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ABSTRACT: There has been growing interest in using dietary intervention to improve the lipid profile. This work aims at analyzing the effects and the comparison of the enrichment of a diet with beta-glucans or rice bran in mildly hypercholesterolemic men.
The subjects initially consumed a 3-week Step 1 American Heart Association diet with rice bran-enriched foods. After this adaptation period, volunteers were randomly assigned to follow a crossover, controlled trial that consisted of two treatment with beta-glucan- or rice bran-enriched foods, each of 4 weeks, with a 3-week wash-out, like the adaptation period, between periods. Fasted blood samples were collected on days 0, 21, 49, 70 and 98 in both study arms for measuring low-density lipoprotein (LDL)-cholesterol (primary outcome), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B and glucose levels.
Twenty-four men (mean age: 50.3±5.3, mean body mass index: 24.9±1.9) completed the 14-week trial. Subjects in the 3-week adaptation period experienced significant reductions in the mean level of LDL cholesterol, total cholesterol, total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, apo A-I, apo A-I/apo B and glucose. During the intervention diet periods, a difference was found between treatment groups for the mean change in LDL (0.21 (95% confidence interval (CI): 0.02-0.40), P=0.033) and total cholesterol (0.34 (95% CI: 0.20-0.47), P<0.001). Other parameters evaluated were not significantly affected by the diet consumed.
The results of the present crossover clinical trial showed that beta-glucan-enriched foods are more effective in lowering serum LDL levels, compared with rice bran-enriched foods.
European journal of clinical nutrition 04/2011; 65(7):864-71. · 3.07 Impact Factor
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ABSTRACT: Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies.
In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched controls. In the same subjects, the so-called "lag-time", an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method.
Before treatment, peroxide levels were significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs 168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/-33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/-10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lag-time and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels.
These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.
Journal of endocrinological investigation 11/2006; 29(10):899-904. · 1.57 Impact Factor
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G Goi,
R Cazzola,
C Tringali,
L Massaccesi,
S Russo Volpe,
M Rondanelli,
E Ferrari,
C J Baquero Herrera, B Cestaro,
A Lombardo,
B Venerando
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ABSTRACT: In this study, a comparison between elderly (>70 years) and young subjects reveals that elder people are subject to a higher oxidative stress, which causes an increase in plasma hydroperoxide levels (18%) and a decrease in antioxidant defenses (25%). Moreover, the marked decrease of the erythrocyte membrane fluidity observed in elderly subjects was likely to affect the behavior of some membrane glycohydrolases. In fact, a significant decrease of beta-d-glucuronidase and neutral sialidase (30 and 50%, respectively) was detected. Activity differences were also observed when erythrocytes were further distinguished according to their biological age. Striking differences between young and elderly subjects were observed for beta-d-glucuronidase and neutral sialidase in young and senescent erythrocytes, respectively. Overall beta-d-glucuronidase decreases with the subjects' age, while neutral sialidase levels are higher in the elderly. This is presumably due to the localization of these enzymes in distinct plasma membrane micro-domains, which are differently peroxidized. A possible role of these enzymes in signaling praecox membrane alterations has also been evidenced.
Experimental Gerontology 03/2005; 40(3):219-25. · 3.74 Impact Factor
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ABSTRACT: Physical exercise is characterized by an increase in oxygen consumption by the whole body. This leads to a decrease in antioxidant levels that could promote both an increase in the markers of lipoprotein peroxidation and damage to the erythrocyte membrane with consequent modification of membrane fluidity.
Different markers of oxidative stress, erythrocyte membrane fluidity and antioxidant status were determined in 20 professional soccer players and 20 sedentary controls. Plasma lipoperoxides and kinetics of Cu-stimulated plasma peroxidation were measured together with hydrosoluble (albumin, uric acid and vitamin C), liposoluble (vitamin E and bilirubin) and enzymatic (superoxide dismutase and glutathione peroxidase) serum antioxidants. Erythrocyte membrane rigidity was determined by measuring fluorescence anisotropy (rs) of the fluorescent probe 1, 3, 5 diphenylexatriene.
The sportsmen showed higher levels of the following plasmatic antioxidants: ascorbic acid (P<0.0001), uric acid (P<0.0001), alpha-tocopherol (P=0.03) and superoxide dismutase activity (P=0.0001). According to this evidence, the lipoperoxide levels (P=0.0158), the duration of the latency phase of plasma peroxidation (P=0.0123) and erythrocytes membrane fluidity (P=0.0152) were found to be significantly higher in the soccer players.
Athletes undergoing regular and adequate training show improved antioxidant status together with a more fluid membrane status, which could contribute to improving both peripheral resistance to insulin and all the functional metabolic interchanges in the cellular membrane.
European Journal of Clinical Investigation 10/2003; 33(10):924-30. · 3.02 Impact Factor
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ABSTRACT: To assess whether plasma peroxidation and plasma levels of antioxidant compounds are correlated with clinical and biochemical activity in complicated Crohn's disease patients, and to evaluate whether the relief of obstructive complication by conservative surgery has any effect on the oxidative stress.
From May 1998 to May 2000, 20 Crohn's disease patients were studied. Basal peroxidative state (basal thiobarbituric acid reactive substances), peroxidative state after stimulation with copper sulfate (stimulated thiobarbituric acid reactive substances], lag time of plasma peroxidation susceptibility, plasma levels of vitamin E and A, C reactive protein, erythrocyte sedimentation rate and Crohn's disease activity index, were determined, before surgery, then 2 months and 1 year after surgery. A group of 134 healthy volunteers were used as controls. All patients were treated by conservative surgical procedures (i.e., strictureplasty and/or minimal resections). Student t test for paired and unpaired data and Spearman R correlation coefficient were calculated.
Peroxidative plasma levels, as well as inflammatory indices, are significantly reduced 2 months and 1 year after surgery (p < 0.005), but basal levels of peroxidation and antioxidant scavengers seem to be disregulated in Crohn's disease patients compared to those in controls (p < 0.005). A correlation was found between basal thiobarbituric acid reactive substances, lag-time and erythrocyte sedimentation rate (R:0.51; p < 0.05. R:0.56; p < 0.05) and C reactive protein (R:0. 6; p < 0.005. R:0. 65; p < 0.005).
An imbalance between pro- and antioxidant mechanisms, due to chronic gut inflammation, is present in complicated Crohn's disease, and an excess of lipid peroxidation is probably an important pathogenetic factor Conservative surgery can reduce the oxidative stress avoiding repeated or extended resections that could lead to intestinal malabsorption and short bowel syndrome.
Digestive and Liver Disease 10/2002; 34(10):696-701. · 3.05 Impact Factor
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ABSTRACT: Adipose tissue is not simply a storage depot for excess energy intake, it is also able to produce and release several substances with local (autocrine) and systemic (endocrine) actions. An up-to-date review of our knowledge in this area is given here. Several of the compounds deriving from adipose tissue have been shown to play a role in obesity-related health complications. The production of cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha), IL-6, and leptin, is implicated in the development of several disorders. Insulin resistance is one of the most clinically significant.
Minerva gastroenterologica e dietologica 01/2002; 47(4):205-7.
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ABSTRACT: Modifications in dietary fat profile have shown to affect body weight gain and adiposity. This may occur through the changes of cell membrane fluidity, in particular of the peripheral muscle tissue. The decreased availability of diet polyunsaturated fatty acids (in particular of the to-3 series), that are able to induce membrane fluidification, together with an excessive intake of both saturated fatty acids and cholesterol, that on the contrary are able to rigidify the same membranes, promoter both a progressive immobilization of membrane proteins and a consequent decrease in their functional rate of liver lipoproteins VLDL, enriched in saturated fats and cholesterol. This lipoprotein increase promotes both the fat deposition in the adipose tissues and a further increase in the muscle membrane rigidity that is followed by a further enhancement in the peripheral resistance to insulin. A diert rich both in polyunsaturated fatty acids and antioxidants (vitamin and oligoelements), and in essential amino acids together with a preferential choice of complex carbohydrates (amylose, amylopectine, etc) in comparison to simple sugars (glucose, fructose, saccharose, lactose, etc) may significantly contribute to the maintenance of the correct degree of membrane fluidity and, as a consequence, to the physiologically correct body weight.
Minerva gastroenterologica e dietologica 01/2002; 47(4):181-5.
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ABSTRACT: Obesity is now recognized as a major risk factor for many pathologies. The state of obesity is associated with an increase in reactive oxygen species; persistent overconsumption of calories in the obese may be exposing them to excessive damage besides maintaining the state of obesity. It is possible that dietary modification and association with assumption of antioxidant and omega-3 oral integration contributes to a reduction in reactive oxygen species generation and a corresponding reduction in indexes of oxidative damage, including lipid peroxidation.
Given this back-ground, the pro/anti-oxidant balance, biochemical parameters and the body composition were studied in two groups of obese women: a first group of 10 obese women were studied before and after eight weeks of dietary restriction and a second group of 12 obese women were studied before and after eight weeks of dietary restriction and oral administration of antioxidant and omega-3.
In summary, as regards the preliminary results of clinical outcome parameters, interestingly enough the glycemic levels fall markedly in association with both dietary restriction and oral integration with antioxidant and omega-3. Another important finding of this study is that of calcium levels and phase angle (measured by impedenzometry) increase in the group treated with dietary restriction and oral administration of antioxidant and omega-3.
Studies that aimed to explore whether oxidative status predicts clinical outcome would provide important details on the putative link between oxidative status and state of obesity.
Minerva gastroenterologica e dietologica 01/2002; 47(4):195-204.
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ABSTRACT: To investigate the effects of a hypocaloric balanced diet therapy and a supplementation with antioxidant and omega-3 polyunsaturated fatty acids on the oxidative balance and erythrocytes membrane fluidity status.
A randomised, double-blind, placebo-controlled study of the association between a hypocaloric balanced diet therapy and a supplementation with antioxidant and omega-3 was done on 40 women with 25 < BMI < 33. The inclusion criteria were the following: absence of dismetabolic pathologies, of previous hypocaloric diet therapy and/or supplementation and of hormonal treatments. Each subjects consumed a balanced diet with a daily caloric intake equal to: Kcal of basal metabolism (determined by indirect calorimetry) x LAF (1.64) 800 Kcal. At the start and after two months of treatment, the blood chemistry and anthropometrics parameters, the plasmatic reactive oxygen species (ROS) and antioxidant defence levels and erythrocyte membrane fluidity status were measured.
The preliminary results of this study show that the weight loss, found in both groups investigated, determines a significant decrease of ROS. Furthermore, the association of the hypocaloric diet with antioxidant and omega-3 polyunsaturated fatty acids caused a significant increase of both plasmatic antioxidant defences and erythrocytes membrane fluidity status.
The correlations found between the above parameters and the blood chemistry and anthropometrics variables suggest that the supplementation with antioxidant and omega-3 polyunsaturated fatty acids could ameliorate the effects of hypocaloric diet on the obesity treatment and may give some clinical benefit through the decrease of the values of atherosclerosis risk factors.
Minerva gastroenterologica e dietologica 12/2001; 47(4):187-94.
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ABSTRACT: The antioxidant properties of milk casein subunits (alpha-casein, beta-casein and kappa-casein) were evaluated in liposomal models. All the subunits of casein are able to inhibit Fe-induced peroxidation of arachidonic acid inserted into multilamellar liposomes of dipalmitoylphosphatidylcholine (0.2 mM and 0.8 mM, respectively). The peroxidation was monitored as thiobarbituric acid reactive substances, and the strongest inhibitory effect occurred when 500 micrograms of alpha-casein were added to 0.5 ml of liposomal suspension. At this concentration, peroxidation was completely inhibited in our experimental conditions (incubation for 2 h at room temperature, with a mixture of ferrous sulfate and ascorbate, 50 and 500 microM final concentration, respectively). The mechanisms of antioxidant action are complex, but the strongest effect is achieved by modifying the Fe2+/Fe3+ equilibrium; in fact, caseins seem to favour the autoxidation of iron, and thus inhibit lipid peroxidation.
International Journal of Food Sciences and Nutrition 08/1999; 50(4):291-6. · 1.15 Impact Factor
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ABSTRACT: The effect of alpha-tocopherol enrichment of low- and high-density lipoproteins on Cu(2+)-catalyzed lipid peroxidation in the hydrophobic core and in the hydrophilic envelope of lipoproteins was investigated by using two pyrene derivatives, namely, cholesteryl pyrenyl hexanoate (P6Chol) and pyrene dodecanoyl sulfatide (P12CS). The progressive decrease in fluorescence of P6Chol was used to monitor lipid peroxidation in the core of LDL and HDL, whereas that of P12CS was used to follow lipid peroxidation in the envelope of both lipoproteins. alpha-Tocopherol enrichment of LDL and HDL was obtained by incubating blood plasma at 37 degrees C with different concentrations of the vitamin (25-500 microM) before lipoprotein separation. The incorporation of alpha-tocopherol in LDL and HDL presents a progressive, time-dependent increase up to 200 microM alpha-tocopherol, then a plateau up to 500 microM. In the envelopes, the added tocopherol causes a great decrease in the rate of peroxidation and a dramatic increase in the latency phase in both lipoproteins. In the cores the lengthening of latency phase resulting from alpha-tocopherol enrichment was by far greater in LDL than in HDL, and the decrease in the rate of peroxidation in both lipoproteins was less than in the envelopes.
Journal of Nutritional Science and Vitaminology 02/1999; 45(1):39-48. · 1.20 Impact Factor
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ABSTRACT: In human ageing and with many pathologies correlated to the senile functional decay of cells, membrane damage often occurs in some organ or tissue, which provokes lipid peroxidation in the membrane and accelerates the disorder in structure and function of the membrane. When lipid peroxides accumulate sufficiently, they leak from the organ or tissue into the bloodstream and increase the lipid peroxide level in blood lipoproteins. The increased lipid peroxides in the blood attack the blood vessel and promote atherogenesis. This paper describes the possible involvement of free radicals in this damage, both to tissues and to blood vessels, which contributes to the senile functional decay of the tissues.
European Journal of Cancer Prevention 04/1997; 6 Suppl 1:S25-30. · 2.13 Impact Factor
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ABSTRACT: An excess of free-radical production has been linked to many diseases and to the ageing process. Oxidant by-products of normal metabolism can cause extensive damage to DNA, protein and lipid. Exposure to ultraviolet light, cigarette smoke and other environmental pollutants may also increase the free radical burden. The accumulation of unrepaired oxidative damage products is likely to be a major factor in cellular ageing. Many repair processes are available to the cell, including enzyme and structural defences. The large group of natural antioxidants is also part of a protective mechanism. High consumption of fruit and vegetables in the diet is associated with a lowered risk of degenerative diseases. At present, however, there are few data to support the routine use of exogenous antioxidants to prevent and treat these diseases.
European Journal of Cancer Prevention 04/1997; 6 Suppl 1:S31-6. · 2.13 Impact Factor
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ABSTRACT: Physical activity raises oxygen demand by many fold, causing a parallel increase in the formation of oxygen radical species. Vitamins are concerned with either energy metabolism or free radical scavenging. This review outlines the possible damage to cell structures following strenuous exercise and the role of vitamins as part of natural anti-oxidant defence systems. A brief discussion is included on the relationship between physical activity, the immune system and cancer.
European Journal of Cancer Prevention 04/1997; 6 Suppl 1:S55-67. · 2.13 Impact Factor
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ABSTRACT: Moderate wine intake has been associated with low risk for cardiovascular disease, possibly due to its polyphenol content. We investigated the influence of these compounds on peroxidative indices of blood. Forty Sprague-Dawley rats were divided into four groups given the same AIN-76 diet but different types of isocaloric beverage: red wine, alcohol and dealcoholated wine and water with added sucrose. Rats consumed about 35 ml day(-1) of beverage and 17 g day(-1) of diet for a total of about 95 kcal day(-1). Plasma alpha-tocopherol was higher in the alcohol group and the peroxidation kinetic slope was higher in the control and dealcoholated wine groups. Ascorbic acid in whole blood was higher in the alcohol group than the others. Erythrocytic glutathione peroxidase activity was lower in the red wine group. The other variables studied, were not significantly different in the four groups. Despite the significant differences observed, the oxidative status of blood does not appear seriously altered by heavy ingestion of wine and thus of polyphenols. Probably the balanced diet and adequate intake of micronutrients were sufficient to counteract any oxidative damage.
International Journal of Food Sciences and Nutrition 04/1996; 47(2):181-9. · 1.15 Impact Factor
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ABSTRACT: Synaptosomes obtained from rat striata lesioned by central injection of endothelin-1 (ET-1) were analyzed for the levels of lipid peroxidation products, the susceptibility to lipid peroxidation, the phospholipid and free fatty acid composition and the activity of Na+,K(+)-ATPase one hour after ET-1 treatment. The intrastriatal injection of ET-1 promoted an increase of endogenous thiobarbituric reactive substances (TBARS), as index of free radical mediated lipid damage, and a greater susceptibility to iron/ascorbate-induced lipid peroxidation. The pattern of free fatty acids showed a significant decrease of arachidonic and docosahexaenoic acid consequent to ET-1 treatment. The analysis of lipid composition showed a significant loss of phospholipids: among phospholipid species, sphingomyelin and phosphatidylethanolamine plasmalogen were particularly reduced by ET-1 treatment. The activity of membrane-bound Na+,K(+)-ATPase was also significantly reduced in synaptosomes obtained from ET-1 lesioned striata. Taken together these results indicate a significant modification of synaptosomal membrane of ET-1 treated rat striata, possibly due to a free radical mediated damage.
Neurochemical Research 07/1995; 20(6):689-95. · 2.24 Impact Factor
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ABSTRACT: There is epidemiological evidence that a moderate consumption of alcohol could reduce coronary heart disease. To corroborate this statement and to see how the consumption of red wine affects phospholipid and fatty acid patterns and antioxidant status, a survey was conducted on 58 adult males (20-75 years old). A questionnaire was used to discover their medical history, various constitutional and life-style factors, food habits, and nutrient intake; and the type and amount of alcoholic intake were investigated by means of a questionnaire. Subjects were divided into two groups of nondrinkers and average drinkers (mean 46.5 +/- 4.4, range 30.2-63.4 g/day), and the effect of alcohol was made on the following variables: gamma-glutamyltranspeptidase, apolipoprotein AI, apolipoprotein B, total and high-density lipoprotein-cholesterol, triglycerides, and antioxidant vitamins were determined in plasma; and phospholipids the fatty acids of phosphatidylcholine (PC) and phosphatidylethanolamine total cholesterol, alpha-tocopherol, beta-carotene, and retinol were determined in red blood cells (RBCs). There were no significant differences between the two groups in protein, fat, carbohydrate, retinol equivalent, alpha-tocopherol content, and cholesterol/saturated fat index of their diet. Analysis of the plasma levels of biochemical variables--adjusted for age, smoking (number of cigarettes/day), and body mass index--showed a significant increase of gamma-glutamyltranspeptidase and apolipoprotein AI concentration in the average drinkers compared with nondrinkers. Plasma alpha-tocopherol and retinol levels were also significantly higher in average drinkers. In the latter group, ANCOVA demonstrated a lower percentage of sphingomyelin in RBCs, with a lower sphingomyelin/PC ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcoholism Clinical and Experimental Research 05/1995; 19(2):517-22. · 3.34 Impact Factor
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ABSTRACT: The peroxidative potential of whole plasma was studied in thirteen control subjects and twenty-three diabetic patients divided into two groups on the basis of their metabolic control, defined as good (n = 12) or poor (n = 11) according to the fasting blood glucose, glycated hemoglobin and fructosamine levels. The amounts of thiobarbituric reactive substances (TBARS) were determined before and after an exhaustive peroxidation induced by incubation with cupric sulfate; the kinetics of Cu-dependent plasma peroxidation, determined by the time course of endogenous fluorescence emission at 430 nm, were also evaluated. Our data indicate that in diabetic patients, and particularly in those with a long-lasting poor metabolic control, a significant increase in plasma susceptibility to peroxidative stress is evident only when we consider the lag-time of fluorescence emission in the course of Cu-induced plasma peroxidation. A good inverse correlation was observed between the lag-time and the blood glucose concentration, the glycated hemoglobin and the fructosamine blood levels. Furthermore a multivariate analysis, performed by Principal Component Analysis, strongly supports the relation between the extent and duration of the diabetic pathology, and the decrease in the lag-time of oxidation.
Biochemistry and molecular biology international 05/1994; 32(5):983-94.
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B Cestaro
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ABSTRACT: Axon growth and axon regeneration are complex processes requiring an adequate supply of certain metabolic precursors and nutrients.
This article reviews the studies examining some of the processes of protein modification fundamental to both nerve regeneration and to the continuous and adequate supply of specific factors such as arginine, S-adenosylmethionine and polyamines.
The process of arginylation notably increases following nerve injury and during subsequent regeneration of the nerve, with the most likely function of arginine-modification of nerve proteins being the degradation of proteins damaged through injury. It appears that defective methyl group metabolism may be one of the leading causes of demyelination, as suggested by the observation of reduced cerebrospinal fluid concentrations of s-adenosylmethionine (SAMe) and 5-methyltetrahydrofolate, the key metabolites in methylation processes, in patients with a reduction in myelination of corticospinal tracts. Polyamine synthesis, which depends strongly on the availability of both SAMe and arginine, markedly increases in neurons soon after an injury. This "polyamine-response" has been found to be essential for the survival of the parent neurons after injury to their axons. Polyamines probably exert their effects through involvement in DNA, RNA and protein synthesis, or through post-translational modifications that are indicated as the most relevant events of the "axon reaction."
Nerve regeneration requires the presence of arginine, s-adenosylmethionine, and polyamines. Further studies are needed to explore the mechanisms involved in these processes.
Acta neurologica Scandinavica. Supplementum 02/1994; 154:32-41.
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ABSTRACT: Several investigators have observed that a moderate intake of alcohol can have a positive effect on health (lowering the risk of cardiovascular disease, gall-stones, etc.). Our objective was to investigate how some blood constituents are affected by the consumption of different levels of alcohol. Erythrocyte phospholipids and fatty acids composition and plasma fat-soluble vitamins were determined in 28 volunteers who were divided into three groups according to their alcohol intake: non-drinkers, moderate drinkers--consumption of 20-60 g/day, and heavy drinkers--more than 60 g/day. A relation was seen between alcohol consumption and vitamin status; furthermore alpha-tocopherol and beta-carotene were significantly lower in heavy drinkers. The erythrocyte phospholipid compositions of the non- and moderate drinkers showed no significant differences whereas a definite relation was noted when the alcohol intake was higher than 60 g/day. In conclusion it is possible to say that a moderate alcohol intake does not have any significant effect on the phospholipid and fatty acid composition; only the vitamin status is significantly influenced, but to confirm our results it is essential to evaluate other variables involved in this problem such as the lifestyle, physical activity and the eating habits of the subjects tested.
Minerva medica 10/1993; 84(9):447-52. · 0.90 Impact Factor
