Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:7440-70-2 (calcium)
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1. The potential of the potassium channel activator, cromakalim (BRL 34915), as a bronchodilator has been evaluated in guinea-pig models in comparison with nifedipine. Some effects of the compounds on guinea-pig tracheal spirals have been studied in an attempt to elucidate their different efficacies in vivo. 2. When given by the intraduodenal route to anaesthetized guinea-pigs, cromakalim (3 and 10 mg kg-1) inhibited 5-hydroxytryptamine (5-HT)-induced bronchospasm for at least 60 min. When given by the i.v. route, the dose of cromakalim producing 50% inhibition of the 5-HT response was 84 micrograms kg-1. Nifedipine failed to show any protective effect up to 100 micrograms kg-1, i.v. and was lethal at higher dose levels. 3. Cromakalim protected conscious guinea-pigs from asphyxic collapse in response to histamine aerosol. The maximal effect occurred 60 min following oral dosing, with 2.5 mg kg-1 providing complete protection for almost half of the animals. Nifedipine had only a weak protective effect even at a high dose level of 50 mg kg-1, p.o. 4. Cromakalim prolonged the time before convulsive cough in response to an antigen challenge in actively sensitized guinea-pigs. Its minimum protective dose was 1 mg kg-1, p.o. Nifedipine (50 mg kg-1, p.o.) was ineffective. 5. Cromakalim inhibited both spontaneous and prostaglandin E2-induced tone in guinea-pig isolated tracheal spirals with IC50 values, relative to the maximum inhibition achieved by isoprenaline (10(-3)M), of 1.1 x 10(-6)M and 8.9 x 10(-7)M, respectively. Its maximal effect was 89% of that produced by isoprenaline. Removal of the epithelium did not influence its activity. Studies using the two enantiomers showed that the activity of cromakalim resided almost entirely in the (-)-enantiomer. 6. Nifedipine (2 x 10-SM) achieved only 49% of the relaxant effect of 10 -3M isoprenaline in isolated tracheal spirals. Addition of cromakalim (10- 5 M) at the end of the nifedipine concentrationresponse experiment caused further relaxation to 94% of the effect of isoprenaline. 7. It is concluded that cromakalim has greater potential than nifedipine as a bronchodilator. It appears that opening of potassium channels, with consequent hyperpolarization and stabilization of the membrane potential, prevents calcium entering the cytosol through routes that are unaffected by calcium entry blockers.
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PMID:Evaluation of the potassium channel activator cromakalim (BRL 34915) as a bronchodilator in the guinea-pig: comparison with nifedipine. 320 91

Tracheopathia osteochondroplastica (TPO) is a rare, but increasingly recognised condition in which there is accumulation of calcium phosphate with benign submucous proliferation of cartilage and bone beneath the tracheal mucosa, often with squamous metaplasia of the mucosal columnar epithelium. This condition is usually asymptomatic, but may be slowly progressive, causing haemoptysis, dry cough and dyspnoea. We report a case of TPO in which there was rapid progression of tracheal stenosis such that the size of endotracheal tube that the upper airway would accept changed from 8.00 mm to 3.0 mm during a six-week period. This extreme reduction in airway calibre had not been detected on spirometry nine days prior to his final admission. This is the first report of such rapid progression of tracheal stenosis associated with TPO.
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PMID:Rapid progression of tracheal stenosis associated with tracheopathia osteo-chondroplastica. 323 Feb 4

A 76-year-old on long-term Lasix and Pyrogastrone presented with stridor. This became worse with local irritation, e.g. on coughing or during indirect laryngoscopy. Indirect laryngoscopy showed a narrow glottis with an otherwise normal larynx. Blood investigation showed a low serum potassium with a raised bicarbonate level, and a serum calcium level just within the acceptable normal range. A diagnosis of laryngospasm secondary to drug-induced hypokalaemic alkalosis was made. This was treated with the withdrawal of the above drugs and supplementing potassium orally.
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PMID:Stridor due to drug-induced hypokalaemic alkalosis. 357 25

A cross-sectional epidemiological study was carried out among 141 male subjects exposed to inorganic manganese (Mn) in a Mn oxide and salt producing plant (mean age 34.3 years; duration of exposure, mean 7.1 years, range 1-19 years). The results were compared with those of a matched control group of 104 subjects. The intensity of Mn exposure was moderate as reflected by the airborne Mn levels and the concentrations of Mn in blood (Mn-B) and in urine (Mn-U). A significantly higher prevalence of cough in cold season, dyspnea during exercise, and recent episodes of acute bronchitis was found in the Mn group. Lung ventilatory parameters (forced vital capacity, FVC; forced expiratory volume in one second, FEV1; peak expiratory flow rate, PEFR) were only mildly altered in the Mn group (smokers) and the intensity and the prevalence of these changes were not related to Mn-B, Mn-U, or duration of exposure. There was no synergistic effect between Mn exposure and smoking on the spirometric parameters. Except for a few nonspecific symptoms (fatigue, tinnitus, trembling of fingers, increased irritability), the prevalence of the other subjective complaints did not differ significantly between the control and Mn groups. Psychomotor tests were more sensitive than the standardized neurological examination for the early detection of adverse effects of Mn on the central nervous system (CNS). Significant alterations were found in simple reaction time (visual), audioverbal short-term memory capacity, and hand tremor (eye-hand coordination, hand steadiness). A slight increase in the number of circulating neutrophils and in the values of several serum parameters (ie, calcium, ceruloplasmin, copper, and ferritin) was also found in the Mn group. There were no clear-cut dose-response relationships between Mn-U or duration of Mn exposure and the prevalence of abnormal CNS or biological findings. The prevalences of disturbances in hand tremor and that of increased levels of serum calcium were related to Mn-B. The response to the eye-hand coordination test suggests the existence of a Mn-B threshold at about 1 microgram Mn/100 ml of whole blood. This study demonstrates that a time-weighted average exposure to airborne Mn dust (total dust) of about 1 mg/m3 for less than 20 years may present preclinical signs of intoxication.
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PMID:Epidemiological survey among workers exposed to manganese: effects on lung, central nervous system, and some biological indices. 357 89

Hypersensitivity reactions to heparin preparations with a wide spectrum of clinical manifestations have been reported frequently in the past, but are a rarity now. A 88 year old man was admitted for physical therapy of a collum femoris fracture. Treatment with a diuretic, Reserpine and Verapamil was continued. Chest x-ray revealed a large thoracic aortic aneurysm. From the 12th to the 18th day of low dose heparin prophylaxis with calcium heparin, 7500 U twice daily, at least eight attacks of asthma or cyanosis were observed, starting about two hours after heparin injection. The last attack began suddenly with wheezing, tachypnoea and cough and was associated with apprehension, a sudden blood pressure increase and severe cyanosis. Ventilation improved with oxygen and a beta 2-stimulator, but hypertension and cyanosis lasted for three hours. After discontinuation of heparin no further attacks occurred. Causes other then heparin could not be found. Despite the use of porcine mucosa heparin, avoidance of preservatives and use of low doses a hypersensitivity reaction occurred in our case. The delayed onset after preceding subcutaneous application as well as difficulties in separating the reaction from complications of underlying disease may delay heparin discontinuation.
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PMID:[Asthma attacks in low-dose preventive use of heparin in a male with femoral neck fracture and aortic aneurysm]. 366 60

Ptychodiscus brevis, which causes Florida red tide, produces Ptychodiscus brevis toxin (PBTX) known to contain neurotoxins and to induce rhinorrhea, tearing, and cough in normal humans and wheezing in asthmatic subjects. It was previously reported (J Allergy Clin Immunol 69:418, 1982; 73:824, 1984) that PBTX causes canine tracheal smooth muscle contraction via stimulation of sodium channels in the axons of parasympathetic postganglionic nerves and the release of acetylcholine from these nerve endings. This was postulated to be an asthma-triggering mechanism. In this article the toxins were evaluated to determine if they also stimulate sodium channels on adrenergic nerve endings and release norepinephrine. Rat vas deferens was selected as the experimental tissue. Both PBTX and norepinephrine contracted rat vas deferens. Prazosin 10(-6) mol/L blocked the response to PBTX (3 micrograms/ml) (88.3% to 27.3% contraction [n = 6; p less than 0.001]) and the response to norepinephrine (EC50 was shifted from 1.67 X 10(-6) mol/L to 1.25 X 10(-4) mol/L in the presence of prazosin 10(-6) mol/L [n = 6; p less than 0.001]). Phentolamine 10(-6) mol/L also blocked both PBTX and norepinephrine. Tetrodotoxin 10(-7) mol/L, a sodium channel blocker, completely blocked the response to PBTX but not to norepinephrine. The response to PBTX was significantly reduced from 1.53 gm of tension in controls to 0.29 gm of tension (n = 6; p = 0.002) in tissues obtained from rats pretreated with reserpine (2 mg/kg per day for 2 days, injected intraperitoneally). Verapamil 10(-5) mol/L blocked the PBTX response, and PBTX caused no contraction in calcium-free media.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The mechanism of Ptychodiscus brevis toxin-induced rat vas deferens contraction. 404 Jan 40

During a seventeen day period an A. niger fungus ball evolved within a healed tuberculous cavity of a patient. Symptoms were a cough with a chocolate brown expectoration and dyspnea. The patient died and necropsy was performed. Crystals of calcium oxalate were deposited in the cavity lining and in the adjacent tissue of the lung. Fibrosis, mononuclear infiltration and intraalveolar purulent exudate were seen in these tissues. Some small vessels presented recent thrombosis and deposition of calcium oxalate. The bronchus connected with the cavity presented a disrupted epithelial layer, edema, polymorphonuclear infiltration and birefringent crystals. Scattered areas of tubular atrophy, glomerular sclerosis and lymphoid infiltration were seen in the cortex of the kidney. Oxalate crystals were also seen within the renal tubuli.
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PMID:Oxalosis associated with an aspergillus niger fungus ball. Report of a case. 721 9

Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were compared in terms of quality of life, efficacy, and tolerability, in a multicenter, double-blind trial lasting for 50 weeks in 461 mild or moderate hypertensive patients. Both drugs were similarly effective in lowering blood pressure while maintaining quality of life. Apart from class-typical effects, such as edema for calcium antagonists, and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients [eight amlodipine (4%); nine enalapril (4%)] were withdrawn from the trial due to drug-related adverse events, demonstrating that tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. Both drugs reduced the calculated risk of coronary heart disease over the next 10 years. It was concluded that amlodipine compared favorably with enalapril as an effective and well-tolerated antihypertensive drug.
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PMID:A double-blind, long-term, comparative study on quality of life, safety, and efficacy during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicenter study. 752 82

An international trial recruited 1,049 patients from 122 investigators. After a 2- to 4-week, single-blind placebo run-in, patients were treated unblinded for 1 year. Therapy was started with trandolapril 2 mg once daily. The dose was increased to 4 mg/day if, after 1 month, blood pressure was not normalized, and then was combined with diuretics and/or calcium antagonists in increasing doses if necessary. At the cutoff point for this interim analysis. 481 patients had been treated for over 12 months and 960 for 3 months. At end point, trandolapril produced a significant decrease in blood pressure (-14 mm Hg for mean supine diastolic blood pressure). Blood pressure was normalized in 60% of the population with monotherapy. Trandolapril, alone or in combination with diuretics or calcium antagonists, was well tolerated clinically and biochemically. Only 3.9% patients reported dry cough. Withdrawals of patients from the study for treatment related reasons were 3.8%. Trandolapril had also an excellent antihypertensive effect and was well tolerated in elderly patients, in patients with glucose intolerance, and in patients with renal dysfunction.
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PMID:Long-term therapy with trandolapril, a new nonsulfhydryl ACE inhibitor, in hypertension: a multicenter international trial. Investigator Study Group. 752 9

The purpose of this article is to report the case of a patient who developed prolonged neuromuscular block after a large dose of clindamycin (2400 mg). A 58-yr-old, 65 kg woman with severe rheumatoid arthritis was admitted for wrist arthrodesis. After d-tubocurarine (3 mg) and fentanyl (1.5 micrograms.kg-1), anaesthesia was induced with thiopentone (4 mg.kg-1) followed by succinylcholine (1.5 mg.kg-1) and was maintained with N2O in O2 and isoflurane (0.75-1.0% end tidal) and ventilation was controlled. No further neuromuscular relaxants were given although full return of neuromuscular activity in response to train-of-four and 100 Hz tetanic stimulation was observed after succinylcholine. An overdose of clindamycin (2400 mg, instead of the intended 600 mg) was given i.v. soon after the start of surgery. At the end of surgery, 75 min later, the patient made no attempt at spontaneous ventilation, was unresponsive to painful stimuli and naloxone (0.2 mg i.v.) was ineffective. Controlled ventilation was continued in the Recovery Room where neuromuscular testing showed a train-of-four ratio of 0.27 which improved to only 0.47 five minutes after calcium chloride (1.5 mg.kg-1 i.v.), and to 0.62 after edrophonium (20 mg) and neostigmine (2 mg). Nine hours later the patient began to cough, the TOF had returned to 1.0 and two hours later the trachea was extubated and spontaneous ventilation was resumed. Large doses of clindamycin can induce profound, long-lasting neuromuscular blockade in the absence of non-depolarizing relaxants and after full recovery from succinylcholine has been demonstrated.
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PMID:Clindamycin-induced neuromuscular blockade. 755 99


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