enkephalin-leu--ala(2)-arg(6)- and Stomach-Ulcer

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

We studied the effect of dalargin and its analogue [Dala]2-leu-enkephalin on the gastric mucosa in indomethacin-receiving animals. Indomethacin treatment was followed by severe injury to the gastric mucosa, decrease in proliferative activity of the epithelium, and stimulation of free-radical processes in gastric tissues. Dalargin significantly decreased the area of erosive and ulcerative lesions, had a normalizing effect on proliferation of epithelial cells, and reduced the degree of oxidative stress. Administration of [Dala]2-leu-enkephalin did not improve the state of the gastric mucosa.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Proliferation; DNA; Drug Interactions; Enkephalin, Leucine-2-Alanine; Epithelial Cells; Free Radicals; Gastric Mucosa; Gastrointestinal Agents; Indomethacin; Luminescence; Male; Oxidative Stress; Rats; Stomach Ulcer; Time Factors

The function of the isolated perfused rat hearts was studied in four groups of experiments. Group 1--included the hearts of intact animals ("absolute control"), group 2--the hearts of rats subjected to 24 hour immobilization in supine position against the background of triple intramuscular injections of placebo (control), group 3 included the hearts of rats, which during 24 hour immobilization stress were thrice injected a synthetic analogue of endogenous opioids Dalargin in a dose of 3 g/kg, and group 4 included the hearts of animals, which during immobilization were administered Dalargin in a dose of 10 g/kg of body mass. Ulcer index as indicator of stress injury of gastric mucosa was also determined. In the control group of experiments (group 2) 24 hour immobilization stress resulted in complete depression of cardiac performance as compared with group 1, and ulcer index approximated 1. In group 3 the indices of cardiac performance even exceeded those in group 1 (intact animals). As compared with group 2, ulcer index in group 3 decreased by 9 times. In application of Dalargin in a dose of 10 g/kg complete preservation of heart function indices and complete prevention of stress injury of gastric mucosa were also observed. Thus, Dalargin possesses cardioprotective and anti-ulcerogenic effect in immobilization stress in rats. Most probably, this phenomenon can be attributed to its ability to inhibit the activity of sympathoadrenal system, which gets enhanced during stress.

Topics: Animals; Anti-Ulcer Agents; Enkephalin, Leucine-2-Alanine; Gastric Mucosa; Heart; Immobilization; In Vitro Techniques; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological; Sympatholytics

Three series of experiments were performed in Wistar male rats. The first series covered the study of the function of isolated perfused hearts and the status of the gastric mucosa in intact animals. In series II and III, Stages IIIB-IV contact burn of 25% body surface was induced by a special device. The animals were observed for 24 hours. Following 23.5 hours of burn, the rats were injected placebo (Series II) or the synthetic Leu-enkephalin analogue dalargin, 10 micrograms/kg in the same amounts as placebo (Series III). After observation, the animals' hearts and stomachs were isolated and explored. In Series II, there was a considerable decrease in all the indices of cardiac function as compared to the controls, the ulcer index that characterizes the severity of stress-induced gastric mucosa injury was found to be 8.2. In Series III, the indices of cardiac function were even substantially higher than those in intact animals, the ulcer index was reduced to 0.01. Thus, dalargin, a Soviet synthetic Leu-enkephalin analogue, possesses marked anti-stress and cardioprotective effects in severe thermal trauma. The paper also considers the likely mechanisms responsible for the phenomena observed.

Topics: Animals; Burns; Disease Models, Animal; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Gastric Mucosa; Heart; Heart Failure; In Vitro Techniques; Male; Models, Cardiovascular; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological

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