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Reversible Increase (reversible + increase)
Selected AbstractsHigh extracellular [Mg2+]-induced increase in intracellular [Mg2+] and decrease in intracellular [Na+] are associated with activation of p38 MAP kinase and ERK2 in guinea-pig heartEXPERIMENTAL PHYSIOLOGY, Issue 12 2008Shang-Jin Kim High extracellular Mg2+ concentrations ([Mg2+]o) caused a remarkable concentration-dependent and reversible increase in intracellular Mg2+ concentrations ([Mg2+]i) in beating and quiescent guinea-pig papillary muscles, accompanied by a definite decrease in intracellular Na+ concentrations ([Na+]i). A change in 1 mm[Mg2+]o evoked a direct change in 0.0161 mm[Mg2+]i and an inverse change in 0.0263 mm[Na+]i. Imipramine completely abolished the high [Mg2+]o -induced decrease in [Na+]i and remarkably diminished the high [Mg2+]o -induced increase in [Mg2+]i in papillary muscles. High [Mg2+]o also produced a significant activation of p38 mitogen-activated protein (MAP) kinase and extracellular signal-related kinase 2 (ERK2) that was inhibited by pretreatment with imipramine. These results suggest that the high [Mg2+]o -induced increase in [Mg2+]i could be coupled with the decrease in [Na+]i, which might involve activation of the reverse mode of Na+,Mg2+ exchange, accompanied by activation of p38 MAP kinase and ERK2 in the guinea-pig heart. [source] Effect of Helicobacter pylori Infection on Gastric Acid Secretion and Meal-Stimulated Serum Gastrin in ChildrenHELICOBACTER, Issue 2 2004Seiichi Kato ABSTRACT Background., Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods., Thirty-six children aged 10,17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2,3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. Results.,H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori- positive patients with duodenal ulcer than in gastritis-only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori- positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre- and post- H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions.,H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection. [source] Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2010Taofeek K. Owonikoko Abstract We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 hr of continuous drug exposure. Vorinostat (1 ,M) inhibited growth by: 17% ± 7% in A549, 28% ± 6% in 128-88T, 39% ± 8% in Calu1 and 41% ± 7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 ,M) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was control 100%; 1 ,M vorinostat, 83% ± 10%; 5 ,M carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat, 46% ± 21%. In A549 and 128-88T, vorinostat potentiated carboplatin induction of gamma-H2AX (a DNA damage marker) and increased ,-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in ,-tubulin acetylation, which reversed upon drug washout. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel. [source] Bi-directional modulation of fast inhibitory synaptic transmission by leptinJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Natasha Solovyova Abstract The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly influences hippocampal excitatory synaptic transmission and synaptic plasticity. However, the effects of leptin on fast inhibitory synaptic transmission in the hippocampus have not been evaluated. Here, we show that leptin modulates GABAA receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells. Leptin promotes a rapid and reversible increase in the amplitude of evoked GABAA receptor-mediated inhibitory synaptic currents (IPSCs); an effect that was paralleled by increases in the frequency and amplitude of miniature IPSCs, but with no change in paired pulse ratio or coefficient of variation, suggesting a post-synaptic expression mechanism. Following washout of leptin, a persistent depression (inhibitory long-lasting depression) of evoked IPSCs was observed. Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI 3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast, blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to induce inhibitory long-lasting depression, suggesting that this process is independent of PI 3-kinase/Akt. In conclusion these data indicate that the hormone leptin bi-directionally modulates GABAA receptor-mediated synaptic transmission in the hippocampus. These findings have important implications for the role of this hormone in regulating hippocampal pyramidal neuron excitability. [source] Angiotensin II promotes the phosphorylation of cyclic AMP-responsive element binding protein (CREB) at Ser133 through an ERK1/2-dependent mechanismJOURNAL OF NEUROCHEMISTRY, Issue 6 2001Martín Cammarota In cells from the adrenal medulla, angiotensin II (AII) regulates both the activity and mRNA levels of catecholamine biosynthetic enzymes whose expression is thought to be under the control of cAMP-responsive element (CRE) binding protein (CREB). In this study, we evaluated the effect of AII stimulation on CREB phosphorylation at Ser133 (pCREB) in bovine adrenal chromaffin cells (BACC). We found that AII produces a rapid and AII type-1 receptor (AT1)-dependent increase in pCREB levels, which is blocked by the MEK1/2 inhibitor U0126 but not by H-89, SB203580 or KN-93, suggesting that it is mediated by the extracellular-regulated protein kinases 1 and 2 (ERK1/2) and not by cAMP-dependent protein kinase (PKA), p38 mitogen-activated protein kinase (p38MAPK) or Ca2+/calmodulin-dependent protein kinases (CaMKs) dependent pathways. Gel-shift experiments showed that the increase in pCREB levels is accompanied by an ERK1/2-dependent upregulation of CRE-binding activity. We also found that AII promotes a rapid and reversible increase in the activity of the non-receptor tyrosine kinase Src and that the inhibition of this enzyme completely blocks the AII-induced phosphorylation of ERK1/2, the CREB kinase p90RSK and CREB. Our data support the hypothesis that in BACC, AII upregulates CREB functionality through a mechanism that requires Src-mediated activation of ERK 1/2 and p90RSK. [source] Presynaptic Noradrenergic Regulation of Glutamate Inputs to Hypothalamic Magnocellular NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2003C. Boudaba Abstract Glutamate and norepinephrine transmitter systems play critical roles in the synaptic control of hypothalamic magnocellular neurones. We recently reported on a norepinephrine-sensitive glutamate circuit within the paraventricular nucleus (PVN) that projects to magnocellular neurones. Here, we present evidence for norepinephrine regulation of glutamate release in the PVN and supraoptic nucleus (SON) via actions on presynaptic terminals. Whole-cell synaptic currents were recorded in magnocellular neurones of the SON and PVN in an acute slice preparation. Bath application of norepinephrine (100 µm) caused a robust, reversible increase in the frequency of spontaneous glutamatergic excitatory postsynaptic currents in 100% of SON neurones (246%) and in 88% of PVN magnocellular neurones (259%). The norepinephrine-induced increase in glutamate release was mediated by activation of both presynaptic ,1 receptors and ,2 receptors, but the ,1 -receptor component was the predominant component of the response. The presynaptic actions of norepinephrine were predominantly, although not completely, resistant to blockade of Na-dependent spikes, implicating a presynaptic terminal locus of action. Interestingly, the spike-dependent component of the response was greater in PVN than in SON magnocellular neurones. This robust presynaptic facilitation of glutamate release by norepinephrine, combined with the known excitatory postsynaptic actions of norepinephrine, activational effects on local glutamate circuits, and inhibitory effects on ,-aminobutyric acid release, indicate a strong excitatory role of norepinephrine in the regulation of oxytocin and vasopressin release during physiological stimulation. [source] Changes in gingival crevicular fluid inflammatory mediator levels during the induction and resolution of experimental gingivitis in humansJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2010Steven Offenbacher Offenbacher S, Barros S, Mendoza L, Mauriello S, Preisser J, Moss K, de Jager M, Aspiras M. Changes in gingival crevicular fluid inflammatory mediator levels during the induction and resolution of experimental gingivitis in humans. J Clin Periodontol 2010; 37: 324,333. doi: 10.1111/j.1600-051X.2010.01543.x Abstract Aim: The goal of this study is to characterize the changes in 33 biomarkers within the gingival crevicular fluid during the 3-week induction and 4-week resolution of stent-induced, biofilm overgrowth mediated, experimental gingivitis in humans. Methods: Experimental gingivitis was induced in 25 subjects for 21 days followed by treatment with a sonic powered toothbrush for 28 days. Clinical indices and gingival crevicular fluids were collected weekly during induction and biweekly during resolution. Samples were analysed using a bead-based multiplexing analysis for the simultaneous measurements of 33 biomarkers within each sample including cytokines, matrix-metalloproteinases (MMPs) and adipokines. Prostaglandin-E2 was measured by enzyme-linked immunoadsorbant assay. Statistical testing using general linear models with structured covariance matrices were performed to compare stent to contralateral (non-stent) changes in clinical signs and in biomarker levels over time. Results: Gingivitis induction was associated with a significant 2.6-fold increase in interleukin 1- , (IL- ,), a 3.1-fold increase in IL-1, and a significant decrease in multiple chemokines as well as MMPs-1, -3 and 13. All changes in clinical signs and mediators rebounded to baseline in response to treatment in the resolution phase. Conclusions: Stent-induced gingivitis is associated with marked, but reversible increases in IL- ,a and IL-1, with suppression of multiple chemokines as well as selected MMPs. [source] | |||||||||||||