The matrix metalloproteinases (MMPs) play a key role in the normal physiology of connective tissue during development, morphogenesis, and wound healing. Dysregulation of their activity has been implicated in numerous diseases including encephalopathy and the process of bone loss. Thus, MMPs may play a role in the encephalopathy and post-transplantation bone disease by immunosuppressive drugs such as cyclosporine (CsA) and tacrolimus. Gelatin zymography of MMP-9 and MMP-2 was performed in the glioma cells and osteoblast after CsA or tacrolimus treatment. Glioma cells or rat osteoblast ROS17/2.8 cells were treated with CsA or tacrolimus to make final concentration from 2 to 250 µM. After incubation, gelatin zymography of MMP-9 and MMP-2 was performed. And the density for the MMP bands were measured using luminescent image analyzer system. Both MMP-9 and MMP-2 activities in the osteoblast cells were decreased depending on the concentration of CsA or tacrolimus. MMP-2 activity was increased after CsA or tacrolimus treatment in the glioma cells. However, MMP-9 activities were decreased after CsA or tacrolimus treatment in the glioma cells. These results indicate that dysregulation of MMPs in the osteoblast and in the glioma cells by immunosuppressive drugs may one of the contributing factors in post-transplantation bone disease and in the encephalopathy by tacrolimus or cyclosporine.
Animals ; Bone Diseases ; Connective Tissue ; Cyclosporine ; Gelatin ; Glioma* ; Matrix Metalloproteinases ; Morphogenesis ; Osteoblasts* ; Physiology ; Rats ; Tacrolimus ; Wound Healing

PURPOSE: We tested the effect of team-based learning (TBL) on medical education through the second-year premedical students’ TBL scores in biochemistry classes over 5 years. METHODS: We analyzed the results based on test scores before and after the students’ debate. The groups of students for statistical analysis were divided as follows: group 1 comprised the top-ranked students, group 3 comprised the low-ranked students, and group 2 comprised the medium-ranked students. Therefore, group T comprised 382 students (the total number of students in group 1, 2, and 3). To calibrate the difficulty of the test, original scores were converted into standardized scores. We determined the differences of the tests using Student t-test, and the relationship between scores before, and after the TBL using linear regression tests. RESULTS: Although there was a decrease in the lowest score, group T and 3 showed a significant increase in both original and standardized scores; there was also an increase in the standardized score of group 3. There was a positive correlation between the pre- and the post-debate scores in group T, and 2. And the beta values of the pre-debate scores and “the changes between the pre- and post-debate scores” were statistically significant in both original and standardized scores. CONCLUSION: TBL is one of the educational methods for helping students improve their grades, particularly those of low-ranked students.
Biochemistry* ; Education, Medical ; Education, Premedical ; Humans ; Learning* ; Linear Models ; Schools, Medical

Hemolysis is one of the side effects of cyclosporine(CsA). Some experimental and clinical data have strongly suggested that CsA-induced hemolysis is resulted from the increased production of free radical species by CsA. Melatonin, a pineal secretory product, acts as a highly efficient free radical scavenger. Thus, melatonin may have a protective effect on the CsA-induced hemolysis. To test this hypothesis, the final concentration of 4.2x106/mL with human erythrocytes was incubated in test tube at 37 degrees C water bath with 1.67 mg/mL of CsA and 72 nmol/mL of melatonin. The degree of hemolysis and the amount of malondialdehyde which gives an indirect index of oxidative injury were measured in group 1 containing only isotonic buffer solution, in group 2 containing only CsA, and in group 3 containing both CsA and melatonin. The degrees of hemolysis in group 2 were higher than those of group 1. The degrees of hemolysis in group 3 were higher than those of group 1, and lower than those of group 2. The amounts of malondialdehyde in group 2 were higher than those of group 1. The amounts of malondialdehyde in group 3 were higher than those of group 1, and lower than those of group 2. These results indicate that the direct contact of erythrocytes with CsA results in free radical mediated hemolysis and the hemolysis by CsA can be prevented with melatonin.
Humans

To clarify the mechanism of the protective effect of hemodialysis on lipid peroxidation in RBC membrane structures, the level of malondialdehyde (MDA) which is the lipid peroxidation product, and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) were determined before and after hemodialysis in the RBCs from 20 patients with end stage renal disease (ESRD), and from 14 healthy subjects. Before dialysis, MDA levels in the RBCs from the patients with ESRD were higher than those from healthy controls. SOD and catalase activities in the RBCs were lower. After hemodialysis, MDA, SOD, and catalase in the RBCs from the patients with ESRD were normalized. These results indicate that hemodialysis treatment is helpful to protect the peroxidative darnage through normalizing the activities of antioxidant enzymes.
Catalase ; Dialysis ; Erythrocytes* ; Glutathione Peroxidase ; Humans ; Kidney Failure, Chronic* ; Lipid Peroxidation ; Malondialdehyde* ; Membranes ; Renal Dialysis* ; Superoxide Dismutase

During simulated weightlessness and spaceflight, variations in plasma and urinary catecholamine(GA) levels haute been observed. The alterations of metabolism of CA In liver, the main site of metabolism, ate yet not known We measured the activity of catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO) In rat liver as Indicators of CA metabolism before and during head-down suspension The rats were placed In a -45 degress antiorthostatic position for 2 weeks. Head-down suspension resulted In decrease other hepatic MAO B activity By contrast, the activities of other hepatic degrading enzymes, COMT and MAO A, did not altered These findings Indicate that a prolonged exposure to simulated weightlessness exerts no remarkable effect on CA degradation in rat liver.
Animals ; Liver* ; Metabolism ; Monoamine Oxidase ; Plasma ; Rats* ; Space Flight ; Transferases ; Weightlessness

Suppressed superoxide dismutase activity, which is responsible for the dismutation of superoxide anion to hydrogen peroxide, is known to be one of the factors leading to lipid peroxidation in the erythrocyte membrane structures in the patients with end stage renal disease. In this study, copper and zinc levels were determined in the erythrocytes and plasma from 14 hemodialysis patients to explain the decreased activity of superoxide dismutase in erythrocytes. Before dialysis, superoxide dismutase, copper and zinc levels in erythrocytes were lower than those from healthy controls. Superoxide dismutase activity was normalized perfectly after hemodialysis. Copper level in the erythrocytes was normalized after hemodialysis, but its level was still lower than that in healthy controls. Zinc level in the erythrocytes was not changed after hemodialysis. Before hemodialysis, copper and zinc levels in plasma were higher than those from healthy controls. Copper level in the plasma was higher after hemodialysis than before hemodialysis. Zinc level in the plasma was not changed after hemodialysis. It is suggested that copper levels in erythrocytes from patients with hemodialysis affects partially to the superoxide dismutase activity, and superoxide dismutase activity is influenced more by copper levels than by zinc levels during hemodialysis.
Copper ; Dialysis ; Erythrocyte Membrane ; Erythrocytes* ; Humans ; Hydrogen Peroxide ; Kidney Failure, Chronic* ; Lipid Peroxidation ; Plasma ; Renal Dialysis ; Superoxide Dismutase* ; Superoxides* ; Zinc

Proteins are known to be carbamylated as a result of reactions with ureaderived cyanate. We investigated the effect of carbamylation by cyanate on the catalase activity which is known that its decreased activity contributes to cataract formation, and on the lens protein. Catalase and lens protein were carbamylated by incubation with cyanate at 37degrees C. The extent of carbamylation was monitored by following the loss of free amino group using trinitrobenzenesulphonic acid. The level of carbamylated protein was 76% in patients with cataract. Carbamylated proteins in normal lens from rabbits and carbamylated catalase were increased as the time of exposure to cyanate activity. Our results suggest that cyanate is an inhibitor of catalase, and carbamylation of catalase as a result of reaction with ureaderived cyanate may contribute to cataract formation.
Catalase* ; Cataract ; Humans ; Rabbits

To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.
Allopurinol/*pharmacology ; Animal ; Bile Ducts ; Cholestasis/*pathology ; Enzyme Inhibitors/*pharmacology ; Free Radicals ; Ligation ; Liver/*pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Superoxides/metabolism ; Xanthine Oxidase/analysis/*antagonists & inhibitors

BACKGROUND AND OBJECTIVES: Cisplatin (CP), an antitumor agent widely used in the treatment of head and neck cancers, has side effects such as ototoxicity and nephrotoxicity. These side effects are closely related to oxidative stress. In the present study, we attempted to suppress CP-induced ototoxicity in rats by administering melatonin, an antioxidant. MATERIALS AND METHOD: Male Sprague-Dawley rats were divided into different groups and were treated as follows: 1) saline control, 2) CP (16 mg/kg, i.p.), 3) CP plus melatonin (10 mg/kg, i.p.). The rats were sacrificed at the 6th day after CP treatment. RESULTS: CP-treated rats showed increase in cochlear malondialdehyde, hydrogen peroxide, glutathione peroxidase and glutathione reductase levels, and the decrease in cochlear superoxide dismutase (SOD) and catalase levels. CP-treated rats showed markedly decreased in the number of stereocilia on the inner hair cells and mildly decreased in the number of outer hair cells in organ of Corti under the light and scanning electron microscopic examination. Light and electron microscopic findings, and cochlear hydrogen peroxide, malondialdehyde, SOD, catalase, glutathione peroxidase and glutathione reductase levels were restored in the rats injected with CP plus melatonin than those with CP alone. CONCLUSION: These results suggest that melatonin suppresses CP-induced ototoxicity via the suppression of the increased production of reactive oxygen species.
Animals ; Catalase ; Cisplatin* ; Glutathione Peroxidase ; Glutathione Reductase ; Hair ; Head ; Humans ; Hydrogen Peroxide ; Male ; Malondialdehyde ; Melatonin* ; Neck ; Organ of Corti ; Oxidative Stress ; Rats* ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; Stereocilia ; Superoxide Dismutase

BACKGROUND: Cisplatin (CP), an antitumor agent widely used in the treatment of cancers, has nephrotoxicity. This side effect is closely related to oxidative stress. In the present study, we attempted to reduce CP-induced nephrotoxicity in rats by administering melatonin, an antioxidant. METHODS: Male Sprague-Dawley rats were divided into different groups and were treated as follows: (1) saline control; (2) CP (16 mg/kg, i.p.); (3) CP plus melatonin (10 mg/kg, i.p.). The rats were sacrificed at the 6th day after CP treatment. To evaluate renal damage, BUN, serum creatinine, creatinine clearance and microscopic examination were done. Hydrogen peroxide which is one of the oxygen free radicals, and malondialdehyde which is known as a marker of the oxygen free radical mediated injury, and the activities of the antioxidant enzymes such as superoxied dismutase, catalase, and glutathione peroxidase were also measured. RESULTS: CP-treated rats showed the increase of BUN, serum creatinine, malondialdehyde, hydrogen peroxide and superoxide dismutase (SOD) in kidney. And CP-treated rats also showed the decrease of creatinine clearance and catalase levels. CP-treated rats showed severe tubular necrosis in proximal convoluted tubules under the light microscopic examination. The light microscopic finding and all of the parameters except SOD were restored in the rats injected with CP plus melatonin than those with CP alone. SOD level was higher in the rats injected with CP plus melatonin than that with CP alone. CONCIUSION: These results suggest that melatonin suppresses CP-induced nephrotoxicity by suppressing the production of reactive oxygen species via the activation of SOD and catalase.
Animals ; Catalase ; Cisplatin* ; Creatinine ; Free Radicals ; Glutathione Peroxidase ; Humans ; Hydrogen Peroxide ; Kidney ; Male ; Malondialdehyde ; Melatonin* ; Necrosis ; Oxidative Stress ; Oxygen ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; Superoxide Dismutase