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A. K. Al-Asmari and N. M. Abdo PHARMACOLOGICAL CHARACTERIZATION OF RAT PAW EDEMA INDUCED BY Cerastes gasperettii cerastes ; VENOM. J. Venom. Anim. Toxins incl. Trop. Dis., 2006, 12, 3, p. 402, for example, cilexetil.
Zorad S.2, Tybitanclova K.2, Dou J.2, Benicky J.1, Hutanu D.1, Zhou, J.1, Saavedra J.M.1, 1 Section on Pharmacology, NIMH, Bethesda, MD, USA; 2 Inst. Exp. Endocrinology, SAS, Bratislava, Slovakia; stefan.zorad savba.sk Aim: Recent data suggest that Angiotensin II receptor type 1 AT1 ; antagonists besides lowering blood pressure reduce obesity-related metabolic disturbances. In order to verify the possible insulin-sensitizing effects of AT1 receptor blockade in adipose tissue we treated male Wistar Kyoto rats with Candesartan cilexetil Cc; 10 mg kg day ; for 18 weeks. Methods: Adipocyte cell size was determined by light microscopy after colagenase digestion of adipose tissue. Circulated levels of hormones in serum were determined by RIA. Gene expression of adipokines and RAS components in adipose tissue were evaluated by real-time PCR. AT1 and AT2 receptor protein levels were determined by immunoblot. Results: Significant loss in body weight without change in food intake was observed at the end of the experiment. In epididymal and retroperitoneal adipose tissue significant decrease in mass was noticed due to hypotrophy. Serum leptin was decreased and serum adiponectin was increased in treated rats. Cc lowered leptin and TNF expression and elevated adiponectin, fatty acid synthase and PPAR mRNA. In addition, Cc treatment resulted in the increase of epididymal AT2 receptor gene and protein expression. Conclusion: We propose that Cc modulates adipokines production and release and regulates fat tissue cellularity. These effects might be the consequence of local AT1 receptor inhibition and or AT2 receptor stimulation, probably involving PPAR activation. Increased adiponectin and PPAR together with decreased TNF suggest insulinsensitising action of long-lasting AT1 receptor blockade. Supported by DIRP, NIMH and by VEGA 2 5090 25.
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Embryos generally led to a 10- to 100-fold reduction of MMVp. Independent of embryonic stage and time of virus exposure, recipients receiving in vivo embryos exposed to a minimum of 102 TCID50 ml MMVp seroconverted by day 42 after ET, while 10 washing steps in the IVF-ET procedure were sufficient to remove the virus to a non-infectious dose. The results indicate that MMVp can be transmitted to recipients even after washing in vivo embryos 10 times prior to ET, but there is minimal risk of transmission of MMVp by in vitro-produced embryos to recipients if spermatozoa become contaminated with such viral loads as used in the present study. PS47 Development and Validation of a Multiplexed Fluorometric ImmunoassayTM for Serodiagnosis of Rabbit Infectious Diseases EM Seletskaia, RA Rigden, N Le, SM Jennings, WR Shek, RK Dhawan * Diagnostic Reagents, Charles River Laboratories, Wilmington, MA A Multiplexed Fluorometric ImmunoassayTM MFIATM ; for serosurveillance of laboratory rabbits was developed using the Luminex xMAP bead-based technology. Antigen coupled beads for adenovirus, CAR bacillus, C. piliforme, E. cuniculi, lymphocytic choriomeningitis virus, pneumonia virus of mice, reovirus-3, rotavirus-A, simian virus-5, and Sendai virus were part of the 14-member rabbit MFIA bead panel. Conventional antigens whole virus or partially purified lysate ; or purified recombinant antigens were individually coupled to the different color-coded bead sets. Internal tissue control beads were coated with the lysate of the wild baculovirus-infected Sf9 insect cells to determine the sample related nonspecific antibody binding. In addition, rabbit IgG and goat anti-rabbit IgG were added to the MFIA panel as system and sample suitability controls, respectively, to validate individual runs of the MFIA. Multiplex assays were run using high and low immune sera controls for the viral antigens and a non-immune serum was added as a negative control. In the validation study, 16 known positive sera from naturally or experimentally infected rabbits for one or more of the above mentioned infectious agents and 16 known negative rabbit sera from specific pathogen free colonies were tested using multiple technicians on multiple days. The antibody status of validation positive and negative samples was previously determined by indirect immunofluorescent antibody IFA ; test which was the only method used in the lab for serological analysis of rabbit sera. A total of 2442 assays were performed and analytical performance of the rabbit MFIA assay including selectivity and limit of detection was found to be comparable to or better than those obtained by IFA. Similarly, the diagnostic sensitivity and specificity of rabbit MFIA was 95% compared to 90% for IFAs of individual infectious agents indicating that MFIA is an acceptable alternative assay for serodiagnosis of adventitious infectious agents of laboratory rabbits.
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| Cilexetil treatmentCurves-somerset and curves-franklin the beginning of your road to improvement as well as now. When trying to lose weight, eat a healthier diet, or exercise more, look back to when you started to adopt those changes and remind yourself how far you've come. Using a third-person perspective to notice the progress you've made in a self-improvement program can help motivate you toward your goals, a recent study reveals. If you have trouble imagining yourself from the thirdperson, enlist a close and honest friend to point out the positive improvements you've made. Women who breast-fed for at least one year were about 15 percent less likely to develop type 2 diabetes than those who never breast-fed. For each additional year of breast-feeding, there was an additional 15 percent decreased risk. However, both breast-feeders and bottlefeeders studied faced very low absolute risks of developing the disease. In the first study, which began in 1976, 6.3 percent of women who breast-fed less than one year or not at all developed diabetes, compared with 5.5 percent of women who breast-fed for more than a year. In the second study, which began in 1989, the rates were 1.9 percent and 1.1 percent respectively. "If it does have an effect, it's very small, " said Dr. Lisa Schwartz of Dartmouth Medical School, co-director of a research group that studies how medical information is sometimes hyped. She was not involved in the breast-feeding study. With diabetes the nation's sixth-leading cause of death and 82 million U.S. women of childbearing age, even a small risk reduction could have a big effect, Stuebe said. Continuous breast-feeding for at least one year appeared to be slightly better than breast-feeding each child for shorter durations, but the differences were minimal, Stuebe said. Schwartz said the results may reflect the healthy lifestyles of women who breast-feed rather than breast-feeding itself. But the researchers said that taking habits such as exercise, diet and smoking into account did not change the results. Dr. Ruth Lawrence of the University of Rochester in New York, author of a medical textbook on breast-feeding, called the results compelling. She noted that previous research has suggested that breast-feeding might reduce women's risk of breast and ovarian cancer.
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Credible authority in the field of laparoscopic surgery. Furthermore, he has enlisted the participation of several nationally and internationally recognized experts in the field of laparoscopic surgery as contributors to the book. Features: The material can be divided into five separate sections: "traditional" general surgical laparoscopic procedures; subspecialty laparoscopic surgical procedures, such as urology, thoracic surgery, pediatric surgery; anesthetic considerations and physiologic changes associated with laparoscopic surgery; technologic advancements in laparoscopic surgery; and medicolegal aspects of laparoscopic surgery. The illustrations and schematic diagrams contained in each of these chapters are very helpful. Many chapters contain black-andwhite photographs of actual laparoscopic procedures, with color plates of the photographs collected in total at the end of the book. It might be more helpful to the reader if the color plates were placed in the text at the appropriate position instead of the black-and-white photographs, but this is a minor shortcoming and does not diminish the overall value of the book. Assessment: All in all, I found this second edition to be an excellent extension of material contained in the first edition. This book will be an extremely practical resource to any individual interested in minimally invasive surgery.
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This MANAGED CARE supplement is derived from the proceedings of a conference conducted April 2628, 2002 in Dallas. It is supported by an unrestricted educational grant from Janssen Pharmaceutica. The opinions expressed herein are those of the participants and faculty and do not necessarily reflect the views of MediMedia USA Inc., the publisher, editor, or editorial board of MANAGED CARE, or the University of Arizona College of Pharmacy, for instance, angiotensin ii receptor antagonists.
This case, the plaintiffs do not contend that they can -- and we conclude that in all likelihood they cannot -- establish that Zeneca's patent litigation was baseless, particularly in light of the subsequent series of decisions upholding the validity of the same patent. Cf. id. at 60 n.5 "A winning lawsuit is by and clomiphene.
110 See, for example, William K. Hubbard, Senior Associate Commissioner for Policy, Planning and Legislation, Food and Drug Administration, "Continuing Concerns over Imported Pharmaceuticals, " Testimony before the Subcommittee on Oversight and Investigations, U.S. House Committee on Energy and Commerce, June 7, 2001. 111 Michael F. Conlan, "How Safe Is the Drug Supply?" Drug Topics, October 15, 2001, for example, hydrochlorothiazide.
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Sites located among 136 to + 10 the MDR1 promoter 11 ; . Cotransfection of HL-60 cells with MDR1 reporter gene and increasing amounts of ZNRD1 expression vectors resulted in a linear increase in MDR1 promoter activity, and the data were confirmed by transfection experiments in leukemia cells. The increase in the steady-state levels of the P-gp protein in ZNRD1 transfected cells and the ability of ZNRD1 to induce the MDR1 reporter gene in transient transfections argue that ZNRD1 is a transcriptional regulator of the MDR1 gene. We assumed that the role of ZNRD1 might depend not only on the promoter sequences but also on the association of ZNRD1 with different cofactors. The precise mechanism by which ZNRD1 influences MDR1 gene expression is the subject of future experimental work. However, how HL-60-Z1 and HL-60-Z2 cells resisted to 5-FU and CDDP could not be explained by up-regulation of P-gp, which suggested that other mechanisms might exist. Thus, we further tested whether the GST-mediated drugdetoxifying system was involved in ZNRD1-related MDR. GST catalyzed the conjugation of reduced glutathione to some electrophilic anticancer drugs, which deprived these drugs of the possibility to reach their cellular targets 31 ; . It has been reported that increased GST activity and reduced glutathione content in drug-resistant tumor cells were associated with resistance to nitrogen mustards, melphalan, and CDDP 32 35 ; . detected total GST activity and intracellular GST content in leukemia cells. However, GSTmediated drug-detoxifying system was not found significantly involved in ZNRD1-mediated MDR. Apoptosis was a common pathway that finally mediated the killing functions of anticancer drugs, which was an and clozapine.
Mr. Elhassan is a fourth-year medical student at Johns Hopkins University School of Medicine, and Dr. Chow is Director of General Internal Medicine, Department of Medicine, Sinai Hospital of Baltimore, MD.
Pected to increase Ca release from intracellular stores. Figure 5 illustrates effects of the membrane-permeable Ca 2 -chelator BAPTA-AM 50 mM ; , the intracellular Ca 2 -release inhibitor procaine 0.3 mM ; , the intracellular ryanodine receptor agonist ryanodine 20 mM ; , and the intracellular Ca 2 -release inhibitor TMB-8 20 mM ; Chiou and Malagodi 1975; Fujiwara et al. 1994 ; , on responses induced by a period of oxygen and glucose deprivation. All these drugs prolonged the latency of the rapid depolarization and partially or completely restored the membrane potential after reintroduction of oxygen and glucose. Average latencies for generating the rapid depolarization in the presence of these drugs is shown in Figure 6A. The latency was prolonged significantly by BAPTA-AM 50 mM ; , ryanodine 40 mM ; , TMB-8 20 mM ; , and procaine 0.3 mM and 1 mM ; . these drugs, procaine 0.3 mM ; slightly depressed TTX-sensitive spike amplitudes, which were elicited by depolarizing current pulses 1.52 nA, 2 ms, 0.2 Hz ; , by 10 20% of the control n 5 ; . Figure 6B illustrates the recovery percent ; of neurons in the presence of BAPTA-AM, ryanodine, TMB-8, or procaine. All the agents had some protective effect against the and mebeverine and cilexetil, because losartan potassium.
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Hemodynamic data from all of the groups are summarized in Table 1. Baseline heart rates and mean blood pressures were not significantly different among groups with exception of group 4 were intravenous administration of spirapril caused a significant decrease in mean arterial pressure 786 mm Hg versus 966 mm Hg in the controls, p 0.05 ; , and this effect was evident within a few minutes following the injection of drug and
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Mutation in the Mediterranean region has culminated in many studies that highlight their frequency and necessity for screening. FACTOR V LEIDEN Table III 162-182 lists the frequencies for Factor V Leiden in the general population and in patients with DVT in Mediterranean countries. As expected, where general population frequency is high then more patients have DVT attributed to Factor V Leiden. An international comparative study of allele frequencies for Factor V Leiden indicates that Eastern Mediterranean populations harbor a relatively high mutant allele frequency similar to some Scandinavian and Northern European populations.183187 The frequency is less in Asians and South Americans and the condition appears to be absent in Oriental and other non European populations.100.
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The AT1 -receptor blockers offer a favourable clinical profile, including effective blood-pressure reduction, good tolerability and increasing evidence of protection against target-organ damage. However, the differences in pharmacological properties between the available agents are reflected in certain differences in clinical properties. Antihypertensive efficacy Each of the available AT1 -receptor blockers has proven antihypertensive efficacy. However, there are marked differences between them in the maximal antihypertensive effect 14 , and in the duration of action. In one randomized study, for example, hypertensive patients received candesartan dilexetil 816 mg, losartan 50100 mg, or placebo for 8 weeks; ambulatory blood pressure was measured for 36 hours after dosing and clinic blood pressure was measured 24 and 48 hours after the last dose 15 . Candesartan produced significantly greater reductions in ambulatory blood pressures than losartan, which were sustained for at least 36 hours after dosing Fig. 3 ; . In contrast, in losartan-treated patients blood pressure had returned almost to baseline levels at 36 hours after dosing Fig. 3 ; . Moreover, significant reductions in both systolic and diastolic clinic blood pressures were seen 48 hours after the last dose of candesartan, whereas blood pressures in losartan-treated patients were not significantly different from baseline levels. Indeed, blood pressures in candesartan-treated patients 48 hours after the last dose were comparable with those seen in losartan-treated patients 24 hours after dosing.
Receptor26 or PDGF receptor27 via AT1 receptor. However, it is still unclear whether the activation of EGF or PDGF receptors by Ang II can occur in an in vivo situation. In the present work, we obtained the first evidence that vascular PDGF- receptor tyrosine phosphorylation, but not PDGFreceptor or EGF receptor tyrosine phosphorylation, was enhanced in hypertensive rats and that this enhanced PDGFreceptor activation was at least in part mediated by AT1 receptor, as shown by the significant inhibitory effects of perindopril and candesartan cillexetil but not amlodipine. Interestingly, although 0.2 mg kg perindopril or candesartan cilexetil alone failed to suppress aortic PDGF- receptor tyrosine phosphorylation, their combination significantly decreased aortic PDGF- receptor tyrosine phosphorylation as much as 2 mg kg of each agent alone. Taken together with the fact that the PDGF- receptor plays a central role in vascular smooth muscle cell proliferation and migration in vivo, 28 30 these findings support the notion that combination therapy with an ACE inhibitor and an AT1 receptor antagonist may be useful for the treatment of vascular remodeling. In the present work, either bradykinin accumulation14 or AT2 receptor31 might be responsible for the beneficial effects of the combination of low doses of perindopril and candesartan cilexetil. Our results show that treatment with Hoe140 did.
CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections OIs ; among hematopoietic stem cell transplant HSCT ; recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as regardlessoftransplanttype i.e., allogeneicorautologous ; orcellsource i.e., bone marrow, peripheral blood, or placental or umbilical cord blood ; . Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients and atacand.
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