Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Hyaluronic acid in incision wound fluid: a clinical study with the Cellstick device in children.

When inserted into a human incision wound, the Cellstick device harvests inflammatory cells and collects wound fluid, reflecting time-related changes in cell populations and in wound fluid composition. Hyaluronic acid has been postulated to be an important factor in scar reduction in wound healing and in scarless fetal wound healing. The aim of this work was to determine the concentration and variation of hyaluronic acid and proportions of wound cells in closed surgical wounds in children at two time points. The Cellstick device was inserted subcutaneously into the wound at the end of an elective inguinal hernia operation on 37 healthy boys, and the devices were removed 3+/-1 or 24+/-3 hours after surgery. Haluronic acid concentration was measured from the wound fluid and a differential count of the wound cells was performed. There was a significant decrease in hyaluronic acid concentration from 3+/-1 to 24+/-3 hours after surgery (p<0.001, Kruskal-Wallis anova). The variance of hyaluronic acid concentration in wound fluid differed between the wounds at the two time points (p<0.01, Levene test for homogeneity of variance). A positive correlation between hyaluronic acid concentration and patient age (r=0.91, p<0.05, Spearman) at 3+/-1 hours post surgery and between HA and wound lymphocytes (r=0.38, p<0.05, Spearman) was also found. We conclude that the hyaluronic acid concentration in wound fluid peaks early in children and decreases significantly by 3 to 24 hours after surgery, and the concentrations in the wound fluid of healthy boys are more variable 3 hours than at 24 hours after surgery.

Wound cell variation in closed surgical wounds as measured with two independent methods.

BACKGROUND AND AIMS: It is not known, to what extent the observed cellular changes in healing surgical wounds are species-, individual- or site-specific or whether they depend on the research method used. The aim of this study was to compare two independent methods for harvesting wound cells from porcine wounds after two time intervals, and to assess individual changes of wound cell composition. MATERIAL AND METHODS: In a standardised wound model in six pigs, with eight dorsal skin incision wounds in each, the Cellstick device and the Wound Edge Contact (WEC) method were used to collect inflammatory cells from the same wounds at hour 6 or 24 post-surgery. The wound cells were stained by the May-Grünwald-Giemsa (MGG) -method and counted differentially. RESULTS: A significant difference was found between the 6 and 24 hour Cellstick specimen in the proportions of wound neutrophils (p = 0.007), lymphocytes (p = 0.02) and monocytes (p < 0.001). The differential counts of wound cells within each individual animal did not significantly differ from each other. Instead, a significant difference was found in the wound neutrophils (p = 0.001), lymphocytes (p = 0.04) and monocytes (p < 0.001) between the wounds of individual animals. The WEC method revealed the same significant differences in the wound cell proportions. CONCLUSIONS: The Cellstick and the WEC method gave analogous results with equal variances from the incision wounds for up to at least 24 hours after injury.

Duration of surgery and patient age affect wound healing in children.

The migration of inflammatory cells into a wound and their subsequent changes during wound healing are essential for the complex processes of tissue repair to occur. The aim of this work was to investigate the number of wound leukocytes during early wound healing at different time periods in children. Wound cells of 184 children aged 0-15 years, operated on for a benign disease in the lower abdominal region, were harvested with the Cellstick(R) device. The device was removed from the wound at 3, 6, or 24 hours after surgery and differential cell counts were performed. The cellular patterns were significantly influenced by the age of the patient and by the duration of the surgery. The proportions of neutrophils, lymphocytes, and monocytes changed significantly from 3-24 hours. Our results suggest that there is a distinct time-related change in the pattern of inflammatory cells in the early phase of wound healing in children. This pattern is affected by the age of the child and by the duration of the surgery.

Correlation between interleukin-6 and matrix metalloproteinase-9 in early wound healing in children.

Interleukin-6 and matrix metalloproteinase-9 concentrations in the wound fluid and their associations to cellular changes were determined in early wound healing. Wound healing of 75 children who underwent elective operations was studied with the Cellstick(R) device, which was inserted into the wound at the end of the operation and removed 3 or 24 hours post-wounding. Differential counts of the wound cells and interleukin-6 and matrix metalloproteinase-9 concentrations in the wound fluid were analyzed. Interleukin-6 and the matrix metalloproteinase-9 concentrations increased in parallel (r = 0.81). The proportion of wound neutrophils increased (p < 0.0001) and lymphocytes decreased (p < 0. 0001) between the observation times. The number of wound neutrophils had a strong correlation with both interleukin-6 (adjusted R2 = 0.41, p < 0.0001) and matrix metalloproteinase-9 concentrations (adjusted R2 = 0.37, p < 0.0001). The extracellular matrix degradation process of the early wound healing seems to be closely linked to the inflammatory response. Both of these measured markers are associated significantly with the neutrophil proportion in the wound.

Cytokines and cardiomyocyte death.

Cytokines have been associated with the pathogenesis of acute coronary syndromes and chronic heart failure (CHF), which are both associated with cardiomyocyte loss. In CHF, increased serum concentrations of proinflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha) and also soluble TNF receptor have been found. Both TNF and Fas-ligand have been able to induce programmed cell death (apoptosis) of cardiomyocytes in various experimental studies. In ischaemic conditions of the heart, increased serum levels of soluble Fas receptor have been found. The proinflammatory cytokines interleukin 1 (IL-1), IL-2 and interferon-gamma can induce TNF production from target cells, including myocytes. TNF and some other cytokines are able to induce nitric oxide production, which depresses cardiac function and can induce apoptosis. However, anti-inflammatory cytokines such as IL-10, IL-4 and IL-13, secreted by T-helper type 2 lymphocytes and other cells, inhibit the production of proinflammatory cytokines. Preliminary studies suggest that cardiotrophin-1, produced by cardiomyocytes, is able to inhibit cytokine-induced cardiomyocyte apoptosis in vitro. As growth hormone is able to inhibit the production of proinflammatory cytokines in many cell types, it may also play an important role in the regulation of apoptosis induced by these cytokines. When the cytokine-induced pathways leading to altered gene expression of cardiomyocytes are understood, this knowledge may aid in the development of drugs that prevent progressive cardiomyocyte loss, in particular by inhibiting cytokine-induced apoptosis.

Blood transfusion with autologous and leukocyte-depleted or standard allogeneic red blood cells and the immune response to open heart surgery.

Allogeneic blood transfusions have been associated with impaired outcome in surgical patients. This effect may be mediated by leukocytes. Animal experiments have shown that at least some of the effect can be modified by removal of leukocytes from transfused blood. Therefore, we compared the effects of autologous + leukocyte-depleted against standard allogeneic red blood cell transfusion on postoperative immunosuppression in 24 men undergoing coronary artery bypass surgery. In the autologous + leukocyte-depleted red blood cell transfusion group, patients received 800 +/- 200 mL (mean +/- SD) autologous blood and 2.2 +/- 2.0 units (mean +/- SD) of leukocyte-depleted saline-adenine-glucose-mannitol (SAGM) red blood cells. In the standard red blood cell transfusion group, patients were transfused with 5.5 +/- 1.4 units (mean +/- SD) of SAGM red blood cells. Leukocyte and differential counts; percentages of lymphocyte subpopulations (CD3-, CD4-, CD8-, CD16-, CD20-, CD25-, and B5-positive lymphocytes) and monocytes (CD14); phytohemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; unstimulated and pokeweed mitogen-stimulated production of IgG, IgM, or IgA; and serum interleukin-6, interleukin-1 beta, and serum C-reactive protein concentrations were measured preoperatively and on postoperative Days 1, 7, and 21. Significant changes were seen in these variables, but there were no differences between the groups. Three of the 12 patients in the allogeneic leukocyte-containing red blood transfusion group became human lymphocyte antigen (HLA) alloimmunized. No infections or other complications occurred in any patients. We conclude that HLA alloimmunization was the only effect that could be modified by use of autologous blood.

Activated monocytes induce arthritis-associated changes in mitochondria of cultured synovial fibroblasts.

We have recently shown that synovial fibroblasts cultured from patients with reactive or rheumatoid arthritis exhibit increased autofluorescence when compared with controls. Morphological studies suggested that this increase was related to the anomalous structure of mitochondria in cells cultured from rheumatoid or non-rheumatoid inflammatory synovial tissue. The present study describes attempts to find an explanation for these observations. The effects of conditioned media of cultured mononuclear cells were tested on normal synovial fibroblasts. Conditioned media of monocytes stimulated with lipopolysaccharide or poly-IC induced an increase in the cellular autofluorescence and changes in the morphology of mitochondria in normal fibroblasts. These changes were indistinguishable from those seen in synovial fibroblasts cultured from various arthritides. Indomethacin or gold salts did not abolish the effects of monocyte-conditioned media. Abnormal mitochondria could not be induced in the presence of cycloheximide. This study describes a new aspect of monocyte-fibroblast interactions during rheumatoid and non-rheumatoid inflammation of synovial tissue.