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The effects of ketamine and lidocaine on free radical production after tourniquet-induced ischemia-reperfusion injury in adults.
Peker, K, Ökesli, S, Kıyıcı, A, Deyişli, C
Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES. 2019;(2):111-117
Abstract
BACKGROUND The primary aim of this study was to compare the effects of a small-dose infusion of 2 antioxidant agents, ketamine and lidocaine, on ischemia-reperfusion injury (IRI) in patients undergoing elective lower limb surgery. Ischemia-modified albumin (IMA), lactate, and blood gas levels were all measured and assessed. METHODS A total of 100 patients who underwent lower extremity surgery were randomized into 3 groups. After spinal anesthesia, the ketamine group (Group K, n=33) was given a ketamine infusion, a lidocaine infusion was administered to the lidocaine group (Group L, n=33), and in the control group (Group C), 0.9% a sodium chloride infusion was performed. Blood samples were obtained for IMA analysis before anesthetic administration (baseline), at 30 minutes of tourniquet inflation (ischemia), and 15 minutes after tourniquet deflation (reperfusion). Arterial blood gas measurements were determined before anesthetic administration and 15 minutes after tourniquet deflation. RESULTS The lactate and IMA levels at reperfusion were significantly lower in both the ketamine group and the lidocaine group when compared with the control group. CONCLUSION The administration of both ketamine and lidocaine infusions significantly decreased skeletal muscle IRI-related high lactate and IMA levels. These results suggest the possibility of the clinical application of ketamine or lidocaine infusions in cases of skeletal muscle-related IRI.
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Hepatic Effects of Estrogen on Plasma Distribution of Small Dense Low-Density Lipoprotein and Free Radical Production in Postmenopausal Women.
Nii, S, Shinohara, K, Matsushita, H, Noguchi, Y, Watanabe, K, Wakatsuki, A
Journal of atherosclerosis and thrombosis. 2016;(7):810-8
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Abstract
AIM: Hepatic effects of estrogen therapy on low-density lipoprotein (LDL) subfraction or oxidative stress have not been previously evaluated. The purpose of the present study was to investigate whether the differential hepatic effects of estrogen affect plasma distribution of small dense LDL and free radical production in postmenopausal women. METHODS In all, 45 postmenopausal women were given 0.625 mg/day of oral conjugated equine estrogen (CEE) (n=15), 1.0 mg/day of oral 17β estradiol (E2) (n=15), or 50 μg/day of transdermal 17βE2 (n=15) for 3 months. Subjects received either estrogen alone or with dydrogesterone at 5 mg/day. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, metallic ions, and derivatives of reactive oxygen metabolites (d-ROMs) were measured. RESULTS CEE, but not oral 17βE2, increased the plasma concentrations of triglyceride, copper (Cu), and d-ROMs and the ratio of small dense LDL/total LDL cholesterol, a marker for plasma distribution of small dense LDL. Transdermal 17βE2 decreased d-ROMs concentrations but did not significantly change other parameters. Plasma concentrations of SHBG increased in the 3 groups. Estrogen-induced changes in triglyceride correlated positively either with changes in SHBG (R=0.52, P=0.0002) or the ratio of small dense LDL/total LDL cholesterol (R=0.65, P<0.0001). Changes in Cu also correlated positively either with changes in SHBG (R=0.85, P<0.0001) or d-ROMs (R=0.86, P<0.0001). CONCLUSION The hepatic effects of different routes or types of estrogen therapy may be associated with plasma distribution of small dense LDL and free radical production in postmenopausal women.
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[Pharmacological correction of free radical disturbances and endotoxicosis in patients with diffuse peritonitis at the postoperative period].
Bagnenko, SF, Mirzabaev, AT, Batotsyrenov, BV, Gorbachev, NB, Miroshnichenko, VN, Batotsyrenova, KhV, Velikiĭ, KF
Vestnik khirurgii imeni I. I. Grekova. 2011;(5):14-6, 18
Abstract
The examination and treatment of 64 patients have shown that inclusion of complex antioxidant cytoflavin in intensive therapy at the postoperative period of diffuse peritonitis allows the hypoxia degree to be decreased that in its turn results in quicker recovery of the antioxidant system and decreased activity of peroxidation and endotoxicosis level. The clinical course of the postoperative period of diffuse peritonitis with cytoflavin included in intensive therapy is characterized by shorter terms of artificial lung ventilation, shorter time of staying in critical condition, more favorable course of complications.
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Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia.
Hamilton, PK, Hughes, SM, Plumb, RD, Devine, A, Leahey, W, Lyons, KS, Johnston, D, McVeigh, GE
Clinical science (London, England : 1979). 2010;(5):359-66
Abstract
In addition to lowering cholesterol, statins may alter endothelial release of the vasodilator NO and harmful superoxide free radicals. Statins also reduce cholesterol intermediates including isoprenoids. These are important for post-translational modification of substances including the GTPases Rho and Rac. By altering the membrane association of these molecules, statins affect intracellular positioning and hence activity of a multitude of substances. These include eNOS(endothelial NO synthase), which produces NO (inhibited by Rho), and NADPH oxidase, which produces superoxide (dependent on Rac). Statins may improve endothelial function by enhancing production of NO while decreasing superoxide production. A total of 40 hypercholesterolaemic patients were randomized to treatment with either atorvastatin or placebo; 20 normolipidaemic patients were also studied. Platelet nitrite, NO and superoxide were examined as was the cellular distribution of the GTPases Rho and Rac at baseline and after 8 weeks of treatment.Following atorvastatin therapy, platelet NO was increased (3.2 pmol/10(8) platelets) and superoxide output was attenuated [-3.4 pmol min(-1) (10(8) platelets)(-1)] when compared with placebo. The detection of both Rho and Rac was significantly reduced in the membranes of platelets, implying reduced activity. In conclusion, the results of the present study show altered NO/superoxide production following statin therapy. A potential mechanism for this is the change in the distribution of intracellular GTPases, which was considered to be secondary to decreases in isoprenoid intermediates, suggesting that the activity of the former had been affected by atorvastatin.
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Sedentary aging increases resting and exercise-induced intramuscular free radical formation.
Bailey, DM, McEneny, J, Mathieu-Costello, O, Henry, RR, James, PE, McCord, JM, Pietri, S, Young, IS, Richardson, RS
Journal of applied physiology (Bethesda, Md. : 1985). 2010;(2):449-56
Abstract
Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 + or - 6 yr) and six aged (71 + or - 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 + or - 62%) and during exercise (+143 + or - 40%), and this was further complemented by a greater increase in alpha-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 + or - 96% and +298 + or - 120%). Lipid hydroperoxides were also elevated at rest (0.190 + or - 0.169 vs. 0.148 + or - 0.071 nmol/mg total protein) and during exercise (0.567 + or - 0.259 vs. 0.320 + or - 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of alpha/beta-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans.
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[The free-radical processes and antioxidant therapy in brain ischemia].
Solov'eva, EIu, Mironova, OP, Baranova, OA, Bekman, EM, Aseĭchev, AV, Fedin, AI, Azizova, OA
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2008;(6):37-42
Abstract
A role of the free-radical processes and disturbances of oxidative-restorative blood homeostasis and nervous tissue in the pathogenesis of brain ischemic pathology and other diseases are reviewed. Attention is focused on the search for optimal ways of pharmacological correction of oxidative stress in the schemes of complex treatment of chronic blood circulation insufficiency and on the necessity of combined application of several antioxidants with different mechanisms of action which reciprocally potentiate each other. Experimental and clinical suppositions of the use of a-lipoic acid as one of the most studied antioxidant in the treatment of brain ischemia as well as the results of own studies on the preparation berlition which contains a-lipoic acid used in the neuroprotective therapy of chronic brain ischemia for correction of free-radical processes are discussed.
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Atorvastatin therapy lowers circulating cholesterol but not free radical activity in advance of identifiable clinical benefit in the treatment of mild-to-moderate AD.
Sparks, DL, Sabbagh, MN, Connor, DJ, Lopez, J, Launer, LJ, Petanceska, S, Browne, P, Wassar, D, Johnson-Traver, S, Lochhead, J, et al
Current Alzheimer research. 2005;(3):343-53
Abstract
Cholesterol-induced production of amyloid beta (Abeta) as a putative neurotoxin in Alzheimer's disease (AD), along with epidemiological evidence, suggests that statin drugs may provide benefit in treatment of the disorder. We tested the effect of once daily atorvastatin calcium (80 mg; two 40 mg tablets) on cognitive and/or behavioral decline in patients with mild-to-moderate AD. The study was designed as a pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to study medication employing last-observation-carried-forward (LOCF) ANCOVA as the primary statistical method of assessment. Alternate statistical methods were employed to further explore the effect of atorvastatin treatment on progression of deterioration. Of the 98 individuals with mild-to-moderate AD (Mini-Mental State Examination score of 12-28) providing Informed Consent, 71 were eligible for randomization, 67 were randomized and 63 completed the 3-month visit and were statistically evaluable. The primary outcome measures were change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) performance and the Clinical Global Impression of Change (CGIC). Secondary outcome measures included the MMSE, Geriatric Depression Scale (GDS), the Neuropsychiatric Inventory (NPI) and the ADCS Activities of Daily Living inventory (ADCS-ADL). Tertiary outcome measures included levels of total circulating cholesterol, LDL and VLDL, and circulating activity of the free radical scavenger enzymes superoxide dismutase (SOD) and glutathione peroxidase (GpX). Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared to placebo, but did not elicit a difference in circulating SOD or GpX activities. The observed beneficial clinical effect reached significance for the GDS (p = 0.040) and the ADAS-cog at 6 months (p = 0.003), was all but significant for the ADAS-cog (p = 0.055) at 12 months, and was of marginal significance for the CGIC (p = 0.073) and NPI (p = 0.071) at 12 months when employing the primary statistical approach (ANCOVA with LOCF). Application of repeated measures ANCOVA statistics revealed the difference was significant for the CGIC and marginally significant for the ADAS-cog, but not significant for the other clinical indices. This evaluation indicated significant time-by-treatment interactions (altered progression) for the ADAS-cog and MMSE, but not the CGIC. Application of random intercept regression analysis revealed a significant difference for the CGIC, ADAS-cog and MMSE. Regression analysis also indicated that atorvastatin produced change in the slope of deterioration on the MMSE. Accordingly, atorvastatin therapy may be an effective treatment and may slow the progression of AD among mild-to-moderately affected patients.
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Oxidative stress and damage induced by abnormal free radical reactions and IgA nephropathy.
Chen, JX, Zhou, JF, Shen, HC
Journal of Zhejiang University. Science. B. 2005;(1):61-8
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Abstract
OBJECTIVE To estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients' bodies. METHODS Seventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric methods. RESULTS Compared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P<0.0001), while those of VC, VE and beta-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P<0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those of VC, VE, beta-CAR, SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P<0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, beta-CAR, SOD, CAT and GPX were decreased gradually (P<0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%-92.5%, and the correct rates for the HAV were 70.0%-91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters' reliability coefficient (alpha) were used to estimate the oxidative damage of the IgAN patients as 0.8145, the standardized item alpha=0.9730, F=53273.5681, P<0.0001. CONCLUSIONS A series of free radical chain reactions caused serious pathological aggravation in the IgANP' bodies, thus resulting in oxidative damage in their bodies. In treating IgANP, therefore, it is necessary that suitable dose antioxidants should be supplemented to them so as to alleviate the oxidative damage in their bodies.
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Effect of hemodiafiltration against radical stress in the course of blood purification.
Tomo, T, Matsuyama, K, Nasu, M
Blood purification. 2004;:72-7
Abstract
The involvement of radical stress has been suggested as a cause for complications in patients on dialysis, such as arteriosclerosis, dialysis-related amyloidosis, etc. It has been reported that the increase in radical stress is not only seen in renal failure, but that its amplified effect is also seen in the process of blood purification. Our group has reported on the radical stress-reducing effect of HDF. We performed four types of blood purification (HD; on-line HDF; pre, on-line HDF; post, P/P HDF) in patients on maintenance dialysis using the polysulfone (APS) dialyzer. The change in radical related markers such as pentosidine (total, free) and CML (total, free), and the CTL/Cr ratio, and the hydroperoxide radicals were studied. In HDF (post, pre), the amplification rate of hydroperoxide radicals was significantly low, whereas the reduction rate of CTL/Cr ratio as index for hydroxy radicals was significantly higher in on-line HDF than in HD. Both the total CML and T-pentosidine increased in HD but showed a decrease in HDF. As HDF uses large amounts of replacement solution, the following effects can be expected: (a) suppression of the amplification of hydroperoxide radicals and suppression of the amplification of hydroxy radicals, and (b) suppression of fat oxidation by AGEs themselves. These antiradical stress effects are presumed to be exerted by effective removal of radical carrier protein, denatured protein, and complement protein in HDF, by dilution of radicals by massive use of replacement solution, and by the sequential reduction of the excitation and amplification effects.
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Role of free radicals and antioxidants in nasal polyps.
Dagli, M, Eryilmaz, A, Besler, T, Akmansu, H, Acar, A, Korkmaz, H
The Laryngoscope. 2004;(7):1200-3
Abstract
OBJECTIVES/HYPOTHESIS The aim of this study is to determine the role of free radicals and antioxidants in nasal polyps. STUDY DESIGN Prospective, randomized, controlled study. METHODS Thirty-one patients with nasal polyposis and a control group consisting of 19 patients with septal deviation and lower turbinate hypertrophy were included in the study. Levels of the antioxidants retinol, beta-carotene, alpha-tocopherol, and ascorbic acid were measured from the sera of the patients with nasal polyposis and the control group. Plasma levels of superoxide dismutase activity (SOD), glutathione peroxidase (GSHPX) activity, and reduced glutathione (GSH) were also obtained. As a peroxidation product, the levels of the malondialdehyde-thiobarbituric acid (MDA) combination were measured from the plasma of patient and control groups. Measurements of MDA, GSH, and alpha-tocopherol levels were also taken from the polyp tissue and turbinate mucosa of the control group. RESULTS The blood levels of antioxidants and MDA as an oxidant were significantly different in the patient group compared with the control group (P <.01). The tissue levels of antioxidants and MDA were significantly different in the patients with polyposis compared with the control group (P <.01). The blood and tissue anti-oxidant levels were found to be decreased, and MDA levels as an oxidant increased significantly in the patient group with polyposis when compared with the control group, and there was a negative correlation between oxidative stress and antioxidants. CONCLUSION This study demonstrates that oxidative stress and tissue and blood antioxidants in the patients with polyposis were significantly different compared with the control group. The blood and tissue antioxidant levels decreased, and MDA levels, as an oxidant, increased significantly in the patient group with polyposis when compared with the control group. The current study demonstrates that there is strong evidence related to oxidative stress in the pathogenesis of nasal polyposis, and antioxidants can have a preventive role in free-radical-mediated tissue damage in nasal polyposis.