Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxygen free radical-induced lipid peroxidative reactions that occur during resuscitation from normothermic cardiac arrest may contribute to the degree of neurologic dysfunction sustained. A blinded, randomized experimental trial was performed to determine whether U74006F, a potent inhibitor of lipid peroxidation, reduces morbidity and 24-hour mortality after 10 minutes of normothermic cardiopulmonary arrest; ventricular fibrillation was induced by electrical stimulation in 24 open-chest, halothane-anesthetized dogs, and circulation was reestablished by direct cardiac compressions, administration of a standardized drug regime, and internal countershocks. When spontaneous circulation was restored, a bolus injection of 1.5 mg/kg U74006F (n = 12) or 25 mM citrate vehicle (n = 12) was infused intravenously in 15 minutes and an infusion was continued at 0.125 mg/kg/hr for the next 12 hours. In the drug-treated group, plasma U74006F concentration averaged 0.13 microgram/ml between 3 and 12 hours after cardiac arrest. By 24 hours after arrest, 10 of 12 (83%) vehicle-treated dogs had died but only four of 12 (33%) U74006F-treated dogs had died (p = 0.017). U74006F-treated dogs survived significantly longer (mean +/- SEM 22 +/- 1 hr) than vehicle-treated dogs (18 +/- 1 hr), with significantly better neurologic function 1, 2, and 24 hours after arrest. Plasma fatty acid hydroperoxide concentrations 12 hours after arrest were 88 +/- 81 pmol/ml in U74006F-treated and 241 +/- 49 pmol/ml in vehicle-treated dogs (p less than 0.05). Vitamin E concentrations were significantly higher in the plasma of U74006F-treated dogs 2, 3, and 6 hours after arrest compared with vehicle-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the aminosteroid U74006F after cardiopulmonary arrest in dogs. 318 22

Vitamin E (tocopherol) concentrations in blood plasma were determined in 48 infants and correlated with their nutritional status. Infants were divided into two groups as following: group I (n : 12) estimated well-nourished, and group II (n : 36) appreciated undernourished. Clinical nutritional status was evaluated according to their weight, height and skinfold thickness of triceps percentiles. Plasma vitamin E levels were analysed by a modification of the spectrophotometric micro-technique of Fabiank et al. (using 0.2 ml of plasma). There was difference in serum tocopherol levels between two groups: 1.21 (0.21) mg/dl: mean (+/- SEM) in group I in front of 1.84 (0.18) mg/dl in group II (0.10 greater than p greater than 0.05). On the other hand, vitamin E concentrations were correlated with the skinfold thickness of triceps percentiles by a logarithm curve: y = 2.25-0.31 1n X (r: 0.35, p less than 0.02). Probably, serum vitamin E levels do not reflect the tissue store status in undernourished infants without malabsorption.
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PMID:[Serum vitamin E in well-nourished and malnourished infants]. 366 50

Thirty elderly (mean +/- SEM: 73.8 +/- 2.1 y) nondiabetic, moderately obese (body mass index = 28.3 +/- 0.6 kg/m2) patients with stable effort angina underwent an oral-glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). The study was of a randomized, placebo-controlled, double-blind, and crossover design. Anthropometric indexes were stable throughout the study. Despite similar fasting and 2-h plasma glucose concentrations, vitamin E administration (compared with placebo) lowered fasting (88 +/- 14 and 68 +/- 9 pmol/L, P < 0.02) and 2-h (348 +/- 43 and 263 +/- 28 pmol/L, P < 0.05) plasma insulin concentrations, plasma triglyceride concentrations (1.34 +/- 0.06 and 1.07 +/- 0.03 mmol/L, P < 0.05), and the ratio of plasma LDL to HDL cholesterol (7.64 +/- 0.31 and 5.52 +/- 0.38, P < 0.02). Vitamin E administration was associated with higher nonoxidative glucose metabolism (18.1 +/- 0.5 and 10.6 +/- 0.7 mumol.kg lean body mass-1.min-1, P < 0.03) than was placebo administration during the euglycemic glucose clamp. We conclude that chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly insulin-resistant patients with coronary heart disease.
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PMID:Chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly patients with coronary heart disease. 770 30

Vitamin E was quantified in renal cell carcinomas (RCC) and in 'intact' renal cortex, obtained from 31 patients subjected either to unilateral nephrectomy or to partial resection of the only kidney. Histologically, 14 tumors consisted predominantly of clear cells (group 1) and 17 of other cell types (group 2). In both groups, a significant increase in vitamin E concentration, as compared to the 'intact' cortex, was observed: 167.8 +/- 27.9 and 68.2 +/- 15.2 micrograms/g wet tissue weight (mean +/- SEM) for groups 1 and 2, respectively, versus 10.1 +/- 0.53 micrograms/g wet tissue weight for the cortex. Although the total lipid content was also increased in tumors (especially in group 1), the vitamin E concentration in tumor tissue, calculated per milligram of total lipids, proved to be much higher in both groups than in 'intact' cortex. A significant positive correlation was observed between vitamin E and total lipid content in group 1 and 2 carcinomas. It was also found that vitamin E accumulation in RCC is unlikely to be attributed to an enhanced lipid deposit in the tumor cells. Thus, in 8 tumors of group 2 the vitamin E levels were markedly enhanced although these tumors did not differ from the cortex in total lipid concentrations. Vitamin A content determined in 17 carcinomas, when calculated per milligram of total lipids, was the same as in 'intact' cortex.
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PMID:Liposoluble vitamins E and A in human renal cortex and renal cell carcinomas. 777 11

Vitamin E was quantified in the cortex and medulla of human, rat, canine and rabbit kidneys. For the all species investigated the vitamin concentrations, calculated both per g wet tissue weight and per mg tissue protein, was shown to be 1.4-2.2 times higher in medullary layer than in cortical one. The least vitamin E levels were observed in rabbit kidneys of which the cortical and medullary concentrations were 4.4 +/- 0.3 mkg (M +/- SEM) and 6.3 +/- 0.56 mkg per g wet tissue weight, respectively. In human renal cortex and medulla the vitamin concentrations were found to be 10.6 +/- 0.66 mkg and 16.2 +/- 1.1 mkg per g wet tissue weight, respectively. Close values were observed for other species studied as well. The increased renal medullary vitamin E concentrations are likely related to the higher phospholipid metabolism and enhanced prostaglandin synthesis in this tissue.
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PMID:[Vitamin E content in cortical and medullary layers of mammalian kidney]. 805 6

Vitamin E is an endogenous antioxidant and is known to afford protection against lipid peroxidation. If lipid peroxidation was an important factor in the pathogenesis of reoxygenation injury in heart, then both the extent of lipid peroxidation and cell injury would be expected to be exacerbated in vitamin E-deficient hearts. To study reoxygenation injury in the present experiments, rat hearts were perfused in the Langendorff mode with a modified Krebs-Henseleit buffer under anoxic conditions for 60 min before resuming normoxic perfusion for 20 min. Creatine phosphokinase (CPK) activity and malonyldialdehyde (MDA), a product of lipid peroxidation, were assayed in the perfusate effluent from hearts during reoxygenation injury. Also, myocardial MDA and vitamin E contents were measured in extracts of freeze-clamped heart tissue obtained immediately before and 2 min after reoxygenation. Experiments were performed on hearts from groups of weanling rats fed either a vitamin E-deficient or vitamin E-supplemented diet (50 I.U. vitamin E/kg) for 5 to 6 weeks. After 5 weeks, the myocardial vitamin-E content was 103.8 +/- 5.3 (n = 5) and 11.5 +/- 1.6 (n = 4) ng/mg protein (mean +/- SEM) in the vitamin E-supplemented and vitamin E-deficient groups respectively. Perfused hearts from both dietary groups showed a peak of enzyme release 2 to 3 min after the reintroduction of oxygen, and enzyme release from vitamin E-deficient hearts was two-fold greater than enzyme release from vitamin E-supplemented hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No evidence of malonyldialdehyde formation during reoxygenation injury in vitamin E-deficient rat heart. 824 Feb 24

There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu(2+) was increased by 157% (110-232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185-259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122-192%) (P<0.005) and 177% (101-267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115-169%) (P<0.005) and 171% (122-192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104-153%) (P<0.05) on 200 mg/day and 240% (97-360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12. 7+/-2.6 (mean+/-SEM) to 16+/-3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4+/-2.0 to 19.2+/-3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA resembled that reported with another antioxidant, probucol. Some evidence has suggested that increased CETA is potentially deleterious and it might therefore counteract beneficial effects of vitamin E or probucol on the susceptibility of lipoproteins to oxidation.
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PMID:Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity. 1078 43

Vitamin E content of cardiac tissue has been proposed to play a major role in the damage caused by myocardial ischemia-reperfusion (I-R). Previous studies using in vitro models have examined vitamin E deficiency and I-R-induced myocardial damage with equivocal results. The purpose of this study was to use an in vivo model of myocardial I-R to determine the effects of vitamin E deficiency on myocardial I-R-induced damage. Female Sprague-Dawley rats (4-mo old) were assigned to either: 1) control diet (CON), or 2) vitamin E deficient diet (VE-DEF). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU vitamin E/kg diet. The VE-DEF diet was the AIN-93M diet prepared with tocopherol stripped corn oil and no vitamin E. Following a 14-week feeding period, significant differences (p < 0.05) existed in mean myocardial VE levels between groups (mean values +/- SEM: CON = 48.2 +/- 3.5; VE-DEF = 12.4 +/- 1.4 micrograms VE/g wet weight). Animals from both experimental groups were subjected to an in vivo I-R protocol consisting of 25 minutes of left coronary artery occlusion followed by 10 minutes of reperfusion. No group differences (p > 0.05) existed in cardiac performance (peak arterial pressure or ventricular work) or the incidence of ventricular arrhythmias during the I-R protocol. VE-DEF animals had significantly higher (p < 0.05) levels of myocardial lipid peroxidation and lower (p < 0.05) protein thiols following I-R compared to the CON animals. These data suggest that although vitamin E deficiency increases oxidative damage resulting from myocardial I-R, it does not affect cardiac performance during the insult.
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PMID:Vitamin E deficiency fails to affect myocardial performance during in vivo ischemia-reperfusion. 1121 54

Paclitaxel is a promising anti-cancer drug as well as a radiosensitizer for chemotherapy and radiotherapy applications. Because of the poor solubility of paclitaxel in water and most pharmaceutical reagents, it is usually formulated with an adjuvant called Cremophor EL, which causes severe side effects. This work develops new dosage forms of paclitaxel for controlled release application, which do not require the adjuvant and, thus, can avoid its associated side effects. Paclitaxel was encapsulated into the PLGA matrix with various additives such as polyethylene glycol (PEG), isopropyl myristate (IPM) and d-alpha tocopheryl polyethylene glycol (Vitamin E TPGS). These additives were used to enhance the release rate of paclitaxel from the polymer matrix. Spray-drying and an hydraulic press were used to prepare paclitaxel-PLGA microspheres and discs. The microspheres and discs were given different irradiation doses to investigate their effects on the surface morphology (characterized by SEM, AFM and XPS) and in vitro release properties. There seems to be a small effect of the ionizing radiation on various formulations. Although the irradiation did not cause observable changes on the morphology of the polymer matrix, the release rate can be enhanced by a few per cent. It was found that PEG has the highest enhancement effect for release rate among all the additives investigated in this study.
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PMID:Release of paclitaxel from polylactide-co-glycolide (PLGA) microparticles and discs under irradiation. 1288 Nov 13

Within the past decade, more than half of the drug candidates generated are poorly water soluble and therefore overcoming the low aqueous solubility of drug candidates becomes critical for product development. Vitamin E TPGS (VeTPGS), a non-ionic surfactant, has been used in both liquid and solid dosage forms to solubilize compounds and improve their bioavailability. To prepare solid dosage forms using VeTPGS, VeTPGS is often mixed with other excipients, mostly polymers. However, there is still a lack of understanding of miscibility between VeTPGS and polymers from a thermodynamic point of view. In this paper, the miscibility of VeTPGS with polymers has been studied in the light of the Flory-Huggins (F-H) theory with an objective to understand the effect of dispersion forces (solubility parameter) and nondispersive interactions on the miscibility between VeTPGS and polymers. A series of polymers with similar solubility parameters and structure similarity were selected. Binary blends of polymers and VeTPGS were prepared using a vapor evaporation technique followed by XRPD, DSC, and SEM characterization. Results suggest that the miscibility between VeTPGS and PMMA is very likely due to a specific interaction between the hydrophobic portion of VeTPGS (Vitamin E) and PMMA.
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PMID:An investigation of the thermodynamic miscibility between VeTPGS and polymers. 1795 Oct 16


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