Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity: a randomized study.

BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND+control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.

The antioxidant capacity of milk--the application of different methods in vitro and in vivo.

Milk contains a wide array of compounds with established or putative pro- or anti-oxidant function. The functions of these compounds have been intensively studied. This review focusses on some important aspects in this wide field namely the methodology for measurement of the total antioxidant capacity (TAC), the content of TAC and some related compounds in human and animal milks and infant formulas, and the effect of milk intake on antioxidant status in the body and on the activity of dietary flavonoids as studied in vitro and in vivo. Regarding methodology TAC in milk can be measured by spectrophotometric and electrochemical methods and some of their characteristics are reviewed. Milk, whey, high-molecular-weight and low-molecular-weight (LMW) fractions of whey have all been found to have antioxidant capacity using these techniques. The major antioxidant in the LMW fraction has been identified as urate. An extensive literature survey was made regarding data on the antioxidant capacity and related variables of milk obtained from different sources (human milk, infant formulas and animal milk) and subjected to different treatments. Differences in TAC between milks from different sources have been observed but due to the variety of techniques used no clear pattern is evident at present. Another important aspect is the putative effects of the intake of milk products on the antioxidant status of the consumer. A few studies performed in adults and premature infants are reviewed and it is stated that too little information is available to make any firm conclusions in this regard. Finally, a high interest has been devoted to the possible interference of milk with the antioxidant properties of flavonoid-rich food like tea. Most in vitro studies show an inhibition by milk on tea flavonoid activity whereas the results from the corresponding in vivo studies are equivocal. Our general conclusion is that several compounds in various milk fractions contribute to the antioxidant capacity of milk and that much further work is needed to unravel the complex interactions among the pro- and antioxidants, and their putative health effects on the consumer.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Occurrence of selenoprotein enzyme activities and mRNA in bovine mammary tissue.

To elucidate the possible role of selenoproteins for milk formation and mammary gland physiology, the activities of selenoprotein enzymes and the expression of selenoprotein genes were studied in the bovine mammary gland. Messenger RNA was demonstrated for selenoprotein P, thioredoxin reductase 1, and for glutathione peroxidase (GPx) 1, 3, and 4. Significant differences in mRNA expression between the cows were seen for GPx 1 and GPx 3. The enzyme activity of glutathione peroxidase varied approximately 16-fold among cows, and the activity of thioredoxin reductase and the concentration of soluble Se varied approximately 6-fold among cows. There were positive correlations between glutathione peroxidase activity, thioredoxin reductase activity, and soluble Se, the correlation between glutathione peroxidase activity and soluble Se being the strongest. Furthermore, selenoprotein P expression correlated with GPx 1 mRNA expression and with soluble Se. There was also a correlation between glutathione peroxidase activity and the mRNA expression of GPx 1. The general conclusion from the data was that the activity of glutathione peroxidase and thioredoxin reductase and the mRNA expression of selenoprotein P and GPx 1 and 3 were influenced by Se status, but the expression of GPx 4 and thioredoxin reductase 1 were not. These results indicate that the Se status in mammary tissue is an important regulator of selenoprotein activity and expression, but that other factors are also in operation.

Bioavailability of selenium from bovine milk as assessed in subjects with ileostomy.

OBJECTIVE: To assess the absorption of dietary selenium in humans, especially of milk selenium. DESIGN: : 1-day meal studies in subjects with ileostomy. SETTING: Hospital outpatient clinics. SUBJECTS: Three subjects in the pilot study and nine subjects in the main study (eight men/ four women). INTERVENTION: Different beverages, 1 l/day, were given in addition to basal diets (soft drink, 1 week; low-fat milk, 3 weeks; fermented low-fat milk, 3 weeks and soft drink, 1 week). Ileostomy effluents were collected during the last 2 days in each of the four periods. RESULTS: On days when the subjects were given 1 l of low-fat milk, the estimated fractional absorption of total dietary selenium was 65.5 (2.3)% (mean (s.d.), n=18), which was similar to the value when fermented low-fat milk was given (64.1 (3.2)%). However, both the calculated amount of milk selenium absorbed (10.9 (2.4) vs 9.4 (1.7) microg selenium) and its fractional absorption (73.3 (16.1) vs 64.1 (11.2)%, n=18) were significantly higher for milk than for fermented milk. CONCLUSIONS: Selenium from milk and other sources is well absorbed in subjects with ileostomy. The real absorption may be even higher than the values shown.

Human experimental exposure to N-methyl-2-pyrrolidone (NMP): toxicokinetics of NMP, 5-hydroxy- N-methyl-2-pyrrolidone, N-methylsuccinimide and 2-hydroxy- N-methylsuccinimide (2-HMSI), and biological monitoring using 2-HMSI as a biomarker.

OBJECTIVE: N-methyl-2-pyrrolidone (NMP) is a strong and selective organic solvent with an extensive and increasing use. It has been reported to be a compound that is toxic to the reproductive system. The aim of this study was to evaluate toxicokinetics parameters for NMP and its metabolites, 5-hydroxy- N-methyl-2- pyrrolidone (5-HNMP), N-methylsuccinimide (MSI) and 2-hydroxy- N-methylsuccinimide (2-HMSI), and to develop a method for biological monitoring of NMP exposure that uses 2-HMSI as a biomarker. METHODS: Six healthy, male volunteers were exposed to NMP in an exposure chamber for 8 h at concentrations of 10, 25 and 50 mg/m(3). In addition, three of the subjects were exposed a second time at 50 mg/m(3). Air levels were monitored by Amberlite XAD-7 sampling and gas chromatography (GC) analysis. Levels of NMP and the metabolites in plasma and urine were analysed by GC or GC with mass spectrometry detection. RESULTS: The concentration of 2-HMSI in plasma and urine rose during exposure and reached a peak approximately 15 h after the end of exposure. It then decayed according to a one-compartment model with a half-time of about 18 h. There were very close correlations between the NMP air levels, on the one hand, and concentrations of 2-HMSI in plasma (r=0.98) and creatinine-adjusted urinary 2-HMSI levels (r=0.96), on the other. The renal clearances were 0.13, 1.4, 0.12 and 1.2 l/h for NMP, 5-HNMP, MSI and 2-HMSI, respectively. The total clearances were 11.4, 3.2, 8.5 and 1.1 l/h for NMP, 5-HNMP, MSI and 2-HMSI, respectively. The apparent volumes of distribution were 41, 28, 120 and 28 l for NMP, 5-HNMP, MSI and 2-HMSI, respectively. CONCLUSIONS: Toxicokinetics parameters for NMP, 5-HNMP, MSI and 2-HMSI have been estimated. Furthermore, 2-HMSI is applicable as a biomarker of exposure to NMP, and the levels in plasma and urine may be used to indicate an exposure over three days.

Molecular phylogeny of the model annelid Ophryotrocha.

Annelids of the genus Ophryotrocha are small opportunistic worms commonly found in polluted and nutrient-rich habitats such as harbors. Within this small group of about 40 described taxa a large variety of reproductive strategies are found, ranging from gonochoristic broadcast spawners to sequential hermaphroditic brooders. Many of the species have a short generation time and are easily maintained as laboratory cultures. Thus they have become a popular system for exploring a variety of biological questions including developmental genetics, ethology, and sexual selection. Despite considerable behavioral, reproductive, and karyological studies, a phylogenetic framework is lacking because most taxa are morphologically similar. In this study we use 16S mitochondrial gene sequence data to infer the phylogeny of Ophryotrocha strains commonly used in the laboratory. The resulting mtDNA topologies are generally well resolved and support a genetic split between hermaphroditic and gonochoristic species. Although the ancestral state could not be unambiguously identified, a change in reproductive strategy (i.e., hermaphroditism and gonochorism) occurred once within Ophryotrocha. Additionally, we show that sequential hermaphroditism evolved from a simultaneous hermaphroditic ancestor, and that characters previously used in phylogenetic reconstruction (i.e., jaw morphology and shape of egg mass) are homoplasic within the group.

Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

N-methylsuccinimide in plasma and urine as a biomarker of exposure to N-methyl-2-pyrrolidone.

OBJECTIVE: N-Methyl-2-pyrrolidone (NMP) is a selective and powerful organic solvent. The aim of this study was to investigate whether the NMP metabolite N-methylsuccinimide (MSI) in plasma and urine can be used as a biomarker of exposure to NMP. METHODS: Six healthy subjects were exposed to 10, 25, and 50 mg NMP/m3 in an exposure chamber for 8 h. The air levels were monitored by XAD-7 solid sorbent sampling, and analysed by gas chromatography (GC). Plasma and urine were sampled for two days following the exposure, and the levels of MSI were analysed by GC with mass spectrometric detection. RESULTS: The concentration of MSI in plasma and urine rose during the exposure, and reached a peak at about 4 h after the end of the exposure. The concentration then decayed according to a one-compartment model with a half-time of approximately 8 h. About 1% of the inhaled NMP was excreted in urine as MSI. There were very close correlations between the NMP air levels and, on the one hand, the MSI concentrations in plasma collected at the end of exposure (r = 0.98), or the urinary MSI concentration collected during the last 2 h of exposure (r = 0.96), on the other. CONCLUSIONS: MSI in plasma or urine is applicable as a biomarker of exposure to NMP. The concentration in plasma and urine mainly reflects the exposure over one day.

Acute health effects common during graffiti removal.

OBJECTIVE: The aim of this study was to identify possible health effects caused by different cleaning agents used in graffiti removal. METHODS: In 38 graffiti removers working 8-h shifts in the Stockholm underground system, the exposure to organic solvents was assessed by active air sampling, biological monitoring, and by interviews and a questionnaire. Health effects were registered, by physical examinations, porta7ble spirometers and self-administered questionnaires. The prevalence of symptoms was compared with 49 controls working at the underground depots, and with 177 population controls. RESULTS: The 8-h time-weighted average exposures (TWA) were low, below 20% of the Swedish permissible exposure limit value (PEL) for all solvents. The short-term exposures occasionally exceeded the Swedish short-term exposure limit values (STEL), especially during work in poorly ventilated spaces, e.g. in elevators. The graffiti removers reported significantly higher prevalence of tiredness and upper airway symptoms compared with the depot controls, and significantly more tiredness, headaches and symptoms affecting airways, eyes and skin than the population controls. Among the graffiti removers, some of the symptoms increased during the working day. On a group basis, the lung function registrations showed normal values. However, seven workers displayed a clear reduction of peak expiratory flow (PEF) over the working shift. CONCLUSIONS: Though their average exposure to organic solvents was low, the graffiti removers reported significantly higher prevalence of unspecific symptoms such as fatigue and headache as well as irritative symptoms from the eyes and respiratory tract, compared with the controls. To prevent adverse health effects it is important to inform the workers about the health risks, and to restrict use of the most hazardous chemicals. Furthermore, it is important to develop good working practices and to encourage the use of personal protective equipment.

Air and biological monitoring of solvent exposure during graffiti removal.

OBJECTIVE: The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures. METHODS: Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews. RESULTS: Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and gamma-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high. CONCLUSIONS: Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the health risks and to restrict the use of the most toxic chemicals. Furthermore, it is important to develop good working procedures and to encourage the use of personal protection equipment.

Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker.

OBJECTIVES: The aims were to study the toxicokinetics of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) in blood and urine after exposure to N-methyl-2-pyrrolidone (NMP) and to study the suitability of 5-HNMP as a biomarker for assessing NMP exposure. METHODS: Six male volunteers were exposed for 8 hours to NMP concentrations of 0, 10, 25, and 50 mg/m3. Blood and urine were sampled before, during, and up to 40 hours after exposure. Aliquots of urine and plasma were purified, derivatized, and analyzed for 5-HNMP on a gas chromatograph/mass spectrometer in the electron impact mode. RESULTS: The mean plasma concentration [P-(5-HNMP)] after 8-hour NMP exposure to 10, 25, and 50 mg/m3 was 8.0, 19.6, and 44.4 micromol/l, respectively. The mean urinary concentration [U-(5-HNMP)] for the 2 last hours of exposure was 17.7, 57.3, and 117.3 mmol/mol creatinine, respectively. The maximal P-(5-HNMP)and U-(5-HNMP) concentrations occurred 1 hour and 0-2 hours, respectively, after the exposure. The half-times of P-(5-HNMP) and U-(5-HNMP) were 6.3 and 7.3 hours, respectively. The 5-HNMP urinary concentrations were 58% of the calculated retained dose. There was a close correlation (r) between P-(5-HNMP) (r=0.98) and U-(5-HNMP) (r=0.97) with NMP exposure. CONCLUSIONS: 5-HNMP is an excellent biomarker for assessing exposure to NMP. Its plasma and urinary half-times (6-7 hours), the minimal risk for contamination during sampling in occupational settings, and the close correlation of P-(5-HNMP) and U-(5-HNMP) with NMP exposure makes 5-HNMP suitable for monitoring exposure to NMP. 5-HNMP in plasma is recommended.

Psychological test performance during experimental challenge to toluene and n-butyl acetate in cases of solvent-induced toxic encephalopathy.

OBJECTIVES: This study determined whether performance in neurobehavioral tests deteriorates during subjectively annoying chemical challenge below known neurotoxic thresholds among persons with toxic encephalopathy with subjective hypersensitivity to chemicals. METHODS: Subjects with symptoms and previous neuropsychological test results compatible with toxic encephalopathy (TE) of either type 2A (N=12) or 2B (N=12) and unexposed referents (N=12) were challenged in an exposure chamber. In a counterbalanced design, the subjects were exposed on 2 occasions to increasing air concentrations of n-butyl acetate and toluene at levels well below the thresholds for neurotoxic effects. Attention and motor speed tests were given (i) in room air outside the chamber before the challenge, (ii) in room air inside the chamber before the exposure, (iii) at 12 ppm (44 or 56 mg/m3), and (iv) at 48 ppm (at 180 or 228 mg/m3). RESULTS: For both substances the TE groups showed a slight increase (deterioration) in the simple reaction-time task during chemical exposure, but not in the complex reaction-time task or in the digit symbol test of the Wechsler Adult Intelligence Scale. Contrary to reference subjects, the TE subjects did not show any improvement or learning effect in the digit symbol test over the chamber phases. n-Butyl acetate tended to affect cognitive functioning more obviously than toluene did. Suggestion or expectancy effects were not observed in any group in the clean-air baseline conditions. CONCLUSIONS: The results do not support the notion that men with subjective hypersensitivity to chemicals would be more affected than healthy men regarding cognitive functioning during annoying solvent exposure below thresholds for acute neurotoxic effects.

Selenoprotein P in plasma in relation to cancer morbidity in middle-aged Swedish men.

The premorbid level of selenoprotein P in plasma from subjects with cancer at different sites was compared with that from control subjects in a nested case-control study. A health screening of 12,500 middle-aged men was performed during 1974-1982 in Malmö, Sweden, and from the 400 cancer cases that were identified during follow-up until the end of 1988, 302 plasma samples were available for analysis of selenoprotein P. Two living controls per case of the same screening day and age were chosen. Selenoprotein P levels in subgroups of major cancer sites were lower in cases than in controls for the respiratory tract (1.20 and 1.30 arbitrary units, respectively; p < 0.05) cancer group. The odds ratio for overall cancer risk in the lowest quintile of selenoprotein P level compared with that in the highest was 5.2 [p (for trend) = 0.01]. In subgroups of major cancer sites, the odds ratios for cancer risk in the lowest tertile compared with the highest were 6.0 [p (for trend) = 0.004] in the respiratory tract and 3.4 [p (for trend) = 0.002] in the digestive tract. In cases + controls, selenoprotein P was lower in smokers than in nonsmokers (p < 0.05). Selenoprotein P was significantly correlated to plasma albumin, fasting blood glucose, and body mass index and inversely correlated to plasma alpha 1-antitrypsin and gamma-glutamyl transferase. The results suggest that a low plasma selenoprotein P level is associated with higher future risk of respiratory and digestive tract cancer in middle-aged men.

Antioxidative factors in milk.

Lipid auto-oxidation in milk is affected by a complex interplay of pro- and antioxidants. Several of these compounds are also important nutrients in the human diet and may have other physiological effects in the gastrointestinal tract and other tissues. Among antioxidative enzymes superoxide dismutase catalyses the dismutation of superoxide anion to hydrogen peroxide. The degradation of hydrogen peroxide can be catalysed by catalase and the selenoprotein glutathione peroxidase. The latter enzyme can also degrade lipid peroxides. Lactoferrin may have an important role by binding pro-oxidative iron ions. The occurrence of different forms of these antioxidative proteins in milk and available data on their functional role are reviewed. More remains to be learnt of individual compounds and as an example the potential role of seleno compounds in milk is virtually unknown. Antioxidative vitamins in milk can provide an important contribution to the daily dietary intake. Moreover vitamin E and carotenoids act as fat-soluble antioxidants, e.g. in the milk fat globule membrane, which is regarded as a major site of auto-oxidation. Vitamin C is an important water-soluble antioxidant and interacts in a complex manner with iron and fat-soluble antioxidants. The concentrations of these compounds in milk are affected by cow feeding rations and milk storage conditions. Since milk contains a number of antioxidants many reactions are possible and the specific function of each antioxidant cannot easily be defined. There are indications that other compounds may have antioxidative function and measurement of total antioxidative capacity should be a useful tool in evaluating their relative roles.

Islet constitutive nitric oxide synthase and glucose regulation of insulin release in mice.

We have studied, by a combined in vitro and in vivo approach, the relation between the inhibitory action of N(G)-nitro-l-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide synthase (NOS), on the activity of islet constitutive NOS (cNOS) and glucose regulation of islet hormone release in mice. The cNOS activity in islets incubated in vitro at 20 mM glucose was not appreciably affected by 0.05 or 0.5 mM L-NAME, but was greatly suppressed (-60%) by 5 mM L-NAME. Similarly, glucose-stimulated insulin release was unaffected by the lower concentrations of L-NAME but greatly enhanced in the presence of 5 mM of the NOS inhibitor. In incubated islets inhibition of cNOS activity resulted in a modestly enhanced insulin release in the absence of glucose, did not display any effect at physiological or subphysiological glucose concentrations, but resulted in a markedly potentiated insulin release at hyperglycaemic glucose concentrations. In the absence of glucose, glucagon secretion was suppressed by L-NAME. The dynamics of glucose-induced insulin release and (45)Ca(2+) efflux from perifused islets revealed that L-NAME caused an immediate potentiation of insulin release, and a slight increase in (45)Ca(2+) efflux. In islets depolarized with 30 mM K(+) in the presence of the K(+)(ATP) channel opener, diazoxide, L-NAME still greatly potentiated glucose-induced insulin release. Finally, an i.v. injection of glucose to mice pretreated with L-NAME was followed by a markedly potentiated insulin response, and an improved glucose tolerance. In accordance, islets isolated directly ex vivo after L-NAME injection displayed a markedly reduced cNOS activity. In conclusion, we have shown here, for the first time, that biochemically verified suppression of islet cNOS activity, induced by the NOS inhibitor L-NAME, is accompanied by a marked potentiation of glucose-stimulated insulin release both in vitro and in vivo. The major action of NO to inhibit glucose-induced insulin release is probably not primarily linked to changes in Ca(2+) fluxes and is exerted mainly independently of membrane depolarization events.

Consumption of oat milk for 5 weeks lowers serum cholesterol and LDL cholesterol in free-living men with moderate hypercholesterolemia.

The aim of this study was to investigate whether consumption of a newly developed oat milk deprived of insoluble fiber would result in lower serum cholesterol and low-density lipoprotein (LDL) cholesterol levels in men with moderate hypercholesterolemia. The study had a randomized, controlled double-blind design, and oat milk was compared with an identically flavored control drink. Sixty-six men were recruited from a screening program and were randomly assigned to two groups. Each group took either oat milk or a control drink (rice milk) for 5 weeks (0.75 liters/day) and then switched to the other drink regimen for another 5-week period with a 5-week washout period between the test periods. The oat milk contained more dietary fiber, especially beta-glucan (0.5 g/100 g), than the control drink (<0.02 g/100 g). Both drinks were well appreciated and got similar sensory evaluation, indicating that the double-blind design had been attained. In the final analysis 52 subjects remained. Compared with the control drink, intake of oat milk resulted in significantly lower serum total cholesterol (6%, p = 0.005) and LDL cholesterol (6%, p = 0.036) levels. The decrease in LDL cholesterol was more pronounced if the starting value was higher (r = -0.55, p < 0.001). The concentration of high-density lipoprotein cholesterol was not significantly different after consumption of the two drinks. Serum triglycerides did not change significantly after intake of oat milk, but a significant increase was observed after intake of the control drink (p = 0.003). It is concluded that also oat milk deprived of insoluble fiber has cholesterol-reducing properties.

Nitric oxide and hydroperoxide affect islet hormone release and Ca(2+) efflux.

We have investigated the influence of the intracellular free radical donors hydroxylamine (giving nitric oxide [NO]) and tert-butylhydroperoxide (giving hydroperoxide ["H2O2"]) on glucose- and cyclic adenosine monophosphate (cAMP)-induced transduction signaling in islet hormone release. Both donors dose dependently inhibited glucose-stimulated insulin release and induced modest (hydroxylamine) or profound (tertbutylhydroperoxide) suppression of 45Ca2+-efflux from perifused islets. By contrast, both donors stimulated glucagon release. Similar effects on hormone release were displayed after K+-depolarization. Insulin and glucagon release stimulated by activation of the cAMP system through isobutylmethylxanthine (IBMX) at basal glucose was modestly potentiated by low concentrations of both donors. These effects were still observed, although less pronounced, in K+-depolarized islets. In vitro as well as in vivo, the NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester inhibited IBMX-induced glucagon release, but did not affect insulin release. The results suggest that NO and hydroperoxide inhibit glucose-stimulated insulin release by perturbing Ca2+ fluxes and probably acting through S-nitrosylation (NO) or oxidation (hydroperoxide) of thiol groups critical to the secretory process. These effects are largely independent of depolarization events. By contrast, both NO and hydroperoxide can potentiate cAMP-stimulated hormone release presumably at a distal site in the stimulus-secretion coupling.

Plasma levels of selenium, selenoprotein P and glutathione peroxidase and their correlations to fish intake and serum levels of thyrotropin and thyroid hormones: a study on Latvian fish consumers.

OBJECTIVE: To study the relationships between fish intake and different markers of selenium status and thyroid hormone function. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Sixty-eight men (age 24-79 years) were recruited among coastal fishermen and inland subjects from Latvia. None of the subjects was on selenium medication or had any known endocrine disease. MAIN OUTCOME MEASURES: Correlations between fish intake, plasma levels of selenium, selenoprotein P, glutathione peroxidase, organic mercury in erythrocytes and TSH in serum. RESULTS: Selenium in plasma ranged from 0.30 to 1.56 micromol/l, selenoprotein P from 0.54 to 2.21 arbitrary units relative to pooled plasma, and glutathione peroxidase from 1.20 to 5.73 mg/l. The number of fish meals per month was correlated with plasma selenium, selenoprotein P and glutathione peroxidase (r = 0.63, r = 0.62 and r = 0.50, respectively; P<0.001). Plasma selenium was correlated with selenoprotein P and glutathione peroxidase (r = 0.88 and r = 0.67, respectively; P < 0.001), and also selenoprotein P and glutathione peroxidase were correlated (r = 0.63, P < 0.001). The mean plasma selenium level in those with a high fish intake (21-50 fish meals/month), was 81% higher than in those with lowest fish intake. TSH in serum was inversely correlated with plasma selenium and selenoprotein P. Thyroid hormone levels were not correlated with plasma selenium, selenoproteins or fish intake. CONCLUSIONS: In this study group, selenium from fish intake had a marked impact on all variables studied on selenium status. No impact of selenium status on T3 and T4 levels was observed. The slightly negative correlation of selenium status with TSH levels might indicate a higher TSH secretion at low selenium status.