Pharmacologic therapy for acute pancreatitis

While conservative management such as fluid,bowel rest,and antibiotics is the mainstay of current acute pancreatitis management,there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis.Extensive review of preclinical studies,which include assessment of therapies such as anti-secretory agents,protease inhibitors,anti-inflammatory agents,and anti-oxidants are discussed.Many of these studies have shown therapeutic benefit and improved survival in experimental models.Based on available preclinical studies,we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis.To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies.Despite these discouraging clinical studies,there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients.Better understanding of acute pancreatitis pathophysiology and lessons learnedfrom past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.

Stronger inhibition of gastric acid secretion by lafutidine, a novel H_2 receptor antagonist, than by the proton pump inhibitor lansoprazole

AIM: To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg. METHODS: Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug. RESULTS: The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg. CONCLUSION: In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidinethan by LPZ.

Gastroprotective effect of aqueous stem bark extract of Ziziphus jujuba L.against HCl/Ethanol-induced gastric mucosal injury in rats

OBJECTIVE: To evaluated the gastroprotective effects of standardized aqueous extract of Ziziphus jujuba(Z. jujuba) stem bark against acidified ethanol-induced gastric ulcers as well as anti helicobacter pylori activity of the plant extract in rats.METHODS: Five groups of rats were orally pre-treated with normal saline(0.9%) as ulcer group, 150 mg/kg of ranitidine as positive control group, 100, 200 and 400 mg of standardized extract solution as the experimental groups. Two hours later, acidified ethanol solution was given by gavages in order to induce of gastric ulcer. The antibacterial effect of extract against clinical strains of Helicobacter pylori(H. pylori) was evaluated through disc diffusion test.RESULTS: The ulcer group exhibited significantly severe mucosal injury as compared with ranitidine or extract group which shows significant protective action against gastric mucosal injury. The extract showed no effect on H. pylori.CONCLUSION: The present study indicates that Z.jujuba stem bark extract had a potential antiulcer activity which might be due to its protective activity, providing a direct, protective effect on the gastric mucosa. Our study showed that anti-H. pylori activity was not among gastroprotective mechanism of Z. jujuba. Further pre-clinical and clinical investigations for evaluating natural active agents and efficacy of this plant are recommended.

Antidiarrheal activity of hexane extract of Citrus limon peel in an experimental animal model

OBJECTIVE： Acute diarrhea is one of the major illnesses that cause death in children, despite clinical interventions and the use of oral rehydration therapy. Thus, there is need to discover other effective, affordable and accessible treatments for this disease. Therefore, this study was carried out to investigate the effects of hexane extract of Citrus limon peel （HECLP） on castor oil-induced diarrhea in rats. METHODS： Diarrhea was induced in male albino Wistar rats weighing 100-150 g. The antidiarrheal activity of HECLP at different oral dosages （5, 10 and 20 mg/kg） was investigated by counting the number of wet fecal pellets. Animals were further treated with propranolol, prazosin, nifedipine and atropine to assess the effects of receptor blockers on the activities of the extract. The effects of HECLP on castor oil-induced enteropooling and the intestinal transit time of activated charcoal were also evaluated. RESULTS： Each of the 3 doses of C. limon significantly reduced （P 〈 0.05） the number of wet fecal pellets produced by animals, with 20 mg/kg HECLP producing the highest percentage inhibition （34.2%） Wet fecal pellet inhibition by the standard drug Ioperamide （3 mg/kg p.o.） was 68.4% relative to the negative control. Blockage of 13 adrenergic receptors by propanolol abolished the antidiarrheal effects of HECLP. Intestinal fluid accumulation was inhibited by 68.7% and 78.5% by 20 mg/kg HECLP and Ioperamide respectively. Furthermore, 20 mg/kg HECLP significantly （P 〈 0.05） reduced the percentage intestinal transit time （21.4% ± 1.42%）, relative to the control （34.2% ±4.29%）; atropine （5 mg/kg, intraperitoneal injection） significantly （P 〈 0.001） reduced the percentage intestinal transit time to 11.2% ±0.85%. CONCLUSION： These results suggest that C. limon peel possesses antidiarrheal effects through antisecretory and antimotility mechanisms that act through the β adrenergic system.