Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease.

Prolonged use of total parenteral nutrition can lead to nonalcoholic fatty liver disease, ranging from hepatic steatosis to cirrhosis and liver failure. It has been demonstrated that omega-3 fatty acids are negative regulators of hepatic lipogenesis and that they can also modulate the inflammatory response in mice. Furthermore, they may attenuate hepatic steatosis even in leptin-deficient ob/ob mice. We hypothesized that omega-3 fatty acid supplementation may protect the liver against hepatic steatosis in a murine model of parenteral nutrition in which all animals develop steatosis and liver enzyme disturbances. For testing this hypothesis, groups of mice received a fat-free, high-carbohydrate liquid diet ad libitum for 19 d with enteral or i.v. supplementation of an omega-3 fatty acid emulsion or a standard i.v. lipid emulsion. Control mice received food alone or the fat-free, high-carbohydrate diet without lipid supplementation. Mice that received the fat-free, high-carbohydrate diet only or supplemented with a standard i.v. lipid emulsion developed severe liver damage as determined by histology and magnetic resonance spectroscopy as well as elevation of serum liver function tests. Animals that received an i.v. omega-3 fatty acid emulsion, however, showed only mild deposits of fat in the liver, whereas enteral omega-3 fatty acids prevented hepatic pathology and led to normalization of liver function tests. In conclusion, whereas standard i.v. lipid emulsions fail to improve dietary-induced steatotic injury to the liver, i.v. supplementation of omega-3 fatty acids partially and enteral supplementation completely protects the liver against such injury.

In situ inhibition of uterine activity by indomethacin: possible relevance to preterm labor prevention after fetal surgery.

PURPOSE: This report is an analysis of the effects of local indomethacin delivery on uterine activity in vitro. METHODS: Isolated strips of time-dated pregnant rats' myometrium were placed within controlled tissue baths. Spontaneous muscular activity was recorded by a force transducer connected to a polygraph at cumulative concentrations of indomethacin. Statistical analysis was by single-factor analysis of variance (ANOVA), with P values of less than.05 considered significant. RESULTS: Within a narrow concentration range, the effects of indomethacin on frequency and amplitude of myometrial contractions were nonmonotonic, with an increase in frequency at levels that began to depress amplitude. However, both amplitude and frequency were significantly depressed and eventually totally abolished at most concentrations studied (P <.05). CONCLUSIONS: Indomethacin administered in situ consistently inhibits or completely arrests overall myometrial activity. The concept of local myometrial delivery of indomethacin, possibly via slow release systems, may prove clinically useful as an adjuvant to its systemic administration in preterm labor prevention after fetal surgery, warranting further trials in vivo.

Clostridium botulinum toxin inhibits myometrial activity in vitro: possible application on the prevention of preterm labor after fetal surgery.

BACKGROUND/PURPOSE: The current study aimed to analyze the effects of Clostridium botulinum toxin (Botox) on pregnant myometrium activity in vitro. METHODS: Strips of myometrium were obtained from pregnant Wistar rats on gestational day 13 through 15 and placed under controlled conditions within tissue baths containing DeJalon solution. Muscular activity, including amplitude and frequency of contractions, was recorded by a force transducer connected to a polygraph. After stable baseline values were recorded, different concentrations of Botox were added to the tissue baths. Myometrial activity data points for each drug concentration were entered as mean percentual variations of the baseline. A total of 26 uterine samples from 13 animals were studied. Statistical analysis was by single-factor analysis of variance (ANOVA) with P <.05 considered significant. RESULTS: Except for a narrow concentration range, when the effects were nonmonotonic, both amplitude and frequency of myometrial contractions were significantly depressed (P <.05) and eventually totally abolished at most concentrations studied, albeit in a potentially biphasic pattern. Those effects could be reversed by a complete washout of the tissue bath. CONCLUSIONS: Within appropriate concentrations, Botox consistently inhibits or completely arrests myometrial activity in potentially reversible fashion. This agent may prove valuable in premature labor prevention after fetal surgery.