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Optimum Dose (optimum + dose)
Selected AbstractsDose Range-Finding Studies With Frovatriptan in the Acute Treatment of MigraineHEADACHE, Issue 2002Alan Rapoport MD Objective.,To determine the optimum dose of frovatriptan for the acute treatment of migraine. Background.,Frovatriptan is a new triptan developed for the acute treatment of migraine. The dose-response characteristics and safety of frovatriptan have been investigated across a broad range of doses from 0.5 to 40 mg. Design.,Two randomized, placebo-controlled, double-blind, parallel-group trials, with a total of 1453 patients, were performed to determine the optimal dose of the 5-HT1B/1D agonist, frovatriptan, for the acute treatment of migraine. The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg in the low-dose study. Results.,At 2 hours postdosing for initial moderate or severe headache (International Headache Society grades 2 or 3), there was an approximate two-fold difference in the proportion of patients taking frovatriptan doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours postdose, and 2.5 mg was identified as the lowest effective dose for the relief of migraine and accompanying symptoms. Above 2.5 mg, no dose-response relationship was observed for any efficacy parameters. There was an increase in the incidence of adverse events from 10 mg and above, but the vast majority were rated as mild in severity and did not impact upon tolerability in a significant manner. Conclusions.,Frovatriptan was well tolerated throughout the dose range of 0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and tolerability for the acute treatment of migraine. [source] Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidenceHEPATOLOGY RESEARCH, Issue 3 2009Monika Bhadauria Aim:, The curative effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of the plant species Ventilago maderaspatana Gaertn, was evaluated against carbon tetrachloride (CCl4) induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural alterations in rats. Methods:, Female rats were administered CCl4 (1.5 mL/kg, ip) followed by varying doses of emodin (20, 30 and 40 mg/kg, oral po) after 24 h of CCl4 administration. Animals were euthanized after 24 h of last administration to determine liver function tests in serum, hepatic light microscopic and ultrastructural changes, activity of CYP enzymes, microsomal lipid peroxidation and protein contents, hexobarbitone induced sleep time and bromosulphalein retention. Results:, The CCl4 induced-toxic effects were observed with sharp elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and ,-glutamyl transpeptidase. An initial study for an optimum dose of emodin among different dose levels revealed that a 30 mg/kg dose was effective in restoring all the enzymatic variables and liver histoarchitecture in a dose dependent manner. Exposure to CCl4 diminished the activities of CYP enzymes (i.e. aniline hydroxylase and amidopyrine-N-demethylase and microsomal protein contents with concomitant increase in microsomal lipid peroxidation). Emodin at 30 mg/kg effectively reversed the CCl4 induced hepatotoxic events, which was consistent with ultrastructural observations. Hexobarbitone-induced sleep time and plasma bromosulphalein retention also improved liver functions after emodin therapy. Conclusion:, By reversal CYP activity and ultrastructural changes, emodin shows a strong hepatoprotective abilities. [source] Antihyperlipidemic activity of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, in streptozotocin-diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2010Govindasamy Chandramohan Abstract Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on carbohydrate metabolism was investigated, and its antihyperglycemic effect was shown previously (Chandramohan et al., Eur J Pharmacol 2008;590:437,443). In this study we investigated the effect of 3-HMX on plasma and tissue lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180,200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. The normal and diabetic rats were treated with 3-HMX (40 mg/kg BW/day) for 45 days. The levels of total cholesterol, triglycerides, free fatty acids, and phospholipids were assayed in the plasma besides lipoprotein-cholesterol (high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very low density lipoprotein-cholesterol (VLDL-C)) and tissues (liver, kidney, heart, and brain). Total cholesterol, triglyceride, free fatty acid, and phospholipid (LDL-C and VLDL-C in plasma only) levels increased in plasma and tissues significantly, whereas plasma HDL-C significantly decreased in diabetic rats. Treatment with 3-HMX or glibenclamide reversed the above-mentioned changes and improved toward normalcy. Histological study of liver also confirmed the biochemical findings. Thus administration of 3-HMX is able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:95,101, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20317 [source] Evaluation of the radioprotective effect of Ageratum conyzoides Linn. extract in mice exposed to different doses of gamma radiationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2003Ganesh Chandra Jagetia The effect of various doses (0, 25, 50, 75, 100, 125, 150, 300, 600 and 900 mg kg,1) of the alcoholic extract of the plant Ageratum conyzoides Linn. (ACE), on the alteration of radiation-induced mortality in mice exposed to 10 Gy of gamma radiation was studied. The acute toxicity studies showed that the drug was non-toxic up to a dose of 3000 mg kg,1, the highest dose that could be tested for acute toxicity. Administration of ACE resulted in a dose-dependent decline in radiation-induced mortality up to a dose of 75 mg kg,1, the dose at which the highest number of survivors (70.83%) was observed. Thereafter, the number of survivors declined with increasing doses of ACE and a nadir was reached at 900 mg kg,1 ACE. Since the number of survivors was highest for 75 mg kg,1 ACE, this was considered the optimum dose for radioprotection and used in further studies in which mice were treated with 75 mg kg,1 ACE before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation. The treatment of mice with 75 mg kg,1 ACE reduced the severity of symptoms of radiation sickness and mortality at all exposure doses, and a significant increase in survival was observed compared with the non-treated irradiated group. The ACE treatment effectively protected mice against the gastrointestinal as well as bone marrow related death, as revealed by the increased number of survivors at all irradiation doses. The dose reduction factor was found to be 1.3. To understand the mechanism of action, various doses of ACE were evaluated for their in-vitro scavenging action on 1,1-diphenyl-2-picrylhydrazyl (DPPH), a chemically stable free radical. ACE was found to scavenge DPPH radicals in a concentration-dependent manner, indicating that the radioprotection afforded by ACE may be in part due to the scavenging of reactive oxygen species induced by ionizing radiation. [source] Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitroJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2001Gamal M. M. El Maghraby The potential use of ultradeformable and standard liposomes as skin drug delivery systems was investigated in-vitro. An improved experimental design gave a good measure for skin deposition of drug. This avoided the contamination that can occur due to incomplete washing of the donor before direct determination of the amount of drug in the skin. The design used aqueous ethanolic receptor which is believed to diffuse into skin, disrupting deposited liposomes (if any) and thus releasing both bound and free drug. The receptor fluid was refined by testing different concentrations of ethanol. The applied dose was also optimized. Using the improved design and the optimum dose, an ultradeformable formulation was compared with four traditional liposomes for skin delivery of 5-fluorouracil (5-FU). The best receptor was 50% aqueous ethanol and the optimum dose was 20 ,L. The ultradeformable formulation was superior to standard liposomes in the skin delivery of 5-FU. Of the traditional liposomes, the non-rigid preparation was the best. However, stabilization of the liposome membrane with cholesterol abolished the benefit of this non-rigid preparation. It was concluded that ultradeformable vesicles are promising agents for skin delivery of drugs. [source] Analgesia for circumcision in a paediatric population: comparison of caudal bupivacaine alone with bupivacaine plus two doses of clonidinePEDIATRIC ANESTHESIA, Issue 6 2001P. Sharpe FRCA Background:,Clonidine is often used to improve the duration and quality of analgesia produced by caudal epidural blockade, although the optimum dose of clonidine with bupivacaine remains uncertain. Methods:,We compared the effect of clonidine, 1 and 2 ,g·kg,1, added to bupivacaine (1.25 mg·kg,1) with that of bupivacaine alone in 75 male children undergoing elective circumcision. Results:,There was a trend towards increasing duration of analgesia with increasing dose of clonidine [group B (bupivacaine) 280.7 (171.6) min, C1 (bupivacaine + clonidine 1 ,g·kg,1) 327.8 (188.3) min and C2 (bupivacaine + clonidine 2 ,g·kg,1) 382.0 (200.6) min], although this difference was not statistically significant. Mean time to arousal from anaesthesia was significantly prolonged with clonidine 2 ,g kg,1 (group C2 21.3 (13,36) min, group C1 14.0 (6,25) min and group B 14.4 (2,32) min. Supplementary analgesic requirements and incidence of adverse effects were low, with no differences between the groups. Conclusions:,For paediatric circumcision, under general anaesthesia, the addition of clonidine 2 ,g·kg,1 to low volume (0.5 ml·kg,1) caudal anaesthetics has a limited clinical benefit for children undergoing circumcision. [source] Attract-and-kill strategy.PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 10 2007Laboratory studies on hatched larvae of Culex pipiens Abstract The attract-and-kill strategy is a new pest management technique that presupposes the intelligent combination of an attracting agent (e.g. pheromone) and a killing agent (e.g. insecticide). In the present study, the potential combination of the microencapsulated synthetic oviposition pheromone 6-acetoxy-5-hexadecanolide with an insecticide has been tested. Initially, polyurea microcapsules containing 6-acetoxy-5-hexadecanolide, the synthetic mixture of diastereomers of the oviposition pheromone of the mosquito species Culex quinquefasciatus Say (Diptera: Culicidae), were studied. Laboratory bioassays were performed to confirm the bioactivity of the microencapsulated pheromone on the oviposition activity of Culex pipiens L. biotype molestus Førskal (Diptera: Culicidae) with the aim of determining the optimum dose for oviposition response. Its effect was dose dependent, revealing an optimum dose of 300 mg of dried microcapsules. Attractancy over time was also studied. The microencapsulated pheromone was found to be sufficiently attractive to gravid female mosquitoes for a period of 40 days. Finally, the combination of the synthetic pheromone with the control agent temephos showed both an acceptable oviposition activity and sufficient larvicidal effect. Copyright © 2007 Society of Chemical Industry [source] EFFECTS OF ADMINISTRATION OF ORAL MAGNESIUM ON PLASMA GLUCOSE AND PATHOLOGICAL CHANGES IN THE AORTA AND PANCREAS OF DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005Nepton Soltani SUMMARY 1.,Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of the complications of diabetes. The purpose of the present study was to determine the relationship between oral Mg supplementation and changes in plasma glucose, calcium, haemogolobin, Ca/Mg ratio, blood pressure and the histology of the pancreas and vascular system in streptozotocin-induced diabetic rats. 2.,Ten days after the induction of diabetes in male Wistar rats, half the diabetic animals were divided into six groups, receiving 0, 1, 3, 10, 30 or 50 g/L MgSO4 added into the drinking water for 8 weeks. Plasma glucose and Mg were measured at days 1, 2, 3, 5, 7, 14 and 21 to find the optimum dose of Mg and the time-course of its effect. In addition, histological observations were undertaken. Eight weeks later, all animals were decapitated, the pancreas and thoracic aorta were removed carefully and immersed immediately in 10% formaldehyde for histological study. 3.,To evaluate the effects of Mg on plasma glucose, calcium, haemoglobin, Mg and blood pressure, another group of animals was divided into four experimental groups, as follows: (i) non-diabetic controls received tap water for 8 weeks; (ii) acute diabetics received tap water for 10 days; (iii) chronic diabetic controls received tap water for 8 weeks; and (iv) Mg-treated chronic diabetic rats received 10 g/L MgSO4 added into the drinking water 10 days after the induction of diabetes for 8 weeks. 4.,Magnesium dose dependently affects plasma glucose levels. The peak effect was reached during the first 24 h following oral administration. Administration of 10 g/L MgSO4 results in the return of normal structure in the diabetic pancreas and aorta. Moreover, this concentration of MgSO4 causes glucose, haemoglobin, calcium, the Ca/Mg ratio and blood pressure to reach normal levels. Although the Mg level increases slightly following the administration of 10 g/L MgSO4 to diabetic rats, it never reaches control levels. 5.,On the basis of the results of the present study, it may be concluded that chronic Mg administration may have beneficial effects on diabetes. [source] | |||||||||||||