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Graded Doses (graded + dose)
Selected AbstractsProtective effect of Nardostachys jatamansi on oxidative injury and cellular abnormalities during doxorubicin-induced cardiac damage in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2006Rajakannu Subashini Nardostachys jatamansi is a medicinally important herb of Indian origin. It has been used for centuries in the Ayurvedic and Unani systems of medicine for the treatment of various ailments. We have evaluated the effect of N. jatamansi (rhizomes) on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in doxorubicin (adriamycin)-induced cardiac damage. Preliminary studies on the effect of the graded dose of extract showed that 500 mg kg,1 orally for seven days was found to be optimum and hence all further study was carried out with this particular dose. Rats administered doxorubicin (15 mg kg,1, i.p.) showed myocardial damage that was manifested by the elevation of serum marker enzymes (lactate dehydrogenase, creatine phosphokinase, aspartate aminotransaminase and alanine aminotransaminase). The animals showed significant changes in the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) and lipid peroxidation levels. Pretreatment with N. jatamansi extract significantly prevented these alterations and restored the enzyme activity and lipid peroxides to near normal levels. Restoration of cellular normality accredits the N. jatamansi with a cytoprotective role in doxorubicin-induced cardiac damage. [source] Toxic responses of medaka, D-rR strain, to polychlorinatednaphthalene mixtures after embryonic exposure by in ovo nanoinjection: A partial life-cycle assessmentENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Sergio A. Villalobos Abstract Polychlorinated naphthalenes (PCNs) are organic compounds with some chemical properties and uses similar to polychlo-rinated biphenyls. Polychlorinated naphthalenes have been detected in biota from certain aquatic environments. The toxicities of several PCN technical mixtures (Halowax) to medaka (Oryzias latipes) were determined by use of an embryo nanoinjection method. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of four to five graded doses (0.3,30 ng/egg) of Halowax 1014, Halowax 1013, or Halowax 1051 in triolein. Following exposure, embryos developed, and fry were reared to sexual maturity (4 months), at which time they were euthanized. Responses were evaluated as early life stage (ELS) and early adult life stage (EALS) assessments. For ELS, lethality and sublethal alterations in embryos and larvae (<16 d old), such as craniofacial, cardiovascular, and myoskeletal deformities and abnormal or delayed hatch, were monitored for the first 9 d, and a dose severity index was computed. The EALS assessment examined the survival of 16-d-old larvae until early adulthood (123 ± 3 d old), including gonadosomatic index (GSI) and morphometry. Halowax 1014 was found to be the most toxic mixture (LD50 4.2 ng/egg), whereas Halowax 1013 and 1051 were significantly less toxic (LD50s could not be determined). The gonadosomatic index of females was significantly less in fish dosed with Halowax 1014 or 1051. The LD50 for medaka embryos nanoinjected with 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) is about 0.75 pg/egg. Thus, Halowax 1014 was 5,585-fold less potent than TCDD. For Halowax 1014, ELS assessments accurately predicted the results of EALS assessments. [source] Changes in Muscle Mass, Muscle Strength, and Power but Not Physical Function Are Related to Testosterone Dose in Healthy Older MenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2008Thomas W. Storer PhD OBJECTIVES: To examine the effect of graded doses of testosterone on physical function and muscle performance in healthy, older men. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: General clinical research center. PARTICIPANTS: Community-dwelling healthy men aged 60 to 75 (N=44). INTERVENTION: Monthly treatment with a gonadotropin-releasing hormone agonist plus 25, 50, 125, or 300 mg/wk of intramuscular injections of testosterone enanthate for 20 weeks. MEASUREMENTS: Skeletal muscle mass (SMM) was estimated using dual-energy X-ray absorptiometry. Leg press strength was measured by one repetition maximum, leg power by Nottingham Leg Rig, and muscle fatigability by repetitions to failure in the leg press exercise. Stair climbing, 6-meter and 400-meter walking speed, and a timed-up-and-go (TUG) test were used to assess physical function. RESULTS: Significant testosterone dose- and concentration-dependent increases were observed in SMM (P<.001) and maximal strength (P=.001) but not muscle fatigability. Leg power also increased dose-dependently (P=.048). In contrast, changes in self-selected normal and fast walking speed over 6 or 400 meters, stair climbing power, and time for the TUG were not significantly related to testosterone dose, testosterone concentrations, or changes in muscle strength or power, or SMM. CONCLUSION: Testosterone administration was associated with dose-dependent increases in SMM, leg strength, and power but did not improve muscle fatigability or physical function. The observation that physical function scores did not improve linearly with strength suggests that these high-functioning older men were already in the asymptotic region of the curve describing the relationship between physical function and strength. [source] Comparison of the Effects of Deramciclane, Ritanserin and Buspirone on Extracellular Dopamine and Its Metabolites in Striatum and Nucleus Accumbens of Freely Moving RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2008Tiina M. Kääriäinen Dual probe in vivo microdialysis in freely moving rats was used to compare the effects of graded doses of deramciclane fumarate (3, 10 and 30 mg/kg), 5-HT2A/C antagonist ritanserin (1 mg/kg) and a partial 5-HT1A agonist buspirone hydrochloride (5 mg/kg) on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus accumbens and striatum assayed by high performance liquid chromatography with electrochemical detection. The indirect dopamine agonist, D-amphetamine sulfate (2 mg/kg), was used as a positive control. Ritanserin, buspirone and deramciclane 3 and 10 mg/kg had no significant effects on the extracellular dopamine levels in either brain area but deramciclane 30 mg/kg significantly increased accumbal dopamine as well as DOPAC and HVA in both brain areas. As expected, the positive control D-amphetamine significantly increased both striatal and accumbal dopamine levels. The effects of buspirone or the highest deramciclane dose and D-amphetamine on DOPAC and HVA levels were opposite; buspirone and deramciclane increased while D-amphetamine decreased the metabolite levels in both brain areas. The results indicate that a single high dose of deramciclane has the neuroleptic- or buspirone-like effect, particularly in mesolimbic regions. There is at least a 5-fold margin between the anxiolytic and neuroleptic doses of deramciclane in the rat. [source] | ||||||||||