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Effective Dose (effective + dose)
Kinds of Effective Dose Selected AbstractsAtrial, SA Nodal, and AV Nodal Electrophysiology in Standing Horses: Normal Findings and Electrophysiologic Effects of Quinidine and DiltiazemJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2007Colin C. Schwarzwald Background: Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. Hypotheses: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. Animals: Fourteen healthy horses. Methods: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during programmed electrical stimulation at baseline, after administration of quinidine gluconate (10 mg/kg IV over 30 minutes, n = 7; and 12 mg/kg IV over 5 minutes followed by 5 mg/kg/h constant rate infusion for the remaining duration of the study, n = 7), and after coadministration of diltiazem (0.125 mg/kg IV over 2 minutes repeated every 12 minutes to effect). Results: Quinidine significantly prolonged the atrial effective refractory period, shortened the functional refractory period (FRP) of the AV node, and increased the ventricular response rate during atrial pacing. Diltiazem increased the FRP, controlled ventricular rate in a rate-dependent manner, caused dose-dependent suppression of the sinoatrial node and produced a significant, but well tolerated decrease in blood pressure. Effective doses of diltiazem ranged from 0.125 to 1.125 mg/kg. Conclusions and Clinical Importance: Standard electrophysiologic techniques allow characterization of drug effects in standing horses. Diltiazem is effective for ventricular rate control in this pacing model of supraventricular tachycardia. The use of diltiazem for rate control in horses with atrial fibrillation merits further investigation. [source] Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicityTHE JOURNAL OF GENE MEDICINE, Issue 1 2007Anna Kanerva Abstract Background Adenoviruses can cause severe toxicity in immunocompromised individuals. Although clinical trials have confirmed the potency and safety of selectively oncolytic adenoviruses for treatment of advanced cancers, increasingly effective agents could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. Methods We analyzed the effect of chlorpromazine, an inhibitor of clathrin-dependent endocytosis and apigenin, a cell cycle regulator, on adenovirus replication and toxicity. First, we evaluated the in vitro replication of a tumor targeted Rb-p16 pathway selective oncolytic adenovirus (Ad5/3-,24) and a wild-type adenovirus in normal cells, fresh liver samples and in ovarian cancer cell lines. Further, we analyzed the in vitro cell killing efficacy of adenoviruses in the presence and absence of the substances. Moreover, the effect on in vivo efficacy, replication and liver toxicity of the adenoviruses was evaluated. Results We demonstrate in vitro and in vivo reduction of adenovirus replication and associated toxicity with chlorpromazine and apigenin. Effective doses were well within what would be predicted safe in humans. Conclusions Chlorpromazine and apigenin might reduce the replication of adenovirus, which could provide a safety switch in case replication-associated side effects are encountered in patients. In addition, these substances could be useful for the treatment of systemic adenoviral infections in immunosuppressed patients. Copyright © 2006 John Wiley & Sons, Ltd. [source] Neoadjuvant therapy as a paradigm to develop systemic cancer therapyDRUG DEVELOPMENT RESEARCH, Issue 7 2008Guru SonpavdeArticle first published online: 23 DEC 200 Abstract Neoadjuvant systemic therapy preceding definitive surgical resection permits the in vivo assessment of tumor response and induces pathologic downstaging in several malignancies. Since pathologic complete response (pCR) and biologic activity can be determined rapidly, the signal of efficacy of a systemic regimen is evident with a relatively small number of patients before long-term follow-up. Additionally, emerging data suggest that modulation of pharmacodynamic biomarkers after brief neoadjuvant therapy may correlate with long-term clinical outcomes. Early evidence for in vivo resistance and elucidation of mechanisms of resistance may assist with selection of rational combinations of agents as subsequent therapy to improve outcomes. Evidence of biologic anti-tumor activity in target-enriched subsets can be determined with a small number of patients in proof of principal pilot trials. Biologic activity against molecular targets and downstream anti-proliferative and pro-apoptotic activity may help with the selection of the lowest effective dose, which may lead to efficacious and safe therapy. Therefore, this paradigm has the potential to enable the efficient use of resources and accelerate the pace of systemic therapy development. It may also be possible to determine molecular and biologic characteristics that predict for sensitivity. Drug Dev Res 69:388,397, 2008. © 2008 Wiley-Liss, Inc. [source] Dose,response and time course relationships for vitellogenin induction in male western fence lizards (Sceloporus occidentalis) exposed to ethinylestradiolENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2002Sandra M. Brasfield Abstract The long-term goal of this research is to develop and validate an in vivo reptile model for endocrine-mediated toxicity using fence lizards (Sceloporus spp.). One of the best defined estrogenic responses in oviparous vertebrates is induction of the yolk precursor protein, vitellogenin (Vtg). In this study, dose,response and time course relationships for Vtg induction were determined in male western fence lizards (Sceloporus occidentalis) given intraperitoneal injections of 17,-ethinylestradiol (EE2). Plasma Vtg was quantified directly with an antibody-capture enzyme-linked immunosorbent assay (ELISA) and indirectly using plasma alkalinelabile phosphate (ALP) in order to compare these two methods. Both ELISA and ALP predicted similar median effective dose (ED50 [dose causing a 50% maximal response]) values for plasma Vtg induction (0.167 mg/kg for ELISA and 0.095 mg/kg for ALP). In addition, both ELISA and ALP detected significant Vtg induction at a dose of 0.0003 mg/kg of EE2, which was the lowest dose used in our study. A decrease in body weight at the highest dose (10 mg/kg) and an increase in hepatosomatic index at the four highest doses were observed. Serial dilutions of plasma from an EE2 -exposed male revealed a high correlation between plasma Vtg and ALP determinations in this species. In conclusion, our data show that plasma ALP may be a suitable alternative for measuring plasma Vtg compared with developing a Vtg ELISA in fence lizards exposed to estrogenic compounds. [source] The individual tolerance concept is not the sole explanation for the probit dose-effect model,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Michael C. Newman Abstract Predominant methods for analyzing dose- or concentration-effect data (i.e., probit analysis) are based on the concept of individual tolerance or individual effective dose (IED, the smallest characteristic dose needed to kill an individual). An alternative explanation (stochasticity hypothesis) is that individuals do not have unique tolerances: death results from stochastic processes occurring similarly in all individuals. These opposing hypotheses were tested with two types of experiments. First, time to stupefaction (TTS) was measured for zebra fish (Brachydanio rerio) exposed to benzocaine. The same 40 fish were exposed during five trials to test if the same order for TTS was maintained among trials. The IED hypothesis was supported with a minor stochastic component being present. Second, eastern mosquitofish (Gambusia holbrooki) were exposed to sublethal or lethal NaCl concentrations until a large portion of the lethally exposed fish died. After sufficient time for recovery, fish sublethally exposed and fish surviving lethal exposure were exposed simultaneously to lethal NaCl concentrations. No statistically significant effect was found of previous exposure on survival time but a large stochastic component to the survival dynamics was obvious. Repetition of this second type of test with pentachlorophenol also provided no support for the IED hypothesis. We conclude that neither hypothesis alone was the sole or dominant explanation for the lognormal (probit) model. Determination of the correct explanation (IED or stochastic) or the relative contributions of each is crucial to predicting consequences to populations after repeated or chronic exposures to any particular toxicant. [source] The Effects of Ascorbic Acid on Penicillin-induced Epileptiform Activity in RatsEPILEPSIA, Issue 7 2007Mustafa Ayyildiz Summary:,Purpose: Epileptic seizure results from excessive discharge in a population of hyperexcitable neurons. A number of studies help to document the effects of active oxygen free radical scavengers such as ,-tocopherol or ascorbic acid (vitamin C). In the present study, we examined the effects of ascorbic acid, at the six different doses, on penicillin-induced epileptiform activity. Methods: A single microinjection of penicillin (2.5 ,l, 500 units, intracortically) into the left sensorimotor cortex induced epileptiform activity within 2,5 min, progressing to full seizure activity lasting ,3,5 h. In the first set of experiments, 30 min after penicillin injection, six different doses of ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered intraperitoneally (IP). The other group of animals received the effective dose of ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was stopped 24 h before penicillin treatment. Another group of rats received the effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin treatment. In the second set of experiments, the lipid peroxidation (MDA) and reduced glutathione (GSH) levels of brain were measured in the control, control + ascorbic acid, penicillin, and penicillin + ascorbic acid groups. Results: Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin injection), decreased both the frequency and amplitude of penicillin-induced epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400 mg/kg, 30 min after penicillin injection), decreased the frequency of epileptiform activity without changing the amplitude. Ascorbic acid, at the lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin injection), did not change either the frequency or amplitude of epileptiform activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose in changing the frequency and amplitude of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin treatment caused a significant delay in the onset of penicillin-induced epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did not change the latency of epileptiform activity. The most effective dose of ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the increase in lipid peroxidation level (MDA) occurring after penicillin-induced epileptiform activity. Conclusions: These data indicate that ascorbic acid has neuroprotective activity against penicillin-induced epileptiform electrocorticogram activity. [source] Synergistic Combinations of Anticonvulsant Agents: What Is the Evidence from Animal Experiments?EPILEPSIA, Issue 3 2007Daniėl M. Jonker Summary:,Purpose: Combination therapy is often used in the treatment of seizures refractory to monotherapy. At the same time, the pharmacodynamic mechanisms that determine the combined efficacy of antiepileptic drugs (AEDs) are unknown, and this prevents a rational use of these drug combinations. We critically evaluate the existing evidence for pharmacodynamic synergism between AEDs from preclinical studies in animal models of epilepsy to identify useful combinations of mechanisms and to determine whether study outcome depends on the various research methods that are in use. Methods: Published articles were included if the studies were placebo-controlled, in vivo, or ex vivo animal studies investigating marketed or experimental AEDs. The animal models that were used in these studies, the primary molecular targets of the tested drugs, and the methods of interpretation were recorded. The potential association of these factors with the study outcome (synergism: yes or no) was assessed through logistic regression analysis. Results: In total, 107 studies were identified, in which 536 interaction experiments were conducted. In 54% of these experiments, the possibility of a pharmacokinetic interaction was not investigated. The majority of studies were conducted in the maximal electroshock model, and other established models were the pentylenetetrazole model, amygdala kindling, and the DBA/2 model. By far the most widely used method for interpretation of the results was evaluation of the effect of a threshold dose of one agent on the median effective dose (ED50) of another agent. Experiments relying on this method found synergism significantly more often compared with experiments relying on other methods (p < 0.001). Furthermore, experiments including antagonists of the AMPA receptor were more likely to find synergism in comparison with all other experiments (p < 0.001). Conclusions: Intensive preclinical research into the effects of AED combinations has not led to an understanding of the pharmacodynamic properties of AED combinations. Specifically, the majority of the preclinical studies are not adequately designed to distinguish between additive, synergistic, and antagonistic interactions. Quantitative pharmacokinetic,pharmacodynamic studies of selectively acting AEDs in a battery of animal models are necessary for the development of truly synergistic drug combinations. [source] Mice Carrying the Szt1 Mutation Exhibit Increased Seizure Susceptibility and Altered Sensitivity to Compounds Acting at the M-ChannelEPILEPSIA, Issue 9 2004James F. Otto Summary:,Purpose: Mutations in the genes that encode subunits of the M-type K+ channel (KCNQ2/KCNQ3) and nicotinic acetylcholine receptor (CHRNA4) cause epilepsy in humans. The purpose of this study was to examine the effects of the Szt1 mutation, which not only deletes most of the C-terminus of mouse Kcnq2, but also renders the Chnra4 and Arfgap-1 genes hemizygous, on seizure susceptibility and sensitivity to drugs that target the M-type K+ channel. Methods: The proconvulsant effects of the M-channel blocker linopirdine (LPD) and anticonvulsant effects of the M-channel enhancer retigabine (RGB) were assessed by electroconvulsive threshold (ECT) testing in C57BL/6J- Szt1/+ (Szt1) and littermate control C57BL/6J+/+ (B6) mice. The effects of the Szt1 mutation on minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures were evaluated by varying stimulation intensity and frequency. Results:Szt1 mouse seizure thresholds were significantly reduced relative to B6 littermates in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Mice were injected with LPD and RGB and subjected to ECT testing. In the minimal clonic seizure model, Szt1 mice were significantly more sensitive to LPD than were B6 mice [median effective dose (ED50) = 3.4 ± 1.1 mg/kg and 7.6 ± 1.0 mg/kg, respectively]; in the partial psychomotor seizure model, Szt1 mice were significantly less sensitive to RGB than were B6 mice (ED50= 11.6 ± 1.4 mg/kg and 3.4 ± 1.3 mg/kg, respectively). Conclusions: These results suggest that the Szt1 mutation alters baseline seizure susceptibility and pharmacosensitivity in a naturally occurring mouse model. [source] Chronic erythropoietin treatment affects different molecular pathways of diabetic cardiomyopathy in mouseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2009N. Shushakova Abstract Background, Recent studies in mice experimental models with acute ischaemic injury revealed that erythropoietin (EPO) has numerous tissue-protective effects in the heart, brain and kidneys. We therefore explored the tissue-protective properties of chronic EPO treatment in an experimental model of the db/db mouse with diabetic heart injury. Material and methods, We randomly treated 11 db/db mice with placebo (saline), 0·4 ,g of the continuous erythropoietin receptor activator (CERA) per week (n = 11) or 1·2 ,g CERA per week (n = 11) for 14 weeks, and analysed cardiac tissue. The lower CERA dose was a non-haematologically effective dose, whereas the second increased the haematocrit. Results, Compared with mice in the placebo group, CERA-treated mice had a reduction in TGF-,1 and collagen I expression in cardiac tissue (P < 0·01 vs. higher dose CERA). In addition, an increased expression of the pro-survival intracellular pathway p-AKT was observed (P < 0·05 vs. higher dose CERA). The values for the lower C.E.R.A had an intermediate nonsignificant effect. Furthermore, we were able to show that atrial natriuretic peptide (ANP) expression was increased in both CERA groups. Conclusions, Chronic treatment with CERA protects cardiac tissue in diabetic animals, i.e. it inhibits molecular pathways of cardiac fibrosis, and the effects are dose-dependent. [source] Long-Term Migraine Prevention With Topiramate: Open-Label Extension of Pivotal TrialsHEADACHE, Issue 7 2006Alan Rapoport MD Objective.,To demonstrate that topiramate is an effective and generally well-tolerated migraine preventive therapy when used for up to 14 months. Background.,Topiramate 100 and 200 mg/d significantly reduced mean monthly migraine frequency during 2 large, 26-week, randomized, placebo-controlled trials. Only a small number of clinical trials have examined the long-term (,1 year) effectiveness and safety of migraine preventive therapies. Methods.,Five hundred sixty-seven patients with an established history of migraine with or without aura were enrolled in this 8-month, open-label extension of 2 large (49 US and 52 US and Canadian medical centers), randomized, double-blind, placebo-controlled, parallel group, 26-week trials of identical design. To be eligible for the open-label extension, patients were required to have either completed the double-blind phase of the 2 pivotal migraine prevention trials or withdrew after 4 weeks due to lack of efficacy. All eligible patients, regardless of type or dose of study medication (topiramate or placebo) received in the double-blind phase, were titrated to a clinically effective dose of open-label topiramate based on physician judgment of patient response. Efficacy of topiramate was measured as the change in mean monthly migraine frequency. Results.,The mean topiramate dose during the open-label extension phase was 124.7 mg/d and 150.3 mg/d for patients on placebo (n = 159) or topiramate (n = 408), respectively, during the double-blind phase (N = 567, 91% female, mean age 39.4 years). Patients on topiramate for up to 14 months had 2.2 ± 2.4 (mean ± SD) migraines per month after completion of the open-label extension phase (3.4 ± 2.6 at double-blind endpoint). Patients on topiramate during the open-label extension phase only (placebo during the double-blind phase) had 3.0 ± 2.9 migraines per month at open-label extension endpoint (4.9 ± 3.0 migraines per month at double-blind endpoint). Discontinuation rates due to adverse events during the double-blind phase were 22.2% for patients on topiramate and 11.0% for patients on placebo. Discontinuation rates due to adverse events during the open-label extension phase were 8.6% for those patients who had already received topiramate during the double-blind phase and 20.9% for those patients who had previously received placebo. Conclusions.,Patients receiving topiramate experienced a sustained reduction in migraine frequency for up to 14 months. The effectiveness and safety of topiramate was consistent with that observed during 2 26-week pivotal trials. [source] Dose 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] Olanzapine as an Abortive Agent for Cluster HeadacheHEADACHE, Issue 8 2001Todd D. Rozen MD Objective.,To evaluate olanzapine as a cluster headache abortive agent in an open-label trial. Background.,Cluster headache is the most painful headache syndrome known. There are very few recognized abortive therapies for cluster headache and fewer for patients who have contraindications to vasoconstrictive drugs. Methods.,Olanzapine was given as an abortive agent to five patients with cluster headache in an open-label trial. The initial olanzapine dose was 5 mg, and the dose was increased to 10 mg if there was no pain relief. The dosage was decreased to 2.5 mg if the 5-mg dose was effective but caused adverse effects. To be included in the study, each patient had to treat at least two attacks with either an effective dose or the highest tolerated dose. Results.,Five patients completed the investigation (four men, one woman; four with chronic cluster, one with episodic cluster). Olanzapine reduced cluster pain by at least 80% in four of five patients, and two patients became headache-free after taking the drug. Olanzapine typically alleviated pain within 20 minutes after oral dosing and treatment response was consistent across multiple treated attacks. The only adverse event was sleepiness. Conclusions.,Olanzapine appears to be a good abortive agent for cluster headache. It alleviates pain quickly and has a consistent response across multiple treated attacks. It appears to work in both episodic and chronic cluster headache. [source] Dose-response effects of zaleplon as compared with triazolam (0·25 mg) and placebo in chronic primary insomniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2000Christopher L Drake Abstract The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0·25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0·25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0·25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0·25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0·25 mg) produced increases in total sleep time (,25 min) and decreases in latency to persistent sleep at a dose of 0·25 mg. Copyright © 2000 John Wiley & Sons, Ltd. [source] Intrathecal sufentanil decreases the median effective dose (ED50) of intrathecal hyperbaric ropivacaine for caesarean deliveryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010X. CHEN Background: The addition of opioid to local anaesthetics has become a well-accepted practice of spinal anaesthesia for caesarean delivery. Successful caesarean delivery anaesthesia has been reported with the use of a low dose of intrathecal hyperbaric ropivacaine coadministered with sufentanil. This prospective, double-blinded study determined the median effective dose (ED50) of intrathecal hyperbaric ropivacaine with and without sufentanil for caesarean delivery, to quantify the sparing effect of sufentanil on the ED50 of intrathecal hyperbaric ropivacaine. Methods: Sixty-four parturients undergoing elective caesarean delivery with combined spinal,epidural anaesthesia were randomized into two groups: Group R (ropivacaine) and Group RS (ropivacaine plus sufentanil 5 ,g). The initial dose of ropivacaine was 13 mg in Group R and 10 mg in Group RS. The effective dose was defined as a T6 level attained within 10 min and no supplemental epidural anaesthetic required during surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the dose of ropivacaine for the next patient using an up,down sequential allocation. Results: The ED50 of intrathecal ropivacaine was 11.2 mg [confidence interval (CI) 95%: 11.0,11.6] in Group R vs. 8.1 mg (CI 95%: 7.8,8.3) in Group RS. Motor block was markedly more intense in Group R than in Group RS, and the incidence of shivering was lower in Group RS than in Group R. There were no differences in the onset time of sensory block or motor block, in the incidence of hypotension, nausea and vomiting. Conclusion: Intrathecal sufentanil 5 ,g produced a 28% reduction of ED50 of intrathecal hyperbaric ropivacaine for caesarean delivery. [source] Antifungal effects of herbal essential oils alone and in combination with ketoconazole against Trichophyton spp.JOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2004S. Shin Abstract Aims:, To determine the effects of herbal essential oils on Trichophyton spp. growth and to evaluate the effects of Pelargonium graveolens oil and its main components citronellol and geraniol combined with ketoconazole against Trichophyton spp. Methods and Results:, Growth inhibition of six Trichophyton spp. by herbal essential oils was accessed and the combined effects of P. graveolens oil and its main components citronellol and geraniol were evaluated using a checkerboard microtitre assay against T. schoenleinii, T. erinacei and T. soudanense. The essential oil fraction of P. graveolens and its main components, geraniol and citronellol, exhibited strong synergism with ketoconazole against T. schoenleinii and T. soudanense, with fractional inhibitory concentration (FIC) indices in the range of 0·18,0·38. Conclusions:, The antifungal effects of ketoconazole against Trichophyton spp. are enhanced significantly by administering it in combination with the essential oil fraction of P. graveolens or its main components, because of strong synergism, especially against T. soudanense and T. schoenleinii. Significance and Impact of the Study:, The combination of ketoconazole and the essential oil fraction from P. graveolens or its main components for treatment of infections caused by Trichophyton species may reduce the minimum effective dose of ketoconazole, and thus minimize the side-effects of ketoconazole. [source] INHIBITION OF HELICOBACTER PYLORI BY PHENOLIC EXTRACTS OF SPROUTED PEAS (PISUM SATIVUM L.)JOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2006CHIA-YU HO ABSTRACT Infection by Helicobacter pylori is associated with gastric and duodenal ulcers. Conventional treatments to eradicate it have side-effects such as diarrhea and dizziness. The excessive use of antibiotics could also lead to antibiotic-resistant bacteria. The use of plant phenolic phytochemicals can be an alternative because of their health benefits due to both antioxidant activity and antimicrobial activity. The pea (Pisum sativum), the world's second most important pulse crop, produces phenolic phytochemicals with antimicrobial potential. Because the synthesis of phenolic compounds increases with stress, we investigated the anti- H. pylori effectiveness of extracts from pea sprouts, germinated in the dark condition following treatment with either distilled water or acetyl salicylic acid. The peas were germinated for 8 days and the sprouted samples were measured for total soluble phenolic content, antioxidant and guaiacol peroxidase activity. Subsequently, the sprout extracts were tested for anti- H. pylori activity using the agar diffusion method and the effective dose was determined based on phenolic content. The results showed that both acetyl salicylic acid-treated and untreated pea sprouts at days 5 and 8 had anti- H. pylori activity. The minimum volume for inhibition was 50 ,L of extracts. The inhibitory effects were dose dependent. From this study, the potential to use natural phenolic phytochemicals from pea sprouts to control H. pylori was found to be promising. This provides a strategy and foundation to design legume phenolics as functional ingredients against H. pylori. [source] The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Dr Nobuko Futaki Abstract Objectives Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effecls of lornoxicam in relatioin to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. Methods A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01,1 mg/kg), celecoxib (0.3,30 mg/kg) or loxoprofen (0.3,30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall,Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzme-immunoassay. Key findings In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornnoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen siginificantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Conclusions Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus. [source] The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis modelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008Suk-Yun Kang Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25,200 mg kg,1) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE2) production in the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg,1 in the zymosan experiment, we used this dose of UA in a subsequent study using an adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg,1, per oral, once a day for 10 days) was started from day 12 after adjuvant injection. UA dramatically inhibited paw swelling, plasma PGE2 production and radiological changes in the joint caused by CFA injection. Moreover, UA significantly suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as the spinal Fos expression, as determined by immunohistochemistry, which was increased by CFA injection. In addition, overall anti-arthritic potency of UA was comparable with ibuprofen (100 mg kg,1, oral) while UA did not induce significant gastric lesions as compared with the ibuprofen treatment group. These findings strongly suggest that UA is a useful suppressive compound for rheumatoid arthritis treatment with low risk of gastric problems. [source] Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat tracheaJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2004Maki Yoshimura Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca2+ concentration. Since intracellular Ca2+ is partly regulated by phosphatidylinositol (PI) response and is important for smooth muscle contraction, selegiline may affect airway smooth muscle tension. We examined the effects of selegiline on acetylcholine (ACh)- and KCl-induced contractile and PI responses in rat trachea. The trachea was cut into 3-mm-wide ring segments or 1-mm-wide slices. ACh (3 ,M, 50% effective dose) or KCl (40mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [3H]myo -inositol and 3 ,M ACh in the presence of selegiline, and [3H]inositol monophosphate (IP1) was measured. Selegiline dose-dependently attenuated ACh- and KCl-induced tracheal ring contractions. Fifty-percent inhibitory doses (ID50) of selegiline against ACh- and KCl-induced contraction were 120±30 ,M and 80±20 ,M, respectively. Basal and ACh-induced IP1 accumulation were 2.20±0.20 Bq and 7.88±0.23 Bq, respectively, and selegiline at a dose of 1000 ,M attenuated ACh-induced IP1 accumulation (5.44±0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage-operated Ca2+ channels and the PI response. [source] Does Dihydrohonokiol, a Potent Anxiolytic Compound, Result in the Development of Benzodiazepine-like Side Effects?JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2000HISASHI KURIBARA The aims of this study were to assess whether dihydrohonokiol, 3,-(2-propenyl)-5-propyl-(1,1,-biphenyl)-2,4,-diol (DHH-B), a potent anxiolytic compound, developed benzodiazepine-like side effects. A 1 mgkg,1 dose of diazepam, almost equivalent to the minimum dose for the anxiolytic effect, disrupted the traction performance, potentiated hexobarbital-induced sleeping and impaired learning and memory performance. DHH-B, even at a dose of 1 mg kg,1 (i.e. five times higher than the minimum dose for significant anxiolytic effect) neither developed diazepam-like side effects nor enhanced the side effects of diazepam. Rather, the potentiation by diazepam of hexobarbital-induced sleeping was reduced by 1 mg kg,1 DHH-B. Furthermore, mice treated with 10 daily administrations of 1 and 5 mg kg,1 diazepam, but not 0.2,5 mg kg,1 DHH-B, showed precipitated withdrawal symptoms characterized by hyper-reactivity, tremor and tail-flick reaction when they were challenged with flumazenil (10 mg kg,1 i.p.). These results suggest that, unlike the benzodiazepine anxiolytic diazepam, DHH-B is less likely to induce motor dysfunction, central depression, amnesia or physical dependence at the effective dose required for the anxiolytic effect. [source] Spinal 2-chloroprocaine: effective dose for ambulatory surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2008A. SELL Background: There is an interest in finding a safe, short-acting spinal anaesthetic, suitable for ambulatory surgery. In this prospective study, we evaluated the effective dose of plain 2-chloroprocaine (2-CP) for lower limb surgery, including knee arthroscopy and saphenectomy. Methods: Sixty-four ASA physical status I,III patients undergoing elective lower limb surgery were randomly allocated to one of the four local anaesthetic groups for spinal anaesthesia in a double-blind manner. The patients (n=16 patients in each group) received 35, 40, 45 or 50 mg of 10 mg/ml isobaric 2-CP. Results: In all patients, anaesthesia was sufficient for the planned surgery. The median peak block height (T9) was similar in all four groups (P=0.66). Time to complete sensory block regression was faster in the 35 mg group (111 min, mean) and in the 40 mg group (108 min) than in the 50 mg group (134 min, P=0.005). No differences in time to complete motor block regression were observed (P=0.3). Home discharge time was faster in the 35 mg group (123 min) and in the 40 mg group (122 min) than in the 50 mg group (165 min, P=0.001). No complications related to spinal anaesthesia were observed and no transient neurologic symptoms (TNS) were reported at the 3-day follow-up. Conclusion: Spinal 2-CP, 10 mg/ml 35, 40, 45 and 50 mg provide reliable sensory and motor block for ambulatory surgery, while reducing the dose of 2-CP to 35 and 40 mg resulted in a spinal block of faster ambulation. [source] The optimal bolus dose of alfentanil for tracheal intubation during sevoflurane induction without neuromuscular blockade in day-case anaesthesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2008J. Y. KIM Background: The purpose of this study was to determine the optimal bolus dose of alfentanil required to provide successful intubating conditions following inhalation induction of anaesthesia using 5% sevoflurane and 60% nitrous oxide without neuromuscular blockade in adult day-case anaesthesia. Methods: Twenty-four adults, aged 18,60 years, undergoing general anaesthesia for short ambulatory surgery were enroled into the study. After vital capacity induction, with sevoflurane 5% and 60% nitrous oxide in oxygen, pre-determined dose of alfentanil was injected over 30 s. The dose of alfentanil was determined by modified Dixon's up-and-down method (2 ,g/kg as a step size). Ninety seconds after the end of bolus administration of alfentanil, the trachea was intubated. Systolic blood pressure, heart rate and SpO2 were recorded at anaesthetic induction, before, 1 min and 3 min after intubation. Results: The bolus dose of alfentanil for successful tracheal intubation was 10.7±2.1 ,g/kg in 50% of patients during inhalation induction. From probit analysis, 50% effective dose (ED50) and ED95 values (95% confidence limits) of alfentanil were 10.7 ,g/kg (8.0,12.9 ,g/kg) and 14.9 ,g/kg (12.9,31.1 ,g/kg), respectively. Conclusions: Using the modified Dixon's up-and-down method, the bolus dose of alfentanil for successful tracheal intubation was 10.7±2.1 ,g/kg in 50% of adult patients during inhalation induction using 5% sevoflurane and 60% nitrous oxide in oxygen without neuromuscular blocking agent in day-case anaesthesia. [source] Pharmacodynamics of Carvedilol in Conscious, Healthy DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2006Sonya G. Gordon The purpose of the study reported here was to determine the magnitude and duration of beta-blocking efficacy, determine an effective dose and dosing interval, and document safety and tolerability of carvedilol given orally in clinically normal dogs. Pharmacodynamic data were evaluated in conscious, unrestrained, healthy hound dogs at baseline and after long-term oral administration of carvedilol (1.5 mg/kg of body weight PO q12h for >5 days). At baseline, heart rate (HR) and blood pressure (BP) data were collected continuously for 24 hours, and complete echocardiography was performed. This protocol was repeated after long-term oral carvedilol administration. Additionally, isoproterenol was administered to evaluate the magnitude and duration of the nonselective beta-blocking efficacy of carvedilol. An isoproterenol challenge was performed 0.75, 1.5, 2.25, 4, 6, 12, and 24 hours after carvedilol administration, with echocardiography being performed once at 2 hours. Plasma samples were obtained prior to each challenge time point for determination of plasma carvedilol concentration. Time series regression analysis indicated no difference between baseline and carvedilol-induced HR or BP trend lines in 6 of 8 dogs. In 2 of 8 dogs, HR, after long-term carvedilol administration, was reduced. Carvedilol attenuated isoproterenol-induced changes in HR by 54,76% through 12 hours and by 30% at 24 hours. The BP changes were attenuated by 80,100% through 12 hours. These data suggest that carvedilol (1.5 mg/kg PO q12h) in healthy, conscious dogs confers nonselective beta blockade for 12 hours, with minimal effects on resting HR, BP, and echocardiographic variables. Additionally, the magnitude of beta blockade correlated strongly to peak plasma carvedilol concentration, suggesting that therapeutic drug monitoring may be clinically useful. [source] Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory diseaseJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002B. HIBBARD Hibbard, B., Robb, E. J., Chester Jr., S. T., Dame, K. J., Boucher, J. F., Alaniz, G. R. Dose determination and confirmation of a long-acting formulation of Ceftiofur (Ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap.25, 175,180. The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil® 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1,8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4,8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4,5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4,5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time. [source] Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epitheliumMOLECULAR ORAL MICROBIOLOGY, Issue 4 2000D. Tanaka The bactericidal activity of synthetic LL-37, a cathelicidin, was assessed against Actinobacillus actinomycetemcomitans (three strains) and Capnocytophaga spp. (three strains). All strains were sensitive to LL-37, and exhibited 99% effective dose of 7.5-to-11.6 ,g/ml. An amidated form of LL-37, pentamide-37, killed with about the same efficacy as LL-37. Partial inhibition of killing was noted at physiologic concentrations of NaCl, and complete inhibition was observed at 400 mM NaCl. At approximately the 99% effective dose , i.e., 10 ,g/ml , LL-37 also lost activity against A. actinomycetemcomitans in the presence of native or heat-inactivated 10,15% normal human AB serum. Pentamide-37 was less sensitive to serum inhibition than LL-37. In conclusion, certain oral, gram-negative bacteria are sensitive to the bactericidal activity of LL-37 at low concentrations of serum and salt, a condition likely to be found within the membrane-delimited phagolysosome. Modified forms of LL-37, such as pentamide-37, may be more suitable for future therapeutic application in the presence of serum. [source] Diapause disruption with tebufenozide for early-instar control of the spruce budworm, Choristoneura fumiferanaPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 8 2007Daniel Doucet Abstract In North America, the eastern spruce budworm, Choristoneura fumiferana Clem., is an important coniferous pest against which tebufenozide has proven effective as a control product. By acting as an ecdysone agonist, tebufenozide can induce precocious moulting in late (fifth,sixth) instars but can also be carried over to the next generation owing to its persistence on foliage. The authors conducted laboratory experiments on first-instar larvae treated with tebufenozide dissolved in acetone. Larvae exposed to doses equal to or above 0.1 µg cm,2 displayed precocious moulting in the second instar after hibernaculum spinning, which effectively disrupted diapause. Larger doses induced moulting in first instars. Evidence is provided that this dose,response difference is related to whether or not an effective dose of tebufenozide is ingested by the first instar prior to the peak of moulting hormone (20-hydroxyecdysone) in first instars. Doses ineffective to kill first instars are carried over to the second instar, where they induce a precocious moult. This type of response to tebufenozide is dependent on the presence of a moulting machinery (the EcR,USP receptor complex) that is ready for ecdysone transduction. Interestingly, ecdysone levels are low in second instars, as measured by a radioimmunoassay, which suggests that diapause in spruce budworm is maintained by a suppression of ecdysone production. Thus, diapause disruption by tebufenozide may well provide an alternative control strategy for this important pest. Copyright © 2007 Society of Chemical Industry [source] Validation of Phage T7 Biological Dosimeter by Quantitative Polymerase Chain Reaction Using Short and Long Segments of Phage T7 DNA ,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2003M. Hegedüs ABSTRACT Phage T7 can be used as a biological dosimeter; its reading, the biologically effective dose (BED), is proportional to the inactivation rate |ln (n/n0)|. For the measurement of DNA damage in phage T7 dosimeter, a quantitative polymerase chain reaction (QPCR) methodology has been developed using 555 and 3826 bp fragments of phage T7 DNA. Both optimized reactions are so robust that an equally good amplification was obtained when intact phage T7 was used in the reaction mixture. In the biologically relevant dose range a good correlation was obtained between the BED of the phage T7 dosimeter and the amount of ultraviolet (UV) photoproducts determined by QPCR with both fragments under the effect of five various UV sources. A significant decrease in the yield of photoproducts was detected by QPCR in isolated T7 DNA and in heated phage compared with intraphage DNA with all irradiation sources. Because the yield of photoproducts was the same in B, C and A conformational states of T7 DNA, a possible explanation for modulation of photoproduct frequency in intraphage T7 DNA is that the presence of bound phage proteins induces an alteration in DNA structure that can result in increased induction of photoproducts. [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] Relationship between leaf emergence and optimum spray timing for leaf blotch (Rhynchosporium secalis) control on winter barleyPLANT PATHOLOGY, Issue 3 2006C. S. Young For wheat, the optimum time to apply fungicide to control disease on a given leaf layer is usually at, or shortly after, full leaf emergence. Data from field experiments on barley were used to investigate whether the same relationship was applicable to control of leaf blotch on barley. Replicated plots of winter barley were sown in the autumns of 1991, 1992 and 1993 at sites in southwest England with high risk of Rhynchosporium secalis infection. Single fungicide treatments at four doses (0·25, 0·5, 0·75 or 1·0 times the label rate) were applied at one of eight different spray times, starting in mid-March in each year, with intervals of 10,11 days between spray timings. Disease was assessed every 10,11 days and area under the disease progress curve (AUDPC) values were used to construct fungicide dose by spray time response surfaces for each of the upper four leaves, for each year. Spray timings shortly before leaf emergence were found to minimize the AUDPC for each year and leaf layer, and also the effective dose (the dose required to achieve a specified level of control), similar to wheat. Fungicide treatments on barley were effective for a longer period before leaf emergence than afterwards, probably because treatments before emergence of the target leaf reduced inoculum production on leaves below. This partly explains why fungicides tend to be applied earlier in the growth of barley compared with wheat. [source] Effect of Oxytocin Treatment on Artificial Insemination with Frozen,Thawed Semen in Murciano,Granadina GoatsREPRODUCTION IN DOMESTIC ANIMALS, Issue 4 2009MP Viudes-de-Castro Contents The site where the semen is deposited appears to be one of the most important factors affecting pregnancy of inseminated goats. In Murciano,Granadina (MG) goats, post-cervical insemination is achieved in a limited number of females. An effective way to increase fertility rate could be by increasing post-cervical inseminations. Effect of exogenous oxytocin application to facilitate the cervical penetration and its effect on kidding rate and prolificacy in MG goats were investigated. Oestrus was synchronized using progesterone-impregnated sponges for 11 days. Females were randomly divided into three groups (n = 190) and received either an i.v. injection of 100 or 200 IU of oxytocin or saline solution 15 min before being inseminated. Data on semen deposition depth were recorded for each animal using a catheter scaled in centimetres (up to 4 cm). Depth of semen deposition was affected by the oxytocin treatment (p < 0.05). Oxytocin enhanced cervical passage only with the dose of 200 IU compared with the control group, increasing the deposition depth (2.9 cm vs 1.9 cm). No significant effect of oxytocin treatment on kidding rate and prolificacy was detected. Depth of semen deposition affected kidding rate (p < 0.01). In conclusion, oxytocin treatment improved the depth of semen deposition in AI of MG goats, but kidding rate and prolificacy was not affected. More studies must be conducted to assess the minimal effective dose required for sufficient cervical dilation, and to determine the effects of such doses of oxytocin on uterine motility, sperm transport and fertility in goats. [source] | ||||||||||||||||||||||||||||||||||||||||