67 research outputs found

    Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation

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    <p>Abstract</p> <p>Background</p> <p>Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.</p> <p>Methods</p> <p>Quadruplicate <it>ex vivo </it>human chorionic plate arterial rings were used in all studies. <b><it>Series 1 and 2 </it></b>examined the role of the K<sup>+ </sup>channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K<sup>+ </sup>(K<sub>Ca++</sub>) channels (<b><it>Series 1A+B</it></b>) or glibenclamide, which blocks the ATP sensitive K<sup>+ </sup>(K<sub>ATP</sub>) channel (<b><it>Series 2</it></b>), modulated sevoflurane-mediated vasodilation. <b><it>Series 3 – 5 </it></b>examined the role of the Ca<sup>++ </sup>channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca<sup>++ </sup>channel (<b><it>Series 3</it></b>), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca<sup>++ </sup>channels (<b><it>Series 4A+B</it></b>), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca<sup>++ </sup>channel (<b><it>Series 5A+B</it></b>), modulated sevoflurane-mediated vasodilation.</p> <p>Results</p> <p>Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the K<sub>Ca++ </sub>and K<sub>ATP </sub>channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K<sup>+ </sup>channels. Blockade of the voltage-operated Ca<sup>++</sup>channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca<sup>++</sup>channels did not alter sevoflurane vasodilation.</p> <p>Conclusion</p> <p>Sevoflurane appears to block chorionic arterial K<sub>Ca++ </sub>and K<sub>ATP </sub>channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the <it>in vitro </it>foeto-placental circulation.</p

    Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia

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    BACKGROUND: Yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. The disease is usually transmitted among wild rodents through a flea vector. The sources and routes of transmission of plague are poorly researched in Africa, yet remains a concern in several sub-Saharan countries. In Zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenance and propagation of the bacterium. In this study, we undertook plague surveillance by using PCR amplification of the plasminogen activator gene in fleas. FINDINGS: Xenopsylla species of fleas were collected from 83 rodents trapped in a plague endemic area of Zambia. Of these rodents 5 had fleas positive (6.02%) for Y. pestis plasminogen activator gene. All the Y. pestis positive rodents were gerbils. CONCLUSIONS: We conclude that fleas may be responsible in the transmission of Y. pestis and that PCR may provide means of plague surveillance in the endemic areas of Zambia

    Microplate assay for quantitation of neutral lipids in extracts from microalgae

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    Lipid quantitation is widespread in the algae literature, but popular methods such as gravimetry, gas chromatography and mass spectrometry (GC-MS), and Nile red cell staining suffer drawbacks, including poor quantitation of neutral lipids, expensive equipment, and variable results among algae species, respectively. A high-throughput microplate assay was developed that uses Nile red dye to quantify neutral lipids that have been extracted from algae cells. Because the algal extracts contained pigments that quenched Nile red fluorescence, a mild bleach solution was used to destroy pigments, resulting in a nearly linear response for lipid quantities in the range of 0.75 to 40 μg. Corn oil was used as a standard for quantitation, although other vegetable oils displayed a similar response. The assay was tested on lipids extracted from three species of Chlorella and resulted in close agreement with triacylglycerol (TAG) levels determined by thin layer chromatography. The assay was found to more accurately measure algal lipids conducive to biodiesel production and nutrition applications than the widely used gravimetric assay. Assay response was also consistent among different species, in contrast to Nile red cell staining procedures

    Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

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    <p>Abstract</p> <p>Background</p> <p>Hypertonic saline (HTS) reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury.</p> <p>Methods</p> <p>Adult male Sprague Dawley rats were used in all experiments. <b><it>Series 1 </it></b>examined the potential for HTS to reduce the severity of evolving oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12) or hypertonic saline (HTS, n = 12), and the extent of lung injury assessed after 6 hours. <b><it>Series 2 </it></b>examined the potential for HTS to enhance the resolution of oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6) or hypertonic saline (HTS, n = 6), and the extent of lung injury assessed after 6 hours.</p> <p>Results</p> <p>In <b><it>Series I</it></b>, HTS significantly reduced bronchoalveolar lavage (BAL) neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 10<sup>3</sup> cells.ml<sup>-1</sup>]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in <b><it>Series 2</it></b>, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 10<sup>3</sup> cells.ml<sup>-1</sup>], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml<sup>-1</sup>].</p> <p>Conclusion</p> <p>These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.</p

    Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

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    <p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan<sup>® </sup>manikin.</p> <p>Results</p> <p>The Airtraq<sup>® </sup>reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview<sup>® </sup>increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq<sup>® </sup>devices.</p> <p>Conclusion</p> <p>The Airtraq<sup>® </sup>laryngoscope performed more favourably than the Macintosh and Truview<sup>® </sup>devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

    Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

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    <p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan<sup>® </sup>manikin.</p> <p>Results</p> <p>The Airtraq<sup>® </sup>reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview<sup>® </sup>increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq<sup>® </sup>devices.</p> <p>Conclusion</p> <p>The Airtraq<sup>® </sup>laryngoscope performed more favourably than the Macintosh and Truview<sup>® </sup>devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

    Optimal Design of Intervention Studies to Prevent Influenza in Healthy Cohorts

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    Background: Influenza cohort studies, in which participants are monitored for infection over an epidemic period, are invaluable in assessing the effectiveness of control measures such as vaccination, antiviral prophylaxis and nonpharmaceutical interventions (NPIs). Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements. Methodology and Principal Findings: In the context of a randomized controlled trial of an NPI with a constrained budget, we used a simulation approach to examine which approaches to measuring outcomes could provide greater statistical power to identify an effective intervention against confirmed influenza. We found that for a short epidemic season, the optimal design was to collect respiratory specimens at biweekly intervals, as well as following report of acute respiratory illness (ARI), for virologic testing by reverse transcription polymerase chain reaction (RT-PCR). Collection of respiratory specimens only from individuals reporting ARI was also an efficient design particularly for studies in settings with longer periods of influenza activity. Collection of specimens only from individuals reporting a febrile ARI was less efficient. Collection and testing of sera before and after influenza activity appeared to be inferior to collection of respiratory specimens for RT-PCR confirmation of acute infections. The performance of RT-PCR was robust to uncertainty in the costs and diagnostic performance of RT-PCR and serological tests

    Cystatin C and Cardiovascular Disease

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    Background Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. Objectives The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. Methods We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. Results Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10−14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10−211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10−5). A causal effect of cystatin C was not detected for any individual component of CVD. Conclusions Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD

    Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

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    Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature
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