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Various Doses (various + dose)
Selected Abstracts(11Z)-hexadec-11-enal enhances the attractiveness of Diatraea saccharalis main pheromone component in wind tunnel experimentsJOURNAL OF APPLIED ENTOMOLOGY, Issue 2 2005B. Kalinová Abstract:, GC-EAD and GC-MS analysis of pheromone gland extracts of sugarcane borer, Diatraea saccharalis, revealed two antennally active compounds, (9Z,11E)-hexadeca-9,1-dienal and (11Z)-hexadec-11-enal, in approximately 10 : 1 ratio. Various doses of identified compounds were investigated in wind tunnel experiments individually and in a 10 : 1 ratio. At all tested doses (9Z,11E)-hexadeca-9,1-dienal alone elicited upwind orientation and source location only in a minority of tested males. An admixture of (11Z)-hex-11-enal enhanced the attractiveness of (9Z,11E)-hexadeca-9,11-dienal significantly. This two-component blend (100 pg) was as attractive as natural pheromone extracted from three female pheromone glands. The data suggest that (11Z)-hexadec-11-enal is a part of the D. saccharalis sex pheromone. [source] Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemiaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2009Rajanikant G. Krishnamurthy Abstract Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate- or ,-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre- and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood,brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygen-glucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood,brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia. © 2009 Wiley-Liss, Inc. [source] Effects of buspirone and alprazolam treatment on the startle-potentiated startle responseDEPRESSION AND ANXIETY, Issue 3 2004Randall L. Commissaris Ph.D. Abstract The startle potentiated startle (SPS) paradigm has been reported to be an effective procedure for studying the conditioned enhancement of acoustic startle in the absence of electric shocks or extinction. This study examines the effects of two anxiolytic treatments, buspirone and alprazolam, on this SPS effect. Subjects were tested in the SPS paradigm 2 days a week (Monday and Thursday) for 10 weeks. Each startle test session consisted of 10 Noise Alone trials (115 dB acoustic noise burst presented for 40 ms) and 10 Light+Noise trials (115 dB acoustic stimuli presented during the latter 40 ms of a 3,540 ms period in which a 15-watt light was illuminated). Although there was no difference in startle amplitude on Noise Alone trials when compared to Light+Noise trials initially, by the end of the first test session and continuing throughout the duration of the experiment, startle amplitude on Light+Noise trials was significantly (approximately 50,75%) greater than on Noise Alone trials. After five control (i.e., no injection) SPS test sessions, once-weekly drug challenges were conducted over the course of 7 weeks. In these weekly drug challenges, subjects received acute treatment with various doses of the benzodiazepine anxiolytic alprazolam (0.25, 0.5, 1.0 mg/kg) or the novel anxiolytic buspirone (1.0, 2.0, 4.0 mg/kg); subjects also received vehicle treatment (0.5% methylcellulose) on one treatment day. All treatments were administered intraperitoneally (IP), 15 min before the start of startle testing. Consistent with previous reports, buspirone increased and alprazolam decreased startle amplitude on the Noise Alone trials; these effects were dose-related. Both agents reduced the magnitude of the SPS effect when it was expressed as the Light+Noise startle amplitude minus the Noise Alone startle amplitude. These findings are similar to the effects of these treatments in the traditional shock-based fear-potentiated startle paradigm. Depression and Anxiety 19:146,151, 2004. © 2004 Wiley-Liss, Inc. [source] Whole body extract of Mediterranean fruit fly males elicits high attraction in virgin femalesENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2008Vassilis G. Mavraganis Abstract The search for effective female attractants emanating from the host or body of fruit flies has been an area of intensive research for over three decades. In the present study, bodies of male Mediterranean fruit flies, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), were extracted with diethyl ether or methanol and subjected to gas chromatography,mass spectrometry. Analysis revealed substantial qualitative and quantitative differences between males from a laboratory culture and wild males captured alive in an orchard. Most notably, the hydrocarbon sesquiterpene (±)-,-copaene, which is known to be involved in the sexual behaviour of the species, was found in substantial amounts in wild males, but was not detected in laboratory males. In laboratory tests, 15 laboratory or wild male equivalents of diethyl ether extracts or combined diethyl ether and methanol extracts, or, to a lesser extent, methanol extracts alone, were found to attract virgin females. In a citrus orchard, traps baited with combined diethyl ether and methanol extracts of wild males attracted significantly more virgin females than traps baited with various doses of pyranone or blends of other compounds identified in the extracts or reported in the literature, such as ethyl acetate, ethyl-(E)-3-octenoate, and 1-pyrroline. Traps baited with blends of compounds, however, displayed substantial attractiveness compared to control (non-baited) traps. These results are important for better understanding the mating system of C. capitata as well as for further improving existing monitoring and control systems. [source] Dose- and time-dependent responses for micronucleus induction by X-rays and fast neutrons in gill cells of medaka (Oryzias latipes)ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004Akinori Takai Abstract Medaka fish (Oryzias latipes) were exposed to various doses of X-rays or fast neutrons, and the frequency of micronucleated cells (MNCs) was measured in gills sampled at 12- or 24-hr intervals from 12 to 96 hr after exposure. The resulting time course of MNC frequency was biphasic, with a clear peak 24 hr after exposure, irrespective of the kind of radiation applied and the dose used. The half-life of MNCs induced in the gill tissues by the two exposures fluctuated around 28 hr, with no significant dose-dependent trend for either X-ray- or neutron-exposed fish. As assayed 24 hr after exposure, the MNC frequency increased linearly over the control level with increasing doses of both X-rays and fast neutrons. The relative biological effectiveness (RBE) of fast neutrons to X-rays for MNC induction was estimated to be 4.3 ± 0.6. This value is close to the RBE value of 5.1 ± 0.3 reported for fast neutron induction of somatic crossing-over mutations in Drosophila melanogaster that arise from recombination repair of DNA double-strand breaks. These results and other data support our conclusion that the medaka gill cell micronucleus assay is a reliable short-term test for detecting potential inducers of DNA double-strand breaks. Environ. Mol. Mutagen. 44:108,112, 2004. © 2004 Wiley-Liss, Inc. [source] Removal of benzo(a)pyrene diol epoxide (BPDE)-DNA adducts as a measure of DNA repair capacity in lymphoblastoid cell lines from sisters discordant for breast cancerENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2002Grazyna Motykiewicz Abstract The mutagen sensitivity assay is one of the approaches used to investigate individual DNA repair capacity. This method is based on the premise that after in vitro treatment with a test mutagen, DNA from subjects with defective repair will be more damaged than DNA from those with an efficient repair system. However, very little is known about unmeasured processes that occur between cell treatment and final assessment of DNA damage. To develop a more precise assay, we modified the traditional mutagen sensitivity assay to also include measurement of DNA damage after culturing cells in the absence of mutagen. First, we treated apparently normal and xeroderma pigmentosum lymphoblastoid cell lines with various doses of benzo(a)pyrene diol epoxide (BPDE) and harvested cells at different time points. A polyclonal antiserum against BPDE-DNA was used to quantitate levels of adducts by immunoslot-blot and immunohistochemistry. Selected conditions included treatment with 10 ,M BPDE, a 4-hr culture in mutagen-free medium, and immunohistochemical measurement of BPDE-DNA adducts. The method was then applied in a pilot study to 50 lymphoblastoid lines from sisters discordant for breast cancer. There was no significant difference between cases and controls in the level of BPDE-DNA adducts in lymphoblasts harvested immediately after BPDE treatment. However, after a 4-hr culture in mutagen-free medium, the level of adducts was significantly higher (P = 0.006) among cases than in controls. There was a two-fold increase in mean adduct removal in lines from nonaffected as compared to affected sisters (44% and 22% decrease, respectively). DNA repair capacity was predictive of case status (P = 0.04) in logistic regression analysis. This method, which can be easily applied to large numbers of samples, should be useful in studies to investigate the role of DNA repair in cancer risk. Environ. Mol. Mutagen. 40:93,100, 2002. © 2002 Wiley-Liss, Inc. [source] Inhibition of microsomal triglyceride transfer protein: Another mechanism for drug-induced steatosis in miceHEPATOLOGY, Issue 1 2003Philippe Lettéron Although many steatogenic drugs inhibit mitochondrial fatty acid ,-oxidation, limited information is available on possible effects on hepatic lipoprotein secretion. In the endoplasmic reticulum (ER) lumen, microsomal triglyceride transfer protein (MTP) lipidates apolipoprotein B (Apo B), to form triglyceride (TG)-rich very low density lipoprotein (VLDL) particles, which follow vesicular flow to the plasma membrane to be secreted, whereas incompletely lipidated Apo B particles are partly degraded. We studied hepatic MTP activity, the lipoproteins present in the ER lumen, and hepatic lipoprotein secretion 4 hours after administration of a single dose of amineptine (1 mmol/kg), amiodarone (1 mmol/kg), doxycycline (0.25 mmol/kg), tetracycline (0.25 mmol/kg), tianeptine (0.5 mmol/kg), or pirprofen (2 mmol/kg) in mice. These various doses have been shown previously to markedly inhibit fatty acid oxidation after a single dose, and to trigger steatosis either after repeated doses (doxycycline) or a single dose (other compounds) in mice. In the present study, amineptine, amiodarone, pirprofen, tetracycline, and tianeptine, but not doxycycline, inhibited MTP activity in vitro, decreased ex vivo MTP activity in the hepatic homogenate of treated mice, decreased TG in the luminal VLDL fraction of hepatic microsomes of treated mice, and decreased in vivo hepatic lipoprotein secretion (TG and Apo B). In conclusion, several steatogenic drugs inhibit not only mitochondrial ,-oxidation, as previously shown, but also MTP activity, Apo B lipidation into TG-rich VLDL particles, and hepatic lipoprotein secretion. Drugs with these dual effects may be more steatogenic than drugs acting only on ,-oxidation or only MTP. [source] Curcumin reduces indomethacin-induced damage in the rat small intestineJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2007Nageswaran Sivalingam Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical medicine. Their utility is, however, often limited by the adverse effects they produce in the gastrointestinal tract. Oxidative stress has been shown to occur in the small intestine in response to the oral administration of indomethacin, an NSAID commonly used in toxicity studies. In view of this, the effect of curcumin, an agent with anti-oxidant properties, was evaluated on indomethacin-induced small intestinal damage in a rat model. Rats were pretreated with various doses of curcumin (20 mg kg,1, 40 mg kg,1 and 80 mg kg,1) before administering indomethacin at 20 mg kg,1. Various parameters of oxidative stress and the extent of small intestinal damage produced by indomethacin, with and without pretreatment with curcumin, were measured. Macroscopic ulceration was found to occur in the small intestine in response to indomethacin. The viability of enterocytes from indomethacin-treated animals was significantly lower than those from control animals. Drug-induced oxidative stress was also evident as seen by increases in the levels of malondialdehyde and protein carbonyl and in activities of pro-oxidant enzymes such as myeloperoxidase and xanthine oxidase in indomethacin-treated rats. Concomitant decreases were seen in the activities of the antioxidant enzymes catalase and glutathione peroxidase in these animals. Pretreatment with curcumin was found to ameliorate these drug-induced changes. Thus, curcumin appears to hold promise as an agent that can potentially reduce NSAID-induced small intestinal damage. Copyright © 2007 John Wiley & Sons, Ltd. [source] USE OF CLARIFYING AGENTS AND ULTRA FILTER TO DECREASE FUMARIC ACID, HMF AND INCREASE CLARITY OF APPLE JUICEJOURNAL OF FOOD QUALITY, Issue 3 2006YAHYA TULEK ABSTRACT In this study, the effects of eight different processing treatments of apple juice (AJ) production (Process 1: Ultra filtration [UF], Process 2: Activated charcoal [AC], Process 3: polyvinylpolypyrolidone [PVPP], Process 4: Gelatine [G] + Bentonite [B], Process 5: [G + B] + UF, Process 6: [G + B] + AC, Process 7: [G + B] + PVPP and Process 8: [G + B] + Kieselguhr [K]) on the fumaric acid (FA), hydroxymethylfurfural (HMF), color and clearness values of AJ were investigated. With the exception of Processes 1 and 5, AC, K, PVPP, G and B were used at various doses in other processes. FA, HMF, color and clearness values of control sample were determined as 3.24 mg/L, 3.84 mg/L, 48.5 (%T) and 94.1 (%T), respectively. The highest proportional decrement in FA and HMF values of the samples were observed with Process 6 at the level of 5. The fifth level of Process 6 resulted in 35.8% (3.24,2.08 mg/L) and 35.9% (3.84 to 2.46 mg/L) reductions in FA and HMF values, respectively. On the other hand, the best improvement in clearness of AJ was obtained with Process 6 at the fourth level and obtained as 98.9 (%T). [source] Physicochemical Changes in Alaska Pollock Surimi and Surimi Gel as Affected by Electron BeamJOURNAL OF FOOD SCIENCE, Issue 1 2004J. JACZYNSKI ABSTRACT: Alaska pollock surimi and surimi gels (cooked) were subjected to various doses of electron beam (e-beam). Shear stress of surimi gels increased as the dose increased up to 6 to 8 kGy and then decreased. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed gradual degradation of myosin heavy chain as the dose increased. The degradation was slower for frozen samples. The integrity of actin was slightly affected by high doses (25 kGy). The amount of sulfhydryl groups and the level of surface hydrophobicity of Alaska pollock surimi decreased as the dose increased, suggesting formation of disulfide bonds and hydrophobic interactions. The sulfhydryl groups and hydrophobicity of surimi gels increased as the dose increased up to 6 kGy and then decreased. [source] Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2007Jung-Hwan Oh Abstract Background and Aim:, Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients. Methods:, A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed. Results:, Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers. Conclusion:, A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes. [source] Diazoxide, a KATP opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyaminesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001M Rahgozar Abstract Background and Aims: Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5,-triphosphate (ATP)-dependent potassium channels (KATP) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of KATP channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied. Methods: Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations. Results: Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU. Conclusion: The KATP channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU. [source] Estrogen administration during superovulation increases oocyte quality and expressions of vascular endothelial growth factor and nitric oxide synthase in the ovaryJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2010Choong-Sik Ha Abstract Aims:, This study investigated whether estrogen administration during superovulation enhances oocyte quality using a mice model. We also investigated whether this estrogen treatment regulates the expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), in the ovary. Method:, Female mice were co-injected with various doses of estrogen (1 µM, 10 µM and 100 µM) and pregnant mare serum gonadotrophin during superovulation, followed by human chorionic gonadotrophin injection 48 hours later. Then they were mated with individual males. After 18 hours, zygotes were flushed and cultured to blastocyst. The expression of VEGF and eNOS in the ovary was examined using Western blot and immunohistochemistry. The control group was superovulated without estrogen. Results:, Both numbers of ovulated zygotes and the rate of embryo development to blastocyst were significantly increased in the 1-µM estrogen dose compared to the control group. VEGF and eNOS expressions were stimulated by estrogen treatment. In particular, VEGF expression was significantly increased at 1-µM estrogen concentration, whereas, eNOS expression was significantly increased in all estrogen concentrations compared to controls. Conclusions:, The study showed that estrogen co-injection during superovulation increased the ovarian response, embryo developmental competence and expressions of VEGF and eNOS in the ovary. [source] Nitric Oxide Mediates Inhibitory Effect of Interleukin-1, on Estrogen Production in Human Granulosa-Luteal CellsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2001Hisako Tobai Abstract Objective: To investigate the effect of IL-1, on NO production and steroidogenesis in human granulosa-luteal cells obtained from women undergoing in vitro fertilization procedures. Subjects and Methods:To investigate the effect of IL-1,, granulosa-luteal cells were cultured with various doses of IL-1, (0, 0.05, 0.5, 5, 50, 100 ng/ml), IL-1, (5 ng/ml) with NG -nitro-L-arginine-methyl ester (l-NAME), selective inhibitors of NOS, sodium nitroprusside (SNP), NO donors and Genistain, a tyrosine kinase inhibitor. Results:IL-1, induced a dose-dependent stimulation of NO production and inhibited the production of estradiol in a significant way in a dose-dependent manner. l-NAME significantly decreased NO production and increased the production of estradiol and progesterone. SNP significantly increased NO production and caused decreases in the production of both estradiol and progesterone. Genistain decreased NO production and significantly increased the production of estradiol and progesterone. Inducible NOS (iNOS) messenger RNA was present in granulosa-luteal cells before treatment with IL-1,. Conclusions:IL-1, stimulated NO production, and NO inhibited the production of estradiol. [source] Inhibition of intestinal absorption of cholesterol by surface-modified nanostructured aluminosilicate compoundsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009Pavel Gershkovich Abstract The aim of this work was to assess the ability of aqueous suspensions of surface-modified nanostructured aluminosilicate (NSAS) compounds to reduce the intestinal absorption of cholesterol in a rat model. The rats were divided into 10 treatment groups which included several NSAS compounds at various doses, ezetimibe at 10 mg/kg, stigmastanol at 50 mg/kg, and normal saline. All compounds and controls were independently administered by oral gavage and then a mixture of [3H]cholesterol and cold cholesterol in 10% Intralipid® was immediately administered orally to the animals. Systemic blood was sampled and the concentration of cholesterol in plasma was determined by means of radioactivity. Protonation of NSAS using an ion-exchange column resulted in significant inhibition of cholesterol absorption relative to the control group (31.5% and 38.6% reduction in absorption of cholesterol for 50 and 100 mg/kg doses, respectively). Other surface-ion modifications of NSAS compounds did not show significant effect on intestinal cholesterol absorption. The inhibition of cholesterol absorption by ezetimibe was superior and by stigmastanol was equal to the effect of protonated NSAS in the doses investigated in this study. In conclusion, protonated NSAS material seems to inhibit significantly the intestinal absorption of dietary cholesterol in a rat model. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2390,2400, 2009 [source] Bilobalide in ginkgo biloba extract is a major substance inducing hepatic CYPsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2007Keizo Umegaki In a search for substances related to the marked induction of hepatic cytochrome P450 (CYP) by ginkgo biloba extract (GBE), mice were given either GBE (1000 mg kg,1) or fractions of GBE for 5 days. The content and activity of CYPs were induced markedly by a bilobalide-rich fraction, but not by flavonoid-rich fractions. The level of induction by the bilobalide-rich fraction was almost the same as that induced by the unfractionated GBE, suggesting that bilobalide is largely responsible for the CYPs induction. To confirm these findings, mice were given various doses of bilobalide (10.5, 21 and 42 mg kg,1), or GBE (1000 mg kg,1, containing bilobalide at 42 mg kg,1). Treatment with bilobalide induced CYPs markedly and in a dose-dependent manner, and the level of induction was quite similar between bilobalide (42 mg kg,1) and GBE. Treatment with GBE and with bilobalide greatly induced pentoxyresorufin O-dealkylase activity. These findings indicate that bilobalide is the major substance in GBE that induces hepatic CYPs. [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] Expanding the Utility of the Biphasic Alcohol Effects Scale (BAES) and Initial Psychometric Support for the Brief-BAES (B-BAES)ALCOHOLISM, Issue 5 2009Sandra Y. Rueger Background:, The utility of one of the most widely used subjective alcohol assessment tools, the Biphasic Alcohol Effects Scale (BAES) has been somewhat limited based on lack of psychometric studies in large and diverse samples, a range of alcohol doses, the length of the measure, and the original instructional set which precluded baseline measurement and disclosed to subjects that they received alcohol. Methods:, The current study investigated the factor structure of the BAES with a modified instructional set at pre-drink baseline and after consumption of various doses of alcohol, in a sample of 190 men and women, heavy and light social drinkers. This study tested the psychometric properties of a brief version of the BAES (Brief-BAES or B-BAES). Results:, Results demonstrated robust support of the stimulant and sedative constructs across all conditions, and demonstrated strong psychometric support for the 6-item B-BAES. Discussion:, This is the first comprehensive study to expand the utility of the BAES by instructional set, baseline measurement, at various alcohol doses, and by drinking history and sex. In addition, the introduction of the B-BAES may further increase the utility of this scale, particularly in paradigms with repeated measurement or time constraints. [source] The effect of gamma irradiation on the microbial load, mineral concentration and sensory characteristics of liquorice (Glycyrrhiza glabra L)JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2003Mahfouz Al-Bachir Abstract Ground liquorice roots were exposed to various doses (0, 5, 10, 15 and 20,kGy) of gamma radiation from a 60Co source. Irradiated and non-irradiated samples were stored at room temperature. Microbial population, viscosity, concentrations of some minerals and the sensory properties of the extracts were evaluated after 0 and 12 months of storage. Tests carried out immediately after irradiation showed that the microbial count had been reduced and that the dose required to reduce the count by 1 log cycle (D10) was about 2,kGy. No effect was observed on the total dissolved solids in extracts of liquorice roots. Glycyrrhizinic acid concentration in the extracts and the viscosities of suspensions produced from irradiated roots were lower than those from non-irradiated ones. Sensory evaluation indicated that there were no significant differences (P,<,0.05) in colour, taste or flavour between extracts produced from irradiated and non-irradiated roots. However, after 12 months of storage, some mineral ion (Na+, Ca2+ and K+) concentrations in extracts produced from irradiated roots were lower than in those from non-irradiated ones; no significant differences (P,<,0.05) in viscosity were found between suspensions of irradiated and non-irradiated roots. © 2002 Society of Chemical Industry [source] Growth inhibitory effects of pegylated IFN ,-2b on human liver cancer cells in vitro and in vivoLIVER INTERNATIONAL, Issue 8 2006Hirohisa Yano Abstract: Purpose: We investigated the effects of pegylated IFN-,2b (PEG-IFN-,2b) on the growth of human liver cancer cells. Methods: The effect of PEG-IFN-,2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-, receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-,2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-,2b or IFN-,2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined. Results: PEG-IFN-,2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-,2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-,2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-,2b was significantly stronger than that of non-PEG-IFN-,2b in vivo. Conclusions: Continuous contact with PEG-IFN-,2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-,2b for the prevention and treatment of HCC. [source] Cardiac 17O MRI: Toward direct quantification of myocardial oxygen consumptionMAGNETIC RESONANCE IN MEDICINE, Issue 6 2010Kyle S. McCommis Abstract A new 17O-labeled blood contrast agent was injected intravenously in control dogs. Electrocardiogram (ECG)-triggered myocardial T1, imaging was performed to obtain spin-locking T1,-weighted myocardial signals for the detection of resultant metabolite H217O water in the heart. Bolus and slow injection methods of various doses of the 17O-labeled and 16O-labeled agents were carried out in order to evaluate the sensitivity of this method and determine the optimal injection method. Bolus injection provided approximately 1% signal reduction, whereas slow injection with larger amount of agent yielded 11.9 ± 0.6% signal reduction. Myocardial oxygen consumption rate was determined by a technique to quantify cerebral oxygenation consumption rate previously developed in 17O brain studies. With either injection method, myocardial oxygen consumption rate at rest was 5.0 , 5.6 ,mol/g/min. Therefore, it appears feasible to detect metabolically generated HO water in vivo in the heart, using the 17O-labeled blood tracer. Myocardial oxygen consumption rate can then be quantified in vivo, which may open new doors for the assessment of myocardial metabolism. Magn Reson Med 63:1442,1447, 2010. © 2010 Wiley-Liss, Inc. [source] Temporal events in the intravenous challenge model for experimental Candida albicans infections in female miceMYCOSES, Issue 3 2005Donna M. MacCallum Summary We characterized the intravenous (i.v.) challenge model for disseminated Candida albicans infection in female BALB/c and DBA/2 mice. Clearance of fungi from the bloodstream and appearance of fungi in tissues were measured at intervals after challenge with various doses of C. albicans. The wild-type isolate SC5314 and derived strains CAF2,1 and CAI-4 transformed with CIp10 were of equal virulence in the model. Variability in mouse survival times, kidney fungal burdens and cachexia was lowest when challenge inocula were within the range 104,105 CFU g,1 body weight in BALB/c mice, but brain fungal burdens and outcomes in DBA/2 mice were variable for all inocula tested. Critical times in the development of infections in optimally challenged BALB/c mice were at 5,10 h (bloodstream fully cleared of fungi), 24 h (start of exponential fungal growth in kidneys) and 48 h (50% of blood cultures become positive). Differential involvement of right and left kidneys occurred almost exclusively in mice challenged with <2 × 104 CFU g,1. We conclude that the i.v. challenge model in female BALB/c mice is now sufficiently well characterized to permit more refined experimentation in future virulence studies with C. albicans mutants. [source] Evaluation of anticancer activity of the alkaloid fraction of Alstonia scholaris (Sapthaparna) in vitro and in vivoPHYTOTHERAPY RESEARCH, Issue 2 2006Ganesh Chandra Jagetia Abstract The anticancer effect of various doses of an alkaloid fraction of Sapthaparna, Alstonia scholaris (ASERS), was studied in vitro in cultured human neoplastic cell lines (HeLa, HepG2, HL60, KB and MCF-7) and in Ehrlich ascites carcinoma bearing mice. Treatment of HeLa cells with 25 µg/mL ASERS resulted in a time dependent increase in the antineoplastic activity and the greatest activity was observed when the cells were exposed to ASERS for 24 h. However, exposure of cells to ASERS for 4 h resulted in 25% viable cells and hence this time interval was considered to be the optimum time for treatment and further studies were carried out using this time. Treatment of various cells with ASERS resulted in a concentration dependent decline in the viable cells and a nadir was reached at 200 µg/mL in all the cell lines studied. The IC50 was found to be 5.53, 25, 11.16, 10 and 29.76 µg/mL for HeLa, HePG2, HL60, KB and MCF-7 cells, respectively. Similarly, administration of ASERS, once daily for 9 consecutive days to the tumor bearing mice caused a dose dependent remission of the tumor up to 240 mg/kg body weight, where the greatest antitumor effect was observed. Since 240 mg/kg ASERS showed toxic manifestations, the next lower dose of 210 mg/kg was considered as the best effective dose, in which 20% of the animals survived up to 120 days post-tumor-cell inoculation as against no survivors in the saline treated control group. The ASERS treatment resulted in a dose dependent elevation in the median survival time (MST) and the average survival time (AST) up to 240 mg/kg ASERS and declined thereafter. The surviving animals were healthy and disease free. The effect of ASERS was better than cyclophosphamide, which was used as a positive control, where all the animals succumbed to death by 40 days and the MST and AST were 19.5 and 18.3 days, respectively. The effective dose of 210 mg of ASERS was 3/10 of the LD50 dose, which increased the MST and AST up to 54 and 49.5 days, respectively. Copyright © 2006 John Wiley & Sons, Ltd. [source] The evaluation of the radioprotective effect of chyavanaprasha (an ayurvedic rasayana drug) in mice exposed to lethal dose of , -radiation: a preliminary studyPHYTOTHERAPY RESEARCH, Issue 1 2004Ganesh Chandra Jagetia Abstract The effect of various doses of 50% ethanolic extract of chyavanaprasha (an Ayurvedic rejuvenating herbal preparation) was studied on the survival of mice exposed to 10 Gy of , -radiation. Treatment with chyavanaprasha, consecutively for ,ve days before irradiation, delayed symptoms of radiation sickness and onset of mortality when compared with the non-drug treated irradiated controls. All doses of chyavanaprasha provided a signi,cant protection against gastrointestinal (GI) death (death of animals within 10 days after exposure to radiation), however, highest protection against GI death was observed for 15 mg/kg chyavanaprasha. Chyavanaprasha also provided a signi,cant protection against the bone marrow death after 10 to 40 mg/kg. However, the best protection was seen for 15 mg/kg, where the highest number of survivors was observed at the end of 30 days post-irradiation. The drug was non-toxic up to a dose of 6 g/kg b. wt., the highest drug dose that could be tested. Our study demonstrates that chyavanaprasha can provide good radioprotection at a very low non-toxic dose. Copyright © 2004 John Wiley & Sons, Ltd. [source] Treatment of mice with a herbal preparation (Mentat) protects against radiation-induced mortalityPHYTOTHERAPY RESEARCH, Issue 8 2003Ganesh Chandra Jagetia Abstract The effect of various doses (0, 5, 10, 20, 40, 80, 100, 120 and 160 mg/kg b. wt.) of 50% ethanolic extract of mentat (a herbal preparation) was studied on the survival of mice exposed to 10 Gy of , -radiation. Treatment of mice with different doses of mentat consecutively for ,ve days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. Most of the doses of mentat provided protection against the gastrointestinal (GI) death, however, the highest protection against GI death was observed for 80 mg/kg mentat. This was also true for bone marrow deaths, where the highest number of survivors were observed at 30 days post-irradiation in this group (i.e. 80 mg/kg) when compared with the other doses of mentat. The evaluation of acute toxicity showed that mentat was non-toxic up to a dose of 1.5 g/kg b. wt., where no drug-induced mortality was observed. The LD50 dose of mentat was found to be 1.75 g/kg b. wt. Our study demonstrates that mentat can provide good radioprotection at a dose of 80 mg/kg, which is far below its toxic dose. Copyright © 2003 John Wiley & Sons, Ltd. [source] Noradrenergic Control of Arginine Vasopressin Release from the Ewe Hypothalamus In Vitro: Sensitivity to OestradiolREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2008SPS Ghuman Contents The present study aims at ascertaining the influence of ,1 -adrenoreceptors on arginine vasopressin (AVP) release in vitro and determine whether E2 modulates the ,1 -adrenoreceptor and AVP interaction. Ten minutes after ewe killing, sagittal midline hypothalamic slices (from the anterior preoptic area to the mediobasal hypothalamus with the median eminence, 2 mm thick, 2 per sheep) were dissected, placed in oxygenated minimum essential media- , (MEM- ,) at 4°C and within 2 h were singly perifused at 37°C with oxygenated MEM- , (pH 7.4; flow rate 0.15 ml/min), either with or without E2 (24 pg/ml). After 4 h equilibration, 10 min fractions were collected for 4 h interposed with 10 min exposure at 60 min to a specific ,1 -adrenoreceptor agonist or antagonist at various doses (0.1,10 mm). At the end of all perifusions, slices responded to KCl (100 mm) with AVP efflux (p < 0.05). Release of AVP was enhanced (p < 0.05) by the ,1 -adrenoreceptor agonist (methoxamine 10 mm; no E2, n = 7 perifusion chambers: from 14.3 ± 2.7 to 20.9 ± 3.9, with E2, n = 10: from 10.7 ± 1.2 to 18.4 ± 3.4 pg/ml) or the antagonist (thymoxamine 10 mm; no E2, n = 5: from 9.5 ± 3.1 to 30.4 ± 6.0, with E2, n = 10: from 10.8 ± 0.9 to 39.1 ± 6.3 pg/ml). With the agonist, the response occurred only at 80 min (p < 0.05) both in the presence and absence of E2. Whereas, after the antagonist, values were higher (p < 0.05) throughout the post-treatment period (80,170 min) without E2, but declined by 150 min in the presence of E2. Furthermore, the response to the ,1 -adrenoreceptor antagonist was greater (p < 0.05; 90,140 min) than the agonist only in the presence of E2. In conclusion, these results reveal direct ,1 -adrenoreceptor-mediated control of the hypothalamic AVP neuronal system which is modulated by E2. [source] , -Amino Butyric Acid Control of Arginine Vasopressin Release from the Ewe Hypothalamus In Vitro: Sensitivity to OestradiolREPRODUCTION IN DOMESTIC ANIMALS, Issue 5 2007SPS Ghuman Contents The present study aims to ascertain the influence of , -amino butyric acid (GABA)A or B receptors on arginine vasopressin (AVP) release in vitro and determine whether E2 modulates GABA,AVP interaction. Within 10 min of ewe killing, saggital midline hypothalamic slices (from the anterior preoptic area to the mediobasal hypothalamus along with the median eminence, 2-mm thick, two per ewe) were dissected, placed in oxygenated minimum essential media (MEM)- , at 4°C and within 2 h were singly perifused at 37°C with oxygenated MEM- , (pH 7.4; flow rate 0.15 ml/min), either with or without E2 (24 pg/ml). After 4-h equilibration, 10-min fractions were collected for 4 h interposed with a 10-min exposure at 60 min to a specific GABAA or B receptor agonist or antagonist at various doses (0.1,10 mm). GABAA (muscimol; no E2, n = 7 perifusion chambers, with E2, n = 11) or GABAB (baclofen; no E2, n = 8, with E2, n = 15) agonists (10 mm) did not influence AVP concentrations. However, AVP release increased (p < 0.05) 20,30 min after exposure to 10 mm GABAA or B antagonists (bicuculline, no E2, n = 7: from 4.6 ± 0.7 to 33.0 ± 0.4, with E2, n = 17: from 11.9 ± 1.4 to 32.8 ± 6.0; CGP52432, with E2, n = 14: from 14.0 ± 2.6 to 28.8 ± 3.9 pg/ml). At the end of the collection period, hypothalamic slices responded to KCl (100 mm) with AVP efflux (p < 0.05). GABAB but not GABAA antagonist-stimulated AVP release was enhanced in the presence of E2. In summary, AVP release is under the inhibitory influence of GABA input with further potentiation by E2 through GABAB receptors in vitro. [source] Resistin induces expression of proinflammatory cytokines and chemokines in human articular chondrocytes via transcription and messenger RNA stabilizationARTHRITIS & RHEUMATISM, Issue 7 2010Zhiqi Zhang Objective To elucidate the effects of resistin on human articular chondrocytes and to generate a picture of their regulation at the transcriptional and posttranscriptional levels. Methods Human articular chondrocytes were cultured with resistin. Changes in gene expression were analyzed at various doses and times. Cells were also treated with the transcription inhibitor actinomycin D after resistin treatment or with the NF-,B inhibitor IKK-NBD before resistin treatment. Gene expression was tested by quantitative real-time polymerase chain reaction. Computational analysis for transcription factor binding motifs was performed on the promoter regions of differentially expressed genes. TC-28 chondrocytes were transfected with CCL3 and CCL4 promoter constructs, pNF-,B reporter, and NF-,B and CCAAT/enhancer binding protein , (C/EBP,) expression vectors with or without resistin. Results Resistin-treated human articular chondrocytes increased the expression of cytokines and chemokines. Levels of messenger RNA (mRNA) for matrix metalloproteinase 1 (MMP-1), MMP-13, and ADAMTS-4 also increased, while type II collagen ,1 (COL2A1) and aggrecan were down-regulated. The cytokine and chemokine genes could be categorized into 3 groups according to the pattern of mRNA expression over a 24-hour time course. One pattern suggested rapid regulation by mRNA stability. The second and third patterns were consistent with transcriptional regulation. Computational analysis suggested the transcription factors NF-,B and C/EBP, were involved in the resistin-induced up-regulation. This prediction was confirmed by the cotransfection of NF-,B and C/EBP, and the IKK-NBD inhibition. Conclusion Resistin has diverse effects on gene expression in human chondrocytes, affecting chemokines, cytokines, and matrix genes. Messenger RNA stabilization and transcriptional up-regulation are involved in resistin-induced gene expression in human chondrocytes. [source] Liposome-Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in Rats: Effect of Oxygen AffinityARTIFICIAL ORGANS, Issue 2 2009Dai Fukumoto Abstract Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P50 = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O2 affinity (h-LEH, P50 = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of cortical infarction. h-LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l-LEH provided no significant protection. h-LEH provided better protection than l-LEH. The protective effect of both high- and low-affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h-LEH over l-LEH supports an optimal O2 delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion. [source] S -Nitrosylated Pegylated Hemoglobin Reduces the Size of Cerebral Infarction in RatsARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi Abstract Cell-free hemoglobin-based oxygen carriers have well-documented safety and efficacy problems such as nitric oxide (NO) scavenging and extravasation that preclude clinical use. To counteract these effects, we developed S -nitrosylated pegylated hemoglobin (SNO-PEG-Hb, P50 = 12 mm Hg) and tested it in a brain ischemia and reperfusion model. Neurological function and extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery in the rat. Infarction extent was determined from the integrated area in the cortex and basal ganglia detected by triphenyltetrazolium chloride staining in rats receiving various doses of SNO-PEG-Hb (2, 0.4, and 0.08 mL/kg) and compared with rats receiving pegylated hemoglobin without S -nitrosylation (PEG-Hb) or saline of the same dosage. Results indicated that successive dilution revealed SNO-PEG-Hb but not PEG-Hb to be effective in reducing the size of cortical infarction but not neurological function at a dose of 0.4 mL/kg. In conclusion, SNO-PEG-Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg) showed to be most effective in reducing the size of cortical infarction, however, without functional improvement. [source] | ||||||||||||||||||||||||||||