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Institute
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An imbalance between formation and detoxification of oxygen radicals leads to oxidant stress that may increase in more intense oxidative metabolism caused by a high intake of metabolizable energy to provide metabolic intermediates for the milk synthesis and secretion. This hypothesis was tested using dairy cows and the concentration of hydroperoxides in lipids (LHP) extracted from circulative lipoprotein particles of low and very low density (LDL and VLDL/chylomicrons) as oxidant stress indicator. The particles were prepared by ultracentrifugation of serum obtained by coccygeal bleeding (13 cows, 1. parity, n=8 and 2. parity, n=5, lactation stage, 53 +/- 1.4 days post partum) and purified by precipitation. Concentrations of LHP-LDL/mg Lipoprotein correlated significantly with daily milk yield (r = 0.73, P = 0.004) or daily milk energy output (r = 0.77, P = 0.003) in contrast to LHP of VLDL/chylomicron particles. Thus, some evidence was obtained for an almost linear, positive relationship between milk productivity and oxidant stress occurring in LDL
OBJECTIVE - We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (S-I), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference. RESEARCH DESIGN AND METHODS - Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992-1994) were analyzed. Usual dietary intake was assessed via a 114- item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. S-I and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying S-I with AIR. Multiple linear regression modeling was employed. RESULTS - No association was observed between glycemic index and S-I fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with S-I insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with S-I and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR. CONCLUSION - Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects. on insulin sensitivity and adiposity, but also on pancreatic functionality
The structure of interaction products resulting from the reaction of unmodified glucose with benzyl isothiocyanate is reported. Prior to their identification, the main products of this reaction were isolated using solid- phase extraction (SPE) as well as preparative HPLC. They were then identified by NMR and MS as 3-benzyl-4-hydroxy-5-(D- arabino-1,2,3,4-tetrahydroxybutyl)- 1,3-oxazolidine-2-thione, 3-benzyl-4-hydroxy-4-hydroxymethyl-5-(D-erythro-1,2,3- trihydroxypropyl)- 1,3-oxazolidine-2-thione, N-benzyl-(D-gluco-4,5-dihydroxy-6-hydroxymethyl-tetrahydropyrano)[2,3-b] oxazolidine-2-thione and 3-benzyl-4-(N-benzyl amino)-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-thiazolidine-2-thione . The identity of the last compound was secured by X-ray crystal structure data. (C) 2004 Elsevier Ltd. All rights reserved
1 Two isoforms of the rat prostaglandin E-2 receptor, rEP3 alpha-R and rEP3 beta-R, differ only in their C- terminal domain. To analyze the function of the rEP3-R C-terminal domain in agonist induced desensitization, a cluster of Ser/Thr residues in the C-terminal domain of the rEP3 alpha-R was mutated to Ala and both isoforms and the receptor mutant (rEP3 alpha-ST341-349A-R) were stably expressed in HEK293 cells. 2 All rEP3-R receptors showed a similar ligand- binding profile. They were functionally coupled to Gi and reduced forskolin-induced cAMP-formation. 3 Repeated exposure of cells expressing the rEP3 alpha-R isoform to PGE(2) reduced the agonist induced inhibition of forskolin-stimulated cAMP-formation by 50% and led to internalization of the receptor to intracellular endocytotic vesicles. By contrast, Gi- response as well as plasma membrane localization of the rEP3 beta-R and the rEP3 alpha-ST341-349A-R were not affected by prior agonist-stimulation. 4 Agonist-stimulation of HEK293-rEP3 alpha-R cells induced a time- and dose-dependent phosphorylation of the receptor most likely by G protein-coupled receptor kinases and not by protein kinase A or protein kinase C. By contrast, upon agonist-stimulation the rEP3 beta-R was not phosphorylated and the rEP3 alpha-ST341-349A-R was phosphorylated only weakly. 5 These results led to the hypothesis that agonist-induced desensitization of the rEP3 alpha-R isoform is mediated most likely by a GRK-dependent phosphorylation of Ser/Thr residues 341 - 349. Phosphorylation then initiates uncoupling of the receptor from Gi protein and receptor internalization
INTRODUCTION: For obtaining reliable information about physical activity in epidemiological studies, validated and easy-to-use instruments are required. Therefore, a new simplified physical activity record based on 15-min recording intervals was developed and validated. SUBJECTS: Nonobese volunteers (n = 31). MEASUREMENTS: Physical activity was recorded over a 7-day period without detailed instructions. Energy expenditure was calculated (EEsPAR) and compared to energy expenditure measured by doubly labelled water technique (EEDLW). RESULTS: A good agreement between EEsPAR (12.1 +/ 3.0) and EEDLW (11.7 +/- 3.3) with a mean difference of 0.33 +/- 1.55 MJ (r = 0.880, P < 0.001) was observed. The absolute difference between EEsPAR and EEDLW was <10% in 65% of the subjects. The difference between EEsPAR and EEDLW was independent of gender, age, body weight, and body mass index. A weak positive association between the difference and total body fat was observed (r = 0.618, P < 0.001), suggesting a slight tendency to overestimate EEsPAR with increasing total body fat. CONCLUSION: The new simplified physical activity protocol needs no detailed instructions, provides valid estimates of physical activity in nonobese free-living adults and can be used in epidemiological studies to assess total daily energy expenditure and physical activity level
Background: Estimating dietary intake is important for both epidemiological and clinical studies, but often lacks accuracy. Objective: To investigate the accuracy and validity of energy intake estimated by an easy-to-use semiquantitative food record (EISQFR) compared to total energy expenditure ( TEE) estimated by doubly labelled water technique (EEDLW). Design: TEE was measured in 29 nonobese subjects using the doubly labelled water method over a period of 14 days. Within this period, subjects reported their food consumption by a newly developed semiquantitative food record for 4 consecutive days. Energy intake was calculated using the German Food Code and Nutrition Data Base BLS II.3. Results: A good correlation was observed between EISQFR and EEDLW (r = 0.685, P<0.001). The mean difference between EISQFR and EEDLW was - 1.7 +/- 2.6 MJ/ day ( - 14 +/- 21%, P = 0.002). An underestimation of EISQFR <10% was observed in nine subjects (31%), of 10 - 20% in six subjects (21%), and of >20% in nine subjects (31%). In five subjects (17%), an overestimation of EISQFR was observed. Conclusions: The easy-to-use semiquantitative food record provided good estimates of EI in free-living and nonobese adults without prior detailed verbal instructions. The presented food record has limitations regarding accuracy at the individual level
Background Soy protein is effective in lowering plasma cholesterol, LDL cholesterol and triglyceride concentrations. It has not been conclusively answered, whether and to what extent other soy constituents may also contribute to this effect. Objective To investigate the change in blood lipid levels after application of two soy-based supplements containing soy protein either without (SuproSoy(R)) or with (Abacor(R)) soy fiber and phospholipids in a randomized placebo-controlled triple-armed study. Methods 121 hypercholesterolemic adults ( 66 females, 55 males) were recruited and randomly assigned to one of three treatments. Over 8 weeks they received daily either 25 g soy protein ( as a component of the supplements Abacor(R) or SuproSoy(R)) or 25 g milk protein ( as a component of placebo). Serum lipids were measured at baseline and after 4, 6 and 8 weeks. Results After 8 weeks of supplementation total cholesterol levels were reduced by 8.0 +/- 9.6% (Abacor(R)) and 3.4 +/- 8.3% (SuproSoy(R)); LDL cholesterol levels by 9.7 +/- 11.7% ( Abacor(R)) and 5.4 +/- 11.6% ( SuproSoy(R)); and Apolipoprotein B levels by 6.9 +/- 14.6% (Abacor(R)) and 4.0 +/- 12.4 % (SuproSoy(R)). Serum levels of HDL cholesterol and triglycerides remained unchanged. Conclusions A preparation combining isolated soy protein with soy fibers and phospholipids showed twice the lipid-lowering effect of a preparation containing isolated soy protein alone. Therefore, such soy-based supplements can be useful in reducing the cardiovascular risk
Curcumin is a dietary compound with diverse anti-inflammatory and anticarcinogenic effects in several experimental models. A mechanism by which curcumin exerts these actions might be the direct modification of protein thiols, thereby altering the activity of the affected proteins. An early event in inflammatory signaling cascades is the recruitment of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) to the IL-1 receptor (IL-1 RI) upon stimulation with IL-1. IRAK recruitment was shown recently to be inhibited by agents that modify thiols of IRAK. We asked, therefore, whether IRAK is also a target for curcumin. Curcumin indeed blocked IRAK thiols in a murine T-cell line stably overexpressing IRAK (EL-4(IRAK)), which resulted in the inhibition of IRAK recruitment to the IL-1RI and phosphorylation of IRAK and IL-1RI-associated proteins. Inhibitory effects were not reversible by thiol-reducing agents. Thus, modification by curcumin did not occur by oxidation but rather by alkylation, as is typical for electrophilic compounds reacting as Michael addition acceptors. The block in one of the earliest events in the IL-1 signaling cascade can explain the often observed inhibition of IL-1-mediated signaling steps by curcumin further downstream. Hence, thiol modification might be a crucial step in the anti-inflammatory functions of curcumin
Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs