Pretreatment with Lovastatin Improves Depression-Like Behavior After Traumatic Brain Injury Through Activation of the AMPK Pathway.

BACKGROUND: The beneficial effect of pretreatment with statins on traumatic brain injury (TBI)-induced depression and anxiety and its mechanism of action remain unclear. In this study, we combined epidemiological and experimental animal data to clarify this issue. METHODS: We used the Taiwan National Health Insurance database to identify patients who were diagnosed with TBI from 2000 to 2013 and compared patients with and without statin treatment matched by age, sex, and underlying comorbidities in a 1:1 ratio. The risk of developing depression and/or anxiety was compared between patients with and without a statin using Cox proportional hazards regression. We also used a rat model to assess the effect of lovastatin pretreatment on neurobehavioral and neuropathological changes following TBI. RESULTS: The risk of developing depression was lower in the 41,803 patients in the statin cohort than nonstatin cohort (adjusted hazard ratio, 0.91 [95% confidence interval, 0.83-0.99]). In animal models, the lovastatin group had significantly reduced infarct volume, decreased immobility time and latency to eat, a reduced number of Fluoro- Jade-positive cells and levels of glial fibrillary acidic protein and tumor necrosis factor-alpha, and increased adenosine monophosphate -activated protein kinase (AMPK) and its upstream kinase liver kinase B1 in the hippocampal dentate gyrus. These effects were blocked in AMPK inhibitor-pretreated TBI rats. CONCLUSIONS: Our epidemiological data showed that a decreased risk of depression was associated with statin pretreatment, which was supported by an animal study. The underlying mechanism for this appears to involve AMPK activation in the statin pretreatment-induced alleviation of TBI.

Synthesis and In Vitro Photocytotoxicity of 9-/13-Lipophilic Substituted Berberine Derivatives as Potential Anticancer Agents.

The objective of this study was to synthesize the 9-/13-position substituted berberine derivatives and evaluate their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e), and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in comparison with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at the 9-/13-position of berberine may have facilitated its penetration into test cells and hence enhanced its photocytotoxicity on the human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e, and 7e induced HepG2 cells to arrest at the S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine derivatives 5e, 6e, and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level, and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e, and 7e greatly enhanced photocytotoxicity. Taken together, the test data led us to conclude that berberine derivatives with a dodecyl group at the 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

Immediate effects of various physical therapeutic modalities on cervical myofascial pain and trigger-point sensitivity.

OBJECTIVE: To investigate the immediate effect of physical therapeutic modalities on myofascial pain in the upper trapezius muscle. DESIGN: Randomized controlled trial. SETTING: Institutional practice. PATIENTS: One hundred nineteen subjects with palpably active myofascial trigger points (MTrPs). INTERVENTION: Stage 1 evaluated the immediate effect of ischemic compression, including 2 treatment pressures (P1, pain threshold; P2, averaged pain threshold and tolerance) and 3 durations (T1, 30s; T2, 60s; T3, 90s). Stage 2 evaluated 6 therapeutics combinations, including groups B1 (hot pack plus active range of motion [ROM]), B2 (B1 plus ischemic compression), B3 (B2 plus transcutaneous electric nerve stimulation [TENS]), B4 (B1 plus stretch with spray), B5 (B4 plus TENS), and B6 (B1 plus interferential current and myofascial release). MAIN OUTCOME MEASURES: The indexes of changes in pain threshold (IThC), pain tolerance (IToC), visual analog scale (IVC), and ROM (IRC) were evaluated for treatment effect. RESULTS: In stage 1, the IThC, IToC, IVC, and IRC were significantly improved in the groups P1T3, P2T2, and P2T3 compared with the P1T1 and P1T2 treatments (P<.05). In stage 2, groups B3, B5, and B6 showed significant improvement in IThC, ItoC, and IVC compared with the B1 group; groups B4, B5, and B6 showed significant improvement in IRC compared with group B1 (P<.05). CONCLUSIONS: Ischemic compression therapy provides alternative treatments using either low pressure (pain threshold) and a long duration (90s) or high pressure (the average of pain threshold and pain tolerance) and short duration (30s) for immediate pain relief and MTrP sensitivity suppression. Results suggest that therapeutic combinations such as hot pack plus active ROM and stretch with spray, hot pack plus active ROM and stretch with spray as well as TENS, and hot pack plus active ROM and interferential current as well as myofascial release technique, are most effective for easing MTrP pain and increasing cervical ROM.