Kinetics of the appearance of cereal alkylresorcinols in pig plasma

Alkylresorcinols (AR) are phenolic lipids found in high amounts in wholegrain wheat and rye. They may be important as bioactive components and/or biomarkers of wholegrain wheat and rye intake. AR absorption was studied with pigs during a habitual diet and after a single meal of AR-rich diet. In study 1, four pigs were fed wholegrain rye (RD) and white wheat bread (WD) for 1 week in a cross-over design. Arterial and venous AR concentrations were determined over 540min after feeding on days 5 and 7. In study 2, four pigs were fed a synthetic, starch-based diet for 5d, and arterial and venous AR concentrations were determined over 960min after feeding a single meal of RD. In study 1, plasma AR concentrations after consuming RD peaked at 120min, remained elevated between 120 and 420min, and were re-elevated on refeeding at 480min. In study 2, AR appeared in the plasma after 60min, peaked at 180-240min, and remained elevated after 960min. The apparent elimination half-life was 3·93h, and the maximum plasma concentration was 666 (sem 35) nmol/l. Arterial and venous plasma AR concentrations were similar, suggesting that AR are absorbed via the lymphatic system. AR concentrations in pig plasma increase rapidly after a meal containing AR, and persist in plasma for at least 5d, indicating that AR may be a useful biomarker of wholegrain wheat and rye intak

Antioxidant treatment attenuates lactate production in diabetic nephropathy

The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 wk after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned 13C/1H-volume rat coil. The rats received intravenous hyperpolarized [1-13C]pyruvate and were imaged using a slice-selective 13C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels, indicating an intact glucose-alanine cycle, or [13C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes. </jats:p

Kinetics of the appearance of cereal alkylresorcinols in pig plasma

Alkylresorcinols (AR) are phenolic lipids found in high amounts in wholegrain wheat and rye. They may be important as bioactive components and/or biomarkers of wholegrain wheat and rye intake. AR absorption was studied with pigs during a habitual diet and after a single meal of ARrich diet. In study 1, four pigs were fed wholegrain rye (RD) and white wheat bread (WD) for 1 week in a cross-over design. Arterial and venous AR concentrations were determined over 540 min after feeding on days 5 and 7. In study 2, four pigs were fed a synthetic, starch-based diet for 5 d, and arterial and venous AR concentrations were determined over 960 min after feeding a single meal of RD. In study 1, plasma AR concentrations after consuming RD peaked at 120 min, remained elevated between 120 and 420 min, and were re-elevated on refeeding at 480 min. In study 2, AR appeared in the plasma after 60 min, peaked at 180–240 min, and remained elevated after 960 min. The apparent elimination half-life was 3·93 h, and the maximum plasma concentration was 666 (SEM 35) nmol/l. Arterial and venous plasma AR concentrations were similar, suggesting that AR are absorbed via the lymphatic system. AR concentrations in pig plasma increase rapidly after a meal containing AR, and persist in plasma for at least 5 d, indicating that AR may be a useful biomarker of wholegrain wheat and rye intake.The present study was supported by the Nordic Industrial Fund; the Danish Agricultural and Veterinary Research Council; Cerealia AB, Sweden; Wasabro¨d AB, Sweden; Vaasan & Vaasan, Finland; Fazer Oululainen, Finland. A.-M. L. was supported by the Sigrid Juse´lius Foundation, Helsinki, Finland and Finska La¨karesa¨llskapet, Helsinki, Finland

An investigation of the apparent breast cancer epidemic in France: screening and incidence trends in birth cohorts

<p>Abstract</p> <p>Background</p> <p>Official descriptive data from France showed a strong increase in breast-cancer incidence between 1980 to 2005 without a corresponding change in breast-cancer mortality. This study quantifies the part of incidence increase due to secular changes in risk factor exposure and in overdiagnosis due to organised or opportunistic screening. Overdiagnosis was defined as non progressive tumours diagnosed as cancer at histology or progressive cancer that would remain asymptomatic until time of death for another cause.</p> <p>Methods</p> <p>Comparison between age-matched cohorts from 1980 to 2005. All women residing in France and born 1911-1915, 1926-1930 and 1941-1945 are included. Sources are official data sets and published French reports on screening by mammography, age and time specific breast-cancer incidence and mortality, hormone replacement therapy, alcohol and obesity. Outcome measures include breast-cancer incidence differences adjusted for changes in risk factor distributions between pairs of age-matched cohorts who had experienced different levels of screening intensity.</p> <p>Results</p> <p>There was an 8-fold increase in the number of mammography machines operating in France between 1980 and 2000. Opportunistic and organised screening increased over time. In comparison to age-matched cohorts born 15 years earlier, recent cohorts had adjusted incidence proportion over 11 years that were 76% higher [95% confidence limits (CL) 67%, 85%] for women aged 50 to 64 years and 23% higher [95% CL 15%, 31%] for women aged 65 to 79 years. Given that mortality did not change correspondingly, this increase in adjusted 11 year incidence proportion was considered as an estimate of overdiagnosis.</p> <p>Conclusions</p> <p>Breast cancer may be overdiagnosed because screening increases diagnosis of slowly progressing non-life threatening cancer and increases misdiagnosis among women without progressive cancer. We suggest that these effects could largely explain the reported "epidemic" of breast cancer in France. Better predictive classification of tumours is needed in order to avoid unnecessary cancer diagnoses and subsequent procedures.</p

Complete genome sequence of the industrial bacterium Bacillus licheniformis and comparisons with closely related Bacillus species

BACKGROUND: Bacillus licheniformis is a Gram-positive, spore-forming soil bacterium that is used in the biotechnology industry to manufacture enzymes, antibiotics, biochemicals and consumer products. This species is closely related to the well studied model organism Bacillus subtilis, and produces an assortment of extracellular enzymes that may contribute to nutrient cycling in nature. RESULTS: We determined the complete nucleotide sequence of the B. licheniformis ATCC 14580 genome which comprises a circular chromosome of 4,222,336 base-pairs (bp) containing 4,208 predicted protein-coding genes with an average size of 873 bp, seven rRNA operons, and 72 tRNA genes. The B. licheniformis chromosome contains large regions that are colinear with the genomes of B. subtilis and Bacillus halodurans, and approximately 80% of the predicted B. licheniformis coding sequences have B. subtilis orthologs. CONCLUSIONS: Despite the unmistakable organizational similarities between the B. licheniformis and B. subtilis genomes, there are notable differences in the numbers and locations of prophages, transposable elements and a number of extracellular enzymes and secondary metabolic pathway operons that distinguish these species. Differences include a region of more than 80 kilobases (kb) that comprises a cluster of polyketide synthase genes and a second operon of 38 kb encoding plipastatin synthase enzymes that are absent in the B. licheniformis genome. The availability of a completed genome sequence for B. licheniformis should facilitate the design and construction of improved industrial strains and allow for comparative genomics and evolutionary studies within this group of Bacillaceae