Macroalgal protein hydrolysates from Palmaria palmata influence the 'incretin effect' in vitro via DPP-4 inhibition and upregulation of insulin, GLP-1 and GIP secretion.

PURPOSE: This study investigated metabolic benefits of protein hydrolysates from the macroalgae Palmaria palmata, previously shown to inhibit dipeptidylpeptidase-4 (DPP-4) activity in vitro. METHODS: Previously, Alcalase/Flavourzyme-produced P. palmata protein hydrolysate (PPPH) improved glycaemia and insulin production in streptozotocin-induced diabetic mice. Here the PPPH, was compared to alternative Alcalase, bromelain and Promod-derived hydrolysates and an unhydrolysed control. All PPPH's underwent simulated gastrointestinal digestion (SGID) to establish oral bioavailability. PPPH's and their SGID counterparts were tested in pancreatic, clonal BRIN-BD11 cells to assess their insulinotropic effect and associated intracellular mechanisms. PPPH actions on the incretin effect were assessed via measurement of DPP-4 activity, coupled with GLP-1 and GIP release from GLUTag and STC-1 cells, respectively. Acute in vivo effects of Alcalase/Flavourzyme PPPH administration on glucose tolerance and satiety were assessed in overnight-fasted mice. RESULTS: PPPH's (0.02-2.5 mg/ml) elicited varying insulinotropic effects (p < 0.05-0.001). SGID of the unhydrolysed protein control, bromelain and Promod PPPH's retained, or improved, bioactivity regarding insulin secretion, DPP-4 inhibition and GIP release. Insulinotropic effects were retained for all SGID-hydrolysates at higher PPPH concentrations. DPP-4 inhibitory effects were confirmed for all PPPH's and SGID counterparts (p < 0.05-0.001). PPPH's were shown to directly influence the incretin effect via upregulated GLP-1 and GIP (p < 0.01-0.001) secretion in vitro, largely retained after SGID. Alcalase/Flavourzyme PPPH produced the greatest elevation in cAMP (p < 0.001, 1.7-fold), which was fully retained post-SGID. This hydrolysate elicited elevations in intracellular calcium (p < 0.01) and membrane potential (p < 0.001). In acute in vivo settings, Alcalase/Flavourzyme PPPH improved glucose tolerance (p < 0.01-0.001) and satiety (p < 0.05-0.001). CONCLUSION: Bioavailable PPPH peptides may be useful for the management of T2DM and obesity.

Oral spray wintertime vitamin D3 supplementation has no impact on inflammation in Gaelic footballers.

Vitamin D inadequacy [total 25(OH)D <50 nmol/L] is widespread in athletes. The biologically active metabolite, 1,25-dihydroxyvitamin D, may be involved in regulating inflammation although in vitro findings have not been consistently replicated in human intervention trials. This study, conducted at a latitude of 55°N, aimed to assess inflammatory biomarkers in Gaelic footballers before and after a wintertime vitamin D3 intervention. Samples from a 12-week double-blind, randomized, placebo-controlled trial, in which 42 Gaelic footballers received 3000 IU (75 µg) vitamin D3 daily or placebo via oral spray solutions, were analysed for a range of inflammatory biomarkers. Cytokines (interleukin-8 and tumor necrosis factor-α), cathelicidin and high sensitivity C-reactive protein were quantified by multiplex assay, enzyme-linked immunosorbent assay and clinical biochemistry, respectively. White blood cell, lymphocyte, and neutrophil concentrations were determined by full blood profile. Data on total 25-hydroxyvitamin D, measured by LC-MS/MS, were available from the previous study. Vitamin D3 supplementation significantly increased mean total 25-hydroxyvitamin D concentrations from 47 to 84 nmol/L (P = 0.006); yet this had no effect on white blood cell count (P = 0.699), lymphocyte (P = 0.694), neutrophil (P = 0.594), interleukin-8 (P = 0.334), tumor necrosis factor-α (P = 0.587), cathelicidin (P = 0.745) or high sensitivity C-reactive protein concentration (P = 0.621) compared to placebo. 12-weeks vitamin D3 supplementation did not impact the immune profile of Gaelic footballers. This is likely because biomarkers were within their respective normal range or at a concentration similar to that of the general population at baseline. Future studies are encouraged to use inflammation as their primary outcome measure and recruit athletes at risk of compromised immunity.

Indices of adiposity as predictors of cardiometabolic risk and inflammation in young adults.

BACKGROUND: Studies investigating obesity and cardiometabolic risk have focused on 'at-risk' populations and methodological inconsistencies have produced equivocal findings. The present cross-sectional study investigated indices of body composition as predictors of cardiometabolic risk and their relationship with inflammation in apparently healthy young adults. METHODS: A fasting blood sample was taken from consenting adults (160 males, 32 females, aged 18-40 years) for assessment of cardiometabolic risk markers (blood pressure, lipid profiles and insulin resistance) and inflammatory markers (C-reactive protein, tumour necrosis factor-α, interleukin-6, interleukin-10 and adiponectin). Together with anthropometry, fat mass (FM) and fat-free mass (FFM) were determined by dual-energy X-ray absorptiometry. FM was expressed in absolute terms (kg), as well as relative to total body weight (%), height [FM index (FMI, kg m(-2) )] and FFM (FM : FFM,%). RESULTS: Although anthropometric indices were associated with most cardiometabolic risk markers, the strongest relationship was observed with FMI. Relative to having a low cardiometabolic risk (≤2 markers above clinically relevant cut-offs), each kg m(-2) increase in FMI, increased the likelihood of having an increased cardiometabolic risk by 29% (odds ratio = 1.29; 95% confidence interval = 1.12-1.49). Inflammatory markers were not associated with body composition or cardiometabolic risk. CONCLUSIONS: FMI was the strongest predictor of overall cardiometabolic risk but not inflammation per se. However, anthropometric indices, such as body mass index and waist-to-height ratio, remain valuable surrogate measures of adiposity in this group, particularly when risk markers are considered independently.

Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers.

Red meat from grass-fed animals, compared with concentrate-fed animals, contains increased concentrations of long-chain (LC) n-3 PUFA. However, the effects of red meat consumption from grass-fed animals on consumer blood concentrations of LC n-3 PUFA are unknown. The aim of the present study was to compare the effects on plasma and platelet LC n-3 PUFA status of consuming red meat produced from either grass-fed animals or concentrate-fed animals. A randomised, double-blinded, dietary intervention study was carried out for 4 weeks on healthy subjects who replaced their habitual red meat intake with three portions per week of red meat (beef and lamb) from animals offered a finishing diet of either grass or concentrate (n 20 consumers). Plasma and platelet fatty acid composition, dietary intake, blood pressure, and serum lipids and lipoproteins were analysed at baseline and post-intervention. Dietary intakes of total n-3 PUFA, as well as plasma and platelet concentrations of LC n-3 PUFA, were significantly higher in those subjects who consumed red meat from grass-fed animals compared with those who consumed red meat from concentrate-fed animals (P < 0·05). No significant differences in concentrations of serum cholesterol, TAG or blood pressure were observed between groups. Consuming red meat from grass-fed animals compared with concentrate-fed animals as part of the habitual diet can significantly increase consumer plasma and platelet LC n-3 PUFA status. As a result, red meat from grass-fed animals may contribute to dietary intakes of LC n-3 PUFA in populations where red meat is habitually consumed.

Associations between maternal inflammation during pregnancy and infant birth outcomes in the Seychelles Child Development Study.

PROBLEM: Markers of maternal inflammation may determine infant birth outcomes. METHOD OF STUDY: Maternal serum samples were collected at 28 weeks gestation (n = 1418) in the Seychelles Child Development Study Nutrition Cohort 2 and analyzed for immune markers by MSD multiplex assay, including cytokines from the Th1 (IFN-γ, IL-1ß, IL-2 and TNF-α) and Th2 (IL-4, IL-5, IL-10) subsets, with IL-6, MCP-1, TARC, sFlt-1 and VEGF-D. Associations of log-transformed immune markers with birthweight, length, head circumference and gestational age were assessed by multiple linear regression models, which were adjusted for maternal age, BMI, parity, child sex, gestational age and socioeconomic status. RESULTS: Neither total Th1, Th2 nor Th1:Th2 were significantly associated with any birth outcome. However, the angiogenesis marker VEGF-D was predictive of a lower birthweight, (ß = -0.058, P = 0.017) and birth length (ß = -0.088, P = 0.001) after adjusting for covariates. Higher concentrations of CRP were predictive of a lower birthweight (ß = -0.057, P = 0.023) and IL-2 (ß = 0.073, P = 0.009) and the chemokine MCP-1 (ß = 0.067, P = 0.016) were predictive of a longer gestational age. CONCLUSIONS: In our cohort of healthy pregnant women, we found no evidence for associations between the Th1 or Th2 inflammatory markers with birth outcomes. However, VEGF-D and CRP appear to predict lower birthweight and IL-2 and MCP-1 a longer gestation. Greater understanding is required of the variation in these immune markers at different gestational stages, as well as the factors which may regulate their balance in healthy pregnancy. n = 233.

Regioselective palladium-catalyzed arylation of 2-furaldehyde.

An efficient regioselective method for the direct arylation of 2-furaldehyde to provide a range of pi-diverse 5-aryl-2-formylfuran derivatives is described. The method employs functionalized aryl halides and a catalytic amount of palladium(II) chloride under relatively mild conditions.

Visual search in depth.

The accuracy of saccade localisation during visual search was examined for a search target defined by the single features of orientation or depth or by a conjunction of the two features. Subjects were required to move their eyes to the target which appeared in one of eight possible locations, arranged circularly around fixation, with non-targets filling the remaining seven positions. Search for a target defined by a single feature resulted in approximately 70% correct first saccades in both cases, while search for the conjunction target resulted in only 40% correct first saccades. Furthermore, averaged latency for conjunction search was longer than for simple search. Nevertheless, some subjects showed a remarkably good ability to locate a conjunction target with a single saccade of short latency. An analysis of first saccades in terms of their speed and accuracy indicates that the target selection is not preceded by a covert scanning of the display but rather is a result of parallel processing of the visual information provided. We also relate our study to the study of conjunction search reported by Nakayama and Siverman [Nakayama, K., & Silverman, G.H. (1986). Serial and parallel processing of visual feature conjunctions. Nature, 320, 264-265.].

Vitamin D deficiency is associated with inflammation in older Irish adults.

CONTEXT: Inadequate vitamin D status is common within elderly populations and may be implicated in the etiology of autoimmune disease and inflammation. Few studies have investigated the relationship between vitamin D status and age-related immune dysfunction in humans. OBJECTIVE: The aim of this study was to investigate the association between vitamin D status and immune markers of inflammation in a large sample of older adults. DESIGN, SETTING, AND PARTICIPANTS: An observational investigation of 957 Irish adults (>60 years of age) recruited in Northern Ireland (55°N latitude) as part of the Trinity Ulster Department of Agriculture aging cohort study. MAIN OUTCOME MEASURE: We measured serum 25-hydroxyvitamin D (25(OH)D) by liquid chromatography tandem mass spectrometry and serum cytokines IL-6, TNF-α, IL-10, and C-reactive protein (CRP) by ELISA. RESULTS: Concentrations of IL-6, CRP, and the ratios of IL-6 to IL-10 and CRP to IL-10 were significantly higher in individuals with deficient (<25 nmol/L) serum 25(OH)D compared with those with sufficient (>75 nmol/L) status after adjustment for age, sex, and body mass index (P < .05). Vitamin D status was a significant predictor of the IL-6 to IL-10 cytokine ratio, and those participants defined as deficient were significantly more likely to have an IL-6 to IL-10 ratio >2:1 compared with those defined as sufficient. CONCLUSIONS: This study demonstrated significant associations between low vitamin D status and markers of inflammation (including the ratio of IL-6 to IL-10) within elderly adults. These findings suggest that an adequate vitamin D status may be required for optimal immune function, particularly within the older adult population.

Prenatal methyl mercury exposure in relation to neurodevelopment and behavior at 19 years of age in the Seychelles Child Development Study.

BACKGROUND: Fish are important sources of protein and contain a variety of nutrients, such as n-3 long-chain polyunsaturated fatty acids (PUFA), essential for normal brain development. Nevertheless, all fish also contain methyl mercury (MeHg), a known neurotoxicant in adequate dosage. Our studies of the Seychelles Child Development Study (SCDS) Main Cohort enrolled in 1989-1990 (n=779) have found no consistent pattern of adverse MeHg effects at exposures achieved by daily fish consumption. Rather, we have observed evidence of improved performance on some cognitive endpoints as prenatal MeHg exposure increases in the range studied. These observations cannot be related to MeHg and may reflect the role of unmeasured covariates such as essential nutrients present in fish. To determine if these associations persist into young adulthood, we examined the relationship between prenatal MeHg exposure, recent PUFA exposure and subjects' neurodevelopment and behavior at 19 years of age. METHODS: We examined 533 participants using the following test battery: the Profile of Mood States-Bipolar (POMS-Bi); Finger Tapping; Kaufman Brief Intelligence Test (K-BIT); measures of Fine Motor Control and Complex Perceptual Motor Control; and Visual Spatial Contrast Sensitivity. We collected the following covariates: maternal IQ, family life course stressors, socioeconomic status, and subjects' recent postnatal MeHg, sex, and computer use. Primary analyses (based on N=392-475) examined covariate-adjusted associations in multiple linear regression models with prenatal MeHg as the primary exposure measure. Secondary analyses additionally adjusted for total n-6 and fish-related n-3 PUFA measured in the subjects' serum at the 19-year examination. RESULTS: Study participants had a mean prenatal MeHg exposure of 6.9 ppm, and a mean recent postnatal exposure of 10.3 ppm. There were no adverse associations between prenatal MeHg and any of the measured endpoints. For recent postnatal MeHg exposure, however, adverse associations were observed for Finger Tapping (non-dominant hand) among women and for the K-BIT Matrices for both sexes, with or without adjustment for PUFA. CONCLUSION: Our findings continue to provide no evidence for an adverse effect of prenatal MeHg exposure on development in a cohort that consumes fish daily. Observations for postnatal MeHg exposure will need to be confirmed using more comprehensive exposure measures.

An examination of a temporal anisotropy in the visual integration of spatial frequencies.

Three pairs of experiments were conducted to investigate the importance of spatial-frequency-processing delays imposed by the visual system on the efficacy of their subsequent integration. In the first pair of experiments filtered versions of a natural image were found to be easily discriminable from the full-bandwidth image. These images were then placed into triplets and presented sequentially. Subjects were required to detect the presence of a full-bandwidth target image within the sequence. As with previous results a low-to-high progression of spatial-frequency information did increase the number of errors of full-bandwidth-image detection within the triplets where it was not present. However, this was not found across all conditions and was suggested to be due to the increased discriminability of the constituent images which form the image triplets. The second experiment was a repetition of the first with more confusable component images. Again the weak order effect on target detection was found. It was suggested that this may be due to the nature of the stimulus used. The third pair of experiments repeated the design of the first pair of experiments but with Gabor patches which provide localised spatial-frequency information. It was found that a low-to-high progression of spatial frequencies resulted in more false detections of the target. The results are interpreted as supporting an integration mechanism which operates with greater efficacy when the presentation of spatial-frequency information mirrors that naturally imposed by the neural delays involved in the processing of spatial frequencies.