Reversal of impaired calcium homeostasis in the rat diaphragm subjected to Monocrotaline-induced pulmonary hypertension.

Monocrotaline (MCT) pneumotoxicity is known to alter the structure of pulmonary vascular wall and impairs endothelial cell function resulting in pulmonary hypertension. Its effect on the diaphragm muscle has not yet been elucidated. This study examines the effect of MCT pneumotoxicity on calcium transport in the rat diaphragm. Pulmonary hypertension induced by MCT pneumotoxicity caused a significant increase (P < 0.001) in calcium accumulation in strips isolated from rat diaphragms. Treatment of rats having received MCT with Indapamide reduced calcium uptake by diaphragmatic strips to levels that are not significantly different from the control (P > 0.05). Treatment with Indapamide alone did not elicit any change in calcium accumulation in the diaphragmatic strips. Treatment of the animals with MCT, Indapamide or both did not produce any significant change (P > 0.05) in the cell volume of the diaphragmatic strips. Pulmonary hypertension increased calcium uptake by the muscle cells in the rat diaphragm which may alter diaphragmatic contractility; an effect that was prevented by Indapamide.

Comparative study of antituberculous drug resistance among Mycobacterium tuberculosis isolates recovered at the American University of Beirut Medical Center: 1996-1998 vs 1994-1995.

PURPOSE: To study the overall current prevalence of antituberculous drug resistance among M. tuberculosis isolates recovered at the American University of Beirut Medical Center (AUBMC) between 1996-1998 in comparison to those reported on isolates recovered in 1994-1995. MATERIALS AND METHODS: Seventy-four consecutive M. tuberculosis isolates recovered from the same number of newly diagnosed cases of tuberculosis (TB), between January 1996 and December 1998 (referred to as 1998), were tested against isoniazid (INH), rifampicin (RIF), streptomycin (STM) and ethambutol (ETH), using the BACTEC-TB susceptibility procedure and system. The results were compared to those reported on the isolates recovered in 1994-1995 (referred to as 1995). RESULTS: A comparison between the results obtained in 1998 vs 1995 showed the following, respectively: The male to female ratio was 3.1:1 vs 2:1 and the mean ages were almost similar in males, 33.4 vs 34.1 years but were slightly higher in females 38.2 vs 32.7 years. Children (< or = 15 yrs) represented 10.8% vs 8.3% of the study population. The prevalence of resistance, to one or more drugs, was almost the same, 24% vs 26% but the overall percentages of single drug resistance were generally higher in 1998 vs 1995 against all the tested drugs except INH: INH (20.2% vs 23.9%), RIF (16.2% vs 12.5%), STM (13.5% vs 7.3%) and ETH (8.1% vs 3%). Among the resistant isolates, the profiles of resistance indicated decrease in resistance to one and two drugs, 6.7% vs 11.5% and 5.4% vs 10.4%, respectively, but showed increase in resistance to three and four drugs, 8.1% vs 2.1% and 4% vs 2.1%, respectively. Increase in resistance to two or more drugs was also observed, 17.6% vs 14.6%, and the prevalence of multidrug resistance, defined as resistance to at least both INH and RIF, was also increased, 14.7% vs 11.4%. CONCLUSIONS: This study shows a high prevalence and persistence of TB drug resistance tested in our Medical Center in Lebanon. In addition, the shift in the increase of resistance from one and two drugs to three and four drugs are very ominous and should be considered when treating patients in this country. Moreover, such information calls for scrutinizing the existing local TB control programs as part of the global efforts to minimize the incidence of this highly morbid infectious disease.

Effects of capsaicin and capsaicin desensitization on alanine accumulation in rat hemidiaphragms.

1. Alanine accumulation in rat hemidiaphragms is significantly inhibited by capsaicin in a dose-dependent pattern that produced maximal effect at 1 mM. 2. The inhibitory effect of capsaicin on alanine accumulation by rat hemidiaphragms was enhanced upon preincubation with 5 mM ouabain. However, preincubation with 1 mM Verapamil did not alter the inhibitory effect of capsaicin. 3. Chemical ablation of the capsaicin-sensitive primary afferent fibers abolished the inhibitory effect of capsaicin on alanine accumulation in the rat hemidiaphragms.

Digoxin-stimulated calcium transport across rat diaphragm interactions with aminophylline and verapamil.

1. The effect of digoxin on calcium transport across muscle strips isolated from rat diaphragms was investigated. 2. Digoxin at concentrations ranging between 0.2-5.0 ng/ml in the incubation solution increased significantly (P less than 0.5) intracellular calcium in the diaphragm muscle strips in a dose-dependent pattern. 3. The inclusion of digoxin (2 ng/ml) and aminophylline (18.75 micrograms/ml) in the incubation medium showed a significant increase (P less than 0.001) in calcium uptake suggesting a synergistic effect on intracellular calcium accumulation. 4. The presence of digoxin with verapamil in the incubation medium showed a partial alleviation of the inhibitory effect of verapamil on calcium transport. 5. The effect of increasing calcium concentration in the presence of digoxin and digoxin plus aminophylline in the incubation medium, showed a nonsaturable linear relationship between calcium concentration and intracellular calcium accumulation.