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Selected AbstractsAntidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulationDIABETES OBESITY & METABOLISM, Issue 11 2008R. R Ortiz-Andrade Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [source] Influence of isolation on the recovery of pond mesocosms from the application of an insecticide.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2007Abstract The influence of relative isolation on the ecological recovery of freshwater outdoor mesocosm communities after an acute toxic stress was assessed in a 14-month-long study. A single concentration of deltamethrin was applied to 8 out of 16 outdoor 9-m3 mesocosms to create a rapid decrease of the abundance of arthropods. To discriminate between external and internal recovery mechanisms, four treated and four untreated (control) mesocosms were covered with 1-mm mesh screen lids. The dynamics of planktonic communities were monitored in the four types of ponds. The abundance of many phytoplankton taxa increased after deltamethrin addition, but the magnitude of most increases was relatively small, probably due to low nutrient availability and the survival of rotifers. The greatest impact on zooplankton was seen in Daphniidae and, to a lesser extent, calanoid copepods. Recovery (defined as when statistical analysis failed to detect a difference in the abundance between the deltamethrin-treated ponds and corresponding control ponds for two consecutive sampling dates) of Daphniidae was observed in the water column 105 and 77 d after deltamethrin addition in open and covered mesocosms, respectively, and <42 d for both open and covered ponds at the surface of the sediments. Rotifers did not proliferate, probably because of the survival of predators (e.g., cyclopoid copepods). These results confirm that the recovery of planktonic communities after exposure to a strong temporary chemical stress mostly depends upon internal mechanisms (except for larvae of the insect Chaoborus sp.) and that recovery dynamics are controlled by biotic factors, such as the presence of dormant forms and selective survival of predators. [source] REVIEW: The alcohol-preferring P rat and animal models of excessive alcohol drinkingADDICTION BIOLOGY, Issue 3-4 2006Richard L. Bell ABSTRACT The alcohol-preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol-non-preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge-like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1-hour access periods/day, which approximates the 24-hour intake of P rats with free-choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re-exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge-like or relapse-like drinking. [source] Insecticidal activity of 23 essential oils and their major compounds against adult Lipaphis pseudobrassicae (Davis) (Aphididae: Homoptera)PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 11 2005Blair J Sampson Abstract Essential oils from 23 species of plants comprising 14 genera and 4 plant families were obtained by Clevenger-type water distillation. The major compounds in these essential oils were identified with GC-MS and their insecticidal activity against adult turnip aphids, Lipaphis pseudobrassicae (Davis), tested with dosage-mortality bioassays. We examined mortality only for viviparous adults because sizeable aphid populations on crucifer (Brassicaceae) hosts are largely produced by these wingless, parthenogenic females. Twenty-two of the oils were directly applied to aphid females in randomized blocks at concentrations of 0.0, 1.0, 2.5, 5.0 and 10.0 mg ml,1. Essential oils mixed with a non-toxic emulsifying agent, dimethyl sulfoxide (DMSO), more easily penetrated the waxy insect cuticle. Probit analysis and LC50 at three different exposures showed aphids were quickly incapacitated and killed by aliphatic aldehydes, phenols and monocyclic terpenes contained in Bifora and Satureja oils and at applied concentrations as low as 0.3 to 1.0 mg ml,1. Only enough Pimpinella isaurica oil and its three phenylpropanoid fractions were available for testing at a single concentration of 10 mg ml,1. We could not spare any additional P. isaurica oil for testing at other concentrations. Phenylpropanoids isolated from P. isaurica oil when recombined or left naturally blended in the oil were highly bioactive against L. pseudobrassicae at 10 mg ml,1. Copyright © 2005 Society of Chemical Industry [source] Control of non-adrenergic non-cholinergic reflex motor responses in circular muscle of guinea-pig small intestine by Met-enkephalinAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2002Chr. Ivancheva Summary 1 A triple organ bath method allowing the synchronous recording of the motor activity of the circular muscle layer belonging to the oral and anal segments of guinea-pig small intestine adjacent to an electrically stimulated middle segment was developed to study the ascending and descending reflex motor responses. 2 Electrical field stimulation (0.8 ms, 40 V, 5 Hz, 10 s) applied to the middle part of the segments elicited tetrodotoxin (1 ,m)-sensitive ascending and descending contractile responses of the nonstimulated parts, oral and anal, respectively. The ascending contraction was more pronounced as compared with the descending contraction. 3 In the presence of phentolamine (5 ,m), propranolol (5 ,m) and atropine (3 ,m) a significant decrease in the amplitude of the ascending contraction was seen and a descending relaxation, instead of a contraction was observed. 4 Met-enkephalin applied at a single concentration (0.1 ,m) or cumulatively (0.001,1 ,m) inhibited both non-adrenergic non-cholinergic (NANC) descending relaxation and ascending contraction with similar efficacy but different potency, IC50 being 5.9 ± 0.3 and 39.0 ± 4 nm, respectively. Naloxone (0.5 ,m) prevented the effects of Met-enkephalin. 5 L-NNA (0.5 mm), an inhibitor of nitric oxide synthesis, increased the ascending contraction and strongly reduced but not abolished the descending relaxation. l -Arginine (0.5 mm) restored the motor responses to the initial level in l -NNA-pretreated preparations, d -Arginine (0.5 nm) had no effects. 6 Met-enkephalin (0.1 ,m) depressed the l -NNA-dependent increase of the ascending contraction and failed to change the l -NNA-resistant part of the descending relaxation. 7 Met-enkephalin did not alter spontaneous NANC mechanical activity. SNP (1 or 10 ,m), an exogenous donor of nitric oxide, caused a concentration-dependent relaxation. The effects of SNP persisted in Met-enkephalin (0.1 ,m)-pretreated preparations. 8 NANC reflex ascending contraction and descending relaxation were synchronously induced by a local nerve stimulation indicating a functional coactivation of NANC orally projected excitatory and anally directed inhibitory pathways. Acting prejunctionally, Met-enkephalin provided a negative controlling mechanism inhibiting both ascending and descending, mainly nitric oxide mediated, reflex responses. A higher sensitivity of the descending relaxation to Met-enkephalin was observed suggesting an essential role of opioid(s) in reducing the efficacy of descending motor activity. [source] | |||||||||||||