Arbaprostil: A synthetic prostaglandin E analog that protects the gastric mucosa, prevents ulceration, and promotes healing of peptic ulcers. The protective effect is independent of acid inhibition. It is also a potent inhibitor of pancreatic function and can inhibit the growth of experimental tumors.Prostaglandins E, Synthetic: Analogs or derivatives of prostaglandins E that do not occur naturally in the body. They do not include the product of the chemical synthesis of hormonal PGE.Gastric Acid: Hydrochloric acid present in GASTRIC JUICE.Alcohols: Alkyl compounds containing a hydroxyl group. They are classified according to relation of the carbon atom: primary alcohols, R-CH2OH; secondary alcohols, R2-CHOH; tertiary alcohols, R3-COH. (From Grant & Hackh's Chemical Dictionary, 5th ed)Alcohol Drinking: Behaviors associated with the ingesting of alcoholic beverages, including social drinking.Alcohol Dehydrogenase: A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen.KetonesAlcohol Oxidoreductases: A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).Butanols: Isomeric forms and derivatives of butanol (C4H9OH).PropanePurinergic P2Y Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Salts: Substances produced from the reaction between acids and bases; compounds consisting of a metal (positive) and nonmetal (negative) radical. (Grant & Hackh's Chemical Dictionary, 5th ed)Disaccharides: Oligosaccharides containing two monosaccharide units linked by a glycosidic bond.Nitroso CompoundsNitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Benzopyrans: Compounds with a core of fused benzo-pyran rings.Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)S-Nitrosothiols: A group of organic sulfur-containing nitrites, alkyl thionitrites. S-Nitrosothiols include compounds such as S-NITROSO-N-ACETYLPENICILLAMINE and S-NITROSOGLUTATHIONE.Nitrosation: Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Prostaglandins, Synthetic: Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Alkenes: Unsaturated hydrocarbons of the type Cn-H2n, indicated by the suffix -ene. (Grant & Hackh's Chemical Dictionary, 5th ed, p408)Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.Prostaglandins F, Synthetic: Analogs or derivatives of prostaglandins F that do not occur naturally in the body. They do not include the product of the chemical synthesis of hormonal PGF.Zinc Compounds: Inorganic compounds that contain zinc as an integral part of the molecule.Magnesium Compounds: Inorganic compounds that contain magnesium as an integral part of the molecule.Iron Compounds: Organic and inorganic compounds that contain iron as an integral part of the molecule.Calcium Compounds: Inorganic compounds that contain calcium as an integral part of the molecule.Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of SILICON DIOXIDE. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight [28.084; 28.086].Organosilicon Compounds: Organic compounds that contain silicon as an integral part of the molecule.Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)Aminosalicylic Acids: A group of 2-hydroxybenzoic acids that can be substituted by amino groups at any of the 3-, 4-, 5-, or 6-positions.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Colitis, Ulcerative: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.Drugs, Generic: Drugs whose drug name is not protected by a trademark. They may be manufactured by several companies.Pericarditis: Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.Inflammatory Bowel Diseases: Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Intestine, Small: The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Tilia: A plant genus of the family TILIACEAE. Some species in this genus are called Limetree which is nearly the same as the common name for lime (CITRUS AURANTIIFOLIA). Some people are allergic to the POLLEN.Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Sodium Selenite: The disodium salt of selenious acid. It is used therapeutically to supply the trace element selenium and is prepared by the reaction of SELENIUM DIOXIDE with SODIUM HYDROXIDE.Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of GLUTATHIONE PEROXIDASE.Selenic Acid: A strong dibasic acid with the molecular formula H2SeO4. Included under this heading is the acid form, and inorganic salts of dihydrogen selenium tetraoxide.Selenium Compounds: Inorganic compounds that contain selenium as an integral part of the molecule.Yeast, Dried: The dry cells of any suitable strain of SACCHAROMYCES CEREVISIAE or CANDIDA. It can be obtained as a by-product from the brewing of beer or by growing on media not suitable for beer production. Dried yeast serves as a source of protein and VITAMIN B COMPLEX.Selenomethionine: Diagnostic aid in pancreas function determination.Selenious Acid: A selenium compound with the molecular formula H2SO3. It used as a source of SELENIUM, especially for patients that develop selenium deficiency following prolonged PARENTERAL NUTRITION.

Protective effects of arbaprostil against indomethacin-induced gastric lesions in rats: significance of maintained gastric blood flow. (1/6)

The purpose of the present study was to investigate the relationship between the effects of 15(R)-15-methylprostaglandin E2 (arbaprostil) on gastric blood flow (GBF) and its protective effects on gastric lesions in rats. The GBF of anesthetized rats was measured by two different methods: Total blood flow into the stomach (total GBF) was determined by means of an ultrasonic pulsed Doppler flow meter; and gastric mucosal blood flow (mucosal GBF) was measured by nonradioactive microspheres. Systemic blood pressure (SBP), heart rate (HR) and gastric vascular resistance (GVR) were recorded simultaneously. Arbaprostil (10-100 micrograms/kg) given i.v. did not affect resting total or mucosal GBF even though it decreased SBP and GVR. Significant improvement of the total and mucosal GBF decreased by indomethacin pretreatment (10 mg/kg, i.v.) was observed by administration of arbaprostil (10-100 micrograms/kg, i.v.) in a dose-dependent manner. Furthermore, i.v.-administration of this agent, in the same dose-range, prevented the formation of gastric lesions induced by indomethacin. The present result suggests that mitigation for the ischemic state of the gastric mucosa may be one of the important mechanisms for the prophylactic and curative effect of arbaprostil on gastric lesions induced by indomethacin.  (+info)

Acid-promoted epimerization of arbaprostil, 15(R)-15-methylprostaglandin E2, elicits gastric antisecretory activities in rats. (2/6)

Gastric acid antisecretory activities of 15(R)-15-methylprostaglandin E2 (arbaprostil) preincubated or not preincubated with 0.9% physiological saline, the pH of which was precisely adjusted to less than 4.30, were examined in pylorus-ligated rats, and compared with those of 15(S)-15-methylprostaglandin E2 (15(S), epimer of arbaprostil). 15(S), unlike arbaprostil without preincubation, when s.c.-administered to rats significantly inhibited gastric acid secretion in a dose-dependent manner (30-300 micrograms/kg). However, arbaprostil preincubated at 37 degrees C for 30 min with 0.9% saline, at pHs of 4.30, 2.75 and 1.20, respectively, showed the following order of pH-dependent antisecretory activities: 1.20 greater than 2.75 greater than 4.30. An increase in 15(S) formation from arbaprostil in a pH-dependent manner was also observed by radioisotopic experiments under the same incubation conditions using [3H]-labeled arbaprostil. The present result suggests that the gastric antisecretory effect of arbaprostil can be mainly explained in terms of the formation of 15(S) after oral administration.  (+info)

Gastric antisecretory activity of 15(R)-15-methylprostaglandin E2, arbaprostil, in dogs. (3/6)

The gastric antisecretory activity of 15(R)-15-methylprostaglandin E2 (arbaprostil) was compared with that of natural prostaglandin (PG) E2 in Pavlov pouch dogs. Arbaprostil significantly inhibited pentagastrin- and food-stimulated gastric secretion when it was administered directly into the pouch at a dose of 10-30 micrograms/pouch and 30-300 micrograms/pouch, respectively. Natural PGE2, however, was inactive up to 1000 micrograms/pouch. The data indicate that arbaprostil is a potent, long-acting orally active antisecretory drug that may be useful for the treatment of peptic ulcer disease.  (+info)

Effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various gastric lesions induced in rats. (4/6)

We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers.  (+info)

Femtomole analysis of prostaglandin pharmaceuticals. (5/6)

An analytical method is described whereby the major classes of prostaglandins are fully resolved by microcolumn liquid chromatography and detected at the subfemtomole level by laser-induced fluorescence. The prostaglandins are labeled with the fluorescent reagent 4-bromo-methyl-7-methoxycoumarin and are subsequently separated on a high-efficiency fused-silica microcolumn (0.2 mm i.d., 1.06 m length, 150,000 theoretical plates). The optimal chromatographic conditions consist of a 3-micron octadecylsilica packing material and an isocratic mobile phase of 47.6% methanol, 23.8% acetonitrile, and 28.6% water. The prostaglandin derivatives are detected directly on the microcolumn by laser fluorimetry, using a helium/cadmium laser (325 nm, 15 mW) as the excitation source together with a simple filter/photo-multiplier optical detection system. In real sample matrices, the prostaglandin PGF2 alpha is readily quantifiable from the detection limit (0.3 fmol) to the formulation strength of the therapeutic agent Lutalyse (Upjohn), spanning more than six orders of magnitude in concentration. The simplicity and general applicability of the present analytical methodology and instrumentation suggest that this technique can be used to attack a wide variety of biomedically important problems with exceptional sensitivity and selectivity.  (+info)

Dose response inhibition in man of meal-stimulated gastric acid secretion by 15(R)-15-methyl prostaglandin E2, given orally. (6/6)

15(R)-15-methyl prostaglandin E2 was given orally to healthy male volunteers. Thirty minutes later a 10% peptone meal was introduced into the stomach, and the acid response was measured by continuous intragastric titration with 0.5 N NaOH for the next two hours. The prostaglandin inhibited acid output in a dose dependent manner; the ED50 (dose inhibiting acid output by 50%) was as little as 10 micrograms per subject (or approximately 140 ng/kg). This compound is the most potent orally active inhibitor of gastric acid secretion in man that is known. It is likely that the antisecretory and cytoprotective properties shared by 15(R)-15-methyl prostaglandin E2 would be beneficial in the treatment of peptic ulcer and in preventing recurrences.  (+info)