Diminution in Kerosene-Mediated Induction of Drug Metabolizing Enzymes by Asbestos in Rat Lungs

Abstract: In order to determine the pulmonary toxicity of kerosene and its ignition product (soot) in asbestos exposed subjects, the activities of phase I and phase II drug metabolizing enzymes in rat lungs after single intratracheal coexposure to Indian chrysotile asbestos and kerosene or its soot and Indian chrysotile were assayed. Exposure to kerosene or its soot resulted in a significant increase in the level of microsomal cytochrome P-450 and the activity of P-450 dependent monooxygenase, benzo(a)pyrene hydroxylase, as well as in the activities of microsomal epoxide hydrase and cytosolic glutathione-S-transferase (GST). However, in chrysotile exposed animals a reverse pattern in these parameters was recorded. The co-exposure to chrysotile and kerosene or chrysotile and soot led to a significant depletion in cytochrome P-450 level and a decrease in the activities of benzo(a)pyrene hydroxylase, epoxide hydrase and GST when compared to kerosene and soot controls, respectively. These results suggest that asbestos by altering the pulmonary drug metabolizing enzyme system may increase the toxic potential of kerosene and its ignition product in the respiratory system.     

Marked Q-T prolongation due to encainide therapy

Summary Encainide is a type Ic antiarrhythmie agent. During encainide therapy, mild Q-T interval prolongation can be seen, usually associated with prolongation of the Q-R-S interval. The present case report describes an unusual and marked prolongation of the Q-T interval with no Q-R-S interval prolongation in a patient who was treated with encainide for atrioventricular nodal reentrant tachycardia. The drug metabolite profile in this patient's serum indicated an unusual elevation of the 3-methoxy-O-demethyl encainide metabolite, versus O-demethyl encainide. This elevated metabolite level suggests that 3-methoxy-O-demethyl encainide has a significant effect on prolongation of repolarization. An abnormal metabolism of encainide may be the underlying mechanism by which some patients would manifest an unusual prolongation of Q-T interval during encainide therapy.     

In vitro antibacterial activity of the volatile oil of Nigella sativa seeds against multiple drug-resistant isolates of Shigella spp. and isolates of Vibrio cholerae and Escherichia coli

The antibacterial activity of the volatile oil of Nigella sativa seeds was studied against 37 isolates of Shigella dysenteriae 1, Shigella flexneri, Shigella sonnei and Shigella boydii and 10 strains of Vibrio cholerae and Escherichia coli. Most of the strains were clinically resistant to ampicillin, co-trimoxazole and tetracycline. All the strains tested showed promising sensitivity to the volatile oil. The minimum inhibitory concentration (MIC) of the volatile oil for Shigella, Vibrio and Escherichia strains tested was between 50–400 μg/mL.     

Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial.

OBJECTIVE: To determine the clinical and endoscopic response of candida esophagitis to antifungal therapy and to compare the two oral antifungal agents, fluconazole and ketoconazole. DESIGN: Multicenter, randomized, double-blind trial. SETTING: Fifteen U.S. centers including university, private practice, and county hospital settings. PATIENTS: A total of 169 patients with the acquired immunodeficiency syndrome (AIDS); odynophagia, dysphagia, or retrosternal pain; white esophageal plaques at endoscopy; and pseudohyphae on esophageal brushings or biopsies. INTERVENTION: Patients were randomly assigned to fluconazole (100 mg/d) or ketoconazole (200 mg/d). Doses were doubled at week 1 or 2 if no symptomatic improvement had occurred during the preceding week. Therapy was continued for 2 weeks after resolution of symptoms or for a maximum of 8 weeks. MEASUREMENTS: Patients were clinically evaluated weekly, and laboratory tests were done every 2 weeks. Endoscopy was repeated within 5 days after the end of therapy. RESULTS: A total of 143 patients were clinically evaluable (assessed within 7 days after therapy), and 129 patients were endoscopically evaluable (endoscopy repeated after therapy). Endoscopic cure occurred in 91% of patients treated with fluconazole and in 52% of those given ketoconazole for a difference of 39% (95% Cl, 24% to 52%; P less than 0.001). Esophageal symptoms resolved in 85% of fluconazole-treated patients and in 65% of ketoconazole-treated patients for a difference of 20% (Cl, 6% to 34%; P = 0.006). Intention-to-treat analyses also yielded statistically significant differences for the comparisons listed above. Side effects were minimal and comparable in the two groups; only one patient in each group had therapy discontinued for adverse effects that were possibly related to the study medications. CONCLUSIONS: Fluconazole is associated with significantly greater rates of endoscopic and clinical cure than ketoconazole in patients with AIDS and candida esophagitis. Both drugs appear to be safe and well tolerated.     

Abnormality of type IX collagen in a patient with diastrophic dysplasia

There is growing evidence that a spectrum of chondrodysplasias are caused by mutations in the gene coding for type II collagen. The basic molecular defect in diastrophic dysplasia has not been defined, but it appears not to be in collagen type II. Cartilage contains other tissue-specific collagens, types IX, X, and XI, but no mutations have yet been found in their genes in clinical disease. Type IX collagen is hypothesized to play a role in the regulation of type II collagen fibril organization and structure in cartilage extracellular matrix. In this study, we have examined iliac crest growth cartilage from a patient with diastrophic dysplasia. Although collagen fibrils were markedly increased in diameter on transmission electron microscopy, type II collagen appeared to be normal biochemically. Type XI collagen was also normal. However, type IX collagen appeared abnormal on sodium dodecyl sulfate polyacrylamide gel electrophoresis with a pronounced excess of the COL1 domain of the molecule in pepsin extracts. The findings point to an abnormality in structure or metabolism of type IX collagen in diastrophic dysplasia. © 1994 Wiley-Liss, Inc.     

Geriatric heart failure, depression, and nursing home admission: an observational study using propensity score analysis.

OBJECTIVE: Heart failure (HF) and depression are both common in older adults, and the presence of depression is known to worsen HF outcomes. For community-dwelling older adults, admission to a nursing home (NH) is associated with loss of independent living and poor outcomes. The objective of this study was to examine the effect of depression on NH admission for older adults with HF. METHODS: Using the 2001-2003 National Hospital Discharge Survey datasets, the authors identified all community-dwelling older adults who were discharged alive with a primary discharge diagnosis of HF. The authors then identified those with a secondary diagnosis of depression. Using a multivariable logistic regression model, the authors then determined probability or propensity to have depression for each patient. The authors used propensity scores for depression to match all 680 depressed patients with 2,040 nondepressed patients. Finally, the authors estimated the association between depression and NH admission using bivariate and multivariable logistic regression analyses. RESULTS: Patients had a mean (+/- standard deviation) age of 79 (+/- 8) years, 72% were women, and 9% were blacks. Compared with 17% nondepressed patients, 25% depressed patients were discharged to a NH. Depression was associated with 50% increased risk of NH admission (unadjusted relative risk [RR]: 1.50; 95% confidence interval [CI]: 1.28-1.74). The association became somewhat stronger after multivariable adjustment for various demographic and care covariates (adjusted RR: 1.60; 95% CI: 1.35-1.68). CONCLUSION: In ambulatory older adults hospitalized with HF, a secondary diagnosis of depression was associated with a significant increased risk of NH admission.     

Airway responsiveness to beta-adrenergic agonist (salbutamol) in asthma.

Despite the controversy of airway responsiveness to beta2-agonist drugs in asthma, in a previous study we showed increased responsiveness of asthmatic airways to isoprenaline. Therefore, in the present study of airway sensitivity to other beta2-agonists, salbutamol and its relationship to histamine responsiveness was reexamined. The threshold bronchodilator concentrations of inhaled salbutamol required for a 20% increase in forced expiratory flow in 1 sec (FEV1), (PC20) was measured in 20 normal and 19 asthmatic adults. Airway responsiveness to histamine, as the concentration that caused a 20% decrease in FEV1, was also measured in 11 normal and 12 asthmatic subjects; and the correlation between PC20 salbutamol and PC20 histamine was evaluated. Sensitivity to salbutamol was greater in asthmatics (PC20 = 7.24 mg/L) than in non-asthmatics (PC20 = 124.25 mg/L, p < 0.001). Airway responsiveness to histamine in asthmatics (PC20 = 0.18 g/L) was also significantly greater than in normal subjects (PC20 = 19.46 g/L, p < 0.001). There was a significant correlation between PC20 salbutamol and histamine (Rs = 0.6052, p < 0.005). Maximum response to both salbutamol and histamine and slope of concentration-response curves of both agents were significantly greater in patients with asthma than in normal subjects (p < 0.001 and p < 0.005 for maximum response and slope, respectively). The increased sensitivity of asthmatics to inhaled salbutamol suggests that they also may be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways.