Adverse reaction to Ficus Carica: reported case of a possible cross-reactivity with Der p1.

BACKGROUND: Ficus carica is an edible fruit, belonging to the Moraceae family, rarely described as cause of food allergy. We describe the first case of fig allergy that occurred as a cross-reactivity between fig and Derp 1. CASE PRESENTATION: We present a case of a 10-years-old-girl, with a history of no-seasonal mild intermittent rhinitis, who experienced an immediate reaction after ingestion of a fresh fig. Skin prick tests (SPT) with commercial extracts of food, airborne allergens, latex and panallergens (profilin, PR-10 and lipid transfer protein) were performed. SPT revealed a sensitization only for dermatophagoides farina and dermatophagoides pteronyssinus which was then confirmed with by specific IgE assay (UniCAP, Phadia, Uppsala, Sweden). We also carried out a positive SPT with a commercial fig allergen (Lofarma, Milan, Italy) and prick-by-prick (PBP) both with skin and pulp of green raw and cooked fig. Fig specific serum IgE levels were 1.08 U/ml and specific IgE for rDer p1 was 16.20 U/ml (total serum IgE = 377 U/ml). In contrast specific IgE levels for latex, LTP, profilin, PR-10 and pollen allergens were negative. CONCLUSION: The ficin, the major fig allergen, belongs to cysteine protease family like Der p 1. The symptoms presented by our patient could be related to a cross reactivity between these two proteins which present a structural homology.

LTP allergy/sensitization in a pediatric population.

Plant lipid transfer proteins (LTPs) are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have been described as the most common food allergens in the Mediterranean area. LTP allergy is widely described in adults, but it represents an emerging allergen also in the pediatric population. Little is known about the real prevalence and the clinical features of this allergy in children and it still often remains underdiagnosed in these patients. An early identification and a deeper knowledge of this allergy in childhood can avoid severe systemic reactions and improve the child's quality of life. Pediatricians should always consider the possibility of LTP involvement in cases of plant-derived food allergy.

Histopathology of the skin in rheumatic diseases.

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.

Tight junction dynamics: the role of junctional adhesion molecules (JAMs).

Junctional adhesion molecules (JAMs) are a family of adhesion molecules localized at the tight junction of polarized cells and on the cell surface of leukocytes. The last 20 years of research in this field has shown that several members of the family play an important role in the regulation of cell polarity, endothelium permeability and leukocytes migration. They mediate these pleiotropic functions through a multitude of homophilic and heterophilic interactions with intrafamily and extrafamily partners. In this article, we review the current status of the JAM family and highlight their functional role in tight junction dynamics and leukocyte transmigration.

LRP1/CD91 is up-regulated in monocytes from patients with haemophilia A: a single-centre analysis.

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.

Use of dried stoned olive pomace in the feeding of lactating buffaloes: effect on the quantity and quality of the milk produced.

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.

Reduced circulating endothelial progenitor cell number in healthy young adult hyperinsulinemic men.

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.

Italian Men Tested for BRCA1/2 Mutation: Psychological Distress during 6-Month Follow-Up.

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.

Phenolic compounds in olive oil: antioxidant, health and organoleptic activities according to their chemical structure.

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.

Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.

Inhibitory role of oxytocin on TNFα expression assessed in vitro and in vivo.

AIM: Oxytocin administration to diet-induced obese (DIO) rodents, monkeys and humans decreases body weight and fat mass with concomitant improvements in glucose metabolism. Moreover, several studies show an immunomodulatory role of oxytocin in a number of settings (such as atherosclerosis, injury, sepsis). This study aims to shed some light on the effects of oxytocin on macrophage polarization and cytokine production, as well as its possible impact on these parameters in adipose tissue in DIO mice with impaired glucose metabolism. METHODS: Mouse bone marrow cells were differentiated into macrophages and treated with oxytocin. Macrophage proliferation, cytokine secretion and macrophage populations were determined. For experiments in vivo, DIO mice were treated with oxytocin for 2 weeks. Body weight and composition and glucose tolerance were subsequently followed. At the end of treatment, adipose tissue macrophage populations, plasma cytokine levels and cytokine expression in adipose tissue were determined. RESULTS: In bone marrow-derived macrophages, oxytocin induced an anti-inflammatory phenotype (decreased M1/M2 ratio). In M1-derived macrophages, oxytocin decreased TNFα secretion, with no effects on the other cytokines tested nor any effect on cytokine secretion by M2-derived macrophages. Oxytocin treatment in DIO mice in vivo led to decreased body weight accompanied by an improvement in glucose tolerance, with no changes in plasma cytokine levels. In adipose tissue, oxytocin decreased Tnfα expression without modifying the M1/M2 macrophage ratio. CONCLUSION: Oxytocin treatment decreases TNFα production both in vitro (in bone marrow-derived macrophages) and in vivo (in epididymal adipose tissue) in DIO mice. This effect may also be contributory to the observed improvement in glucose metabolism.

Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B.

High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2. It occurred concomitant with a rapid and marked reduction of viremia. Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection.

Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress.

Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B(5)). Here we show that Vanin-1(-/-) mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body gamma-irradiation or paraquat. This protection is correlated with reduced apoptosis and inflammation and is reversed by treating mutant animals with cystamine. The better tolerance of the Vanin-1(-/-) mice is associated with an enhanced gamma-glutamylcysteine synthetase activity in liver, probably due to the absence of cysteamine and leading to elevated stores of glutathione (GSH), the most potent cellular antioxidant. Consequently, Vanin-1(-/-) mice maintain a more reducing environment in tissue after exposure to irradiation. In normal mice, we found a stress-induced biphasic expression of Vanin-1 regulated via antioxidant response elements in its promoter region. This process should finely tune the redox environment and thus change an early inflammatory process into a late tissue repair process. We propose Vanin-1 as a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level. Therefore, Vanin/pantetheinase inhibitors could be useful for treatment of damage due to irradiation and pro-oxidant inducers.

Cooling treatment of olive paste during the oil processing: Impact on the yield and extra virgin olive oil quality.

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 C6 aldehydes that seem to be more stable than C6 alcohols and esters.

[The treatment of diffuse cutaneous systemic sclerosis with autologous hemopoietic stem cells transplantation (HSCT): our experience on 2 cases]. / Trattamento della forma diffusa di sclerosi sistemica con trapianto autologo di cellule staminali emopoietiche: esperienza su due casi.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (HSCT) is a treatment option which may be considered for severe diffuse cutaneous systemic sclerosis (dcSSc) patients not responding to cyclophophamide (CY). We present two cases of dcSSc not responding to CY >10 g who were successfully treated with HSCT. PATIENTS AND METHODS: Two dcSSc patients were unresponsive to monthly i.v. pulse of CYC (0.75 g m²). Both patients had significant reduction of DLCO and mild-moderate pulmonary hypertension and HSCT was considered due to the rapid progression of the disease. Following informed consent and ethics committee approval, HSCT was performed. Mobilisation was performed with CY 4 g/m² and recombinant human granulocyte colony stimulating factor (rHu GCSF) followed by a successful apheresis (CD34+ cells, >7X106). Conditioning regimens were: CY 100mg/kg body weight plus thiotepa 10 mg/ kg in the first patient and CY 200 mg/kg in the second. Both graft products were CD34 selected. No arrhythmias occurred during the procedure and no other severe side effects were observed during hospitalisation. RESULTS: Follow up: Patients underwent a monthly follow up with physical examination, pulmonary function tests and echocardiography every 3 months. Chest CT has been performed 6 months post transplantation. The following was observed: skin score (from 40 to 10 for the first patient and from 38 to 12 for the second one), LVEF and pulmonary function remained stable, PAP decreased from 45 mmHg to 35 mmHg and from 40 to 32 mmHg. No late complications or cardiac toxicity was observed. CONCLUSION: These two dcSSc cases demonstrate that HSCT may be successfully performed without serious side effects in cases in whom despite a cumulative CY dose was ineffective. This suggests an "immunological threshold" effect which may be exploited in other severe, therapy refractory autoimmune cases.

Effect of an olive phenolic extract on the quality of vegetable oils during frying.

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.

Methodology for the assessment of lung protection. Human pulmonary artery endothelial cell preservation using haemaccel.

This investigation was designed to show an original methodology for the assessment of lung preservation and to analyze the efficacy of a low potassium polygelin solution (haemaccel [HM]) on isolated human pulmonary artery endothelial cells. The effects of HM were compared with those of low potassium dextran (LPD), Belzer (University of Wisconsin [UWS]), and Euro-Collins solutions. The viability of the endothelial cultures was assessed by means of both total protein content and recovery of metabolic cellular function expressed as the protein synthesis rate after 6 hr and 16 hr of incubation at 10 degrees C. Our results failed to show any significant difference in the total protein content for HM, LPD, and UWS, both after 6 and 16 hr of incubation; however, the Euro-Collins-preserved sample revealed a significant drop in this parameter as early as 6 hr after the start. This finding was regarded as a clear indication of cellular cytotoxicity. In contrast, the metabolism recovery capacity of the cells varied significantly between HM and UWS at 6 hr and among HM, LPD, and UWS at 16 hr; at 6 hr, however, no significant difference was observed between HM and LPD. In conclusion, HM appears to exert a more significant effect on human pulmonary artery endothelial cell metabolism recovery than do the other fluids, thus suggesting its suitability as a long-term pulmonary perfusate.

An effective solution for prolonged preservation of cultured human pulmonary artery endothelial cells.

Pulmonary endothelium is considered the compartment most susceptible to preservation damage. This investigation was designed to analyze the efficacy of an original, University of Parma low-potassium-albumin solution (SPAL UP) on cultured human pulmonary artery endothelial cells (HPAEC) and to compare its effects with those of University of Wisconsin solution (UW) and Euro-Collins solution (EC). Cryopreserved HPAEC tertiary cultures were inoculated at the density of 5000 cells/cm2 in 9-cm2 well-plates; subcultures were then incubated at 10 degrees C for 6 hr and 16 hr in 2 ml/well of SPAL UP, UW, and EC. The HPAEC viability after incubation was assessed by evaluating the total protein content and the expression of cytotoxicity, and by analyzing the rate of protein synthesis and expression of cellular functionality after stress. Results after 6 hr of preservation showed that SPAL UP had a less significant cytotoxic effect than EC, exerted a less depressing effect on cellular metabolism, and enhanced functional recovery of endothelial cells compared with UW. At the second time interval (16 hr), SPAL UP provided a less cytotoxic effect than UW; besides, SPAL UP-induced cytotoxicity was similar to that of warm control. In conclusion, in vitro preliminary data regarding the use of SPAL UP in HPAEC preservation suggest its suitability as solution for prolonged lung protection.

Antiviral cell-mediated immune responses during hepatitis B and hepatitis C virus infections.

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.