795 research outputs found
Loss-of-function polymorphisms in the organic cation transporter OCT1 are associated with reduced postoperative tramadol consumption.
The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+)O-desmethyltramadol in the liver. In this study, the influence of OCT1 genetic polymorphisms on pharmacokinetics and analgesic efficacy of tramadol in patients recovering from surgery was analyzed in addition to the CYP2D6 genotype. Postoperative patients who received tramadol through patient-controlled analgesia were enrolled. Genotypes resulting in 0, 1, or 2 active OCT1 alleles were determined as well as CYP2D6 genotypes. The primary endpoint was the 24-hour postoperative tramadol consumption in patients with 0 vs at least 1 active OCT1 allele. Secondary endpoint was the OCT1-dependent plasma concentration (areas under the concentration-time curves) of the active tramadol metabolite (+)O-desmethyltramadol. Of 205 patients, 19, 82, and 104 carried 0, 1, and 2 active OCT1 alleles, respectively. Cumulative tramadol consumption through patient-controlled analgesia was lowest in patients with 0 active OCT1 allele compared with the group of patients with 1 or 2 active alleles (343 ± 235 vs 484 ± 276 mg; P = 0.03). Multiple regression revealed that the number of active OCT1 alleles (P = 0.014), CYP2D6 (P = 0.001), pain scores (P < 0.001), and the extent of surgery (0.034) had a significant influence on tramadol consumption. Plasma areas under the concentration-time curves of (+)O-desmethyltramadol were 111.8 (95% confidence interval: 63.4-160.1), 80.2 (65.1-95.3), and 64.5 (51.9-77.2) h·ng·mL in carriers of 0, 1, or 2 active OCT1 alleles (P = 0.03). Loss of OCT1 function resulted in reduced tramadol consumption and increased plasma concentrations of (+)O-desmethyltramadol in patients recovering from surgery. Therefore, analyzing OCT1 next to CYP2D6 genotype might further improve future genotype-dependent dose recommendations for tramadol
Current practice of acute pain management in children - a national follow-up survey in Germany
OBJECTIVES
This study aimed to summarize the current standard practices for acute pain management in children in Germany and the implementation of these procedures. The last survey on acute pain management in children was performed in 1999, highlighting the need for an up to date review.
METHODS
A questionnaire was mailed to German departments of anesthesiology (n = 885), asking for structures and processes of acute pain management in children. Results were compared between hospitals with and without an acute pain service and with and without a pediatric department.
RESULTS
Of the 407 responding hospitals (response rate of 46%), 342 treated children younger than 14 years. These were considered for analysis. Of the 342 hospitals, 42% contained either a general pediatric department or a department of pediatric surgery, and the majority of the responding hospitals had an acute pain service (83%). Pain intensities were measured at least once per shift in 40% of the institutions, and at least once or twice a day in 27%. Of the institutions, 31% did not document pain scores regularly, without any difference between hospitals with or without a pediatric department. Standard operating procedures for acute pain management existed in 68% of the hospitals, with large differences in content and length. Opioids were administered to children in 85% of the hospitals. Nonopioid analgesics were the first choice baseline analgesics in most hospitals. Peripheral regional and epidural analgesia were performed in children in 18% and 8% of the hospitals, respectively (21%/16% with a paediatric department, 16%/1% without; P < 0.001).
CONCLUSION
Current practice of pediatric pain management varied widely and the recommendations of guidelines, like regular pain management, were frequently not met. However, improvements could be observed since 1999, for example, an increase in regular pain measurements (4% vs 67%). Furthermore, pain management in hospitals running a pediatric department had a higher degree of organization, and more sophisticated analgesic techniques
Ein simpler Prädiktor für postoperative Schmerzen?
Eine Studie aus Schweden hat untersucht, ob Schmerzen im Zusammenhang mit einer venösen Kanülierung sowie Propofol-Injektion als Prädiktoren für postoperativen Schmerz geeignet sind
A Validated Reversed-Phase HPLC Method for the Determination of Atorvastatin Calcium in Tablets
A Reversed-Phase Liquid Chromatographic (RP-LC) assay method was developed for the quantitative determination of atorvastatin calcium in the presence of its degradation products. The assay involved an isocratic elution of atorvastatin calcium in a LiChroCARTR 250*4 mm HPLC Cartridge LiChrospherR 100 RP-18 (5 μm) column using a mobile phase consisting of 0.1% acetic acid solution: acetonitrile (45:55, v/v), pH = 3.8. The flow rate was 0.8 mL/min and the analytes monitored at 246 nm. The assay method was found to be linear from 8.13 to 23.77 μg/mL. All the validation parameters were within the acceptance range. The developed method was successfully applied to estimate the amount of atorvastatin calcium in tablets.Fil: Simionato, Laura Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Ferello, L.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Stamer. S.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Repetto, M. F.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Zubata, P. D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin
Automatic detection of lameness in gestating group-housed sows using positioning and acceleration measurements
Lameness is an important issue in group-housed sows. Automatic detection systems are a beneficial diagnostic tool to support management. The aim of the present study was to evaluate data of a positioning system including acceleration measurements to detect lameness in group-housed sows. Data were acquired at the Futterkamp research farm from May 2012 until April 2013. In the gestation unit, 212 group-housed sows were equipped with an ear sensor to sample position and acceleration per sow and second. Three activity indices were calculated per sow and day: path length walked by a sow during the day (Path), number of squares (25×25 cm) visited during the day (Square) and variance of the acceleration measurement during the day (Acc). In addition, data on lameness treatments of the sows and a weekly lameness score were used as reference systems. To determine the influence of a lameness event, all indices were analysed in a linear random regression model. Test day, parity class and day before treatment had a significant influence on all activity indices (P<0.05). In healthy sows, indices Path and Square increased with increasing parity, whereas variance slightly decreased. The indices Path and Square showed a decreasing trend in a 14-day period before a lameness treatment and to a smaller extent before a lameness score of 2 (severe lameness). For the index acceleration, there was no obvious difference between the lame and non-lame periods. In conclusion, positioning and acceleration measurements with ear sensors can be used to describe the activity pattern of sows. However, improvements in sampling rate and analysis techniques should be made for a practical application as an automatic lameness detection system
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Acute Regulation of P-glycoprotein at the Blood-Brain Barrier by Peripheral Inflammatory Pain
P-glycoprotein (Pgp; ABCB1) is a well known transporter involved in energy-dependent-drug efflux activity. At the brain capillary endothelium, its luminal membrane location is ideal for its ascribed role in the physiological efflux of a wide array of structurally and functionally diverse compounds from the brain. This is a critical issue in regards to the delivery of central nervous system (CNS)-acting therapeutics. Moreover, a dysregulation of Pgp has been implicated in specific CNS disease states, including Alzheimer's disease, epilepsy, and brain cancer where an upregulation of Pgp has been well established as a mediator of multi-drug resistance. Inflammation is a common component in all of these conditions. Previously our laboratory has reported changes in BBB molecular and functional properties during inflammatory pain (Huber et al. 2001). This has led us to investigate the effects of peripheral inflammatory pain on Pgp efflux transport properties at the BBB, in vivo. In the present study we examined the effects of lambda-carrageenan-induced inflammatory pain (i.e. hyperalgesia; CIP) on the molecular and functional properties of Pgp at the BBB. Western blots using enriched fractions of isolated rat brain microvessels revealed that Pgp expression at the BBB was increased by CIP and that this increase occurred predominantly within the membrane region of the cell. Additionally, both in situ brain perfusions and whole body antinociceptive profiling of the Pgp substrate and opioid analgesic, [3H] morphine, indicate that changes in Pgp at the BBB, mediated by peripheral inflammation, can impact brain uptake of morphine. To further elucidate the mechanism(s) behind the rapid upregulation (3 h) of Pgp at this region, we explored regulation of Pgp at the plasma membrane. Our findings show that CIP induces a movement of Pgp within these domains and that Pgp co-localizes with caveolin-1 and clathrin, key structural proteins associated with caveolae and clathrin-pit lipid rafts, respectively. Our data indicate for the first time that peripheral inflammatory pain induces functional and molecular changes in Pgp, a critical efflux transporter, at the BBB in vivo and that these alterations may be mediated in part via a proteolipidic re-organization mechanism
Water Quality in the Central Nebraska Basins, Nebraska, 1992-95
Frenzel, S.A., Swanson, R.B., Huntzinger, T.L., Stamer, J.K., Emmons, P.J., and Zelt, R.B., 1998, Water Quality in the Central Nebraska Basins, Nebraska, 1992-95: U.S. Geological Survey Circular 1163; National Water-Quality Assessment Program Summary of major issues and findings Environmental setting and hydrologic conditions Major issues and findings Nitrate content in water is related to agricultural land management Agricultural activities potentially affect the management of publicwater supplies Water quality in the Platte River alluvial aquifer may be affected by surface-water quality in areas of ground-water withdrawals Aquatic environments potentially are altered by human activities Aquatic and migratory species are affected directly by changes in the physical characteristics of the Platte River Water-quality conditions in a national context Stream quality Ground-water quality Study design and data collection Summary of compound detections and concentra
Strengthening SMEs to make export competitive
The importance of SMEs in any economy cannot be overlooked as they form a major chunk in the economic activity of nations. India has nearly three million SMEs, which account for almost 50 per cent of industrial output. However, SMEs which form the backbone of industrial development in India are not export competitive and contribute only about 34 percent of exports. It is this feature of the SMEs that make it an ideal target to realize its potential export competitive. Drawing from the experiences of countries that have successfully promoted the export competitiveness of SMEs, this paper has identified ways in which SMEs in India can have an access to external markets through exports, which include simplification of procedures, incentives for higher production, preferential treatments to SMEs in the market development fund, linking up SMEs with Transnational Companies or large domestic exporting firms; and formation of clusters and networks in order to reinforce their external competitiveness.Small and Medium Enterprises (SMEs), SWOT Analysis, Export, India
Cell Senescence Reduced the Mechanotransduction Sensitivity of Porcine Angular Aqueous Plexus Cells to Elevation of Pressure
Citation: Lei Y, Stamer WD, Wu J, Sun X. Cell senescence reduced the mechanotransduction sensitivity of porcine angular aqueous plexus cells to elevation of pressure. Invest Ophthalmol Vis Sci. 2014;55:232455: -232855: . DOI:10.1167 PURPOSE. To investigate the effect of pressure/flow on the barrier function and protein expression of normal and senescent porcine aqueous humor plexus (AAP) cells, which are the porcine equivalent of human Schlemm's canal endothelial cells. METHODS. AAP cells were grown for 2 weeks in physiological (5% O 2 ) or hyperoxic conditions (40% O 2 ) to model cell senescence. Control and senescent AAP cells were subjected to control and elevated hydrostatic pressure gradient of 10 mm Hg for 72 hours. Hydraulic conductivity (HC) and transendothelial electric resistance (TEER) were measured. The expressions of senescence-associated b-galactosidase and DNA damage marker 8-hydroxy-2 0 -deoxyguanosine (8-OHdG) were monitored, and the protein expression profile was analyzed by Western blot. RESULTS. After 14 days of hyperoxia, AAP cells stained positive for 8-OHdG and b-galactosidase. Pressure elevation/flow resulted in significant increase of HC in control cells (from 1.37 6 0.12 to 1.64 6 0.18 lL/mm Hg/min/cm 2 , P < 0.05), but not in senescent cells (1.15 6 0.17 and 1.08 6 0.10 lL lL/mm Hg/min/cm 2 ). TEER changes were consistent with the HC results. Western blot analysis showed that the expression level of myosin light chain, claudin-5, and VE-cadherin significantly reduced under pressure elevation in control cells but not in senescent cells. CONCLUSIONS. AAP cells are mechano-sensitive; however, cell senescence rendered the cells less responsive to mechanical stimulus, which may have pathological consequences
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