Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease.

INTRODUCTION: Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. METHODS: Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. RESULTS: 48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. CONCLUSION: Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.

Potential risk factors associated with contact dermatitis, lameness, negative emotional state, and fear of humans in broiler chicken flocks.

The objectives of this study were to 1) identify determinants of poor welfare in commercial broiler chicken flocks by studying the associations between selected resource-based measures (RBM, potential risk factors), such as litter quality and dark period, and animal-based welfare indicators (ABM), such as foot pad dermatitis and lameness, and 2) establish the breadth of effect of a risk factor by determining the range of animal welfare indicators associated with each of the risk factors (i.e., the number of ABM related to a specific RBM). Eighty-nine broiler flocks were inspected in 4 European countries (France, Italy, the United Kingdom, and the Netherlands) in a cross-sectional study. The ABM were contact dermatitis (measured using scores of foot-pad dermatitis and hock burn, respectively), lameness (measured as gait score), fear of humans (measured by the avoidance distance test and the touch test), and negative emotional state (measured using qualitative behavior assessment, QBA). In a first step, risk factors were identified by building a multiple linear regression model for each ABM. Litter quality was identified as a risk factor for contact dermatitis. Length of dark period at 3 wk old (DARK3) was a risk factor for the touch test result. DARK3 and flock age were risk factors for lameness, and the number of different stockmen and DARK3 were risk factors for QBA results. Next, the ABM were grouped according to risk factor and counted. Then, in a second step, associations between the ABM were investigated using common factor analysis. The breadth of a risk factor's effect was judged by combining the number (count) of ABM related to this factor and the strength of association between these ABM. Flock age and DARK3 appeared to affect several weakly correlated ABM, thus indicating a broad range of effects. Our findings suggest that manipulation of the predominant risk factors identified in this study (DARK3, litter quality, and slaughter age) could generate improvements in the related ABM and thereby enhance the birds' overall welfare status.

Complete nucleotide sequence of a putative new cytorhabdovirus infecting lettuce.

The full-length nucleotide sequence of the genomic RNA of a new cytorhabdovirus infecting lettuce was determined. Six open reading frames were found in the antigenomic sequence of the 12,926-nt negative-sense viral RNA genome. The genomic organisation was similar to that of lettuce necrotic yellows virus (LNYV), the type member of the genus Cytorhabdovirus: 3'-N-P-3-M-G-L-5', where N is the capsid protein gene, P the putative phosphoprotein gene, 3 a gene coding for a putative protein of unknown function, M the putative matrix protein gene, G the glycoprotein gene, and L the putative polymerase gene. Amino acid sequence comparison with the corresponding sequences of other rhabdoviruses revealed the closest relationship to LNYV, with identities ranging from 41% for the matrix proteins and 65% for the L polymerase proteins. These results indicate that this virus may be a member of a new cytorhabdovirus species, for which the name Lettuce yellow mottle virus (LYMoV) is proposed.

A RT/PCR-partial restriction enzymatic mapping (PREM) method for the molecular characterisation of the large satellite RNAs of Arabis mosaic virus isolates.

The satellite RNA of the grapevine isolate NW of Arabis mosaic virus (ArMV) was cloned and sequenced, and showed 75% identity at the nucleotide level to the satellite RNA of the lilac isolate of ArMV. In order to survey ArMV isolates from various geographical origins and natural hosts for the presence of large satellite RNAs and analyse their degree of variability, a RT/PCR-partial restriction enzymatic mapping (PREM) method was developed. The method is based on the incorporation of 5-methyl-dCTP in the RT/PCR reaction, and the subsequent digestion of the RT/PCR products by methyl-sensitive restriction enzymes. Satellites RNAs were detected by RT/PCR in eight isolates out of 47, six of them originating from grapevine, one from hop and one from lilac. The partial restriction digestion patterns allowed to distinguish six different types of satellites. Cloning and sequencing of the different satellites confirmed these results, the PREM proving able to discriminate sequences with 96% identity. The sizes of the different satellites varied between 1092 and 1139 nucleotides, their encoded proteins between 338 and 360 amino acids. Conserved domains were found in the amino and carboxy-termini between the sequences of the proteins encoded by the satellites of the different isolates of ArMV.

[ACE inhibition in patients with myocardial infarct and ventricular dysfunction: inappropriate application of therapy standards in patient samples]. / ACE-Inhibition bei Myokardinfarktpatienten mit eingeschränkter Ventrikelfunktion: Umsetzung von Therapiestandards in Bevölkerungsstichproben.

Several reports indicate the benefit of ACE inhibitors for patients with left ventricular systolic dysfunction after acute myocardial infarction (MI). We sought to determine the implementation of the treatment guidelines in patient samples from the general population. Furthermore we aimed to identify patient characteristics associated with the use of ACE inhibitors. Screening of two MI-registries allowed the identification of 226 MI patients with left ventricular dysfunction. Patients were considered to be eligible for ACE inhibitor therapy when a EF < or = 40% was documented in the patient records of cardiac rehabilitation clinics (REG-MI, n = 147) or detected by standardised echocardiography (KORA, n = 78). On average 5.5 years following MI, a standardised questionnaire and a detailed medical history was obtained. Specifically, information was collected regarding current medication and potential contraindications for ACE inhibitors. MI patients with LV dysfunction received ACE inhibitors in 62% (REG-MI) and 45% (KORA). The doses prescribed were substantially smaller than target doses used in the large-scale studies (REG-MI: 40 +/- 4%, KORA: 23 +/- 3%, % of target doses). Only 13% (REG-MI) and 3% (KORA) received more than 50% of the target dosage. Additionally, actual doses of the most frequently used ACE inhibitors were significantly different (captopril: 23 +/- 2%, enalapril: 42 +/- 5% of target doses). The likelihood of receiving ACE inhibitors was significantly higher in patients with written recommendation for such medication (odds ratio 6.02, confidence interval 1.93-20.16) and in patients visiting cardiologists (odds ratio 3.69, confidence interval 1.26-11.07) as revealed by multivariate analysis of the REG-MI database. Despite national and international guidance, a large proportion of MI patients with left ventricular dysfunction is not receiving ACE inhibitors, and when used, the doses prescribed are markedly smaller than target doses used in clinical trials that established the utility of these drugs. Medical care by cardiologists and written recommendation of ACE inhibition in patient records were independent predictors of a more appropriate prescription of ACE inhibitors.

Eleven single nucleotide polymorphisms and one triple nucleotide insertion of the human TGF-beta III receptor gene.

We found 11 single nucleotide polymorphisms and one triple nucleotide insertion in the cDNA of the human transforming growth factor beta (TGF-beta) III receptor gene (TGFBR3) located on 1p33-p32, encoding beta-glycan, a component of the TGF-beta receptor system. Inside the 5' untranslated region (UTR), a G-->A polymorphism was identified at position 311. In the open reading frame (ORF), a non-conservative T-->C polymorphism was identified at position 392, and three conservative polymorphisms were found at positions 563 (G-->A), 1548 (G-->A), and 2370 (C-->T). A triple nucleotide insertion (GCA) was identified at position 1419. Inside the 3' UTR, six polymorphisms were identified: four G-->A, at positions 2918, 3055, 3098, and 3355; one T-->A, at position 3183; and one G-->C, at position 3966. In addition to these changes, some divergences from the published sequence were observed in all 12 chromosomes tested. These included, in the ORF, an additional C after position 555, two additional G after position 563, and an additional T after position 1388. No T was found at position 1394. The alterations translate to a changed amino acid sequence. Inside the 3' UTR, additional discrepancies were identified. The discovered changes and polymorphisms may be useful for further genetic studies of TGFBR3 receptor deficiencies.

Inotropic response of stunned hypertrophied myocardium: responsiveness of hypertrophied and normal postischemic isolated rat hearts to calcium and dopamine stimulation.

OBJECTIVE: Severely hypertrophied myocardium was described to have a reduced tolerance towards ischemia. For non-hypertrophied hearts inconclusive findings on the Ca(2+)-responsiveness are reported. Information sensitivity to reversible ischemia and on postischemic Ca(2+)-responsiveness of hearts with clinically common moderate hypertrophy is lacking. Thus, the responsiveness of hypertrophied and normal postischemic myocardium to positive inotropic stimulation should be investigated in the present study. METHODS AND RESULTS: Hearts from spontaneously hypertensive rats (SHR, 4 months old) with significant LV-hypertrophy (+ 50%) and hearts from normotensive 4 months old Wistar rats were investigated using an isovolumic beating isolated heart model (8 hearts/each of the 8 groups). Functional recovery after 30 min of no-flow ischemia was 78 +/- 1% and 77 +/- 3% of preischemic control data in hypertrophied and non-hypertrophied hearts assessed as developed left ventricular pressure (non-ischemic controls: 95 +/- 2% in hypertrophied and 93 +/- 3% in non-hypertrophied controls). Maximum short-term stimulation with Ca2+ revealed a decreased peak left ventricular pressure of 124 +/- 4% in hypertrophied and 120 +/- 5% in non-hypertrophied postischemic hearts, as compared with non-ischemic controls 138 +/- 3% and 157 +/- 5%, respectively ( p < 0.01). A maximum dose of dopamine stimulated hypertrophied and non-hypertrophied postischemic hearts comparable to Ca2+. Analysing the dose-response curve for Ca(2+)-stimulation, the sensitivity expressed as fraction of the maximum was identical in non-ischemic and postischemic myocardium of hypertrophied and non-hypertrophied ventricles in spite of the reduced peak values. CONCLUSION: The findings demonstrate that after moderate reversible ischemia the steady-state function is similarly decreased in hypertrophied and non-hypertrophied postischemic myocardium. The maximum response to Ca2+ is significantly reduced in both types of myocardium, while the Ca2+ sensitivity is unchanged. Identical results after maximum dopamine stimulation as after Ca2+ indicate that the releasibility of Ca2+ and the beta-adrenoceptors are not the critical causes for the postischemic dysfunction in hypertrophied or non-hypertrophied myocardium.

Preconditioning preserves energy metabolism in prolonged low-flow ischemia.

BACKGROUND: A reduction in coronary flow leads to a parallel decrease in contractile function. Thus, a flow/function balance is established in the myocardium under certain circumstances avoiding the development of a necrosis (referred to as "hibernating" myocardium). The impact of a preconditioning period on this critical balance was examined. METHODS: In 116 isovolumetrically beating rat hearts, 3 h of hypoperfusion with 15% of control coronary flow were performed followed by 1 h reperfusion; 40 hearts served as controls. As a preconditioning period, in half of the rat hearts a 5 min no-flow ischemia followed by 10 min reperfusion was performed, preceding the prolonged hypoperfusion. RESULTS: Systolic function was identically reduced in both groups after 3 h hypoperfusion (LVP: 39 +/- 2 mmHg, 40 +/- 2 mmHg vs. controls 90 +/- 3 mmHg; p < 0.01). Without preconditioning hypoperfusion resulted in a marked initial decrease in function. This period was followed by an adaptation to a higher steady state level of function compared with non-preconditioned hypoperfused hearts (p < 0.05). After preconditioning hypoperfusion directly resulted in this level of contraction. Contractile reserve was reduced (p < 0.01) identically in both hypoperfusion groups. Adenine nucleotides were decreased (p < 0.01) after 3 h hypoperfusion to 2.1 +/- 0.2 mumol/gww vs. controls (4.7 +/- 0.2 mumol/gww). After initial preconditioning adenine nucleotides were better preserved (3.2 +/- 0.2 mumol/gww) going ahead with a creatine phosphate overshoot of 126% (p < 0.01). After reperfusion, systolic function and contractile reserve were identical in both groups. CONCLUSION: A period of preceding no-flow ischemia followed by reperfusion modifies functional adaptation to hypoperfusion and preserves high energy phosphates. Therefore, the metabolic balance during hypoperfusion is improved by preconditioning, although no impact on contractile reserve or the functional status of reperfused myocardium after low-flow ischemia can be seen.