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Tolerable Dose (tolerable + dose)
Selected AbstractsThe Effect of Beta-Blocker (Carvedilol) Therapy on N-Terminal Pro-Brain Natriuretic Peptide Levels and Echocardiographic Findings in Patients with Congestive Heart FailureECHOCARDIOGRAPHY, Issue 2 2007Fuat Gundogdu M.D. Background: The favorable effects of beta-blockers on decreasing mortality in contemporary heart failure management have been demonstrated in recent years. N-terminal pro-brain natriuretic (NT-proBNP) peptide levels increase in patients with heart failure. The purpose of this study was to investigate the correlation between the NT-proBNP levels and echocardiographic findings for the patients who received carvedilol therapy in addition to standard therapy for congestive heart failure. Methods and Results: A total of 25 patients with symptomatic congestive heart failure and 25 healthy individuals were enrolled in the study. Before introducing beta-blocker into their therapy regimens, baseline transthoracic echocardiography recordings were made and venous blood samples were drawn for establishing NT-proBNP levels. The patients were administered with a minimum dose of carvedilol. Three months after reaching the maximum tolerable dose, blood samples were drawn from the patients once again for NT-proBNP measurements, and transthoracic echocardiography was performed. There was a significant drop in plasma NT-proBNP levels at the end of the study in comparison to the baseline values (baseline: 381.20±35.06 pg/mL, at the end of the third month: 254.44±28.64 pg/mL; P < 0.001). While left ventricular end-diastolic and end-systolic diameters were observed to have significantly decreased as a result of the therapy (P < 0.001), left ventricular ejection fraction (P<0.001) was established to have increased significantly. Conclusions: Carvedilol therapy resulted in a marked decrease in plasma NT-proBNP levels and increase left ventricular ejection fraction in patients with congestive heart failure. [source] The Effect of Acute Ethanol Intoxication on Salivary Proteins of Innate and Adaptive ImmunityALCOHOLISM, Issue 4 2008Napoleon Waszkiewicz Background:, Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems. Methods:, Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6-hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva. Results:, At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002, p = 0.043, and p = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively). Conclusion:, Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens. [source] Synthesis and Structure-Activity Relationship Studies of Pyrazole-based Heterocycles as Antitumor AgentsARCHIV DER PHARMAZIE, Issue 7 2010Ahmad M. Farag Abstract Several 4-cyano-1,5-diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4-cyano-1,5-diphenyl-1H -pyrazole-3-carboxylate 1. The newly synthesized compounds were tested in vivo for their anti-estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen-dependent tumors. 3-(5-Mercapto-1,3,4-oxadiazole-2-yl)-1,5-diphenyl-1H -pyrazole-4-carbonitrile 13 revealed the highest cytotoxic activity with a GI50 value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti-estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3-(5-(Methylthio)-4-phenyl-4H -1,2,4-triazol-3-yl)-1,5-diphenyl-1H -pyrazole-4-carbonitrile 7 was found to have the highest anti-estrogenic activity, while 1,5-diphenyl-3-[5-(phenylamino)-1,3,4-thiadiazol-2-yl]-1H -pyrazole-4-carbonitrile 11 showed the lowest activity. The oral LD50 values revealed that most of the tested compounds are relatively nontoxic. [source] Age dependence of cataract induced by ultraviolet radiation-B in miceACTA OPHTHALMOLOGICA, Issue 2007Y ZHANG Purpose: To investigate for the C57BL/6 mouse if there is an age dependence of the dose-response function for in vivo UVR-300 nm induced forward light scattering in the lens. Methods: Each of four age groups of 25 mice aged 3, 6, 12, or 24 weeks were randomly distributed on five age group specific UVR-B dose levels. The dose levels selected for each age group were derived from the expected maximum tolerable dose (MTD). Expected MTDs were set to 1.9, 3.2, 4.8, and 6.0 kJ/m^2 for the 3, 12, and 24 weeks mice, respectively, based on published data for the albino Sprague Dawley rat. Each animal was unilaterally exposed to UVR-B to the pre-determined dose, delivered during 15 minutes. All mice were sacrificed two days after exposure and both lenses were extracted for; macroscopic imaging in incident illumination against a grid and in dark-field illumination, and measurement of intensity of forward light scattering. The difference of intensity of forward light scattering between the exposed and the contralateral not exposed lens was fitted against dose received using regression based on a second order polynomial model. Results: Two days after exposure, subcapsular opacities were observed in the exposed lenses from all dose groups except at 0 kJ/m^2. In all age groups, the difference of intensity of forward light scattering increased with increasing UVR-B dose. The increase was age dependent. Conclusions: In the pigmented C57BL/6 mouse, an increasing in vivo dose of UVR-300 nm induces an increasing intensity of forward light scattering that is age dependent in the age interval 3-24 weeks. This finding should be considered in future design of experiments on UVR-effects to the mouse lens. [source] Asparagus PR cannot compete with first-line diuretics in lowering the blood pressure in treatment-requiring antihypertensivesPHYTOTHERAPY RESEARCH, Issue 9 2009Sigrun Chrubasik Abstract A six week clinical surveillance of 163 patients receiving maximally tolerable doses of Asparagus P®, a proprietary mixture pulversied dried asparagus root and parsley leaf, has not indicated any clinically useful antihypertensive effect. The profile of adverse events (with 7 patients leaving the surveillance early because of renally related complaints) contraindicates its use in hypertension or to promote flushing of the efferent tract in rental inflammatory conditions or urolithiasis. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||