Oxidative and pre-inflammatory stress in wedge resection of pulmonary parenchyma using the radiofrequency ablation technique in a swine model

<p>Abstract</p> <p>Background</p> <p>Radiofrequency ablation (RFA) is a thermal energy delivery system used for coagulative cellular destruction of small tumors through percutaneous or intraoperative application of its needle electrode to the target area, and for assisting partial resection of liver and kidney. We tried to evaluate the regional oxidative and pre-inflammatory stress of RFA-assisted wedge lung resection, by measuring the MDA and tumor Necrosis Factor Alpha (TNF-α) concentration in the resected lung tissue of a swine model.</p> <p>Method</p> <p>Fourteen white male swines, divided in two groups, the RFA-group and the control group (C-group) underwent a small left thoracotomy and wedge lung resection of the lingula. The wedge resection in the RFA-group was performed using the RFA technique whereas in C-group the simple "cut and sew" method was performed. We measured the malondialdehyde (MDA) and TNF-α concentration in the resected lung tissue of both groups.</p> <p>Results</p> <p>In C-group the MDA mean deviation rate was 113 ± 42.6 whereas in RFA-group the MDA mean deviation rate was significantly higher 353 ± 184 (p = 0.006). A statistically significant increase in TNF-α levels was also observed in the RFA-group (5.25 ± 1.36) compared to C-group (mean ± SD = 8.48 ± 2.82) (p = 0.006).</p> <p>Conclusion</p> <p>Our data indicate that RFA-assisted wedge lung resection in a swine model increases regional MDA and TNF-a factors affecting by this oxidative and pre-inflammatory stress of the procedure. Although RFA-assisted liver resection can be well tolerated in humans, the possible use of this method to the lung has to be further investigated in terms of regional and systemic reactions and the feasibility of performing larger lung resections.</p

Effects of lifestyle intervention in persons at risk for type 2 diabetes mellitus - results from a randomised, controlled trial

Background: Lifestyle change is probably the most important single action to prevent type 2 diabetes mellitus. The purpose of this study was to assess the effects of a low-intensity individual lifestyle intervention by a physician and compare this to the same physician intervention combined with an interdisciplinary, group-based approach in a real-life setting. Methods: The “Finnish Diabetes Risk score” (FINDRISC) was used by GPs to identify individuals at high risk. A randomised, controlled design and an 18 month follow-up was used to assess the effect of individual lifestyle counselling by a physician (individual physician group, (IG)) every six months, with emphasis on diet and exercise, and compare this to the same individual lifestyle counselling combined with a group-based interdisciplinary program (individual and interdisciplinary group, (IIG)) provided over 16 weeks. Primary outcomes were changes in lifestyle indicated by weight reduction ≥ 5%, improvement in exercise capacity as assessed by VO2 max and diet improvements according to the Smart Diet Score (SDS). Results: 213 participants (104 in the IG and 109 in the IIG group, 50% women), with a mean age of 46 and mean body mass index 37, were included (inclusion rate > 91%) of whom 182 returned at follow-up (drop-out rate 15%). There were no significant differences in changes in lifestyle behaviours between the two groups. At baseline 57% (IG) and 53% (IIG) of participants had poor aerobic capacity and after intervention 35% and 33%, respectively, improved their aerobic capacity at least one metabolic equivalent. Unhealthy diets according to SDS were common in both groups at baseline, 61% (IG) and 60% (IIG), but uncommon at follow-up, 17% and 10%, respectively. At least 5% weight loss was achieved by 35% (IG) and 28% (IIG). In the combined IG and IIG group, at least one primary outcome was achieved by 93% while all primary outcomes were achieved by 6%. Most successful was the 78% reduction in the proportion of participants with unhealthy diet (almost 50% absolute reduction). Conclusion: It is possible to achieve important lifestyle changes in persons at risk for type 2 diabetes with modest clinical efforts. Group intervention yields no additional effects. The design of the study, with high inclusion and low dropout rates, should make the results applicable to ordinary clinical settings

Rapid Accumulation of CD14+CD11c+ Dendritic Cells in Gut Mucosa of Celiac Disease after in vivo Gluten Challenge

Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c(+) dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c(+) or CD103(+)) and CD163(+)CD11c(-) macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge.Treated HLA-DQ2(+) CD patients (n = 12) and HLA-DQ2(+) gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry.In treated CD patients, the gluten challenge increased the density of CD14(+)CD11c(+) DCs, whereas the density of CD103(+)CD11c(+) DCs and CD163(+)CD11c(-) macrophages decreased, and the density of CD1c(+)CD11c(+) DCs remained unchanged. Most CD14(+)CD11c(+) DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed.Rapid accumulation of CD14(+)CD11c(+) DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes

Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO) to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1) TNF-α production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction

Effect of voluntary exercise upon the metabolic syndrome and gut microbiome composition in mice

The metabolic syndrome is a cluster of conditions that increase an individual's risk of developing diseases. Being physically active throughout life is known to reduce the prevalence and onset of some aspects of the metabolic syndrome. Furthermore, previous studies have demonstrated that an individual's gut microbiome composition has a large influence on several aspects of the metabolic syndrome. However, the mechanism(s) by which physical activity may improve metabolic health are not well understood. We sought to determine if endurance exercise is sufficient to prevent or ameliorate the development of the metabolic syndrome and its associated diseases. We also analyzed the impact of physical activity under metabolic syndrome progression upon the gut microbiome composition. Utilizing whole-body low-density lipoprotein receptor (LDLR) knockout mice on a "Western Diet," we show that long-term exercise acts favorably upon glucose tolerance, adiposity, and liver lipids. Exercise increased mitochondrial abundance in skeletal muscle but did not reduce liver fibrosis, aortic lesion area, or plasma lipids. Lastly, we observed several changes in gut bacteria and their novel associations with metabolic parameters of clinical importance. Altogether, our results indicate that exercise can ameliorate some aspects of the metabolic syndrome progression and alter the gut microbiome composition

Phytochemical investigation of the leaves of tetracera scandens Linn and in vitro antidiabetic activity of hypoletin

Tetracera scandens Linn. (Dilleniaceae), locally known as Mempelas Kasar, is traditionally used in folk remedies by various indigenous people in different countries including Malaysia for the treatment of rheumatism, inflammatory diseases, hepatitis, internal pains, urinary disorders, dysentery, sore throat, gout and diabetes infirmities; for lowering hypertension; and for child birth. In this study, phytochemical analysis of T. scandens leaf methanol (MeOH) extract was carried out for the first time and afforded three terpenoids (stigmasterol, betulinic acid and an isomeric mixture of sitosterol (∆5) glycoside and stigmasterol (∆5,22) glycoside) and six flavonoids (namely, kaempferol, quercetin, isoscutellarein, hypoletin, astragalin and kaempferol-3-O-(6″-O-p-trans-coumaroyl) glucoside, a rare compound which has been isolated for the first time from family Dilleniaceae). Structures of all compounds were elucidated through extensive UV–Vis, mass, IR and NMR spectral analysis. The occurrence of all these compounds is being reported for the first time from this plant. Due to the rare occurrence of hypoletin (3′,4′,5,7,8-pentahydroxyflavone) in plants, its in vitro antidiabetic effect was explored. Hence, the treatment of hypoletin in a dose-dependent manner was examined on the induction of lipid accumulation by using Oil Red O staining and glucose regulation in 3T3-L1 adipocytes in vitro with regard to its preventive role in the management of diabetes. After 8 days, morphological changes and high lipid accumulation activity were observed in cells treated with 10 μg/mL of hypoletin concentration (P < 0.01). In addition, the intracellular fat accumulation increased by up to 79.7 % relative to MDI-treated control cells at a dose of 10 μg/mL. Furthermore, insulin-induced 2-deoxy-d-[3H] glucose uptake was significantly increased (P < 0.001) in hypoletin-treated cells as compared to control (DMSO cells). Our results suggest that hypoletin could be useful for the management of type 2 diabetes due to its adipocyte stimulation and glucose uptake activity