Dose-dependent Response (dose-dependent + response)

Distribution by Scientific Domains


Selected Abstracts


In vitro effects of lidocaine on the contractility of equine jejunal smooth muscle challenged by ischaemia-reperfusion injury

EQUINE VETERINARY JOURNAL, Issue 1 2010
M. GUSCHLBAUER
Summary Reasons for performing study: Post operative ileus (POI) in horses is a severe complication after colic surgery. A commonly used prokinetic drug is lidocaine, which has been shown to have stimulatory effects on intestinal motility. The cellular mechanisms through which lidocaine affects smooth muscle activity are not yet known. Objectives: To examine the effects of lidocaine on smooth muscle in vitro and identify mechanisms by which it may affect the contractility of intestinal smooth muscle. Hypothesis: Ischaemia and reperfusion associated with intestinal strangulation can cause smooth muscle injury. Consequently, muscle cell functionality and contractile performance is decreased. Lidocaine can improve basic cell functions and thereby muscle cell contractility especially in ischaemia-reperfusion-challenged smooth muscle. Methods: To examine the effects of lidocaine on smooth muscle function directly, isometric force performance was measured in vitro in noninjured and in vivo ischaemia-reperfusion injured smooth muscle tissues. Dose-dependent response of lidocaine was measured in both samples. To assess membrane permeability as a marker of basic cell function, release of creatine kinase (CK) was measured by in vitro incubations. Results: Lidocaine-stimulated contractility of ischaemia-reperfusion injured smooth muscle was more pronounced than that of noninjured smooth muscle. A 3-phasic dose-dependency was observed with an initial recovery of contractility especially in ischaemia-reperfusion injured smooth muscle followed by a plateau phase where contractility was maintained over a broad concentration range. CK release was decreased by lidocaine. Conclusion: Lidocaine may improve smooth muscle contractility and basic cell function by cellular repair mechanisms which are still unknown. Improving contractility of smooth muscle after ischaemia-reperfusion injury is essential in recovery of propulsive intestinal motility. Potential relevance: Characterisation of the cellular mechanisms of effects of lidocaine, especially on ischaemia-reperfusion injured smooth muscle, may lead to improved treatment strategies for horses with POI. [source]


Multiple profiling of soil microbial communities identifies potential genetic markers of metal-enriched sewage sludge

FEMS MICROBIOLOGY ECOLOGY, Issue 3 2008
Catriona 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]


Attenuated apoptosis response to Fas-ligand in active ulcerative colitis

INFLAMMATORY BOWEL DISEASES, Issue 12 2008
Jakob B. Seidelin MD
Abstract Background: From mainly carcinoma cell line studies, apoptosis has been thought to play a major role in the pathogenesis of ulcerative colitis (UC). Apoptosis has been suggested to be due to a Fas ligand / Fas receptor interaction, but has never been studied in cells from patients with active UC. The aim was to investigate both the spontaneous and the cell death receptor ligand-induced apoptosis in UC. Methods: Twenty patients with UC and 16 control subjects who underwent routine colonoscopy either for the control or surveillance of their disease or where the diagnosis of irritable bowel syndrome was subsequently reached were included. Cultures of isolated colonic crypts were obtained from biopsies and cultured for 4 to 16 hours with Fas ligand or Fas ligand and costimulation with interferon-, (IFN-,). Control experiments were performed on HT29 cells. Apoptosis was assessed by independent methods. Results: Isolated colonocytes from healthy subjects or patients with remission in UC had a dose-dependent response to Fas ligand. This response was abolished in patients with active UC (P < 0.002), and costimulation with IFN-, did not alter this response. Patients with active UC had an increased apoptosis rate of 9.5% compared with controls (P < 0.05). Conclusions: The current study indicates that colonocytes do not respond to cytokine exposure and inflammation by an increased vulnerability, as previously thought. Colonocytes seem to activate cytoprotective programs in response to inflammation. Apart from supporting the regeneration process during inflammation, this response could additionally cause an increased susceptibility to neoplastic transformation. (Inflamm Bowel Dis 2008) [source]


Effects of lipopolysaccharide on platelet-derived growth factor isoform and receptor expression in cultured rat common bile duct fibroblasts and cholangiocytes

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2009
Tae-Hyeon Kim
Abstract Background and Aim:, Little is known about the role of platelet-derived growth factor (PDGF) in biliary fibrosis in the setting of bacterial colonization of the biliary tree. We therefore sought to investigate whether exposure to bacterial lipopolysaccharide (LPS) alters PDGF isoform and receptor expression in cultured rat common bile duct fibroblasts (CBDF) and normal rat cholangiocytes (NRC). Methods:, Collagen content in cells and media was assessed by colorimetric assay and gel electrophoresis. mRNA levels of PDGF-A and -B, and PDGF-Receptors (PDGF-R) , and , were measured by relative quantitative real-time PCR. Protein levels of PDGF-AA, AB and BB were measured by ELISA, and PDGF-R, and PDGF-R, by Western blot. Results:, In CBDF, LPS increased total soluble collagen synthesis and secretion. PDGF-R, and , mRNA and protein were also increased by LPS treatment in CBDF. Lipopolysaccharide treatment elicited an increase in PDGF-A and -B mRNA levels in CBDF. In NRC, levels of PDGF-A mRNA increased in a dose-dependent fashion following LPS treatment, whereas PDGF-B mRNA showed no response. PDGF-AA secretion was higher by CBDF than by NRC. PDGF-BB levels were also higher in CBDF than in NRC. While PDGF-BB levels did not respond to LPS treatment in CBDF, there was a dose-dependent response of this isoform to LPS in NRC. Intracellular and secreted PDGF-AB increased with LPS treatment in NRC. Conclusions:, These results support a model in which chronic bacterial colonization of the biliary tree induces fibrosis through PDGF-dependent mechanisms. [source]


Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo study

JOURNAL OF PERIODONTAL RESEARCH, Issue 6 2001
Francisco H. Nociti Jr
The present study investigated the effect of nicotine administration on periodontal breakdown resulting from ligature-induced periodontitis in rats. Twenty adult male Wistar rats were used. After anesthesia, a mandibular first molar was randomly assigned to receive a cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments, of daily intraperitoneal injections: A , saline solution, B , 0.37 mg of nicotine/kg, C , 0.57 mg of nicotine/kg and D , 0.73 mg of nicotine/kg. Thirty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Statistical analysis (ANOVA) revealed greater bone loss (p<0.05) in the ligated teeth of animals which received nicotine (groups B/C/D) than in the ligated teeth of animals which received saline solution (group A). In addition, a dose-dependent response was observed among the nicotine groups. A negative effect of nicotine was observed in the unligated teeth of the experimental groups (p<0.05). Therefore, daily administration of nicotine enhanced, in a dose-dependent manner, the effects of local factors in producing periodontal breakdown. Furthermore, the nicotine seemed to have a direct deleterious effect on the periodontal tissues. [source]


Effects of repeated low-dose UVB irradiation on the hyphal growth of Candida albicans

MYCOSES, Issue 1 2006
J. Brasch
Summary Ultraviolet B light (UVB) can have negative phototropic effects on fungi. Candida albicans is often found on human skin exposed to UVB. Therefore, it is of medical interest to know whether a negative phototropic response to UVB irradiation can support an invasive growth of this potentially dangerous agent. In our study we investigated how repeated irradiation with low doses of UVB can influence the hyphal growth of C. albicans. Six randomly chosen strains of C. albicans were tested. Formation of hyphae was induced and maintained within transparent agar plates. The fungi were exposed to UVB three times daily for 7 days from either the obverse or the reverse side during incubation. The wavelength spectrum was in the range of 310,315 nm, single doses were between 0.0018 and 0.432 J cm,2. After 7 days the morphology and growth direction of C. albicans cells were determined microscopically. All six strains showed a common and dose-dependent response to UVB irradiation: the progression of hyphal growth was inhibited, no phototropic effects were seen and as a new finding an increased formation of blastospores was observed. We conclude that an irradiation of human skin colonized by C. albicans with doses of UVB that can occur under natural or artificial conditions is unlikely to trigger skin invasion by C. albicans. [source]


The peptide hormone xenin induces gallbladder contractions in conscious dogs

NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2007
Y. Kamiyama
Abstract, Xenin is a 25-amino acid peptide isolated from human gastric mucosa. The biological activities of xenin include modulating intestinal motility and affecting exocrine pancreatic secretion and gastric acid secretion. The physiological effect of xenin on the gastrointestinal tract, however, is incomplete. The objective of this study is to investigate the effects of xenin on the gastrointestinal tract motility of conscious dogs. Gastrointestinal tract and gallbladder contractions were monitored by chronically implanted force transducers. Synthetic xenin was injected intravenously during the interdigestive state with or without pretreatment with cholinergic blockers. The effects of xenin following cholecystectomy and truncal vagotomy were also investigated. Xenin induced gallbladder and jejunal contractions, although a dose-dependent response was shown only with gallbladder contractions. These effects were inhibited by pretreatment with cholinergic blockers, but were not enhanced by truncal vagotomy. The jejunal contractions were completely inhibited by cholecystectomy. The only direct effect of xenin in terms of gastrointestinal motility was to induce gallbladder contractions in conscious dogs. The neural pathway mediating xenin's action was cholinergic, but not the vagal. This novel finding indicates a new role of xenin. [source]


Integrative functional genomics of salt acclimatization in the model legume Lotus japonicus

THE PLANT JOURNAL, Issue 6 2008
Diego H. Sanchez
Summary The model legume Lotus japonicus was subjected to non-lethal long-term salinity and profiled at the ionomic, transcriptomic and metabolomic levels. Two experimental designs with various stress doses were tested: a gradual step acclimatization and an initial acclimatization approach. Ionomic profiling by inductively coupled plasma/atomic emission spectrometry (ICP-AES) revealed salt stress-induced reductions in potassium, phosphorus, sulphur, zinc and molybdenum. Microarray profiling using the Lotus Genechip® allowed the identification of 912 probesets that were differentially expressed under the acclimatization regimes. Gas chromatography/mass spectrometry-based metabolite profiling identified 147 differentially accumulated soluble metabolites, indicating a change in metabolic phenotype upon salt acclimatization. Metabolic changes were characterized by a general increase in the steady-state levels of many amino acids, sugars and polyols, with a concurrent decrease in most organic acids. Transcript and metabolite changes exhibited a stress dose-dependent response within the range of NaCl concentrations used, although threshold and plateau behaviours were also observed. The combined observations suggest a successive and increasingly global requirement for the reprogramming of gene expression and metabolic pathways to maintain ionic and osmotic homeostasis. A simple qualitative model is proposed to explain the systems behaviour of plants during salt acclimatization. [source]


The role of auxin-binding protein 1 in the expansion of tobacco leaf cells

THE PLANT JOURNAL, Issue 6 2001
Jin-Gui Chen
Summary Tobacco leaf was used to investigate the mechanism of action of auxin-binding protein 1 (ABP1). The distributions of free auxin, ABP1, percentage of leaf nuclei in G2 and the amount of auxin-inducible growth were each determined in control tobacco leaves and leaves over-expressing Arabidopsis ABP1. These parameters were compared with growth of tobacco leaves, measured both spatially and temporally throughout the entire expansion phase. Within a defined window of leaf development, juvenile leaf cells that inducibly expressed Arabidopsis ABP1 prematurely advanced nuclei to the G2 phase. The ABP1-induced increase in cell expansion occured before the advance to the G2 phase, indicating that the ABP1-induced G2 phase advance is an indirect effect of cell expansion. The level of ABP1 was highest at the position of maximum cell expansion, maximum auxin-inducible growth and where the free auxin level was the lowest. In contrast, the position of maximum cell division correlated with higher auxin levels and lower ABP1 levels. Consistent with the correlations observed in leaves, tobacco cells (BY-2) in culture displayed two dose-dependent responses to auxin. At a low auxin concentration, cells expanded, while at a relatively higher concentration, cells divided and incorporated [3H]-thymidine. Antisense suppression of ABP1 in these cells dramatically reduced cell expansion with negligible effect on cell division. Taken together, the data suggest that ABP1 acts at a relatively low level of auxin to mediate cell expansion, whereas high auxin levels stimulate cell division via an unidentified receptor. [source]