Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

4-Hydroxydibenzyl: a novel metabolite from the human gut microbiota after consuming resveratrol.

Resveratrol (RSV) was known to be metabolised by the gut microbiota to dihydroresveratrol, lunularin (LUNU), and (or) 3,4'-dihydroxy-trans-stilbene (DHST). We describe here for the first time that LUNU can be further dehydroxylated, but only at the 3-position, to yield 4-hydroxydibenzyl, a novel metabolite found in human urine after RSV intake in 41 out of 59 healthy participants. In contrast, DHST was not further dehydroxylated, and thus, 4-hydroxy-trans-stilbene was not detected as a gut microbial metabolite of RSV. Faecal in vitro incubations confirmed the in vivo results.

Does the use of health technology assessment have an impact on the utilisation of health care resources? Evidence from two European countries.

OBJECTIVES: A centralised approach to health technology assessment (HTA) may facilitate optimal use of HTA resources. A regional approach may increase the chances of local implementation of recommendations. This study aimed to compare assessment procedures in England (centralised HTA approach) with Spain (regional HTA approach) discussing key challenges and opportunities from both approaches. METHODS: We compared technology assessments of anticancer medicines in the two jurisdictions from 2008 to 2015. To assess the implementation of HTA recommendations, we assessed trends in medicine usage using regression methods. We used IQVIA data, from 2011 to 2016, for a sample of 11 medicines. We used CatSalut data from Catalonia to assess the implementation of local recommendations. RESULTS: In England, 66 assessments were undertaken by the National Institute for Health and Care Excellence (NICE), using a standardised methodology. In Spain, there were 79 reports undertaken by a range of bodies using a shared process and coordinated through the GENESIS collaboration; the assessment methods used varied substantially. Overall, the recommendations in the two jurisdictions were similar. Regression analyses indicate that where there is a positive recommendation by HTA bodies, the usage of the medicine responds most strongly (p < 0.001) in Catalonia (4.892), followed by England (3.120) and Spain (1.693). CONCLUSIONS: This study suggests that medicine utilisation does respond to the positive recommendations of HTA bodies. However, if HTA capacity is organised primarily regionally, considerable effort may be required in coordination, to ensure consistent and rigorous assessments and adequate implementation of HTA findings.

Multiple Criteria Decision Analysis for HTA across four EU Member States: Piloting the Advance Value Framework.

Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results. The AVF was applied in the evaluation of three drugs for metastatic, castrate resistant, prostate cancer (abiraterone, cabazitaxel and enzalutamide) in the post-chemotherapy indication. Decision conferences were organised in four European countries in collaboration with their HTA or health insurance organisations by involving relevant assessors and experts: Sweden (TLV), Andalusia/Spain (AETSA), Poland (AOTMiT) and Belgium (INAMI-RIZIV). Participants' value preferences, including performance scoring and criteria weighting, were elicited through a facilitated decision-analysis modelling approach using the MACBETH technique. Between 6 and 11 criteria were included in each jurisdiction's value model, allocated across four criteria domains; Therapeutic Benefit criteria consistently ranked first in relative importance across all countries. Consistent drug rankings were observed in all settings, with enzalutamide generating the highest overall weighted preference value (WPV) score, followed by abiraterone and cabazitaxel. Dividing drugs' overall WPV scores by their costs produced the lowest "cost per unit of value" for enzalutamide, followed by abiraterone and cabazitaxel. These results come in contrast with the actual country HTA recommendations and pricing decisions. Overall, although some differences in value preferences were observed between countries, drug rankings remained the same. The MCDA methodology employed could act as a decision support tool in HTA, due to the transparency in the construction of value preferences in a collaborative manner.

Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammation.

Urolithin A (Uro-A) is an anti-inflammatory and cancer chemopreventive metabolite produced by the gut microbiota from the polyphenol ellagic acid. However, in vivo conjugation of Uro-A to Uro-A glucuronide (Uro-A glur) dramatically hampers its activity. We describe here for the first time the tissue deconjugation of Uro-A glur to Uro-A after lipopolysaccharide (LPS)-induced inflammation, which could explain the systemic in vivo activity of free Uro-A in microenvironments subjected to inflammatory stimuli.

Re-examining the role of the gut microbiota in the conversion of the lipid-lowering statin monacolin K (lovastatin) into its active ß-hydroxy acid metabolite.

Monacolin K (MK, lovastatin), a naturally occurring statin, only exerts lipid-lowering effects in its active ß-hydroxy acid form (MKA). This activation was thought to be mediated by the gut microbiota (GM). We report here for the first time that the GM does not convert MK into MKA (a spontaneous pH-dependent conversion) but catabolises MKA. The GM might hamper the lipid-lowering effects by degrading the active metabolite MKA.

Economic evaluation of the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) from the national payer perspective: introduction of a new treatment to the patient journey. A simulation of three European countries.

Background: The aim of this study was to develop a spending predictor model to evaluate the direct costs associated with the management of ABSSSIs from the National health-care provider's perspective of Italy, Romania, and Spain. Methodology: A decision-analytic model was developed to evaluate the diagnostic and clinical pathways of hospitalized ABSSSI patients based on scientific guidelines and real-world data. A Standard of Care (SoC) scenario was compared with a dalbavancin scenario in which the patients could be discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases (i.e., hospital information system). A probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWA) were performed. Results: Overall, the model estimated an average annual number of patients with ABSSSIs of approximately 50,000 in Italy, Spain, and Romania. On average, the introduction of dalbavancin reduced the length of stay by 3.3 days per ABSSSI patient. From an economic perspective, dalbavancin did not incur any additional cost from the National Healthcare perspective, and the results were consistent among the countries. The PSA and OWA demonstrated the robustness of these results. Conclusion: This model represents a useful tool for policymakers by providing information regarding the economic and organizational consequences of an early discharge approach in ABSSSI management.

The gut microbiota urolithin metabotypes revisited: the human metabolism of ellagic acid is mainly determined by aging.

Understanding individuals' response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n = 839) that aging is the main factor that determines the gut microbiota involved in the ellagic acid-ellagitannin metabolism (urolithin metabotypes), with potential consequences for human health.

Consumption of pomegranate decreases plasma lipopolysaccharide-binding protein levels, a marker of metabolic endotoxemia, in patients with newly diagnosed colorectal cancer: a randomized controlled clinical trial.

Gut microbiota dysbiosis alters the intestinal barrier function, increases plasma lipopolysaccharide (LPS) levels, which promotes endotoxemia, and contributes to the onset and development of colorectal cancer (CRC). We report here for the first time the reduction of plasma LPS-binding protein (LBP) levels, a marker of endotoxemia, after pomegranate consumption in newly diagnosed CRC patients.

Donors Older Than 75 Years Do Not Influence the Appearance of Biliary Complications After Liver Transplantation.

BACKGROUND: In recent years, several studies have shown that the age of the donor may be related to an increase in the occurrence of biliary complications (BCs), which remain the main cause of morbidity after liver transplantation. This study analyzed the type and management of these BCs, the impact of BCs on graft and patient survival rates, and the influence of some characteristics of donors and recipients on BC appearance in patients transplanted with donors 75 years of age or older. PATIENTS AND METHODS: From 2003 to 2016, 100 liver transplantations with donors 75 years of age or older (15.6%) were performed in our hospital. The data were compared with a control group of 400 patients with younger donors (case-control 1:4 per chronology). RESULTS: The BC rate in the group of patients transplanted with organs from elderly donors was 18%, compared to 21.5% in the control group. Specifically, in the immediate post-transplantation period, 14% of the elderly donor group and 13.8% of the control group presented some BCs, with no statistically significant differences in the incidence, type, and treatment of BCs between the two groups. The occurrence of BCs was not a factor associated with graft and patient survival rates. In the global population, donor death by cerebral vascular accident and male donors have influenced the occurrence of BCs. CONCLUSIONS: The advanced age of the donor has not influenced BC rates after transplantation.

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid.

The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B2), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.

Mediterranean and western dietary patterns are related to markers of testicular function among healthy men.

STUDY QUESTION: Are there any associations of dietary patterns with semen quality, reproductive hormone levels, and testicular volume, as markers of testicular function? SUMMARY ANSWER: These results suggest that traditional Mediterranean diets may have a positive impact on male reproductive potential. WHAT IS KNOWN ALREADY: The Mediterranean diet has been related to lower risk of multiple chronic diseases, but its effects on reproduction potential are unclear. STUDY DESIGN, SIZE, DURATION: Cross-sectional sample of 215 male university students recruited from October 2010 to November 2011 in Murcia Region (Spain). PARTICIPANTS/MATERIALS, SETTING, METHODS: Two hundred and nine healthy men aged 18-23 years were finally included in this analysis. Diet was assessed using a validated food frequency questionnaire, and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns with semen quality parameters, reproductive hormone levels and testicular volume adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: We identified two dietary patterns: a Mediterranean (characterized by high intakes of vegetables, fruits and seafood) and a Western pattern (characterized by high intakes of processed meats, French fries and snacks). The Mediterranean pattern was positively associated with total sperm count (P, trend = 0.04). The Western pattern was positively related to the percentage of morphologically normal sperm (P, trend = 0.008). We found an inverse association between adherence to the Western pattern and sperm concentration among overweight or obese men (P, trend = 0.04). LIMITATIONS, REASONS FOR CAUTION: As with all cross-sectional studies, causal inference is limited. However, participants were blinded to the study outcomes thus reducing the potential influenced their report of diet. Although we adjusted for a large number of known and suspected confounders, we cannot exclude the possibility of residual confounding or chance findings. WIDER IMPLICATIONS OF THE FINDINGS: This study was carried out on healthy and young men, so it is difficult to predict whether and how the observed differences in semen quality translate into reproductive success for men in couples trying to conceive. These results suggest that traditional Mediterranean diets may have a positive impact on male reproductive potential.

Longer anogenital distance is associated with higher testosterone levels in women: a cross-sectional study.

OBJECTIVE: Animal models have suggested that anogenital distance (AGD) at birth reflects androgen levels during in utero development and predicts adult AGD. A recent study showed an association between perineal length and androgen levels in men, suggesting that serum testosterone levels in adulthood will depend on factors involved during the fetal period. The aim of this study is to assess the relationship between AGD measures and reproductive hormone levels in women. DESIGN: Cross-sectional study conducted between February and November 2011. SETTING: University-affiliated fertility clinics. POPULATION: 100 young college students. METHODS: Physical and gynaecological examinations were conducted on university students. All participants provided a blood sample for determination of reproductive hormones and completed an epidemiological questionnaire on lifestyles and gynaecological history. We used multiple linear regression analysis to examine the associations between perineal length measurements [anus-fourchette (AGDAF ) and anus-clitoris (AGDAC )] and reproductive hormone levels. MAIN OUTCOME MEASURES: Anogenital distance measurements and reproductive hormone levels. RESULTS: In the multiple linear regression analyses, AGDAF was positively associated with serum testosterone levels. Serum testosterone increased 0.06 ng/ml (95%CI 0.01, 0.10; P = 0.02) for each 1-cm increase in AGDAF . None of the measurements was associated with other reproductive hormones. CONCLUSIONS: Anogenital distance may predict normal reproductive development in women, and may be a new tool of potential clinical interest to evaluate ovarian function. Our results suggest that serum testosterone levels in adulthood may depend on factors operating in the prenatal period.

Bioavailability of phenolics from an oleuropein-rich olive (Olea europaea) leaf extract and its acute effect on plasma antioxidant status: comparison between pre- and postmenopausal women.

PURPOSE: Preclinical studies suggest a potential protective effect of oleuropein in osteoporosis, and one of the proposed mechanisms is the modulation of the oxidative stress. Oleuropein bioavailability and its effect on antioxidant status in pre- and postmenopausal women are unknown. The aim of the present study was to investigate the oral bioavailability of an olive leaf extract rich in oleuropein (40 %) and its effect on antioxidant status in postmenopausal women compared to premenopausal women. METHODS: Premenopausal (n = 8) and postmenopausal women (n = 8) received 250 mg of olive leaf extract, blood samples (t = 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 h) were taken, and 24-h urine divided into five fractions was collected. Olive-leaf-extract-derived metabolites were analyzed in plasma and urine by HPLC-ESI-QTOF and UPLC-ESI-QqQ, and pharmacokinetics parameters were determined. Ferric reducing antioxidant ability and malondialdehyde levels were measured in plasma. RESULTS: Plasma levels of hydroxytyrosol glucuronide, hydroxytyrosol sulfate, oleuropein aglycon glucuronide and oleuropein aglycon derivative 1 were higher in postmenopausal women. MDA levels were significantly decreased (32%) in postmenopausal women and inversely correlated with hydroxytyrosol sulfate levels. Postmenopausal women excreted less sulfated metabolites in urine than premenopausal women. CONCLUSIONS: Our results suggest that postmenopausal women could be a target population for the intake of olive phenolics in order to prevent age-related and oxidative stress-related processes such as osteoporosis.

Incentives for market penetration of biosimilars in Belgium and in five European countries.

Biosimilars are products similar to a biological already authorized and no longer protected by a patent. As the biological product, they contain a biological substance produced by or derived from a living organism. Alike with generics, biosimilars are potential tool to ensure savings for health systems. The current lack of market penetration of biosimilars may be seen by national authorities as a lost opportunity in terms of cost- containment. The objective of this paper is therefore to analyze the current situation in Belgium and to identify potential measures to stimulate biosimilar uptake in Belgium through an analysis of the experience in five European countries: France, Germany, The Netherlands, Spain and Sweden. This international comparison was performed using a two steps analysis: a structured review of the literature followed by a validation from experts in each country. Potential incentives and constraints were identified, i.e., prescription quotas/target, clinical guidelines, primary substitution, reference price system, fixed payment and public tendering. However, the literature reviewed provided little evaluation of the effectiveness of these policies in terms of biosimilar uptake or potential savings. The impact of these policies on biosimilar related savings is currently based on expectation and assumptions. Such kind of studies is therefore essential in the future.

Personalised medicine as a challenge for public pricing and reimbursement authorities ­ A survey among 27 European countries on the example of trastuzumab.

OBJECTIVES: To survey possible funding models and pricing practices as well as prices for the treatment package of trastuzumab and its accompanying diagnostic test in European countries, as an example of personalised medicines. METHODS: Qualitative descriptive data on national pharmaceutical pricing and funding policies applied to trastuzumab and its accompanying diagnostic test were obtained from a survey among competent authorities from 27 European countries as of August 2011. Further, price data (for the years 2005-2013) of trastuzumab in the respective European countries were surveyed and analysed. RESULTS: In 2011, testing and treatment mainly took place in hospitals or in specific day-care ambulatory clinics. In the European countries either both trastuzumab and the accompanying diagnostic test were funded from hospital budgets (n = 13) or only medicines were funded from the third party payers such social insurances and the test from hospital budgets (n = 14). Neither combined funding of both medicine and diagnostic test by third party payers was identified in the surveyed countries nor did the respondents from the competent authorities identify any managed entry agreements. National pricing procedures are different for trastuzumab versus its diagnostic test, as most countries apply price control policies for trastuzumab but have free pricing for the diagnostic test. The ex-factory price is, on average, €609 per 150 mg vial with powder in 2013; in nine countries the price of trastuzumab went down from 2005 till 2013. CONCLUSION: The example of trastuzumab and its accompanying diagnostic test highlights some problems of the interface between different funding streams (out-patient and hospital) but also with regard to the interface between the medicine applied in combination with a medical device. The findings suggest a need for further developing and refining policy options to address the identified interface issues.

Urolithins, ellagitannin metabolites produced by colon microbiota, inhibit Quorum Sensing in Yersinia enterocolitica: Phenotypic response and associated molecular changes.

The mammalian enteropathogen Yersinia enterocolitica produces two main N-acylhomoserine lactones (AHLs) involved in Quorum Sensing (QS)-mediated infection processes, such as virulence, biofilm maturation and motility. Ellagitannin (ET)-rich fruits exhibit anti-QS activity but in vivo effects against intestinal pathogens may be associated to the ETs gut microbiota derived metabolites, urolithin-A (Uro-A) and urolithin-B (Uro-B). In this work we show that urolithins, at concentrations achievable in the intestine through the diet, reduce the levels of N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL) in Y. enterocolitica and inhibit QS-associated biofilm maturation and swimming motility. These inhibitory effects were not associated to downregulation of the expression of some of the genes involved in the synthesis of AHLs (yenI and yenR) or in motility (flhDC, fliA, fleB). Our results suggest that urolithins may exert antipathogenic effects in the gut against Y. enterocolitica and highlight the need to investigate the antipathogenic in vivo properties of plant derived metabolites.

Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation.

PURPOSE: The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis. METHODS: Sprague-Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1ß and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration. RESULTS: Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma. CONCLUSION: These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.

Effect of mediterranean forest parasite with Curculio sp. on nutritional value of acorn for Iberian pig feeding and fat characteristics.

Sixteen Iberian barrows of the same age with an average initial live weight of 100.1kg were randomly distributed in two groups of eight pigs each. One group was fed healthy acorns and the other group received acorns infested of Curculio sp. The subcutaneous backfat from pigs fed healthy acorns had higher C18:1n-9, MUFA and C20:5n-3 and lower C18:0 and SFA proportions than that from the pigs fed acorns infested with Curculio. The consumption of acorns infested with Curculio sp. led to a reduction of C18:1n-9, MUFA, C18:2n-6, C18:3n-3, C22:5n-3 and PUFA proportions in neutral lipids from Longissimus dorsi muscle with respect to consumption of healthy acorns, whereas in polar lipids it produced a reduction in C18:1n-9, MUFA and C18:4n-3 proportions and an increase in C18:2n-6, C20:4n-6, n-6 and C20:5n-3 proportions and of n-6/n-3 ratio with respect to the healthy acorns consumption. The pigs fed healthy acorns had higher intramuscular fat percentage in Longissimus dorsi than pigs fed with acorns infested with Curculio (9.95 vs 7.09% SEM=0.60).

Transcriptional changes in human Caco-2 colon cancer cells following exposure to a recurrent non-toxic dose of polyphenol-rich chokeberry juice.

Berries and red fruits are important dietary sources of polyphenols [1]. In vitro and animal studies have demonstrated the bioavailability and the anti-proliferative and anticarcinogenic properties of these fruits or of their phenolic components [2, 3]. Consumption of berries may contribute to the reduction of colon cancer by mechanisms not yet understood. Gene expression analysis using microarrays allows for a more comprehensive study of the possible molecular mechanisms by which food or food components may prevent certain cancers of the gastrointestinal tract [4]. The aim of this research is to investigate the anti-proliferative effects of a polyphenol-rich berry juice on a human model of colon cancer cells and its association to transcriptional changes in relation to colon cancer.