The fiber and/or polyphenols present in lingonberries null the glycemic effect of the sugars present in the berries when consumed together with added glucose in healthy human volunteers

This study was undertaken on the broad hypothesis that lingonberry (Vaccinium vitis-idaea L.) has potential to reduce postprandial glycemic and lipemic response. More specifically, 2 postprandial crossover studies with healthy normal-weight male subjects were conducted to study the influence of commercial lingonberry powder on postprandial glycemia and lipemia. The test meals contained fat-free yoghurt with either glucose (50 g) or triacylglycerols (35 g) with or without (control) the lingonberry powder. The lingonberry powder provided the meals with a known amount of fiber and a known amount and composition of sugars, and it was a rich source of polyphenols. Postprandial glucose, insulin, and triacylglycerol responses were analyzed. There were no significant differences in the postprandial glucose concentration between the meals in the glycemia trial despite the fact that the lingonberry meal contained more glucose and fructose. When the meal did not contain added sugar but, instead, added triacylglycerol, no glycemia or lipemia-lowering effect was detected. On the contrary, there were indications of higher glycemic and insulinemic effect after the lingonberry meal. The results of this study indicate that the fibers and/or polyphenols present in lingonberries null the glycemic effect of the sugars present in the berries when consumed together with added glucose. By contrast, the lingonberry powder did not affect the postprandial lipemic response.     

HLA-B27 modulates nuclear factor kappaB activation in human monocytic cells exposed to lipopolysaccharide

OBJECTIVE: To study whether HLA-B27 modifies some key factors controlling inflammatory responses on lipopolysaccharide (LPS) stimulation in human monocytic cells. METHODS: U937 human monocytic cells were stably transfected with either HLA-B27 genomic DNA, HLA-B27 complementary DNA, HLA-A2 genomic DNA, or with the resistant vector pSV2neo (mock) alone. The cells were stimulated with LPS. Electrophoretic mobility shift assay was performed to determine nuclear factor kappaB (NF-kappaB) and heat-shock factor 1 activities, Western blotting was performed to detect the expressions of inhibitory kappaBalpha (IkappaBalpha) and heat-shock proteins (HSPs), and enzyme-linked immunosorbent assay was performed to measure tumor necrosis factor alpha (TNFalpha) secretion. RESULTS: The expression of HLA-B27 modulated the response to LPS in U937 human monocytic cells. Stimulation with LPS led to faster degradation of IkappaBalpha regulatory proteins, accompanied by faster and prolonged activation of NF-kappaB in HLA-B27-expressing cells compared with HLA-A2 and mock transfectants. The secretion of TNFalpha upon LPS stimulation correlated well with the activation of NF-kappaB. No activation of the heat-shock response was observed. CONCLUSION: Our data indicate that HLA-B27 has effects on host responses to LPS that are unrelated to antigen presentation. Two crucial events in the development of arthritis, the activation of NF-kappaB and the secretion of TNFalpha, were found to be enhanced in HLA-B27-expressing cells upon LPS stimulation. Because LPS is known to be present in the inflamed joints of patients with reactive arthritis (ReA), the enhanced inflammatory response of HLA-B27-positive cells upon LPS stimulation offers an attractive explanation for the role of HLA-B27 in the development of ReA.     

Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adults

Two Finnish cohorts, comprising 56 children with severe early-onset obesity (relative weight for height greater than or equal to +70% before age 10) and 252 morbidly obese adults (body mass index, > or = 40 kg/m(2)), were screened for melanocortin-4 receptor (MC4R) mutations. We identified a pathogenic mutation (S127L) in one child, causing severe early-onset obesity. We describe the phenotype of this particular mutation for the first time. We also identified a novel (I226T) polymorphism in the coding and two new variations (-439delGC and 1059C>T) outside the coding region of the MC4R gene. Three previously described polymorphisms (V103I, T112M, and I125L) were identified. In vitro functional studies of variants T112M, S127L, and I226T supported a pathogenic role of the S127L mutation, because signaling properties of the receptor in response to the MC4R agonists alpha-MSH, beta-MSH, and gamma(1)-MSH were impaired. The S127L mutation did not affect receptor inhibition by the antagonist agouti-related protein. Localization of the three variant receptors was similar to that of wild type. In conclusion, a pathogenic MC4R mutation was found among subjects with severe early-onset obesity but not among morbidly obese adults. Impaired function of the S127L receptor was due to reduced activation, not a defect of protein transport to the cell membrane.     

Intravenous drug dependence in adolescence

Purpose To explore psychosocial background and preceding substance use related to intravenous drug dependence (IDD) among adolescents.

Methods A clinical sample of 278 adolescents (age 12–17) admitted to psychiatric inpatient hospitalization between April 2001 and January 2004 was studied. Data concerning psychosocial variables and substance use were gathered from the Schedule for Affective Disorder and Schizophrenia for School‐Age Children Present and Lifetime (K‐SADS‐PL), the European Addiction Severity Index (EuropASI) and the interview schedule of the First Treatment Demand protocol of the Pompidou Group of the Council of Europe.

Results The prevalence of IDD was increased if the adolescent was living without biological father or mother, had history of truancy or had been transferred to special class. Initiation age of IDD was significantly lower if the adolescent was living without biological father or mother, the mother of the adolescent was employed full‐time or if the adolescent had been transferred to special class. Early substance experiment was associated with IDD and with earlier initiation of intravenous use. The progression from regular tobacco use to IDD was faster among girls compared to boys.

Implications Common milestones in the progression of IDD are school problems, disturbed relations to parents and previous substance experiments at young age.     

From the Cover: Dominant suppression of inflammation by glycan-hydrolyzed IgG

A unique anti-inflammatory property of IgG, independent of antigen specificity, is described. IgG with modification of the heavy-chain glycan on asparagine 297 by the streptococcal enzyme endo-β-N-acetylglucosaminidase (EndoS) induced a dominant suppression of immune complex (IC)-mediated inflammation, such as arthritis, through destabilization of local ICs by fragment crystallizable–fragment crystallizable (Fc-Fc) interactions. Small amounts (250 µg) of EndoS-hydrolyzed IgG were sufficient to inhibit arthritis in mice and most effective during the formation of ICs in the target tissue. The presence of EndoS-hydrolyzed IgG disrupted larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining. Neither complement binding in vitro nor antigen–antibody binding per se was affected.