Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochalasin is known to inhibit the antidiuretic hormone-induced hydro-osmotic response (bulk water flow) in the amphibian urinary bladder without altering hormone-stimulated diffusional water permeability or short-circuit current. In addition, histological studies have shown that the mold metabolite induces the formation of large intracellular vacuoles or lakes in the epithelial cells. We report here a transmission electron microscopic time-course study which indicates that during the early phases of the ADH response cytochalasin causes the formation of numerous multivesicular bodies or aggregates derived from individual basolateral pinocytotic vesicles. Because of their apparent hypertonic nature, the vesicles, as well as the vesicular aggregates, accumulate water during hormone-stimulated hydro-osmotic flow. As a result, the multivesicular bodies dilate and fuse to form the large intracellular lakes characteristic of cytochalasin treatment in the presence of both an applied osmotic gradient and vasopressin. In the presence of mucosal ruthenium red, the luminal glycocalyx was heavily stained with this tracer. At no time, however, even in the presence of hormone, was there any evidence for the uptake of this dye at the apical epithelial border. In the presence of serosal ruthenium red, the lateral intercellular spaces, basolateral pinocytotic vesicles, basal lamina, and collagen, as well as other subepithelial structures, were ruthenium positive. With cytochalasin D, vasopressin, and serosal ruthenium red, both the pinocytotic vesicles and the multivesicular bodies demonstrated an apparent membrane associated ruthenium positive coat. The tracer data indicates that the basolateral pinocytotic vesicles, increased by the presence of hormone, are indeed endocytotic in nature. The mucopolysaccharide coat associated with these structures may be involved in ionic and/or fluid transport.
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PMID:Antidiuretic hormone response in the amphibian urinary bladder: time course of cytochalasin-induced vacuole formation, an ultrastructural study employing ruthenium red. 243 Mar 46

Alternations of stomach mucose caused by ethanol are in direct correlation with its concentration. ADH in stomach mucose is an efficient barrier against ethanol system toxicity. It stimulates higher secretion of HC1, dilutes protective barrier of mucose and phospholipids in membranes. Inflammatory reaction also participates in the damage of stomach mucose, with a share of products of arachidonic metabolism and free radicals. After ethanol administration the pancreas blood circulation diminishes and resistance in microcirculation increases. This can cause necroses in periphery of lobules. Activated phospholipase C may result in hypersecretion of Ca2+ dependent proteinkinases. Ischemic changes participate in alcohol impairment of pancreas and increase its vulnerability to enzyme attract and free radical reactions. Ethanol excesses may result in diarrhoea, dyspepsia, malnutrition and cause morphologic alternations of intestinal mucose (erosion, hemorrhagia). Absorption of nutrients and vitamins is affected by inhibition of active transport or by decrease of enzyme activity. Ethanol increases mucose permeability, alteres intestinal motility and damages absorption of water and electrolytes. In chronic alcoholics lower villi and changes in bacterial flora are described. The following mechanism of ethanol caused liver injury are observed: acetaldehyde toxicity, change in NAD+/NADH ratio connected with acidosis, cytoskeletal impairment, inhibition of protein synthesis and their secretion, relative perivenular hypoxia, activation of fibrogenesis, increased formation of free radicals with lipid peroxidation and immunological reaction. In hepatocyte there are morphological changes (megamitochondria, etc.) and functional changes (inhibition of glycolysis, inhibition of Krebs cycle and beta oxidation of fatty acids). Ethanol intake activates leukocytes, trombocytes, endothelial and Kupffer cells and their mediators, which result in increase of collagen and proteoglycans synthesis furthermore in fibrotic changes in liver.
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PMID:[Ethanol metabolism and pathobiochemistry of organ damage--1992. III. Mechanisms of damage to the gastrointestinal tract and the liver by ethanol]. 799 16

Three decades of research in ethanol metabolism have established that alcohol is hepatotoxic not only because of secondary malnutrition, but also through metabolic disturbances associated with the oxidation of ethanol. Some of these alterations are due to redox changes produced by the NADH generated via the liver ADH pathway, which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Exaggeration of the redox change by the relative hypoxia, which prevails physiologically in the perivenular zone, contributes to the exacerbation of the ethanol-induced lesions in zone III. Gastric ADH also explains first-pass metabolism by ethanol; its activity is low in alcoholics and in females and is decreased by some H2 blockers. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last 20 years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450 (P4502E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by P4502E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anesthetic agents, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion, but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation, decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes GSH depletion, free-radical-mediated toxicity, and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis; both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and lipocytes); ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding may eventually improve therapy with drugs and nutrients. Encouraging results have been obtained with some "super" nutrients. On the one hand, SAMe, the active form of methionine, was found to attenuate the ethanol-induced depletion in SAMe and GSH and associated mitochondrial lesions. On the other hand, phosphatidylcholine, purified from polyunsaturated lecithin, was discovered to oppose the ethanol-induced fibrosis by decreasing the activation of lipocytes to transitional cells, and possibly also by stimulating collagenase activity, an effect for which dilinoleoylphosphatidylcholine, its major phospholipid species, was found to be responsible.
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PMID:Biochemical factors in alcoholic liver disease. 833 2

Alcohol affects the liver through metabolic disturbances associated with its oxidation. Redox changes produced by the hepatic alcohol dehydrogenase pathway affect lipid, carbohydrate and protein metabolism. Ethanol is also oxidized in liver microsomes by the ethanol-inducible cytochrome P4502E1, resulting in ethanol tolerance and selective hepatic perivenular damage. Furthermore, P4502E1 activates various xenobiotics, explaining the increased susceptibility of the heavy drinker to the toxicity of anesthetics, commonly used medications (i.e. isoniazid), analgesics (i.e. acetaminophen), and chemical carcinogens. Induction of microsomal enzymes also contributes to vitamin A depletion, enhances its hepatotoxicity and results in increased acetaldehyde generation from ethanol, with formation of protein adducts, glutathione depletion, free-radical-mediated toxicity, and lipid peroxidation. Chronic ethanol consumption strikingly enhances the number of hepatic collagen-producing activated lipocytes. Both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and activated lipocytes) ethanol and/or its metabolite acetaldehyde increase collagen accumulation and mRNA for collagen. Gender differences are related, in part, to lower gastric ADH activity (with consequent reduction of first pass ethanol metabolism) in young women, decreased hepatic fatty acid binding protein and increased free-fatty acid levels as well as lesser omega-hydroxylation, all of which result in increased vulnerability to ethanol. Elucidation of the biochemical effects of ethanol are now resulting in improved therapy: in baboons, S-adenosyl-L-methionine attenuates the ethanol-induced glutathione depletion and associated mitochondrial lesions, and polyenylphosphatidylcholine opposes the ethanol-induced hepatic phospholipid depletion, the decrease in phosphatidylethanolamine methyltransferase activity and the activation of hepatic lipocytes, with full prevention of ethanol-induced septal fibrosis and cirrhosis; its dilinoleoyl species also increases collagenase activity in lipocytes. The efficacy of this compound in man is now being studied in randomized multicenter clinical trials.
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PMID:Susceptibility to alcohol-related liver injury. 897 51

Pancreatic cancer is one of the most aggressive malignant diseases. We recently reported that N-cadherin plays a key role in tumor progression and metastasis in pancreatic cancer. For this study, we sought to determine if an N-cadherin-blocking peptide (ADH-1) could prevent N-cadherin-mediated tumor progression in a mouse model for pancreatic cancer. The effect of ADH-1 on N-cadherin-mediated cell scattering and migration on collagen I was examined using pancreatic cancer cells. We also examined the influence of ADH-1 on cell apoptosis. Furthermore, in vivo animal studies were performed using orthotopic injection of N-cadherin overexpressing BxPC-3 cells with or without ADH-1 treatment. BxPC-3 and Capan-1 cells exhibited increased expression of N-cadherin in response to collagen I. This increase in N-cadherin promoted cell scattering and migration in response to collagen I. ADH-1 prevented these changes, but did not inhibit upregulation of N-cadherin. TUNEL assays and immunoblots for caspase-3 showed that ADH-1 induced apoptosis in a concentration dependent and N-cadherin dependent manner in pancreatic cancer cells. ADH-1 treatment resulted in significant reductions in tumor growth and lung metastasis in a mouse model for pancreatic cancer. The N-cadherin antagonist, ADH-1 has significant antitumor activity against N-cadherin-expressing cells using in vitro assays and in an orthotopic mouse model for pancreatic cancer, raising the possibility that N-cadherin antagonists have therapeutic potential for the treatment of pancreatic cancer in humans.
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PMID:ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. 1772 21

A novel, biocompatible, and nontoxic dermal filler using hyaluronic acid (HA) hydrogels was successfully developed for tissue augmentation applications. Instead of using highly reactive cross-linkers such as divinyl sulfone (DVS) for Hylaform, 1,4-butanediol diglycidyl ether (BDDE) for Restylane, and 1,2,7,8-diepoxyoctane (DEO) for Puragen, HA hydrogels were prepared by direct amide bond formation between the carboxyl groups of HA and hexamethylenediamine (HMDA) with an optimized carboxyl group modification for effective tissue augmentation. The HA-HMDA hydrogels could be prepared within 5 min by the addition of HMDA to HA solution activated with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrate (HOBt). Five kinds of samples, a normal control, a negative control, a positive control of Restylane, adipic acid dihydrazide grafted HA (HA-ADH) hydrogels, and HA-HMDA hydrogels, were subcutaneously injected to wrinkled model mice. According to the image analysis on dorsal skin augmentation, the HA-HMDA hydrogels exhibited the best tissue augmentation effect being stable longer than 3 months. Furthermore, histological analyses after hematoxylin-eosin (H&E) and Masson's trichrome staining revealed the excellent biocompatibility and safety of HA-HMDA hydrogels. The dermal thickness and the dermal collagen density in wrinkled mice after treatment with HA-HMDA hydrogels for 12 weeks were comparable to those of normal mice. Compared with HA-DVS hydrogels and Restylane, the excellent tissue augmentation by HA-HMDA hydrogels might be ascribed to the biocompatible residues of amine groups in the cross-linker of HMDA. The HA-HMDA hydrogels will be investigated further as a novel dermal filler for clinical applications.
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PMID:Effect of cross-linking reagents for hyaluronic acid hydrogel dermal fillers on tissue augmentation and regeneration. 2007 98

The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1-3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.
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PMID:Rat strain differences in susceptibility to alcohol-induced chronic liver injury and hepatic insulin resistance. 2081 53

Scaffolds of tissue engineering for particular sites, for example, nerve, cardiac, and bone tissues, require a comprehensive design of 3D biomaterials that covers all aspects of physical structures and chemical composition, needed for desired cell regeneration. Injectable and in situ forming hydrogel scaffolds, possessing highly hydrated and interconnected structures, have demonstrated several advantages for use in regenerative medicine. In this study, we have developed a new design of injectable hydrogels based on collagen, aldehyde modified-nanocrystalline cellulose, and chitosan loaded with gold nanoparticles (Collagen/ADH-CNCs/CS-Au). The results of experiments exposed that the various molar ratios of Collagen/CNCs and the presence of CS-Au content have a significant effect on the microscopic morphology, equilibrium swelling, in vitro degradation, and mechanical properties of the hydrogels. The cytotoxicity analysis was performed for the NIH 3T3 cell line, which displays the effectiveness and non-toxicity of the developed hydrogels towards the destruction of the cells. The achieved results suggested that the prepared hydrogel network has great potential as a new biomaterial for tissue engineering applications.
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PMID:An injectable chitosan-based hydrogel scaffold containing gold nanoparticles for tissue engineering applications. 3218 43