Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Accelerator Measurements of Magnetically Induced Radio Emission from Particle Cascades with Applications to Cosmic-Ray Air Showers.

For 50 years, cosmic-ray air showers have been detected by their radio emission. We present the first laboratory measurements that validate electrodynamics simulations used in air shower modeling. An experiment at SLAC provides a beam test of radio-frequency (rf) radiation from charged particle cascades in the presence of a magnetic field, a model system of a cosmic-ray air shower. This experiment provides a suite of controlled laboratory measurements to compare to particle-level simulations of rf emission, which are relied upon in ultrahigh-energy cosmic-ray air shower detection. We compare simulations to data for intensity, linearity with magnetic field, angular distribution, polarization, and spectral content. In particular, we confirm modern predictions that the magnetically induced emission in a dielectric forms a cone that peaks at the Cherenkov angle and show that the simulations reproduce the data within systematic uncertainties.

The role of product inhibition as a yield-determining factor in enzymatic high-solid hydrolysis of pretreated corn stover.

Industrially, enzymatic hydrolysis of lignocellulose at high solid content is preferable over low solids due to a reduction in processing costs. Unfortunately, the economic benefits are counteracted by a linear decrease in yield with solid content, referred to as the "solid effect" in the literature. In the current study, we investigate the contribution of product inhibition to the solid effect (7-33 % solids). Product inhibition was measured directly by adding glucose to high-solid hydrolysis samples and indirectly through variation of water content and beta-glucosidase concentration. The results suggest that the solid effect is mainly controlled by product inhibition under the given experimental conditions (washed pretreated corn stover as substrate). Cellobiose was found to be approximately 15 times more inhibitory than glucose on a molar scale. However, considering that glucose concentrations are at least 100 times higher than cellobiose concentrations under industrial conditions, glucose inhibition of cellulases is suggested to be the main cause of the solid effect.

La obesidad abdominal es esencial para el riesgo de tromboembolismo venoso en el síndrome metabólico: el estudio de tromso / Abdominal obesity is essential for the risk of venous thromboembolism in the metabolic syndrome: the thrombus study

ANTECEDENTES: el síndrome metabólico es un conjunto de factoresde riesgo cardiovascular, como la obesidad abdominal, hipertensión, dislipidemia y resistenciaa la insulina, asociado con un mayor riesgo de enfermedades cardiovasculares y mortalidad porcualquier causa. OBJETIVOS: el propósito del estudio fue evaluar el impacto del síndrome metabólico y sus componentes individuales, sobre el riesgo de tromboembolismo venoso (TEV) en un estudio poblacional prospectivo. MÉTODOS: Los componentes individuales del síndrome metabólico se registraron en 6170 sujetos de 25 a84 años en el Estudio de Tromsø en 1994-1995, y por primera vez los eventos de TEV se registraron hasta el 1 de septiembre de 2007...

Variant of the Thermomyces lanuginosus lipase with improved kinetic stability: a candidate for enzyme replacement therapy.

Lipases with high kinetic stability and enzymatic efficiency in the human gastro-intestinal tract may help against exocrine pancreatic insufficiency. Here we mimic gastric conditions to study how bile salts and pH affect the stability and activity of Thermomyces lanuginosus lipase (TlL) and its stabler variant StL using spectroscopy, calorimetry and gel electrophoresis. Both enzymes resist trypsin digestion with and without bile salts. Bile salts activate native TlL and StL equally well, bind weakly to denatured TlL and StL at lower pH and precipitate native TlL and StL at pH 4. StL refolds more efficiently than TlL from gastric pH in bile salts, regaining activity when refolding from pH as low as 1.8 and above while TlL cannot go below pH 2.6. StL also unfolds 10-40 fold more slowly in the denaturant guanidinium chloride and the anionic surfactant SDS. We ascribe StL's superior performance to general alterations in its electrostatic potential which makes it more acid-resistant. These superior properties make StL a good candidate for pancreatic enzyme replacement therapy.

Mediterranean diet and incidence of hip fractures in a European cohort.

UNLABELLED: Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus.

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability. At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4-6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity is not directly linked to intrinsic kinetic stability [its resistance to the general chemical denaturant guanidinium chloride (GdmCl)], because TlL unfolds more slowly in GdmCl at pH 6.0 than at pH 8.0. However, the estimated net charge drops from approximately -12 to approximately -5 between pH 8 and 6. SDS denatures TlL at pH 6.0 by nucleating via a critical number of bound SDS molecules on the surface of native TlL to form clusters. These results imply that SDS sensitivity is connected to the availability of appropriately charged regions on the protein. We suggest that conformational rigidity is a necessary but not sufficient feature of SDS resistance, because this has to be combined with sufficient negative electrostatic potential to avoid extensive SDS binding.

Effects of non-ionic surfactants on the interactions between cellulases and tannic acid: a model system for cellulase-poly-phenol interactions.

Addition of non-ionic surfactants (NIS) is known to accelerate enzymatic lignocellulose hydrolysis. The mechanism behind this accelerating effect is still not elucidated but has been hypothesized to originate from favorable NIS-lignin interactions which alleviate non-productive adsorption of cellulases to lignin. In the current work we address this hypothesis using tannic acid (TAN) as a general poly-phenolic model compound (for lignin and soluble phenolics) and measure the mutual interactions of cellulases (CBHI, CBHII, EGI, EGII and BG), TAN and NIS (Triton X-100) using isothermal titration calorimetry (ITC). The experimental results suggest rather strong enzyme-specific interactions with TAN in reasonable agreement with enzyme specific lignin inhibition found in the literature. Enzyme-TAN interactions were disrupted by the presence of NIS by a mechanism of strong TAN-NIS interaction. The presence of NIS also alleviated the inhibitory effect of TAN on cellulase activity. All together the current work provides strong indications that favorable NIS-poly-phenol interactions alleviate non-productive cellulase-poly-phenol interactions and hence may provide a mechanism for the accelerating effect of NIS on lignocellulose hydrolysis.

Reliability of Diagnostic Tests for Helicobacter pylori Infection.

Introduction. Helicobacter pylori (H. pylori) infection is very common worldwide. A reliable diagnosis is crucial for patients with H. pylori-related diseases. At followup, it is important to confirm that eradication therapy has been successful. There is no established gold standard for the diagnosis of H. pylori infection. Material and Methods. A sample of 304 volunteers from the general population was screened for H. pylori infection with serology, (13)C-urea breath test (UBT), rapid urease test (RUT) on fresh biopsy, culture from biopsy, and histological examination. Culture was used as gold standard. Results. The sensitivity was 0.99 for serology, 0.90 for UBT, 0.90 for RUT, and 0.90 for histological examination. Corresponding specificities were 0.82, 0.99, 0.98, and 0.97, respectively. The accuracy was 0.86 for serology, 0.96 for UBT, 0.95 for RUT, 0.93 for culture, and 0.95 for histology. There was a strong correlation between the results of UBT and the histological scores of H. pylori colonisation as well as between the results of UBT and the scores of RUT. Conclusion. There were only minor differences in accuracy between the three invasive tests for H. pylori infection in this population. RUT may be recommended as the first choice since a result is obtained within hours. The accuracy of UBT was comparable to the invasive tests, and it is recommended for situations when endoscopy is not needed.

Incidence of and potential risk factors for gallstone disease in a general population sample.

BACKGROUND: Several epidemiological studies have been published, but there are few reports on relations between gallstone incidence, symptomatology and risk factors. METHODS: Of 621 randomly selected individuals aged 35-85 years in a general population who had been screened previously with ultrasonography and found to have no gallbladder stones, 503 (81.0 per cent) were re-examined after a minimum interval of 5 years. At baseline and re-examination, heredity for gallstone disease was explored and body mass index, digestive symptoms including abdominal pain, quality of life, alcohol and smoking habits, use of non-steroidal anti-inflammatory drugs and oestrogen, parity and blood lipid levels were recorded. RESULTS: Forty-two (8.3 per cent) of the 503 subjects developed stones. Subjects were followed for a total of 3025.8 person-years, yielding an incidence for newly developed gallstones of 1.39 per 100 person-years. A positive association for gallstone development was found only for length of follow-up and plasma low-density lipoprotein-cholesterol levels at baseline. Weekly alcohol consumption was inversely related to gallstone development. CONCLUSION: The incidence of gallstones in this population was 1.39 per 100 person-years. Gallstone development was related to length of follow-up and LDL-cholesterol levels, and inversely related to alcohol consumption.

Abdominal obesity is essential for the risk of venous thromboembolism in the metabolic syndrome: the Tromsø study.

SUMMARY BACKGROUND: The metabolic syndrome is a cluster of cardiovascular risk factors, including abdominal obesity, hypertension, dyslipidemia and insulin resistance, associated with increased risk of cardiovascular diseases and all cause mortality. OBJECTIVES: The purpose of the study was to assess the impact of the metabolic syndrome, and its individual components, on the risk of venous thromboembolism (VTE) in a prospective population-based study. METHODS: Individual components of the metabolic syndrome were registered in 6170 subjects aged 25-84 years in the Tromsø Study in 1994-1995, and first ever VTE events were registered until 1 September 2007. RESULTS: The metabolic syndrome was present in 21.9% (1350 subjects) of the population. There were 194 validated first VTE events (2.92 per 1000 person-years) during a mean of 10.8 years of follow-up. Presence of metabolic syndrome was associated with increased risk of VTE (HR, 1.65; 95% CI, 1.22-2.23) in age- and gender-adjusted analysis. The risk of VTE increased with the number of components in the metabolic syndrome (P < 0.001). Abdominal obesity was the only component significantly associated with VTE in multivariable analysis including age, gender, and the individual components of the syndrome (HR, 2.03; 95% CI, 1.49-2.75). When abdominal obesity was omitted as a diagnostic criterion, none of the other components, alone or in cluster, was associated with increased risk of VTE. CONCLUSIONS: Our study provides evidence for the metabolic syndrome as a risk factor for TE. Abdominal obesity appeared to be the pivotal risk factor among the individual components of the syndrome.

Defined indications for elective cholecystectomy for gallstone disease.

BACKGROUND: This study examined symptomatology and quality of life following elective cholecystectomy for symptomatic gallstone disease with defined indications for surgery. METHODS: In this prospective study of 200 consecutive patients (161 women; median age 46.5 (range 24-79) years), strict indications for elective cholecystectomy were stipulated. Digestive symptoms and quality of life were recorded with a self-administered questionnaire before and at 3 and 12 months after surgery. RESULTS: Of 149 patients who experienced abdominal pain with typical location before surgery, 136 (91.3 per cent) reported total remission or reduced frequency of that type of pain 12 months later. Of 35 patients who reported atypical or multiple pain location before operation, 27 (77 per cent) experienced reduced frequency or disappearance of that type of pain. Frequency of pain episodes, atypical or multiple pain location, specific food intolerance and frequency of disturbing abdominal gas at baseline correlated positively with the frequency of abdominal pain episodes at 12 months after surgery. There was a tendency towards an inverse relation to age. CONCLUSION: The frequency of persistent abdominal pain after elective cholecystectomy was low among patients with typical pain location before surgery. Atypical pain location, and frequent pain episodes before operation significantly reduced the chance of becoming pain-free.

Agreement between Cochrane Neonatal reviews and clinical practice guidelines for newborns in Denmark: a cross-sectional study.

OBJECTIVE: To assess agreement between Cochrane Neonatal Group reviews and clinical practice guidelines in Denmark. DESIGN: Retrospective analysis of clinical guidelines for newborn infants. MATERIALS: All Cochrane neonatal reviews and Danish clinical guidelines for newborn infants. MAIN OUTCOME MEASURES: The recommendations from the Cochrane reviews and local clinical guidelines were compared and classified as being in agreement, in partial agreement or in disagreement. Authors of guidelines were asked whether Cochrane reviews had been considered during guideline development and reasons for any disagreements. Heterogeneity among departments was assessed. RESULTS: 173 interventions evaluated in Cochrane neonatal reviews were included. All 17 Danish neonatal departments agreed to participate, but only 14 (82%) delivered data. Agreement between reviews and guidelines was observed for a median of 132 interventions (76%) (range 129-134), partial agreement was observed for 31 interventions (18%) (range 29-33), and disagreement was observed for 10 interventions (6%) (range 8-13) (kappa = 0.56, range 0.53-0.59). Most of the latter 10 interventions were not recommended in the reviews but were recommended in the guidelines. There were numerous reasons for disagreement, the most common being usage of evidence with higher bias risks than randomised trials in guidelines development. Overall, Cochrane reviews were rarely (10%) used during guideline development. For nine guideline topics (5%) there was diversity among the Danish departments' recommendations. CONCLUSIONS: There is good agreement between Cochrane reviews and neonatal guidelines in Denmark. However, Cochrane reviews were rarely used for guideline development. Heterogeneity among guidelines produced by the various neonatal departments seems moderate.

Development of symptoms and complications in individuals with asymptomatic gallstones.

BACKGROUND: Gallbladder stones are common in the developed world. Complications of gallstones contribute substantially to healthcare costs and may be life threatening. The identification of individuals likely to develop complications would be of benefit in clinical practice as elective cholecystectomy could then be performed. METHODS: Seven hundred and thirty-nine subjects aged 35-85 years from the general population were screened for gallbladder problems by ultrasonography and questionnaire assessment of putative risk factors and digestive symptoms. Gallstones, cholesterolosis or sludge in the gallbladder were diagnosed in 123 (16.3 per cent) of 739 subjects, 120 of whom were followed for a median of 87 (range 3-146) months to May 2003 or until treatment was required. RESULTS: Fourteen patients were admitted to hospital and treated for gallstone-related complications or symptoms. The cumulative risk of being treated during the first 5 years after detection of asymptomatic gallstones was 7.6 per cent and there was no indication of this risk levelling off. There were no significant differences between treated and untreated subjects with regard to digestive symptoms or any of the risk factors monitored at the initial screening, although treated subjects were significantly younger than those who were not treated. CONCLUSION: Nearly one in ten individuals with asymptomatic gallbladder stones in the general population may be expected to develop symptoms or complications that require treatment within 5 years. Age may be inversely related to the incidence of complications.

Duodenal intraepithelial lymphocyte-count revisited.

BACKGROUND: The number of intraepithelial lymphocytes in the duodenum was determined 30 years ago, the suggested normal upper limit being 40 lymphocytes per 100 epithelial cells. METHODS: Duodenal mucosa was analysed from 18 healthy individuals and 56 consecutive patients biopsied because of epigastralgia (17 cases), diarrhoea (10 cases), oesophagitis (10 cases), iron-deficiency (9 cases) and B12-deficiency (10 cases) showing normal histology, along with 10 cases of active coeliac disease. The biopsies were fixed in 4% formalin overnight and embedded in paraffin. Three micrometre thick sections were stained with haematoxylin and eosin and CD3. At least 300 epithelial cells were counted, the number of intraepithelial lymphocytes was given as the mean/100 epithelial cells. Extensive statistical analyses were performed. RESULTS: In the healthy individuals the mean number (s) of intraepithelial lymphocytes/100 epithelial cells was 10.8 (2.6) and 13.2 (3.8) in H&E and CD3 stained sections, respectively. The upper limit of the confidence interval for CD3 staining was 29. There was no significant difference between normal individuals and the clinical groups, with the exception of coeliac disease. CONCLUSION: Two-step analysis of intraepithelial lymphocyte-determination is suggested: (a) semi-quantitative estimate on H&E-stained sections (normal ratio of 1:5 between lymphocytes and enterocytes; upper normal limit 20 lymphocytes) and (b) CD3-staining and counting if intraepithelial lymphocytosis is suspected. The upper normal range of intraepithelial lymphocytes is set at 25 CD3+ lymphocytes/100 epithelial cells. Values between 25 and 29 are regarded as 'borderline' and 30 or more represent pathologic intraepithelial lymphocytosis in the duodenum.

Relationship of gastroscopic features to histological findings in gastritis and Helicobacter pylori infection in a general population sample.

BACKGROUND AND STUDY AIM: Various gastroscopic features may be interpreted as signs of gastritis, but the significance of such features in relation to histomorphology is uncertain. The aim of this study was to determine how macroscopic findings were related to histomorphological changes and the presence of Helicobacter pylori in the gastric mucosa, in a sample of the general population. SUBJECTS AND METHODS: 488 adult individuals, randomly selected from a general population, were screened with gastroscopy and biopsy. The macroscopic features recorded were erythema (diffuse, spotty, linear), erosions, absence of rugae in the gastric corpus, and presence of visible vessels. Gastritis was classified microscopically according to the Sydney system. The presence of H. pylori was determined histologically and using the urease test on fresh biopsy specimens. RESULTS: The sensitivity and specificity of absence of rugae for moderate to severe atrophic gastritis in the gastric corpus were 67 % and 85 %, respectively. Corresponding values for severe atrophy were 90 % and 84 %. The sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy in the corpus were 48 % and 87 %, and for severe atrophy the values were 80 % and 87 %, respectively. Considering the antrum, the sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy was 14 % and 91 %, respectively. With regard to chronic inflammation (moderate to severe in the corpus or antrum), none of the features, alone or in combination, showed a sensitivity of more than 56 %. No endoscopic features (alone or in combination) showed a sensitivity of more than 57 % for H. pylori infection. CONCLUSIONS: Except for the absence of rugae and visible vessels in the gastric corpus, macroscopic features as observed during gastroscopy are of very limited value in the evaluation of whether or not gastritis or H. pylori infection are present. This is in accordance with most previous studies in patient populations, and it must be emphasized that the diagnosis of gastritis should be based on histological examination of the gastric mucosa.

Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia.

The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, HELICOBACTER PYLORI and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer's disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.

Immunolocalization of cholecystokinin-2 receptors in rat gastric mucosa.

BACKGROUND: Gastrin exerts trophic effects on the gastric mucosa by mechanisms not yet completely elucidated. Our aim was to localize the cholecystokinin-2 (CCK2) receptor in epithelial cells of foetal and adult rat stomachs in order to determine the cell types that are directly affected by gastrin. METHODS: Gastric tissue was subjected to indirect double immunofluorescence staining with antiserum against the C-terminal decapeptide of the CCK2 receptor and antibodies against 5' bromo-2-deoxyuridine, which had been injected into the rats I h before they were killed, the acid pump H,K-ATPase, the membrane-cytoskeletal linker ezrin, pepsin/pepsinogen or histidine decarboxylase. RESULTS: Undifferentiated foetal gastric epithelial cells expressed CCK2 receptors, whereas stem cells of adult gastric glands did not exhibit immunoreactivity. However, other epithelial cells in the progenitor zone of adult gastric glands did express CCK2 receptors. Some of these cells were faintly stained for H,K-ATPase; pepsin/pepsinogen was also detected in this region. Parietal cells in the isthmus/pit region of the glands contained ezrin, and some showed weak immunoreactivity for the CCK2 receptor. As expected, enterochromaffin-like cells also expressed CCK2 receptors. CONCLUSION: Our findings are consistent with the hypothesis that a CCK2 receptor mediates direct effects of gastrin on gastric epithelial cells during both stomach organogenesis and adult life.