Dietary fat influences Ia antigen expression and immune cell populations in the murine peritoneum and spleen.

Peritoneal cells (PEC) and splenocytes were obtained from Listeria monocytogene (LM)-infected or noninfected mice fed a 20% fat diet rich in either (n-3) polyunsaturated fatty acids [(n-3) PUFA diet], linoleate [(n-6) PUFA diet], oleate (MONO diet), or saturated fatty acids (SAT diet) for 6 wk and were assessed for T cells, B cells, macrophages and Ia expression by flow cytometric analysis. In the peritoneum of noninfected mice, dietary fat did not affect total cell yield or the percentage of B cells, macrophages or Ia+ cells, but the (n-3) PUFA-fed group had a greater percentage of T cells than did the other groups. Among the LM-infected mice, the (n-3) PUFA-fed group generally had the highest percentage of B cells and the lowest percentages of T cells, macrophages and Ia+ cells in the peritoneum. Listeria monocytogene infection elevated peritoneal T cell numbers in all mice except the (n-3) PUFA-fed group. The density of Ia molecules on PEC was 40% lower in mice fed the (n-3) PUFA diet. In the spleen, dietary fat also influenced the immune cell populations and Ia+ cells. Two-color staining of spleen cells revealed that Ia+ splenocytes were predominately B cells. These data demonstrate that dietary fats influence Ia expression and immune cell populations and that the effects observed in one immune tissue or cell type may not be readily extrapolated to others.     

Source of hydrogen peroxide and of chemiluminescence observed in activated human platelet preparations

Human platelet suspensions can be observed to produce small amounts of H2O2 (0.04 nmoles H2O2/min/2.5 X 10(5) cells/cu mm) and measurable chemiluminescence when exposed to target particles for phagocytosis, such as latex spherules. Both H2O2 production and chemiluminescence are characteristic of phagocytosing polymorphonuclear leukocytes (PMN) and analysis of the purified platelets indicates contamination by PMN at the level of 0.2%. The amount of H2O2 produced and the chemiluminescence observed can be duplicated by adding latex spheres to a preparation of PMN at a concentration equivalent to the contaminant in the platelet preparations. We conclude that the H2O2 produced and chemiluminescence observed from activated platelets is due to the presence of small amounts of contaminating PMN. These studies emphasize the importance of controlling for PMN contamination in studies of platelet biochemistry and physiology.     

Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials

The majority of evidence suggests that n-6 polyunsaturated fatty acids, including linoleic acid (LA), reduce the risk of cardiovascular disease as reflected by current dietary recommendations. However, concern has been expressed that a high intake of dietary n-6 polyunsaturated fatty acid contributes to excess chronic inflammation, primarily by prompting the synthesis of proinflammatory eicosanoids derived from arachidonic acid and/or inhibiting the synthesis of anti-inflammatory eicosanoids from eicosapentaenoic and/or docosahexaenoic acids. A systematic review of randomized controlled trials that permitted the assessment of dietary LA on biologic markers of chronic inflammation among healthy noninfant populations was conducted to examine this concern. A search of the English- and non-English-language literature using MEDLINE, the Cochrane Controlled Trials Register, and EMBASE was conducted to identify relevant articles. Fifteen studies (eight parallel and seven crossover) met inclusion criteria. None of the studies reported significant findings for a wide variety of inflammatory markers, including C-reactive protein, fibrinogen, plasminogen activator inhibitor type 1, cytokines, soluble vascular adhesion molecules, or tumor necrosis factor-α. The only significant outcome measures reported for higher LA intakes were greater excretion of prostaglandin E2 and lower excretion of 2,3-dinor-thromboxane B(2) in one study and higher excretion of tetranorprostanedioic acid in another. However, the authors of those studies both observed that these effects were not an indication of increased inflammation. We conclude that virtually no evidence is available from randomized, controlled intervention studies among healthy, noninfant human beings to show that addition of LA to the diet increases the concentration of inflammatory markers.     

Predicting individual outcomes after radical cystectomy: an external validation of current nomograms

Study Type – Prognosis (outcomes research)
Level of Evidence 2c

OBJECTIVE

To determine whether published nomograms, i.e. The International Bladder Cancer Nomogram Consortium (IBCNC) and the Bladder Cancer Research Consortium (BCRC) statistical models for predicting disease recurrence and survival of patients after radical cystectomy, are feasible for routine use in intermediate‐volume institutions in Europe, as although these nomograms had high accuracy by internal validation tests, they stem from high‐volume centres and have not been validated elsewhere and thus their general applicability remains unproven.

PATIENTS AND METHODS

We externally validated the published nomograms. Information about treatments, pathological details, and recurrence and survival status was retrospectively collected from 246 patients. The expected survival according to the nomograms was calculated. The predictive accuracy of the proposed models was calculated by Harrell’s concordance indices. To assess the independent prognostic value of the variables proposed by IBCNC and BCRC, stepwise multivariable Cox regressions based on Akaike’s Information Criterion (AIC) for the different endpoints were used. A best model for prediction was created on the basis of our data.

RESULTS

The IBCNC and the BCRC nomograms showed an improvement in the predictive accuracy of recurrence, all‐cause and bladder‐cancer‐specific survival after radical cystectomy of up to 4% compared to Tumour‐Node‐Metastasis stage‐based predictions. According to the calculated AIC values for the different models, all nomograms performed better than the TNM classification.

CONCLUSIONS

The BCRC and IBCNC nomograms provided accurate predictions when they were applied to an external cohort of patients from low‐ to intermediate‐volume centres. The prediction of recurrence and survival based on the addressed nomograms is better than TNM stage‐based prediction. The application of such nomograms can be supported on a sound basis, but further amendments are warranted.     

Prognostic Role of Lymphovascular Invasion in Patients with Urothelial Carcinoma of the Upper Urinary Tract: An International Validation Study

Background

Lymphovascular invasion (LVI) identified following pathologic slide review has been shown to be an independent predictor of recurrence-free survival (RFS) and cancer-specific survival (CSS) in a multicenter series of patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). However, the validity of LVI in everyday practice, where pathologic re-review of all slides is uncommon, has not been assessed.

Objective

Our aim was to evaluate the prognostic role of LVI in an international cohort of patients treated with RNU for UTUC without pathologic slide review.

Design, setting, and participants

Data from 762 patients treated with RNU for UTUC without neoadjuvant chemotherapy were collected at nine centers located in Europe, Asia, and Canada.

Measurements

We evaluated patients’ characteristics, RFS, and CSS.

Results and limitations

LVI was present in 148 patients (19.4%). At a median follow-up of 34 mo, 23.5% of the patients developed disease recurrence and 19.8% died of UTUC. The 5-yr RFS and CSS rates were 79.3% and 82.1%, respectively, in the absence of LVI compared with 45.1% and 45.8%, respectively, in the presence of LVI (p values <0.0001). On multivariable Cox regression analyses, LVI was an independent predictor of RFS (hazard ratio [HR]: 3.3; p = 0.005) and CSS (HR: 5.9; p < 0.0001). Similarly, among patients with pN0/Nx disease, LVI was an independent predictor of RFS (HR: 2.1; p = 0.001) and CSS (HR: 2.3; p < 0.0001).

Conclusions

In a large multicenter series of patients treated with RNU for UTUC and for which no pathologic slide review was performed, LVI was present in approximately 20% and was an independent predictor of both RFS and CSS. LVI status should always be included in the pathologic report of RNU specimens, and patients with LVI should be considered for adjuvant therapy studies.     

Erythrocyte membrane phospholipid polyunsaturated fatty acids are related to plasma C-reactive protein and adiponectin in middle-aged German women and men

Purpose  

Modulation of circulating inflammatory markers and adiponectin may link PUFA to risk of diabetes and cardiovascular diseases. We investigated erythrocyte n-6 and n-3 PUFA in relation to plasma C-reactive protein (CRP) and adiponectin, and whether the Pro12Ala polymorphism in the PPARγ2 gene (PPARG2) modified these associations.     

A polymorphism in the gene encoding AdipoR1 affects olfactory recognition

Polymorphisms in the gene encoding adiponectin receptor 1 (AdipoR1) are associated with insulin resistance, fatty liver, increased risk for type 2 diabetes and cardiovascular disease. AdipoR1 is expressed in the central nervous system and in the olfactory mucosa of mice and humans. We therefore hypothesized that a common polymorphism in AdipoR1 might alter olfactory function. We investigated a group of 222 healthy subjects (male: n = 147, female: n = 75) for olfactory recognition, and genotyped them for the polymorphism rs6666089 in the human AdipoR1 gene. This polymorphism has been previously shown to be associated with insulin resistance. Olfactory recognition was tested using standardized sniffing sticks, and parameters of glucose metabolism and serum adiponectin levels were assessed. We found a significant olfactory impairment in carriers of the AdipoR1 polymorphism rs6666089 (olfactory recognition: GG: 89.4 ± 1.2%, GA: 86.9 ± 1.4%, AA: 77.2 ± 4.8%, additive model, P = 0.0004, adjusted for age). Adiponectin levels had no impact on olfactory recognition. Fasting plasma glucose, fasting plasma insulin, body mass index and HbA1c did not differ between the genotype groups. In conclusion, the presence of a genetic variation in AdipoR1 is associated with decreased olfactory recognition in healthy subjects. Adiponectin signalling may have an important role in olfactory function and regulation of appetite.