Search

Background/Objectives: A general lack of studies comparing the effect of both dynapenic abdominal obesity and sarcopenic obesity on worsening disability and hospitalization risk should be recognized. The aim of the current study was to evaluate, with a 5.5-year follow-up, the prognostic value of sarcopenic obesity and dynapenic abdominal obesity definitions on worsening disability and hospitalization risk in a sample of older adults. Subjects/Methods: In 177 women and 97 men aged 68-78 years, the following outcomes were evaluated at baseline: appendicular skeletal muscle mass (ASMM), percent fat mass (FM%), leg isometric strength, body mass index (BMI), lipid profile, vitamin D3, albumin, fibrinogen, glycemia, physical activity level, income, smoking status, and comorbidities. The rate of reported disabilities and hospitalization were also assessed at baseline, 1, 2, 3, and 5.5-years follow-up. The study population was classified into: (i) non-sarcopenic/obese (NS/O), sarcopenic/non-obese (S/NO), sarcopenic/obese (S/O), non-sarcopenic/non-obese (NS/NO, reference category) according to relative ASMM/FM% tertiles; (ii) non-dynapenic/abdominal obese (ND/AO), dynapenic/non-abdominal obese (D/NAO), dynapenic/abdominal obese (D/AO), non-dynapenic/non-abdominal obese (ND/NAO, reference category) according to muscle strength/waist circumference tertiles. Results: The prevalence of D/AO and S/O was 12.0 and 8.0%, respectively. Only 2 subjects were both D/NAO and S/O (0.8%). D/NAO subjects showed a worsening disability risk of 1.69 times (95% CI: 1.11-2.57), ND/AO subjects showed a 2-fold increased risk (95% CI: 1.34-2.98), while being D/AO more than trebled the risk, even after adjustment for confounding factors (HR: 3.39, 95%; CI: 1.91-6.02). By dividing the study population according to the relative ASMM/FM% tertiles, no groups showed an increased risk of worsening disability. The hospitalization risk, even after adjustment for potential confounders, was 1.84 (95% CI: 1.06-3.19) for D/AO. Dividing the study population according to the relative ASMM/FM% tertiles, no groups showed increased risk of hospitalization. Conclusions: Our results showed that dynapenic abdominal obesity and sarcopenic obesity seem to indicate two distinct phenotypes associated with different health risk profiles. The distribution of participants in waist circumference and muscle strength tertiles allowed for a more accurate risk stratification for worsening disability and hospitalization., (Copyright © 2020 Rossi, Urbani, Fantin, Nori, Brandimarte, Martini, Zoico, Mazzali, Babbanini, Muollo and Zamboni.)

Background: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1 / 2 mutations, which indicate a relevant genetic role., Methods: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants' electronic clinical records were reviewed. Patients' data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1 / 2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives., Results: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1 / 2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers., Discussion: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 by S. Karger AG, Basel.)

Introduction . Male breast cancer (MBC) is a rare disease, whose main risk factor is genetic vulnerability. Despite care of men with MBC is modeled on care of women, men's experiences with the disease and concerns related to the status of genetic mutation carrier are unique. So far, little is known concerning the psychological impact in BRCA1/2 testing, especially with regard to specific subset of individuals, such as male subjects and the elderly., Methods: We assessed self-reported anxiety and depression levels in 26 male subjects presenting at Unit of Breast Surgery in Breast Unit of AOUI Verona (MBC patients, n  = 7; high-risk unaffected subjects, n  = 7; high-risk unaffected subjects., Results: Among the 17 unaffected men tested, 7 (41%) received a positive test (either BRCA1 or BRCA2 pathogenic variant) and 10 (59%) a negative test. Of the 9 MBC patients tested, only one subject received a positive test result. No significant differences were observed in mean scores, mean change from baseline to follow-up, either for those with T + or T- test results. Discussion . Genetic testing for BRCA1/2 mutation was not associated in our sample with increased level of psychological distress as measured with HADS in a short-term evaluation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 F. Pellini et al.)

Background Aims: In 2016, specifications for both pre-cryopreserved and post-thawed cord blood were defined in the sixth edition of NetCord Foundation for the Accreditation of Cellular Therapy (FACT) Standards for Cord Blood Banks. However, for several experts, harmonization regarding flow cytometry analysis performed on post-thawed samples is still a concern. A multicenter study led by Héma-Québec aimed to provide scientific data to support the cord blood accreditation bodies such as NetCord FACT in the revision of standards., Methods: Twelve cord blood units were processed for plasma and red cell reduction following standard operating procedures. Cord blood unit aliquots were shipped to eight participating centers under cryogenic conditions for analysis before and after standardization of protocol. Repeatability of stem cell count, measured pre- and post-intervention with the centers, was estimated using multilevel linear regression models with a heterogeneous compound symmetry correlation structure among repeated measures., Results: Excellent inter-center repeatability was reported by each participant regarding the viable CD34+ cells concentration, and a successful improvement effect of protocol standardization was also observed. However, we observed that better control over the critical parameters of the protocol did not have a significant effect on improving homogeneity in the enumeration of CD45+ cells., Conclusions: The current practice in cord blood selection should now also consider relying on post-thaw CD34+ concentration, providing that all cord blood banks or outsourcing laboratories in charge of the analysis of post-thaw CB samples take into account the consensual recommendations provided in this work and adhere to a good-quality management system., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2019 International Society for Cell and Gene Therapy. All rights reserved.)

Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, microglia cells are distributed throughout the brain and are constantly surveilling the central nervous system (CNS). In response to CNS injury, microglia quickly react by secreting a wide array of apoptotic molecules. Virgin olive oil (VOO) is universally recognized as a symbol of the Mediterranean diet. In the current study, using lipopolysaccharide (LPS)-stimulated BV2 microglia, the anti-inflammatory effects of VOO phenolic extracts from Moraiolo cultivar (MVOO-PE) were investigated. The results showed that low concentration of MVOO-PE prevented microglia cell death and attenuated the LPS-induced activation of toll-like receptor 4 (TLR4)/NOD-like receptor pyrin domain-containing-3 (NLRP3) signaling cascade. The levels of TLR4 and NF-kB were diminished, as well as NLRP3 inflammasome and interleukin-1β (IL-1β) production. Cyclooxygenase-2 (COX-2) isoenzyme and ionized calcium binding adaptor molecule 1 (Iba-1) inflammatory mediator were also reduced. By modulating the TLR4/NLRP3 axis, MVOO-PE pretreatment was able to significantly down-regulate the mRNA expression of inflammatory mediators and suppress the cytokine secretion. Finally, we showed protective effect of MVOO-PE in a transwell neuron-microglia co-culture system. In conclusion, these results suggest that MVOO-PE could exerts anti-inflammatory activity on brain cells and become a promising candidate for preventing several neuroinflammatory diseases.

Background: Consensus among dermatologists and rheumatologists in the diagnosis and assessment of musculoskeletal diseases in psoriasis (PsO) patients is needed. This study assesses characteristics of musculoskeletal pain in patients with PsO for the presence of psoriatic arthritis (PsA) and evaluation of a novel 16-item visual instrument (PsA-Disk)., Methods: Data were collected from eight dermatological/rheumatological centres across Italy. Patients with PsO completed PEST (Psoriasis Epidemiology Screening Tool) and PsA-Disk questionnaires during the first visit. A rheumatological visit was performed to confirm the presence of PsA. Both validity and reliability of PsA-Disk were assessed., Results: A total of 573 patients with PsO were examined at the first visit, and 120 (21%) were diagnosed with PsA. Patients with PsA compared with patients with PsO ( n = 119) presented statistically significant differences for: nail involvement, PEST score ⩾3, higher erythrocyte sedimentation rate (ESR), Nail Psoriasis Severity Index (NAPSI)-feet, NAPSI-(hands + feet) and PsA-Disk scores (73.9 ± 32.1 versus 58.1 ± 39.8, p  < 0.001). Patients with PsA with knee arthritis had higher PsA-Disk scores (98.4 ± 26 versus 71.5 ± 31.9, p  = 0.006) that were also correlated with number of swollen ( r  = 0.2, p < 0.05) and tender joints ( r = 0.24, p = 0.021), patient ( r = 0.4, p < 0.001) and physician-pain-visual analogue scale (VAS; r = 0.33, p < 0.001), patient global assessment (PGA)-VAS ( r = 0.23, p = 0.025), physician-health assessment questionnaire (HAQ; r = 0.38, p = 0.011), Disease Activity Score (DAS)-44 ( r = 0.25, p = 0.023) and Disease Activity in Psoriatic Arthritis (DAPSA; r = 0.31, p = 0.005). The instrument had excellent reliability in terms of internal consistency (Cronbach's alpha = 0.90) and stability (intraclass correlation = 0.98). Moderate agreement between PsA-Disk and PEST (Cohen's kappa = 0.46) was observed, while construct validity appeared appropriate [PsA + patients: PsA-Disk score (interquartile range; IQR) =71 (50-96); PsA-patients: PsA-Disk score (IQR)=50 (20-90); p < 0.001]., Conclusion: PsA-Disk may be considered a valid novel instrument aiding both dermatologists and rheumatologists in the rapid detection and assessment of musculoskeletal disease characteristics., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rheumatological systemic autoimmune diseases, such as connective tissue diseases, rheumatoid arthritis or spondyloarthritis, are characterized by the presence of joint involvement associated with extra-articular manifestations. Among them, cutaneous diseases are often the most relevant and representative clinical manifestation, as in psoriatic arthritis, scleroderma or systemic lupus erythematosus. In this context, it is useful for rheumatologists to understand better skin diseases and their histopathological features. Evaluation of skin biopsy specimens can be helpful not only to confirm the diagnosis in both classic and clinically atypical variants, but also to improve further our knowledge of the pathogenetic mechanisms and the close link between skin and articular diseases. In this review, we discuss the clinical features, diagnostic evaluation and the histopathological features of skin manifestation of the most relevant rheumatological autoimmune diseases.

Irrigation is widely used for the production of table olives because it increases fruit size and yield. However, irrigation also determines less accumulation of total phenols, an increase in water content, a decrease of firmness, lower concentrations of soluble sugars in the mesocarp, thus positively or negatively affecting the fermentation process for the production of table olives. In this study we tested the hypothesis that green fruits of cultivar Itrana obtained by different irrigation regimes had different phenolic concentration that responded differentially to spontaneous or inoculated fermentation. Fruits were harvested from two orchards in the Latina province of Latium, Italy, which had been irrigated with different volumes of water during the growing season to compare the evolution of spontaneous and inoculated fermentation processes. We measured fruit characteristics at harvest, changes in the concentrations of secoiridoids and lignans, and main microbial groups abundance during fermentation. At harvest and during fermentation the concentration of phenolic compounds was higher in fruits sampled from trees that had received less water in the field. Differences were observed between spontaneous and inoculated fermentations, with a prevalence of lactic acid bacteria (LAB) in inoculated samples. In particular, oleuropein concentration completely disappeared only from samples inoculated with the two selected strains used as starters. The inoculum with selected LAB positively influenced the fermentation process of green olives, whereas the irrigation regime previously experienced by trees did not alter fermentation.

Background: Clinical grade processing of harvested bone marrow is required in various clinical situations, particularly in the management of ABO mismatching in allogeneic haematopoietic stem cell transplantation (HSCT) and in regenerative medicine., Material and Methods: We report a single-centre experience using a fully automated, clinical grade, closed system (Sepax, Biosafe, Switzerland). From 2003 to 2015, 125 procedures were performed in our laboratory, including buffy-coat production for HSCT (n=58), regenerative medicine in an orthopaedic setting (n=54) and density-gradient separation in a trial for treatment of critical limb ischaemia (n=13)., Results: Buffy coat separation resulted in a median volume reduction of 85% (range, 75-87%), providing satisfactory red blood cell depletion (69%, range 30-88%) and a median recovery of CD34 cells of 96% (range, 81-134%) in the setting of allogeneic HSCT. Significantly greater volume reduction (90%; range, 90-92%) and red blood cell depletion (88%; range, 80-93%) were achieved by the new SmartRedux software released for Sepax2, validated in the last eight allogeneic HSCT. The density gradient separation programme resulted in complete red blood cell depletion associated with high CD34 recovery (69%; range, 36-124%). No reactions related to the quality of the product were reported. Time to engraftment following allogeneic HSCT was in the normal range. No cases of microbiological contamination related to the manipulation were reported., Discussion: Clinical grade, automated bone marrow manipulation with Sepax was shown to be effective, giving operator-independent results and could be used for a broad range of clinical applications.

The influence of light exposure on the quality of commercially available extra-virgin olive oils (EVOOs) of different chemical composition was studied as a function of storage (11weeks) under conditions simulating market storage. By mildly stripping the polyphenols from oil 'A', with high levels of polyphenols and oleic acid, and oil 'B', exhibiting a medium level of polyphenols and a low level of oleic acid, 'C' and 'D' EVOOs were obtained. Ten EVOOs were produced as mixtures of these four oils. The initial concentrations of oleic acid and polyphenols in the 14 oils ranged from 64.5 to 77.7% and 18.1 to 1476.7mg/kg, respectively. The extinction coefficient K 270 well reflected the EVOO product quality. EVOOs richer in oleuropein derivatives showed superior oxidative stability, which resulted in lower off-flavour volatile compound production and α-tocopherol and polyphenols losses, and thus, higher EVOO sensory and health benefits., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Fruit development and oil quality in Olea europaea L. are strongly influenced by both light and water availability. In the present study, the simultaneous effects of light environment and irrigation on fruit characteristics and oil quality were studied in a high-density orchard over two consecutive years. Olive fruits were harvested from three canopy positions (intercepting approximately 64%, 42% and 30% of above canopy radiation) of fully-productive trees subjected to full, deficit or complementary irrigation., Results: Fruits receiving 61-67% of above canopy radiation showed the highest fruit weight, mesocarp oil content and maturation index, whereas those intercepting only 27-33% showed the lowest values. Palmitoleic and linoleic acids increased in oils obtained from fruits exposed to high light levels, whereas oleic acid and the oleic-linoleic acid ratio decreased. Neither canopy position, nor irrigation affected K 232 , K 270 , ΔK and the concentration of lignan in virgin olive oils (VOOs). Total phenols, 3,4-DHPEA-EDA [2-(3,4-hydroxyphenyl)ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] and p-HPEA-EDA (decarboxymethyl ligstroside-aglycone) increased in VOOs produced from fruits harvested from the top of the canopy, whereas full irrigation decreased total phenols and 3,4-DHPEA-EDA concentrations with respect to the complementary irrigation treatment., Conclusion: Light and water availability are crucial not only for tree productivity, but also they clearly affect olive oil quality. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

Olive fruits and oils contain an array of compounds that contribute to their sensory and nutritional properties. Phenolic compounds in virgin oil and olive-derived products have been proven to be highly beneficial for human health, eliciting increasing attention from the food industry and consumers. Although phenolic compounds in olive fruit and oil have been extensively investigated, allowing the identification of the main classes of metabolites and their accumulation patterns, knowledge of the molecular and biochemical mechanisms regulating phenolic metabolism remains scarce. We focused on the role of polyphenoloxidase ( PPO ), peroxidase ( PRX ) and β-glucosidase (β- GLU ) gene families and their enzyme activities in the accumulation of phenolic compounds during olive fruit development (35-146 days after full bloom), under either full irrigation (FI) or rain-fed (RF) conditions. The irrigation regime affected yield, maturation index, mesocarp oil content, fruit size, and pulp-to-pit ratio. Accumulation of fruit phenolics was higher in RF drupes than in FI ones. Members of each gene family were developmentally regulated, affected by water regime, and their transcript levels were correlated with the respective enzyme activities. During the early phase of drupe growth (35-43 days after full bloom), phenolic composition appeared to be linked to β-GLU and PRX activities, probably through their effects on oleuropein catabolism. Interestingly, a higher β-GLU activity was measured in immature RF drupes, as well as a higher content of the oleuropein derivate 3,4-DHPEA-EDA and verbascoside. Activity of PPO enzymes was slightly affected by the water status of trees during ripening (from 120 days after full bloom), but was not correlated with phenolics content. Overall, the main changes in phenolics content appeared soon after the supply of irrigation water and remained thereafter almost unchanged until maturity, despite fruit growth and the progressive decrease in pre-dawn leaf water potential. We suggest that enzymes involved in phenolic catabolism in the olive fruit have a differential sensitivity to soil water availability depending on fruit developmental stage.

In recent years, the temperature of processed olives in many olive-growing areas was often close to 30°C, due to the global warming and an early harvesting period. Consequently, the new trends in the extraction process have to include the opportunity to cool the olives or olive paste before processing to obtain high quality EVOO. A tubular thermal exchanger was used for a rapid cooling treatment (CT) of olive paste after crushing. The results did not show a significant difference in the oil yield or any modifications in the legal parameters. The cooling process determined a significant improvement of phenolic compounds in all the three Italian cultivar EVOOs analyzed, whereas the volatile compounds showed a variability largely affected by the genetic origin of the olives with C 6 aldehydes that seem to be more stable than C 6 alcohols and esters., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the antioxidant and antimicrobial effects of a phenolic extract from olive vegetation water on fresh salmon steaks stored at 4°C under modified atmosphere. Twenty-four salmon steaks were respectively immersed in solutions of the diluted phenolic extract at 1.5 g/L (A), 3 g/L (B), and water only as a control (CTR), packaged within a protective atmosphere (70% carbon dioxide, 25% nitrogen and 5% oxygen) and then stored at 4°C. After 2 h, and 3 and 6 days of storage, the fish samples were analysed for the total viable count, Enterobacteriaceae count, pH, colour (CIE L*a*b* colour system), phenolic composition, atocopherol content, antioxidant activity by 2,2- diphenyl- 1-picrylhydrazyl (DPPH˙) assay, and thiobarbituric reactive substances (TBARS). A 3 g/L phenolic extract contributed positively to the hygienic quality of the salmon by reducing the microbial growth during storage. The treated samples were slightly yellower than the CTR but only at the beginning of storage. The flesh contained 6.2% of the total polyphenols present in the initial solutions, with various percentages of the single fractions. After 6 days storage, the α- tocopherol content in the CTR and A samples was statistically lower than the B group that also showed the lowest DPPH˙ and TBARS values. In conclusion, the phenolic extract increased the microbiological quality and antioxidant concentration and decreased the lipid oxidation of salmon steaks during storage at 4°C under modified atmosphere., Competing Interests: the authors declare no potential conflict of interest.

This study optimizes the application of portable Near Infrared-Acousto Optically Tunable Filter (NIR) device to meet the increasing demand for cost-effective, non-invasive and easy-to-use methods for measuring physical and chemical properties during olive fruit development. Fruits from different phenotypically cultivars were sampled for firmness, total and specific phenols detection by HPLC, total anthocyanins, chlorophyll and carotenoids detection by spectrophotometry. On the same fruits, a portable NIR device in diffuse reflectance mode was employed for spectral detections. Predictive models for firmness, chlorophyll, anthocyanins, carotenoids and rutin were developed by Partial Least Square analysis. Oleuropein, verbascoside, 3,4-DHPEA-EDA, and total phenols were used to develop a validation model. Internal cross-validation was applied for calibration and predictive models. The standard errors for calibration, cross-validation, prediction, and RPD ratios (SD/SECV) were calculated as references for the model effectiveness. The determination of the optimal harvesting time facilitates the production of high quality extra virgin olive oil and table olives., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Olive mill wastewater polyphenol extract was tested for antimicrobial activity against 64 strains of Pseudomonas fluorescens responsible for mozzarella discolouration. The extract showed a minimum inhibitory concentration (MIC) 50 value of 5 mg/mL and a MIC 90 value of 7 mg/mL. The MBC 50 and MBC 90 values corresponded to 6 and 8 mg/mL, respectively. The MIC concentration (7 mg/mL) was demonstrated to have a bacteriostatic effect while maintaining the bacterial concentration on the levels of the inoculum for 48 hours. The 3/2 MIC concentration was responsible for four logs CFU/mL depletion in colony count after 24 h. As the extract concentration decreased from MIC value, no inhibitory effects were recorded., Competing Interests: the authors declare no potential conflict of interest.

Several studies have demonstrated that the use of natural preservatives through animal diets could increase the shelf life of meat and meat products since many plant-derived substances show antioxidant and antimicrobial properties. The aim of this work was to study the effect of olive cake dietary supplementation on beef oxidative stability and antimicrobial activity during storage. Beef cattle were randomly divided into three homogeneous groups that were assigned to one of the three diets: a commercial unified based diet administered for 90 days until slaughter (CTR), CTR diet supplemented with 0.5% olive cake administered for 90 days until slaughter (OC1), and CTR diet supplemented with 0.5% olive cake and administered for 60 days followed by the administration of the CTR diet for 30 days until slaughter (OC2). Beefsteaks were overwrapped with oxygen-permeable packaging and analysed at four different storage times (zero, three, six and nine days). At the four sampling times considered from all of the samples, total viable count (TVC), Enterobacteriaceae counts, colour coordinates (CIE L*a*b* colour system), peroxide value (PV), thiobarbituric reactive substances (TBARs) determinations and descriptive sensory analyses were performed. No differences in TVC and Enterobacteriaceae count were detected among the groups over all of the sampling times considered. Differences were recorder among groups for PV, TBARS, colour and sensory analysis. The addition of olive cake in the animal diet had an effect on lipid oxidation reducing the level of PV, TBARS and retarding colour deterioration and the development of off odour in OC meat during storage., Competing Interests: the authors declare no potential conflict of interest.

The concentration of phenolic and volatile compounds in virgin olive oil (VOO) is closely related to the different operative conditions applied to the mechanical extraction process of the olive oil. However, the great qualitative and quantitative variability of these compounds indicates an important role played by genetic and agronomic aspects. A heat exchanger was placed in front of a traditional, covered malaxer to study the impact of flash thermal conditioning (FTC) of olive paste on the quality of VOO, which is highly influenced by phenolic release and aroma generation. The VOO flash thermal conditioning of five major Italian cultivars showed a higher concentration of phenols (range of increase percentage, 9.9-37.3%) compared to the control trials, whereas the FTC treatment featured a differentiated impact on the volatile fractions, associated with the genetic origins of the olives.

The potential of a phenolic extract (PE) from olive vegetation water (OVW) to limit the negative effects of frying was tested after adding it at different concentrations to a refined olive oil (RO). Its efficacy was also compared to ROs containing butylated hydroxytoluene (BHT) and an extra virgin olive oil (EVOO) with a high polyphenol content. Analyses of the oils collected after 30min, 1, 2, 4, 6, 8, 10 and 12h of frying at 180°C, demonstrated that degradation of the polyphenols was proportional to the original content; at a concentration of at least 400mg/kg of polyphenols, PE was able to reduce oxidation of the tocopherols and the emission of low-molecular-weight aldehydes better than BHT and with similar results to the EVOO. In addition, secoiridoid oxidative compounds were examined by high-performance liquid chromatography/triple quadrupole tandem mass spectrometry with electrospray ionisation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns' immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero.

Response surface modeling (RSM) was used to optimize temperature and oxygen concentration during malaxation for obtaining high quality extra virgin olive oils (EVOOs). With this aim, those chemical variables closely related to EVOO quality, such as the phenolic and the volatile compounds, have been previously analyzed and selected. It is widely known that the presence of these substances in EVOOs is highly dependent on genetic, agronomic, and technological aspects. Based on these data, the two parameters were optimized during malaxation of olive pastes of four important Italian cultivars using some phenols and volatile compounds as markers; the optimal temperatures and oxygen levels, obtained by RSM, were as follows for each cultivar: 33.5 °C and 54 kPa of oxygen (Peranzana), 32 °C and 21.3 kPa (Ogliarola), 25 °C and 21.3 kPa (Coratina), and 33 °C and 21.3 kPa (Itrana). These results indicate the necessity to optimize these malaxing parameters for other olive cultivars.

Over the last few decades, multiple biological properties, providing antioxidant, anti-inflammatory, chemopreventive and anti-cancer benefits, as well as the characteristic pungent and bitter taste, have been attributed to Extra Virgin Olive Oil (EVOO) phenols. In particular, growing efforts have been devoted to the study of the antioxidants of EVOO, due to their importance from health, biological and sensory points of view. Hydrophilic and lipophilic phenols represent the main antioxidants of EVOO, and they include a large variety of compounds. Among them, the most concentrated phenols are lignans and secoiridoids, with the latter found exclusively in the Oleaceae family, of which the drupe is the only edible fruit. In recent years, therefore, we have tackled the study of the main properties of phenols, including the relationships between their biological activity and the related chemical structure. This review, in fact, focuses on the phenolic compounds of EVOO, and, in particular, on their biological properties, sensory aspects and antioxidant capacity, with a particular emphasis on the extension of the product shelf-life.

Dried stoned olive pomace (DSOP) was administered to dairy water buffaloes, and their productive performance and milk composition were analysed. Sixteen pluriparous lactating buffaloes were divided into two uniform groups (control and experimental), taking into consideration the following parameters: milk production (2,192 and 2,102 kg) and duration of lactation (254 and 252 d) of the previous year, distance from calving (51 and 43 d), milk production (9.71 and 10.18 kg/d), body condition score (BCS) (6.44 and 6.31) and weight (617 and 653 kg) at the beginning of the trial. Both diets had the same formulation: second cut alfalfa hay 20%, corn silage 42%, concentrate 38% but the two concentrates differed in their formulation, the experimental one contained 15.50% of DSOP as fed. The employed DSOP showed high amounts of secoiridoids, such as 3,4-dihydroxyphenylethanol (3,4-DHPEA) (1.2 g/kg DM), 3,4-dihydroxyphenylethanol-elenolic acid di-aldehyde (3,4-DHPEA-EDA) (12.6 g/kg DM), p-hydroxyphenylethanol-elenolic acid di-aldehyde (p-HPEA-EDA) (5.6 g/kg DM) and lignans, which are known to be powerful bioactive compounds. The control diet had an energy-protein content of 0.86 Milk FU/kg DM and 143.3 g/kg DM of crude protein, whereas the experimental diet of 0.87 Milk FU/kg DM and 146.6 g/kg DM of crude protein. Each animal of the two groups received 17 kg DM/d and each buffalo of the experimental group, by way of the concentrate, ingested 1.05 kg DM/d of DSOP. The trial lasted 40 days. No significant difference was found between the BCS (6.41 and 6.53), live weight (625.93 and 662.50 kg) and milk production (9.69 and 10.08 kg/d) of the two groups, as was the case for fat, protein, lactose, pH and coagulating parameters of the two milks. The milk fat of the experimental group had a significantly higher content of total tocopherols (10.45 vs 8.60 μg/g, p<0.01) and retinol (3.17 vs 2.54 μg/g, p<0.01). The content of the reactive substances with tiobarbituric acid (TBARs) was significantly lower in the milk fat of the experimental group (12.09 vs 15.05 μg MDA/g, p<0.01). The acid content of the milk fat of the experimental group had a significantly higher content (p<0.05) of C18:0 and of C18:3ω6. LC-MS/MS analysis showed the presence of 3,4-DHPEA (36.0 μg/L) in the milk of the DSOP-fed buffaloes, while other phenols were not found. DSOP, in the quantity utilized, can be used in the feeding of the lactating buffalo; the dietetic-nutritional characteristics of the milk are improved due to a greater contribution of tocopherols, retinol and the presence of hydroxytyrosol.

Secoiridoid derivatives are the most important antioxidants of virgin olive oil (VOO), and their oxidation products could be used as molecular markers of VOO freshness to define the VOO autoxidation state. The aim of this research was to characterise the dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA) oxidation products to find analytical indicators that could be used as early evaluation index of the VOO autoxidation state. 3,4-DHPEA-EDA was oxidised by enzymatic and Fenton reactions. Terpenic structure oxidation products accumulated in VOO during the autoxidation process, thus they may be used as early evaluation index of the VOO autoxidation state before fatty acids oxidation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The quality of virgin olive oil (VOO) is strictly related to the concentrations of phenolic and volatile compounds, which are strongly affected by the operative conditions of the VOO mechanical extraction process. The aim of this work is to study the impact of a new technology such as flash thermal conditioning (FTC) on olive paste structural modification and on VOO quality. The evaluation of olive paste structure modification by cryo-scanning electron microscopy (cryo-SEM) showed that the application of FTC after crushing produces significant differences in terms of the breaking of the parenchyma cells and aggregation of oil droplets in comparison to the crushed pastes. The virgin olive oil flash thermal conditioning (VOO-FTC) featured a higher concentration of volatile compounds compared to that in the control, particularly of all saturated and unsaturated aldehydes and esters, whereas the phenolic concentration was higher in VOO obtained from the traditional process (VOO-C).

The low-density lipoprotein receptor-related protein 1 (LRP1) is an ubiquitously expressed endocytic receptor that, among its several functions, is involved in the catabolism of coagulation factor VIII (FVIII) and in the regulation of its plasma concentrations. Although LRP1/CD91 polymorphisms have been associated with increased FVIII levels and a consequent thrombotic risk, no data are available on LRP1/CD91 expression in patients with inherited FVIII deficiency. With the aim of elucidating this issue, 45 consecutive patients with haemophilia A (HA) (18 severe, 5 moderate and 22 mild HA) were enrolled in this cross-sectional, single-centre survey. The LRP1/CD91 mean fluorescence intensity (MFI) in monocytes from HA patients was significantly higher than that detected in 90 healthy blood donors (105 vs. 67, P < 0.001). This over-expression was independent of hepatitis C virus infection status and varied according to the severity of the haemophilia, being higher in patients with more severe FVIII deficiency. In conclusion, our study documents for the first time that LRP1/CD91 is over-expressed on monocytes from HA patients, with the intensity of expression varying according to the severity of the FVIII deficiency. Further studies are needed to assess the clinical implications of these findings., (© 2013 Blackwell Publishing Ltd.)

The effect of the malaxation temperature under sealed conditions on the qualitative and quantitative composition of the phenolic compounds in virgin olive oils produced from four Italian cultivars was assessed for two atmospheric conditions. In both cases, the results show a positive relationship between temperature and the concentration of the derivatives of the secoiridoid aglycones; the effect of the temperature on the oxidoreductases that promote oxidation (polyphenoloxidase and peroxidase) was investigated to determine their optimal temperatures and thermal stability. While olive peroxidase (POD) showed the highest activity at 37°C and high stability in the temperature range tested, polyphenoloxidase (PPO) exhibited the optimum activity at approximately 50°C, but showed low stability at 40°C, with a large variation in stability according to the olive cultivar. These results may contribute to an understanding of the increase in the phenol concentration found in virgin olive oils obtained following higher temperatures of malaxation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background & Aims: In patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, antiviral functions of T cells are impaired; these might be increased by blocking T-cell co-inhibitory pathways, such as preventing interaction between the receptor programmed death (PD)-1 and its ligand, PD-L1. We attempted to optimize the restoration of T-cell functions in patients with chronic HBV or HCV infection with a combination of reagents that block PD-1 interaction with PD-L1 and stimulate T-cell signaling via CD137, a member of the tumor necrosis factor-receptor family., Methods: We assessed the effects of CD137 stimulation (via CD137L), alone or in combination with antibodies that block PD-1 interaction with PD-L1 (anti-PD-L1), on proliferation and production of interferon-γ and interleukin-2 by intrahepatic and peripheral T cells from patients with chronic HBV or HCV infection. We also analyzed expression of different co-stimulatory molecules on virus-specific CD8+ and forkhead box P3+CD4+ cells by flow cytometry., Results: Incubation of intrahepatic T cells with CD137L and anti-PD-L1 increased their responses to HBV, but not HCV. However, HCV-specific T cells isolated from peripheral blood were sensitive to these reagents. Virus-specific T cells from some, but not all patients, had increased responses to anti-PD-L1 when CD137L was added because in some cases the combination of anti-PD-L1 and CD137L overstimulated T cells, leading to their inhibition. Intrahepatic HBV- and HCV-specific CD8+ T cells had different costimulatory profiles; liver cells from patients with chronic HBV infection had a higher proportion of forkhead box P3+ regulatory T cells, with higher levels of PD-1, compared with liver cells from patients with chronic HCV infection., Conclusions: A combination of reagents that prevent interaction between PD-1 and its ligand and activate CD137 signaling increase responses of intrahepatic HBV-specific T cells and circulating HCV-specific T cells. This strategy might be developed to increase T-cell responses to these viruses in patients with chronic hepatitis B or C, and tailoring the dose of CD137L administered will help optimize results., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Olive (Olea europaea L.) fruits contain numerous secondary metabolites, primarily phenolics, terpenes and sterols, some of which are particularly interesting for their nutraceutical properties. This study will attempt to provide further insight into the profile of olive phenolic compounds during fruit development and to identify the major genetic determinants of phenolic metabolism., Results: The concentration of the major phenolic compounds, such as oleuropein, demethyloleuropein, 3-4 DHPEA-EDA, ligstroside, tyrosol, hydroxytyrosol, verbascoside and lignans, were measured in the developing fruits of 12 olive cultivars. The content of these compounds varied significantly among the cultivars and decreased during fruit development and maturation, with some compounds showing specificity for certain cultivars. Thirty-five olive transcripts homologous to genes involved in the pathways of the main secondary metabolites were identified from the massive sequencing data of the olive fruit transcriptome or from cDNA-AFLP analysis. Their mRNA levels were determined using RT-qPCR analysis on fruits of high- and low-phenolic varieties (Coratina and Dolce d'Andria, respectively) during three different fruit developmental stages. A strong correlation was observed between phenolic compound concentrations and transcripts putatively involved in their biosynthesis, suggesting a transcriptional regulation of the corresponding pathways. OeDXS, OeGES, OeGE10H and OeADH, encoding putative 1-deoxy-D-xylulose-5-P synthase, geraniol synthase, geraniol 10-hydroxylase and arogenate dehydrogenase, respectively, were almost exclusively present at 45 days after flowering (DAF), suggesting that these compounds might play a key role in regulating secoiridoid accumulation during fruit development., Conclusions: Metabolic and transcriptional profiling led to the identification of some major players putatively involved in biosynthesis of secondary compounds in the olive tree. Our data represent the first step towards the functional characterisation of important genes for the determination of olive fruit quality.

Strains of Lactobacillus plantarum, Pediococcus acidilactici, Pediococcus pentosaceus and Leuconostoc mesenteroides subsp. mesenteroides were identified from 8 cultivars of sweet cherry by partial 16S rRNA gene sequence and subjected to typing by Random Amplified Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR) analysis. Representative isolates from each species and each cultivar were screened based on the kinetics of growth on cherry puree added of (10%, v/v) stem infusion (CP-SI). A protocol for processing and storage of CP-SI, which included fermentation by selected autochthonous P. pentosaceus SWE5 and L. plantarum FP3 (started CP-SI) or spontaneous fermentation (unstarted CP-SI), was set up. Starters grew and remained viable at elevated cell numbers (ca. 9.0 log cfu g(-1)) during 60 days of storage at 4 °C. The number of presumptive lactic acid bacteria of the unstarted CP-SI did not exceed the value of ca. 3.0 log cfu g(-1). Consumption of carbohydrates (e.g., glucose and fructose) by starter lactic acid bacteria was limited as well as it was the lactic acid fermentation. Consumption of organic acids (e.g., malic acid) and free amino acids was evident, especially, throughout storage. Compared to CP-SI before processing, the concentrations of total phenolic compounds and anthocyanins did not vary in the started CP-SI. The concentration of anthocyanins slightly decreased in the unstarted CP-SI. The antioxidant activity, expressed as the scavenging activity toward DPPH radical, was found at highest level in the started CP-SI which approached that found in CP-SI before processing. During storage, viscosity and, especially, color indexes of started CP-SI were higher than those found in the unstarted CP-SI. Fermentation by autochthonous lactic acid bacteria seemed to also positively interfere with the sensory attributes of CP-SI., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Aims: The number of Endothelial Progenitor Cells (EPCs) is considered a novel marker of cardiovascular (CV) disease. It is not clear which are the main determinants of EPC number in apparently healthy subjects in the absence of overt clinical CV or metabolic abnormalities. We evaluated the main clinical determinants of EPC levels in a population of healthy subjects with normal glucose tolerance., Methods and Results: EPC number was determined in 122 healthy subjects (73M/49F;36.6 ± 8yrs). Blood samples were collected to test biochemical variables. OGTT was performed and insulin resistance/compensatory hyperinsulinemia was defined according to fasting plasma insulin (FPI) levels. EPCs were identified as cells co-expressing CD133/CD34/KDR antigens by flow-cytometry. CD133(+)/KDR(+) count inversely correlated with BMI (rho=-0.18;p < 0.05), waist circumference (-0.2;<0.05), diastolic (-0.23;<0.01) and systolic blood pressure (-0.21;<0.05), uric acid (-0.24;<0.005), PAI-1 (-0.197; <0.05) and FPI (-0.2;<0.05) and directly correlated with HDL cholesterol (0.182;<0.05). CD34(+)/CD133(+)/KDR(+) count inversely correlated with uric acid (-0.28;<0.005) and FPI (-0.2;<0.05). EPC number was lower in males (p < 0.05) and gender was the only independent predictor of EPC count (p < 0.05). By dividing the population in four subgroups based on gender and insulin resistance, CD133(+)/KDR(+) levels were lower in insulin resistant compared to insulin sensitive males (p < 0.05) with no differences in females., Conclusion: The male gender is an independent predictor of low EPC levels in healthy subjects. This might contribute to explaining the higher CV risk in males compared to pre-menopausal age-matched females. In this study a reduced EPC number seems to be associated with insulin resistance in male subjects., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Functional milk beverages (FMB100 and FMB200) fortified with phenolic compounds (100 and 200mg/l) extracted from olive vegetable water, and fermented with γ-amino butyric acid (GABA)-producing (Lactobacillus plantarum C48) and autochthonous human gastro-intestinal (Lactobacillus paracasei 15N) lactic acid bacteria were manufactured. A milk beverage (MB), without addition of phenolic compounds, was used as the control. Except for a longer latency phase of FMB200, the three beverages showed an almost similar kinetic of acidification, consumption of lactose and synthesis of lactic acid. Apart from the beverage, Lb. plantarum C48 showed a decrease of ca. Log 2.52-2.24 cfu/ml during storage. The cell density of functional Lb. paracasei 15N remained always above the value of Log 8.0 cfu/ml. During fermentation, the total concentration of free amino acids markedly increased without significant (P > 0.05) differences between beverages. The concentration of GABA increased during fermentation and further storage (63.0 ± 0.6-67.0 ± 2.1mg/l) without significant (P > 0.05) differences between beverages. After fermentation, FMB100 and FMB200 showed the same phenolic composition of the phenol extract from olive vegetable water but a different ratio between 3,4-DHPEA and 3,4-DHPEA-EDA. During storage, the concentrations of 3,4-DHPEA-EDA, p-HPEA and verbascoside of both FMB100 and FMB200 decreased. Only the concentration of 3,4-DHPEA increased. As shown by SPME-GC-MS analysis, diactetyl, acetoin and, especially, acetaldehyde were the main volatile compounds found. The concentration of phenolic compounds does not interfere with the volatile composition. Sensory analyses based on triangle and paired comparison tests showed that phenolic compounds at the concentrations of 100 or 200mg/l were suitable for addition to functional milk beverages., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background Aims: The human mesenchymal stromal cell (hMSC), a type of adult stem cell with a fibroblast-like appearance, has the potential to differentiate along the mesenchymal lineage and also along other cell lineages. These abilities make hMSC a promising candidate for use in regenerative medicine. As the hMSC represents a very rare population in vivo, in vitro expansion is necessary for any clinical use. hMSC characterization is commonly carried out through the expression of specific markers and by the capability of differentiating toward at least adipo-, osteo- and chondrocytic lineages. Commitment processes also result in significant changes in the ultrastructure in order to acquire new functional abilities; however, few studies have dealt with the ultrastructural characteristics of hMSC according to the time of incubation and type of media., Methods: The immunophenotype, functional characteristics and ultrastructural features of bone marrow (BM) hMSC cultured in two different media were investigated. The media chosen were Iscove's modified Dulbecco's medium (IMDM) and the Dulbecco's modified Eagle medium (DMEM). The latter has been recommended recently by two international transplantation and cytotherapy societies, the International Society of Cellular Therapy (ISCT) and European Group for Blood and Bone Marrow Transplantation (EBMT), for hMSC expansion for clinical applications., Results and Conclusions: The present results indicate that culture conditions greatly influence hMSC ultrastructural features, proliferation, growth and differentiation. In particular, our findings demonstrate that DMEM preserves the hMSC stem features better. Furthermore, the results obtained in IMDM suggest that a small size does not always correlate with conditions of cell immaturity and a greater proliferative potential.

CD133 is a hallmark of primitive myeloid progenitors. We have addressed whether human cord blood cells selected for CD133 can generate dendritic cells, and Langerhans cells in particular, in conditions that promote that generation from CD34(+) progenitors. Transforming growth factor-β1 (TGF-β1) and anti-TGF-β1 antibody, respectively, were added in some experiments. With TGF-β, monocytoid cells were recognized after 7 days. Immunophenotypically immature dendritic cells were present at day 14. After 4 more days, the cells expressed CD54, CD80, CD83, and CD86 and were potent stimulators in mixed lymphocyte reaction; part of the cells expressed CD1a and langerin, but not Birbeck granules. Without TGF-β, only a small fraction of cells acquired a dendritic shape and expressed the maturation-related antigens, and lymphocytes were poorly stimulated. With anti-TGF-β, the cell growth was greatly hampered, CD54 and langerin were never expressed, and lymphocytes were stimulated weakly. In conclusion, CD133(+) progenitors can give rise in vitro, through definite steps, to mature, immunostimulatory dendritic cells with molecular features of Langerhans cells, although without Birbeck granules. Addition of TGF-β1 helps to stimulate cell growth and promotes the acquisition of mature immunophenotypical and functional features. Neither langerin nor Birbeck granules proved indispensable for lymphocyte stimulation.

The isolation and identification of a phytocomplex from olive mill waste waters (OMWW) was achieved. The isolated phytocomplex is made up of the following three phenolic compounds: hydroxytyrosol (3,4-DHPEA), tyrosol (p-HPEA) and the dialdehydic form of decarboxymethyl elenolic acid, linked with (3,4-dihydroxyphenyl)ethanol (3,4-DHPEA-EDA). The purification of this phytocomplex was reached by partial dehydration of the OMWW, followed by liquid-liquid extraction with ethyl acetate and middle pressure liquid chromatography (MPLC) on a Sephadex LH-20 column. The phytocomplex accounted for 6% of the total phenolic content of the OMWW. The phytocomplex and individual compounds were tested for antioxidant capacity by the oxygen radical absorbance capacity (ORAC) method. The ORAC phytocomplex produced 10,000 ORAC units/g dry weight, whereas the cellular antioxidant activity, measured by the cellular antioxidant activity in red blood cell (CAA-RBC) method, demonstrated that the phytocomplex and all of the components are able to permeate the cell membrane thus exhibiting antioxidant activity inside the red blood cells. Our phytocomplex could be employed in the formulation of fortified foods and nutraceuticals, with the goal to obtain substantial health protective effects due to the suitable combination of the component molecules.

With the aim to select new olive cultivars with superior physical and chemical properties than the cultivar Chemlali Sfax, the present study focused on the comparison of the chemical composition and the sensory profile of the virgin olive oils (VOOs) of two wild olive trees (Oleasters K and M) with those of VOOs obtained from Chemlali Sfax and Neb Jmel olive cultivars, all growing in the coastal region of Tunisia. Despite the variability in the chemical composition (fatty acids, pigments, and phenolic and volatile compounds) and the organoleptic profile of the VOOs of the oleasters and the cultivars, the quality indices (free fatty acids, peroxide value, and spectrophotometric indices K232 and K270) as well as the fatty acid composition of all VOOs studied met the commercial standards. Both the α-tocopherol and phenol contents varied between the genotypes. The Neb Jmel and Oleaster K VOOs had more than two times higher total phenol levels than the Chemlali Sfax and Oleaster M VOOs. Also the contents of volatile compounds differed between the olive oils studied. Chemlali Sfax and Oleaster K oils were more abundant in aldehydes, whereas Oleaster M VOO had higher contents of alcohols. These results were confirmed by a sensorial analysis showing that the later oil was deprived for consumption despite its abundance in α-tocopherol. In conclusion, the oleasters studied revealed to be interesting, since they produced oils with good quality characteristics in terms of minor compounds (phenols and volatiles) compared to the Chemlali Sfax cultivar., (Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.)

Background Aims: Bone marrow (BM) is the most used source of hemopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) in both hematologic settings and regenerative medicine. We compared the feasibility and reproducibility of two gravity separation techniques, with or without the use of a density gradient, in terms of both hematopoietic and mesenchymal human BM progenitors., Methods: A total of 16 BM samples was processed to obtain mononuclear cells (MNC) and buffy coats (BC). The efficiency of the two procedures was evaluated by recovery of white blood cells (WBC), MNC and CD34(+) cells, clonogenic assays, red blood cell (RBC) depletion, cell viability, expression of embryonic transcriptional regulators and MSC assessment., Results: The two procedures yielded a comparable recovery of HSC. Non-density gradient separation (NDGS) of BM resulted in four times higher MSC recovery and higher expression of embryonic stem cell markers (Nanog and Sox2) compared with density-gradient separation (DGS). MSC derived from both procedures was comparable in terms of phenotype, differentiation and proliferation potential., Conclusions: NDGS is less time consuming, provides a better MSC enrichment and appears to be a suitable cell preparation method for clinical applications.

Background: Pancreatic islet transplantation is a promising cell-based therapy for type 1 diabetes (insulin-dependent diabetes mellitus), a disease triggered by the immune response against autoantigens of beta-cells. However, the recurrence of immune response after transplantation and the diabetogenic and growth-stunting side effects of immunosuppressants are major challenges to the application of islet transplantation. Mesenchymal stem cells (MSCs) have recently been reported to modulate the immune response in allogeneic transplantation., Methods: The ability of MSCs, either syngeneic or allogeneic to recipients, to prevent acute rejection and improve glycemic control was investigated in rats with diabetes given a marginal mass of pancreatic islets through the portal vein., Results: Reduced glucose levels and low-grade rejections were observed up to 15 days after transplantation upon triple-dose administration of MSCs, indicating that MSCs prolong graft function by preventing acute rejection. The efficacy of MSCs was associated with a reduction of pro-inflammatory cytokines and was independent of the administration route. Efficacy was similar for MSCs whether syngeneic or allogeneic to recipients and comparable to that of immunosuppressive therapy., Conclusions: The results show that MSCs modulate the immune response through a down-regulation of pro-inflammatory cytokines, suggesting that MSCs may prevent acute rejection and improve graft function in portal vein pancreatic islet transplantation.

Background & Aims: Natural killer (NK) cells are essential early after infection, not only for viral containment but also for timely and efficient induction of adaptive responses. An inhibitory effect of hepatitis C virus (HCV)-E2 proteins on NK cells has been reported, but the features of NK cell responses in the acute phase of hepatitis C are still largely undefined. Therefore, the aim of this study was to characterize the function and phenotype of NK cells in the acute phase of infection and compare individuals with chronic and self-limited outcomes., Methods: Twenty-two individuals with acute HCV infection, 14 with chronic evolution, and 8 with self-limited infection, were studied using NK phenotypic and functional assays., Results: An increased expression of NKG2D on both CD56(bright) and CD56(dim) NK cells was detected in patients with acute HCV, irrespective of the outcome, as compared with healthy controls. Also, interferon gamma production and cytotoxicity by NK cells were higher in individuals with acute HCV infection than in healthy controls. Subset analysis showed increased interferon gamma production in both NK cell subsets carrying group 1 and group 2 HLA-C-specific killer cell immunoglobulin-like receptors. However, increased CD107a was noted only on NK cells expressing the group 1 HLA-C-specific killer cell immunoglobulin-like receptor and was maximal in self-limited infection., Conclusions: Our data show that in the acute phase of HCV infection, NK cells are activated regardless of outcome, with no evidence of a suppressive effect of HCV on NK cell function., (2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The aim of the present work was to verify whether extra-virgin olive oil, a food naturally containing phenolic antioxidants, has the potential to protect from the pro-aging effects of a high-calorie diet. Male rats were fed from age 12 months to senescence a high-calorie diet containing either corn oil (CO), or extra-virgin olive oil with high (H-EVOO) or low (L-EVOO) amounts of phenols. The prolonged high fat intake led to obesity, liver lipid degeneration and insulin resistance, which were not counteracted by high phenol intake. No difference in overall survival was found at the end of the experiment in the animals treated with H-EVOO compared to the other groups. However, we did detect a protective effect of olive oil on some age-related pathologies and on blood pressure, of which the former was associated with the antioxidant content. Concomitantly, a decrease in DNA oxidative damage in blood cells and plasma TBARS and an increase in liver superoxide dismutase were detected following H-EVOO consumption. Thus, although olive oil phenols cannot reverse the detrimental effects of a prolonged intake of high amounts of fat, improving the quality of olive oil in terms of antioxidant content can be beneficial., (Copyright 2010 Elsevier Inc. All rights reserved.)

Rebuilding brain structure and neural circuitries by transplantation of fetal tissue is a strategy to repair the damaged nervous system and is currently being investigated using striatal primordium in Huntington's disease (HD) patients. Four HD patients underwent bilateral transplantation with human fetal striatal tissues (9-12 week gestation). Small blocks of whole ganglionic eminencies were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the putamen. Follow-up period ranged between 18 and 34 months (mean, 24.7 months). Surgery was uneventful. Starting from the fourth month after grafting, neo-generation of metabolically active tissue with striatal-like MRI features was observed in 6 out of 8 grafts. The increase in D2 receptor binding suggested striatal differentiation of the neo-generated tissue in 3 patients. New tissue, connecting the developing grafts with the frontal cortex and, in one case, with the ventral striatum, was also observed. The new tissue growth halted after the ninth month post transplantation. All patients showed stabilization or improvement in some neurological indices. No clinical and imaging signs, suggestive of graft uncontrolled growth, were seen. This study provides the first evidence in humans that neuroblasts of a striatal primordium can develop and move into the brain after neurotransplantation. Primordium development resulted in the building of a new structure with the same imaging features as the corresponding mature structure, combined with short- and long-distance targeted migration of neuroblasts. The results of this study support both the reconstructive potential of fetal tissue and the remarkably retained plasticity of adult brain. Further studies are necessary to assess the clinical efficacy of the human fetal striatal transplantation., (Copyright 2009 Elsevier Inc. All rights reserved.)

Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA in serum and/or in the liver of patients negative for hepatitis B surface antigen (HBsAg). Occult infection may impact in several different clinical contexts including the risk of HBV transmission with transfusion or transplantation, and endogenous viral reactivation. The gold standard test for detection of occult infection is the amplification of HBV DNA. However, the serological assay for the long-lasting antibody response to the highly immunogenic HBV core antigen (anti-HBc) represents a qualified candidate as a surrogate for DNA amplification, or for increasing overall sensitivity when assessing the risk of occult hepatitis in peripheral blood. The risk of occult hepatitis associated with anti-HBc seropositivity has been demonstrated extensively, and the presence of antibody response to HBc can be considered a sentinel marker of occult HBV infection.

Hydrophilic phenols are the most abundant natural antioxidants of virgin olive oil (VOO), in which, however, tocopherols and carotenes are also present. The prevalent classes of hydrophilic phenols found in VOO are phenolic alcohols and acids, flavonoids, lignans and secoiridoids. Among these substances the last two classes include the most concentrate phenols of VOO. Secoiridoids, like aglycone derivatives of oleuropein, demethyloleuropein and ligstroside, are present in olive fruit as most abundant VOO phenolic antioxidants. Several important biological properties (antioxidant, anti-inflammatory, chemopreventive and anti-cancer) and the characteristic pungent and bitter tasty properties have been attributed to VOO phenols. Relationships between polyphenols activities and their chemical structures are discussed in this paper.

The sensory and health properties of virgin olive oil (VOO) are highly related to its volatile and phenolic composition. Oxygen control in the pastes during malaxation may be a new technological parameter to regulate enzymatic activities, such as polyphenoloxidase, peroxidase, and lipoxygenase, which affect the phenolic and volatile composition of VOO. In this work, we monitored CO2 and O2 concentrations during industrial-scale olive paste malaxation with various initial O2 concentrations within the malaxer headspace. Results show that the O2 concentration in the malaxer headspace did not affect CO2 production during processing, whereas a strong influence was observed on the changes of the phenolic composition of olive pastes and VOOs, with high correlation coefficient for the total phenols (R = 0.94), especially for oleuropein and demethyloleuropein derivatives (R = 0.81). In contrast, aroma production during malaxation was minimally affected by the O2 concentration in the malaxer headspace.

Background: Some epidemiological and experimental studies suggest that olive oil, despite its elevated caloric content, may have protective activity against colon cancer, partially due to its phenolic content. However, little experimental evidence exists to support this claim in vivo., Aim of the Study: To test the effect of olive oils with different phenolic content in a well-characterized model of colon carcinogenesis, comparing them with corn oil (CO)., Methods: F344 rats were fed AIN-76 based diets for the entire experimental period; the diets contained 23% (w/w) of lipids from three different sources: extra-virgin olive oil rich in phenolic compounds (EV), rectified olive oil (ROO) with the same fatty acid composition but devoid of phenolic compounds and CO as a control diet. One week later, rats were induced with 1,2-dimethylhydrazine (DMH) (150 mg/kg b.w. x 2 times) to measure preneoplastic lesions (aberrant crypt foci (ACF) and mucin depleted foci (MDF)) and tumours in the intestine., Results: Thirteen weeks after DMH, the numbers of ACF and MDF were similar in the different groups (ACF/colon were 344.9 +/- 27.0, 288.6 +/- 28.5 and 289.8 +/- 21.4 in CO, EV and ROO groups, respectively, means +/- SE; MDF/colon were 8.83 +/- 1.2, 8.41 +/- 1.5 and 8.75 +/- 1.6 in CO, EV and ROO groups, respectively, means +/- SE). Thirty-two weeks after DMH, the incidence of tumours (rats with tumours/rats in the group) did not differ among the different groups (20/21, 18/19 and 20/20 in the CO, EV, and ROO groups, respectively). Similarly, the number of tumours/ rat in the colorectum (both adenomas and cancers) was not different in the three different groups (2.33 +/- 0.26, 2.42 +/- 0.41 and 2.25 +/- 0.40 in CO, EV and ROO groups, respectively, means +/- SE)., Conclusions: Olive oil, irrespective of its phenolic content, does not affect DMH-induced colon carcinogenesis in F344 rats compared with CO.

MSCs have been proposed as possible treatment in MS: In this study MSCs obtained from 10 MS patients and 6 healthy donors (HD) were compared in terms of phenotypical and functional characteristics. We show that MSCs isolated from MS and HD differ significantly for IP10 production. Therefore, although MSCs isolated from MS patients exhibit the same properties of HD MSCs in terms of proliferation, phenotype, in vitro differentiation, TLR expression, immunosuppressive ability, inhibition of DC differentiation and activation, the use of autologous MSCs in cell therapy of autoimmune diseases should be submitted to attentive evaluation and treatment.