Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function.     

Behavioral effects of clozapine: comparison with thioridazine, chlorpromazine, haloperidol and chlordiazepoxide in squirrel monkeys

The behavioral effects of the antipsychotic drug, clozapine, were compared with those of thioridazine, chlorpromazine, haloperidol and chlordiazepoxide. Behavior of squirrel monkeys was controlled by different consequences of a lever-pressing response (presentation of food, presentation of electric shock or termination of a stimulus associated with electric shock) under different schedules of reinforcement (a fixed-interval schedule or a multiple schedule with alternating fixed-ratio and fixed-interval components). The effects of thioridazine (0.2-24.6 mumol/kg), chlorpromazine (0.03-2.8 mumol/kg) and haloperidol (0.001-0.08 mumol/kg) were largely independent of the type of schedule or the type of consequent event that maintained responding: each drug produced dose-related decreases in responding under all conditions in which they were studied. Clozapine (0.1-9.2 mumol/kg) and chlordiazepoxide (0.9-167.4 mumol/kg) also only decreased responding under most schedule conditions; however, intermediate doses of either drug markedly increased responding maintained by presentation of food under the fixed-interval schedule (whether programmed singly or as a component of the multiple schedule). Only clozapine increased responding maintained by presentation of electric shock under the fixed-interval schedule. Thus, the behavioral effects of clozapine differed qualitatively from those of representative antipsychotic and antianxiety drugs.     

Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study

The results of a randomized, double-blind, placebo-controlled multicenter trial of fenofibrate in the treatment of type IV/V hyperlipoproteinemia are reported. Ten study centers in the United States recruited 147 adults with a history of type IV or V hyperlipoproteinemia. After a six- to 12-week dietary stabilization period and a four-week placebo period, patients whose 12-hour fasting total plasma triglyceride levels ranged from 350 to 1,500 mg/dl were continued in the study; 55 patients with levels of 350 to 499 mg/dl were placed in group A and 92 with levels of 500 to 1,500 mg/dl in group B. Patients in each group were randomly assigned to receive 100 mg of fenofibrate or placebo three times daily for eight weeks. In both groups A and B fenofibrate-treated patients showed statistically significant reductions in levels of total cholesterol, very-low-density lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein triglycerides, and significant increases in high-density lipoprotein cholesterol; patients in group B also showed a significant increase in low-density lipoprotein cholesterol levels. Sixteen of the 75 fenofibrate-treated patients and 11 of the 72 placebo patients reported adverse events that were potentially drug related; most of these were gastrointestinal and a few reported musculoskeletal and skin reactions. It is concluded that fenofibrate is an effective and safe agent in the treatment of type IV/V hyperlipoproteinemia.     

The bumper stitch for drainage tube securement: preliminary study

Tube dislodgment is a common problem in drainage procedures. The present report compares a securement technique known as the bumper stitch, which aims to reduce tube motion and suture erosion, versus the traditional air knot. A total of 61 patients were enrolled, and 12 bumper stitches and 54 air knots were observed. Eighty-three percent of bumper tubes had no play (ie, in-and-out motion), versus 41% of the air knot tubes (P = .02); the mean amount of play with the bumper was 0.4 mm, versus 4.7 mm for the air knot (P = .007). The bumper stitch significantly reduces tube play and may therefore aid in reducing dislodgment.     

Treatment options for articular cartilage defects of the knee

The treatment of symptomatic articular cartilage defects of the knee has evolved tremendously in the past decade. Previously, there were limited treatment options available to patients who suffered from either partial-thickness or full-thickness cartilage lesions. Because articular cartilage has a limited capacity for healing, patients were often treated symptomatically until they became candidates for osteotomy or total joint replacement. Recently, both reparative and restorative procedures have been developed to address this significant source of morbidity in young active patients. Microfracture is a reparative technique that induces a healing response to occur in an area of articular cartilage damage. Osteochondral autografts and allografts in addition to autologous chondrocyte implantation are restorative techniques aimed at recreating a more normal articular surface. Both types of procedures have been developed to alleviate the symptoms associated with focal chondral defects, as well as limit their potential to progress to a diffuse degenerative arthritis. Treatment can vary depending on both cartilage defect and patient factors. This article summarizes the various treatment options that have recently become available.