Thyroid dysfunction during gestation and gestational diabetes mellitus: a complex relationship.

PURPOSE: Gestational diabetes mellitus (GDM) and thyroid dysfunction during gestation (GTD) are the two most prevalent endocrinopathies during pregnancy. The aim of the present review is to provide an overview of the peculiar aspects of GDM and GTD, to highlight the potential interactions and clinical consequences of these two frequent clinical conditions. METHODS: A literature review regarding GDM and GTD was carried out with particular interest on meta-analyses and human studies dealing with the (i) shared risk factors between GDM and GTD, (ii) the epidemiological link between GTD and GDM, (iii) physiopathologic link between GTD and GDM, (iv) clinical consequences of GDM and GTD, and (v) post-partum implications of GDM and GTD. RESULTS: The association between GDM and GTD is common and may be explained by the insulin-resistance state due to maternal GTD, to alterations in the placentation process or to the many shared risk factors. Discrepant results of epidemiologic studies can be explained, at least in part, by the changes in diagnostic criteria and screening strategies throughout the years for both conditions. GDM and GTD impact pregnancy outcome and have post-partum long-term consequences, but more studies are needed to prove an additional adverse effect. CONCLUSIONS: Based on the epidemiological and physio-pathological link between GDM and GTD, it could be suggested that a diagnosis of GTD could lead to screen GDM and the other way round.

Binding mode of Pyridoclax to myeloid cell leukemia-1 (Mcl-1) revealed by nuclear magnetic resonance spectroscopy, docking and molecular dynamics approaches.

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family proteins. Its amplification is one of the most frequent genetic aberrations found in human cancers. Pyridoclax, a promising BH3 mimetic inhibitor, interacts directly with Mcl-1 and induces massive apoptosis at a concentration of 15 µM in combination with anti-Bcl-xL strategies in chemo-resistant ovarian cancer cell lines. In this study, a combined experimental and theoretical approach was used to investigate the binding mode of Pyridoclax to Mcl-1. The representative poses generated from dynamics simulations compared with NMR data revealed: (i) Pyridoclax bound to P1 and P2 pockets of Mcl-1 BH3 binding groove through its styryl and methyl groups establishing mainly hydrophobic contacts, (ii) one of the ending pyridines interacts through electrostatic interaction with K234 side chain, a negatively charged residue present only in this position in Mcl-1. Communicated by Ramaswamy H. Sarma.

Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease.

BACKGROUND: Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined. METHODS: Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice. RESULTS: The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice. CONCLUSIONS: A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.

Importance and functions of European grasslands.

The European agricultural policy is not simple and needs to accommodate also social and environmental requirements. Grassland will continue to be an important form of land use in Europe, but with increased diversity in management objectives and systems used. Besides its role as basic nutrient for herbivores and ruminants grasslands have opportunities for adding value by exploiting positive health characteristics in animal products from grassland and through the delivery of environmental benefits. In fact grasslands contribute to a high degree to the struggle against erosion and to the regularizing of water regimes, to the purification of fertilizers and pesticides and to biodiversity. Finally they have aesthetic role and recreational function as far as they provide public access that other agricultural uses do not allow. But even for grassland it is very difficult to create a good frame for its different tasks (1) the provision of forage for livestock, (2) protection and conservation of soil and water resources, (3) furnishing a habitat for wildlife, both flora and fauna and (4) contribution to the attractiveness of the landscape. Nevertheless it is the only crop, able to fulfil so many tasks and to fit so many requirements.

Agri-environmental grass hay: nutritive value and intake in comparison with hay from intensively managed grassland.

Chemical composition, digestibility, nutritive value and intake of hay from an agri-environmental management (EH) were compared with those from hay (Lolium perenne) from an intensive management (IH). IH was of low to moderate quality because of unfavourable weather conditions. EH was harvested mid-June of 2000 (EH1) and 2001 (EH2) on the same sward that had not received mineral fertilizer for 10 years. The EH was characterized by a species-rich botanical composition. On average, it had lower contents of protein (32%), NDF (9%) and ash (35%), and a higher concentration of water-soluble carbohydrates (117%) than IH. Digestibility of dry and organic matter, determined with sheep, was not different between IH and EH and averaged 59 and 63%, respectively. Crude fibre and NDF digestibility were lower in EH (58 and 57%, respectively) than in IH (70 and 69%, respectively). Net energy value for lactation did not differ between IH and EH and amounted to 4.78 MJ per kg DM. True protein digested in the small intestine and rumen degraded protein balance were lower in EH (63 and -60 g per kg DM) than in IH (71 and -33 g per kg DM). Intake of hay was investigated in Holstein-Friesian heifers and Belgian Blue double-muscled heifers (mean BW 280 +/- 22 kg and 269 +/- 21 kg, respectively), and in Belgian Blue non-lactating and non-pregnant double-muscled cows (initial BW 642 +/- 82 kg), using a cross-over design. Hay was freely available. It was supplemented with 1 kg concentrate daily. Dry matter intake from hay was higher for EH than for IH in heifers (4% and 13%, respectively in Holstein-Friesian and Belgian Blue heifers) and in cows (22%). Hay from an agri-environmental management may be used for low-performing animals, as energy intake only exceeded maintenance requirements by 20 to 35%. Several characteristics of EH were different between years, such as dry matter digestibility, net energy value for lactation and fermentable organic matter content.

Limits to nitrogen use on grassland.

Data from nitrogen (N) response experiments on grassland in Belgium and the Netherlands were analysed with the help of a descriptive crop N response model, to identify permissible doses below which no accumulation occurs of residual mineral soil N in autumn. N(min). Using different years as separate sets, a total of 29 data sets were obtained from eight locations on various soil types. A large variation was found in N(min) base levels (unfertilised) between locations and between years at a given location. For doses low enough not to affect crop N recovery, every 100 kg N applied was associated with 3-4 kg residual N(min) in autumn. This is considered very low compared to N(min) base levels, but values differed significantly from zero. After normalising N-doses from different sources (mineral fertiliser and cattle slurry) with the help of a coefficient expressing effectiveness based on crop N uptake, no difference was found between fertiliser and slurry in terms of their effect on residual Nmin. The above also holds for nitrate leaching as measured. The sources do differ, however, with respect to long-term effects and these are quantified with a first-order approximation. It it shown that, also after incorporation of long-term effects, much higher N-doses on grassland are justified than the 170 kg N per ha per year in animal manures currently proposed by the European Commission. On normal productive cut grassland as in the analysed experiments, total N doses in cattle slurry up to 400 kg per ha per year have very little effect on residual N(min), if not accompanied by high fertiliser doses. Introducing limits to the use of animal manures on grassland without limiting the input of mineral fertiliser-N lacks any scientific ground.

Effect of N fertilisation rate, energy supplementation and supplementation strategy on efficiency of N utilisation in the sheep rumen.

The effect of nitrogen (N) fertilisation (200 vs. 400 kg N ha-1 year-1) of pasture cut in the beginning (end of May) and the end (end of August) of the grazing season and of simultaneous or separated feeding of maize and grass (400 kg N ha-1 year-1) on efficiency of N utilisation in the rumen has been studied using four rumen cannulated wethers. Doubling N fertiliser rate increased grass CP production by about 60%, but induced extensive excess of rumen degradable N, reflected in high urinary urea excretion (rpearson = 0.747). The latter was lower (74% at the maximum) when feeding less fertilised or older grass or when supplementing with maize silage. Although simultaneous feeding of maize silage with grass changed patterns of rumen ammonia concentrations, no change in urinary excretion of purine derivatives was observed. Hence, faecal or urinary N excretion was unaffected by the supplementation strategy. Microbial growth efficiency was estimated from urinary excretion of purine derivatives and fermented OM. The latter was calculated from total rumen CH4 production, based on rumen fermentation stoichiometry and taking into account proportional concentrations of individual volatile fatty acids. Higher levels of intake tended to improve rumen microbial growth efficiency slightly (rpearson = 0.406), which, however, could not compensate for the reduced effective rumen DM degradability (rpearson = -0.442). The latter was apparently associated with a partial shift of the fermentation from the rumen to the hindgut, as suggested from the negative correlation (rpearson = -0.745) between faecal RNA concentrations and rumen effective degradability.

Nutritional assessment in Duchenne muscular dystrophy.

A specific-weight chart and simple clinical tools are sufficient to obtain an accurate diagnosis of undernutrition or obesity among patients with Duchenne muscular dystrophy (DMD). The authors collected weight-for-age measures from a sample of 252 boys and anthropometric data from 109 of those boys with DMD. The data confirm the accuracy of the DMD ideal-weight chart previously proposed by Griffiths and Edwards (1988). Obesity may occur from the age of seven years; its prevalence seems to reach 54 per cent by the age of 13 years. Undernutrition occurs after the age of 14 years, involving 54 per cent of boys at about 18 years of age. Obese boys show a centralized body-fat distribution, in agreement with other obese populations.

Resting energy expenditure and food-induced thermogenesis in obese children.

Nineteen overweight girls 14.54 +/- 0.38 years of age were studied. Results were compared with those obtained in eight age-matched (14.07 +/- 0.51 years) and sex-matched normal weight controls. Energy expenditure (EE) was determined using open-circuit indirect calorimetry at rest, both after a 12-h fast and after an oral sucrose load of 3 g/kg ideal body weight. Food-induced thermogenesis (FIT) was evaluated by computing the area under the curve of the EE response above resting energy expenditure (REE) during the first 3 h after the sucrose load, REE (kcal/day) was higher in the overweight patients (1,818 +/- 46 vs. 1,527 +/- 67; p = 0.002); REE standardized by fat-free mass (FFM) (kcal/kg FFM/day) was lower in obese children than in controls (35.2 +/- 1.0 vs. 44.9 +/- 1.9; p = 0.0001). A linear correlation between REE and FFM was evidenced in both controls and overweight subjects (r = 0.78 and 0.68, respectively; p = 0.05 and p < 0.001, respectively). Actual REE in the obese children was significantly lower than the value predicted by applying the regression equation of REE on FFM in controls to the actual FFM in obese children (paired t test; p = 0.003). FIT was identical in overweight and normal weight subjects, regardless of whether it was expressed in absolute value, as the percentage calorie intake, or standardized by FFM.(ABSTRACT TRUNCATED AT 250 WORDS)