Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children
SCIENTIFIC REPORTS
Authors: Hathout, Yetrib; Conklin, Laurie S.; Seol, Haeri; Gordish-Dressman, Heather; Brown, Kristy J.; Morgenroth, Lauren P.; Nagaraju, Kanneboyina; Heier, Christopher R.; Damsker, Jesse M.; van den Anker, John N.; Henricson, Erik; Clemens, Paula R.; Mah, Jean K.; McDonald, Craig; Hoffman, Eric P.
Abstract
Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes.
A modified combined approach to harvest connective tissue grafts with high quality, less morbidity, and faster healing
INTERNATIONAL JOURNAL OF ESTHETIC DENTISTRY
Authors: Ho, Feng-Chuan
Abstract
Harvesting good-quality connective tissue grafts (CTGs) is important in periodontal surgery. Compared with CTGs, free gingival grafts (FGGs) have a slower healing process and higher donor site morbidity. As far as graft quality and anatomic limitations are concerned, deepithelialized free gingival grafts (DE-FGGs) are superior to CTGs. In the current study, a modified combined approach is proposed that aims to address the disadvantages of conventional FGG harvesting methods. This approach entails harvesting a thin and narrow DE-FGG, repositioning the epithelial layer, and applying a plastic stent. The outcomes of this improved method indicate fast healing at the donor sites, fewer postoperative complications, and better esthetic results at the recipient sites.