Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice

IntroductionControlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of the present study was to investigate the effects of levosimendan on markers for diaphragm nitrosative and oxidative stress, inflammation and proteolysis in a mouse model of endotoxemia and mechanical ventilation.MethodsThree groups were studied: (1) unventilated mice (CON, n =8), (2) mechanically ventilated endotoxemic mice (MV LPS, n =17) and (3) mechanically ventilated endotoxemic mice treated with levosimendan (MV LPS + L, n =17). Immediately after anesthesia (CON) or after 8 hours of mechanical ventilation, blood and diaphragm muscle were harvested for biochemical analysis.ResultsMechanical ventilation and endotoxemia increased expression of inducible nitric oxide synthase (iNOS) mRNA and cytokine levels of interleukin (IL)-1β, IL-6 and keratinocyte-derived chemokine, and decreased IL-10, in the diaphragm; however, they had no effect on protein nitrosylation and 4-hydroxy-2-nonenal protein concentrations. Levosimendan decreased nitrosylated proteins by 10% (P <0.05) and 4-hydroxy-2-nonenal protein concentrations by 13% (P <0.05), but it augmented the rise of iNOS mRNA by 47% (P <0.05). Levosimendan did not affect the inflammatory response in the diaphragm induced by mechanical ventilation and endotoxemia.ConclusionsMechanical ventilation in combination with endotoxemia results in systemic and diaphragmatic inflammation. Levosimendan partly decreased markers of nitrosative and oxidative stress, but did not affect the inflammatory response.     

Plasma from septic shock patients induces loss of muscle protein

Introduction  

ICU-acquired muscle weakness commonly occurs in patients with septic shock and is associated with poor outcome. Although atrophy is known to be involved, it is unclear whether ligands in plasma from these patients are responsible for initiating degradation of muscle proteins. The aim of the present study was to investigate if plasma from septic shock patients induces skeletal muscle atrophy and to examine the time course of plasma-induced muscle atrophy during ICU stay.     

Gastric function in children with cystic fibrosis: effect of diet on gastric lipase levels and fat digestion

The effect of diet, usual (44 +/- 4% energy as fat), high-fat (49 +/- 4% energy as fat), and moderate-fat (33 +/- 2% energy as fat), on gastric function (lipase and pepsin activities, pH, emptying rate) and intragastric digestion of fat were assessed in six children with cystic fibrosis. Fasting and postprandial activity of digestive enzymes, gastric pH, and gastric volume measured before, during, and after 120 min of feeding did not differ significantly as a function of fat intake. Postprandial gastric lipase output (units per kilogram of body weight) during usual, moderate-fat, and high-fat diets was close to or higher than (38.8 +/- 7.2, 44.9 +/- 8.6, and 54.8 +/- 5.5 U/kg per 20 min) gastric lipase output of premature infants (22.5 +/- 6.4 to 28.3 +/- 6.6 U/kg per 20 min) or of healthy adults (5.4 +/- 0.4 U/kg per 15 min) fed a high-fat diet. Postprandial pepsin output was higher (4749 +/- 797, 6117 +/- 925, and 5444 +/- 819 U/kg per 20 min) than in premature infants (597 +/- 77 to 743 +/- 97 U/kg per 20 min) or healthy adults (781 +/- 56 U/kg per 15 min). Eighty minutes after feeding gastric lipolysis reached 20 to 36%. This study shows that gastric lipase activity is high in cystic fibrosis patients maintained on diets providing 32% to 49% energy as fat, and that gastric lipase level did not increase over the ranges of dietary fat intake tested.     

Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia

Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. For this purpose, we first determined the genomic organization of ITGA6, and placed the gene on chromosome 2q by high resolution radiation hybrid mapping. Heteroduplex analysis of PCR products containing the individual exons of ITGA6, followed by direct nucleotide sequencing, revealed that the proband was homozygous for a G-to-T transversion in the +1 position of intron 12. This mutation, 1856+1G-->T, affects an invariant base of the 5' donor splice site predicting aberrant splicing involving exon 12. The mutation was verified in the proband's DNA by restriction enzyme digestion which also confirmed that the parents were heterozygous carriers of this mutation. Altered expression of alpha6 integrin, which forms a heterodimer with the beta4 subunit at the dermal-epidermal junction, would explain fragility and blistering as a result of minor trauma to the skin.      

正交试验法优选石榴的提取工艺

目的：研究石榴中有效成分熊果酸的最佳提取条件。方法：采用正交试验法,以溶剂用量、提取时间和提取次数３个因素,每个因素选取了３个水平进行实验。结果：因素Ｂ对熊果酸的含量有显著影响。因素Ａ和因素Ｃ则有一定的影响。结论：最佳工艺Ａ３Ｂ２Ｃ１,即用１０倍量９５％ＥｔｏＨ提取１次,每次２ｈ。     

Five cases of anti-tumor necrosis factor alpha-induced psoriasis presenting with severe scalp involvement in children

Although anti-tumor necrosis factor alpha (TNF-α) agents are commonly used to treat psoriasis and other inflammatory diseases in adults and children, numerous reports have documented new-onset or flaring psoriasis in adults treated for the other conditions. Individual case reports have documented similar observations in three children. We report a series of anti-TNF-α-induced psoriasis in children with juvenile idiopathic arthritis or inflammatory bowel disease treated at a large children's hospital. All five patients presented with severe scalp involvement. One child was treated with adalimumab for juvenile idiopathic arthritis, and four received infliximab for inflammatory bowel disease. The five patients developed psoriasis 2 to 10 months after initiating anti-TNF-α therapy. They presented with erythematous, scaly, crusted scalp lesions. Three of the five patients were initially treated with griseofulvin for presumed tinea capitis. The anti-TNF-α agent was discontinued at the time of diagnosis in two cases. Topical steroids were the mainstay of psoriasis therapy, with improvement in four of five patients. Anti-TNF-α agents have been associated with the onset or worsening of psoriasis in adults, but this has rarely been reported in children. We describe five pediatric cases of anti-TNF-α-induced psoriasis presenting with severe scalp involvement and review their subsequent management. We hope that clinicians caring for patients receiving anti-TNF-α agents will consider psoriasis from the onset of cutaneous symptoms and institute appropriate therapy or referral.