Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nephrotoxic side effects of the immunosuppressant cyclosporin A in animals and humans are well known. Misoprostol, a prostaglandin E analog, is used clinically in organ-transplant recipients taking cyclosporin A to protect against these side effects. We reported previously that long-term treatment of rats with cyclosporin A causes a diminution in myocardial peak contractile stress. There is an associated spontaneous sarcomere activity and rest depression of force in the absence of a change in myofilaments sensitivity to intracellular Ca2+. Here we investigated the potential protective effects of misoprostol on the myocardium of cyclosporin A-treated rats. Rats were treated with either cyclosporin A, misoprostol, or their combination. Force-[Ca2+]o and -[Sr2+]o, and force-interval relations as well as the sarcomere length were studied in trabeculae isolated from the right ventricles. At suboptimal [Ca2+]o, cyclosporin A shifted the force-[Ca2+]o relation to the left but reduced peak contractile stress by approximately 35% at the highest (optimal) [Ca2+]o. Co-treatment with misoprostol prevented the leftward shift, and treatment with misoprostol alone did not cause a leftward shift. The diminution of peak stress, however, did not recover with misoprostol treatment, and stress was further reduced. Treatment with only misoprostol also reduced stress generated by the muscles more than that by cyclosporin A alone. Intriguingly, activation of the myofilaments by Sr2+ failed to recover peak stress to control levels in any group treated with misoprostol. Unlike cyclosporin A, however, rest potentiation of force was more pronounced, and spontaneous sarcomere activity was absent with misoprostol. No histopathologic changes were observed with cyclosporin A or misoprostol treatment. Misoprostol modifies the cyclosporin A-induced changes in the Ca2+ handling, but further decreases the stress generated by the muscles.
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PMID:Effect of misoprostol on myocardial contractility in rats treated with cyclosporin A. 967 34

A 74-year-old widowed white man with chronic rheumatoid arthritis presented with nausea and weight loss. He was diagnosed with failure to thrive and admitted for hydration. Misoprostol was determined to be the etiology of his symptoms and he was discharged home. Three days later, he killed himself with a gunshot to the head. Clinicians often fail to recognize those at high risk for suicide. Suicidal risk is increased in both psychiatric and physical illness, and particularly when both are present. Psychiatric illness, particularly depression, often underlies chronic medical illness. The purpose of this case report is to remind health care providers of the strong association between depression and chronic medical illness, and to consider this in all patients, including those who present solely with physical symptoms. Recognizing this association and screening for it, as recommended by the U.S. Preventive Services Task Force, may prevent the unnecessary tragedy of suicide.
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PMID:A shot in the dark: failing to recognize the link between physical and mental illness. 1744 78