Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic administration of a diet containing 7% ethanol (36% of total calories) for 8 days to male C57/BL6 mice resulted in significant changes in functioning of macrophages. Peritoneal exudate macrophages from the ethanol-fed mice released more tumor cell cytotoxic materials upon culturing in vitro than cells from controls. However, peritoneal exudate cells continued to respond to exogenous beta carotene in vitro to produce additional cytotoxic materials. Phagocytosis of sheep red blood cells in vitro was suppressed in cells from ethanol treated mice. The number of splenic lymphocytes of various subsets was significantly changed by the ethanol exposure. Total T cells and T suppressor cells were lower, with a significant decrease in B cells containing IgM on their surface. The percentage of spleen cells showing markers for macrophage functions and their activation were significantly reduced. It is concluded that short-term chronic consumption of dietary ethanol, which was sufficient to produce physical dependence, results in significant alterations in lymphocyte subtypes and suppression of some macrophage functions.
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PMID:Changes in lymphocyte subsets and macrophage functions from high, short-term dietary ethanol in C57/BL6 mice. 297 May 67

Inhibitors of gastric acid secretion, particular proton pump inhibitors, are effective drugs in the treatment and prophylaxis of acid-related diseases. Proton pump inhibitors are therefore prescribed widely, often for minor complaints. Gastric acidity kills swallowed microorganisms, and acid secretion must be of biological importance because it is maintained in phylogenesis. Acid secretion is controlled by feedback mechanisms, mainly via gastrin. A decrease in acidity always causes an increase in plasma gastrin. The trophic effect of gastrin leads to hyperplasia and neoplasia of the enterochromaffin-like (ECL) cell. ECL cell derived tumours in man were previously regarded as rare, and also as rather benign. It is now clear that the ECL cell gives rise to a significant proportion of gastric carcinomas. Moreover, ECL cell carcinoids secondary to hypergastrinaemia may develop into highly malignant tumours. Treatment with a proton pump inhibitor is followed by rebound acid hypersecretion and decreased efficiency of H2-blockers, thus such treatment may induce a type of physical dependence. It is therefore reasonable to be cautious and not to treat younger (< 50 years) patients for long periods of time with profound inhibitors of gastric acid secretion. Chromogranin A in the blood is a sensitive marker of the ECL cell mass, and it could be used to survey patients on long-term proton pump inhibitors.
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PMID:Personal review: is profound acid inhibition safe? 1132 70

Activation of cannabinoid CB1 receptors suppresses pathological pain but also produces unwanted side effects, including tolerance and physical dependence. Inhibition of fatty-acid amide hydrolase (FAAH), the major enzyme catalyzing the degradation of anandamide (AEA), an endocannabinoid, and other fatty-acid amides, suppresses pain without unwanted side effects typical of direct CB1 agonists. However, FAAH inhibitors have failed to show efficacy in several clinical trials suggesting that the right partnership of FAAH inhibition and pathology has yet to be identified. We compared efficacy of chronic treatments with a centrally penetrant FAAH inhibitor (URB597), a peripherally restricted FAAH inhibitor (URB937) and an orthosteric pan-cannabinoid agonist (WIN55,212-2) in suppressing neuropathic pain induced by the chemotherapeutic agent paclitaxel. Each FAAH inhibitor suppressed the development of paclitaxel-induced neuropathic pain and reduced the maintenance of already established allodynia with sustained efficacy. Tolerance developed to the anti-allodynic efficacy of WIN55,212-2, but not to that of URB597 or URB937, in each dosing paradigm. Challenge with the CB1 antagonist rimonabant precipitated CB1-dependent withdrawal in paclitaxel-treated mice receiving WIN55,212-2 but not URB597 or URB937. When dosing with either URB597 or URB937 was restricted to the development of neuropathy, paclitaxel-induced allodynia emerged following termination of drug delivery. These observations suggest that both FAAH inhibitors were anti-allodynic rather than curative. Moreover, neither URB597 nor URB937 impeded the ability of paclitaxel to reduce breast (4T1) or ovarian (HeyA8) tumor cell line viability. In fact, URB597 and URB937 alone reduced 4T1 tumor cell line viability, albeit with low potency, and the dose matrix of each combination with paclitaxel was synergistic in reducing 4T1 and HeyA8 tumor cell line viability according to Bliss, Highest Single Agent (HSA) and Loewe additivity models. Both FAAH inhibitors synergized with paclitaxel to reduce 4T1 and HeyA8 tumor cell line viability without reducing viability of non-tumor HEK293 cells. Neither FAAH inhibitor reduced viability of non-tumor HEK293 cells in either the presence or absence of paclitaxel, suggesting that nonspecific cytotoxic effects were not produced by the same treatments. Our results suggest that FAAH inhibitors reduce paclitaxel-induced allodynia without the occurrence of CB1-dependence in vivo and may, in fact, enhance the anti-tumor actions of paclitaxel in vitro.
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PMID:Brain permeant and impermeant inhibitors of fatty-acid amide hydrolase suppress the development and maintenance of paclitaxel-induced neuropathic pain without producing tolerance or physical dependence in vivo and synergize with paclitaxel to reduce tumor cell line viability in vitro. 3073 35