Effectiveness of Repetitive Facilitative Exercise Combined with Electrical Stimulation Therapy to Improve Very Severe Paretic Upper Limbs in with Stroke Patients: A Randomized Controlled Trial.

Background: The difference in the effects of combined therapy with repetitive facilitative exercise (RFE) and neuromuscular electrical stimulation (NMES) on stroke upper limb paralysis was only reported by a pilot study; it has not been investigated in many patients. Objective: We investigated the effect of combined therapy with RFE and NMES on stroke patients with severe upper paresis. Methods: This study included 99 of the very severe paresis stroke patients with scores of zero or 1a in the Finger-Function test of the Stroke Impairment Assessment Set (SIAS). We randomly divided the patients into four groups, namely, NMES, RFE, RFE under NMES, and conventional training (CT) groups. A total of 20 min of group-specific training in addition to 40 min of conventional exercise per day, seven times a week for 4 weeks after admission, was performed. The upper extremity items of the Fugl-Meyer Assessment (FMA) were evaluated before and after the training period. Results: The total score gains of the FMA, FMA wrist item, and FMA finger item were significantly larger in the RFE under NMES group than those in the CT group (p < 0.05). Conclusion: The combination of voluntary movement and electrical stimulation may promote the activation of paralyzed muscles and improve distal function for very severe paralyzed upper limbs.

Histone deacetylase inhibitors sensitize 5-fluorouracil-resistant MDA-MB-468 breast cancer cells to 5-fluorouracil.

Resistance to 5-fluorouracil (5-FU) is a serious problem in cancer therapy and overcoming it is required in order to improve the efficacy of cancer chemotherapy. Histone deacetylase (HDAC) inhibitors are used in cancer treatments and, recently, it has been reported that HDAC inhibitors can overcome resistance to various anti-cancer drugs in vitro. In the present study, a 5-FU-resistant breast cancer cell line was established, and the effects of HDAC inhibitors in these cells were examined. The 5-FU-resistant cell line MDA-MB-468 (MDA468/FU) was established by continuous exposure of the parental cells to 5-FU. This subline was characterized by high resistance to 5-FU, higher mRNA expression levels of thymidylate synthetase and dihydropyrimidine dehydrogenase (DPD), and lower mRNA expression levels of uridine monophosphate synthetase (UMPS) than the parental cells. Gimeracil, a DPD inhibitor, did not affect the sensitivity of MDA468/FU cells to 5-FU. Oteracil, a UMPS inhibitor, decreased the cytotoxicity of 5-FU in MDA468 cells, but not in MDA468/FU cells. The HDAC inhibitors, valproic acid and suberanilohydroxamic acid sensitized the two cell lines to 5-FU in a concentration-dependent manner. In conclusion, the results of the present study revealed that HDAC inhibitors increase the sensitivity to 5-FU in 5-FU-sensitive and -resistant cells.