Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics.

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug-delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour-killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium-doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The drug-loaded cements were tested in an in vitro model of human OS cell line SAOS-2, engineered OS cell line (SAOS-2-eGFP) and U2-OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase-3/7 activities, respectively. To determine if OS cells grown on doped-scaffolds change their migratory ability and invasiveness, a wound-healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived-mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme-linked immunosorbent assay test, and (iii) the osteogenic process was studied by real-time polymerase chain reaction array. The delivery system induced cell-killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.

In vivostudy of iron oxide-calcium phosphate composite nanoparticles for delivery to atherosclerosis.

Atherosclerosis is a macrophage-related inflammatory disease that remains a leading cause of death worldwide. Magnetic iron oxide (IO) nanocrystals are clinically used as magnetic resonance imaging contrast agents and their application as a detection agent for macrophages in arterial lesions has been studied extensively. We recently fabricated heparin-modified calcium phosphate (CaP) nanoparticles loaded with a large number of IO nanocrystals via coprecipitation from a supersaturated CaP solution supplemented with heparin and ferucarbotran (IO nanocrystals coated with carboxydextran). In this study, we further increased the content of IO nanocrystals in the heparin-modified IO-CaP composite nanoparticles by increasing the ferucarbotran concentration in the supersaturated CaP solution. The increase in nanoparticle IO content caused a decrease in particle diameter without impairing its dispersibility; the nanoparticles remained dispersed in water for up to 2 h due to electrostatic repulsion between particles due to the surface modification with heparin. The nanoparticles were more effectively taken up by murine RAW264.7 macrophages compared to free ferucarbotran without showing significant cytotoxicity. A preliminaryin vivostudy showed that the nanoparticles injected intravenously into mice delivered more IO nanocrystals to macrophage-rich carotid arterial lesions than free ferucarbotran. Our nanoparticles have potential as a delivery agent of IO nanocrystals to macrophages in arterial lesions.

Variable neuroprotective role of Filipendula ulmaria extract in rat hippocampus.

We evaluated the influence of an antioxidant-rich extract of Filipendula ulmaria L. on anxiety levels induced by nano-sized particles of different calcium phosphates. Rats in experimental groups were administered with either nano-sized hydroxyapatite, tricalcium phosphate, or amorphous calcium phosphate in the presence of Filipendula ulmaria extract. Appropriate behavioral tests were performed to assess anxiety levels, while oxidative status and apoptosis parameters were determined in the hippocampus samples. The applied calcium phosphates increased oxidative stress markers in hippocampal tissue, accompanied by an enhanced pro-apoptotic mechanism. Moreover, the hippocampal immunoreactivity for brain-derived neurotrophic factor and GABAergic-A receptors was significantly lower following calcium phosphate nanoparticles intake. The observed functional and morphological alterations in the rat hippocampus occurred simultaneously with the anxiogenic response estimated in behavioral testing. The neuroprotective effect of Filipendula ulmaria was markedly manifested by the attenuation of oxidative damage induced by amorphous calcium phosphate and enhanced anti-apoptotic action in the rat hippocampus. The increased hippocampal immunoreactivity for brain-derived neurotrophic factor, GABAergic-A receptors and significant anxiolytic-like effects of Filipendula ulmaria may suggest a beneficial role of antioxidant supplementation in preventing anxiogenic response to nano-sized calcium phosphates.

Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration.

Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-ß superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, ß-tricalcium phosphate (ß-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/ß-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/ß-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/ß-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/ß-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/ß-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/ß-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/ß-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

Effects of dietary monocalcium phosphate supplementation on the anti-oxidative capacity, anti-bacteria function in immune organs of obscure puffer (Takifugu obscurus) after infection with Aeromonas hydrophila.

The purpose of the present study was to explore the impaired anti-bacteria ability in immune organs and immune systems of obscure puffer induced by chronic dietary phosphorus (P) deficiency. Fish were fed diets supplemented with 6 g/kg P (P6) and 0 g/kg P (P0) respectively for 15 weeks, and lower final body weight, feed intake, weight gain, whole body P content and bone P content were observed in fish fed P0 diet (P < 0.05). Then the fish were continued to feed for 3 weeks and intraperitoneal injection with PBS (P6+PBS) and Aeromonas hydrophila (A.hydrophila) (P6 + A.hydrophila and P0 + A.hydrophila), and sampled at 3, 6, 12 and 24 h. The results showed that dietary P deficiency lowered survival rate, total hemocyte count, whereas enhanced ROS production and apoptosis rate of obscure puffer compared to the 6 g/kg P supplemented group after infection. Moreover, compared to the P sufficient group, puffer fish fed P deficient diet decreased the expressions of antioxidant genes catalase (cat) and glutathione reductase (gr), immune-related genes toll-like receptor 2 (tlr-2) and anti-inflammatory factors transforming growth factor ß1 (tgf-ß1) and interleukin 11 (il-11) while increased pro-inflammatory cytokines tumor necrosis factor α (tnf-α), interleukin 1ß (il-1ß) and interleukin 8 (il-8) in head kidney post-infection. In addition, dietary P deficiency decreased the hepatic gene expressions of anti-apoptotic factor B-cell lymphoma 2 (bcl-2) and bax-inhibitor 1 (bi-1), accompanied by increasing the mRNA expressions of pro-apoptotic factor caspase 3, caspase 8 and caspase 9 compared to the P sufficient group after A.hydrophila infection. In conclusion, dietary P deficiency impaired the anti-bacteria function of the immune system as well as immune organs by increasing oxidative stress and aggravating the inflammatory response and apoptosis in obscure puffer under the A.hydrophila challenge.

Chemotherapy-induced oral mucositis management: A retrospective analysis of MuGard, Caphosol, and standard supportive care measures.

BACKGROUND: Oral mucositis, a common complication of several different anticancer therapies, causes significant morbidity in cancer patients. It is characterized by the destruction of the mucosa throughout the gastrointestinal tract including the oral cavity. Limited data exist regarding the treatment of established oral mucositis with oral mucoadhesive hydrogel (MuGard) or supersaturated calcium phosphate oral rise (Caphosol) compared to standard topical therapies. OBJECTIVES: To evaluate the effects of MuGard and Caphosol compared to standard topical therapy in the treatment of established oral mucositis. METHODS: A retrospective chart review was performed including adults receiving MuGard, Caphosol, and/or standard topical therapy for the treatment of established oral mucositis while admitted to a community teaching hospital. A post hoc propensity score was used to match patients receiving newer agents (Mugard/Caphosol) to those receiving standard topical therapy (ST). RESULTS: One hundred and forty-seven patients were included for analysis (125 ST, 15 MuGard, 7 Caphosol). From this population, 14 patients in each group were matched. The primary endpoint of median change in average daily pain score at days 3 and 7, compared to baseline, demonstrated no difference between matched groups at day 3 (ST 0, MuGard/Caphosol 0.18, p = 0.830) or day 7 (ST 0, MuGard/Caphosol 0.8, p = 0.494). No differences were noted between groups in opioid usage, oral mucositis symptom duration or progression, or incidence of documented infection. CONCLUSION: MuGard and Caphosol did not demonstrate any benefits compared to standard topical therapy at reducing pain scores or increasing mucosal recovery in the treatment of oral mucositis.

Self-healing and injectable hybrid hydrogel for bone regeneration of femoral head necrosis and defect.

BACKGROUND: HA modified by bisphosphonate (BP) (HA-BP) was synthesized by chemical reaction and possessed promising properties such as self-healing, injection ability, and strong adhesion. The main aim of this study was to confirm its role in promoting osteogenic differentiation in vitro and bone regeneration in vivo. METHODS: The cell biocompatibility of this material was determined using the CCK-8 assay. Alkaline phosphatase (ALP), osteocalcin (OT), vascular endothelial growth factor (VEGF), and collagen I were assessed by quantitative real-time polymerase chain reaction (Q-PCR) in the treated group. The number and density of calcium nodules and ALP were evaluated by Alizarin Red staining and ALP staining. We have successfully developed an animal model simulating osteonecrosis of the femoral head (ONFH). Utilizing this animal model, the impact of HA-BP/CaP on bone formation was assessed. The amount of bone regeneration at 1 and 2 months after HA-BP/CaP injection was estimated by micro-computed tomography (micro-CT) analysis and H&E, collagen I, and periostin staining. RESULTS: The number of cells gradually increased in the experimental group over time and was close to that of the blank control group. ALP, collagen I, and VEGF expression was significantly higher in the experimental group than in the blank group (VEGF, ALP, both **p < 0.01; collagen I, ***p<0.001). In addition, the number and density of calcium nodules and ALP was clearly greater in the material group than in the control group. The quantification analysis showed that the mineral contents of regenerated bone at 1 and 2 months after HA-BP/CaP injection were significantly greater than those in the control group, according to micro-CT evaluation (**p<0.01). The amount of organic components in the HA-BP/CaP group was greater than that in the control group after decalcification and H&E staining. In addition, collagen I and periostin staining further confirmed the results of H&E staining. CONCLUSION: This material can boost proliferation and osteogenic differentiation of MC3T3-E1 cells in vitro. It can intensely accelerate bone regeneration in vivo, which is a promising strategy for tissue engineering.

Osteoclast-Responsive, Injectable Bone of Bisphosphonated-Nanocellulose that Regulates Osteoclast/Osteoblast Activity for Bone Regeneration.

An injectable bone may serve as a minimally invasive therapy for large orthopedic defects and osteoporosis and an alternative to allografting and surgical treatment. However, conventional bone substitutes lack the desirable biodegradability, bioresponsibility, and functionality to regulate the bone regeneration process. Here, we report an injectable, bioresponsive bone composed of bisphosphonate-modified nanocellulose (pNC) as a bone substitute for bone regeneration. Composites composed of nanofibrillated cellulose and ß-tricalcium phosphate (ß-TCP) mimic bone structures in which apatite reinforces collagen fibrils. Bisphosphonate groups on nanocellulose provide reversible, physical cross-linking with ß-TCP, apatite formation, binding property to bone, and pH responsiveness. When the pH drops to ∼4.5, which corresponds to an osteoclast-induced pH decrease, pNC-ß-TCP composite degrades and releases pNC. pNC suppresses osteoclast formation and pit formation. This osteoclast-responsive property allows for controlling the degradation rate of the composite. Moreover, the composite of pNC, α-tricalcium phosphate (α-TCP), and ß-TCP enhances osteoblast differentiation. This injectable bone substitute of pNC that regulates osteoclast/osteoblast activity has enormous potential for the treatment of bone diseases and prevention of locomotive syndrome.

Local administration of aspirin with ß-tricalcium phosphate/poly-lactic-co-glycolic acid (ß-TCP/PLGA) could enhance osteoporotic bone regeneration.

Composite materials ß-tricalcium phosphate (ß-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into ß-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified ß-TCP (TP) was prepared by mixing sieved granules of ß-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and ß-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/ß-TCP/ASP occured in a dose-dependent manner.

Nd:YAG laser and calcium sodium phosphosilicate prophylaxis paste in the treatment of dentin hypersensitivity: a double-blind randomized clinical study.

AIM: This double-blind, placebo-controlled, randomized clinical trial evaluated the effectiveness of Nd:YAG laser and a calcium sodium phosphosilicate-containing paste (NovaMin®) in the treatment of cervical dentin hypersensitivity (CDH). MATERIALS AND METHODS: Seventy patients were randomly allocated into the following experimental groups: control-placebo, calcium sodium phosphosilicate paste (NovaMin®), and Nd:YAG laser (1 W, 10 Hz, 85 J/cm2). Pain was evaluated by means of a visual analog pain scale (VAS) after evaporative stimulation with a jet of air and tactile stimulation with an exploratory probe, before treatment (baseline) and after 5 min, 1week, and 4 weeks. When patients presented more than one tooth with CDH, the mean of the values obtained was calculated. Irradiation with Nd:YAG laser was performed twice in the mesial-distal and twice in the occlusal-gingival direction. The NovaMin®-containing paste was applied with a rubber cup at low speed for 60 s. Patients of the placebo group received simulations of the two treatments. As the data presented normal distribution, the two-way ANOVA repeated measures test was used. RESULTS: In all the experimental times, reduction in pain was demonstrated in comparison with baseline for all treatments (p < 0.05); however, there was no difference among the experimental groups in any of the time intervals evaluated (p > 0.05). CONCLUSION: All treatments were equally effective in reducing the pain of CDH. CLINICAL RELEVANCE: Nd:YAG laser irradiation and the calcium sodium phosphosilicate paste could reduce the symptoms of CDH; thus, they stand out as viable alternatives for the treatment of this condition.

Escherichia coli-derived BMP-2-absorbed ß-TCP granules induce bone regeneration in rabbit critical-sized femoral segmental defects.

PURPOSE: This study investigated whether Escherichia coli-derived bone morphogenetic protein (BMP)-2 (E-BMP-2) adsorbed onto ß-tricalcium phosphate (ß-TCP) granules can induce bone regeneration in critical-size femoral segmental defects in rabbits. METHODS: Bone defects 20 mm in size and stabilized with an external fixator were created in the femur of New Zealand white rabbits, which were divided into BMP-2 and control groups. E-BMP-2-loaded ß-TCP granules were implanted into defects of the BMP-2 group, whereas defects in the controls were implanted with ß-TCP granules alone. At 12 and 24 weeks after surgery, radiographs were obtained of the femurs and histological and biomechanical assessments of the defect area were performed. Bone regeneration was quantified using micro-computed tomography at 24 weeks. RESULTS: Radiographic and histologic analyses revealed bone regeneration in the BMP-2 group but not the control group; no fracturing of newly formed bone occurred when the external fixator was removed at 12 weeks. At 24 weeks, tissue mineral density, the ratio of bone volume to total volume, and volumetric bone mineral density of the callus were higher in the BMP-2 group than in control animals. In the former, ultimate stress, extrinsic stiffness, and failure energy measurements for the femurs were higher at 24 weeks than at 12 weeks. CONCLUSION: E-BMP-2-loaded ß-TCP granules can effectively promote bone regeneration in long bone defects.

Influenza A(H5N1) Virus Subunit Vaccine Administered with CaPNP Adjuvant Induce High Virus Neutralization Antibody Titers in Mice.

The highly pathogenic avian influenza H5N1 virus continues to spread globally in domestic poultry with sporadic transmission to humans. The possibility for its rapid transmission to humans raised global fears for the virus to gain capacity for human-to-human transmission to start a future pandemic. Through direct contact with infected poultry, it caused the largest number of reported cases of severe disease and death in humans of any avian influenza strains. For pandemic preparedness, use of safe and effective vaccine adjuvants and delivery systems to improve vaccine efficacy are considered imperative. We previously demonstrated CaPtivate's proprietary CaP nanoparticles (CaPNP) as a potent vaccine adjuvant/delivery system with ability to induce both humoral and cell-mediated immune responses against many viral or bacterial infections. In this study, we investigated the delivery of insect cell culture-derived recombinant hemagglutinin protein (HA) of A/H5N1/Vietnam/1203/2004 virus using CaPNP. We evaluated the vaccine immunogenicity in mice following two intramuscular doses of 3 µg antigen combined with escalating doses of CaPNP. Our data showed CaPNP-adjuvanted HA(H5N1) vaccines eliciting significantly higher IgG, hemagglutination inhibition, and virus neutralization titers compared to non-adjuvanted vaccine. Among the four adjuvant doses that were tested, CaPNP at 0.24% final concentration elicited the highest IgG and neutralizing antibody titers. We also evaluated the inflammatory response to CaPNP following a single intramuscular injection in guinea pigs and showed that CaPNP does not induce any systemic reaction or adverse effects. Current data further support our earlier studies demonstrating CaPNP as a safe and an effective adjuvant for influenza vaccines.

Effects of different anti-caries agents on microhardness and superficial microstructure of irradiated permanent dentin: an in vitro study.

BACKGROUND: To compare different anti-caries agents on microhardness and micromorphology of irradiated permanent dentin in vitro, and try to find the most effective agent to prevent radiation-dentin-destruction. METHODS: A total of 120 dentin samples were prepared from 60 human teeth and randomly divided into 8 groups (n = 15), [ (1)] blank control [2]; irradiation control [3]; irradiation+ fluoride [4]; irradiation+ casein phosphate polypeptide-amorphous calcium phosphate (CPP-ACP) [5]; irradiation+ CPP-ACP+ fluoride [6]; irradiation+ infiltration resin [7]; irradiation+ infiltration resin+ fluoride [8]; irradiation+ infiltration resin+ CPP-ACP. Seven samples of each groups were chosen randomly for microhardness test and eight for scanning electron microscope observation. RESULTS: A decrease of microhardness (P < 0.05) and an obvious morphological change were presented on dentin surface after radiotherapy. After applications of anti-caries agents, the morphological destructions were effectively restored. The infiltration resin plus fluoride group (56.00 ± 4.02 Kg/mm2), infiltration resin plus CPP-ACP group (56.05 ± 3.69 Kg/mm2), infiltration resin group (54.70 ± 4.42Kg/mm2) and CPP-ACP plus fluoride group (53.84 ± 6.23Kg/mm2) had the highest dentin microhardness value after radiotherapy, and no statistically significant difference were found between them. CONCLUSIONS: Infiltration resin, CPP-ACP, fluoride and their pairwise combination can effectively prevent radiation-dentin-destruction. Among them, infiltration resin with CPP-ACP, infiltration resin with fluoride, CPP-ACP with fluoride, and infiltration resin have the most protective effects on irradiation-dentin-destructions.

Magnetic Composite Scaffolds for Potential Applications in Radiochemotherapy of Malignant Bone Tumors.

Background and objectives: Cancer is the second leading cause of death globally, an alarming but expected increase. In comparison to other types of cancer, malignant bone tumors are unusual and their treatment is a real challenge. This paper's main purpose is the study of the potential application of composite scaffolds based on biopolymers and calcium phosphates with the inclusion of magnetic nanoparticles in combination therapy for malignant bone tumors. Materials and Methods: The first step was to investigate if X-rays could modify the scaffolds' properties. In vitro degradation of the scaffolds exposed to X-rays was analyzed, as well as their interaction with phosphate buffer solutions and cells. The second step was to load an anti-tumoral drug (doxorubicin) and to study in vitro drug release and its interaction with cells. The chemical structure of the scaffolds and their morphology were studied. Results: Analyses showed that X-ray irradiation did not influence the scaffolds' features. Doxorubicin release was gradual and its interaction with cells showed cytotoxic effects on cells after 72 h of direct contact. Conclusions: The obtained scaffolds could be considered in further studies regarding combination therapy for malignant bone tumors.

Caries-Preventive Effect of NaF, NaF plus TCP, NaF plus CPP-ACP, and SDF Varnishes on Sound Dentin and Artificial Dentin Caries in vitro.

The aim of this study was to compare the caries-preventive effect of different fluoride varnishes on sound dentin as well as on artificial dentin caries-like lesions. Bovine dentin specimens (n = 220) with one sound surface (ST) and one artificial caries lesion (DT) were prepared and randomly allocated to 11 groups. The interventions before pH cycling were as follows: application of a varnish containing NaF (22,600 ppm F-; Duraphat [NaF0/NaF1]), NaF plus tricalcium phosphate (22,600 ppm F-; Clinpro White Varnish Mint [TCP0/TCP1]), NaF plus casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP; 22,600 ppm F-; MI Varnish [CPP0/CPP1]), or silver diamine fluoride (SDF; 35,400 ppm F-; Cariestop 30% [SDF0/SDF1]) and no intervention (NNB/N0/N1). During pH cycling (14 days, 6 × 120 min demineralization/day) half of the specimens in each group were brushed (10 s; 2 times/day) with either fluoride-free ("0"; e.g., TCP0) or 1,100 ppm F- ("1"; e.g., TCP1) dentifrice slurry. In another subgroup, the specimens were pH cycled but not brushed (NNB). Differences in integrated mineral loss (ΔΔZ), lesion depth (ΔLD), and colorimetric values (ΔΔE) were calculated between the values after initial demineralization and those after pH cycling, using transversal microradiography and photographic images. After pH cycling, no discoloration could be observed. Furthermore, NNB, N0, and N1 showed significantly increased ΔZDT/LDDT and ΔZST/LDST values, indicating further demineralization. In contrast, CPP0, CPP1, SDF0, and SDF1 showed significantly decreased ΔZDT/LDDT values, indicating remineralization (p ≤ 0.004; paired t test). CPP0, CPP1, SDF0, and SDF1 showed significantly higher changes in ΔΔZDT/ΔLDDT and ΔΔZST/ΔLDST than NNB, N0, and N1 (p < 0.001; Bonferroni post hoc test). In conclusion, under the conditions chosen, all fluoride varnishes prevented further demineralization. However, only NaF plus CPP-ACP and SDF could remineralize artificial dentin caries-like lesions under net-demineralizing conditions, thereby indicating that NaF plus CPP-ACP and SDF may be helpful to high-caries-risk patients.

Hip osteonecroses treated with calcium sulfate-calcium phosphate bone graft substitute have different results according to the cause of osteonecrosis: alcohol abuse or corticosteroid-induced.

INTRODUCTION: The aim of the study was to assess the factors influencing the final results of treatment of the femoral head osteonecrosis (ONFH) with core decompression and bone substitute grafting. The special interest was focused on comparison between alcohol- and steroid-induced ONFHs. MATERIAL AND METHODS: In this prospective study, a total of 53 patients (58 hips) in the mean age of 35.5 years were included: 29 had a history of alcohol use (32 hips) and 24 of steroid use (26 hips). The mean follow-up was 4.2 years (minimum 3 years). RESULTS: At last follow-up, significant improvements were noted in the Harris Hip Score (HHS) (mean 44.0 vs 55.9 points, p < 0.00002) and VAS scores (mean 7.0 vs 5.8 points, p < 0.0002) for the whole ONFH cohort, comparing to pre-operative status. The degree of improvement did not differ between Ficat and Arlet grade II and grade III (mean 14.9 vs 6.2 points, respectively, p = 0.1). No change was found between the final and initial results in this group in the steroid group (HHS mean 42.2 vs 45.5 points, p = 0.5 and VAS mean 6.8 vs 6.5 points, p = 0.5), but the improvement was noted in the alcohol group (HHS mean 45.5 vs 64.4 points, p < 0.0001; VAS mean 7.1 vs 5.2 points, p < 0.0001) comparing to pre-operative status. CONCLUSIONS: Presented treatment of ONFH significantly improves hip function, offers pain reduction, and gives similar functional improvement for hips scoring grade II and III on the Ficat and Arlet scale. A good response to operative treatment is seen in patients with alcohol-induced ONFH, but not in those with steroid-induced ONFH.

Periodontal regeneration induced by porous alpha-tricalcium phosphate with immobilized basic fibroblast growth factor in a canine model of 2-wall periodontal defects.

We evaluated the effect of porous alpha-tricalcium phosphate (α-TCP) with immobilized basic fibroblast growth factor (bFGF) on periodontal regeneration in a canine model of 2-wall periodontal defects. Identical bone defects were made in the canine mandible; six defects in each animal were filled with porous α-TCP with bFGF bound via heparin (bFGF group), and the remaining defects were filled with unmodified porous α-TCP (control group). Micro-computed tomography and histological evaluation were performed at 2, 4, and 8 weeks post-implantation. The bone mineral content of the bFGF group was higher than that of the control group at 2 and 4 weeks (p < 0.05). Histological evaluation at 2 weeks post-implantation revealed degradation of the porous α-TCP, and bone had formed on the surface of α-TCP particles in the bFGF group. Some of these collagen fibers connected the newly formed cementum with the alveolar bone, revealing the formation of new periodontal ligaments with Sharpey's fibers. At 8 weeks, continuous cortical bone with a Haversian structure covered the top of the bone defects in the bFGF group. These findings indicate that porous α-TCP with immobilized bFGF could promote periodontal regeneration at the early regeneration phase in a canine model of 2-wall periodontal defects.

Renal phosphorus excretion in adult healthy cats after the intake of high phosphorus diets with either calcium monophosphate or sodium monophosphate.

Renal and faecal phosphorus excretion of adult healthy European shorthaired cats after the intake of high phosphorus diets (meat/rice based) with either calcium monophosphate (HP-CaP) or sodium monophosphate (HP-NaP) as main phosphorus source was compared. The control diets (CON-CaP and CON-NaP, respectively) did not contain any added phosphorus. Calcium/phosphorus ratio was adjusted to 1.3/1 by adding calcium carbonate. Twenty-three cats were available for the trials. All cats were fed the control diets for 29 days; then, the HP diets were tested for 29 days against controls in a crossover design. Faeces and urine were collected in the last 10 days of each trial. Phosphorus in food, faeces and urine was measured by photometry after wet digestion. Phosphorus intake amounted to 84 ± 10 mg/kg body weight (BW) in CON-NaP (n = 13) and to 74 ± 7 in CON-CaP (n = 12). In the HP groups, the intake was 255 ± 34 mg/kg BW (HP-NaP; n = 13) and 216 ± 20 mg/kg BW (HP-CaP; n = 12). The sodium monophosphate in group HP-NaP led to a higher renal phosphorus excretion (83 ± 15 mg/kg BW) than the calcium monophosphate (25 ± 5 mg/kg BW; p < 0.05), even though the apparent phosphorus digestibility was higher in HP-CaP than in HP-NaP (p < 0.05). Faecal calcium excretion was strictly correlated to faecal phosphorus excretion (r2  = 0.98). The same was true for calcium and phosphorus balance (r2  = 0.89). In group HP-NaP, seven of 13 cats showed glucosuria. By contrast, in HP-CaP glucosuria was not observed. Highly water-soluble inorganic phosphorus sources such as sodium phosphate are likely to lead to phosphaturia and may present a risk for renal health of cats.

Minimally invasive opening wedge tibia outpatient osteotomy, using screw-to-plate locking technique and a calcium phosphate cement.

Medial knee osteoarthritis on angular varus deformity of a lower limb is very common. Open-wedge high tibial osteotomy is a treatment of choice if cartilage is not excessively worn (Allback 1 or 2). The technique based on a plate fixation and the bone defect filled with calcium phosphate cement is thoroughly described. Data at 1, 3, 6 months and 1 year of a 19 cases continuous and prospective series are collected and analysed. Mean age at the time of operation was 55 years. The average preoperative varus deformity was 5° and corrected to an average postoperative valgus of 4° (range 3°-6°). Each control includes the collection of eventual complications, the measurement of health status (quality of life and functional scores) and antero-posterior and lateral X-rays. All osteotomies were considered healed at 6 weeks without any correction loss except one, probably result of a technical error. There was no difference in clinical and functional results between the group and the literature, but the final result occurred earlier in the treatment when the bone defect was filled with either calcium phosphate cement. Faster recovery involved no specific complication and enabled outpatient treatment in a majority of patients.

[Oral fluid indicators dynamics in pregnant women by topical calcium-phosphate-fluoride gel application]. / Izuchenie pokazatelei rotovoi zhidkosti beremennykh pri mestnom primenenii trekhkomponentnogo kal'tsii-fosfat-ftorsoderzhashchego gelia kak sredstva profilaktiki kariesa.

In this article the most significant oral fluid indicators in pregnant women have been studied before and after the caries prevention course with using the ternary calcium phosphate-fluoride-containing gel. The topical application of the gel has been established to result in improving the majority of studied oral fluid parameters values. In addition the probability risk of the oral fluid indicators impact on the dental caries growth rate was assessed in the paper. Herewith the influence of the same oral fluid parameters on the dental caries growth intensity has been proved to be probably different before and after carrying out the local prophylactic caries impacts.