enkephalin--leucine-2-alanine and Duodenal-Ulcer

In the USSR, uncomplicated duodenal ulcer is usually managed in an inpatient setting. A double-blind, randomized, double-dummy, multiclinic, comparative trial examined the safety and efficacy of oral misoprostol (200 micrograms qid) and intramuscular dalargin (1 mg bid) in duodenal ulcer healing. Dalargin, an enkephalin peptide with gastric antisecretory and cytoprotective properties, is commonly used in the USSR for treating peptic ulcer. The trial characteristics and monitoring were performed in accordance with US standards. Consenting patients of either sex, aged 18 to 70 years, who had a duodenal ulcer of 0.3 to 2.5 cm in diameter were enrolled. Endoscopy, physical examination, and laboratory assessments were performed on entry and after 4 weeks of treatment. The effects of the treatments on complete ulcer healing, dyspeptic symptoms, antacid consumption, adverse drug reactions, and safety were determined. Both treatment groups were well matched for demographic characteristics. The majority of patients were smokers and alcohol users and had a history of recurrent peptic ulcers. Misoprostol was significantly more effective than dalargin in inducing duodenal ulcer healing, both in the intent-to-treat cohort (P = .001) and in the evaluable cohort (P = .0001). Both regimens were well tolerated, and no patients were withdrawn from the study because of adverse reactions. Mild, self-limiting diarrhea was reported more frequently in patients receiving misoprotol (9.4% incidence) than those receiving dalargin (1.9%). The disparity in ulcer healing between the two groups suggests that hospitalization alone is not an optimum treatment in this high-risk patient population.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Duodenal Ulcer; Enkephalin, Leucine-2-Alanine; Female; Humans; Male; Middle Aged; Misoprostol; Treatment Outcome; USSR

Having a large clinical material at their disposal, the authors base the necessity of the search and administration of more effective methods of duodenal ulcer treatment. Analyze the therapeutic effect produced by the enkephalin analogs (dalargin and its combinations with trichopol, de-nol, oxacillin) in connection with infection with Campylobacter . Comparison of the clinico-endoscopic data with the histological and cytological findings enabled arriving at a conclusion about the pathogenetic effect of the antimicrobial drugs. As a rule, the healing of ulcerous defects set in on days 11-14 of the treatment.

Topics: Adolescent; Aluminum Hydroxide; Antacids; Benzocaine; Child; Drug Combinations; Duodenal Ulcer; Enkephalin, Leucine-2-Alanine; Female; Humans; Magnesium Hydroxide; Male; Organometallic Compounds; Wound Healing

The article discusses treatment of 72 patients suffering from duodenal ulcer complicated by bleeding with the Soviet-made preparation Dalargin which is a synthetic analogue of leucine-enkephalin. The preparation was infused intravenously in a dose of 3 mg in physiological solution once daily. No other additional antiulcerative agents were give. The diagnosis was established on the basis of endoscopy. Dalargin led to cicatrization of the ulcers in 20.3 days in 60% of patient, obvious positive dynamics was noted in 32% of patients; in 8% of patients Dalargin proved ineffective. Basal hydrochloric acid secretion reduced by 56% during treatment.

Topics: Adult; Aged; Anti-Ulcer Agents; Clinical Trials as Topic; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Humans; Middle Aged; Peptic Ulcer Hemorrhage; Stomach Ulcer; Wound Healing

The radioligand-receptor method was used to assay the M-cholinereceptors and opioid binding centers in biopsy specimens of the duodenal mucosa from 40 patients with duodenal ulcer as compared with the results of subsequent therapy by means of gastrocepin (20 patients) and dalargin (20 patients). Analysis of the isothermal curve of 3H-QNB-binding with duodenal mucosa membranes within Skatchard's coordinates showed the presence of 2 subtypes of muscarinic receptors blocked (M1) and not blocked (M2) by gastrocepin. The majority of the patients in both groups demonstrated a significant decrease of the dissociation constant as compared to the control (20 patients). In patients with high receptor sensitivity to gastrocepin and dalargin, ulcer cicatrization was noted during the treatment in all the cases. Meanwhile the treatment proved little effective in patients with appreciably decreased receptor sensitivity to the drugs under consideration. The data obtained indicate the possibility of predicting the results of duodenal ulcer treatment by means of the radioreceptor analysis, providing the basis for the individualized treatment choice.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Clinical Trials as Topic; Duodenal Ulcer; Duodenum; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Pirenzepine; Radioligand Assay; Receptors, Muscarinic; Receptors, Opioid

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Female; Humans; Iontophoresis; Male; Middle Aged; Wound Healing

The paper is concerned with the results of clinical assessment of a new peptide drug dalargin in therapy of duodenal peptic ulcer. Assessment of the efficacy of dalargin was compared to that of tagamet and placebo using double "blind" control. A total of 180 males with exacerbation of duodenal ulcer were examined, of them 90 received dalargin only, 70 received tagamet and 20 persons participated in an experiment based on a method of double "blind" control. An average period of duodenal ulcer healing in the patients on dalargin therapy was 21.4 +/- 1.2 days, and by the 28th day complete cicatrization was observed in 87.5% of the patients. In tagamet therapy an average period of cicatrization was 23.7 +/- 1.8 days, by the 28th day ulcer healing was observed in 87.3%. With placebo ulcer healing by the 4th week was observed in 30% of the examinees, in dalargin therapy in 80%. A conclusion was made of high efficacy of dalargin for therapy of peptic ulcer.

Topics: Adolescent; Adult; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Humans; Male; Middle Aged

The paper presents the results of comprehensive examination and treatment of 120 patients with giant and multiple duodenal ulcers at the N. A. Semashko Regional Hospital gastroenterological department. Was suggested, that combined therapy of patients with dalargine was most effective, then traditional therapy of peptic ulcer.

Topics: Administration, Intranasal; Anti-Ulcer Agents; Duodenal Ulcer; Enkephalin, Leucine-2-Alanine; Humans; Iontophoresis; Male; Middle Aged; Peptic Ulcer; Pharmaceutical Preparations; Treatment Outcome

Kept under medical surveillance were 120 patients with duodenal ulcer running an uncomplicated course. All patients and 30 healthy donors were studied for the status of the immunity T-system by spontaneous E-rosette formation (E-RFC) and availability of theophylline-resistant (TPP-RFC) and theophylline-sensitive (TPS-RFC) lymphocytes. With B-system being studied by FAC-rosette formation. All patients with duodenal ulcer displayed a decline in the content of E-RFC, TFP-RFC, TFS-RFC as compared to the indices in controls. Inclusion into the combined therapy of thymalin and dalargin was noted to be associated with a positive dynamics in the rise of T-lymphocytes, their subpopulations to the level in controls, percentage of TFS-RFC. Indices for TFS-RFC did not differ from control ones either before or after the treatment.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; B-Lymphocyte Subsets; Chronic Disease; Drug Evaluation; Duodenal Ulcer; Enkephalin, Leucine-2-Alanine; Female; Humans; Male; Middle Aged; T-Lymphocyte Subsets; Thymus Hormones

The effect of synthetic opiate peptide dalargin, histamine H2-receptors blockers (cimetidin, famotidin) and combination of dalargin with famotidin on proliferative activity of gastroduodenal mucosal epithelium has been studied autoradiographically (3H-thymidine) in 75 patients with duodenal ulcer. Compared to spasmolytics and antacids, the studied drugs (dalargin, cimetidin and famotidin) significantly increased the number of DNA-synthetizing cells in the epithelium of fundal stomach, duodenal cap and ulcer borders. Maximal effect was noticed in combined use of dalargin and famotidin. A correlation existed between clinical and stimulating reparative effect of the drugs.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Autoradiography; Biopsy; Cell Division; DNA; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Digestive System; Enkephalin, Leucine-2-Alanine; Histamine H2 Antagonists; Humans; Injections, Intramuscular; Intestinal Mucosa; Male; Middle Aged; Treatment Outcome

A study of 90 patients with endoscopically proved duodenal ulcer revealed that dalargin and trichopol+dalargin treatment resulted in early scarring of the ulcer and control of gastroesophageal and duodenogastric reflux in the majority of patients. Gastroduodenitis symptoms were not eliminated in a half of all patients. It was shown that persistent manifestations of gastroduodenitis remained in patients with a pronounced pyloric helicobacteriosis and a high titer of antibodies to cells of the gastric mucosa.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Evaluation; Drug Therapy, Combination; Duodenal Ulcer; Enkephalin, Leucine-2-Alanine; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds

Sixty patients with ulcer disease of the duodenum were observed during the phase of remission. The main group (30 patients) received as prophylactic treatment dalargin electrophoresis (20 sessions) on epigastric region. The control group (30 patients) received analogously 2% benzohexonium solution electrophoresis. Within 12 months patients of the main group showed 2.3 rarer remission than patients of the control group. The economic effect is discussed.

Topics: Adult; Anti-Ulcer Agents; Duodenal Ulcer; Duodenoscopy; Enkephalin, Leucine-2-Alanine; Gastric Mucosa; Humans; Iontophoresis; Male; Middle Aged; Recurrence

Changes in the number of DNA-synthesizing nuclei of gastroduodenal mucosa in duodenal ulcer were monitored for patients treated with dalargin versus standard therapy (spasmolytics and antacids). In contrast to the standard treatment, dalargin 20-day administration produced a significant increase in the index of 3H-thymidine-labelled epithelial nuclei in fundal and duodenal bulb mucosa. The capacity for activating DNA synthesis in gastroduodenal mucosa may represent an essential mechanism of dalargin therapeutic action.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Duodenal Ulcer; Endoscopy, Gastrointestinal; Enkephalin, Leucine-2-Alanine; Gastric Mucosa; Humans; Intestinal Mucosa; Male; Reference Values; Wound Healing

The distribution of gastrin-, gamma-endorphin and somatostatin-producing cells in antral and duodenal mucosa was studied in biopsies from 26 patients with duodenal ulcer and from 13 controls by the immunohistochemical (PAP) method. The number of antral somatostatin-producing cells after dalargin treatment was significantly higher in comparison with controls and patients treated with antacids plus atropine. These changes may be connected with the antiulcer activity of dalargin, a new opioid peptide drug.

Topics: Adult; Chromaffin System; Duodenal Ulcer; Duodenum; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enterochromaffin Cells; gamma-Endorphin; Gastrins; Gastrointestinal Hormones; Humans; Male; Pyloric Antrum; Somatostatin

Dalargin injected subcutaneously at a dose of 10 micrograms/kg decreased 4-5 fold ulcer manifestations in rats with cysteamine-induced duodenal ulcers. Intracerebroventricular dose of 2 micrograms diminished the manifestations to a lesser extent Dalargin only at a dose exceeding 500 micrograms intraperitoneally decreased significantly the in vivo binding of 3H-D-Ala2, D-Leu5-enkephalin with brain opiate receptors. We believe that Dalargin injected peripherally in small doses does not penetrate the blood-brain barrier and that its antiulcer activity is due to the interaction with peripheral opioid receptors. It seems possible that the disturbances in the central/peripheral ratio of the opioid activity plays an important role in the pathogenesis of duodenal peptic ulcer.

Topics: Animals; Anti-Ulcer Agents; Brain; Cysteamine; Disease Models, Animal; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Injections, Intraventricular; Injections, Subcutaneous; Male; Rats; Rats, Inbred Strains; Receptors, Opioid

The effect of an opioid antiulcerogenic hexapeptide dalargin on ornithine decarboxylase activity of duodenal mucosa has been studied in rats with experimental duodenal ulcers induced by cysteamine. The intraperitoneal injection of 12.5 micrograms/kg of dalargin inhibited ulcerogenesis and activated the enzyme. The effect of the peptide was antagonized by an opiate antagonist naloxone. 5000 micrograms/kg of dalargin failed to inhibit the ulcer formation or to activate ornithine decarboxylase. Since ornithine decarboxylase activation is a marker of intensified cell proliferation and tissue regeneration, our results suggest that the antiulcerogenic effect of dalargin is due to the enhancement of duodenal mucosa regeneration.

Topics: Animals; Anti-Ulcer Agents; Cysteamine; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Duodenal Ulcer; Duodenum; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Intestinal Mucosa; Male; Ornithine Decarboxylase; Rats; Rats, Inbred Strains

Topics: Anti-Ulcer Agents; APUD Cells; Biopsy; Digestive System; Drug Evaluation; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Humans

Topics: Animals; Anti-Ulcer Agents; Biotransformation; Drug Evaluation, Preclinical; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Guinea Pigs; Hydrolysis; Male; Mice; Rats; Rats, Inbred Strains; Receptors, Opioid; Structure-Activity Relationship

Topics: Adult; Anti-Ulcer Agents; Drug Evaluation; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Hormones; Humans; Infusions, Intravenous; Male; Middle Aged

Topics: Anti-Ulcer Agents; Drug Evaluation; Duodenal Ulcer; Endocrine Glands; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Humans; Male; Time Factors

Topics: Animals; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Duodenal Ulcer; Duodenum; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Injections, Intraperitoneal; Intestinal Mucosa; Male; Ornithine Decarboxylase; Rats; Rats, Inbred Strains

The role and possible clinical use of regulatory peptides, a new type of regulatory substances, is discussed. Special attention is paid to the opioid peptides and their analogues. The new drug dalargin has been developed on the basis of the endogenous opioid peptide leucine-encephalin. Its action has been studied using experimental models. It has been established that the optimal dose (10 micrograms/kg) of dalargin is effective in preventing ulceration in the cystamine duodenal ulcer rat model and the development of stomach erosive lesions in immobilization stress, reducing the degree of liver degeneration in CCl4 poisoning, etc. With an increase of the dose of dalargin the effect "escapes". Dalargin is primarily bound by delta-receptors, it produces no analgetic effect and does not enter the brain. Dalargin exhibits a pronounced cytoprotective and regeneratory action and may take an important place in treating the internal organ diseases.

Topics: Animals; Carbon Tetrachloride Poisoning; Cells, Cultured; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Duodenal Ulcer; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Hemorrhage; Humans; Lymphocytes; Mice; Necrosis; Pancreas; Rats; Receptors, Opioid; Stomach Ulcer