J Gastroenterol Hepatol. 2004 Sep;19 Suppl 3:S49-53.
Management strategies for gastroesophageal reflux disease.
Bak YT.
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. drbakyt@korea.ac.kr
In the treatment of gastroesophageal reflux disease (GERD), the most effective treatment option is the use of proton pump inhibitor (PPI), which minimizes the effect of gastric acid on the distal esophagus. Both the step-up and step-down treatment strategies have advantages and disadvantages. Most physicians would like to choose the step-down therapy rather than the step-up therapy. The 'No-step' PPI therapy (i.e. continuous PPI therapy) is another relevant option. After an initial remission, long-term PPI therapy is an appropriate form of maintenance therapy in many patients. As a treatment plan for non-erosive reflux disease, a standard dose of PPI for 4-8 weeks followed by either the step-down strategy or the on-demand treatment strategy is acceptable. When treating erosive esophagitis, PPI is better than H(2) receptor blockers in healing mucosal breaks and relieving symptoms. Long-term maintenance PPI therapy is reported to be very effective in maintaining the remission of reflux esophagitis for up to 5 years. On-demand PPI is also another good option for a maintenance therapy in erosive esophagitis. In Barrett's esophagus, symptoms seem to be well-controlled with PPIs. Unfortunately, however, PPIs have no effect on the shortening of Barrett's esophagus or in preventing the progression to dysplasia and adenocarcinoma. In summary, after reviewing existing guidelines a rather simple guideline on the management of GERD is suggested - PPI should be given for 4-8 weeks followed by either on-demand or maintenance PPI therapy according to the clinical severity.
PMID: 15324382 [PubMed - indexed for MEDLINE]

Drugs Today (Barc). 2004 Mar;40 Suppl A:3-8.
GERD 2003: issues from the past and a consensus for the future.
Modlin I, Kidd M.
Gastric Pathology Research Group, Department of Surgery, Yale University, School of Medicine, New Haven, CT 06520-8062, USA.
Gastroesophageal reflux disease (GERD) has evolved from a scarcely reported, little understood disease process just a century ago to a now highly prevalent disease with up to 25% of the population complaining of symptoms of reflux. Throughout history attempts have been made to delineate the esophagus and related pathologies, but it has not been until relatively recently that enough has been understood about its screening, diagnosis and treatment to make a substantial impact on sufferers. Although the use of antacids and thereafter histamine 2 receptor antagonists dramatically improved the management of GERD, it was the advent of the proton pump inhibitor (PPI) class of drugs that revolutionized medical care. Although the relationship of hiatus hernia to reflux was well accepted, the modest results of open fundoplication fell into further disregard given the efficacy of PPIs. The PPIs are currently the most effective form of therapy and are equivalent on a milligram for milligram basis. While currently no novel drugs or devices are of proven efficacy for GERD, the development of an acid-suppressive agent of equal efficiency to a PPI but with a more rapid onset of action and a greater duration of effectiveness would be of particular clinical utility for the future. (c) 2004 Prous Science
PMID: 15190381 [PubMed - indexed for MEDLINE]

Life Sci. 2004 Oct 29;75(24):2867-78.
Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer.
Bandyopadhyay U, Biswas K, Sengupta A, Moitra P, Dutta P, Sarkar D, Debnath P, Ganguly CK, Banerjee RK.
Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, 700032, India. ubandyo_1964@yahoo.com
We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has potent antisecretory and antiulcer effects in animal models and has no significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865, 2002). The objective of the present study was to investigate whether Neem bark extract had similar antisecretory and antiulcer effects in human subjects. For this purpose, a group of patients suffering from acid-related problems and gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark. The lyophilised powder of the extract when administered for 10 days at the dose of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric acid secretion. The volume of gastric secretion and its pepsin activity were also inhibited by 63% and 50%, respectively. Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained close to the control values. The bark extract when taken at the dose of 30-60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers monitored by barium meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux disease) and one case of gastric ulcer also healed completely when treated at the dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for organ toxicity after Neem treatment at the doses mentioned above remained more or less close to the normal values suggesting no significant adverse effects. Neem bark extract thus has therapeutic potential for controlling gastric hypersecretion and gastroesophageal and gastroduodenal ulcers.
PMID: 15454339 [PubMed - indexed for MEDLINE]

Life Sci. 2002 Nov 1;71(24):2845-65.
Gastroprotective effect of Neem (Azadirachta indica) bark extract: possible involvement of H(+)-K(+)-ATPase inhibition and scavenging of hydroxyl radical.
Bandyopadhyay U, Biswas K, Chatterjee R, Bandyopadhyay D, Chattopadhyay I, Ganguly CK, Chakraborty T, Bhattacharya K, Banerjee RK.
Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick road, Kolkata 700032, India.
The antisecretory and antiulcer effects of aqueous extract of Neem (Azadirachta indica) bark have been studied along with its mechanism of action, standardisation and safety evaluation. The extract can dose dependently inhibit pylorus-ligation and drug (mercaptomethylimidazole)-induced acid secretion with ED(50) value of 2.7 and 2 mg Kg(-1) b.w. respectively. It is highly potent in dose-dependently blocking gastric ulcer induced by restraint-cold stress and indomethacin with ED(50) value of 1.5 and 1.25 mg Kg(-1) b.w. respectively. When compared, bark extract is equipotent to ranitidine but more potent than omeprazole in inhibiting pylorus-ligation induced acid secretion. In a stress ulcer model, it is more effective than ranitidine but almost equipotent to omeprazole. Bark extract inhibits H(+)-K(+)-ATPase activity in vitro in a concentration dependent manner similar to omeprazole. It offers gastroprotection against stress ulcer by significantly preventing adhered mucus and endogenous glutathione depletion. It prevents oxidative damage of the gastric mucosa by significantly blocking lipid peroxidation and by scavenging the endogenous hydroxyl radical ((z.rad;)OH)-the major causative factor for ulcer. The (z.rad;)OH-mediated oxidative damage of human gastric mucosal DNA is also protected by the extract in vitro. Bark extract is more effective than melatonin, vitamin E, desferrioxamine and alpha-phenyl N-tert butylnitrone, the known antioxidants having antiulcer effect. Standardisation of the bioactive extract by high pressure liquid chromatography indicates that peak 1 of the chromatogram coincides with the major bioactive compound, a phenolic glycoside, isolated from the extract. The pharmacological effects of the bark extract are attributed to a phenolic glycoside which is apparently homogeneous by HPLC and which represents 10% of the raw bark extract. A single dose of 1g of raw extract per kg b.w. (mice) given in one day and application of 0.6g raw extract per kg b.w. per day by oral route over 15 days to a cumulative dose of 9g per kg was well tolerated and was below the LD(50). It is also well tolerated by rats with no significant adverse effect. It is concluded that Neem bark extract has therapeutic potential for the control of gastric hyperacidity and ulcer.
PMID: 12377267 [PubMed - indexed for MEDLINE]