No abstract

Amino acid-based poly(ester urea)s (PEU) are high modulus, resorbable polymers with many potential uses, including the surgical repair of bone defects. In vitro and in vivo studies have previously shown that phenylalanine-based PEUs have nontoxic hydrolytic byproducts and tunable degradation times. Phenylalanine PEUs (poly(1-PHE-6)) have been further modified by tethering osteogenic growth peptide (OGP) to tyrosine-based monomer subunits. These OGP-tethered PEUs have been fabricated into porous scaffolds and cultured in vitro to examine their effect on differentiation of human mesenchymal stem cells (hMSCs) toward the osteogenic lineage. The influence of tethered OGP on the hMSC proliferation and differentiation profile was measured using immunohistochemistry, biochemistry, and quantitative real time polymerase chain reaction (qRT-PCR). In vitro data indicated an enhanced expression of BSP by 130-160% for hMSCs on OGP-tethered scaffolds compared to controls. By 4 weeks, there was a significant drop (60-85% decrease) in BSP expression on OGP-functionalized scaffolds, which is characteristic of osteogenic differentiation. ALP and OSC expression was significantly enhanced for OGP-functionalized scaffolds by week 4, with values reaching 145% and 300% greater, respectively, compared to nonfunctionalized controls. In vivo subcutaneous implantation of poly(1-PHE-6) scaffolds revealed significant tissue-scaffold integration, as well as the promotion of both osteogenesis and angiogenesis.

Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS.

Carpal tunnel syndrome is a common disease treated operatively. During the operation, the patient may be wideawake or sedated. The current literature has only compared separate cohorts. We sought to compare patient experience with both local-only anesthesia and sedation. Methods: Staged bilateral carpal tunnel release utilizing open or endoscopic technique was scheduled and followed through to completion of per-protocol analysis in 31 patients. Patients chose initial hand laterality and were randomized regarding initial anesthesia method: local-only or sedation. Data collection via questionnaires began at consent and continued to 6 weeks postoperatively from second procedure. Primary outcome measures included patient satisfaction and patient anesthesia preference. Results: At final follow-up, 6 weeks postoperatively, high satisfaction (30 of 31 patients per method) was reported with both types of anesthesia. Among these patients, 17 (54%) preferred local-only anesthesia, 10 (34%) preferred sedation, 2 had no preference, and 2 opted out of response. Although anesthesia fees were approximately $390 lower with local-only anesthesia, total costs for carpal tunnel release were not significantly different with respect to the anesthesia cohorts. Total time in surgical facility was approximately 26 minutes quicker with local-only anesthesia, largely due to shorter time in the post-anesthesia care unit. Scaled comparison of worst postoperative pain following the 2 procedures revealed no difference between local-only anesthesia and sedation. Conclusions: Patients reported equal satisfaction scores with carpal tunnel release whether performed under local-only anesthesia or with sedation. In addition, local-only anesthesia was indicated as the preference of patients in 59% of cases.