Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case–control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35–64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 μg/d respectively. Approximately, 32 % of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Low frequency of human papillomavirus detection in prostate tissue from individuals from Northern Brazil

The presence of human papillomavirus (HPV) was evaluated in 65 samples of prostate tumours and six samples of prostates with benign prostatic hyperplasia from individuals from Northern Brazil. We used a highly sensitive test, the Linear Array HPV Genotyping Test, to detect 37 high and low-risk HPV types. In this study, only 3% of tumour samples showed HPV infection. Our findings support the conclusion that, despite the high incidence of HPV infection in the geographic regions studied, HPV was not associated with a higher risk of prostate cancer. To our knowledge, this is the first study evaluating the frequency of HPV detection in prostatic tissue of individuals from Brazil.

Mutant prevention concentrations of fluoroquinolones for Enterobacteriaceae expressing the plasmid-carried quinolone resistance determinant qnrA1.

The influence of qnrA1 on the development of quinolone resistance in Enterobacteriaceae was evaluated by using the mutant prevention concentration parameter. The expression of qnrA1 considerably increased the mutant prevention concentration compared to strains without this gene. In the presence of qnrA1, mutations in gyrA and parC genes were easily selected to produce high levels of quinolone resistance.

A specific protein-enriched enteral formula decreases cortisolemia and improves plasma albumin and amino acid concentrations in elderly patients

Background: Old age is associated with an involuntary and progressive but physiological loss of muscle mass. The aim of this study was to evaluate the effects of exclusive consumption for 6 months of a protein-enriched enteral diet with a relatively high content of branched-chain amino acids on albuminemia, cortisolemia, plasma aminoacids, insulin resistance, and inflammation biomarkers in elderly patients. Methods: Thirty-two patients from the Clinical Nutrition Outpatient Unit at our hospital exclusively consumed a protein-enriched enteral diet for 6 months. Data were collected at baseline and at 3 and 6 months on anthropometric and biochemical parameters and on plasma concentrations of amino acids, cortisol,adrenocorticotropic hormone, urea, creatinine, insulin resistance, and inflammation biomarkers. Results: The percentage of patients with albumin concentration below normal cut-off values decreased from 18% to 0% by the end of the study. At 6 months, concentrations of total plasma (p = 0.008) and essential amino acids(p = 0.011), especially branched-chain amino acids (p = 0.031), were higher versus baseline values, whereas 3-methylhistidine (p = 0.001), cortisol (p = 0.001) and adrenocorticotropic hormone (p = 0.004) levels were lower. Conclusions: Regular intake of specific protein-enriched enteral formula increases plasma essential amino acids, especially branched-chain amino acids, and decreases cortisol and 3-methylhistidine, while plasma urea and creatinine remain unchanged.

Histological and histochemical evaluation of human oral mucosa constructs developed by tissue engineering

Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues is very common. In this context, tissue engineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we developed a new model of artificial oral mucosa generated by tissue engineering using a fibrin-agarose scaffold. For that purpose, we generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal oral mucosa using enzymatic treatments. Then we determined the viability of the cultured cells by electron probe quantitative X-ray microanalysis, and we demonstrated that most of the cells in the primary cultures were alive and had high K/Na ratios. Once cell viability was determined, we used the cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarose extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and the oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa.

Chagas disease, adipose tissue and the metabolic syndrome

Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor ³, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-α, TGF-β and CD4+ and acinar IFN-γ, TNF-α, IL-1β and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-β. Significant positive correlations were found between portal CD4+ and TNF-α, portal CD8+ and TGF-β, portal CD45+RO and TNF-α, acinar CD45+RO and IFN-γ and acinar CD57+ and TGF-β. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4+ T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

Cellular Derivatives and Efficacy in Wound and Scar Management

Biologicals have been used for decades in biopharmaceutical topical preparations. Because cellular therapies are rou-tinely used in the clinic they have gained significant attention. Different derivatives are possible from different cell and tissue sources, making the selection of cell types and establishment of consistent cell banks crucial steps in the initial whole-cell bioprocessing. Various cell and tissue types have been used in treatment of skin wounds including autolo-gous and allogenic skin cells, platelets, placenta and amniotic extracts from either human or animal sources. Experience with progenitor cells show that they may provide an interesting cell choice due to facility of out-scaling and known properties for wound healing without scar. Using defined animal cell lines to develop cell-free derivatives may provide initial starting material for pharmaceutical formulations that help in overall stability. Cell lines derived from ovine tis-sue (skin, muscle, connective tissue) can be developed in short periods of time and consistency of these cell lines was monitored by cellular life-span, protein concentrations, stability and activity. Each cell line had long culture periods up to 37 - 41 passages and protein measures for each cell line at passages 2 - 15 had only 1.4-fold maximal difference. Growth stimulation activity towards two target skin cell lines (GM01717 and CRL-1221; 40 year old human males) at concentrations ranging up to 6 μg/ml showed 2-3-fold (single extracts) and 3-7-fold (co-cultured extracts) increase. Proteins from co-culture remained stable up to 1 year in pharmaceutical preparations shown by separation on SDS- PAGE gels. Pharmaceutical cell-free preparations were used for veterinary and human wounds and burns. Cell lines and cell-free extracts can show remarkable consistency and stability for preparation of biopharmaceutical creams, moreover when cells are co-cultured, and have positive effects for tissue repair.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: Effects on leptin and TNF-alpha.

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Differential tissue tropism of Trypanosoma cruzi strains: an in vitro study

We have previously demonstrated selection favoring the JG strain of Trypanosoma cruziin hearts of BALB/c mice that were chronically infected with an equal mixture of the monoclonal JG strain and a clone of the Colombian strain, Col1.7G2. To evaluate whether cell invasion efficiency drives this selection, we infected primary cultures of BALB/c cardiomyocytes using these same T. cruzi populations. Contrary to expectation, Col1.7G2 parasites invaded heart cell cultures in higher numbers than JG parasites; however, intracellular multiplication of JG parasites was more efficient than that of Col1.7G2 parasites. This phenomenon was only observed for cardiomyocytes and not for cultured Vero cells. Double infections (Col1.7G2 + JG) showed similar results. Even though invasion might influence tissue selection, our data strongly suggest that intracellular development is important to determine parasite tissue tropism.

Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss.

Objective: To analyze the expression of peroxisome proliferator-activated receptor-γ1 and 2 (PPARγ1 and 2), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), and leptin in adipose tissue (AT) of obese women during weight loss following Roux-en-Y gastric bypass (RYGB) and to compare these levels with those obtained in AT of nonobese subjects. Methods: Gene expression was determined by real-time RT-PCR prior to surgery and at 3, 6, and 12 months after RYGB. Results: All obese patients lost weight, reaching a mean BMI of 29.3 ± 1.0 kg/m(2) at 1 year after surgery (-33.9 ± 1.5% of their initial body weight). In obese subjects leptin and 11βHSD1 were over-expressed, whereas PPARγ1 was expressed at lower levels compared to controls. After surgery, leptin and 11βHSD1 gene expression decreased, whereas PPARγ1 expression increased. At 12 months after RYGB, these 3 genes had reached levels similar to the controls. In contrast, PPARγ2 gene expression was not different between groups and types of tissue and remained unchanged during weight loss. We found a positive correlation between BMI and levels of gene expression of leptin and 11βHSD1. Conclusion: Gene expression of leptin, PPARγ1, and 11βHSD1 in AT is modified in human obesity. This default is completely corrected by RYGB. Copyright © 2012 S. Karger GmbH, Freiburg.