Prenatal and Childhood Growth,and Hospitalization for Alcohol Use Disorders in Adulthood: The Helsinki Birth Cohort Study

Background

Small birth size - an indicator of a sub-optimal prenatal environment - and variation in growth after birth have been associated with non-communicable diseases in later life. We tested whether birth size or growth in childhood associated with the risk of hospital admission for alcohol use disorders (AUDs) from early to late adulthood.

Methods

The sample comprised 6544 men and 6050 women born between 1934 and 1944 in Helsinki, Finland. Data on anthropometric measures were extracted from medical records and diagnoses of AUD from the Finnish Hospital Discharge Register and Causes of Death Register covering a 40-year period from 1969 to 2008.

Results

Altogether 171 women (2.8%) and 657 men (10.0%) were diagnosed at a hospital with AUD. After adjusting for major confounders, shorter length at birth, shorter height up to two years of age, and lower weight at two years associated with hospitalization for AUD in women. In men, slower growth in height, particularly from 2 to 7 years, and slower weight gain from 7 to 11 years as well as shorter height and lower weight at 7 and 11 years associated with a diagnosis of AUD in men.

Conclusions

Pre- and postnatal growth associates with the risk for AUD later in life differently in women than in men: the fetal period and infancy seem to be the sensitive periods for women, whereas those for men the occur from toddlerhood onwards.     

Control of ion transport by mitochondrion-rich chloride cells of eurythermic teleost fish: Cold shock vs. cold acclimation

Seawater-acclimated eurythermic mummichogs (Fundulus heteroclitus L.) were acclimated to cold and warm conditions (5 and 20 °C, 4 weeks). Opercular epithelia (OE) from 20 °C-acclimated animals, containing numerous mitochondrion-rich chloride cells were mounted in Ussing-style membrane chambers, cooled to 16, 13, 10, 5 and 2.5 °C, then subjected to hypotonic shock that normally inhibits Cl(-) secretion (as short-circuit current, I(sc)). Cold exposure to 10 °C slowed Cl(-) secretion (Q(10)=1.62 ± 0.204 95% CI) and OEs responded rapidly and reversibly to hypotonic shock, but below 8.0 °C a sharp decrease (Q(10)=5.63 ± 0.736) occurred and the tissue was unresponsive to hypotonicity. By immunocytochemistry, Focal Adhesion Kinase (FAK) phosphorylated at tyrosine-407 (pY(407)) colocalized with CFTR in apical membrane and dephosphorylated with hypotonic shock at 20 °C but failed to dephosphorylate at 5 °C, while opercular epithelia from cold-acclimated fish at 5 and 20 °C responded normally to hypotonic shock. Cold-shock of warm-acclimated OEs also stimulated covering over of mitochondrion- rich cell apical crypts, detected by SEM. Cold-acclimation increased C18:1 and decreased C18:0 fatty acids in liver, indicating homeoviscous adaptation. Eurythermic fish acclimate osmoregulatory systems to cold by maintaining membrane fluidity and preserving complex transport regulation pathways.     

G-protein-coupled receptor-mediated MAPK and PI3-kinase signaling is maintained in Chinese hamster ovary cells after γ-irradiation

To expedite G-protein-coupled receptor (GPCR) drug screening studies, cell lines amenable to transfection (e.g. CHO cells) have been widely used as cellular models. These cells can be frozen in a ready-to-use format, allowing screening of a single batch of cells and validation of the cellular material prior to the screening run. A common method used to deliver frozen cells to screening programs is to γ-irradiate the cells, abrogating cell division after thawing and ensuring consistency in the number of cells analyzed per well. With the recognition that signaling proteins such as ERK and Akt are important markers of GPCR activation, along with the availability of suitable assays for their measurement, these outputs have become important for GPCR screening programs. Here we show that several γ-irradiated and frozen CHO-K1 cell lines expressing transfected GPCRs, initially optimized for performing cAMP or AequoScreen calcium flux assays, can be used for the measurement of GPCR-mediated ERK and Akt phosphorylation. Furthermore, CHO-K1 cells transfected with NOP or GAL(1) receptors show pharmacology for a number of agonists and antagonists that is consistent with non-irradiated cultured lines. These data indicate that γ-irradiated CHO-K1 cells can be reliably used for the measurement of GPCR-mediated kinase signaling outputs.     

Dietary n-3 fatty acids alter the contractile response to thromboxane A(2) agonists of porcine coronary arteries

Dietary supplementation with marine fish oils rich in n-3 fatty acids reduces circulating thromboxane A(2) (TxA(2)). However, the effects on thomboxane A(2) receptor mediated vascular reactivity are uncertain. The aim of this study was to test the hypothesis that dietary modification of TxA(2) levels alters vascular responsiveness to TxA(2) analogues. Juvenile female white pigs were fed a diet enriched in either 5% (w/w) fish oil or beef tallow for 6 weeks. Serum and myocardial tissue levels of eicosapentaenoic and docosahexaenoic acid reached a plateau during this period. Vascular responses were measured in isolated coronary arterial rings with intact endothelium by isometric tension measurement. Arteries from pigs fed fish oil produced a greater maximum vasoconstrictor tension to the TxA(2) analogue U46619 than did rings from pigs fed beef tallow (120 +/- 6% compared to 92 +/- 8%, values represented as a percentage relative to the maximum vasoconstrictor effect obtained to KCl, regression analysis, analysis of variance, P 相似文献