Plasma and urine metabolite profiling reveals the protective effect of Clinacanthus nutans in an ovalbumin-induced anaphylaxis model: 1H-NMR metabolomics approach.

The present study sought to identify the key biomarkers and pathways involved in the induction of allergic sensitization to ovalbumin and to elucidate the potential anti-anaphylaxis property of Clinacanthus nutans (Burm. f.) Lindau water leaf extract, a Southeast Asia herb in an in vivo ovalbumin-induced active systemic anaphylaxis model evaluated by 1H-NMR metabolomics. The results revealed that carbohydrate metabolism (glucose, myo-inositol, galactarate) and lipid metabolism (glycerol, choline, sn-glycero-3-phosphocholine) are the key requisites for the induction of anaphylaxis reaction. Sensitized rats treated with 2000 mg/kg bw C. nutans extract before ovalbumin challenge showed a positive correlation with the normal group and was negatively related to the induced group. Further 1H-NMR analysis in complement with Kyoto Encyclopedia of Genes and Genomes (KEGG) reveals the protective effect of C. nutans extract against ovalbumin-induced anaphylaxis through the down-regulation of lipid metabolism (choline, sn-glycero-3-phosphocholine), carbohydrate and signal transduction system (glucose, myo-inositol, galactarate) and up-regulation of citrate cycle intermediates (citrate, 2-oxoglutarate, succinate), propanoate metabolism (1,2-propanediol), amino acid metabolism (betaine, N,N-dimethylglycine, methylguanidine, valine) and nucleotide metabolism (malonate, allantoin). In summary, this study reports for the first time, C. nutans water extract is a potential anti-anaphylactic agent and 1H-NMR metabolomics is a great alternative analytical tool to explicate the mechanism of action of anaphylaxis.

Metabonomic analysis of serum reveals antifatigue effects of Yi Guan Jian on fatigue mice using gas chromatography coupled to mass spectrometry.

Yi Guan Jian (YGJ), one of the most commonly used traditional Chinese medicines, has been reported to possess significant antifatigue effects. However, the mechanisms underlying its antifatigue effects remain largely unresolved. In this study, a metabonomics approach, involving gas chromatography coupled to mass spectrometry and a multivariate statistical technique, was developed to estimate the extent to which YGJ alleviated the exhausting swimming-induced fatigue of mice. High-dose treatment with YGJ significantly extended the swimming time of fatigued mice. Significant alterations of metabolites involving amino acids, organic acids and carbohydrates were observed in the serum of fatigued mice, which were reversed by YGJ treatment while biochemical indexes returned to normal. These metabolic changes suggest that the antifatigue effect of YGJ is associated with the impairement of amino acid, organic acids and carbohydrates. It also appears that YGJ can induce significant metabolic alterations independent of the exhausting swimming-induced metabolic changes. The significantly altered metabolites induced by YGJ intervention include l-2-amino-acetoacetate, taurine, fumaric acid, malic acid, oxoadipic acid and l-aspartate, all of which are associated with antifatigue properties. This suggests that YGJ exerts chemopreventive effects via antifatigue mechanisms.

Two-dimensional gas chromatography time-of-flight mass spectrometry-based serum metabolic fingerprints of neonatal calves before and after first colostrum ingestion.

Neonatal calves show a remarkable increase in serum IgG levels after first ingestion of colostrum. They can absorb high-molecular IgG from colostrum in the small intestine by nonspecific receptor-independent fluid pinocytosis within 24 h after birth. However, little is known about the temporal changes in serum small-molecule metabolites, such as carbohydrates and AA, in neonatal calves after first colostrum ingestion. In this study, we examined temporal changes in serum metabolites of neonatal calves after first ingestion of colostrum by comprehensive 2-dimensional gas chromatography mass spectrometry (GC×GC-MS). Forty serum samples obtained from 5 calves at 8 time points between 0 and 12 h after first colostrum ingestion were analyzed in triplicate by GC×GC-MS. Multivariate analyses of 120 GC×GC-MS results revealed significant variations in the serum metabolites, primary individual differences among the calves, and secondary temporal changes within each individual calf. Several serum metabolites increased temporally after ingestion in each calf, but only a limited number of compounds were increased universally in all 5 calves. Eight compounds, including oligosaccharides such as lactose, were associated with temporal changes in IgG. Some essential AA that must be supplied from the diet increased temporally after ingestion, but differed from the temporal pattern of the oligosaccharides and IgG. These results suggest that the colostral contents may be absorbed by complex mechanisms that include intestinal pinocytosis for IgG and oligosaccharides, along with others such as specific transporters in the intestinal epithelial cells for AA in calves.

Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects.

BACKGROUND: Lucerastat, an inhibitor of glucosylceramide synthase, has the potential to restore the balance between synthesis and degradation of glycosphingolipids in glycolipid storage disorders such as Gaucher disease and Fabry disease. The safety, tolerability, and pharmacokinetics of oral lucerastat were evaluated in two separate randomized, double-blind, placebo-controlled, single- and multiple-ascending dose studies (SAD and MAD, respectively) in healthy male subjects. METHODS: In the SAD study, 31 subjects received placebo or a single oral dose of 100, 300, 500, or 1000 mg lucerastat. Eight additional subjects received two doses of 1000 mg lucerastat or placebo separated by 12 h. In the MAD study, 37 subjects received placebo or 200, 500, or 1000 mg b.i.d. lucerastat for 7 consecutive days. Six subjects in the 500 mg cohort received lucerastat in both absence and presence of food. RESULTS: In the SAD study, 15 adverse events (AEs) were reported in ten subjects. Eighteen AEs were reported in 15 subjects in the MAD study, in which the 500 mg dose cohort was repeated because of elevated alanine aminotransferase (ALT) values in 4 subjects, not observed in other dose cohorts. No severe or serious AE was observed. No clinically relevant abnormalities regarding vital signs and 12-lead electrocardiograms were observed. Lucerastat Cmax values were comparable between studies, with geometric mean Cmax 10.5 (95% CI: 7.5, 14.7) and 11.1 (95% CI: 8.7, 14.2) µg/mL in the SAD and MAD study, respectively, after 1000 mg lucerastat b.i.d. tmax (0.5 - 4 h) and t1/2 (3.6 - 8.1 h) were also within the same range across dose groups in both studies. Using the Gough power model, dose proportionality was confirmed in the SAD study for Cmax and AUC0-∞, and for AUC0-12 in the MAD study. Fed-to-fasted geometric mean ratio for AUC0-12 was 0.93 (90% CI: 0.80, 1.07) and tmax was the same with or without food, indicating no food effect. CONCLUSIONS: Incidence of drug-related AEs did not increase with dose. No serious AEs were reported for any subject. Overall, lucerastat was well tolerated. These results warrant further investigation of substrate reduction therapy with lucerastat in patients with glycolipid storage disorders. SAD study was registered on clinicaltrials.gov under the identifier NCT02944487 on the 24th of October 2016 (retrospectively registered). MAD study was registered on clinicaltrials.gov under the identifier NCT02944474 on the 25th of October 2016 (retrospectively registered). TRIAL REGISTRATION: A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease. Clinicaltrials.gov: NCT02930655 .

Linking diet, physical activity, cardiorespiratory fitness and obesity to serum metabolite networks: findings from a population-based study.

OBJECTIVE: It is not yet resolved how lifestyle factors and intermediate phenotypes interrelate with metabolic pathways. We aimed to investigate the associations between diet, physical activity, cardiorespiratory fitness and obesity with serum metabolite networks in a population-based study. METHODS: The present study included 2380 participants of a randomly drawn subcohort of the European Prospective Investigation into Cancer and Nutrition-Potsdam. Targeted metabolomics was used to measure 127 serum metabolites. Additional data were available including anthropometric measurements, dietary assessment including intake of whole-grain bread, coffee and cake and cookies by food frequency questionnaire, and objectively measured physical activity energy expenditure and cardiorespiratory fitness in a subsample of 100 participants. In a data-driven approach, Gaussian graphical modeling was used to draw metabolite networks and depict relevant associations between exposures and serum metabolites. In addition, the relationship of different exposure metabolite networks was estimated. RESULTS: In the serum metabolite network, the different metabolite classes could be separated. There was a big group of phospholipids and acylcarnitines, a group of amino acids and C6-sugar. Amino acids were particularly positively associated with cardiorespiratory fitness and physical activity. C6-sugar and acylcarnitines were positively associated with obesity and inversely with intake of whole-grain bread. Phospholipids showed opposite associations with obesity and coffee intake. Metabolite networks of coffee intake and obesity were strongly inversely correlated (body mass index (BMI): r = -0.57 and waist circumference: r = -0.59). A strong positive correlation was observed between metabolite networks of BMI and waist circumference (r = 0.99), as well as the metabolite networks of cake and cookie intake with cardiorespiratory fitness and intake of whole-grain bread (r = 0.52 and r = 0.50; respectively). CONCLUSIONS: Lifestyle factors and phenotypes seem to interrelate in various metabolic pathways. A possible protective effect of coffee could be mediated via counterbalance of pathways of obesity involving hepatic phospholipids. Experimental studies should validate the biological mechanisms.

A soy-based supplement alters energy metabolism but not the exercise-induced stress response.

OBJECTIVE: To determine the changes in endurance capacity as well as in metabolic, hormonal and inflammatory markers induced by endurance training combined with a soy,protein based supplement. DESIGN: Randomized controlled study consisting of moderate endurance training without (GO) or with (G1) a soy protein based supplement. SUBJECTS: Two groups of 15 subjects (10 males and 5 females in each group): healthy sports students aged 23.6 +/- 1.9 years. MEASUREMENTS: Body composition (body mass (BM), body density (BD) by air displacement) and physical fitness (determined by treadmill ergometry) were measured at baseline and after 6 weeks of the intervention; changes in circulating metabolic and hormonal parameters (glucose, lactate, urea, uric acid, ammonia, cortisol, insulin, IGF-1), and exercise-induced stress and inflammatory markers (CK, LDH, myoglobin, hs-CRP, IL-6, IL-10, blood cell counts) were determined after the intervention period in afield test (11.5 km running on hilly ground). RESULTS: 30 participants completed the 6-week study; 28 students were able to perform the field test. No significant changes in BM and BD were noted after intervention with only slight increases in running performance and maximum aerobic capacity in the total group (2%, p=0.016). Subjects in the G1 group showed significant improvements in running velocity and lower lactate values following the intervention (-12%, p=0,003). In addition, the G1 group showed significantly lower differences in the exercise-induced increase of metabolic parameters (triglycerides, uric acid) and insulin in the post-exercise recovery period. CONCLUSIONS: Our data suggest that moderate endurance training in combination with a soy-based protein supplement improves aerobic energy supply and metabolic function in healthy sports students, even without changes in body composition and without changes in the exercise-induced stress and inflammatory reaction.

[Metabonomic study on siwu tang in radiation-induced blood deficient mice].

OBJECTIVE: To study the radiation-induced blood deficiency and the combination of prescription and syndrome of Siwu Tang using ultra performance liquid chromatography-quadrupoles-time of flight mass spectrometer (UPLC-ESI-Q-TOF-MS), in order to discover the changes in metabolic profiles of blood deficient mice induced by radiation, and clarify the relationship between blood deficient syndrome and the mechanism of Siwu Tang. METHOD: Thirty six C57 mice were randomly divided into three groups: the control group and the model model groups and the Siwu Tang group. The model was established by general irradiation with 3.5 Gy60 Coy ray. The animals were sacrificed on the 7th day after radiation and their blood, spleens and thymus were collected and detected using UPLC-ESI-Q-TOF/MS. MarkerLynx XS software was adopted to identify chromatographic peaks in the total ion chromatogram. Data was processed by making principal component analysis and analyzed by orthogonal partial least squares method among these groups, in order to rapidly identify marks through pattern recognition and analysis. RESULT: Compared with the control group, lysophosphatide, glucosiduronic acid, monoacylglycerol, erythronic acid, ceramide, aspartate phosphate ester, glyceryl phosphatide were obviously changed in the sera of the model group. Monoacylglycerol, ceramide, lysophosphatide, hydroxybutyric acid, palmitinic acid, 3-hydroxystearic acid, diethylarginine, neuraminic acid, phosphatidylserine were found in metabolites of their spleens. Methyladenosine, sitosterol, carnitine, phosphatidylinositol, phosphatidylethanolamine, diglyceride, dimethylarginine, ceramide, hydroxybutyric acid, cholesterol were found in thymus of the model group. CONCLUSION: Analysis on physiological functions of these biological markers show that radiation could induce the disorder of the metabolism of lipoid and carbohydrate and affect the synthesis of some amino acids, and Siwu Tang can reverse these effects.

Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations.

OBJECTIVES: Fluoride is a serious health hazard across several nations, and chronic intake of fluoride deranges the carbohydrate, lipid and antioxidant metabolism in general. As there are limited remedial measures to prevent fluorosis, we investigated the role of tamarind leaf as a food supplement in restoration of carbohydrate, lipid and antioxidant metabolism in fluoride-exposed albino rats. METHODS: Albino rats were exposed to fluoride (100 ppm sodium fluoride) through drinking water and fed diet supplemented with tamarind leaf powder (2.5, 5 and 10 g %) for 4 weeks. Carbohydrate, lipid and antioxidant profiles were investigated in both controls and fluoride-exposed animals. RESULTS: While 4-week exposure to fluoride elevated plasma glucose and lipid profiles, simulating diabetic and hyperlipidaemic conditions, the antioxidant defence mechanisms of fluoride-exposed rats were compromised, with elevation and decline in lipid peroxidation and high-density lipoprotein (HDL)-cholesterol, respectively. When the diet was supplemented with tender tamarind leaves (used in southern India as a replacement for tamarind or other sour food ingredients), significant improvements in carbohydrate and lipid profiles occurred as evidenced by decreased plasma glucose and lipid levels, lipid peroxidation, increased hepatic glycogen content, hexokinase activity and cholesterol excretion, with simultaneous improvement in antioxidant profiles of both hepatic and renal tissues. CONCLUSIONS: These findings are significant in view of the need for cost-effective approaches to tackle fluorosis as an environmental hazard and use of food supplements as ameliorative measures.

Therapeutic effect of Saraca asoca (Roxb.) Wilde on lysosomal enzymes and collagen metabolism in adjuvant induced arthritis.

Rheumatoid arthritis is a chronic, progressive and systemic inflammatory disorder mainly affecting the synovial joints. In the present study, we evaluated the anti-arthritic effect of the methanol extract of Saraca asoca (Roxb.) Wilde., (Fabaceae) on adjuvant induced arthritis by assessing paw swelling, body weight, the levels of lysosomal enzymes, protein bound carbohydrates, serum cytokines, urinary collagen and histopathology of joints. It was found that S. asoca methanol extract at doses of 50, 100 and 200 mg/kg reduced the paw thickness and elevated the mean body weight of arthritic rats. The treatment of S. asoca showed a significant reduction in the levels of both plasma and liver lysosomal enzymes. The protein bound carbohydrates and urinary collagen contents were also decreased at a significant level by the treatment of S. asoca methanol extract. The histopathological study of the joints showed the anti-arthritic property of S. asoca which nearly normalized the histological architecture of the joints. Further, we established the anti-arthritic activity of S. asoca methanol extract by measuring the levels of cytokines in both arthritic and treated rats. The treatment of S. asoca reduced the levels of pro-inflammatory cytokines. In conclusion, S. asoca methanol extract was capable of ameliorating the conditions of arthritis in adjuvant induced arthritic rats.

An invertebrate hyperglycemic model for the identification of anti-diabetic drugs.

The number of individuals diagnosed with type 2 diabetes mellitus, which is caused by insulin resistance and/or abnormal insulin secretion, is increasing worldwide, creating a strong demand for the development of more effective anti-diabetic drugs. However, animal-based screening for anti-diabetic compounds requires sacrifice of a large number of diabetic animals, which presents issues in terms of animal welfare. Here, we established a method for evaluating the anti-diabetic effects of compounds using an invertebrate animal, the silkworm, Bombyx mori. Sugar levels in silkworm hemolymph increased immediately after feeding silkworms a high glucose-containing diet, resulting in impaired growth. Human insulin and 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth. Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. These responses were inhibited by wortmannin, an inhibitor of phosphoinositide 3 kinase. Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body. Administration of aminoguanidine, a Maillard reaction inhibitor, repressed the accumulation of Maillard reaction products (advanced glycation end-products; AGEs) in the hyperglycemic silkworms and restored growth, suggesting that the growth defect of hyperglycemic silkworms is caused by AGE accumulation in the hemolymph. Furthermore, we identified galactose as a hypoglycemic compound in jiou, an herbal medicine for diabetes, by monitoring its hypoglycemic activity in hyperglycemic silkworms. These results suggest that the hyperglycemic silkworm model is useful for identifying anti-diabetic drugs that show therapeutic effects in mammals.

Effects of high-dose statin on the human hepatic expression of genes involved in carbohydrate and triglyceride metabolism.

OBJECTIVES: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, lowers plasma cholesterol and triglyceride (TG) levels dose dependently. The aim of this study was to investigate the molecular mechanism(s) of this decrease in plasma TG levels in atorvastatin-treated subjects. RESEARCH DESIGN AND METHODS: Lipoprotein separation and plasma analysis of lipids, glucose and insulin were performed in subjects randomly assigned to placebo (n = 9) or atorvastatin (80 mg per day) (n = 10) for 4 weeks. Liver TG mass was determined in pooled samples. Hepatic expression of several genes involved in carbohydrate and TG metabolism was determined. RESULTS: Atorvastatin lowered plasma levels of very low-density lipoprotein (VLDL) TG (∼50%, P < 0.05) and liver TG mass compared to placebo. Except for cholesterol changes, there were no other significant differences in plasma lipids, glucose or insulin. However, atorvastatin reduced mRNA expression of sterol regulatory element-binding protein 1c (SREBP1c) (>30%, P < 0.05), glucokinase (∼50%, P < 0.05) and angiopoietin-like protein 3 (ANGPTL3) (∼25%, P < 0.01), and induced mRNA expression of acetyl-coenzyme A carboxylase 1 (∼45%, P < 0.05) and glucose-6-phosphatase (∼90%, P < 0.05) compared to placebo. CONCLUSIONS: Following treatment with atorvastatin, reduced ANGPTL3 mRNA expression may contribute to the reduced plasma levels of VLDL TG. The reduced liver TG mass induced by a high dosage of atorvastatin may be important for the treatment of patients with fatty liver.

Immunoglobulin-E reactivity to a glycosylated food allergen (peanuts) due to interference with cross-reactive carbohydrate determinants in heavy drinkers.

BACKGROUND: N-glycans in plant and invertebrate glycoproteins can induce extensive IgE cross-reactivity therefore limiting the specificity of in vitro allergy tests. IgE sensitization to N-glycans (cross-reactive carbohydrate determinants, CCDs) may be increased in heavy drinkers, who therefore show IgE reactivity to aeroallergens, latex, and Hymenoptera venoms. The peanut, a CCD-bearing allergen, is the leading cause of severe food allergic reactions in many populations. AIM OF THE STUDY: To investigate the potential interference of CCDs with determinations of IgE to peanuts in heavy drinkers. METHODS: We determined IgE to peanuts and IgE to a CCD marker (MUXF(3), the N-glycan from bromelain) in 41 heavy drinkers admitted to the hospital and 54 healthy controls. None of the participants reported symptoms of peanut allergy. In cases with positive (>or=0.35 kU/l) IgE to peanuts, we performed inhibition assays with a neoglycoprotein consisting of MUXF(3) molecules coupled to bovine serum albumin (MUXF(3)-BSA) and a similar neoglycoprotein lacking xylose and fucose (MM-BSA). In the same cases, we screened for IgE to a panel of recombinant nonglycosylated peanut allergens. SDS-PAGE immunoblotting and inhibition assays were performed in selected cases. RESULTS: The prevalence of positive IgE to peanuts was 22 and 3.7% in heavy drinkers and healthy controls, respectively (p < 0.001). Peanut-IgE positivity was closely related to the presence of IgE to CCDs. In most (8/9) heavy drinkers with positive IgE to peanuts, reactivity was inhibited by preincubation with MUXF(3)-BSA, but not with MM-BSA. IgE binding to multiple bands on immunoblotting studies was also inhibited by MUXF(3)-BSA preincubation. IgE to nonglycosylated recombinant peanut allergens was uniformly negative. CONCLUSION: Heavy drinking is associated with clinically asymptomatic IgE reactivity to peanuts, a relevant food allergen, in relation to CCD interference.

The effect of Momordica charantia and Mucuna pruriens in experimental diabetes and their effect on key metabolic enzymes involved in carbohydrate metabolism.

The Indian traditional system of medicine prescribed traditional plant therapies. Two such plants, i.e. Momordica charantia (MC) and Mucuna pruriens (MP), earlier shown to reduce hyperglycaemia, were assessed for their anti hyperglycaemic effect on varying degrees of hyperglycaemia and diabetic complications. Alcohol and aqueous extracts of MC (50, 100 and 200 mg/kg/day) and only an alcohol extract of MP (100, 200 and 400 mg/kg/day) were evaluated in a pilot study (plasma glucose >180 mg/dL, 21 days), a chronic study in alloxanized rats (plasma glucose >280mg/dL, 120 days) and streptozotocin (STZ) mice (plasma glucose >400 mg/dL, 60 days). In the pilot study, the maximum antihyperglycaemic effect occurred with an aqueous extract of MC at week 3 and an alcohol extract of MP at week 6 at a dose of 200 mg/kg/day. In chronic alloxanized rats, the selected dose of MC led to a significant fall of 64.33%, 66.96%, 69.7% and 70.53% in plasma glucose levels at 1, 2, 3 and 4 months, respectively. MP showed a decrease of 40.71%, 45.63%, 50.33% and 51.01% at the same time period. In chronic STZ diabetic mice, MC led to a mean reduction of 15.37%, 18.68% and 22.86% in plasma glucose levels on days 40, 50 and 60 of sampling while MP had no significant effect. The alteration in hepatic and skeletal muscle glycogen content and hepatic glucokinase, hexokinase, glucose-6-phosphate and phosphofructokinase levels in diabetic mice were partially restored by MC but not by MP. The mechanism of action of MC and MP is discussed.

Labile iron in parenteral iron formulations and its potential for generating plasma nontransferrin-bound iron in dialysis patients.

BACKGROUND: Labile plasma iron (LPI) associated with iron supplementation has been implicated in complications found in dialysis patients. As LPI can potentially catalyse oxygen radical generation, we determined the presence of labile iron in the parenteral preparations and the frequency of occurrence of LPI in dialysis patients. DESIGN: The capacity to donate iron to apotransferrin (apo-) or to the chelator desferrioxamine (DFO) was measured with fluorescein-Tf (Fl-Tf) and Fl-DFO, respectively. Those probes undergo quenching upon binding to iron. Iron-catalysed generation of oxidant species was determined with dihydrorhodamine. Plasma nontransferrin-bound iron (NTBI), here termed LPI, was determined by mobilization of iron from low-affinity binding sites with oxalate, followed by its quantification with Fl-Tf in the presence of Ga(III). RESULTS: Normal individuals and most (80%) dialysis patients, analysed at least 1 week after iron supplementation showed no detectable (<0.2 microm) LPI. However, approximately 20% of the patients (n = 71) showed significant LPI levels (>0.2 microm), in some cases weeks after iron administration. LPI levels correlated best (r2 = 0.9) with Tf saturation. The iron preparations contained 2-6% low molecular weight and redox-active iron, most of which is chelated by Tf. CONCLUSIONS: Parenteral iron formulations contain a small but significant fraction of redox-active iron, most of which is scavenged by apo-Tf within <1 h. Therefore, oxidant stress associated with iron infusion is likely to be transient. The bulk of the polymeric iron is apparently inaccessible to apo-Tf. Although LPI might return to normal within 2 h of intravenous iron infusion, the long-term persistence of low-level LPI in up to 20% of end stage renal disease (ESRD) patients indicates that complete clearance of the intravenous iron may be more protracted than originally estimated.

Carbohydrate dynamics and the crustacean hyperglycemic hormone (CHH): effects of parasitic infection in Norway lobsters (Nephrops norvegicus).

The effects of a dinoflagellate parasite (Hematodinium sp.) on carbohydrate metabolism were examined in the Norway lobster, Nephrops norvegicus. Five stages of infection were observed. These included uninfected (Stage 0), subpatently infected (SP), and patently infected (Stage 1-4) lobsters. During patent infection, the concentration of glucose in the hemolymph was reduced significantly from its value of 180 microg ml(-1) in uninfected (Stage 0) lobsters to 25.3 microg ml(-1) in Stage 3-4. These changes were accompanied by significantly lower levels of hepatopancreatic glycogen in lobsters at Stage 2 (2.01 mg g(-1)) and Stage 3-4 (0.84 mg g(-1)) of infection than in those at Stage 0 (16.19 mg g(-1)) and Stage 1 (14.71 mg g(-1)). Due to disruption of the normal feedback loops which control the release of crustacean hyperglycemic hormone (CHH), plasma concentrations increased with the severity of infection from 32.2 fmol ml(-1) in Stage 0 to 106.6 fmol ml(-1) in Stage 3-4. The increased CHH concentrations occurred concomitantly with reduced concentrations of plasma glucose and tissue glycogen. A significantly increased hemolymph CHH titer (107.7 fmol ml(-1)) was also observed during SP infection. It is concluded that the parasite places a heavy metabolic load on the host lobster.

[The diet rich in monounsaturated fat modifies in a beneficial way carbohydrate metabolism and arterial pressure]. / La dieta rica en grasa monoinsaturada modifica de forma beneficiosa el metabolismo de los hidratos de carbono y la presión arterial.

OBJECTIVE: Two dietary regimens recommended for the reduction of coronary risk, by way of their effects on lipid profile, are the diet low in saturated fat and a diet rich in monounsaturated fats (MUFA). However the effects of these diets on carbohydrate metabolism in healthy subjects are not well known. The objective of this study was to compare the effect of both diets on various parameters of carbohydrate metabolism. METHODS: 41 healthy young males were submitted to 3 consecutive diets, each for a duration of 4 weeks. The first diet was rich in saturated fat (SAT) (38% fat, 20% saturated). The second was rich in carbohydrates following the recommendations of the NCEP-I (National Cholesterol Education Program type I) (28% fat, 47% carbohydrates). The last one was a diet rich in monounsaturated fatty acids (38% fat, 22% MUFA). At the end of each dietary period, blood pressure (BP) and blood levels of glucose, insulin and free fatty acids were determined. 29 subjects were also submitted to an oral glucose tolerance test (OGTT) at the end of each diet. RESULTS: The SAT diet induced the highest levels of insulin after the OGTT. The consumption of the MUFA diet determined the lowest levels of fasting blood glucose (-0.60 mmol/l [13%], p < 0.0002), insulin (-9 microUl/ml [47%], p < 0.0002) and free fatty acids (-0.11 mmol/l [24%], p = 0.006), compared to the NCEP-I diet. Systolic and diastolic blood pressure were higher in the NCEP-I diet than during the other periods (SBP: +6 mmHg compare with SAT [5%], p = 0.0001; and +5 mmHg compare with MUFA [4%], p = 0.0001; DBP: +20 mmHg compare with MUFA [27%], p = 0.0001) and +6 mmHg compared with SAT [8%], p = 0.0001). CONCLUSION: Of the diets most commonly used for the treatment and prevention of arteriosclerosis, a diet rich in monounsaturated fats is the most beneficial for the healthy population from the point of view of carbohydrate metabolism and blood pressure.

Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run.

BACKGROUND: Athletes consume arginine and/or aspartate as potential nutritional ergogenics. Their metabolic effects are controversial and there is some evidence that ingestion of large doses of single amino acids can adversely affect the nitrogen balance or induce an amino acid imbalance. Nevertheless, the general metabolic influence of an arginine aspartate supplementation during a prolonged exercise bout has not yet been investigated. AIM OF THE STUDY: The aim of this study was, therefore, to investigate the general metabolic impact of a chronic supplementation with arginine aspartate in endurance-trained athletes at rest and during a marathon run. METHODS: Fourteen endurance-trained runners participated in this field study which was carried out according to a double-blind crossover design. 15 g of arginine aspartate or a carbohydrate-based placebo were supplemented daily for 14 days before a marathon run. Blood samples for analysis of metabolites and hormones were collected shortly before the run, after 31 km, at the end of the run, and after a recovery period of two hours. Additionally, the respiratory exchange ratio was determined during the run. RESULTS: The plasma level of carbohydrate (glucose, lactate, pyruvate) and fat metabolites (fatty acids, glycerol, beta-hydroxybutyrate), cortisol, insulin, ammonia, lactate dehydrogenase, and creatine kinase as well as the respiratory exchange ratio were unaffected by the supplementation. In contrast, the plasma level of somatotropic hormone, glucagon, urea, and arginine were significantly increased, and the level of most of the remaining plasma amino acids as well as their sum was significantly reduced. CONCLUSIONS: There was no obvious metabolic benefit derived from the chronic supplementation with arginine aspartate. And since furthermore the consequences of a reduction of the total plasma amino acid level are not known, the practice of using single amino acid supplements as potential ergogenics should be critically reevaluated.

Digestive and metabolic effects of potato and maize fibres in human subjects.

The physiological effects of dietary fibres in humans are due to their physico-chemical properties. However, it is difficult to predict these effects simply by measuring certain characteristics in vitro. Studies in human subjects are still required to assess the effectiveness of new substrates. The aim of the present study in healthy human subjects was to evaluate the effects of two novel fibres, potato (PF) and maize (MF), on fasting and postprandial blood concentrations of carbohydrate and lipid metabolites as well as on stool output and transit time. The chemical composition, water-binding capacity (WBC) and fermentative properties of the fibres were also characterized in order to determine their possible involvement in digestive and metabolic effects. Stools, as well as breath and blood samples, were collected after consumption for 1 month of either a basal diet (control) or a basal diet supplemented with fibre (15 g/d). MF resisted fermentation better than PF and had lower digestibility. However, both fibres increased faecal output of dry matter, neutral sugars and water. There was an inverse relationship between stool weight and orofaecal transit time, although only MF significantly reduced transit time. Orocaecal transit was lengthened by PF, probably because of its high WBC. PF ingestion also decreased postprandial plasma levels of total and esterified cholesterol but had no effect on fasting concentrations. In contrast, MF lowered fasting cholesterolaemia and increased free:esterified cholesterol. These particular physiological and fermentative properties suggest that PF and MF would be suitable ingredients in a healthy diet.

[Topinambur concentrate in the treatment of patients with insulin-dependent diabetes mellitus]. / Kontsentrat topinambura v lechenii bol'nykh insulinozavisimym sakharnym diabetom.

The authors studied activity of home nutricevtic concentrate of topinambur in patients with different clinical forms of insulin-dependent diabetes mellitus. Concentrate of topinambur promoted normal carbohydrate and lipid metabolism, increased ferrum level in serum, had immunomodulating activity. Nutricevtic was the most effective one in patients with not long duration of insulin-dependent diabetes mellitus.