Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen alpha1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor alpha showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.

Choleretic and antispasmodic effects of Lippia integrifolia aqueous extract / Efeitos colerético e antiespasmódico do extrato aquoso de Lippia integrifolia

The aqueous extract of the aerial parts of Lippia integrifolia has been assayed for its choleretic and antispasmodic effects. Doses of 250, 500 and 750 mg/kg administered orally in rats significantly increased the bile flow and the bile acid output. The extract also showed a significant reduction of the contractions induced by acetylcholine, CaCl2 and KCl on isolated rat jejunum. The total caffeoyl quinic acids derivatives content, expressed as chlorogenic acid was 0.10 percent w/v by spectrophotometric determination.

O extrato aquoso das partes aéreas de Lippia integrifolia foi ensaiado quanto aos seus efeitos colerético e antiespasmódico. Doses de 250, 500 e 750 mg/kg administradas oralmente em ratos aumentaram significativamente o fluxo biliar e a saída de ácidos biliares. O extrato também exibiu uma significativa redução das contrações induzidas por acetilcolina, CaCl2 e KCl em jejuno isolado de rato. O conteúdo total de derivados dos ácidos cafeoilquínicos, expressado como ácido clorogênico foi de 0.10 por cento w/v através de determinação espectrofotométrica.

Establishment of an infected necrotizing pancreatitis model by retrograde pancreatic duct injection of sodium taurocholate and E. coli in rats / 华中科技大学学报（医学）（英德文版）

A stable and reliable infected necrotizing pancreatitis (INP) model in rats was established in order to study the pathophysiological mechanism and pathological development rule of INP and explore the new therapeutic methods for the diseases. Forty-six SD rats were randomly divided into 5 groups. The animals in group A received the injection of 5% sodium taurocholate into the pancreatic duct and those in group B underwent that of E. coli into the pancreatic duct. The rats in groups C, D and E were subjected to the injection of 5% sodium taurocholate in combination with different concentrations of E. coli (10(3), 10(4), 10(5)/mL, respectively) into the pancreatic duct. The dose of injection was 0.1 mL/100 g and the velocity of injection was 0.2 mL/min in all the 5 groups. Eight h after the injection, the survival rate of animals was recorded and the surviving rats were killed to determine the serum content of amylase and perform pathological examination and germ cultivation of the pancreatic tissue. The results showed that acute necrotizing pancreatitis model was induced by injection of 5% sodium taurocholate into the pancreatic duct. The positive rate of germ cultivation in group A was 12.5%. The acute necrotizing pancreatitis model was not induced by injection of E. coli into the pancreatic duct and the positive rate of germ cultivation in group B was 0. The INP model was established in groups C to E. The positive rate of germ cultivation was 60%, 100% and 100% and 8-h survival rate 100%, 100% and 70% in groups C, D and E, respectively. It was concluded that a stable and reliable model of INP was established by injection of 5% sodium taurocholate in combination with 10(4)/mL E. coli into the pancreatic duct with a dose of 0.1 mL/100 g and a velocity of 0.2 mL/min. The pathogenesis of INP might be that the hemorrhage and necrosis of pancreatic tissue induced by sodium taurocholate results in weakness of pancreatic tissue in fighting against the germs. Meanwhile, the necrotic pancreatic tissue provides a good proliferative environment for the germs.

Influence of Corticosteroids on the Hepatic Cell and Bile Secretion (1)

Daily administration of glucocorticoids for 10 days to dogs resulted in a significant increase in the hepatic bile secretion in response to secretory stimulants. The response of hepatic bile in testosterone-treated animals was not changed and the response was increased in DOCA--treated animals. A significant increase of liver weight was induced by the animals receiving glucocorticoids. Other organ weight was not changed; however, a slight reduction of kidney weight was seen in prednisolone, dexamethasone, and DOCA treated animals and also in animals supplemented with cortisone following adrenalectomy. The presence of large areas of ballooning and vesicular changes of liver cells was seen in glucocorticoid treated animals, particularly in cases of dexamethasone and prednisolone. Both vesicular changes of liver cell and its glycogen content were increased by the repeated administration of prednisolone and reduced by the cessation of treatment. Special stain and liver glycogen determination demonstrated the material distending the liver cell was glycogen. These findings indicate that long term administration of glucocorticoids results in an increase of liver weight and hepatic glycogen content as well as increased bile secretion.