Interrelationship and competition of α- and λ-tocopherol at the level of intestinal absorption, plasma transport and liver uptake

α- and λ-Tocopherol (T) were measured in the plasma of 3 groups of rats that were fed a normal or modified AIN-76 diet containing normal (NE), high (HE) or low (LE) vitamin E for 3 months. α-T levels (μg/ml±SD; n=10) were 7.6±1.0 (NE), 19.3±5.1 (HE) and 0.48±0.43 (LE). λ-T levels were 0.32±0.16 (NE), 0.02±0.05 (HE) and 0.20±0.30 (LE). 24 hrs after an oral dose of 50 mg λ-T; α-T levels (n=3) were 7.0±1.2 (NE), 10.7±3.7 (HE) and 1.0±0.3 (LE). λ-T levels were 5.7±2.2 (NE), 0.83±0.46 (HE) and 10.8±3.8 (LE). When 3 rats from groups NE and HE were fed low vitamin E for 3 days prior to the administration of 50 mg λ-T; α-T levels were 4.8±1.3 (NE) and 7.1±1.5 (HE); λ-T levels were 5.9±2.0 (NE) and 4.6±2.6 (HE). When rats in group LE received 50 mg α-T, levels increased to 10.0±0.8 μg α-T/ml and were 8 times higher than those of λ-T when a dose of 50 mg of each of α- and λ-T were fed. None or traces of λ-T were found in a liver cytosol protein (32000 MW) that binds α-T specifically (α-TBP) in all three groups. Small amounts of λ-T were detected in α-TBP in LE rats after they were fed 50 mg of λ-T. These data suggest that the mechanisms for intestinal absorption, plasma transport and liver uptake of vitamin E are specific for α-T. Only when the concentration of α-T is low, can λ-T successfully compete for binding sites at these three levels.     

Evaluation of lipid oxidation after ingestion of bakery products enriched with phytosterols, beta-carotene and alpha-tocopherol

BACKGROUND AND AIMS: The aim of this study was to investigate the effect of the consumption of croissants and magdalenas (Spanish muffins), enriched with sterol esters, alpha-tocopherol and beta-carotene, on plasma lipid peroxidation. TBA and conjugated dienes were used as markers of lipid peroxidation. METHODS: The study was made to a population without changes in their diet or lifestyle, and based on a randomized double-blind controlled repeated measures design. The sample size was 57. During 8 weeks, the subjects of the control group (29) received two daily pieces (standard croissant and muffin), whereas those of the experimental group (28) received the same products, but enriched with sterol-esters, alpha-tocopherol and beta-carotene. RESULTS: The treatment has a positive effect on TBA value for control group and that given to experimental group has negative effect. The mean difference between two groups is 3.16 (P = 0.044). Also TBA was found to be significantly correlated with HDL-, LDL-cholesterol and alpha-tocopherol, both before and after treatment, but TBA was only significantly correlated with beta-carotene before treatment. Finally, the effects on LDL-cholesterol, alpha-tocopherol and TBA presented similar correlation matrices in the two groups, most correlation coefficients being significant at group level, in spite of the low sample sizes, revealing the association between treatment effects.     

α-tocopherol concentrations, lipid peroxidation and superoxide dismutase and glutathione peroxidase activities in rat heart and liver after feeding stabilized and unstabilized fish oil

To further examine the relationship between increased consumption of n-3 polyunsaturated fatty acids (PUFAs), antioxidant defence systems and lipid peroxidation, for 6 weeks adult male rats were fed fish oil (FO)-rich diets containing one of two levels of α-tocopherol (4.5 or 1.9 IU vitamin E/g fish oil) either with or without the addition of the antioxidant mix PUFANOX® in order to stabilize the FO; rats fed corn oil or butter served as controls. Feeding FO resulted in increased proportions of the n-3 PUFAs eicosapentaenoic and docosahexaenoic acids in the phospholipids of the plasma, myocardium and liver. Rats fed the PUFANOX®-stabilized FO had higher plasma, myocardial and liver α-tocopherol concentrations compared to those fed the unstabilized FO; α-tocopherol concentrations were highest in rats fed the higher level of α-tocopherol in combination with PUFANOX®. FO feeding increased lipid peroxidation in myocardial and liver extracts. This was highest after feeding the FO diet which contained the lower amount of α-tocopherol and no PUFANOX® and was positively correlated with the n-3 PUFA content of the phospholipids. FO feeding did not alter myocardial and liver superoxide dismutase activity. Myocardial glutathione peroxidase activity was lower after feeding FO, except that containing the higher amount of α-tocopherol plus PUFANOX®. Glutathione peroxidase activity in the liver was lower after FO feeding than after corn oil with no significant differences among the different FO diets. Thus, insufficient antioxidant protection in FO results in decreased antioxidant defences and increased lipid peroxidation. Increasing the content of α-tocopherol and including a stabilizing agent (e.g. PUFANOX®) in FO can prevent at least some of these effects. The results of the present study do not support the idea that intake of FO, by increasing tissue lipid peroxidation, induces the body’s antioxidant defence system.     

α-Tocopherol, fatty acids and their correlations in Bulgarian foodstuffs

HPLC and GC methods were used for the analysis of 33 foodstuffs divided into 7 groups: cereals, oils and fats, milk and dairy products, meat, eggs and poultry, fish and nuts. The richest sources of α-tocopherol (α-T), seed oils, show considerable variations of α-T (11.0 mg% soybean oil–44.88 mg% sunflower seed oil), as does the content of PUFA (12.72 g% olive oil–66.87 g% sunflower seed oil) with approximately the same content of total lipids (TL) (99.79–99.89 g%). A correlation was established between α-T and total lipids r=0.61 (T=4.28, P>99%). An even higher correlation was found between α-T and polyunsaturated fatty acids r=0.80 (T=7.42, P>99%). Regarding the essential n-6 and n-3 fatty acids α-T was established to correlate only with n-6 fatty acids r=0.82 (T=7.50, P>99%).     

Protein-induced alterations in murine hepatic α-aminoadipate δ-semialdehyde synthase activity are mediated posttranslationally

The molecular mechanisms responsible for alterations in lysine α-ketoglutarate reductase (LKR) activity are unknown. Therefore, the aim of these studies was to discern the mechanism(s) responsible for induction of hepatic LKR activity in rodents fed excess dietary protein. Four studies were conducted that used 84 mice. Mice were fed either a high-protein (50% casein) or adequate-protein (20% casein) diet in powder form in study 1 and a high-protein (46% casein) or adequate-protein (21% casein) diet in pellet form in the remaining studies. No significant differences in weight gain between the mice fed the different diets were detected. As expected, mice fed high-protein diets had a greater (P < .05) LKR activity in all 4 experiments. Mice fed high- and adequate-protein diets for 8 days showed no difference (P > .1) in α-aminoadipate δ-semialdehyde synthase (AASS) mRNA in experiment 1. However, after pooling the data from the remaining 3 experiments, mice receiving the high-protein diet had greater (P < .05) AASS mRNA compared to mice fed the adequate protein diet. In this investigation, no differences (P > .1) in AASS protein abundance were detected. The results are consistent with a mechanism in which posttranslational regulation is responsible for hepatic induction of LKR activity in mice fed high-protein diets.     

Carotenoid Content in Different Varieties of Pumpkins

Due to the increasing interest in the supply with antioxidants and especially carotenoids in foods, pumpkins were analysed for their content of α -carotene, β -carotene, and lutein. A wide range of varieties of pumpkins that are commercially available in Austria was analysed. For this study the pumpkins were grown in Austria to obtain data that are relevant for local nutrition. The varieties analysed derived from three species i.e. Cucurbita pepo,C. maxima and C. moschata. Additionally, a cross breed of C. maxima and C. moschata was tested. The content of the carotenoids ranged from 0.06 to 7.4 mg/100 g for β -carotene, from 0 to 7.5 mg/100 g forα -carotene and from 0 to 17mg/100g for lutein.     

Effect of varying amounts of polyunsaturated fat and α-tocopherol on plasma and red cell content of α-tocopherol in the rat

The response of erythrocyte and plasma α-tocopherol levels to changes in dietary linoleate and vitamin E was studied in rats. Sixty wealing rats were fed a diet composed of 15.5% fat made up of a mixture of hydrogenated coconut oil and corn oil to give three levels of linoleic acid (3, 6, 9% by wieght) and three levels of α-tocopherol (30, 50, 100 mg/kg food) in the different experiments. After 8 weeks, blood was drawn by heart puncture, separated and analyzed for α-tocopherol in plasma and erythrocytes. Increased dietary linoleate resulted in a reduced α-tocopherol content of both plasma and red cells. However, only in the red cells were the changes significant when subjected to two way analysis of variance (p<0.05).     

Impact of 17alpha-ethinylestradiol on the plankton in freshwater microcosms--II: responses of phytoplankton and the interrelation within the ecosystem

Effects of 17α-ethinylestradiol (EE) on phytoplankton were investigated in a lentic freshwater microcosm study. Treatment with EE caused a shift in the species composition as shown by a principle response curve. Whereas densities of Cyanophyceae, Dinophyceae, and Chrysophyceae increased, those of Conjugatophyceae and Cryptophyceae decreased. Furthermore, relative density of Chlorophyceae declined after EE treatment. The changes showed taxa-specific time dependencies. Some species, especially the cyanobacterium Cyanobium parvum, bloomed after the treatment. EE treatment promoted total abundance and biomass of phytoplankton. Although the number of species per microcosm increased, the diversity indices (Shannon–Wiener, Simpson) tended to lower values. The ecosystem only partly recovered during the investigated post-treatment period of 6 weeks. Probably at least the main effects were caused indirectly, i.e. via decrease of grazing zooplankton (crustaceans). The relation of EE to variation of phytoplankton composition was closer than those of other abiotic factors, indicating the relevance of its impact. EE also probably affected nutrients of the phytoplankton.     

Impact of 17alpha-ethinylestradiol on the plankton in freshwater microcosms--I: response of zooplankton and abiotic variables

We investigated effects of 17alpha-ethinylestradiol (EE) in vertebrate free 230 L still water microcosms. Zooplankton composition and physico-chemical variables were observed during 4 weeks of pre-application, 6 weeks of dosing via controlled release, and a 12 weeks post-treatment period. In the treated microcosms, time-weighted averages of EE concentration ranged between 7 and 220 ng/L during the dosing period, with concentration maxima up to 724 ng/L. EE exposure resulted in a decrease of species numbers and diversity (Shannon-Wiener, Simpson). Abundances of cladocerans, copepods, and, less unambiguously, rotifers declined. Strongest affected groups were the offspring of cladocerans and copepods and, on species level, the cladoceran species Daphnia longispina and Chydorus sphaericus as well as the rotifer species Keratella quadrata and Polyarthra sp. EE apparently affected the phosphate cycle as indicated by increased phosphate concentrations in the water. During post-treatment period, the treated microcosms recovered, but especially the highest treated microcosms did not fully re-approximate to the controls. Whereas EE affected cladocerans and copepods directly, shifts of rotifers may (partly) be caused indirectly, e.g. by competition with crustaceae. Although not providing an absolute proof, the traits of direct and indirect effects on different taxonomic groups and larval stages as well as the time course of the effects indicate that effects primarily resulted from endocrine activity of EE.     

Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares

Prevalence of hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) infection or colonisation has been associated with antimicrobial consumption. The impact of antibiotic treatment on nasal colonisation is unknown. We conducted a three-month prospective study of 116 patients with extranasal MRSA infection or colonisation, whose nasal MRSA bacterial loads were determined during and after various antibiotic courses over a period of three weeks. Environmental swabs were also taken from the near patient environment. Concomitant nasal MRSA carriage was observed in 76.7% of extranasal MRSA-colonised or -infected patients. The median nasal MRSA bacterial load increased significantly from 2.78 (range 0-6.15) to 5.30 (range 2.90-8.41) log(10) cfu per swab (cfu/swab) (P<0.001) over 21 days during beta-lactam therapy. It also increased from 0 (range 0-4.00) to 4.30 (range 0-7.46) log(10)cfu/swab (P=0.039) over 14 days during fluoroquinolone therapy. Median bacterial loads were significantly higher for beta-lactam- and fluoroquinolone-treated patients on day 7 [4.78, range 0-7.30], day 14 [4.30, range 0-7.60] and day 21 [5.30, range 2.90-8.41] than controls not receiving antibiotics (P<0.05). These loads then decreased by 2-5log(10)cfu/swab 2 weeks after discontinuation of antibiotics. The environment of patients receiving beta-lactam agents (relative risk: 3.55; 95% confidence interval: 1.30-9.62; P=0.018) or fluoroquinolones (4.32; 1.52-12.31; P=0.008) demonstrated more MRSA contamination than the environment around control patients (0.79; 0.67-0.93; P=0.002). Patients on beta-lactam or fluoroquinolone therapy have increased incidence of MRSA colonisation and higher nasal bacterial loads, and appear to spread their MRSA into the near patient environment.     

Blue CrO5 assay: A novel spectrophotometric method for the evaluation of the antioxidant and oxidant capacity of various biological substances

Oxidative stress plays a pivotal role in the ageing process and in the pathogenesis of numerable diseases. The quantification of the phenomenon is of paramount importance. In the present study, we introduce a novel and simple assay, the Blue CrO₅ assay, for the evaluation of the oxidant and antioxidant capacity of various biological samples and known antioxidants. Chromium peroxide (CrO₅) is produced by ammonium dichromate in an acidic environment in the presence of H₂O₂. It is a deep blue potent oxidant compound, miscible and relatively stable in polar organic solvents, that can be easily measured by spectrophotometry. Its reduction by known antioxidants, both water- and lipid-soluble (ascorbate and α-tocopherol, respectively, in this study), detected spectrophotometrically as a decrease in the absorption and depicted in EPR spectra, can act as a measure of the antioxidant capacity of a certain compound. The assay displays significant sensitivity, stability, linearity, specificity and repeatability.     

Genetic polymorphisms in alveolar macrophage response-related genes, and risk of silicosis and pulmonary tuberculosis in Chinese iron miners

Alveolar macrophages (AMs) play a prominent role in influencing the development of lung inflammation and injury. The aim of this study is to investigate the roles of AMs response-related genes TNF-alpha, iNOS, and NRAMP1 (SLC11A1) in susceptibility to silicosis and pulmonary tuberculosis (PTB), and to analyze the interaction of dust exposure and genetic susceptibility to silicosis, interactions of TNF-alpha-308 and Natural Resistance-associated Macrophage Protein 1 (NRAMP1) INT4, D543N polymorphisms to PTB. Several epidemiological designs were used: retrospective investigations on dust exposure, case-control studies of 184 silicosis cases and 111 miners occupationally exposed to silica dust, and 1:2 matched case-control studies of 61 PTB cases and 122 PTB-free miners. The miners and controls were recruited from an iron mining operation in Anhui province, China. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied to detect single nucleotide polymorphisms. Despite the recruitment of high dust exposure among the controls, silicosis patients still had significantly higher dust exposure than controls (242.6 +/- 98.8 vs. 217.6 +/- 100.7 mg a/m(3)). The mutation of iNOS Ser608Leu is associated with protection against silicosis and against severity of silicosis in the miners. There is a 0.47-fold (95% CI: 0.28-0.79) decrease in risk of silicosis for individuals with C/T, T/T genotype compared with the wild-type homozygous (C/C) individuals after adjustment for occupational exposure, smoking, and drinking. The protection effect of the iNOS polymorphism was particularly detected in the > or = 150 mg a/m(3) exposure group (OR: 0.44, 95% CI: 0.22-0.91). However, no interaction of dust exposure with the iNOS polymorphism was observed. Furthermore, the variant NRAMP1 INT4 genotype is significantly associated with PTB in miners. No association of other polymorphisms (NRAMP1 D543N, TNF-alpha-308) and susceptibility to silicosis or PTB in Chinese miners was found. Our data showed a 3.26-fold (95% CI: 1.47-7.23) increased risk of PTB for miners carrying both the NRAMP1 D543N G/G and NRAMP1 INT4 G/C+C/C genotypes. Additionally, in miners with TNF-alpha-308 G/G genotype, the risk of PTB increased 2.38-fold if they carry the NRAMP1 INT4 G/C+C/C genotype (95% CI: 1.14-4.98). In conclusion, the C>T mutation of iNOS Ser608Leu may be an important protective factor to miners. On the other hand, the variant NRAMP1 INT4 may play a role in the development of PTB in Chinese miners. Therefore, the novel information can be used as guideline for further mechanistic investigations and for strengthening specific protection protocols for workers.     

Effect of 1,4-dioxanyl substitution on the adrenergic activity of some standard α-adrenoreceptor agents

A preliminary communication reported on the pharmacology of the potent partial α₂-agonist (2-(1,4-benzodioxan-6-ylamino)-2-imidazoline, a 1,4-dioxan derivative of clonidine. Its degree of agonism/antagonism depended upon the peripheral or central α₂-adrenoreceptor system studied. It was of interest to discover whether a similar substitution of the 1,4-dioxan moiety in other standard α-adrenergic agents would similarly produce high affinity compounds of complex pharmacological profile. The same substitution when introduced into guanfacine, fenmetazole and tolazoline resulted in unpredictable changes in profile with a reduction in α-affinity.     

Influence of Age, Farming Site, and Boiling on Pro-Vitamin A Content in Sweet Potato (Ipomoea batatas(L.) Lam.) Storage Roots

To maximize the availability of pro-vitamin A carotenoids in sweet potato and to recommend the appropriate start of piecemeal harvesting practice, the main carotenoids in storage roots of 17 different sweet potato cultivars were surveyed using HPLC and spectrophotometry methods, and their variation due to production site, storage root age, and boiling was assessed. There was significant variation in carotenoid content among cultivars. Six different carotenoids were consistently detected in significant quantities. Orange-fleshed roots contained higher total carotenoid and β-carotene content than white- and cream-fleshed lines, and alltrans-β-carotene predominated. The effect of storage root age on carotenoid content was significant. Twelve weeks after planting, the yield and amount of pro-vitamin A present in roots of orange-fleshed cultivars evaluated were high enough to provide adequate dietary pro-vitamin A and suggest the start of piecemeal harvesting. The effect of farming site on total carotenoids was significant; however, the amount of β-carotene was not different over three testing sites. Boiling of roots for 30 min caused a reduction in total carotenoids which varied by cultivar; however, further boiling for up to 60 min did not exacerbate the reduction in total carotenoids.     

Effect of single and combined supply of glutamine, glycine, N-acetylcysteine, and R,S-alpha-lipoic acid on glutathione content of myelomonocytic cells

BACKGROUND & AIMS: Several diseases are characterised by decreased glutathione (GSH) levels due to an enhanced formation of oxygen radicals. To increase GSH levels, the additional supply of GSH precursors was suggested. In this study we evaluated the potency of a single and combined administration of the GSH modulating substances glutamine (GLN), N-acetylcysteine (NAC), and glycine (GLY) as well as R,S-alpha-lipoic acid (LA) to enhance intracellular GSH content in a well-defined model system. RESULTS: Exposure of myelomonocytic U937 cells for 24 h to GLN revealed a 1.5-fold enhancement of GSH levels with a concomitant decrease in the formation of reactive oxygen species and lipid peroxidation. Addition of NAC stimulated GSH formation only at subphysiological GLN levels. GLY enhanced GSH levels under GLN starvation, but caused a diminution of GSH content under optimal GLN supply. LA in combination with 2 mmol/l GLN evoked a 3.6-fold enhancement of GSH content compared to GLN starved cells. CONCLUSION: These results demonstrate that the GSH content of U937 cells is dependent on the supply of GLN, NAC, LA, and GLY. Combinations of the single substances can enhance but also decrease the intracellular GSH content, which is of clinical importance when supplying GSH-modulating substances to patients.     

Prevalence of beta-thalassaemia in subcastes of Indian Sindhis: Results from a two-phase survey

OBJECTIVE: To estimate the prevalence of beta-thalassaemia in different subcastes of the Indian Sindhi population who, in general, have a high prevalence of this disease. STUDY DESIGN: A two-phase, community-based survey. METHODS: Asymptomatic, Sindhi volunteers from Nagpur, central India, were recruited into the present study over a 7-year period. The first phase included the use of the Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT). Those positive for NESTROFT or those volunteering for haemoglobin A(2) (HbA(2)) quantification entered the second phase of the survey. Appropriate statistical methods for estimating prevalence from two-phase surveys were used. RESULTS: The prevalence of beta-thalassaemia carriers across the five major Sindhi subcastes varied substantially in the study population. Larkana Sindhis had the highest (17%) whereas Dadu Sindhis had the lowest (8%) frequency of the beta-thalassaemia allele. As a corollary, the projected incidence of beta-thalassaemia major in newborn babies greatly varied by the subcastes of the parents. CONCLUSION: Ethnic subgroups within populations known to commonly carry the beta-thalassaemia gene provide further information that is useful from epidemiological and public health perspectives.     

Butyrate and trichostatin A attenuate nuclear factor κB activation and tumor necrosis factor α secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells

The effects of short-chain fatty acids (butyrate, propionate, and acetate) and trichostatin A (TSA), a typical histone deacetylase inhibitor, on tumor necrosis factor (TNF)-α secretion and nuclear factor κB (NF-κB) activation in peripheral blood mononuclear cells induced with lipopolysaccharide were evaluated in relation to prostaglandin E₂ (PGE₂) secretion. Treatment of cells with butyrate; tributyrin, a prodrug of butyrate; propionate; acetate; and TSA down-regulated TNF-α secretion but all up-regulated PGE₂ secretion. Butyrate, propionate, and TSA inhibited NF-κB activation. The effects of the cyclooxygenase-nonspecific inhibitor, indomethacin; the cyclooxygenase-2 selective inhibitor, N-[2-(cyclohexyloxy)-4-nitro-phenyl] methanesulfonamide; and the general lipoxygenase inhibitor, nordihydroguaiaretic acid, varied in cells treated with each short-chain fatty acids. N-[2-(cyclohexyloxy)-4-nitro-phenyl] methanesulfonamide inhibited the effect of propionate on TNF-α secretion, and nordihydroguaiaretic acid inhibited that of acetate. The results showed that butyrate, propionate, and TSA inhibited TNF-α production via PGE₂ secretion and down-regulated NF-κB activation by lipopolysaccharide. These data suggest that the mechanism of butyrate and propionate action is through histone deacetylation and acetate through lipoxygenase activation in the regulation of proinflammatory responses in cells.     

Comparative study on the inhibitory effects of antioxidant vitamins and radon on carbon tetrachloride-induced hepatopathy

We have previously reported that radon inhalation activates anti-oxidative functions and inhibits carbon tetrachloride (CCl₄)-induced hepatopathy. It has also been reported that antioxidant vitamins can inhibit CCl₄-induced hepatopathy. In the current study, we examined the comparative efficacy of treatment with radon, ascorbic acid and α-tocopherol on CCl₄-induced hepatopathy. Mice were subjected to intraperitoneal injection of CCl₄ after inhaling approximately 1000 or 2000 Bq/m³ radon for 24 h, or immediately after intraperitoneal injection of ascorbic acid (100, 300, or 500 mg/kg bodyweight) or α-tocopherol (100, 300, or 500 mg/kg bodyweight). We estimated the inhibitory effects on CCl₄-induced hepatopathy based on hepatic function-associated parameters, oxidative damage-associated parameters and histological changes. The results revealed that the therapeutic effects of radon inhalation were almost equivalent to treatment with ascorbic acid at a dose of 500 mg/kg or α-tocopherol at a dose of 300 mg/kg. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver were significantly higher in mice exposed to radon than in mice treated with CCl₄ alone. These findings suggest that radon inhalation has an anti-oxidative effect against CCl₄-induced hepatopathy similar to the anti-oxidative effects of ascorbic acid or α-tocopherol due to the induction of anti-oxidative functions.