Drugs online research references
Circulation. 1998 Nov 10;98(19):2065-73.
Cardiac endothelin-1 plays a critical role in the functional deterioration of left ventricles during the transition from compensatory hypertrophy to congestive heart failure in salt-sensitive hypertensive rats.
Iwanaga Y, Kihara Y, Hasegawa K, Inagaki K, Yoneda T, Kaburagi S, Araki M, Sasayama S.
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
BACKGROUND: To investigate whether endogenous ET-1 participates in an adaptive process of left ventricular hypertrophy (LVH) or a maladaptive process from LVH to congestive heart failure (CHF), we used a Dahl salt-sensitive (DS) rat model, in which systemic hypertension caused compensated concentric LVH at the age of 11 weeks followed by marked LV dilatation and global hypokinesis at the age of 17 weeks. METHODS AND RESULTS: By specific sandwich enzyme immunoassay, serum and myocardial ET-1 levels at the LVH stage were not elevated compared with age-matched Dahl salt-resistant (DR) rats, despite the marked increase of LV/body weight ratio (LV/BW). However, at the CHF stage, serum and LV ET-1 levels increased by 3. 8-fold and 5.4-fold, respectively. LV ET-1 contents had close relationships with the fractional shortening (r=0.763) and the systolic wall stress (r=0.858) measured by in vivo transthoracic echocardiography. Immunohistochemistry demonstrated that the remarkably increased ET-1 in LV is located mainly in cardiomyocytes. By competitive reverse transcriptase-polymerase chain reaction, LV prepro-ET-1 mRNA levels increased by 4.1-fold in CHF rats. We randomized 11-week-old LVH rats to chronic treatment with the endothelin receptor antagonist bosentan (Bos, 100 mg. kg-1. d-1, n=14), the alpha1-receptor antagonist doxazosin (Dox, 1 mg. kg-1. d-1, n=12), or vehicle (Cont, n=14). Bos treatment did not alter the LV geometry and function at 15 weeks; however, it attenuated the decrease of LV fractional shortening by 51% (P<0.01) without reducing the LV/BW at 17 weeks. Conversely, Dox, which decreased the blood pressure to the same extent as Bos, did not affect the progression of LV dysfunction. Bos (93%; P<0.0001 versus Cont) but not Dox (42%; P=0.8465 versus Cont) ameliorated the survival rate at 17 weeks (Cont; 36%). CONCLUSIONS: The accelerated myocardial synthesis of ET-1 contributes directly to LV contractile dysfunction during the transition from LVH to CHF. Unelevated levels of LV ET-1 at the established LVH stage and lack of effects on LV mass by chronic bosentan treatment suggest that myocardial growth is mediated through alternative pathways. These studies indicate that chronic ET antagonism may provide an additional strategy for heart failure therapy in humans.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9808606&dopt=Abstract
uibk.ac.at
BACKGROUND: Stromal-cell contractility is known to play an important role in the development of bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH). An in vitro model of single-cell contraction was developed to investigate the effect of alpha1-adrenoceptor agonists and antagonists. METHODS: Human prostatic stromal cells were isolated from prostatectomy and cystoprostatectomy specimens. The cells were cultured in a selective medium supplemented with growth factors and steroid hormones. The culture flasks were coated with a viscous agent to allow cell contraction. Contractions were visualized by means of a cell-culture microscope fitted with a time-lapse video system. For quantitative analysis, the percentage of contracting cells was evaluated. RESULTS: Nineteen percent of the cells were found to contract without stimulation. Following incubation with doxazosin (10 nM, 100 nM, and 1 mM), there was a slight dose-dependent decrease in the number of spontaneously contracting cells, whereas adrenergic stimulation using 10 microM of phenylephrine led to a significant increase in the percentage of contracting cells (55%). Following incubation with 100 nM of doxazosin, the phenylephrine-induced effect was significantly reduced. CONCLUSIONS: This simple in vitro model of cell contraction in the prostate provides a useful means of investigating drug effects on prostatic stromal cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9831216&dopt=Abstract
J Clin Pharm Ther. 1998 Aug;23(4):287-94.
Drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs.
Yuen YH, Chang S, Chong CK, Lee SC, Critchley JA, Chan JC.
Department of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories.
OBJECTIVES: To examine the prescribing patterns, particularly antihypertensive and antidiabetic drugs, in a hospital outpatient clinic and to evaluate the expenditure incurred. METHODS: Prescriptions from a general medical outpatient clinic in a teaching hospital were collected for 4 weeks. Drug expenditures were calculated. RESULTS: A total of 622 prescriptions containing 1903 items were collected. Antihypertensive and antidiabetic drugs accounted for 25.9 and 9.1% usage, respectively. Calcium channel blocking agents, angiotensin converting enzyme inhibitors and beta-blocking agents were the most popular antihypertensive drugs used. Sulphonylureas were the most frequently prescribed antidiabetic agents. Amlodipine, doxazosin and sotalol accounted for 4.5% of all prescription items but 27.8% of the total drug expenditure. CONCLUSION: The use of antihypertensive and antidiabetic drugs accounted for most of the drug usage in this study. Use of newer and more expensive agents has further increased drug expenditure. Monitoring drug usage and their correlations with clinical outcomes are warranted.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9867312&dopt=Abstract
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