36 research outputs found
Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics
No full text[Image: see text] Anesthetics are thought to mediate a portion of their activity via binding to and modulation of potassium channels. In particular, tandem pore potassium channels (K2P) are transmembrane ion channels whose current is modulated by the presence of general anesthetics and whose genetic absence has been shown to confer a level of anesthetic resistance. While the exact molecular structure of all K2P forms remains unknown, significant progress has been made toward understanding their structure and interactions with anesthetics via the methods of molecular modeling, coupled with the recently released higher resolution structures of homologous potassium channels to act as templates. Such models reveal the convergence of amino acid regions that are known to modulate anesthetic activity onto a common three- dimensional cavity that forms a putative anesthetic binding site. The model successfully predicts additional important residues that are also involved in the putative binding site as validated by the results of suggested experimental mutations. Such a model can now be used to further predict other amino acid residues that may be intimately involved in the target-based structure–activity relationships that are necessary for anesthetic binding
The state of the Martian climate
Get PDF60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
Users' guides to the medical literature: how to use an article about mortality in a humanitarian emergency
Get PDFThe accurate interpretation of mortality surveys in humanitarian crises is useful for both public health responses and security responses. Recent examples suggest that few medical personnel and researchers can accurately interpret the validity of a mortality survey in these settings. Using an example of a mortality survey from the Democratic Republic of Congo (DRC), we demonstrate important methodological considerations that readers should keep in mind when reading a mortality survey to determine the validity of the study and the applicability of the findings to their settings
Effects of Post-Resuscitation Treatment with N-acetylcysteine on Cardiac Recovery in Hypoxic Newborn Piglets
Get PDFAIMS: Although N-acetylcysteine (NAC) can decrease reactive oxygen species and improve myocardial recovery after ischemia/hypoxia in various acute animal models, little is known regarding its long-term effect in neonatal subjects. We investigated whether NAC provides prolonged protective effect on hemodynamics and oxidative stress using a surviving swine model of neonatal asphyxia. METHODS AND RESULTS: Newborn piglets were anesthetized and acutely instrumented for measurement of systemic hemodynamics and oxygen transport. Animals were block-randomized into a sham-operated group (without hypoxia-reoxygenation [H-R, n = 6]) and two H-R groups (2 h normocapnic alveolar hypoxia followed by 48 h reoxygenation, n = 8/group). All piglets were acidotic and in cardiogenic shock after hypoxia. At 5 min after reoxygenation, piglets were given either saline or NAC (intravenous 150 mg/kg bolus + 20 mg/kg/h infusion) via for 24 h in a blinded, randomized fashion. Both cardiac index and stroke volume of H-R controls remained lower than the pre-hypoxic values throughout recovery. Treating the piglets with NAC significantly improved cardiac index, stroke volume and systemic oxygen delivery to levels not different from those of sham-operated piglets. Accompanied with the hemodynamic improvement, NAC-treated piglets had significantly lower plasma cardiac troponin-I, myocardial lipid hydroperoxides, activated caspase-3 and lactate levels (vs. H-R controls). The change in cardiac index after H-R correlated with myocardial lipid hydroperoxides, caspase-3 and lactate levels (all p<0.05). CONCLUSIONS: Post-resuscitation administration of NAC reduces myocardial oxidative stress and caused a prolonged improvement in cardiac function and in newborn piglets with H-R insults
Novel study designs to investigate the placebo response
Get PDF<p>Abstract</p> <p>Background</p> <p>Investigating the size and mechanisms of the placebo response in clinical trials have relied on experimental procedures that simulate the double-blind randomized placebo-controlled design. However, as the conventional design is thought to elucidate drug rather than placebo actions, different methodological procedures are needed for the placebo response.</p> <p>Methods</p> <p>We reviewed the respective literature for trials designs that may be used to elucidate the size of the placebo response and the mechanisms associated with it.</p> <p>Results</p> <p>In general, this can be done by either manipulation the information provided to the subjects, or by manipulation the timing of the drug applied. Two examples of each strategy are discussed: the "balanced placebo design" (BDP) and the "balanced cross-over design" (BCD) and their variants are based on false information, while the "hidden treatment" (HT) and the ""delayed response test" (DRT) are based on manipulating the time of drug action. Since most such approaches include deception or incomplete information of the subjects they are suitable for patient only with authorized deception.</p> <p>Conclusion</p> <p>Both manipulating the information provided to subjects (BDP, DCD) or manipulating the timing of drug application (HT, DRT) allows overcoming some of the restrictions of conventional drug trials in the assessment of the placebo response, but they are feasible mostly in healthy subjects for ethical reasons.</p
Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management
Get PDFBACKGROUND: Cyclic Vomiting Syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting and other symptoms, separated by intervals of comparative wellness. This report describes the clinical features, co-morbidities and problems encountered in management of 41 adult patients who met the diagnostic criteria for CVS. METHODS: This is a retrospective study of adults with CVS seen between 1994 and 2003. Follow-up data were obtained by mailed questionnaires. RESULTS: Age of onset ranged from 2 to 49 years. The duration of CVS at the time of consultation ranged from less than 1 year to 49 years. CVS episodes were stereotypic in respect of their hours of onset, symptomatology and length. Ninety-three percent of patients had recognizable prodromes. Half of the patients experienced a constellation of symptoms consisting of CVS episodes, migraine diathesis, inter-episodic dyspeptic nausea and a history of panic attacks. Deterioration in the course of CVS is indicated by coalescence of episodes in time. The prognosis of CVS is favorable in the majority of patients. CONCLUSION: CVS is a disabling disorder affecting adults as well as children. Because its occurrence in adults is little known, patients experience delayed or mis-diagnosis and ineffectual, sometimes inappropriately invasive management
