct fixation: 92+/-2%, 20J/cm(2): 35+/-15%; P<0.0001). A significant decrease in the percentage of bone surfaces covered by functional osteoblasts was observed in freshly harvested (31+/-3%) compared to untreated tissues maintained in culture (11+/-4%, P<0.0001), with no further decrease after 5-ALA-PDT. CONCLUSION: Chondrocytes were more resistant to 5-ALA-PDT than osteoblasts in cell culture, while in tissue culture a loss of functional chondrocytes was observed after 5-ALA-PDT. Since osteoblasts - but not chondrocytes - were sensitive to the tissue culture conditions, devitalized bone with functional cartilage might already be achieved by applying specific tissue culture conditions even without 5-ALA-PDT.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.