Curcumin is a major component of the spice, turmeric (Curcuma longa) often used in food or as a dietary supplement. Many preclinical studies on curcumin suggests benefit in many diseases due to its antioxidant and epigenetic effects. The few human studies and curcumin's unfavorable pharmacokinetics (PK) have limited its potential, leading researchers to study and develop formulations to improve its PK. The purpose of this clinical study is to describe the pharmacokinetics and pharmacodynamics (PK/PD) of commercially marketed curcumin in normal, healthy human volunteers. Twelve volunteers received 4 g of curcumin capsules with standard breakfast. Plasma samples were collected at specified timepoints and analyzed for curcumin levels. RNA was extracted and analyzed for expression of select antioxidant and epigenetic histone deacetylase (HDAC) genes. Plasma levels of parent curcumin were not detected by HPLC‐ITMS/MS/MS. However, curcumin glucuronide, a major metabolite of curcumin, was detected as soon as 30 min. These observations of little to no curcumin and low levels of metabolite are in line with previous studies. Antioxidant genes Nrf2, HO‐1, NQO1, and HDAC1, HDAC2, HDAC3, and HDAC4 were quantified by qPCR. Curcumin glucuronide pharmacokinetics are well‐described by a one‐compartment model and the PK/PD of curcumin glucuronide and its effect on antioxidant and epigenetic gene expression are explained by indirect response model (IDR). Increasing AUC or exposure to curcumin glucuronide was correlated with overall PD response. Physiologically based pharmacokinetic modeling (PBPK) and simulation using Simcyp correlated well with our observed data in the human volunteers. In vitro experiments on curcumin glucuronide in HepG2C8 cells also show that Nrf2‐ARE luciferase activity increases after 24‐hour treatment. These results show that poor bioavailability of curcumin remains a challenge but that oral administration of curcumin delivers detectable levels of curcumin glucuronide and may mediate the antioxidant and epigenetic effects of curcumin.
Support or Funding Information
Grant: This work was supported in part by institutional funds and R01AT007065 from the National Center for Complementary and Alternative Medicines (NCCAM) and the Office of Dietary Supplements (ODS).
This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Radial nerve palsy can occur with humerus fracture, either at the time of injury (primary) or during reduction (secondary). Late-onset radial nerve palsy (not immediately related to injury or reduction) has been very seldom reported in the English literature. We describe a case of late-onset radial nerve palsy, which developed 9 weeks after an attempted closed management of a midshaft humerus fracture. Exploration of the nerve was performed. The radial nerve was found to be stretched over the ends of the fracture. Open reduction and external fixation of the fracture with mobilization of the nerve from the fracture site lead to complete return of radial nerve function occurring by 3 months. We recommend exploration of cases of late-onset radial nerve palsy in contrast to primary or secondary radial nerve palsy, which can be treated conservatively. Our experience suggests that the cause of the palsy is a continuous ongoing pathology and not a single time event as in primary or secondary cases. Radial nerve palsies associated with humeral fracture should be classified as either primary (at the time of injury), secondary (at the time of reduction), or late onset (not related to either injury or reduction).
Background: One risk of bariatric surgery is venous thromboembolism and the optimal strategy to reduce risk requires further clarification. Objectives: The objectives of this study were to identify antiXa goal attainment with the institutional standard chemoprophylaxis, analyze discordance between antiXa and thrombin generation assay (TGA) in terms of adequacy of anticoagulation, and to identify correlations between patient characteristics or covariates and markers of coagulation status. Setting: Large academic medical center in Northeastern United States. Methods: A total of 60 sleeve gastrectomy patients were enrolled in this institutional review board-approved, prospective cohort study. Patients received the institutional standard prophylactic therapy (subcutaneous enoxaparin 40 mg twice daily or unfractionated heparin [UFH]). The UFH dose was weight based, 5000 units ( < 120 kg) or 7500 units ( ≥120 kg) every 8 hours. Various measures of coagulation status were measured at or near steady state. Results: Patients receiving enoxaparin achieved goal antiXa more frequently compared with the UFH group, and statistical significance was demonstrated (93.8 % versus 4.5%, respectively; P < .0001). Target endogenous thrombin potential reduction from baseline was more frequently obtained in the enoxaparin group versus UFH (50% versus 27.7%, respectively; P = .12). AntiXa was below the limit of detection for the majority of UFH patients; while TGA suggested patients did experience anticoagulation at some level of effectiveness. Endogenous thrombin potential change in the enoxaparin group was correlated to several measures of body composition.
Conclusions:Patients receiving enoxaparin achieved goal antiXa more often versus UFH. There was discordance between antiXa and TGA-based assessment of coagulation status. TGA may provide a more robust assessment of the adequacy of chemoprophylaxis. (Surg Obes Relat Dis 2019;15:363-373.)
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