Nonalcoholic Steatohepatitis (NASH) in OB/OB Mice Treated with Yo Jyo Hen Shi Ko (YHK): Effects on Peroxisome Proliferator-Activated Receptors (PPARs) and Microsomal Triglyceride Transfer Protein (MTP)

YHK has antioxidant properties, has a hypoglycemic effect, and may reduce plasma lipid levels. In this study, we examined the hepatic expression of PPAR-α and -γ and MTP in ob/ob mice receiving or not receiving YHK. Ob/ob mice were assigned to receive oral YHK (20 mg/kg/day) fed solution (methionine/choline-deficient [MCD] diet + YHK group) or vehicle (MCD group) by gavage for 4 weeks. Liver fragments were collected for histologic examination and mRNA isolation. PPAR-α and -γ and MTP gene expression was examined by RT-qPCR. YHK treatment was associated with NASH prevention, weight loss, and reduction of visceral fat and of serum concentrations of aminotransferases in comparison to the MCD group. YHK promoted an increment in PPAR-α and MTP and a decrement in PPAR-γ mRNA contents. These findings suggest that modulation of PPAR-α and -γ and MTP RNA expression may be implicated in the protective effect of YHK in experimental NASH, limiting hepatocyte lipid accumulation.     

Yo jyo hen shi ko, a novel Chinese herbal, prevents nonalcoholic steatohepatitis in ob/ob mice fed a high fat or methionine-choline-deficient diet.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Yo jyo hen shi ko (YHK) is a complex compound purported to reduce reactive oxygen species (ROS) by blocking the propagation of radical-induced reactions. The aim of this study was to evaluate the role of the effect of YHK in experimental NASH. METHODS: NASH was induced in male ob/ob mice by a high-fat (HF) diet or methionine/choline-deficient (MCD) diet for 4 weeks. YHK-treated animals received YHK solution orally (20 mg/kg/day) in both experimental diets (n=6; each group) while control animals received only vehicle. RESULTS: The MCD and HF groups developed moderate diffuse macrosteatosis, hepatocellular ballooning, and a diffuse inflammatory infiltrate. With the addition of YHK, there was a marked reduction in macrosteatosis in both groups. This was associated with decreased lipoperoxide and reduced glutathione-GSH concentrations as well as reduced serum aminotransferases and improved histological markers of inflammation. These changes were also associated with weight loss in the MCD+YHK group and diminished weight gain in the HF+YHK group. CONCLUSION: YHK therapy blunts the development of macrosteatosis in these models of NASH and significantly reduces markers of oxidative stress. YHK also diminishes weight gain in this obesity prone model. Our findings warrant further study on the mechanisms involved with these effects.     

Gamma-Hydroxybutyric Acid (GHB) in the Treatment of Alcohol Withdrawal Syndrome: A Randomized Comparative Study Versus Benzodiazepine

BACKGROUND: Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma-hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single-blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS. METHODS: Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5-0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 +/- 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males,4 females; mean age 41.7 +/- 10.4 years).The Clinical Institute Withdrawal Assessment for Alcohol-revised scale (CIWA-Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self-rating Depression Scale for current depression assessment were performed. RESULTS: Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA-Ar total score at baseline and at the different times of observation. Considering the CIWA-Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p < 0.02), agitation on day 5 (p < 0.02) and time of recovery of depression on day 5 (p < 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups. CONCLUSIONS: GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well-tolerated in AWS management.     

The Familial Hypercholesterolemia Regression Study: A Randomized Comparison of Therapeutic Reduction of Both Low-Density Lipoprotein and Lipoprotein(a) Versus Low-Density Lipoprotein Alone

Abstract: Lipoprotein (a) [Lp (a)] is a risk factor for coronary heart disease (CHD), especially in the presence of a raised low-density lipoprotein (LDL)-cholesterol (LDL-C). To ascertain whether reduction of both LDL and Lp(a) is more advantageous than reduction of LDL alone, patients with heterozygous FH and CHD were selected randomly to receive either LDL apheresis fortnightly plus simvastatin 40 mg/day or colestipol 20 g plus simvastatin 40 mg/day. Quantitative coronary angiography was undertaken before and after 2.1 years. Changes in serum lipids were similar in both groups except for the greater reduction of LDL-C and Lp(a) by apheresis. There were no significant differences in primary angiographic endpoints, and none of the angiographic changes correlated with Lp(a). Although LDL apheresis plus simvastatin was more effective than colestipol plus simvastatin in reducing LDL-C and Lp(a), it was not more beneficial in influencing coronary atherosclerosis. Decreasing Lp(a) seems unnecessary if LDL-C is reduced below 130 mg/dl.—     

A Randomized Comparison between Everolimus-Eluting Stent and Cobalt Chromium Stent in Patients with Acute ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Using Routine Intravenous Eptifibatide: The X-MAN (Xience vs. Multi-Link Stent in Acute Myocardial Infarction) Trial,A Pilot Study

The objective of this study is to determine the efficacy and safety of an everolimus-eluting stent (EES/Xience; Abbott Vascular, Santa Clara, CA) compared with a cobalt chromium stent (CoCr/Multi-Link Vision; Abbott Vascular) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with routine administration of eptifibatide infusion. This is a prospective, single center, randomized trial comparing EES (n = 75) and CoCr stent (n = 75) implantation in patients with acute STEMI undergoing primary PCI. Intravenous eptifibatide administration was mandatory by protocol in this pilot study. The primary efficacy endpoint was major adverse cardiac events (MACE) at 30 days, defined as the composite of death, reinfarction, and target vessel revascularization. Secondary safety endpoints were stent thrombosis at 30 days and in-hospital bleeding event. Acute reperfusion parameters were also assessed. One-month MACE rate did not differ between EES and CoCr group (1.3 vs. 1.3%, p = 1.0). No stent thrombosis cases were observed in the EES group. The groups did not differ with respect to in-hospital bleeding events (5 vs. 9%, p = 0.37), achievement of final thrombolysis in myocardial infarction flow 2 or 3 (p = 0.21), achievement of myocardial blush grade 2 or 3 (p = 0.45), creatine kinase-MB level at 8 to 12 hours after stenting (p = 0.29), and left ventricular ejection fraction (p = 0.21). This pilot study demonstrates that after one-month follow-up, the use of EES is as safe and effective as the use of CoCr stents in patients with acute STEMI undergoing primary PCI with routine administration of intravenous eptifibatide.     

Final 5-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: The COMPARE Trial (A Trial of Everolimus-Eluting Stents and Paclitaxel Stents for Coronary Revascularization in Daily Practice)

ObjectivesThis study sought to report the 5-year outcomes of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in an all-comers population undergoing percutaneous coronary intervention (PCI).BackgroundThe medium-term 1 and 2-year results of the prospective randomized COMPARE trial (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) showed superior clinical outcomes with EES compared with PES in an all-comers PCI population. Whether this benefit is sustained over longer-term follow-up is unknown. Furthermore, systematic long-term follow-up data on these metallic drug eluting stents with durable polymers are scarce.MethodsWe randomly assigned 1,800 patients undergoing PCI to EES or PES. The pre-specified composite primary endpoint was death, myocardial infarction (MI), or target vessel revascularization (TVR).ResultsFollow-up at 5 years was completed in 1,791 (99.5%) patients. Treatment with EES compared with PES led to a relative risk reduction of the primary endpoint by 27% (18.4% vs. 25.1%, p = 0.0005), driven by lower rates of MI (7.0% vs. 11.5%, p = 0.001) and TVR (7.4% vs. 11.4%, p = 0.003), but not with mortality (9.0% vs. 10.3%, relative risk 0.88, p = 0.36). Moreover, patients treated with EES compared with PES had lower rates of definite/probable stent thrombosis at 5 years (3.1% vs. 5.9%, p = 0.005). The hazard curves for TVR, MI, and stent thrombosis diverge over the first 3 years and, subsequently, progress in parallel.ConclusionsThe early- and medium-term superiority of EES over PES measured both by safety and efficacy endpoints is sustained at 5 years in this all-comer population. (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice [COMPARE]; NCT01016041)