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Selected AbstractsClenbuterol administration does not attenuate the exercise-induced pulmonary arterial, capillary or venous hypertension in strenuously exercising Thoroughbred horsesEQUINE VETERINARY JOURNAL, Issue 6 2000M. MANOHAR Summary The present study was carried out to ascertain whether ,2 -adrenergic receptor stimulation with clenbuterol would attenuate the pulmonary arterial, capillary and venous hypertension in horses performing high-intensity exercise and, in turn, modify the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Experiments were carried out on 6 healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications) and the clenbuterol (0.8 ,g/kg bwt, i.v.) treatments. The sequence of these treatments was randomised for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, right heart/pulmonary vascular pressures were determined at rest, sub-maximal exercise and during galloping at 14.2 m/s on a 3.5% uphill grade - a workload that elicited maximal heart rate and induced EIPH in all horses. In the control experiments, incremental exercise resulted in progressive significant increments in right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures and all horses experienced EIPH. Clenbuterol administration to standing horses caused tachycardia, but significant changes in mean right atrial or pulmonary vascular pressures were not observed. During exercise performed after clenbuterol administration, heart rate as well as right atrial and pulmonary arterial, capillary and wedge pressures also increased progressively with increasing work intensity. However, these values were not found to be statistically significantly different from corresponding data in the control study and the incidence of EIPH remained unaffected. Since clenbuterol administration also does not affect the transpulmonary pressure during exercise, it is unlikely that the transmural force exerted onto the blood-gas barrier of exercising horses is altered following i.v. clenbuterol administration at the recommended dosage. [source] Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activityJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010R. A. HUANG Huang, R. A., Letendre, L. T., Banav, N., Fischer, J., Somerville, B. Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. J. vet. Pharmacol. Therap.33, 227,237. The pharmacokinetics (PK) and dose proportionality of gamithromycin (ZACTRAN®), a novel azalide, after a single intravenous (i.v.) dose of 3 mg/kg or subcutaneous (s.c.) injection at 3, 6 and 9 mg/kg body weight were studied in 13 male castrate and 13 female Angus cattle. Following i.v. administration, the mean area under the curve extrapolated to infinity (AUCinf) was 4.28 ± 0.536 ,g·h/mL, and mean elimination half-life (t1/2) was 44.9 ± 4.67 h, with a large volume of distribution (Vss) of 24.9 ± 2.99 L/kg and a high clearance rate (Clobs) of 712 ± 95.7 mL/h/kg. For cattle treated with s.c. injection of 3, 6 or 9 mg/kg, mean AUCinf values were 4.55 ± 0.690, 9.42 ± 1.11 and 12.2 ± 1.13 ,g·h/mL, respectively, and the mean elimination half-lives (t1/2) were 51.2 ± 6.10, 50.8 ± 3.80 and 58.5 ± 5.50 h. Gamithromycin was well absorbed and fully bioavailable (97.6,112%) after s.c. administration. No statistically significant (, = 0.05) gender differences in the AUCInf or elimination half-life values were observed. Dose proportionality was established based on AUCInf over the range of 0.5 to 1.5 times of the recommended dosage of 6 mg/kg of body weight. Further investigations were conducted to assess plasma PK, lung/plasma concentration ratios and plasma antibacterial activity using 36 cattle. The average maximum gamithromycin concentration measured in whole lung homogenate was 18 500 ng/g at first sampling time of 1 day (,24 h) after treatment. The ratios of lung to plasma concentration were 265, 410, 329 and 247 at 1, 5, 10 and 15 days postdose. The lung AUCinf was 194 times higher than the corresponding plasma AUCinf. The apparent elimination half-life for gamithromycin in lung was 90.4 h (,4 days). Antibacterial activity was observed with plasma collected at 6 h postdose with a corresponding average gamithromycin plasma concentration of 261 ng/mL. In vitro plasma protein binding in bovine plasma was determined to be 26.0 ± 0.60% bound over a range of 0.1,3.0 ,g/mL of gamithromycin. The dose proportionality of AUC, high bioavailability, rapid and extensive distribution to lung tissue and low level of plasma protein binding are beneficial PK parameters for an antimicrobial drug used for the treatment and prevention of bovine respiratory disease. [source] Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirinJOURNAL OF VIRAL HEPATITIS, Issue 7 2006C. Berg Summary., We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities. [source] Detachment of sprayed colloidal copper oxychloride,metalaxyl fungicides by a shallow water flowPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 6 2009Eva Pose-Juan Abstract BACKGROUND: Flow shear stress induced by rainfall promotes the loss of the pesticides sprayed on crops. Some of the factors influencing the losses of colloidal-size particulate fungicides are quantified by using a rotating shear system model. With this device it was possible to analyse the flow shear influencing washoff of a commercial fungicide formulation based on a copper oxychloride,metalaxyl mixture that was sprayed on a polypropylene surface. A factor plan with four variables, i.e. water speed and volume (both variables determining flow boundary stress in the shear device), formulation dosage and drying temperature, was set up to monitor colloid detachment. RESULTS: This experimental design, together with sorption experiments of metalaxyl on copper oxychloride, and the study of the dynamics of metalaxyl and copper oxychloride washoff, made it possible to prove that metalaxyl washoff from a polypropylene surface is controlled by transport in solution, whereas that of copper oxychloride occurs by particle detachment and transport of particles. Average losses for metalaxyl and copper oxychloride were, respectively, 29 and 50% of the quantity applied at the usual recommended dosage for crops. CONCLUSION: The key factors affecting losses were flow shear and the applied dosage. Empirical models using these factors provided good estimates of the percentage of fungicide loss. From the factor analysis, the main mechanism for metalaxyl loss induced by a shallow water flow is solubilisation, whereas copper loss is controlled by erosion of copper oxychloride particles. Copyright © 2009 Society of Chemical Industry [source] Different angiotensin-converting enzyme inhibitors have similar clinical efficacy after myocardial infarctionBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2008Morten L. Hansen What is already known about this subject ,,Treatment with an angiotensin-converting enzyme (ACE) inhibitor benefits many patients with cardiovascular disease. ,,ACE inhibitors are generally assumed to be equally effective, but this has never been fully verified in clinical trials. What this study adds ,,Studying the association among ACE inhibitors after myocardial infarction demonstrated similarity in clinical outcome and supports a dosage,response relationship. ,,Therefore, for long-term benefits for patients who need treatment with an ACE inhibitor, a focus of treatment at the recommended dosage is most important and not which ACE inhibitor is used. Aim Therapy with angiotensin-converting enzyme (ACE) inhibitors is common after myocardial infarction (MI). Given the lack of randomized trials comparing different ACE inhibitors, the association among ACE inhibitors after MI in risk for mortality and reinfarction was studied. Methods Patients hospitalized with first-time MI (n = 16 068) between 1995 and 2002, who survived at least 30 days after discharge and claimed at least one prescription of ACE inhibitor, were identified using nationwide administrative registries in Denmark. Results Adjusted Cox regression analysis demonstrated no differences in risk for all-cause mortality, but patients using captopril had higher risk of reinfarction (hazard ratio 1.18, 95% confidence interval 1.05, 1.34). However, following adjustment for differences in used dosages, all ACE inhibitors had similar clinical efficacy. Risk of all-cause mortality: trandolapril (reference) 1.00, ramipril 0.97 (0.89, 1.05), enalapril 1.04 (0.95, 1.150), captopril 0.95 (0.83, 1.08), perindopril 0.98 (0.84, 1.15) and other ACE inhibitors or angiotensin II receptor blockers (ARB) 1.06 (0.94, 1.19). Reinfarction: trandolapril (reference) 1.00, ramipril 0.98 (0.89, 1.08), enalapril 1.04 (0.92, 1.17), captopril 1.05 (0.89, 1.25), perindopril 0.96 (0.81, 1.14) and other ACE inhibitors or ARB 0.99 (0.86, 1.14). Furthermore, the association between ARBs and clinical events was similar to ACE inhibitors (trandolapril reference): all-cause mortality 0.99 (0.84, 1.16) and recurrent MI 0.99 (0.83, 1.19). Conclusions Our results suggest a class effect among ACE inhibitors when used in comparable dosages. Focus on treatment at the recommended dosage is therefore most important, and not which ACE inhibitor is used. [source] Treatment of canine pyoderma with ibafloxacin and marbofloxacin , fluoroquinolones with different pharmacokinetic profilesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2004L. J. I. Horspool Dogs with superficial or deep pyoderma (n = 228) presented to first opinion veterinarians (n = 20) were treated orally with either ibafloxacin, at a dosage of 15 mg/kg, or marbofloxacin, at a dosage of 2 mg/kg, once daily for 3,16 weeks. On initial presentation, 35% of the cases were classified as having recurrent pyoderma and 40% as having deep pyoderma. Staphylococci (mainly Staphylococcus intermedius) were isolated from over 90% of the cases. The average treatment periods were 41 ± 26 and 38 ± 21 days in the ibafloxacin and marbofloxacin groups, respectively. One week after the cessation of treatment, 74 and 81% of dogs (P > 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having responded to treatment. One month after the cessation of treatment, 70% of the dogs in each group were still classified as cured or improved, and 3 and 11% (P < 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having relapsed. Despite having different pharmacokinetic profiles, ibafloxacin and marbofloxacin produced similar results when used under field conditions at the recommended dosages. [source] Estimation of the relative antiinflammatory efficacies of six commercial preparations of Harpagophytum procumbens (Devil's Claw)PHYTOTHERAPY RESEARCH, Issue 3 2010Nassima Abdelouahab Ouitas Abstract The current work compared the relative efficacies of six commercial formulations of H. procumbens. Each formulation was assayed for the content of harpagoside (1), harpagide (2), verbascoside (3) and 8- O-p -coumaroyl harpagide (4) and, based on the recommended dosages, the total daily amounts were determined and used to establish anti-/proinflammatory (A/P) factors. The formulations were compared using ex vivo porcine skin for their activities towards COX-2 by Western blotting. The results showed great variation in the amounts of compounds 1,4 within the six formulations examined. The relative proportions of 1,4 also varied widely between the products and this inconsistency was reflected in the A/P factors, which correlated with the COX-2 expression (R2 = 0.9496). Although the data support the beneficial antiinflammatory effects from the use of some of the brands tested, others would appear potentially to exacerbate inflammation. To conclude, a ratio based upon the amount and relative proportions of anti- and proinflammatory compounds can be used to predict relative antiinflammatory properties. Also, with access to a diversity of ostensibly similar commercial products, the patient may experience varying therapeutic responses. Finally, current pharmacopoeia monographs, which are generally concerned with a minimum harpagoside content, are inadequate for ensuring the quality of products based on H. procumbens. Copyright © 2009 John Wiley & Sons, Ltd. [source] A Primary Care Intervention for DepressionTHE JOURNAL OF RURAL HEALTH, Issue 4 2000Jeffrey I. Smith B.S. The study enrolled 479 depressed patients, with 432 (90.2 percent) completing telephone follow-up at six months. Multilevel analytic models revealed that rural enhanced care patients had 2.70 times the odds (P=0.02) of rural usual care patients of taking a three-month course of antidepressant medication at recommended dosages in the six months following baseline; urban enhanced care patients had 2.43 times the odds compared with their urban usual care counterparts (P=0.007). Rural enhanced care patients had 3.00 times the odds of rural usual care patients of making eight or more visits to a mental health specialist for counseling in the six months following baseline (P=0.03). Comparisons of patients in enhanced care practices showed that rural enhanced care patients had 2.00 times the odds (P=0.12) of urban enhanced care patients of making at least one visit to a mental health specialist for counseling in the six months following baseline and had comparable odds to urban enhanced care patients (odds ratio [OR] = 1.06, P=0.77) of making eight or more visits to such specialists during that interval. The study's intervention improved the care received by both rural and urban depressed primary care patients. Moreover, the interventions effect appears to have been greater in rural settings, particularly in terms of increasing depressed rural patients' use of mental health specialists for counseling. [source] Pharmacological profile of the new antihistaminesCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2005J.-P. Tillement Summary The second-generation H1 antihistamines are a highly efficacious drug class in the treatment of allergic rhinitis (AR) and dermatitis, and distinct from the first-generation H1 antihistamines, predominantly because of their non-sedating nature at recommended dosages. Despite a marked chemical heterogeneity, the non-sedating H1 antihistamines have many similarities, in particular, high affinity for H1 receptors, high efficacy, anti-inflammatory effects, which may be independent of direct H1 -receptor function, and lack of central nervous system side-effects. Some studies have suggested that differences in the chemical structures of these compounds generally lead to differences in the pharmacokinetic properties, which determine their overall clinical usefulness. In particular, it has been demonstrated that there are differences in selectivity for H1 receptors, the apparent volume of distribution, metabolism and elimination and interaction with other drugs. A comparison of levocetirizine, fexofenadine, desloratadine and mizolastine (some of the most commonly prescribed drugs in the treatment of AR and dermatitis) has demonstrated that, unlike levocetirizine and fexofenadine, desloratadine and mizolastine can bind to muscarinic receptors and cardiac K+ channels, and therefore have both lower selectivity and the potential to induce muscarinic and serious cardiac side-effects. However, this is noted at higher than recommended doses. Similarly, desloratadine and mizolastine undergo extensive metabolism and, together with fexofenadine, have the potential to interact with other drugs, in turn increasing the potential for severe toxic effects. In contrast, levocetirizine is not metabolized, is eliminated rapidly from the body, does not demonstrate any significant drug interactions and has the lowest volume of distribution. These findings suggest that levocetirizine is likely to be a safer drug than fexofenadine, desloratadine and mizolastine. 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