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Dose Dependent (dose + dependent)
Terms modified by Dose Dependent Selected AbstractsEffect of Flavonoids on Daunorubicin-induced Toxicity in H9c2 CardiomyoblastsPHYTOTHERAPY RESEARCH, Issue 1 2009Gabriela Moj Abstract Daunorubicin (DNR) is one of the most important antitumor agents belonging to the anthracycline group. However, its use is seriously limited by the development of cardiac toxicity. The present study was designed to investigate the effects of quercetin, pycnogenol and naringenin on daunorubicin-induced cytoxicity in H9c2 cells. Protection of H9c2 cardiomyocyte cells was concentration/dose dependent for quercetin > naringenin > pycnogenol = trolox. Quercetin (10,4,10,5 mol/L) after 24 h of co-incubation with DNR significantly increased the cardiomyocyte survival (p < 0.001 and p < 0.05, respectively). A protective effect of other compounds was observed only in the highest concentration/dose used (p < 0.01). After 48 h of incubation quercetin and naringenin significantly decreased daunorubicin-induced cell death at concentrations of 10,4,10,5 mol/L (p < 0.001 and p < 0.01, respectively). The protective effect of pycnogenol and trolox was weaker but significant in the two highest concentrations/doses (p < 0.001 and p < 0.05, respectively). This study also investigated DNR-induced apoptosis and it was shown that both quercetin and naringenin inhibit apoptosis of H9c2 cardiomyocytes cells in vitro. The findings provide evidence that quercetin and naringenin may act as survival factors. The protective effect of flavonoids was compared with that of trolox, a known cardioprotective antioxidant. These results are consistent with the notion that the use of flavonoids may be beneficial in modulating or preventing the cardiotoxicity associated with DNR therapy. Copyright © 2008 John Wiley & Sons, Ltd. [source] Dietary exposure to low doses of bisphenol A: Effects on reproduction and development in two generations of C57BL/6J miceCONGENITAL ANOMALIES, Issue 3 2010Kenichi Kobayashi Abstract The present study was conducted to examine the effects of low-dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F0) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F1 and F2) from each F0 and F1 dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment-related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F0 dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F1 pups. No treatment-related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F1 and F2 adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F1 males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment-related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F1 or F2 males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice. [source] Dose-dependent growth inhibition and bioaccumulation of hexavalent chromium in land snail Helix aspersa aspersaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2000Michaël C, urdassier Abstract The toxicity of Cr6+ was determined in a laboratory environment in the snail Helix aspersa aspersa. The effects on growth were evaluated on animals reared in controlled conditions at the age of one month that had been exposed for 28 d to increasing doses of Cr6+ mixed in with their food. Two experimental groups were set up with concentrations of chromium in the feed of 250 to 1,250 ,g/g (test 1) and 100 to 800 ,g/g (test 2). Growth inhibition was dose dependent, and the mean EC50 calculated at four weeks for tests 1 and 2 were, respectively, 354.7 and 298.8 ,g/g and for the EC10 195.3 and 160.9 ,g/g. The levels of Cr6+ bioaccumulated in the foot and the viscera of the snails were dose dependent in both types of tissues. The highest concentrations occurred in the viscera, the levels being 0.79 ,g/g in the controls and reaching 3,067 ,g/g in the animals exposed to the maximum contamination (1,250 ,g/g). These high levels of bioaccumulation in addition to the lower concentrations of Cr6+ excreted in the feces than those present in the food suggest that chromium is not physiologically regulated by Helix aspersa. The results provide added support for the use of snails as a model to determine the toxicity of substances in laboratory biotests by measuring the effects on growth and by assessing bioaccumulation. [source] Use of Chronic Epilepsy Models in Antiepileptic Drug Discovery: The Effect of Topiramate on Spontaneous Motor Seizures in Rats with Kainate-induced EpilepsyEPILEPSIA, Issue 1 2005Heidi L. Grabenstatter Summary:,Purpose: Potential antiepileptic drugs (AEDs) are typically screened on acute seizures in normal animals, such as those induced in the maximal electroshock and pentylenetet-razole models. As a proof-of-principle test, the present experiments used spontaneous epileptic seizures in kainate-treated rats to examine the efficacy of topiramate (TPM) with a repeated-measures, crossover protocol. Methods: Kainic acid was administered in repeated low doses (5 mg/kg) every hour until each Sprague,Dawley rat experienced convulsive status epilepticus for >3 h. Six 1-month trials (n = 6,10 rats) assessed the effects of 0.3,100 mg/kg TPM on spontaneous seizures. Each trial involved six pairs of TPM and saline-control treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Data analysis included a log transformation to compensate for the asymmetric distribution of values and the heterogeneous variances, which appeared to arise from clustering of seizures. Results: A significant effect of TPM was observed for 12 h (i.e., two 6-h periods) after a 30-mg/kg injection, and full recovery from the drug effect was complete within 43 h. TPM exerted a significant effect at doses of 10, 30, and 100 mg/kg, and the effects of TPM (0.3,100 mg/kg) were dose dependent. Conclusions: These data suggest that animal models with spontaneous seizures, such as kainate- and pilocarpine-treated rats, can be used efficiently for rapid testing of AEDs with a repeated-measures, crossover protocol. Furthermore, the results indicate that this design allows both dose,effect and time-course-of-recovery studies. [source] MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter bindingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Susan Schenk Abstract 3,4-Methylenedioxymethamphetamine (MDMA) self-administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug-naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self-administration was measured during daily 6-h sessions. Dose,effect data were obtained for MDMA (0.25,1.0 mg/kg/infusion) self-administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter- or self-administered MDMA on [3H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self-administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self-administration during the 15-day test period. The percentage of rats that acquired MDMA self-administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self-administration, and cocaine self-administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self-administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter-administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long-term self-administration may lead to long-lasting deficits in serotonin neurotransmission. [source] Regulation of MC1R signalling by G-protein-coupled receptor kinasesEXPERIMENTAL DERMATOLOGY, Issue 9 2004J. C. García-Borrón The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist-dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist-dependent signalling, and 8) cAMP production in agonist-stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. Therefore, GRK2 and GRK6 are key regulators of MC1R signalling and may be important determinants of normal and pathological skin pigmentation. [source] Rough and smooth forms of fluorescein-labelled bacterial endotoxin exhibit CD14/LBP dependent and independent binding that is influencedby endotoxin concentrationFEBS JOURNAL, Issue 8 2000Martha Triantafilou Lipopolysaccharide (LPS, or endotoxin), is a major constituent of the outer membrane of Gram-negative bacteria. Bacteria express either smooth LPS, which is composed of O-antigen (O-Ag), complete core oligosaccharides, and the lipid A, or rough LPS which lack O-Ag but possess lipid A and progressively shorter core oligosaccharides. CD14 has been described as the receptor for complexes of LPS with LPS-binding protein (LBP). Using flow cytometry we have compared the binding of Salmonella minnesota rough LPS (ReLPS) and Escherichia coli smooth LPS labelled with fluorescein isothiocyanate (FITC-LPS) to Chinese hamster ovary (CHO) cells transfected with human CD14 gene (hCD14-CHO), to MonoMac 6 cells and to endothelial cells. Our results showed that both forms of LPS display the same binding characteristics, and that the binding of FITC-LPS to cells was both CD14- and LBP-dependent for LPS concentrations up to 100 ng·mL,1. At LPS concentrations higher than 100 ng·mL,1 we observed CD14/LBP-independent binding. CD14/LBP-dependent binding was dose dependent, saturable, and enhanced in the presence of human pooled serum (HPS), and the monoclonal anti-CD14 antibody (MY4) or unlabelled LPS could outcompete it. [source] Multiple profiling of soil microbial communities identifies potential genetic markers of metal-enriched sewage sludgeFEMS MICROBIOLOGY ECOLOGY, Issue 3 2008Catriona A. Macdonald Abstract The long-term impacts of Cu- and Zn-rich sewage sludge additions on the structure of the microbial community in a field under pasture were investigated using a combination of multiplex-terminal restriction fragment length polymorphism (M-TRFLP) and T-RFLP profiling approaches. Changes in the community structure of bacteria, fungi, archaea and actinobacteria were observed in soils that had previously received Cu- (50,200 mg kg,1 soil) and Zn- (150,450 mg kg,1 soil) rich sewage sludge additions. Changes in the structure of all microbial groups measured were observed at Cu and Zn rates below the current EU guidelines (135 mg kg,1 Cu and 300 mg kg,1 Zn). The response of the fungal community, and to a lesser extent the bacterial and archaeal community, to Cu was dose dependent. The fungal community also showed a dose-dependent response to Zn, which was not observed in the other microbial groups assessed. Redundancy analysis demonstrated that individual terminal restriction fragments responded to both Cu and Zn and these may have potential as genetic markers of long-term metal effects in soil. [source] Use of pharmacokinetics in the coagulation factor treatment of patients with haemophiliaHAEMOPHILIA, Issue 6 2005A. D. Shapiro Summary., Dosing decisions for replacement coagulation factors in patients with haemophilia should be made on an individual patient basis, with the required dose dependent on factors including the clinical situation, the severity of the factor deficiency, and the location and extent of bleeding. Moreover, there is considerable variability in the pharmacokinetics of coagulation products that needs to be considered; in particular, with both factor (F) IX and FVIII products, there is considerable inter-patient variability in in vivo recovery and terminal half-life values. In the present report, we provide a practical guide to calculating and applying pharmacokinetic parameters relevant to the optimal dosing of coagulation products. We discuss the conduct of a pharmacokinetic study in an individual patient, how to calculate pharmacokinetic values from raw data and clinical situations where an individual pharmacokinetic study is helpful. We highlight the importance of considering an individual pharmacokinetic study in all patients starting a new coagulation product. [source] Alcohol intoxication effects on visual perception: An fMRI studyHUMAN BRAIN MAPPING, Issue 1 2004Vince D. Calhoun Abstract We examined the effects of two doses of alcohol (EtOH) on functional magnetic resonance imaging (fMRI) activation during a visual perception task. The Motor-Free Visual Perception Test,Revised (MVPT-R) provides measures of overall visual perceptual processing ability. It incorporates different cognitive elements including visual discrimination, spatial relationships, and mental rotation. We used the MVPT-R to study brain activation patterns in healthy controls (1) sober, and (2) at two doses of alcohol intoxication with event-related fMRI. The fMRI data were analyzed using a general linear model approach based upon a model of the time course and a hemodynamic response estimate. Additionally, a correlation analysis was performed to examine dose-dependent amplitude changes. With regard to alcohol-free task-related brain activation, we replicate our previous finding in which SPM group analysis revealed robust activation in visual and visual association areas, frontal eye field (FEF)/dorsolateral prefrontal cortex (DLPFC), and the supplemental motor area (SMA). Consistent with a previous study of EtOH and visual stimulation, EtOH resulted in a dose-dependent decrease in activation amplitude over much of the visual perception network and in a decrease in the maximum contrast-to-noise ratio (in the lingual gyrus). Despite only modest behavior changes (in the expected direction), significant dose-dependent activation increases were observed in insula, DLPFC, and precentral regions, whereas dose-dependent activation decreases were observed in anterior and posterior cingulate, precuneus, and middle frontal areas. Some areas (FEF/DLPFC/SMA) became more diffusely activated (i.e., increased in spatial extent) at the higher dose. Alcohol, thus, appears to have both global and local effects upon the neural correlates of the MVPT-R task, some of which are dose dependent. Hum. Brain Mapping 21:15,26, 2004. © 2003 Wiley-Liss, Inc. [source] A novel model of sensitization and oral tolerance to peanut proteinIMMUNOLOGY, Issue 3 2004Jessica Strid Summary The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens. [source] Dihomo-,-linolenic acid inhibits tumour necrosis factor-, production by human leucocytes independently of cyclooxygenase activityIMMUNOLOGY, Issue 3 2003Maaike M. B. W. Dooper Summary Dietary oils (such as borage oil), which are rich in ,-linolenic acid (GLA), have been shown to be beneficial under inflammatory conditions. Dihomo-GLA (DGLA) is synthesized directly from GLA and forms a substrate for cyclooxygenase (COX) enzymes, resulting in the synthesis of lipid mediators (eicosanoids). In the present study, the immunomodulatory effects of DGLA were investigated and compared with those of other relevant fatty acids. Freshly isolated human peripheral blood mononuclear cells (PBMC) were cultured in fatty acid (100 µm)-enriched medium for 48 hr. Subsequently, cells were stimulated with lipopolysaccharide (LPS) for 20 hr and the cytokine levels were measured, in supernatants, by enzyme-linked immunosorbent assay (ELISA). Phospholipids were analysed by gas chromatography. Fatty acids were readily taken up, metabolized and incorporated into cellular phospholipids. Compared with the other fatty acids tested, DGLA exerted pronounced modulatory effects on cytokine production. Tumour necrosis factor-, (TNF-,) and interleukin (IL)-10 levels were reduced to 60% of control levels, whereas IL-6 levels were not affected by DGLA. Kinetic studies showed that peak levels of TNF-,, occurring early after LPS addition, were inhibited strongly, whereas IL-10 levels were not affected until 15 hr after stimulation. Both the reduction of cytokine levels and the decrease in arachidonic acid levels in these cells, induced by DGLA, were dose dependent, suggesting a shift in eicosanoid-subtype synthesis. However, although some DGLA-derived eicosanoids similarly reduced TNF-, levels, the effects of DGLA were probably not mediated by COX products, as the addition of indomethacin did not alter the effects of DGLA. In conclusion, these results suggest that DGLA affects cytokine production by human PBMC independently of COX activation. [source] Anti-microbial hand washes for domestic use , their effectiveness in vitro and in normal useINTERNATIONAL JOURNAL OF CONSUMER STUDIES, Issue 3 2001Kay Sharp Abstract The killing or removal of microbes from the hands is a critical factor in food safety as many studies have shown the hands to be both an important source of microbes and powerful agents of cross-contamination in hospital and domestic situations. In response to this concern, a number of novel hand-washing products have appeared on the market. These products contain anti-microbial agents and claim to be more effective at removing bacteria than soap bars and conventional liquid soaps. This study attempts to test these claims by comparing the effectiveness of a conventional soap bar, a conventional liquid soap and an anti-microbial liquid soap containing triclosan. In vitro tests demonstrate that the anti-microbial liquid soap is more effective than conventional liquid soaps in reducing the viability of six bacterial species and that this effect is both time and dose dependent. However, when the three soaps were compared for their ability to reduce microbial counts on the hands no differences were observed between the three products. For all three soaps, counts after washing sometimes went up and sometimes down when compared with pre-wash counts. This was the case both when the soaps were used ,normally', that is, with great variation in the time taken, water and soap volumes used and method of washing and after a standardized, rigorous wash recommended in clinical situations. Furthermore, reduction in microbial counts from hands contaminated by handling raw meat was no greater for the anti-microbial than for the conventional liquid soap. [source] Ingredients in dentifrices and their effect on plaque, gingivitis and mutans streptococciINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 1 2004L Jannesson The main objectives of this thesis were to study: (i) the effect of an enzyme-containing dentifrice (Zendium Dentine®), with addition of xylitol on mutans streptococci (MS) in saliva and dental plaque (Paper I) (ii) the effect of a combination of triclosan and xylitol in a dentifrice (Colgate Total®) on MS in saliva and dental plaque (Paper II), and (iii) the effect of oxybenzone on prostaglandin E2 (PGE2)-production in cell culture and the effect of an oxybenzone-containing dentifrice on plaque, gingivitis and MS (Paper III). In Paper I, the subjects were divided into two test groups: one using a 10% xylitol and the other using a 5% xylitol dentifrice for 3 months. The addition of 10% xylitol to Zendium Dentine® had an inhibitory effect on MS in both saliva and dental plaque, and the effect of xylitol seemed to be dose dependent. In Paper II, three groups were using one of the following dentifrices: (i) Colgate Total® with addition of 10% xylitol; (ii) Colgate Total®; and (iii) Colgate Total® without triclosan and without xylitol. The results showed that the addition of 10% xylitol to Colgate Total® reduced the number of MS in saliva and plaque. This effect was more pronounced at 6 months than at 2 months. In Paper III, the effect of oxybenzone was studied in vitro and in vivo. Human Embryo Palatal Mesenchyme (HEPM) cells were used to test the inhibition of IL-1,-stimulated PGE2 production by different concentrations of oxybenzone. The results revealed that there was no decrease of cell viability up to 50 µm. A dose-dependent inhibition of stimulated PGE2 production was found: 50% inhibition (IC50) was found at 0.6 µm. Paper III also included a double-blind clinical trial testing two fluoride dentifrices: one with the addition of 0.5% oxybenzone and one without. Plaque index was reduced in both groups. There was no difference between the groups. A 25% reduction in gingival index was observed in the oxybenzone group after 6 weeks, compared to 2% in the placebo group, indicating an anti-inflammatory effect of oxybenzone. [source] Composition and functional properties of raw and electron beam-irradiated Mucuna pruriens seedsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 8 2008Rajeev Bhat Summary The proximate, nutritional and functional properties of raw and electron beam-irradiated (0,30 kGy) Mucuna seeds were investigated. Irradiation increased crude protein and crude carbohydrates significantly than crude lipid, crude fibre and energy. Raw seeds were rich in minerals and were not affected by irradiation except for magnesium and phosphorus. Amino acids of raw seeds were comparable to soyabean and FAO/WHO reference pattern and except for 30 kGy, no significant changes were seen in amino acid profile. Raw seeds were rich in unsaturated fatty acids and some of them decreased on irradiation, while linoleic acid steadily elevated (0,14.35 mg g,1 lipid). In vitro protein digestibility was dose dependent and significantly increased up to 15 kGy. Water and oil absorption capacities and foaming capacity significantly increased on irradiation, while protein solubility decreased (15 and 30 kGy) with an improvement of gelation property of seed flour. The cooking time of seeds significantly reduced on irradiation. [source] Plant,Water Relations of Kidney Bean Plants Treated with NaCl and Foliarly Applied GlycinebetaineJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2002C. M. L. Lopez Salinity is at present one of the most serious environmental problems influencing crop growth. It has been extensively demonstrated that salinity affects several physiological processes in the plant, including the plant,water relations of most salt-sensitive crops species. In this study, the effects of salinity on the plant,water relations of kidney bean (Phaseolus vulgaris L.) and the possibility that foliarly applied glycinebetaine improves these water relations are examined. Kidney bean plants were grown in a greenhouse and treated with 0, 30, 50 and 100 mM NaCl, combined with 0, 10 and 30 mM glycinebetaine in foliar applications. Increased salinity levels decreased stomatal conductance, photosynthetic rate, transpiration and leaf relative water content in the 30, 50 and 100 mM treatments relative to the control treatment. Glycinebetaine applications of 10 mM increased stomatal conductance at 50 mM NaCl, ameliorating significantly the effect of salinity on water relations through increases in the leaf relative water content. At 100 mM NaCl, 30 mM glycinebetaine applications in particular contributed to osmotic stress, and had an adverse effect on plants. Our experiment suggests that glycinebetaine can be used as an alternative treatment to reduce the effects of salt stress on the water relations of salt-sensitive plants, but only to limited salinity levels. Furthermore, the improvement in the water status of kidney beans was dose dependent, suggesting that the concentration of glycinebetaine essential for the survival of salt-sensitive plants is species specific and must be determined individually for each plant species. Pflanzen,Wasser-Beziehungen von NaCl-behandelten und mit Glycinbetain besprühten Blättern von Gartenbohnenpflanzen Versalzung ist zur Zeit eine der am meisten wirksamen Umweltprobleme im Hinblick auf das Wachstum von Kulturpflanzen. Es hat umfangreiche Untersuchungen gegeben, die Versalzungswirkungen in ihrem Einfluss auf zahlreiche physiologische Vorgänge in der Pflanze zu untersuchen; hierbei wurden auch die Pflanzen,Wasser-Beziehungen von hochsalzempfindlichen Pflanzenarten berück-sichtigt. In dieser Untersuchung wurden die Einflüsse der Versalzung auf die Pflanzen,Wasser-Beziehungen bei Buschbohnen (Phaseolus vulgaris L.) und die Möglichkeit über Blattbesprühungen mit Glycinbetain die Wasser-Beziehungen zu verbessern, untersucht. Die Buschbohnen wurden im Gewächshaus angezogen und mit 0, 30, 50 mM NaCl in Kombination mit 0, 10, 30 mM Glycinbetain Blattbehandlungen angezogen. Eine Erhöhung der Versalzung führte zu einer Abnahme der stomatären Konduktanz, der Photosyntheserate, der Transpiration und des relativen Blattwassergehaltes bei den Behandlungen mit 30, 50 und 100 mM im Vergleich zur Kontrolle. Glysinbetainanwendungen von 10mM erhöhten die stomatäre Konduktanz bei 50 mM NaCl und verbesserten signifikant den ungünstigen Einfluss der Versalzung auf die Wasser-Beziehungen über eine Erhöhung des relativen Blattwassergehaltes. Verwendung von 100 mM NaCl und 30 mM GB trug zu dem osmotischen Streß durch Versalzung bei und hatten einen ungünstigen Einfluss auf die Pflanzen. Unser Experiment weist darauf hin, dass Glycinbetain eine alternative Möglichkeit ist, um die Einflüsse des Salzstresses auf die Wasser-Beziehungen von salzempfindlichen Pflanzen abzuschwächen; es bestehen aber Begrenzungen bezüglich des Versalzungsgrades, bei denen eine günstige Wirkung nachgewiesen werden kann. Ausserdem ist die Verbesserung im Wasserzustand der Buschbohnen von der Anwendungsstärke abhängig, so dass die Konzentration von GB wesentlich für das Überleben der salzempfindlichen Pflanzenart spezifisch ist und für jede Pflanzenart untersucht werden. [source] Methotrexate induction of human sulfotransferases in Hep G2 and Caco-2 cellsJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2005Xinrong Chen Abstract Methotrexate (MTX) was the first antifolate drug developed for the treatment of cancer. It is also effective in treating inflammatory and autoimmune diseases. Sulfotransferases are phase II drug-metabolizing enzymes and their induction by hormones and endogenous molecules is relatively well known, although xenobiotic drug induction of sulfotransferases has not been well studied. In the present investigation, MTX is shown to be a xenobiotic inducer of human sulfotransferases in transformed human liver (Hep G2) and intestinal (Caco-2) cells. Following MTX treatment, various sulfotransferases were induced in both cell lines. Enzyme assay, Western blot and reverse-transcription polymerase chain reaction (RT-PCR) results demonstrated that protein and mRNA expressions of human simple phenol sulfotransferase (P-PST), human monoamine sulfotransferase (M-PST), human dehydroepiandrosterone sulfotransferase (DHEA-ST) and human estrogen sulfotransferase (EST) were induced in Hep G2 cells; M-PST and DHEA-ST were induced in Caco-2 cells. Inductions in both cell lines were dose dependent. Enzyme activity and Western blot results were in good agreement with RT-PCR results, suggesting that the induction is at the gene transcription level. Folic acid had a significantly lesser effect on sulfotransferases compared with MTX. Interestingly, the induction of different sulfotransferases by MTX was inhibited by high doses of folic acid at both protein and mRNA levels in Hep G2 cells. Methotrexate is the first antifolate and apoptosis-inducing drug to show induction of sulfotransferases in Hep G2 cells and Caco-2 cells. The inhibition by folic acid suggests a possible mechanism for MTX induction. Copyright © 2005 John Wiley & Sons, Ltd. [source] Impaired Energetic Metabolism After Central Leptin Signaling Leads to Massive Appendicular Bone Loss in Hindlimb-Suspended Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008Aline Martin Abstract We previously showed in rats that the leptin effects on bone were dose dependent. Positive effects were observed when serum leptin concentration was in a physiological range. In contrast, important increases in serum leptin levels led to negative effects on bone formation similar to those reported after intracerebroventricular leptin administration in mice. To clarify whether leptin effects on bone depend on administration route and/or animal model, female rats were hindlimb unloaded or not and treated either with intracerebroventricular infusion of leptin or vehicle for 14 days. By increasing cerebrospinal fluid (CSF) leptin concentration, intracerebroventricular infusion of leptin significantly reduced food intake and consequently body weight, abdominal fat, and lean mass of the animals. Leptin infusion inhibited bone elongation over the 14 days and blunted cortical bone thickening at the femoral diaphysis site. Interestingly, leptin effects were site dependent in the cancellous bone envelopes, because tibia metaphysis BMD was lower and lumbar spine BMD was higher under intracerebroventricular leptin. Treated groups showed reduced bone remodeling independently of hindlimb unloading. Multiple downstream pathways were implicated in the mediation of these negative leptin effects on bone including not only stimulation of the sympathetic nervous system but also a decrease in somatotropic axis activity. Therefore, the intracerebroventricular leptin-induced bone loss could be largely related to the concurrent alteration of energetic and metabolic status. In summary, our study supports the hypothesis of a concentration-dependent balance between peripheral and central control of leptin on bone. [source] Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008Jürg A Gasser PhD Abstract Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis. Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties. Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 ,g/kg, alendronate 200 ,g/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (,CT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk. Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ,4 ,g/kg for total BMD, ZOL ,20 ,g/kg for cortical BMD, and ZOL ,4 ,g/kg for cancellous BMD (p < 0.01 versus ovariectomized controls). Alendronate 200 ,g/kg was of equivalent potency to ZOL 20 ,g/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 ,g/kg was equivalent to ZOL 20 ,g/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 ,g/kg, whereas at 100,500 ,g/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 ,g/kg but were significantly reduced by ZOL 100,500 ,g/kg. Alendronate 200 ,g/kg was equivalent to ZOL 100 ,g/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 ,g/kg was of similar potency to ZOL 20 ,g/kg. Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis. [source] Moderate Alcohol Consumption Suppresses Bone Turnover in Adult Female RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001R. T. Turner Abstract Chronic alcohol abuse is a major risk factor for osteoporosis but the effects of moderate drinking on bone metabolism are largely uninvestigated. Here, we studied the long-term dose-response (0, 3, 6, 13, and 35% caloric intake) effects of alcohol on cancellous bone in the proximal tibia of 8-month-old female rats. After 4 months of treatment, all alcohol-consuming groups of rats had decreased bone turnover. The inhibitory effects of alcohol on bone formation were dose dependent. A reduction in osteoclast number occurred at the lowest level of consumption but there were no further reductions with higher levels of consumption. An imbalance between bone formation and bone resorption at higher levels of consumption of alcohol resulted in trabecular thinning. Our observations in rats raise the concern that moderate consumption of alcoholic beverages in humans may reduce bone turnover and potentially have detrimental effects on the skeleton. [source] Occurrence and risk indicators of increased probing depth in an adult Brazilian populationJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2 2005Cristiano Susin Abstract Background/Aims: There is little information about the occurrence and risk indicators for periodontal diseases in Latin America. The present study describes the prevalence, extent and severity of periodontal probing depth (PPD) and assesses the association between demographic, behavioural and environmental risk indicators and the extent and severity of PPD in this population. Materials and Methods: The target population was urban adults aged 30 years in Rio Grande do Sul state in South Brazil. A representative sample was selected using a multi-stage, probability, cluster sampling strategy and included 853 dentate subjects 30,103 years of age. A full-mouth clinical examination was carried out at six sites per tooth on all permanent teeth, excluding third molars, and was conducted in a mobile examination centre. Results: Approximately 65% and 25% of the subjects and 19% and 5% teeth per subject had PPD 5 and 7 mm, respectively. 31.6%, 33.7% and 34.7% subjects had generalized, localized or no PPD 5 mm, respectively. Probing depth increased in prevalence with increasing age, and leveled off at around 50 years of age and beyond. PPD 5 mm was significantly higher in males than in females, and in non-Whites than in Whites. Cigarette smokers had a significantly higher occurrence of PPD 5 mm than non-smokers, and this relationship was dose dependent. A multivariate model showed that generalized PPD 5 mm was associated with subjects aged 40 years, males, non-Whites and moderate or heavy cigarette smokers (relative risk ratios: 2.0, 2.0, 2.2, 2.4 and 6.8, respectively). Conclusion: Moderate and deep probing depth was a common finding in this urban adult Brazilian population. Older age, male gender, non-White race and moderate and heavy cigarette smoking were significant risk indicators of increased PPD, and these may be useful indicators of periodontal disease high-risk groups. [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] Reduction of Carcinogenic N-Nitrosamines and Residual Nitrite in Model System Sausage by IrradiationJOURNAL OF FOOD SCIENCE, Issue 4 2002H. J. Ahn ABSTRACT Gamma irradiation was used to reduce the N-nitrosamines and residual nitrite in model system sausage during storage. Aerobic or vacuum packaged sausage was irradiated at 0, 5,10, 20, and 30 kGy. The residual nitrite levels were significantly reduced by gamma irradiation, and, in vacuum packaging, the reduction was dose dependent. The N-nitrosodimethylamine of the sausage irradiated at 10 kGy or above reduced in aerobic packaging, while a dose of 20 kGy was needed in vacuum packaging. The N-nitrosopyrrolidine reduction was found at 20 and 30 kGy-irradiation. Results indicated that high dose irradiation (> 10 kGy) was needed to reduce the carcinogenic N-nitrosamine and nitrite levels in pork sausage during storage. [source] Effect of naringin on bone cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2006R.W.K. Wong Abstract Statin, a HMG-CoA reductase inhibitor, was shown to increase BMP-2 gene expression for bone formation, by blocking the mevalonate pathway in cholesterol production. We investigated the effect of naringin, a flavonoid available commonly in citrus fruits, which was also a HMG-CoA reductase inhibitor, in UMR 106 osteoblastic cell line in vitro. The control group consisted of cells cultured without any intervention for different time intervals (24 h, 48 h, and 72 h), whereas the experimental (naringin) group consisted of cells cultured with naringin of different concentrations (0.001 µmol/L, 0.01 µmol/L, and 0.1 µmol/L) for the same time intervals of the control. Colorimetric Tetrazolium (MTT) assay, total protein content assay, and alkaline phosphatase activity were used to measure the cellular activities. Results for the naringin group showed an increase in MTT assay compared with the control and the effect was dose dependent. At high concentration (0.1 µmol), the increases ranged from 60% to 80%. In the total protein content assay, naringin also showed an increase compared with control and the effect was also dose dependent. At high concentration (0.1 µmol), the increases ranged from 9% to 20%. In the alkaline phosphatase activity assay, naringin at high concentration (0.1 µmol) significantly increased the activity up to 20%. In conclusion, naringin significantly increased bone cell activities in vitro. This is the first study specifically attempted to investigate the effect of naringin on bone cell activities. Besides statin, this provided another example of mevalonate pathway blockage in the cholesterol production pathway by HMG-CoA reductase inhibition will increase the bone cell activities. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:2045,2050, 2006 [source] Effects of a Novel Cognition-Enhancing Agent on Fetal Ethanol-Induced Learning DeficitsALCOHOLISM, Issue 10 2010Daniel D. Savage Background:, Drinking during pregnancy has been associated with learning disabilities in affected offspring. At present, there are no clinically effective pharmacotherapeutic interventions for these learning deficits. Here, we examined the effects of ABT-239, a histamine H3 receptor antagonist, on fetal ethanol-induced fear conditioning and spatial memory deficits. Methods and Results:, Long-Evans rat dams stably consumed a mean of 2.82 g ethanol/kg during a 4-hour period each day during pregnancy. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, litter size and birth weights were not different between the ethanol-consuming and control groups. Female adult offspring from the control and fetal alcohol-exposed (FAE) groups received saline or 1 mg ABT-239/kg 30 minutes prior to fear conditioning training. Three days later, freezing time to the context was significantly reduced in saline-treated FAE rats compared to control. Freezing time in ABT-239-treated FAE rats was not different than that in controls. In the spatial navigation study, adult male offspring received a single injection of saline or ABT-239 30 minutes prior to 12 training trials on a fixed platform version of the Morris Water Task. All rats reached the same performance asymptote on Trials 9 to 12 on Day 1. However, 4 days later, first-trial retention of platform location was significantly worse in the saline-treated FAE rats compared control offspring. Retention by ABT-239-treated FAE rats was similar to that by controls. ABT-239's effect on spatial memory retention in FAE rats was dose dependent. Conclusions:, These results suggest that ABT-239 administered prior to training can improve retention of acquired information by FAE offspring on more challenging versions of hippocampal-sensitive learning tasks. Further, the differential effects of ABT-239 in FAE offspring compared to controls raises questions about the impact of fetal ethanol exposure on histaminergic neurotransmission in affected offspring. [source] Phycocyanin liposomes for topical anti-inflammatory activity: in-vitro in-vivo studiesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2009Maria Manconia Abstract Objectives The aim of this work was to investigate the anti-inflammatory activity of C-phycocyanin (C-PC) on skin inflammation after topical administration and the influence of liposomal delivery on its pharmacokinetic properties. Methods Liposomes of different size and structure were prepared with different techniques using soy phosphatidylcholine and cholesterol. Vesicular dispersions were characterised by transmission electron microscopy, optical and fluorescence microscopy for vesicle formation and morphology, dynamic laser light scattering for size distribution, and Zetasizer for zeta-potential. C-PC skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either free or liposomal drug dispersed in a Carbopol gel. Key findings The protein was mainly localised in the stratum corneum, while no permeation of C-PC through the whole skin thickness was detected. Two percent C-PC-encapsulating liposomes showed the best drug accumulation in the stratum corneum and the whole skin, higher than that of the corresponding free 2% C-PC gel. Moreover, skin deposition of liposomal C-PC was dose dependent since skin accumulation values increased as the C-PC concentration in liposomes increased. The topical anti-inflammatory activity of samples was evaluated in vivo as inhibition of croton oil-induced or arachidonic acid-induced ear oedema in rats. Conclusions The results showed that C-PC can be successfully used as an anti-inflammatory drug and that liposomal encapsulation is effective in improving its anti-inflammatory activity. [source] Alcohol-Induced Endothelial Changes Are Associated With Oxidative Stress and Are Rapidly Reversed After WithdrawalALCOHOLISM, Issue 10 2005Giorgio Soardo Abstract: Background: Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress Methods: We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure Results: Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium Conclusions: Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage. [source] Differential localization of carbachol- and bicuculline-sensitive pontine sites for eliciting REM sleep-like effects in anesthetized ratsJOURNAL OF SLEEP RESEARCH, Issue 1 2009VICTOR B. FENIK Summary Carbachol, a cholinergic agonist, and GABAA receptor antagonists injected into the pontine dorsomedial reticular formation can trigger rapid eye movement (REM) sleep-like state. Data suggest that GABAergic and cholinergic effects interact to produce this effect but the sites where this occurs have not been delineated. In urethane-anesthetized rats, in which carbachol effectively elicits REM sleep-like episodes (REMSLE), we tested the ability of 10 nL microinjections of carbachol (10 mm) and bicuculline (0.5 or 2 mm) to elicit REMSLE at 47 sites located within the dorsal pontine reticular formation at the levels -8.00 to -10.80 from bregma (B) (Paxinos and Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, San Diego, 1997). At rostral levels, most carbachol and some bicuculline injections elicited REMSLE with latencies that gradually decreased from 242 to 12 s for carbachol and from 908 to 38 s for bicuculline for more caudal injection sites. As the latencies decreased, the durations of bicuculline-elicited REMSLE increased from 104 s to over 38 min, and the effect was dose dependent, whereas the duration of carbachol-elicited REMSLE changed little (104,354 s). Plots of REMSLE latency versus the antero-posterior coordinates revealed that both drugs were maximally effective near B-8.80. At levels caudal to B-8.80, carbachol was effective at few sites, whereas bicuculline-elicited REMSLE to at least B-9.30 level. Thus, the bicuculline-sensitive sites extended further caudally than those for carbachol and antagonism of GABAA receptors both triggered REMSLE and controlled their duration, whereas carbachol effects on REMSLE duration were small or limited by its concurrent REMSLE-opposing actions. [source] The effects of vasoactive agents, platelet agonists and anticoagulation on thrombelastographyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2007J. Kawasaki Background:, Platelet activation is a critical step in primary hemostasis and clot formation. We tested a hypothesis that platelet stimulating effects of vasoactive agents or platelet agonists could be shown using thrombelastography (TEG®) as faster onset or increased clot strength. We further examined if TEG® could be modified to evaluate activated platelets as a reversal of anticoagulation in the presence of partial thrombin inhibition. Methods:, Blood samples were obtained from 126 non-cardiac surgical patients. Effects of vasoactive agents on TEG® and aggregometry were examined using epinephrine, norepinephrine, vasopressin, desmopressin acetate, milrinone and olprinone (Experiment I). Platelet agonists (epinephrine, ADP and collagen) were separately tested on TEG® (Experiment II). Effects of platelet agonists (ADP and collagen) on TEG® under anticoagulation in the absence or presence of abciximab were studied (Experiment III). We also tested antiplatelet effects of milrinone and olprinone in the presence of anticoagulants on TEG® (Experiment IV). Results:, Neither vasoactive agents nor platelet agonists affected TEG® or aggregometry results except for milrinone and olprinone on aggregometry (Experiment I, II). Platelet agonists facilitated clotting in the presence of anticoagulants (Experiment III). Abciximab-treated platelets still exhibited procoagulant effects in the presence of heparin, while not in the presence of argatroban (Experiment III). Platelet inhibition on the modified TEG® was more extensive with milrinone than olprinone, and it was dose dependent (Experiment IV). Conclusion:, Modified TEG® using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist. [source] Comparison of relaxation responses to multiple vasodilators in TxA2 -analog and endothelin-1-precontracted pulmonary arteriesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2007C. Piamsomboon Background:, Peri-operative pulmonary hypertension can lead to right ventricular dysfunction and to an increase in morbidity and mortality. Altered function of the pulmonary vascular endothelium and vasoconstriction play a crucial role in the development of elevated pulmonary vascular resistance. Because pulmonary artery vasoreactivity is dependent on many factors including the constricting agent that precipitated the event therefore the aim of the current study was to investigate the effectiveness of different classes of vasodilator agents to reverse endothelin-1 (ET-1) or thromboxane A2 (TxA2)-induced vasoconstriction in porcine pulmonary artery (PA) in vitro. Methods:, Relaxation responses to vasodilatory drugs were studied in PA precontracted with ET-1 (1 × 10,8 M) or TxA2 analog (U46619, 1 × 10,8 M). All vasodilating drugs were added in a cumulative fashion and isometric tension measurements were obtained using an organ chamber technique. Results:, In both groups relaxation responses to the vasodilators were dose dependent. When ET-1 was used as a constrictor nitroglycerin and milrinone caused nearly complete (80,100%) relaxation, whereas other agents were of limited effectiveness (40,50%). On the other hand, in the vessels constricted with U46619, olprinone, indomethacin, prostaglandin E1 (PGE1), nitroglycerin, milrinone and clevidipine induced complete (90,110%) vasodilatation but brain natriuretic peptide (BNP), l -arginine, and isoproterenol relaxed the vessels maximally by 45,60%. Conclusions:, Nitroglycerin and milrinone are very effective in reversing ET-1 and U46619-induced pulmonary vasoconstriction in vitro. The effectiveness of other drugs studied was dependent on the type of constrictor used. BNP, l -arginine and isoproterenol were shown to have minimal vasodilatory effects in porcine PA. [source] | ||||||||||||||||||||||||||||||||||