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The placebo effect and endogenous opioids.

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L Sher. 2000. The placebo effect and endogenous opioids.. https://doi.org/10.1177/014107680009300315

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At the beginning of the 70-ties various studies showed the existence of endogenous opiates in central nervous system. The chemical structure of first endogenous pentapeptides called enkephalins (met-enkephalin and leu-enkephalin) and their receptor was already known in 1975. Further investigations confirmed the existence of opiates (endorphins) in brain, pituitary gland, spinal cord and other tissues. Endorphins may exert various effects: analgesic (especially dynorphin and b-endorphin), antidiuretic, depressive on respiratory center, constipative, they also cause physical and mental dependence. These peptides, which are not known thoroughly may play a big part in the regulation of many biochemical and hemodynamic processes. Many of these mechanisms are already described and changes in concentrations of endorphins, for example in patients with silent myocardial ischaemia, are basic in the pathogenesis of this disease. Many of these mechanisms are controversial, the role of endogenous opiates in pathogenesis of hypertension or congestive heart failure is still unknown. This study summerizes the present knowledge endorphins and tries to answer whether changes in the concentration of endorphins are primary or secondary to the biochemical and hemodynamic disturbances in 2 diseases.

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Application of micro-electrospray liquid chromatography techniques to FT-ICR MS to enable high-sensitivity biological analysis.

A microbore electrospray (ESI) injection system has been adapted to our 9.4-tesla ESI FT-ICR mass spectrometer, greatly enhancing the stability and sensitivity of the system. Spray was generated from micro-ESI needles made from sharply tapered, polished fused silica capillaries of 25 to 50 microns inner diameter. Micro-ESI permits low-level sample analysis by constant infusion at sub-microL/min flow rate over a wide range of solvent conditions in both positive- and negative-ion mode. The system is flexible and allows rapid conversion to allow routine LC/MS analysis on low-level mixtures presented in biological media. LC/MS analyses were accomplished by replacing micro-ESI needles with capillaries packed with reverse phase retention media to permit analyte concentration and purification prior to analysis (micro-ESI/LC). A unique nano-flow LC pumping system was developed, capable of producing a true unsplit solvent gradient at flow rates below 1 microL/min. The micro-ESI/LC FT-ICR system produces mass spectra from a mixture of three neuroactive peptides at a concentration of 500 amol/microL (5 fmol each total loaded) in biological salts with baseline separation, signal-to-noise ratio of > 10:1 and mass resolving power > 5000. These results represent a reduction in detection limit by a factor of approximately 2 x 10(6) over the best previously published LC/FT-ICR MS data.

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