Attenuation of indirect markers of eccentric exercise-induced muscle damage by curcumin

Purpose: Polyphenolic curcumin is known to have potent anti-inflammatory effects; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise. Methods: Fourteen untrained young men (24 ± 1 years) performed 50 maximal isokinetic (120°/s) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later. They took 150 mg of curcumin (theracurmin) or placebo (starch) orally before and 12 h after each eccentric exercise bout in a randomised, crossover design. Maximal voluntary contraction (MVC) torque of the elbow flexors, range of motion of the elbow joint, upper-arm circumference, muscle soreness, serum creatine kinase (CK) activity, and plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration were measured before, immediately after, and 24, 48, 72 and 96 h after each eccentric exercise. Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA. Results: MVC torque decreased smaller and recovered faster (e.g., 4 days post-exercise: −31 ± 13 % vs. −15 ± 15 %), and peak serum CK activity was smaller (peak: 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L) for curcumin than placebo condition (P \u3c 0.05). However, no significant differences between conditions were evident for other variables, and no significant changes in IL-6 and TNF-α were evident after exercise. Conclusion: It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase

Transdisciplinary unifying implications of circadian findings in the 1950s

A few puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal

Feasibility of Precoagulation Without the Pringle Maneuver for Endoscopic Hepatectomy of Cirrhotic Liver

Various methods, devices, and techniques have been developed to improve safety during laparoscopic hepatectomy procedures. Among these, the Pringle maneuver （PM） is widely used to minimize blood loss during liver transections; however, the risk of ischemic injury associated with this technique is increased by poor hepatic reserve and regeneration dysfunction secondary to liver cirrhosis. This retrospective study evaluated the short-term outcomes and feasibility of precoagulation for endoscopic hepatectomy without PM in patients with liver cirrhosis. Eleven patients with liver cirrhosis who also underwent endoscopic hepatectomy for hepatocellular carcinoma were recruited to undergo either microwave tissue coagulation or radiofrequency ablation for precoagulation before liver transection. A wedge resection without the PM was performed in all patients, with seven patients selected for bipolar radiofrequency ablation and four patients for microwave coagulation therapy. The procedures included video-assisted thoracoscopic hepatectomy in two patients and laparoscopic hepatectomy in nine patients. One patient who underwent radiofrequency ablation developed postoperative bleeding （Clavien-Dindo grade Ⅲ）. In conclusion, precoagulation can help to minimize intraoperative blood loss without the PM, contributing to effective resection of liver tumors. We propose that precoagulation could serve as a standard technique for endoscopic hepatectomy in patients with cirrhosis

トクシマケン イシカイ トウニョウビョウ タイサクハン ダイ1ジ ダイ2ジ カツドウ ノ セイカ

Objective : The effectiveness of diabetes prevention programs for the general population in Tokushima Prefecture was investigated. The programs were designed by Tokushima Medical Association’ s（TMA’s）Steering Committee for Diabetes Prevention. Research design and methods : The committee promoted diabetes prevention by disseminating educational messages on diabetes to the general public and medical care providers, and establishing a referral system among public health centers and medical institutes throughout Tokushima Prefecture during the period from ２００４ to ２００９. The outcome of these activities were evaluated by analyzing data from the Prefectural Health and Nutrition Survey in Tokushima conducted in１９９７（n＝ ９９８）,２００３ （n＝１００８） and ２０１０ （n＝１１３０）, and then comparing these results with those of the national survey at the corresponding times. Results : The percentage of subjects with glucose intolerance at the time of initiation of the prevention program in Tokushima tended to increase from １９９７ to ２００３, but was slightly decreased in ２０１０, although the differences were not statistically significant. However, the percentage of subjects with glucose intolerance was significantly increased throughout Japan during the same period. Obesity parameters, physical activity evaluated by the number of steps and the average total energy intake changed favorably in parallel with changes in the prevalence of diabetes during the study period in Tokushima. Conclusion : The diabetes prevention programs initiated by the TMA’s committee may be useful in ameliorating the situation of diabetes in Tokushima Prefecture

Comparison of Conventional and New-generation Nickel-Titanium Files in Regard to Their Physical Properties

Introduction This study investigated the surface, fractured structure, and physicochemical properties related to cyclic fatigue in various nickel-titanium (NiTi) files.Methods Among a total of 10 groups of NiTi files, conventional NiTi files (ProFile [Dentsply Maillefer, Ballaigues, Switzerland] and K3 [SybronEndo, Orange, CA]) and new-generation NiTi files (ProFile Vortex [PV; Tulsa Dental Specialties, Tulsa, OK], Vortex Blue [VB; Tulsa Dental Specialties], and K3 XF [XF; SybronEndo, Orange, CA]) with the same tip diameter (ISO size 25) and 2 types of taper (0.04 and 0.06) were used in this study. Scanning electron microscopy of the file surface structure, differential scanning calorimetry, and cyclic fatigue resistance tests were conducted.Results Many mechanical grooves were recognized on the file surface. The surface in the ProFile group was extremely smooth compared with that observed for the other files. Many shallow hollows besides mechanical grooves were noted on the surface in the XF group. A smooth curve was observed in the ProFile, K3, and PV groups. Defined peaks in differential scanning calorimetry were observed in the VB and XF groups. The 0.04 taper files exhibited a statistically higher number of cycles to fracture than the 0.06 taper files in all groups (P <.05). Cracks along the mechanical grooves were observed in the NiTi files, with the exception of the XF group. The start of cracking was detected at U-shape sites in the ProFile group, the cutting edge in the PV and VB groups, and radial islands in the K3 and XF groups.Conclusions The present findings suggest that new-generation NiTi files are not necessarily improved compared with conventional files

Combined Supplementation of Pre-Exercise Carbohydrate, Alanine, and Proline and Continuous Intake of Green Tea Catechins Effectively Boost Endurance Performance in Mice

Continuous intake of green tea catechins (GTC) increases fatty acid utilization as an energy source and improves endurance capacity. Conversely, the single pre-exercise intake of maltodextrin (MD) as a carbohydrate source and the gluconeogenic amino acids alanine (Ala) and proline (Pro) effectively maintain blood glucose levels and increase endurance performance. In this study, we investigated the synergistic combinational effect of these interventions on endurance performance in mice. Male BALB/c mice were fed a 0.5% GTC diet or Control diet for 8 weeks. Maximum running time was measured every 2 weeks. MD (2 g/kg body weight (B.W.)), MD (1 g/kg B.W.) + AlaPro (9:1, 1 g/kg B.W.), and vehicle were orally administrated 60 mins before measurements in each diet group. The GTC + MD + AlaPro group showed significantly higher endurance performance than the Control-Vehicle group at all measurements. Indirect calorimetry analysis during running exercise at 4 weeks in the Control and GTC groups supplemented with pre-exercise MD + AlaPro administration revealed significantly higher fat oxidation in the GTC groups compared to the Control group. The combined increase in fatty acid utilization through continuous GTC intake and pre-exercise MD + AlaPro carbohydrate energy supplementation synergistically improves endurance capacity

Moduli inflation from modular flavor symmetries

Abstract We study slow-roll inflation model controlled by the modular flavor symmetry. In the model, the modulus field plays a role of inflaton and the introduction of the stabilizer field coupled to a modular form in the superpotential produces the inflaton potential. In order to generate the flat direction for the slow-roll inflation, we consider the Kähler potential corrected by the modular form. It is noted that the modulus field perpendicular to the inflaton direction is stabilized during the inflation. The model turns out to be consistent with the current observations and behaves similarly to the α-attractor models in some parameter spaces. The inflaton rolls down to the CP-symmetric vacuum at the end of inflation

Moduli inflation from modular flavor symmetries

We study slow-roll inflation model controlled by the modular flavor symmetry. In the model, the modulus field plays a role of inflaton and the introduction of the stabilizer field coupled to a modular form in the superpotential produces the inflaton potential. In order to generate the flat direction for the slow-roll inflation, we consider the K\"{a}hler potential corrected by the modular form. It is noted that the modulus field perpendicular to the inflaton direction is stabilized during the inflation. The model turns out to be consistent with the current observations and behaves similarly to the $\alpha$-attractor models in some parameter spaces. The inflaton rolls down to the CP-symmetric vacuum at the end of inflation.Comment: 45 pages, 19 figures, 2 tables, version to appear in JHEP plus App.

A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients.

A growing number of preclinical studies have demonstrated that curcumin could be a promising anticancer drug; however, poor bioavailability has been the major obstacle for its clinical application. To overcome this problem, we developed a new form of curcumin (Theracurmin) and reported high plasma curcumin levels could be safely achieved after a single administration of Theracurmin in healthy volunteers. In this study, we aimed to evaluate the safety of repetitive administration of Theracurmin in cancer patients

Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers.

[Background] : More and more preclinical studies support the idea that curcumin, a plant-derived natural polyphenol, could be a promising anticancer drug. However, poor bioavailability has limited its efficacy in clinical trials, and plasma curcumin levels remain low despite patients taking gram doses of curcumin. [Methods] : This study aimed to evaluate the safety and pharmacokinetics of newly developed nanoparticle curcumin with increased water solubility (named THERACURMIN). Six healthy human volunteers were recruited and received THERACURMIN at a single oral dose of 150 mg. After an interval of 2 weeks, the same subjects then received THERACURMIN at a single dose of 210 mg. Plasma curcumin levels were measured at 0, 1, 2, 4, 6, and 24 h after THERACURMIN intake using high-performance liquid chromatography (HPLC). [Results] : One subject reported grade 1 diarrhea after intake of 150 mg THERACURMIN. No other toxicities were observed in this study. C max for THERACURMIN at 150 and 210 mg was 189 ± 48 and 275 ± 67 ng/ml (mean ± SEM), respectively, and the area under the curve for 24 h was estimated to be 2, 649 ± 350 and 3, 649 ± 430 ng/ml × h (mean ± SEM), respectively. The t 1/2 was estimated to be 9.7 ± 2.1 h for 150 mg and 13.0 ± 3.3 h for 210 mg. [Conclusion ] : THERACURMIN can safely increase plasma curcumin levels in a dose-dependent manner at least up to 210 mg without saturating the absorption system. To the best of our knowledge, THERACURMIN is the first nanoparticle formulation of curcumin that demonstrates improved bioavailability in human subjects. We believe this compound could be a promising tool when testing the potential anticancer effects of curcumin in clinical trials