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991.
Aditi Mulgaonkar Jürgen Venitz Dirk Gründemann Douglas H. Sweet 《Antimicrobial agents and chemotherapy》2013,57(6):2705-2711
Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in biological fluids, and thus, their disposition depends heavily on active transport and facilitative diffusion. A recent review of the clinical literature indicated that tubular secretion and reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug interactions. In particular, reported in vivo interactions between FQs and cationic drugs affecting renal clearance implicated organic cation transporters (OCTs). In this study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, rufloxacin, and sparfloxacin, were screened for their ability to inhibit transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1-mediated uptake under initial test conditions. None of the FQs inhibited hOCT2, and only moxifloxacin inhibited hOCT3 (∼30%), even at a 1,000-fold excess. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1. Inhibition constants (Ki) were estimated to be 250 ± 18 μM, 161 ± 19 μM, 136 ± 33 μM, and 94 ± 8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a Ki value of 1,598 ± 146 μM. Despite expression in enterocytes (luminal), hepatocytes (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal membrane of hepatocytes, and potentially the basolateral membrane of proximal tubule cells, is likely to play a role in the disposition of these antimicrobial agents. 相似文献
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Participation of family members and quality of patient care – the perspective of adult surgical patients 下载免费PDF全文
997.
Katia Ferrar Tim Olds Carol Maher Ralph Maddison 《Australian and New Zealand journal of public health》2013,37(1):39-46
Objective : To describe New Zealand adolescent time use clusters and correlate cluster profiles. Methods : Data were from the cross‐sectional 2008/2009 National Survey of Children and Young People's Physical Activity and Dietary Behaviours, which surveyed a random sample of 10–16 year‐old New Zealanders (study subset n=679). Time use data were collected using the Multimedia Activity Recall for Children and Adults, and collapsed into 17 age‐adjusted variables for sex‐specific cluster analysis. Cluster associations with socio‐demographic, anthropometric, physical activity and dietary variables were analysed. Results : Three time use clusters were discovered for both boys and girls. For boys, the Techno‐active cluster was characterised by high levels of team sports and TV; the Quiet movers cluster by transport (active and passive) and quiet time; and the Social studious cluster by reading, study activities and social interaction. The boys’ clusters were associated with ethnicity. The girls’Social sporty cluster was characterised by sports and social interaction; the Screenie tasker cluster by TV, computer, chores and work; and the Super studious cluster by reading, study and school‐based activities. The girls’ time use cluster membership was associated with weight status and serves of extra foods. Conclusions : Distinct sex‐specific time use clusters and correlate profiles exist among NZ adolescents. Implications : These findings may assist the development of targeted time use interventions to improve adolescent health and well‐being. 相似文献
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N. H. Rod M. Grønbæk P. Schnohr E. Prescott T. S. Kristensen 《Journal of internal medicine》2009,266(5):467-475
Objective. The aim of this study was to evaluate the long‐term effects of stress on changes in health behaviour and cardiac risk profile in men and women. Design. A prospective cohort study. Setting. The Copenhagen City Heart Study, Denmark. Subjects. The analyses were based on 7066 women and men from the second (1981–1983) and third (1991–1993) wave of the Copenhagen City Heart Study. All participants were asked questions on stress and health behaviour and they had their weight, height, blood pressure and level of blood lipids measured by trained personnel. Main outcome measures. Changes in health behaviour (smoking, physical activity, alcohol consumption, overweight) and cardiac risk profile (cholesterol, HDL cholesterol, blood pressure, diabetes). Results. Individuals with high levels of stress compared to those with low levels of stress were less likely to quit smoking (OR = 0.58; 95% CI: 0.41–0.83), more likely to become physically inactive (1.90; 1.41–2.55), less likely to stop drinking above the sensible drinking limits (0.43; 0.24–0.79), and stressed women were more likely to become overweight (1.55; 1.12–2.15) during follow‐up. Men and women with high stress were more likely to use antihypertensive medication (1.94; 1.63–2.30), and stressed men were more than two times as likely to develop diabetes during follow‐up (2.36; 1.22–4.59). Conclusion. This longitudinal study supports a causal relation between stress and cardiovascular diseases mediated through unfavourable changes in health behaviour and cardiac risk profile. 相似文献
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Lars-Ove Brandenburg Ralph Lucius Azami Tameh Abolfazl Markus Kipp Christoph J. Wruck Thomas Koch Cordian Beyer Thomas Pufe 《Annals of anatomy》2009,191(5):459-468
Invasion of the nervous system and neuronal spread of infection are critical, but poorly understood steps in the pathogenesis of prion diseases. We have thus analyzed the internalization and signal transduction of the neurotoxic fragment of the prion protein PrP106–126 in the rat neuroblastoma cell line B104 by fluorescence microscopy and quantification by ELISA and in primary neuronal cells from mice. Phospholipase D (PLD) is known to be an enzyme involved in the regulation of secretion, endocytosis and receptor signalling. We determined the PLD activity using a transphosphatidylation assay and could show that PLD is involved in PrP106–126 internalization. The determination of receptor activity via quantification of ERK1/2 phosphorylation and cAMP level measurement verified the PrP106–126-induced signal transduction in B104 cells and primary neuronal cells. PrP106−126-induced a decrease in cAMP level in neuronal cells. These studies indicate the involvement of PLD in PrP106–126-endocytosis and mediated cellular signalling by an unidentified inhibitory G-protein-coupled receptor and may allow the development of therapeutic agents interfering with prion uptake and/or PLD function using PLD as a possible pharmaceutical target. 相似文献