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      Collagenous Tissues upon Lithium Treatment: A Quantitative Ultrastructural Study

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          Abstract

          In this review, the influence of lithium treatment in mouse, rat, and rabbit skin, liver, bone, and aorta, as well as arachnoid and dura mater collagen fibrils, is examined using electron microscopy and image processing. Structural changes (fibril architecture and diameter) are detected at the ultrastructural level in specimens from all lithium-treated tissues. The overall collagen fibril architecture is disturbed as compared with specimens from normal species. The mean diameter values of treated collagen fibrils are significantly smaller than those from controls in all tissues examined. The banding patterns of fibrils are normal in all cases. Measurements by a computerized method of measuring axial periodicity of fibrils indicate no effect of lithium on this parameter. Computer analysis shows no differences in charged amino acid composition between lithium-treated and -untreated samples. Under the present experimental conditions, lithium can induce permanent structural collagen alterations.

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          Most cited references37

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          Lithium: occurrence, dietary intakes, nutritional essentiality.

          Lithium is found in variable amounts in foods; primary food sources are grains and vegetables; in some areas, the drinking water also provides significant amounts of the element. Human dietary lithium intakes depend on location and the type of foods consumed and vary over a wide range. Traces of lithium were detected in human organs and fetal tissues already in the late 19th century, leading to early suggestions as to possible specific functions in the organism. However, it took another century until evidence for the essentiality of lithium became available. In studies conducted from the 1970s to the 1990s, rats and goats maintained on low-lithium rations were shown to exhibit higher mortalities as well as reproductive and behavioral abnormalities. In humans defined lithium deficiency diseases have not been characterized, but low lithium intakes from water supplies were associated with increased rates of suicides, homicides and the arrest rates for drug use and other crimes. Lithium appears to play an especially important role during the early fetal development as evidenced by the high lithium contents of the embryo during the early gestational period. The biochemical mechanisms of action of lithium appear to be multifactorial and are intercorrelated with the functions of several enzymes, hormones and vitamins, as well as with growth and transforming factors. The available experimental evidence now appears to be sufficient to accept lithium as essential; a provisional RDA for a 70 kg adult of 1,000 microg/day is suggested.
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            Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model.

            Lithium has long been a primary drug used to treat bipolar mood disorder, even though the drug's therapeutic mechanisms remain obscure. Recent studies demonstrate that lithium has neuroprotective effects against glutamate-induced excitotoxicity in cultured neurons and in vivo. The present study was undertaken to examine whether postinsult treatment with lithium reduces brain damage induced by cerebral ischemia. We found that s.c. injection of lithium dose dependently (0.5-3 mEq/kg) reduced infarct volume in the rat model of middle cerebral artery occlusionreperfusion. Infarct volume was reduced at a therapeutic dose of 1 mEq/kg even when administered up to 3 h after the onset of ischemia. Neurological deficits induced by ischemia were also reduced by daily administration of lithium over 1 week. Moreover, lithium treatment decreased the number of neurons showing DNA damage in the ischemic brain. These neuroprotective effects were associated with an up-regulation of cytoprotective heat shock protein 70 (HSP70) in the ischemic brain hemisphere as determined by immunohistochemistry and Western blotting analysis. Lithium-induced HSP70 up-regulation in the ischemic hemisphere was preceded by an increase in the DNA binding activity of heat shock factor 1, which regulates the transcription of HSP70. Physical variables and cerebral blood flow were unchanged by lithium treatment. Our results suggest that postinsult lithium treatment reduces both ischemia-induced brain damage and associated neurological deficits. Moreover, the heat shock response is likely to be involved in lithium's neuroprotective actions. Additionally, our studies indicate that lithium may have clinical utility for the treatment of patients with acute stroke.
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              THE CHARGE PROFILE OF THE TROPOCOLLAGEN MACROMOLECULE AND THE PACKING ARRANGEMENT IN NATIVE-TYPE COLLAGEN FIBRILS.

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                Author and article information

                Journal
                ScientificWorldJournal
                ScientificWorldJournal
                TSWJ
                The Scientific World Journal
                TheScientificWorldJOURNAL
                2356-6140
                1537-744X
                2004
                11 August 2004
                : 4
                : 605-621
                Affiliations
                Laboratory of Medical Physics, Medical School, Ioannina University, 45110 Ioannina, Greece
                Article
                913841
                10.1100/tsw.2004.119
                5956461
                15349503
                b40a8788-bd92-46d9-b3fa-57030f987d6d
                Copyright © 2004 Margaret Tzaphlidou.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2004
                : 2 August 2004
                : 2 August 2004
                Categories
                Review Article

                Uncategorized
                electron microscopy,ultrastructure,electron-optical data,image analysis,collagen,lithium,skin,liver,bone,cranial arachnoid and dura mater,aorta

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