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Medical Forum / Diseases and Disorders / Lupus / June 2008Mouse Model of Lupus
If one creates hemolysis is a mouse the mouse manifests lupus. Chronic hemolysis produces iron overload. The marker they use for this hemolysis is lactate dehydrogenase / LDH. Sooo .. with such a high rate of hemolysis in Lupus .. why such a high rate of iron deficiency because hemolytic anemia is iron loading. If you have iron .. **loading** ..there is NO .. iron deficiency. "Elevation of serum LDH levels in patients with SLE" Cell Death Differ 1997 Aug; 4(6):463-72. Piredda L, Amendola A, Colizzi V, Davies PJ, Farrace MG, Fraziano M, Gentile V, Uray I, Piacentini M, Fesus L Lack of 'tissue' transglutaminase protein cross-linking leads to leakage of macromolecules from dying cells: relationship to development of autoimmunity in MRLIpr/Ipr mice. Genetic defects of the CD95 (Fas/Apo-1) receptor/ligand system, has recently been involved in the development of human and murine autoimmunity. We investigated whether a deregulation of the ;tissue' transglutaminase (tTG), a multifunctional enzyme which is part of the molecular program of apoptosis, may act as a cofactor in the development of autoimmunity. We found that MRLlpr/lpr, which are characterized by a defect in the CD95 receptor and suffer of a severe systemic lupus erythematosus-like disease, produce large amounts of circulating tTG autoantibodies. This phenomenon is paralleled by an abnormal accumulation of an inactive enzyme protein in the accessory cells of lymphoid organs. To investigate the molecular mechanisms by which tTG inhibition may contribute to the development of autoimmunity we generated a cell culture model system consisting of L929 cells stably transfected with a full length tTG cDNA. When L929 cells were killed by Tumor Necrosis Factor alpha (TNFalpha) a pronounced release of DNA and Lactate Dehydrogenase (LDH) was observed. Overexpression of tTG in these cells largely prevented the leakage of macromolecules determined by TNFalpha treatment, an effect which is abolished by inactivating the enzyme cross-linking activity by a synthetic inhibitor. These in vitro observations provided the basis to explain the increased levels of plasmatic LDH we detected in MRLlpr/lpr mice. These data suggest that lack of an active tTG may represent a cofactor in the development of autoimmunity. Cell death and differentiation [Cell Death Differ] -------------------------------------------------------------------------------- Inoue T, Okamura M, Amatsu K, Negoro N, Koda S, Kohno M, Takeda T, Kanayama Y Serum lactate dehydrogenase and its isozymes in lupus nephritis. [Journal Article] Arch Intern Med 1986 Mar; 146(3):548-52. The relationship between the renal pathologic activity of systemic lupus erythematosus (SLE) and serum lactate dehydrogenase (LDH) was examined in 28 patients with active SLE involving only the kidney. Serum levels of total LDH, LDH1, and LDH2 were significantly higher in the patients with diffuse proliferative lupus nephritis (World Health Organization class IV) than in those with milder renal disease (classes I through III and V). Total LDH levels showed good correlations with the activity index and the total pathologic score of the renal pathologic scoring system, and with the glomerular hypercellularity and overall deposits. The elevated level of LDH was mainly due to elevated levels of its isozymes LDH1 and LDH2. These results suggest that the elevation of serum LDH levels in patients with SLE reflects the renal pathologic changes due to lupus nephritis. Archives of internal medicine [Arch Intern Med] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Jun 21, 6:30 pm, "ironjust...@aol.com" <ironjust...@aol.com> wrote:lactate dehydrogenase / LDH << "LDH may assist in early recognition of disease progression" Annals of Oncology Advance Access published online on February 13, 2008 Prognostic significance of serial determinations of lactate dehydrogenase (LDH) in the follow-up of patients with myelodysplastic syndromes F. Wimazal1, W. R. Sperr1, M. Kundi2, A. Vales1, C. Fonatsch3, R. Thalhammer-Scherrer4, I. Schwarzinger4 and P. Valent1,* 1 Department of Internal Medicine I, Division of Hematology and Hemostaseology 2 Institute of Environmental Health 3 Department of Medical Genetics 4 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria * Correspondence to: Dr P. Valent, Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Tel: +43-1-40400-6085; Fax: +43-1-40400-4030; E-mail: peter.valent@meduniwien.ac.at Background: Early recognition of disease progression in low-risk myelodysplastic syndromes (MDS) is an important decision point concerning intensive therapies. In a screen program searching for dynamic prognostic determinants, we have identified lactate dehydrogenase (LDH) as a most suitable follow-up parameter. Patients and methods: LDH levels were serially determined in 221 patients with de novo MDS (median age 70 years, range 24–94). The increase in LDH was correlated with survival and acute myeloid leukemia (AML) evolution. Results: Confirming previous data, an elevated LDH at diagnosis was found to be associated with an increased probability of AML evolution and decreased probability of survival (P < 0.05). In the follow-up, we found that in patients who progressed (to higher IPSS category or AML), LDH levels were significantly higher in the two 3-month period preceding progression compared with the initial two 3-month period (P < 0.005). In a subgroup of patients, the increase in LDH was accompanied or followed by other signs of disease progression, such as occurrence of thrombocytopenia or appearance of circulating blasts. In multivariate analyses, the LDH increase was found to be an independent prognostic variable. Conclusions: LDH is an interesting follow-up parameter in MDS, which may assist in early recognition of disease progression and thus help in risk stratification and patient selection for interventional therapies. IPSS, LDH, MDS, prognosis Received for publication September 14, 2007. Revision received November 14, 2007. Accepted for publication December 13, 2007. Annals of Oncology, doi:10.1093/annonc/mdm595 © 2008 European Society for Medical Oncology. For Permissions, please email: journals.permissions@oxfordjournals.org Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > If one creates hemolysis is a mouse the mouse manifests lupus. > Chronic hemolysis produces iron overload. [quoted text clipped - 76 lines] > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk On Jun 21, 6:41 pm, "ironjust...@aol.com" <ironjust...@aol.com> wrote: Toxicol Appl Pharmacol. 2007 Jul 1;222(1):33-41. Epub 2007 Mar 31. Resveratrol improves ifosfamide-induced Fanconi syndrome in rats. Sehirli O, Sakarcan A, Velioğlu-Oğünç A, Cetinel S, Gedik N, Yeğen BC, Sener G. Marmara University, School of Pharmacy, Department of Pharmacology, Tibbiye Cad. 34668 Istanbul, Turkey. Regarding the mechanisms of ifosfamide (IFO)-induced urinary toxicity, several hypotheses have been put forward, among which oxidative stress and depletion of glutathione are suggested. This investigation elucidates the role of free radicals in IFO-induced toxicity and the protection by resveratrol, a natural phytoalexin. Wistar albino rats were injected intraperioneally with saline (0.9% NaCl; control), saline+resveratrol (RVT; 10 mg/kg/day), ifosfamide (IFO; 50 mg/kg/day) or IFO+RVT for 5 days. Urine was collected for 24 h during the 5th day, and at the 120th h after the first injections, animals were killed by decapitation and trunk blood was collected. Lactate dehydrogenase (LDH) activity, total antioxidant capacity (AOC) and pro-inflammatory cytokines TNF-alpha, IL-beta and IL-6 were assayed in plasma samples. Kidney and bladder tissues were obtained for biochemical and histological analysis. Formation of reactive oxygen species in the tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. The results demonstrated that IFO induced a Fanconi syndrome characterized by increased urinary sodium, phosphate, glucose and protein, along with increased serum creatinine and urea levels. On the other hand, RVT markedly ameliorated the severity of renal dysfunction induced by IFO. Furthermore IFO caused a significant decrease in plasma AOC, which was accompanied with significant increases in the levels of the pro- inflammatory mediators and LDH activity, while RVT treatment reversed all these biochemical indices. In the saline-treated IFO group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in both tissues, which were in parallel with the increases in CL values. In the RVT-treated IFO group, all of these oxidant responses were prevented significantly. Our results suggest that IFO causes oxidative damage in the renal and bladder tissues and resveratrol, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role in preventing the development of chemotherapeutic drug-induced major toxicity in the urinary system requires further elucidation. PMID: 17481685 [PubMed - indexed for MEDLINE] -------------------------------------------- Researchers Show Resveratrol Works In The Brain By Metal Chelating Effects Researchers now convincingly show that, via its iron-chelating effects, resveratrol is able to cross barriers that protect the brain from entry of toxins (blood/brain barrier) and reduce oxidation (spoilage) of fats and increase the activity of protective antioxidant enzymes in the brain of healthy rodents. The research has application for age-related brain disorders such as Alzheimer's and Parkinson's disease. Resveratrol decreased malondialdehyde (an end product of oxidation of fats) in brain tissues by -300%. Doses ranging (in human equivalents) from 87.5 to 875 milligrams were effective in this regard. Higher doses were not more effective. Resveratrol also significantly increased the activity of antioxidant enzymes superoxide dismutase, catalase and peroxidase by 160%, 270% and 210% (see above chart). The forms of most of these protective enzymes were iron-controlling proteins, confirming that resveratrol's primary action is via its ability to control metallic metals. Loose (free) iron causes tissue damage in all forms of age-related brain disease. While a relatively high dose of resveratrol was shown to be most effective (875 milligrams human equivalent dose), this was only a 7-day study. It is expected that a life-long accumulation of iron in brain tissues will require a high loading dose and a lower maintenance dose. The current fad of ultra-high dose resveratrol supplementation may be beneficial initially, but lead to anemias over longer term use. -Resveratrol News April 2007 http://www.resveratrolnews.com/page77.htm Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > On Jun 21, 6:30 pm, "ironjust...@aol.com" <ironjust...@aol.com> > wrote:lactate dehydrogenase / LDH << [quoted text clipped - 149 lines] > > - Show quoted text - On Jun 21, 6:55 pm, "ironjust...@aol.com" <ironjust...@aol.com> wrote:Metal Chelating Effects << "Iron-chelating agent Edaravone" Edaravone, a Potent Free Radical Scavenger, Prevents Anthracycline- Induced Myocardial Cell Death Circulation Journal Vol. 71 (2007) , No. 11 1815-1820 Ei Ikegami1), Ryuji Fukazawa1), Masaru Kanbe2), Miki Watanabe1), Masanori Abe1), Makoto Watanabe1), Mitsuhiro Kamisago1), Miharu Hajikano1), Yasuhiro Katsube1) and Shunichi Ogawa1) 1) Department of Pediatrics, Nippon Medical School 2) Department of Surgery, Cardiovascular Surgery, Nippon Medical School (Received April 19, 2007) (Revised manuscript received June 22, 2007) (Accepted July 11, 2007) Background It was investigated whether edaravone, a potent free radical scavenger, would protect against anthracycline-induced cardiotoxicity and prevent cardiac function deterioration. Methods and Results Cultured neonatal rat cardiomyocytes were stimulated by daunorubicin 1 μmol/L either with or without edaravone or superoxide dismutase mimetic Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). Cell viability was estimated by measuring the amount of lactate dehydrogenase (LDH) released into the culture medium. Apoptosis was determined by a caspase-3 activity assay and a histone - DNA complex fragment assay. To investigate whether edaravone interfered with daunorubicin's anti-tumor effect, daunorubicin and edaravone were added to human leukemia K562 cells, and the surviving cells were counted. In addition, edaravone's in vivo effect was evaluated using Sprague - Dawley rats. A total of 15 mg/kg doxorubicin was injected intraperitoneally either with or without simultaneous edaravone injection. Two and 6 weeks after the final injection, left ventricular diastolic diameter and left ventricular fraction shortening were assessed echocardiographically. The LDH assay showed that edaravone significantly inhibited LDH release from cardiac myocytes (p=0.0428). The caspase-3 activity and histone - DNA complex fragment assays demonstrated that edaravone's apoptosis suppression effect was much weaker than that of MnTMPyP. The in vivo study showed that edaravone prevented doxorubicin-induced cardiac deterioration. Finally, edaravone was found to not affect daunorubicin's anticancer effect on K562 cells. Conclusions Edaravone protects cardiomyocytes from anthracycline-induced cardiotoxicity via an anti-necrotic rather than an anti-apoptotic effect. (Circ J 2007; 71: 1815 - 1820) Key Words: Apoptosis; Cardiomyopathy; Edaravone; Necrosis; Redox cycling Ei Ikegami, Ryuji Fukazawa, Masaru Kanbe, Miki Watanabe, Masanori Abe, Makoto Watanabe, Mitsuhiro Kamisago, Miharu Hajikano, Yasuhiro Katsube and Shunichi Ogawa “Edaravone, a Potent Free Radical Scavenger, Prevents Anthracycline-Induced Myocardial Cell Death”; Circ J. Vol. 71. 1815-1820. (2007) . doi:10.1253/circj.71.1815 JOI JST.JSTAGE/circj/71.1815 Copyright (c) 2007 THE JAPANESE CIRCULATION SOCIETY -------------------------------------------------------------------------------- http://tinyurl.com/ynpdhm "Iron-chelating agents, N-acetyl-L-cysteine (NAC), apocynin,probucol, and edaravone, are useful in preventing cardiovascular injury and diseases." Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > On Jun 21, 6:41 pm, "ironjust...@aol.com" <ironjust...@aol.com> wrote: > [quoted text clipped - 214 lines] > > - Show quoted text - On Jun 21, 9:40 pm, "ironjust...@aol.com" <ironjust...@aol.com> wrote:Resveratrol << Eugenol as An In Vivo Radioprotective Agent Ashu Bhan TIKU1), Suresh K. ABRAHAM1) and Raosaheb K KALE1) 1) School of Life Sciences, Jawaharlal Nehru University (Received March 19, 2004) (Revision received May 12, 2004) (Accepted May 27, 2004) In the present work, an attempt has been made to evaluate the possible in vivo radioprotection by eugenol. Swiss albino mice were administered different doses of eugenol (75,150 and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The micronucleus test was carried out to determine the genetic damage in bone marrow. Our results demonstrated significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) with all three eugenol doses. Eugenol (150 mg/kg) was also tested against different doses of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant radioprotection. Reduction in the incidence of MnPCEs could be noticed up to 72 h postirradiation (1.5 Gy). Moreover, the level of peroxidative damage and the specific activities of lactate dehydrogenase (LDH) and methylglyoxalase I (Gly I) were observed in the liver of mice treated with eugenol for seven days in comparison to untreated mice. The results revealed that eugenol exerted significant protection against oxidative stress. This possibility was further supported by the enhanced response of Gly I and the lowered activity of LDH. The present findings suggested that eugenol has a radioprotective potential. Eugenol/ Micronucleus test/ Radiation/ Radioprotection/ Oxidative stress Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > On Jun 21, 6:55 pm, "ironjust...@aol.com" <ironjust...@aol.com> > wrote:Metal Chelating Effects << [quoted text clipped - 220 lines] > > - Show quoted text - |
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