Cytotoxicity and biocompatibility of a new bioceramic endodontic sealer containing calcium hydroxide

Abstract: This study evaluated the cytotoxicity and biocompatibility of a new bioceramic endodontic sealer (i.e., Sealer Plus BC) in comparison with those of MTA Fillapex and AH Plus. L929 fibroblasts were cultured and Alamar Blue was used to evaluate cell viability of diluted extracts (1:50, 1:100, and 1:200) from each sealer at 24 h. Polyethylene tubes that were filled with material or empty (as a control) were implanted in the subcutaneous tissue of rats. The rats were killed after 7 and 30 d (n = 8), and the tubes were removed for histological analysis. Parametric data was analyzed using a one-way ANOVA test, and nonparametric data was analyzed via the Kruskal-Wallis test followed by the Dunn test (p < 0.05). A reduction in cell viability was observed in the extracts that were more diluted for Sealer Plus BC when compared to that of Control and AH Plus (p < 0.05). However, the 1:50 dilution of the Sealer Plus BC was similar to that of the Control (p > 0.05). Conversely, more diluted extracts of MTA Fillapex (1:200) and AH Plus (1:100 and 1:200) were similar to the Control (p > 0.05). Histological analysis performed at 7 d did not indicate any significant difference between tissue response for all materials, and the fibrous capsule was thick (p > 0.05). At 30 d, Sealer Plus BC was similar to the Control (p > 0.05) and MTA Fillapex and AH Plus exhibited greater inflammation than the Control (p < 0.05). The fibrous capsule was thin for the Control and for most specimens of Sealer Plus BC and AH Plus. Thus, Sealer Plus BC is biocompatible when compared to MTA Fillapex and AH Plus, and it is less cytotoxic when less-diluted extracts are used.

Comparative Efficacy and Safety of Phosphate Binders in Hyperphosphatemia Patients With Chronic Kidney Disease.

BACKGROUND: In this study, we coordinated a network meta-analysis to establish the efficacy and safety of different agents used in the treatment of hyperphosphatemia patients with chronic kidney disease. METHODS: PubMed, CNKI, and Embase were systematically searched to retrieve relevant studies. Outcomes were presented by mean differences, odds ratios, and corresponding 95% credible intervals for continuous outcomes and binary outcomes, respectively. Each therapy was ranked according to the value of surface under the cumulative ranking curve. Consistencies between direct and indirect comparisons were assessed with a node-splitting plot. RESULTS: In terms of efficacy end points (including levels of serum phosphate, serum calcium, serum intact parathyroid hormone, and serum calcium × phosphorus product), all 7 kinds of agents outperformed or performed at least equally to placebo, with iron-based phosphate-binding agents being potentially the most effective. As for safety end points (including mortality, adverse events, and all-cause discontinuation), almost all agents were equivalent in term of mortality and all-cause discontinuation except in the comparison between iron-based phosphate-binding agents and placebo. Meanwhile, iron-based phosphate-binding agents colestilan and nicotinic acid performed poorly compared with placebo in terms of adverse events. Furthermore, iron-based phosphate-binding agents were potentially the safest agents followed sequentially by calcium-based phosphate-binding agents and placebo. CONCLUSION: Iron-based phosphate-binding agents were the preferable agents when considering efficacy and safety simultaneously.

Repeated measurements of blood lactate concentration as a prognostic marker in horses with acute colitis evaluated with classification and regression trees (CART) and random forest analysis.

The objective of this study was to investigate the prognostic value of single and repeated measurements of blood l-lactate (Lac) and ionised calcium (iCa) concentrations, packed cell volume (PCV) and plasma total protein (TP) concentration in horses with acute colitis. A total of 66 adult horses admitted with acute colitis (<24 h) to a referral hospital in the 2002-2011 period were included. The prognostic value of Lac, iCa, PCV and TP recorded at admission and 6 h post admission was analysed with univariate analysis, logistic regression, classification and regression trees, as well as random forest analysis. Ponies and Icelandic horses made up 59% of the population, whilst the remaining 41% were horses. Blood lactate concentration at admission was the only individual parameter significantly associated with probability of survival to discharge (P < 0.001). In a training sample, a Lac cut-off value of 7 mmol/L had a sensitivity of 0.66 and a specificity of 0.92 in predicting survival. In independent test data, the sensitivity was 0.69 and the specificity was 0.76. At the observed survival rate (38%), the optimal decision tree identified horses as non-survivors when the Lac at admission was ≥4.3 mmol/L and the Lac 6 h post admission stayed at >2 mmol/L (sensitivity, 0.72; specificity, 0.8). In conclusion, blood lactate concentration measured at admission and repeated 6 h later aided the prognostic evaluation of horses with acute colitis in this population with a very high mortality rate. This should allow clinicians to give a more reliable prognosis for the horse.

Bioactivity Potential of EndoSequence BC RRM Putty.

INTRODUCTION: The aim of this study was to characterize and assess the interaction of EndoSequence BC RRM putty (Brasseler USA, Savannah, GA) in contact with blood and simulated body fluid. Tricalcium silicate-based materials are in contact with blood and tissue fluids during and after their setting. These materials are hydraulic; thus, their properties improve in moist conditions. However, specific environmental conditions may modify the material setting. METHODS: EndoSequence BC RRM putty was characterized by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction analysis. This was done before setting and after contact with water, Hank's balanced salt solution, and heparinized whole blood. Furthermore, characterization of an explanted material from a failed root-end surgery was performed. RESULTS: The EndoSequence BC RRM putty was composed of tricalcium silicate, tantalum oxide, and zirconium oxide. The tricalcium silicate reaction led to the formation of calcium hydroxide, and this was evident over the putty in contact with water and Hank's balanced salt solution. In the latter case, there was also the formation of globular crystals synonymous with hydroxyapatite formation. The material in contact with blood exhibited a poorly crystalline surface with additional peaks for calcium, phosphorus, and chlorine, whereas the material retrieved from the failed root-end surgery had deposition of calcium carbonate on its surface. CONCLUSIONS: The environmental conditions affect the hydration of the EndoSequence RMM putty and consequentially the material interaction with the environment. However, in vitro material assessment may not be representative of the clinical situation because carbon dioxide present in vivo leads to the formation of calcium carbonate rather than the hydroxyapatite reported in in vitro studies.

In vivo study of osteogenerating properties of calcium-phosphate coating on titanium alloy Ti-6Al-4V.

The method of formation of bioactive calcium-phosphate coating on medical titanium alloy Ti-6Al-4V (3.5-5.3% V; 5.3-6.8% Al; balance -Ti) by plasma electrolytic oxidation (PEO) has been developed. Evaluation of osteogenerating properties of the coating at fractures of the shaft of the femur on Wistar line laboratory rats has been performed. It has been established that the calcium-phosphate PEO coating accelerates osteogenesis and promotes the formation of a pronounced periosteal callus in the fracture area. The presence of calcium phosphates in the PEO coating surface layer significantly accelerates the growth of bone tissue on the titanium surface.

Characteristics of 22q 11.2 deletion syndrome undiagnosed until adulthood: an example suggesting the importance of psychiatric manifestations.

Patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit various combinations of signs and symptoms including facial dysmorphism, thymus absence, hypoparathyroidism, cellular immunodeficiency and cardiac abnormalities caused by microdeletion of chromosome 22q11.2. Most cases are diagnosed during post-natal cardiac evaluation, though some are diagnosed at later stages. We report the case of a 39-year-old man with 22q11.2DS presenting with seizure due to tardily manifested hypocalcaemia and anxiety disorder. Our experience suggests that 22q11.2DS patients lacking fatal or well-recognised manifestations such as cardiac defects, immunodeficiency and facial dysmorphism tend to survive without medical attention, and are therefore overlooked. Recognition of the age-related variance of the manifestations, and specifically of tardily manifested hypocalcaemia and psychiatric or developmental disorders as manifestations of 22q11.2DS in adulthood, is important for diagnosis and can also help us provide appropriate medical and psychosocial support for newly diagnosed 22q11.2DS patients in adolescence or adulthood and their families.

Oxidant/antioxidant system markers and trace element levels in children with nutritional rickets.

OBJECTIVE: To determine the oxidative stress and trace element levels in vivo in patients with nutritional rachitism associated with vitamin D deficiency. MATERIALS AND METHOD: A total of 30 patients, 18 males and 12 females, were included in the study. Age, sex, medical history, vital, and physical examination findings of each patient documented at presentation were recorded. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels, as well as oxidant and antioxidant system parameters and trace element levels were studied. After being diagnosed with rachitism, the patients were administered a single dose of 300,000 IU vitamin D by intramuscular injection. The same analyses were repeated post-treatment. Thirty children with normal anthropometric measurements were included as the control group. The analyses described above were performed only once for the control group. RESULTS: Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels were different between the controls and children in the patient group (p<0.001). Analysis of trace element levels demonstrated markedly lower pretreatment zinc levels for the patient group compared to the controls, with a statistically significant difference (p=0.001). Comparison of pretreatment oxidant and antioxidant system markers between the patient and control groups demonstrated higher values for vitamin C, ß-carotene, reduced glutathione, and superoxide dismutase in the control group, whereas MDA was higher in the patient group. CONCLUSION: The present study demonstrated increased oxidative stress, reduced antioxidant defence system in patients with nutritional rachitism, with reduced oxidative stress and a pronounced improvement in the antioxidant system with vitamin D treatment.

Effects of lactate consumption on blood bicarbonate levels and performance during high-intensity exercise.

The authors sought to determine the effects of oral lactate consumption on blood bicarbonate (HCO(3)-) levels, pH levels, and performance during high-intensity exercise on a cycle ergometer. Subjects (N = 11) were trained male and female cyclists. Time to exhaustion (TTE) and total work were measured during high-intensity exercise bouts 80 min after the consumption of 120 mg/kg body mass of lactate (L), an equal volume of placebo (PL), or no treatment (NT). Blood HCO(3)- increased significantly after ingestion of lactate (p < .05) but was not affected in PL or NT (p > .05). No changes in pH were observed as a result of treatment. TTE and total work during the performance test increased significantly by 17% in L compared with PL and NT (p = .02). No significant differences in TTE and total work were seen between the PL and NT protocols (p = .85). The authors conclude that consuming 120 mg/kg body mass of lactate increases HCO(3)- levels and increases exercise performance during high-intensity cycling ergometry to exhaustion.

[Effects of magnesium supplementation on calcium and magnesium levels, and redox homeostasis in normolipidemic and food-induced hyperlipidemic rats]. / Magnéziumpótlás hatása a kalcium- és magnéziumszintekre, valamint a redox-homeosztázisra normolipidaemiás és alimentárisan eloidézett hyperlipidaemiás patkányokban.

UNLABELLED: Magnesium supplementation is quite popular because of intention of health and healthy lifestyle. However, there is no information on the metabolic effects of magnesium supplementation in healthy people and in different diseases. AIMS: Authors examined the effects of magnesium-malate on calcium, magnesium levels, and antioxidant parameters in normolipidemic and hyperlipidemic rats. METHODS: Male Wistar rats (n = 40; 150-200 g) were divided into 4 groups (control, control-treated, hyperlipidemic, hyperlipidemic-treated). Rats in the control and control-treated groups were fed with normal diet, while hyperlipidemic and hyperlipidemic-treated groups were fed with fat rich diet (2% cholesterol, 20% sunflower oil, 0.5% cholic acid). After the 9-day-long diet the following parameters were measured: routine laboratory parameters with automatic analysator, metal content using ICP-OES, and redox-parameters using spectrophotometric and luminometric methods. RESULTS: Magnesium-malate failed to produce significant changes in the measured parameters in control animals in most cases. Magnesium-malate decreased significantly serum glucose concentration, alkaline phosphatase and amylase activities in the hyperlipidemic group. Significantly low induced chemiluminescent activity was measured in the plasma and erythrocytes of hyperlipidemic group. The magnesium supplementation did not increase significantly magnesium concentration in different organs although the calcium/magnesium concentration ratio was decreased. CONCLUSIONS: In control animals there was no significant change in the measured parameters in most cases after dietary supplementation with a large amount of magnesium for a short period of time, but magnesium supplementation affected the metal homeostasis, routine laboratory parameters and redox system in hyperlipidemic animals. Although several changes were favorable, it should be emphasized that magnesium supplementation must be applied watchfully particularly in metabolic diseases.

A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease.

BACKGROUND: Hyperphosphatemia in patients with chronic kidney disease (CKD) contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. METHODS: In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR < 30 mL/min/1.73 m² and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH) levels. RESULTS: At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04). The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p < 0.001) and iPTH was significantly lower in the calcium acetate group compared to placebo (150 ± 157 vs. 351 ± 292 pg/mL respectively; p < 0.001). At 12 weeks, the proportions of subjects who had hypocalcemia were 5.4% and 19.5% for the calcium acetate and the placebo groups, respectively, while the proportions of those with hypercalcemia were 13.5% and 0%, respectively. Adverse events did not differ between the treatment groups. CONCLUSIONS: In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00211978.

[Osteopenia in children with juvenile idiopathic arthritis]. / Osteopenia la copiii cu artrita juvenila idiopatica.

UNLABELLED: The aim of the study was to evaluate the presence and etiopathogenesis of osteopenia in 41 children with Juvenile Idiopathic Arthritis (JIA). METHODS: Bone status was evaluated by quantitative ultrasound using a Sunlight Omnisense 7000s Ultrasound Bone Sonometer. Measurements were performed at the distal radius and midshaft tibia. Results were obtained as Speed of sound (SOS) and Z-score. We used standardised clinical evaluation (modified Giannini's criteria, CHAQ). ESR, Fibrinogen, serum calcium, magnesium, alkaline phosphatase, protein electrophoresis, 25-OH vitamin D (RIA) and urinary Hydroxyproline were obtained in all patients. Osteopenia was present in 15 (36.5%) patients. Statistical analysis was performed with SPSS 13.0. RESULTS: Age, sex, age at onset, disease duration, life standards and duration of corticotherapy and methotrexate treatment were not related to osteopenia in our study. The disease activity, evaluated by clinical criteria, ESR and Fibrinogen, was strongly associated with osteopenia (p<0.001). Nutritional status was an independent risk factor for osteopenia (p<0.001). Low serum calcium (p=0.034), magnesium (p=0.010), 25-OH vitamin D (p=0.091) and alkaline phosphatase (p=0.31) were more frequent in patients with osteopenia. Hydroxyproline was increased in all patients with osteopenia (p<0.001). CONCLUSIONS: Osteopenia was a frequent (36.5%) complication of JIA in our study. The disease activity and nutritional status were the most important risk factors for osteopenia. The increase of bone reabsorption was the main pathogenic mechanism of osteopenia in our study. Calcium and magnesium deficits were related to osteopenia. Decrease of bone synthesis was not associated with osteopenia in the present study.

Prediction of coronary artery calcium in young adults using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score: the CARDIA study.

BACKGROUND: Using data from autopsied young people aged 15 to 34 years, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study developed a risk score based on age, sex, smoking status, high-density lipoprotein and non-high-density lipoprotein cholesterol levels, and the presence of obesity, hyperglycemia, and hypertension to predict advanced coronary artery atherosclerosis. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study assessed coronary artery calcium (CAC) by computed tomography in young adults participating in the 15-year examination. The PDAY risk score was calculated from risk factors measured at the CARDIA examinations at years 0, 5, 10, and 15. RESULTS: Odds ratios for amount of CAC (6 ordinal categories) for a 1-point increase in risk score computed from the modifiable risk factors ranged from 1.10 to 1.16 (all statistically significant). Odds ratios for presence of any amount of CAC ranged from 1.09 to 1.15 (all statistically significant), with the highest odds ratio for the risk score at year 0. An increase in risk score between years 0 and 15 increased the odds of CAC, and a decrease in risk score decreased the odds of CAC. A positive family history of cardiovascular disease increased the odds of CAC. The c statistics ranged from 0.752 to 0.770, with the highest discrimination based on the year 0 revised PDAY risk score that included family history and increased the points for the sex differential. CONCLUSION: The PDAY risk score predicts CAC up to 15 years before its assessment, and risk score change during 15 years affects the risk of CAC.

Intravascular HBO(2) saturations, perfusion and hypoxia in spontaneous and transplanted tumor models.

Clinical trials utilizing strategies to manipulate tumor oxygenation, blood flow and angiogenesis are under way, although limited quantitative information exists regarding basic tumor pathophysiology. The current study utilized murine KHT fibrosarcomas, spontaneous mammary carcinomas and first-generation spontaneous transplants to examine heterogeneity in vascular structure and function, to relate these changes to the distribution of tumor hypoxia and to determine whether fundamental relationships among the different pathophysiological parameters exist. Three methods were included: (i) immunohistochemical staining of anatomical and perfused blood vessels, (ii) cryospectrophotometric measurement of intravascular oxyhemoglobin saturations and (iii) fluorescent detection of the EF5 hypoxic marker. While a distinct pattern of decreasing oxygenation with increasing distance from the tumor surface was observed for KHT tumors, striking intertumor variability was found in both spontaneous and first-generation transplants, with a reduced dependence on tumor volume. EF5 hypoxic marker uptake was also much more heterogeneous among individual spontaneous and first-generation tumors compared to KHT. Although mammary carcinomas demonstrated fewer anatomical blood vessels than fibrosarcomas, the proportion of perfused vessels was substantially reduced in KHT tumors, especially at larger tumor volumes. Vascular morphology, tissue histological appearance and pathophysiological parameters differed substantially between KHT tumors and both spontaneous and first-generation tumors. Such differences in vascular structure and function are also likely to correlate with altered response to therapies targeted to the vascular system. Finally, spontaneous differentiation status, tumor morphology, vascular configuration and function were well preserved in first-generation transplanted tumors, suggesting a close relationship between vascular development and function in early-generation transplants and spontaneous tumor models.

Low-temperature synthesis, structure, and bioactivity of gel-derived glasses in the binary CaO-SiO2 system.

Glasses in the binary system CaO-SiO2 for which the molar fraction of CaO is 0 < or = x < or = 0.50, were prepared by means of a sol-gel route starting from tetraethylorthosilicate and calcium nitrate. The textural features of the monoliths obtained were characterized using N2 gas adsorption, helium ultrapycnometry, and mercury porosimetry. In vitro bioactivity tests were performed in simulated body fluid (SBF). The ionic concentration of the SBF after glass immersion was analyzed using inductively coupled plasma atomic emission spectroscopy. The surfaces of the specimens were characterized using X-ray diffraction and scanning electron microscopy coupled with energy dispersive X-ray analysis before and after in vitro testing. The textural characterization revealed that the glasses were mesoporous with cylindrical pores with average diameters ranging from 25 to 663 A depending on the molar fraction of CaO. The in vitro studies showed that all binary CaO-SiO2 gel-glass compositions produced were bioactive. These results indicate that the binary gel-derived CaO-SiO2 system exhibits a level of bioactivity over a similar molar range of SiO2 content as the previously studied ternary CaO-P2O5-SiO2 system.

[Efficacy and tolerance of a calcium-magnesium-aspartate solution in the treatment of hypocalcemic parturient paresis in cows]. / Zur Wirksamkeit und Verträglichkeit einer Kalzium-Magnesium-Aspartat-Lösung bei der Behandlung der hypokalzämischen Gebärparese des Rindes.

The systemic tolerance of a solution of calcium aspartate and magnesium aspartate was studied in 7 cows. Intravenously administered dosages of 500 ml per cow were well tolerated. A twofold increase of the serum calcium concentration was measured. In 2 cows which were treated with 1000 ml of the solution a threefold increased calcium concentration and heart arrhythmia were found. The clinical efficacy of the solution was demonstrated in a study with 44 hypocalcemic cows. A long lasting increase of the serum calcium as well as an enhanced phosphorus concentration were measurable. In conclusion, the calcium-magnesium-aspartate solution seems to be an efficacious and well tolerated alternative for the treatment of hypocalcemia in cows.

Parathyroid function and histology in patients with parathyroid adenoma: correlation of clinical and morphologic findings.

Serum levels of parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, creatinine, and vitamin D and the glomerular filtration rate were compared with the histologic properties and expression of PTH and chromogranin A in excised parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). PTH and chromogranin A were detected immunohistochemically, and their mRNA was demonstrated by in situ hybridization with quantification of their mRNA levels by image analysis. There was a positive correlation between the cellular levels of PTH mRNA and the cellular levels of chromogranin A mRNA (r = 4.4; p < 0.05). However, within certain parts of the adenomas, mostly consisting of chief cells, the expression of PTH mRNA and chromogranin A mRNA was heterogeneous and the levels did not correspond to each other. A reduced suppressibility of PTH in patients with pHPT was confirmed. Although cellular levels of PTH and chromogranin A and their mRNAs were low in the oxyphilic parts of the adenomas, there was no correlation between the amount of oxyphilic cells in the adenomas and the suppressibility of PTH by calcium. There was also no association between the cellular levels of PTH mRNA or chromogranin A mRNA as studied by image analysis and "calcium sensitivity." Our results thus demonstrate that although PTH and chromogranin A mRNA levels are in general correlated to each other there are differences in their expression within and between individual parathyroid adenomas. It therefore seems likely that the expression of PTH and chromogranin A are differentially regulated, and that PTH and chromogranin A may not always be co-secreted. This point could be of importance, as chromogranin A and its cleavage products are known to influence PTH secretion.