Relationship of parental attitudes

Thesis--Universität Erlangen-Nürnberg. / At head of title: Aus dem Seminar für Geschichte der Medizin der Universität Erlangen-Nürnberg. Vita.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or "half-mustard gas", are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

Background: Sulphur mustard gas, 2, 2′-dichlorodiethyl sulphide (HD), is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES), are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS) significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO) production via suppression of inducible NO synthase (iNOS) protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC) would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH) synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. Results: We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels). NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. Conclusion: The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and supports the notion that antioxidants could play a therapeutic role in preventing mustard gas toxicity. Although NAC reduced oxidative stress in LPS stimulated macrophages treated with CEES, it did not reverse CEES-induced loss of NO production. NAC and polymyxin B were found to help prevent CEES toxicity in LPS-treated macrophages.

Background. Tocopherols may protect against prostate cancer and cardiovascular disease (CVD). Methods. We assessed the effect of walnuts, which are rich in tocopherols, on markers of prostate and vascular health in men at risk for prostate cancer. We conducted an 8-week walnut supplement study to examine effects of walnuts on serum tocopherols and prostate specific antigen (PSA). Subjects (n = 21) consumed (in random order) their usual diet +/- a walnut supplement (75 g/d) that was isocalorically incorporated in their habitual diets. Prior to the supplement study, 5 fasted subjects participated in an acute timecourse experiment and had blood taken at baseline and 1, 2, 4, and 8 h after consuming walnuts (75 g). Results. During the timecourse experiment, triglycerides peaked at 4 h, and gamma-tocopherol (γ-T) increased from 4 to 8 h. Triglyceride - normalized γ-T was two-fold higher (P = 0.01) after 8 versus 4 h. In the supplement study, change from baseline was +0.83 ± 0.52 μmol/L for γ-T, -2.65 ± 1.30 μmol/L for alpha-tocopherol (α-T) and -3.49 ± 1.99 for the tocopherol ratio (α-T: γ-T). A linear mixed model showed that, although PSA did not change, the ratio of free PSA:total PSA increased and approached significance (P = 0.07). The α-T: γ-T ratio decreased significantly (P = 0.01), partly reflecting an increase in serum γ-T, which approached significance (P = 0.08). Conclusion. The significant decrease in the α-T: γ-T ratio with an increase in serum γ-T and a trend towards an increase in the ratio of free PSA:total PSA following the 8-week supplement study suggest that walnuts may improve biomarkers of prostate and vascular status.

Oxidative modification of human low-density lipoprotein (LDL) is believed to play an important role in atherogenesis. Vitamin C (ascorbate) and urate are major water-soluble plasma antioxidants in humans. Urate levels (300-395 μM) in human serum are considerably higher than ascorbate levels (30-50 μM). In this study, we compared the ability of urate to protect human LDL from in vitro oxidation with that of ascorbate. LDL was subjected to in vitro oxidation at 30°C with an O2 saturated solution (0.15 M NaCl/0.25 mM EDTA) and 15 mM of a thermally labile water soluble azoinitiator (ABAP or azobis-2-amidinopropane HCl). In parallel experiments, 50 μM ascorbate or 50 μM urate were present in the oxidation buffer. The consumption of α-tocopherol, γ-tocopherol, urate or ascorbate and the formation of lipid hydroperoxides were measured as a function of time in the in vitro oxidation system. The rate of lipid hydroperoxide formation was found to be significantly increased after the LDL tocopherols (α-plus γ-tocopherol) were totally consumed, i.e., after the lag phase. Urate (50 μM) was more effective than ascorbate (50 μM) in extending the lag phase. Moreover, urate was consumed more slowly than ascorbate under identical oxidation conditions. Urate was not, however, as effective as ascorbate in preventing the formation of lipid hydroperoxides before the lag phase. An empirical mathematical model was also developed to describe the oxidation kinetics of LDL α-and γ-tocopherol in the presence or absence of urate or ascorbate.

Both vitamin E and selenium (Se) are antioxidant nutrients that play important roles in preventing in vivo lipid peroxidation. In this investigation, Se and vitamin E were found to influence lipoprotein levels in the spontaneously hypertensive rat (SHR). Four-week-old inbred SHRs were fed a basal (B) diet with 1% cholesterol deficient in both selenium and vitamin E (B+cho diet) or identical diets to which either vitamin E (B+E+cho) or selenium (B+Se+cho) or both micronutrients were added (B+Se+E+cho). Plasma-cho and lipoprotein-cho levels were measured after 6, 12, 16, and 18 weeks of feeding the experimental diets. Rats fed the B+cho diet for at least 12 weeks had plasma-cho levels about twice that observed for rats fed the B+E+Se+cho diet. Plasma-cho levels for rats in the two Se deficient groups (B+cho and B+E+cho) were, however, similar at any time point. Se deficiency was associated with increased plasma-cho, very low density lipoprotein-cho (VLDL-cho) and low-density lipoprotein-cho (LDL-cho). Vitamin E supplementation interacted with Se deficiency to increase plasma VLDL-cho levels. Neither vitamin E alone nor the interaction between vitamin E and Se consistently influenced LDL-cho levels. The percent cholesteryl ester in LDL from rats fed the Se-deficient diets (B+cho or B+E+cho) was at least twice that observed for rats fed the B+E+Se+cho diet. Plasma lipid peroxidation products were highly elevated in rats fed the B+cho diet compared with values for the B+E+cho or the B+E+Se+cho fed rats (which were not significantly different). These results suggest that dietary Se deficiency increases plasma-cho, VLDL-cho, and LDL-cho levels by a mechanism that may be unrelated to its role as an antioxidant nutrient.

No description available.

A recirculating liver perfusion system was used to study the effects of dietary selenium (Se) on the hepatic secretion of very-low-density lipoprotein (VLDL). The perfusate from livers of rats fed on a Se-deficient diet incorporated about 50 % more [1-14C]oleic acid into triacylglycerol (TG) and cholesteryl esters (ChoEs) than did the perfusate from livers of rats fed on a Se-supplemented diet. Similarly, livers from rats fed the Se-deficient diet secreted more VLDL and incorporated about 60 %, more [1-14C]oleic acid into VLDL TG and ChoEs than did livers from rats fed the Se-supplemented diet. The liver perfusate from rats in the Se-deficient group also showed significantly decreased fatty acid oxidation. We conclude that Se is a potent modulator of lipoprotein metabolism. A primary action of Se deficiency appears to be a decrease in fatty acid oxidation and a stimulation of fatty acid esterification, leading to increased VLDL TG and ChoEs formation and secretion.