Nitric oxide inhibits cysteine proteinases and alcohol dehydrogenase 2 of Entamoeba histolytica

Nitric oxide is involved in the neutrophil and macrophage killing of the protozoan parasite Entamoeba histolytica. In the present study, we found that cysteine proteinases, significant contributors to amebic virulence and alcohol dehydrogenase 2, an enzyme absolutely required for the survival of the parasite, are both significantly inhibited by S-nitroso-glutathione, a physiological nitric oxide donor, within the concentration range 0.5-2.0 m M.     

A role for lymphotoxin beta receptor in host defense against Mycobacterium bovis BCG infection

To investigate the role of membrane lymphotoxin (LT)alpha1 / beta2 and its LTbeta receptor (LTbetaR) in the protective immune response to Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection, we have used a soluble fusion molecule (LTbetaR-IgG1). LTbetaR-Ig treatment interferes with granuloma formation mainly in the spleen by inhibiting macrophage activation and nitric oxide synthase activity. In addition, a large accumulation of eosinophils was observed in the spleen of LTbetaR-Ig-treated infected mice. Decreased blood levels of IFN-gamma and increased IL-4 were also observed, suggesting that the LTbetaR pathway is important in BCG infection to favor a Th1 type of immune response. The treatment of transgenic mice expressing high blood levels of a soluble TNFR1-IgG3 fusion protein with LTbetaR-Ig resulted in a still higher sensitivity to BCG infection, and extensive necrosis in the spleen. In conclusion, these results suggest that the LTbetaR and the TNFR pathways are not redundant in the course of BCG infection and protective granuloma formation: the LTbetaR pathway appears to be important in spleen granuloma formation, whereas the TNFR pathway has a predominant role in other tissues.     

Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French -- Canadian population

Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy,the most common neuromuscular disorder in childhood. The generesponsible for childhood SMA has been mapped to the q11. 2– q13. 3 region of chromosome 5. We have extended ourlinkage studies of SMA In the French - Canadian population toInclude microsatellite markers at the D5S125, D5S351, D5S435,JK53CA1/ 2 and MAPI B locl. These markers span about 4 cM ofthe SMA candidate region. We observed significant evidence forlinkage between SMA and all the markers tested. The analysisof recombinant chromosomes provide evidence for the followinggenetic order: D5S125-D5S435-MAP1B-3'-JK53CA1/2 and places D5S351proximal to JK53CA1/2. Furthermore, we confirm the current localizationof the SMA gene distal to D5S435. Finally, we provide demonstrationof significant linkage disequilibrium between childhood-onsetSMA and four of the five marker loci, D5S125, D5S435, D5S351and JK53CA1/2. Analysis of SMA-region haplotypes suggests thatthere may be a predominant SMA allele that is present on about17% of SMA chromosomes in this sample of the French - Canadianpopulation. We conclude that the observed linkage disequilibriumis likely due to genetic drift among regions of Quebec, consistentwith this population's early history.     

High-intensity intermittent running training improves pulmonary function and alters exercise breathing pattern in children

We investigated the effects of short duration running training on resting and exercise lung function in healthy prepubescent children. One trained group (TrG) (n = 9; three girls and six boys; age = 9.7 ± 0.9 year) participated in 8 weeks of high-intensity intermittent running training and was compared to a control group (ContG) (n = 9; four girls and five boys; age = 10.3 ± 0.7 year). Before and after the 8-week period, the children performed pulmonary function tests and an incremental exercise test on a cycle ergometer. After the 8-week period, no change was found in pulmonary function in ContG. Conversely, an increase in forced vital capacity (FVC) (+7 ± 4% ; P = 0.026), forced expiratory volume in one second (+11 ± 6% ; P = 0.025), peak expiratory flows (+17 ± 4% ; P = 0.005), maximal expiratory flows at 50% (+16 ± 10% ; P = 0.019) and 75% (+15 ± 8% ; P = 0.006) of FVC were reported in TrG. At peak exercise, TrG displayed higher values of peak oxygen consumption (+15 ± 4% ; P<0.001), minute ventilation (+16 ± 5% ; P = 0.033) and tidal volume (+15 ± 5% ; P = 0.019) after training. At sub-maximal exercise, ventilatory response to exercise was lower (P = 0.017) in TrG after training, associated with reduced end-tidal partial oxygen pressure (P<0.05) and higher end-tidal partial carbon dioxide pressure (P = 0.026). Lower deadspace volume relative to tidal volume was found at each stage of exercise in TrG after training (P<0.05). Eight weeks of high-intensity intermittent running training enhanced resting pulmonary function and led to deeper exercise ventilation reflecting a better effectiveness in prepubescent children.     

A new species of the medicinal leech (Oligochaeta, Hirudinida, Hirudo) from Transcaucasia and an identification key for the genus Hirudo

A recent molecular phylogenetic study has suggested that the genus Hirudo contains a neglected species previously known as the orientalis coloration type of the medicinal leech Hirudo medicinalis. In this paper, the new species is formally described as Hirudo orientalis sp. n. It can most readily be identified by the grass green coloration of the dorsum, segmentally arranged pairs of black quadrangular or rounded dots on its paramarginal dorsal stripes and similarly arranged, but less regular light-colored markings on the predominantly black venter. It has medium-sized epididymes and an evenly coiled vagina. H. orientalis is known from Transcaucasia, Iran, and Uzbekistan. It is widely used in medicine as the “medicinal leech.” Very little is known about its exact distribution, specific habitat, and conservation status. The paper contains an identification key to all species of the genus Hirudo.     

Validation of MTF measurement for digital mammography quality control

The modulation transfer function (MTF) describes the spatial resolution properties of imaging systems. In this work, the accuracy of our implementation of the edge method for calculating the presampled MTF was examined. Synthetic edge images with known MTF were used as gold standards for determining the robustness of the edge method. These images simulated realistic data from clinical digital mammography systems, and contained intrinsic system factors that could affect the MTF accuracy, such as noise, scatter, and flat-field nonuniformities. Our algorithm is not influenced by detector dose variations for MTF accuracy up to 1/2 the sampling frequency. We investigated several methods for noise reduction, including truncating the supersampled line spread function (LSF), windowing the LSF, applying a local exponential fit to the LSF, and applying a monotonic constraint to the supersampled edge spread function. Only the monotonic constraint did not introduce a systematic error; the other methods could result in MTF underestimation. Overall, our edge method consistently computed MTFs which were in good agreement with the true MTF. The edge method was then applied to images from a commercial storage-phosphor based digital mammography system. The calculated MTF was affected by the size (sides of 2.5, 5, or 10 cm) and the composition (lead or tungsten) of the edge device. However, the effects on the MTF were observed only with regard to the low frequency drop (LFD). Scatter nonuniformity was dependent on edge size, and could lead to slight underestimation of LFD. Nevertheless, this negative effect could be minimized by using an edge of 5 cm or larger. An edge composed of lead is susceptible to L-fluorescence, which causes overestimation of the LFD. The results of this work are intended to underline the need for clear guidelines if the MTF is to be given a more crucial role in acceptance tests and routine assessment of digital mammography systems: the MTF algorithm and edge object test tool need to be publicly validated.     

Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta

Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 10) and from control subjects (n = 7) at baseline and after IL-1beta stimulation. Basal KGF secretion by IPF fibroblasts was similar to controls. In fibroblasts from control subjects, IL-1beta increased c-Jun expression, c-Jun activation, and KGF secretion. SP600125, a specific c-Jun N-terminal kinase (JNK) inhibitor, inhibited the effect of IL-1beta. By contrast, in IPF fibroblasts, IL-1beta did not increase c-Jun expression and c-Jun activation, and weakly increased KGF secretion, whereas SP600125 had no effect. IL-1beta similarly increased JunB expression in fibroblasts from patients with IPF and control subjects. Total JNK content was not different in either unstimulated or IL-1beta-stimulated IPF and control fibroblasts. IL-1beta increased phosphorylated JNK in control and IPF fibroblasts, but this increase was weaker and heterogeneous in IPF. Altogether, our results demonstrate a dysregulation of KGF secretion by IPF fibroblasts. The weak response to IL-1beta is associated with a defect of c-Jun expression and activation and a defect of JNK activation.     

Probiotic Supplementation and High-Intensity Interval Training Modify Anxiety-Like Behaviors and Corticosterone in High-Fat Diet-Induced Obesity Mice

Evidence supports the role of exercise training and probiotics on reducing obesity. Considering the relationship between obesity and high-fat diet with anxiety indices, the aim of this study was to assess the effect of probiotic supplementation and high-intensity interval training (HIIT) on anxiety-like behaviors, corticosterone and obesity indices in high-fat diet (HFD)-induced obesity mice. Thirty male adult C57BL/6 mice were randomly divided into five groups: (1) Control with normal diet (CON), (2) High-fat diet (HFD), (3) HFD + exercise training (HT), (4) HFD + probiotics supplement (HP) and (5) HFD + exercise training +probiotics (HTP). Exercise training consisted of 8 weeks of high-intensity interval training (HIIT) programs. Probiotics supplement included 0.2 mL Lactobacillus rhamnosus GG. Anxiety-like behaviors were measured by open field (OF) and Elevated plus maze (EPM). OF and EPM tests, visceral fat mass (VFM) measurement, and blood sampling for corticosterone were performed after the intervention. Bodyweight was measured at different stages during the intervention. HFD regime in C57BL/6 mice increased bodyweight, VFM, and serum corticosterone levels and anxiety-like behaviors (p < 0.05). HIIT, probiotic and their combination, decreased bodyweight, VFM, and serum corticosterone levels and improved anxiety-like behavior in the HFD mice (p < 0.05). The effect of a combination of HIIT and probiotic on most of the anxiety indices was more than each one separately (p < 0.5). HIIT and probiotic supplements separately or above all in combination, may have beneficial effects in reducing obesity and anxiety indices.     

超临界连续GAS过程制备对苯二酚超细颗粒

针对传统RESS过程中存在着颗粒质量和产量问题,本文分别以超临界CO2作为溶剂在萘的固态和熔融状态下利用RESS过程制备了萘的超细颗粒,研究了萘在固态和熔融态下各种操作变量,如萃取温度和压力、膨胀前温度和喷嘴尺寸等对产品尺寸的影响。结果表明,膨胀前温度和萃取压力的作用规律相同,提高膨胀前温度则颗粒变大,提高萃取温度,颗粒尺寸变小;而在熔融状态下反之,在该研究范围内,喷嘴尺寸的熔融态和固态下对颗粒尺寸影响不大。     

Nichtinvasive Beatmungs- und Lagerungstherapie bei COVID-19

Die Anaesthesiologie - Schwere Verläufe von COVID-19 führen bei Versagen einer unterstützenden nichtinvasiven Beatmung („high flow“, CPAP bzw. NIV) zur Eskalation der...