Toll-like receptor gene polymorphisms in patients with myeloproliferative neoplasms.

Toll-like receptors (TLRs) are a family of transmembrane receptors whose signaling control cellular processes of cell proliferation, survival, apoptosis, angiogenesis, remodeling, and repair of tissues. Polymorphisms in TLR genes can change the balance between pro and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer. Although many studies have demonstrated the direct involvement of TLR signaling in the benefit of tumor cells in certain cancers, little is known about the influence of these gene polymorphisms on myeloproliferative neoplasms (MPNs). In this context, the objective of the study was to investigate a possible association between the TLR polymorphisms and the development of MPNs. 167 patients diagnosed with MPN and 222 healthy controls from the same region were evaluated. Genomic DNA was extracted and the TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and JAK2V617F polymorphisms were genotyped by PCR-RFLP. The statistical analysis was performed by OpenEpi and SNPstat software. The JAK2V617F mutation was found in 68.32% of patients. TLR9-1486C/T CT genotype was less frequent in patients with polycythemia vera (PV) (OR 0.39, 95% CI 0.20-0.78, P = 0.025). When haplotype frequencies were analyzed, -1237T/-1486C (TLR9) was also less frequent in men (OR 0.58, 95% CI 0.36-0.94) and JAK negative men patients (OR 0.43, 95% CI 0.21-0.88). We can infer that the TLR9-1486 CT genotype could be associated with protection for PV and the TLR9-1237T/-1486C haplotype, protection for men, as well as for JAK negative men patients with MPN. There were no associations between TLR2 and TLR4 gene polymorphisms and MPN.

Sensory and chemical profile of a phenolic extract from olive mill waste waters in plant-base food with varied macro-composition.

Phenols from olive mill waste water (OMWW) represent valuable functional ingredients. The negative impact on sensory quality limits their use in functional food formulations. Chemical interactions phenols/biopolymers and their consequences on bioactivity in plant-base foods have been widely investigated, but no studies to date have explored the variation of bitterness, astringency and pungency induced by OMWW phenols as a function of the food composition. The aim of the paper was to profile the sensory and chemical properties of phenols from OMWW in plant-base foods varied in their macro-composition. Four phenol concentrations were selected (0.44, 1.00, 2.25, 5.06 g/kg) to induce significant variations of bitterness, sourness, astringency and pungency in three plant-base food: proteins/neutral pH - bean purée (BP), starch/neutral pH - potato purée (PP), fiber/low pH - tomato juice (TJ). The macro-composition affected the amount of the phenols recovered from functionalized food. The highest recovery was from TJ and the lowest from BP. Two groups of 29 and 27 subjects, trained to general Labelled Magnitude Scale and target sensations, participated in the evaluation of psychophysical curves of OMWW phenols and of functionalized plant-base foods, respectively. Target sensations were affected by the food macro-composition. Bitterness increased with phenol concentration in all foods. Astringency and sourness slightly increased with concentration, reaching the weak-moderate intensity at the highest phenol concentration in PP and TJ only. Pungency was suppressed in BP and perceived at weak-moderate intensity in PP and TJ sample at the highest phenol concentration. Proteins/neutral pH plant-food (BP) resulted more appropriate to counteract the impact of added phenol on negative sensory properties thus allowing to optimize the balance between health and sensory properties.

HLA polymorphisms and risk of red blood cell alloimmunisation in polytransfused patients with sickle cell anaemia.

BACKGROUND: Red blood cell (RBC) alloimmunisation is an event that may occur due to factors such as numerous blood transfusions, age, gender and genetic factors such as human leukocyte antigen (HLA). AIMS/OBJECTIVES: The aim of the present study was to investigate the possibility of alloimmunisation to red blood cell group antigens associated with the HLA of individuals and to relate alloimmunisation to risk factors. METHODS: A total of 172 polytransfused patients with sickle cell anaemia (SCA) (44 alloimmunised, 128 non-alloimmunised) participated in this study. Blood group genotyping was performed by the DNA microarray method and HLA genotyping by polymerase chain reaction - specific sequence of oligonucleotides. RESULTS: The number of transfusions received directly influenced the incidence of alloimmunisation, and the most common alloantibodies were against Rh (48·8%) and Kell (17%) systems. The HLA-C*06 and HLA-DQB1*03 variants were significantly higher in alloimmunised patients. The HLA-DRB1*04 and HLA-DRB1*11 were more often found in individuals who developed the alloantibodies anti-Fya and anti-K, respectively. CONCLUSION: This study suggests that polytransfused patients with SCA possessing the HLA-DQB1*03 and HLA-C*06 allele variants are more susceptible to alloimmunisation. In addition, HLA-DRB1*04 and HLA-DRB1*11 alleles were seen to be associated with the production of anti-Fya and anti-K antibodies, respectively.

JAK2 46/1 haplotype is associated with JAK2 V617F--positive myeloproliferative neoplasms in Brazilian patients.

INTRODUCTION: This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. METHODS: The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. RESULTS: The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. CONCLUSION: In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients.

Evaluation of the association between the JAK2 46/1 haplotype and chronic myeloproliferative neoplasms in a Brazilian population.

OBJECTIVE: The JAK2 46/1 haplotype has recently been described as a major contributing factor to the development of myeloproliferative neoplasm, whether positive or negative forthe JAK2 V617F mutation. The G allele, identified by a single-nucleotide polymorphism known as JAK2 rs10974944, is part of the JAK2 46/1 haplotype. The aim of this study was to verify the association between the presence of the G allele and the development of BCR-ABL-negative chronic myeloproliferative neoplasms in our population. METHODS: Blood and oral mucosa swab samples were obtained from 56 patients of two local Brazilian hospitals who had previously been diagnosed with BCR-ABL-negative chronic myeloproliferative neoplasms. Blood samples from 90 local blood donors were used as controls. The presence of the G allele was assessed using a PCR-RFLP assay after extracting DNA from the samples. RESULTS: The presence of the G allele was strongly associated with the presence of BCR-ABL-negative chronic myeloproliferative neoplasms (p = 0.0001; OR = 2.674; 95% CI = 1.630-4.385) in the studied population. CONCLUSION: In agreement with previous reports, the JAK2 46/1 haplotype, represented in this study by the presence of the G allele, is an important predisposing factor in the oncogenetic development of these neoplasms in our population.

Evaluation of the association between the JAK2 46/1 haplotype and chronic myeloproliferative neoplasms in a Brazilian population

OBJECTIVE: The JAK2 46/1 haplotype has recently been described as a major contributing factor to the development of myeloproliferative neoplasm, whether positive or negative forthe JAK2 V617F mutation. The G allele, identified by a single-nucleotide polymorphism known as JAK2 rs10974944, is part of the JAK2 46/1 haplotype. The aim of this study was to verify the association between the presence of the G allele and the development of BCR-ABL-negative chronic myeloproliferative neoplasms in our population. METHODS: Blood and oral mucosa swab samples were obtained from 56 patients of two local Brazilian hospitals who had previously been diagnosed with BCR-ABL-negative chronic myeloproliferative neoplasms. Blood samples from 90 local blood donors were used as controls. The presence of the G allele was assessed using a PCR-RFLP assay after extracting DNA from the samples. RESULTS: The presence of the G allele was strongly associated with the presence of BCR-ABL-negative chronic myeloproliferative neoplasms (p = 0.0001; OR = 2.674; 95% CI = 1.630-4.385) in the studied population. CONCLUSION: In agreement with previous reports, the JAK2 46/1 haplotype, represented in this study by the presence of the G allele, is an important predisposing factor in the oncogenetic development of these neoplasms in our population.

Food memory and its relation with age and liking: an incidental learning experiment with children, young and elderly people.

The present study compared incidental learning and food memory in children, young adults and elderly people for three sensory modalities (taste, texture and aroma). The relation of gender and liker-status (i.e. how much we like a product) with food memory was also investigated. Participants received a complete meal including a custard dessert used as target under incidental learning conditions. 24h later, participants were confronted with a series of samples consisting of the target and slightly modified versions of the target (distractors) and were unexpectedly asked to perform an "absolute memory" ("Did you eat this sample yesterday?") and a "relative memory" test ("Is the present sample less/equal/more pleasant than the one you ate yesterday?"). Participants also performed a hedonic and a discrimination test. Memory for the custard was poor and did not depend on age, but it was related to gender, and to how much participants liked the product. Females and high-likers outperformed males and low-likers in the absolute memory task, but they were not better in discriminating the products on both the hedonic and the perceptual dimension. Results also showed that, contrary to common belief, not all sensory aspects that can be discriminated in perception and in liking, are equally well remembered.

Comparative effect of glucagon and isoproterenol on hepatic glycogenolysis and glycolysis in isolated perfused liver

The effect of glucagon and isoproterenol (beta-adrenergic agonist) on hepatic glycogenolysis and glycolysis in isolated perfused liver was compared. The levels of isoproterenol and glucagon which promoted the maximal activation of glycogenolysis were 20 muM and 1nM respectively. However, glucagon (1 nM) not only increased glycogenolysis but also inhibited glycolysis. Because adenosine-3'-5'-cyclic monophosphate (cAMP) is a common second messenger to glucagon and isoproterenol, the level of cAMP that simulates the effect of these substances were investigated. The concentration of cAMP that inhibited glycolysis was five times higher (15 muM) than that which stimulated glycogenolysis (3 muM). Similar inhibition of glycolysis was obtained with cAMP agonists resistant to phosphodiesterases, i.e., 8-Br-cAMP and N6-monobutyryl-cAMP (6-MB-cAMP) at the concentration of 3 muM. Thus, apparently glucagon could produce higher cellular levels of cAMP than that obtained with the activation of beta-adrenergic receptors. The higher amount of cAMP could be enough to overcome the action of phosphodiesterases and penetrate in the cytosol creating a favourable gradient to inhibit the enzymes of glycolysis

Alterações displásicas em pólipos gástricos de glândulas fúndicas: relato de caso / Dysplastic changes in gastric polyps of fundus glands: case report

Os pólipos de glândulas fúndicas ocorrem tanto na forma esporádica como na familiar. Em pacientes com popilose adenomatosa familiar (FAP) e popilose adenomatosa familiar atenuada (AFAP),constituem um importante indicador diagnóstico. Podem apresentar focos de displasia, principalmente nos casos familiares.Os autores relatam um caso de polipose gástrica, com pólipos hemartomatosos de glândulas fúndicas contendo focos de displasia, possívelmente associados a um quadro de polipose múltipla familiar. Além disso, apresenta-se breve revisão bibliográfica da associação desses pólipos com a popilose adenomatosa e com adenocarcinoma

Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia.

The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g) with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 microM cAMP was decreased (P<0.05) in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 microM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 microM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP.

Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia

The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g) with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 æM cAMP was decreased (P<0.05) in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 æM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 æM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP

Influence of dietary fat, on fatty acid composition and sensory properties of dry-cured Parma ham.

A feeding trial with 27 pigs was performed in order to estimate the effect of different dietary fats on the fatty acid composition, flavour and sensory properties of dry-cured Parma hams, ripened for 16 months. The animals received a pelleted diet supplemented with different fat sources: tallow (TA), corn oil (CO), and rapeseed oil (RO). The sensory quality of the hams was evaluated by means of sensory analyses and by instrumental procedures such as gas chromatography-mass spectrometry of the volatile aroma compounds. A treatment effect was detected for linolenic acid in RO vs. CO and TA hams (P<0.01) and for MUFA content (P<0.01) that was higher in RO and TA compared with CO. The results of panel test showed a significant difference (P<0.05) between TA vs. CO and RO hams. Volatile compounds showed limited differences even if in CO group the amount of singular compound is higher than TA and RO.

Effects of dietary fats on meat quality and sensory characteristics of heavy pig loins.

This study examined the influence of dietary fat supplementation to heavy pigs on the meat quality and sensory characteristics of loins. The animals were fed diets containing tallow (TA), corn oil (CO) or rapeseed oil (RO) from 25 kg up to 160 kg live weight (LW). The fats were added at 3% as fed from 25 to 110 kg LW, and at 2.5% from 110 kg LW to slaughtering. Diets were fed at 9% BW(0.75). We found no differences between dietary treatments for loin weight, pH, or color of longissimus lumborum (LL) muscle at 45 min and 24 h after slaughtering. No significant differences in moisture, total protein or total lipid content of LL muscle were found. The linolenic acid content of the total lipid of LL muscle was higher in pigs fed RO than those fed TA and CO. The oxidative stability of LL, as determined by induced TBARS, was lower in pigs fed CO - after 60 min of forced oxidation - and in animals fed CO and RO after 300 min, compared to those fed TA. No significant differences in the sensory characteristics of loin were discerned by a panel of trained tasters. These results indicate that long-term nutrition with added fat at the levels we used has little or no effect on the meat quality or sensory characteristics of heavy pig loin.

Multivariate analysis of antioxidant power and polyphenolic composition in red wines.

It has been demonstrated that the dietary intake of compounds having antioxidant activity is very important, and various chemical, biological, and electrochemical methods have been proposed to evaluate the antioxidant power of compounds such as polyphenols. Wine, although nonessential, has a high polyphenol content up to 2-3 g/L in red wines obtained by traditional maceration. The polyphenol content of wines is usually evaluated by the Folin reagent, which provides an appropriate response to the requirements of wine manufacturers. Because the presence of individual polyphenols may be evaluated by HPLC, more or less selective methods toward the various chemical classes of polyphenols have been developed. An HPLC method set up recently was applied to evaluate how individual polyphenols contributed to the overall antioxidant power (AOP) of 60 Italian red wines, trying to identify the effect that individual compounds may have on the total AOP. Application of the multivariate analysis allowed us to detect some determining compounds such as gallic acid and some flavonols. On the basis of the correlation between two traditional chemical methods, namely the total polyphenol determination by the Folin reagent and the flavanol determination by the condensation reaction with p-(dimethylamino)-cinnamaldehyde, it was shown that the use of these two merely chemical methods is well correlated (r = 0.83 and 0.87) to an AOP evaluation of red wines.

Predictive study on Tuscan extra virgin olive oil stability under several commercial conditions.

Industries aim to ensure extra virgin olive oil (EVOO) stability especially during commercial activities up to use by end consumers. The objective of this work was to set up predictive models of EVOO stability during commercial activities. Stability was studied on five lots of a batch of Tuscan virgin olive oil to simulate different commercial activities. Chemical, physical, and sensory analyses were carried out on EVOO samples. Experimental data were processed by multivariate analyses to select significant parameters and by regression analyses to set up kinetic models. A few parameters were found to be significant: hydroxytyrosol and tyrosol contents, carotenoid absorbance at 475 and 448 nm, alpha-tocopherol content, Rancimat induction time, and K(232). It was also shown that the stability of this EVOO was not significantly influenced by different uncontrolled bottling, transport, and storage conditions in supermarkets. Empirical models were set up to predict the time to reach a reference value for K(232).