Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have indicated that some hypertensive patients, following a period of effective treatment with certain antihypertensive drugs, may experience prolonged normotension after drug withdrawal. We have studied the ability of carteolol, a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, to produce such remissions of hypertension. Thirty-four patients whose diastolic blood pressure was controlled at 90 mm Hg or less with carteolol monotherapy (2.5 to 5.0 mg/d for an average of 328 days) were randomized to a nine-month, double-blind, placebo-controlled drug-withdrawal trial. Those patients randomized to continue carteolol therapy had initially responded to carteolol treatment with reduction in blood pressure from 151 +/- 4/99 +/- 2 to 132 +/- 4/80 +/- 2 mm Hg. Those randomized to treatment with placebo had initially responded with blood pressure reductions from 154 +/- 4/97 +/- 2 to 137 +/- 4/81 +/- 2 mm Hg. Changes in mean systolic and diastolic blood pressure (mm Hg +/- SEM) from baseline during carteolol therapy to the final visit at nine months were not different for patients receiving placebo (13 +/- 5/6 +/- 4 mm Hg, recumbent; 11 +/- 6/4 mm Hg, standing) or carteolol (11 +/- 5/7 +/- 3 mm Hg, recumbent; 12 +/- 6/7 +/- 3 mm Hg, standing). The final mean recumbent diastolic blood pressure (86.9 mm Hg) was the same in both groups. Prolonged normotension may follow a period of carteolol treatment, again suggesting the potential importance of periodic withdrawal of antihypertensive medication.
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PMID:Remission of mild to moderate hypertension after treatment with carteolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic activity. 304 36

We studied the effects of aerosolised prostacyclin (PGI2) in three patients with acute severe adult respiratory distress syndrome. 17-50 ng/kg per min, nebulised into the afferent limb of the ventilator circuit, decreased mean pulmonary artery pressure (SEM) from 40.3 (13.5) to 32.0 (3.8) mm Hg (pulmonary vascular resistance fell by 30%); systemic arterial pressure decreased slightly from 76.8 (2.2) to 74.5 (6.1) mm Hg. Concomitantly, the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen increased from 120 (19) to 173 (18), mainly due to redistribution of blood flow from shunt areas to regions of normal ventilation-perfusion. All effects were reversed on drug withdrawal.
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PMID:Aerosolised prostacyclin in adult respiratory distress syndrome. 810 8

A 69 year old woman developed chronic diarrhoea while being treated with ranitidine. Sigmoidoscopy was performed after six weeks and showed typical histological features of lymphocytic colitis. Ranitidine was withdrawn and the diarrhoea resolved. Eight months later, a 72 hour oral rechallenge period of ranitidine, was performed immediately preceded (period 1) and followed (period 2) by sigmoidoscopy and biopsy. Diarrhoea recurred during the rechallenge period and resolved again within one day after drug withdrawal. The mean (SEM) intraepithelial lymphocyte count was not significantly different between periods 1 and 2 (11.9 (0.6) and 13.1 (0.4) per 100, respectively). An immunopathological study of 30 serial sections of biopsy specimens was performed for both periods 1 and 2. The expression of HLA-DR by the rectal epithelium was mild or absent in all sections from period 1, and was considerable in 25 of 30 sections from period 2 (p < 10(-9)). It is suggested that the oral intake of ranitidine was responsible for the diarrhoea and induced the immunopathological signs of activation of the rectal mucosal immune system during the rechallenge period.
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PMID:Ranitidine, diarrhoea, and lymphocytic colitis. 854 50

Recent experiments have shown that: 1) A chronic 10 month daily administration to rats of the benzodiazepine (BDZ) receptor antagonist, flumazenil (FL; 4 mg/kg in drinking water), from the age of 13 through 22 months, significantly retarded the age-related loss of cognitive functions, as ascertained by the radial arm maze tests conducted two months after FL withdrawal. 2) An equal number of 8 rats died in the control and FL-treated group before the behavioral tests were completed and the animals were sacrificed; the life span of the FL-treated 8 rats equaled 24.0 (+/- 0.6 SEM) months, while that of the control 8 rats equaled 22.3 months (+/- 0.7 SEM), and the group difference was marginally significant (p = 0.04 Mann-Whitney test). 3) In rats sacrificed 3 months after FL withdrawal and behavioral testing, the protective action of FL, relative to age-matched controls, was revealed by a significant reduction in the age-related loss of neurons in the hippocampal formation. 4) In the time period of 3 months between the drug withdrawal and sacrificing of the animals, stress experienced by the aging rats during behavioral testing, related to excessive daily handling of the animals and partial food deprivation to motivate them to perform in the radial arm maze, apparently had excitotoxic effects on the hippocampal neurons, as indexed by the presence of 30% neurons in a state of moderate pyknosis found both in the FL group and the age-matched controls. In the 6 months "young" control group, the number of pyknotic neurons equaled only 3.5%. It was concluded that the drug withdrawal and stress of behavioral testing unleashed the previously FL-controlled age-related degeneration. On the basis of these results and the literature, showing that the tone of the GABAergic system increases with age, and particularly in Alzheimer's disease (AD), the hypothesis of brain aging was formulated. It postulates that in mammals, with growing age, and prematurely in humans with AD, the increasing tone of the BDZ/GABAergic system interferes with antero- and retrograde axonal transport through a chronic depolarizing block of preterminal axon varicosities of the ascending aminergic and cholinergic/peptidergic systems, which are indispensable for normal metabolic/trophic glial-neuronal relationships. Such a state leads to discrete anatomic deafferentation of forebrain systems, and particularly of the neocortex, where block of the anterograde axonal transport results in induction of the cortical mRNA responsible for synthesis of the beta-amyloid precursor protein (beta APP). The simultaneous block of retrograde transport from chronically depolarized preterminal axon varicosities may account for toxic accumulation in cortex of the nerve growth factor (NGF) and other trophins, without which the basal forebrain cholinergic neurons degenerate. The general pharmacologic profile of FL has been discussed on the basis of FL administration to animals and healthy and diseased humans. This profile shows that FL: 1) increases brain metabolic functions; 2) reduces emotional responses, thereby stabilizing the functions of the autonomic system in both humans and animals challenged by adverse environmental stimuli; 3) improves cognitive and coordinated motor functions in both humans and animals; 4) uniquely combines anxiolytic, vigilance and cognitive enhancing, i.e. nootropic, properties, which may, in part, stem from FL-induced emotional imperturbability (ataraxy); 5) facilitates habituation of healthy humans and animals to novel but inconsequential environmental stimuli, and promotes non-aggressive interactions among animals; 6) in single i.v. doses, and administered chronically to humans, FL has antiepileptic actions in the Lennox-Gastaut syndrome and other forms of epilepsy characterized by "spike-and-dome" EEG patterns; these actions are likely to depend on FL's disinhibition of the serotonin system; 7) administered in single i.v...
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PMID:GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease; pharmacologic profile of the benzodiazepine antagonist, flumazenil. 871 36