Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6mg center dot day(-1)) induced tolerance during 5 days in Sprague-Dawley rats, after which s.c. ketamine (10mg center dot kg(-1)) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naive rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90min after administration) lasting up to 150min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naive rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans.Peer reviewe

Comparison of different algorithms to map hydrothermal alteration zones using ASTER remote sensing data for polymetallic Vein-Type ore exploration: Toroud-Chahshirin Magmatic Belt (TCMB), north Iran

© 2019 by the authors. Polymetallic vein-type ores are important sources of precious metal and a principal type of orebody for various base-metals. In this research, Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) remote sensing data were used for mapping hydrothermal alteration zones associated with epithermal polymetallic vein-type mineralization in the Toroud-Chahshirin Magmatic Belt (TCMB), North of Iran. The TCMB is the largest known goldfield and base metals province in the central-north of Iran. Propylitic, phyllic, argillic, and advanced argillic alteration and silicification zones are typically associated with Au-Cu, Ag, and/or Pb-Zn mineralization in the TCMB. Specialized image processing techniques, namely Selective Principal Component Analysis (SPCA), Band Ratio Matrix Transformation (BRMT), Spectral Angle Mapper (SAM) and Mixture Tuned Matched Filtering (MTMF) were implemented and compared to map hydrothermal alteration minerals at the pixel and sub-pixel levels. Subtle differences between altered and non-altered rocks and hydrothermal alteration mineral assemblages were detected and mapped in the study area. The SPCA and BRMT spectral transformation algorithms discriminated the propylitic, phyllic, argillic and advanced argillic alteration and silicification zones as well as lithological units. The SAM and MTMF spectral mapping algorithms detected spectrally dominated mineral groups such as muscovite/montmorillonite/illite, hematite/jarosite, and chlorite/epidote/calcite mineral assemblages, systematically. Comprehensive fieldwork and laboratory analysis, including X-ray diffraction (XRD), petrographic study, and spectroscopy were conducted in the study area for verifying the remote sensing outputs. Results indicate several high potential zones of epithermal polymetallic vein-type mineralization in the northeastern and southwestern parts of the study area, which can be considered for future systematic exploration programs. The approach used in this research has great implications for the exploration of epithermal polymetallic vein-type mineralization in other base metals provinces in Iran and semi-arid regions around the world

Risk Factors for West Nile Virus Neuroinvasive Disease, California, 2005

In 2005, 880 West Nile virus cases were reported in California; 305 case-patients exhibited neuroinvasive disease, including meningitis, encephalitis, or acute flaccid paralysis. Risk factors independently associated with developing neuroinvasive disease rather than West Nile fever included older age, male sex, hypertension, and diabetes mellitus

Clinical characteristics, multiorgan dysfunction and outcomes of patients with COVID-19: a prospective case series

BACKGROUND: Characterizing the multiorgan manifestations and outcomes of patients hospitalized with COVID-19 will inform resource requirements to address the long-term burden of this disease. We conducted a descriptive analysis using prospectively collected data to describe the clinical characteristics and spectrum of organ dysfunction, and in-hospital and longer-term clinical outcomes of patients hospitalized with COVID-19 during the first wave of the pandemic at a Canadian centre. METHODS: We conducted a prospective case series involving adult patients (aged ≥ 18 yr) with COVID-19 admitted to 1 of 2 hospitals in London, Ontario, from Mar. 17 to June 18, 2020, during the first wave of the pandemic. We recorded patients\u27 baseline characteristics, physiologic parameters, measures of organ function and therapies administered during hospitalization among patients in the intensive care unit (ICU) and in non-ICU settings, and compared the characteristics of hospital survivors and nonsurvivors. Finally, we recorded follow-up thoracic computed tomography (CT) and echocardiographic findings after hospital discharge. RESULTS: We enrolled 100 consecutive patients (47 women) hospitalized with COVID-19, including 32 patients who received ICU care and 68 who received treatment in non-ICU settings. Respiratory sequelae were common: 23.0% received high-flow oxygen by nasal cannula, 9.0% received noninvasive ventilation, 24.0% received invasive mechanical ventilation and 2.0% received venovenous extracorporeal membrane oxygenation. Overall, 9.0% of patients had cerebrovascular events (3.0% ischemic stroke, 6.0% intracranial hemorrhage), and 6.0% had pulmonary embolism. After discharge, 11 of 19 patients had persistent abnormalities on CT thorax, and 6 of 15 had persistent cardiac dysfunction on echocardiography. INTERPRETATION: This study provides further evidence that COVID-19 is a multisystem disease involving neurologic, cardiac and thrombotic dysfunction, without evidence of hepatic dysfunction. Patients have persistent organ dysfunction after hospital discharge, underscoring the need for research on long-term outcomes of COVID-19 survivors

The Relational Impact of Multiple Sclerosis: An Integrative Review of the Literature Using a Cognitive Analytic Framework

This integrative literature review uses cognitive analytic therapy (CAT) theory to examine the impact of a chronic illness, multiple sclerosis (MS), on relationships and mental health. Electronic searches were conducted in six medical and social science databases. Thirty-eight articles met inclusion criteria, and also satisfied quality criteria. Articles revealed that MS-related demands change care needs and alter relationships. Using a CAT framework, the MS literature was analysed, and five key patterns of relating to oneself and to others were identified. A diagrammatic formulation is proposed that interconnects these patterns with wellbeing and suggests potential “exits” to improve mental health, for example, assisting families to minimise overprotection. Application of CAT analysis to the literature clarifies relational processes that may affect mental health among individuals with MS, which hopefully will inform how services assist in reducing unhelpful patterns and improve coping. Further investigation of the identified patterns is needed

Early Fasting Is Long Lasting: Differences in Early Nutritional Conditions Reappear under Stressful Conditions in Adult Female Zebra Finches

Conditions experienced during early life can have profound effects on individual development and condition in adulthood. Differences in nutritional provisioning in birds during the first month of life can lead to differences in growth, reproductive success and survival. Yet, under natural conditions shorter periods of nutritional stress will be more prevalent. Individuals may respond differently, depending on the period of development during which nutritional stress was experienced. Such differences may surface specifically when poor environmental conditions challenge individuals again as adults. Here, we investigated long term consequences of differences in nutritional conditions experienced during different periods of early development by female zebra finches (Taeniopygia guttata) on measures of management and acquisition of body reserves. As nestlings or fledglings, subjects were raised under different nutritional conditions, a low or high quality diet. After subjects reached sexual maturity, we measured their sensitivity to periods of food restriction, their exploration and foraging behaviour as well as adult resting metabolic rate (RMR). During a short period of food restriction, subjects from the poor nutritional conditions had a higher body mass loss than those raised under qualitatively superior nutritional conditions. Moreover, subjects that were raised under poor nutritional conditions were faster to engage in exploratory and foraging behaviour. But RMR did not differ among treatments. These results reveal that early nutritional conditions affect adult exploratory behaviour, a representative personality trait, foraging and adult's physiological condition. As early nutritional conditions are reflected in adult phenotypic plasticity specifically when stressful situations reappear, the results suggest that costs for poor developmental conditions are paid when environmental conditions deteriorate

Catalysis of iron core formation in Pyrococcus furiosus ferritin

The hollow sphere-shaped 24-meric ferritin can store large amounts of iron as a ferrihydrite-like mineral core. In all subunits of homomeric ferritins and in catalytically active subunits of heteromeric ferritins a diiron binding site is found that is commonly addressed as the ferroxidase center (FC). The FC is involved in the catalytic Fe(II) oxidation by the protein; however, structural differences among different ferritins may be linked to different mechanisms of iron oxidation. Non-heme ferritins are generally believed to operate by the so-called substrate FC model in which the FC cycles by filling with Fe(II), oxidizing the iron, and donating labile Fe(III)–O–Fe(III) units to the cavity. In contrast, the heme-containing bacterial ferritin from Escherichia coli has been proposed to carry a stable FC that indirectly catalyzes Fe(II) oxidation by electron transfer from a core that oxidizes Fe(II). Here, we put forth yet another mechanism for the non-heme archaeal 24-meric ferritin from Pyrococcus furiosus in which a stable iron-containing FC acts as a catalytic center for the oxidation of Fe(II), which is subsequently transferred to a core that is not involved in Fe(II)-oxidation catalysis. The proposal is based on optical spectroscopy and steady-state kinetic measurements of iron oxidation and dioxygen consumption by apoferritin and by ferritin preloaded with different amounts of iron. Oxidation of the first 48 Fe(II) added to apoferritin is spectrally and kinetically different from subsequent iron oxidation and this is interpreted to reflect FC building followed by FC-catalyzed core formation