Odontogenic tumors and giant cell lesions of jaws - a nine year study

<p>Abstract</p> <p>Objectives</p> <p>A definite geographic variation has been observed in the frequency of odontogenic tumors and giant cell lesions of the jaws reported from different parts of the world. However, there are a few studies on these lesions, especially giant cell lesions, reported from India. Hence, this study was designed to provide a demographic data on the odontogenic tumors and giant cell lesions reported from our institute located in the city of Hyderabad. Hyderabad is the capital city of the southern state of Andhra Pradesh in India. A retrospective analysis of odontogenic tumors and giant cell lesions of jaws reported in our institute between the years 2000 and 2009 was done and this data was compared with previous reports from different parts of the world and India.</p> <p>Methods</p> <p>Biopsies of the lesions received between the years 2000 and 2009 were reviewed and patient's history, clinical, radiological and histopathological characteristics were analyzed.</p> <p>Results</p> <p>A total of 77 biopsies were received during the nine year study period. These lesions were more frequently seen in the males, in a younger age group and showed a predilection for the mandible. Most of them presented as radiolucent, slow growing and painless lesions. Ameloblastomas (71.4%) constituted the majority of odontogenic tumors while central giant cell granulomas (7.8%) constituted the majority of giant cell lesions.</p> <p>Conclusion</p> <p>These lesions showed a definite geographic variation with ameloblastomas being the most common odontogenic tumors and odontomas being relatively rarer lesions in our region.</p

A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice

This is the author's accepted manuscript.Purpose To investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease. Methods Glucose-6-phosphate isomerase (GPI)-mediated inflammation was used as a preclinical model of arthritis in DBA/1 mice. CYP3A substrate MDZ was selected to study changes in metabolism and PK during the inflammation. The semi-PBPK model was constructed using mouse physiological parameters, liver microsome metabolism, and healthy animal PK data. In addition, serum cytokine, and liver-CYP (cytochrome P450 enzymes) mRNA levels were examined. Results The in vitro metabolite formation rate was suppressed in liver microsomes prepared from the GPI-treated mice as compared to the healthy mice. Further, clearance of MDZ was reduced during inflammation as compared to the healthy group. Finally, the semi-PBPK model was used to predict PK of MDZ after GPI-mediated inflammation. IL-6 and TNF-α levels were elevated and liver-cyp3a11 mRNA was reduced after GPI treatment. Conclusion The semi-PBPK model successfully predicted PK parameters of MDZ in the disease state. The model may be applied to predict PK of other drugs under disease conditions using healthy animal PK and liver microsomal data as inputs