Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls

BACKGROUND: The inflammatory response has been widely investigated in patients with acute respiratory distress syndrome (ARDS) and pneumonia. Studies investigating the diagnostic values of serum cytokine levels have yielded conflicting results and only little information is available for the differential diagnosis between ARDS and pneumonia. METHODS: Clinical and physiological data, serum concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and quantitative cultures of lower respiratory tract specimens were obtained from 46 patients with ARDS and 20 with severe pneumonia within 24 hours of the onset of the disease and from 10 control subjects with no inflammatory lung disease. Cytokine concentrations were compared between groups and determinants in addition to the diagnosis were tested. RESULTS: Serum TNF-alpha levels were significantly higher in ARDS patients (67 (57) pg/ml) than in patients with severe pneumonia (35 (20) pg/ml; p = 0.031) or controls (17 (8) pg/ml; p = 0.007). For IL-1beta and IL-6 the observed differences were not statistically significant between patients with ARDS (IL-1beta: 34 (65) pg/ml; IL-6: 712 (1058) pg/ml), those with severe pneumonia (IL-1beta: 3 (4) pg/ml, p = 0.071; IL-6: 834 (1165) pg/ml, p = 1.0), and controls (IL-1beta: 6 (11) pg/ml, p = 0.359; IL-6: 94 (110) pg/ml, p = 0.262). TNF-alpha (standardised coefficient beta = 0.410, p<0.001) and IL-1beta (standardised coefficient beta = 0.311, p = 0.006) were most strongly associated with the degree of lung injury, even when the diagnostic group was included in the statistical model. CONCLUSIONS: Serum TNF-alpha levels were higher in patients with ARDS than in those with severe pneumonia or in control subjects. Multivariate results suggest that the levels of systemic TNF-alpha and IL-1beta reflect the severity of the lung injury rather than the diagnosis.     

Antihyperglycemic and hypolipidemic effects of α, β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice

Objectives

Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease. In this study, we tried to investigate the effects of saturated and unsaturated fatty acids on hepatoma cell apoptosis.

Methods

H4IIE liver cells were treated with palmitic acid, linoleic acid, or both with or without the calcium-specific chelator BAPTA-AM after which the expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels, and calcium flux were measured.

Results

Palmitic or linoleic acid (250 ??M) induced H4IIE cell apoptosis, which required calcium flux but not caspase-3. Apoptosis was not observed when cells were co-treated with linoleic acid (125 ??M) and palmitic acid (250 ??M). Importantly, the release of cytochrome C from mitochondria into cytoplasm during cell apoptosis was specifically detected only when linoleic acid (125 ??M), but not palmitic acid (250 ??M), was added to the cells. Depletion of intracellular calcium flux by the calcium-specific chelator, BAPTA-AM, abolished linoleic acid-induced apoptosis. Moreover, in the presence of BAPTA-AM, expression of the unfolded protein response (UPR)-associated genes, CHOP, GRP78, and GRP94, was induced by linoleic acid, but not palmitic acid.

Conclusions

The results suggest that linoleic acid promotes cell apoptosis through the release of cytochrome C, only if the intracellular calcium flux is unperturbed and intact. These results confirm that ER stress contributes to fatty acid-induced liver cell apoptosis.     

Impact of Obesity and Body Fat Distribution on Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Background

Epidemiologic studies have reported a positive correlation between body mass index (BMI) and pancreatic cancer risk, but clinical relevance of obesity and/or body fat distribution on tumor characteristics and cancer-related outcome remain controversial. We sought to assess the influence of obesity and body fat distribution on pathologic characteristics and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma.

Methods

Demographic and biometric data were collected on 328 patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In a subset of patients, pancreatic fatty infiltration and fibrosis were assessed pathologically, and visceral fat area (VFA) was evaluated. Influence of BMI and body fat distribution on tumor characteristics and survival were evaluated.

Results

A significant positive correlation between BMI and VFA was observed, with a wide range of VFA value within each BMI class. According to BMI or VFA distribution, there were no significant differences in patient characteristics, intraoperative or perioperative outcome, or pathologic characteristics, with the exception of significantly higher blood loss in patients with an increased body weight or VFA. Unadjusted overall and disease-free survival between BMI class and VFA quartile were not significantly different.

Conclusions

In this study, obesity and body fat distribution were not correlated with specific tumor characteristics or cancer-related outcome.     

Quantifying excess length of postoperative stay attributable to infections: a comparison of methods

To quantify the net effect of deep surgical site infection (DSSI) on postoperative stay (POS) among patients who had undergone open heart surgery, and to assess the comparability of two methods, two observational studies were conducted: one on a retrospective cohort of 701 operated patients, and the other on a cohort of 31 infected patients versus a cohort of uninfected patients, with 1:1 matching. In addition to DSSI, a further three factors were identified by multivariate analysis as independent POS-related predictor variables. After internal validation of the multivariate model, excess POS attributable to DSSI amounted to 20.7 days (95% confidence interval [CI] 16.7–24.9). In contrast, excess length of stay attributable to DSSI among the matched pairs who survived infection (22) totaled 14.3 days (95% CI 3.2–25.4) and 26.5 days (mean and median differences). Multivariate techniques may prove a more appropriate and reliable analysis than matched-pair comparisons for the purpose of evaluating the extra stay and cost attributable to the nosocomial infections.     

Immunocytochemical localization of retinal binding protein in the octopus retina: a shuttle protein for 11-cis retinal.

The cephalopod retina contains two photopigments that are spatially separated within the photoreceptors; rhodopsin, localized in the light-sensitive rhabdoms, and retinochrome, present in the myeloid bodies of the photoreceptor inner segments. In the light, the chromophore of retinochrome, all-trans retinal, is photoisomerized to 11-cis to form metaretinochrome. Metaretinochrome is believed to serve as a store for 11-cis retinal used in the regeneration or biosynthesis of rhodopsin. Previous studies suggest that a soluble retinal binding protein (RALBP) serves as a shuttle between retinochrome and rhodopsin, and, in the dark, may transport chromophore from the myeloid bodies to the rhabdoms. Our study supports this hypothesis and demonstrates that RALBP is in the correct cellular locations to function as a shuttle. Dark- and light-adapted octopus retinas were labeled with anti-RALBP using immunofluorescence and immunogold techniques. Our results showed that RALBP was distributed differently in the dark- and light-adapted retinas. Our most significant observation was that myeloid bodies from light-adapted retinas were more heavily labeled by anti-RALBP than myeloid bodies in dark-adapted retinas. The rhabdomeres, interphotoreceptor matrix, and inner limiting membrane were also labeled in both light and dark conditions. Based on these results and evidence from previous biochemical studies, we conclude that in the dark RALBP leaves the myeloid bodies and transports 11-cis retinal to the rhabdoms where chromophore exchange with metarhodopsin may occur.