Determination of the Relationship between Serum Calcium, Phosphor and Alkaline Phosphatase with Peripheral Giant Cell Granuloma in Iranian Patients

Peripheral giant cell granuloma (P.G.C.G) is an exophytic lesion with an approximate size of"n0.5-1.5 mm. It usually occurs on gingival and alveolar ridge of mandible particularly in molar and"npremolar region. The relation of serum calcium (Ca), Phosphor (P), and alkaline phosphatase (Alk) levels"nto P.G.C.G is yet controversial. In this descriptive study, 33 patients with P.G.C.G were chosen and"nserum Ca, P, and Alk levels compared with the normal range. In all patients the level of Ca was in the"nnormal range. Phosphor (P) was in the normal range in all patients over 17 years old and 80% under 17"nyears. The level of ALK in 75.8 percent of the patients over 17 years and 90% under 17 years was in the"nnormal range."nIn conclusion, no relationship was found between serum changes and P.G.C.G. It means P.G.C.G can be"ncompeletly independent lesions from serum changes

Towards Bridging Translational Gap in Cardiotoxicity Prediction: an Application of Progressive Cardiac Risk Assessment Strategy in TdP Risk Assessment of Moxifloxacin

Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis. A multi-scale mechanistic modeling framework consisting of physiologically based pharmacokinetics (PBPK) simulations of clinically relevant drug exposures combined with Quantitative Systems Toxicology (QST) models of cardiac electro-physiology could bridge this gap. We illustrate this PBPK-QST approach in cardiac risk assessment as exemplified by moxifloxacin, an anti-tuberculosis drug with abundant clinical cardiac safety data. PBPK simulations of moxifloxacin concentrations (systemic circulation and estimated in heart tissue) were linked with in vitro measurements of cardiac ion channel inhibition to predict the magnitude of QT prolongation in healthy individuals. Predictions closely reproduced the clinically observed QT interval prolongation, but no arrhythmia was observed, even at ×10 exposure. However, the same exposure levels in presence of physiological risk factors, e.g., hypokalemia and tachycardia, led to arrhythmic event in simulations, consistent with reported moxifloxacin-related TdP events. Application of a progressive PBPK-QST cardiac risk assessment paradigm starting in early development could guide drug development decisions and later define a clinical “safe space” for post-approval risk management to identify high-risk clinical scenarios