Adv Exp Med Biol
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Chronic mountain sickness (CMS) is a poorly understood syndrome, characterized by hypoxemia and polycythemia and occurring in persons residing at high altitude. To better characterize the disorder, we have reviewed measurements in more than 750 men and 200 women living at altitude as published and as submitted by colleagues. In men, blood hemoglobin concentration (Hb) and arterial oxygen saturation (SaO2) related to altitude (r=0.72). ⋯ Pulmonary hypertension was related to chronic hypoxia, with an uncertain contribution from polycythemia. In CMS there were profound hypoxemia at night, decrease in cerebral blood flow, and loss of cerebral blood flow regulation, possibly causing the cerebral symptoms. We speculate that the relationship of Hb to SaO2 is more useful than of hemoglobin to altitude, that hypoventilation awake and asleep are the primary causes accentuating altitude-hypoxia, and that the brain is the primary target organ in the disorder.
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Opioids such as morphine are potent analgesic and addictive compounds. Chronic morphine use also induces immunomodulatory and immunosuppressive effects, as especially evident in HIV-infected patients. Morphine acts on the immune cells primarily through its binding to mu-opioid receptors on the plasma membrane. ⋯ The results of the competitive RT/PCR indicated that CEM x174 cells expressed KOR mRNA constitutively, in the order of femto-grams. Treatment of 10 microM of morphine resulted in the up-regulation of KOR gene expression 24 hr post-treatment. The observed morphine effect could be reversed by treating the cells with either naloxone (a KOR-partially selective antagonist) or nor-Binaltorphimine (a KOR-selective antagonist).
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Small, muscular pulmonary arteries (PAs) constrict within seconds of the onset of alveolar hypoxia, diverting blood flow to better-ventilated lobes, thereby matching ventilation to perfusion and optimizing systemic PO2. This hypoxic pulmonary vasoconstriction (HPV) is enhanced by endothelial derived vasoconstrictors, such as endothelin, and inhibited by endothelial derived nitric oxide. However, the essence of the response is intrinsic to PA smooth muscle cells in resistance arteries (PASMCs). ⋯ However, inhibition of complex 1 of the mitochondrial electron transport chain mimics hypoxia in that it inhibits IK, reduces the production of activated O2 species and causes vasoconstriction. We hypothesize that a redox O2 sensor, perhaps in the mitochondrion, senses O2 through changes in the accumulation of freely diffusible electron donors. Changes in the ratio of reduced/oxidized redox couples, such as NADH/NAD+ and glutathione (GSH/GSSG) can reduce or oxidize the K+ channels, resulting in alterations of PA tone.