Proliferation of epithelial rests of Malassez during experimental tooth movement

The epithelial rests of Malassez (ERM), remnants of Hertwig’s epithelial root sheath, are found near the root surface in the periodontal ligament. The functional significance of the ERM is still unknown. The purpose of this study was to examine the behavior of the ERM during experimental tooth movement. Tooth movement was achieved in 12 male Sprague-Dawley rats (each, 120-200 g) by placing elastic bands between the maxillary right first and second molars. The left molars served as controls. The rats were killed after 6, 12, 18, 24, 60, and 72 hours. The mitotic activity of the ERM was assessed by injecting the animals with 5-bromo-2'-deoxyuridine (BrdU) 2 to 3 hours before killing by intracardial perfusion with 4% paraformaldehyde. The molar-bearing segments were dissected and processed for histological examination. The incorporated BrdU was detected by immunohistochemistry. The number of cells in each ERM cluster was counted in all groups. In the 18-, 24-, 60-, and 72-hour experimental groups, the cell numbers were significantly higher than in the controls. The surface areas of the ERM clusters were also measured in all groups, but only in the 18-, 24-, 60-, and 72-hour specimens were the areas significantly higher in the experimental than in the control groups. The ERM cells in the experimental specimens were labeled with anti-BrdU, while those in the controls were not. It was concluded that experimental tooth movement stimulates ERM cells to proliferate and increase in size. These increased activities of the ERM are consistent with a putative role for these cells in collagen turnover in the periodontal ligament that is accelerated during tooth movement.King Saud Universit

Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification

OnlinePublObjectives Attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective. Methods A lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%. Results Over the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay. Conclusions Delaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients.Clara Marquina, Jedidiah Morton, Ella Zomer, Stella Talic, Sean Lybrand, David Thomson, Danny Liew, Zanfina Adem