Heavy metals and trace elements in milk and dairy products in the Lazio region (Central Italy).

A study was carried out to determine the concentration of heavy metals and trace elements in milk and dairy products collected from local farms, supermarkets, or food retailers in the region of Lazio (Central Italy). Persistent exposure to metal contamination is of particular concern for human health, as it can cause different serious disorders. The monitoring of the matrices studied is therefore important, given their high consumption in the daily diet. The elements determined by ICP-MS (Inductively Coupled Plasma - Mass Spectrometry) were lead (Pb), arsenic (As), mercury (Hg), cadmium (Cd), chromium (Cr), nickel (Ni), molybdenum (Mo) and thallium (Tl), for a total of 151 measurements in 98 samples. The results showed that 11.3% of the measurements were quantifiable but below the legal maximum limits (MLs) set by EU regulations. The data obtained may be useful for dietary exposure information, inter-regional comparisons and for planning regional surveillance strategies.

Investigation of ochratoxin A in commercial cheeses and pork meat products by liquid chromatography-tandem mass spectrometry.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium and commonly detected in a wide range of foodstuffs. The purpose of this work was to monitor the presence of OTA in cheeses and pork meat products. A simple and accurate "dilute and shoot" method with no need of immunoaffinity column and isotopic labeled internal standard, by liquid chromatography-tandem mass spectrometry, was validated in accordance with the criteria set out in Commission Regulation (EC) No. 401/2006. The method showed good linearity in solvent and in matrix (R2  ≥ 0.995), limit of detection was 0.2 µg/kg for cheese and 0.3 µg/kg for pork meat products, limit of quantification was fixed at 1 µg/kg, and recovery was estimated at two different concentration levels (1 and 5 µg/kg) and ranged from 75% to 101%. The interday and intraday laboratory precisions were lower than 7%. The matrix effect, the recovery of the extraction process, and the overall process efficiency were evaluated. No significant ME was observed in the two matrices considered. This method was applied to the analysis of 75 samples, coming from official controls implemented by the Lazio Region (Central Italy). In one sample of dry-cured ham, the concentration found (69.3 µg/kg) was well above the guidance value recommended by the Italian Ministry of Health (1 µg/kg). These data together with the detection of OTA in three grated cheeses suggest the importance of monitoring these products. Considering the high dietary intake of these matrices, especially among vulnerable populations, further research should be devoted to estimate exposure and risk assessment for OTA.

Turmeric (Curcuma longa L.) food supplements and hepatotoxicity: an integrated evaluation approach.

INTRODUCTION: Turmeric is the common name for the rhizome of Curcuma longa L. In the recent years, food supplements containing turmeric have been marketed and widely used by an increasing number of consumers. Spontaneous reports of suspected adverse reactions to food supplements are collected within the Phytovigilance system. METHODS: An ad hoc multidisciplinary group investigated the suspected cases of hepatotoxicity reported to the Italian Phytovigilance system associated with the assumption of turmeric food supplements with the methodology specific to pharmacovigilance as well as for the evaluation of the quality and safety of food supplements. RESULTS: A cluster of 28 spontaneous reports of acute hepatitis, mostly with cholestasis, associated with turmeric products were sent to the Italian Phytovigilance system in the first six months of 2019. In all cases, except one, the causality assessment was at least possible. The suspected products were collected and analysed for the presence of drugs, heavy metals, aflatoxins, pesticides, synthetic dyes and pyrrolizidine alkaloids. CONCLUSION: On the basis of the results of all the activities performed by multidisciplinary group, regulatory intervention was taken. This study highlights the importance of developing an integrated evaluation approach for the evaluation of the adverse effects associated with the use of food supplements.

Details of the Contents of Paranoid Thoughts in Help-Seeking Adolescents with Psychotic-Like Experiences and Continuity with Bullying and Victimization: A Pilot Study.

Background: Psychosis recognizes an interaction between biological and social environmental factors. Adversities are now recognized to be consistently associated with psychotic-like experiences (PLEs). The purpose of this study was to describe the contents of paranoid symptoms and to focus on their relationship with bullying and victimization in help-seeking adolescents. Methods: Help-seeking adolescents who screened positive for PLEs participated in the study. They performed a battery self-report questionnaire for data collection (paranoia: the Specific Psychotic Experiences Questionnaire (SPEQ); the content of paranoid thoughts: the Details of Threat (DoT); bullying victimization: the Multidimensional Peer Victimization Scale (MPVS); depression: the Children's Depression Inventory (CDI); and anxiety: the Multidimensional Anxiety Scale (MASC)). Results: The participants were 50 adolescents (52% female; mean age: 170 months). The contents of their paranoid symptoms were related to victimization and, in particular, the certainty of threats was correlated with physical (0.394, p < 0.01) and verbal bullying (0.394, p < 0.01), respectively. The powerfulness of the threats correlated with verbal victimization (0.295, p < 0.05). The imminence of the threats was linked to verbal (0.399, p < 0.01) victimization. Hours under threat correlated with verbal (0.415, p < 0.01) victimization. The sureness of the threat had a moderate correlation with physical (0.359, p < 0.05) and verbal (0.443, p < 0.01) victimization, respectively. The awfulness of the threat was linked to social manipulation (0.325, p < 0.05). Conclusions: We described the content of the persecutory symptoms. The powerfulness, imminence, sureness, and awfulness of threats correlated with the level of physical, verbal and social manipulation victimization. Teachers and family must actively monitor early signs of bullying victimization, and school psychologists should promote preventive and therapeutic intervention. From a social psychiatry perspective, the prevention of bullying victimization is necessary.

Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition.

Alzheimer's disease is the most common type of dementia, affecting millions of people worldwide. One of its main consequences is memory loss, which is related to downstream effectors of cyclic adenosine monophosphate (cAMP). A well-established strategy to avoid cAMP degradation is the inhibition of phosphodiesterase (PDE). In recent years, GEBR-32a has been shown to possess selective inhibitory properties against PDE type 4 family members, resulting in an improvement in spatial memory processes without the typical side effects that are usually correlated with this mechanism of action. In this work, we performed the HPLC chiral resolution and absolute configuration assignment of GEBR-32a. We developed an efficient analytical and semipreparative chromatographic method exploiting an amylose-based stationary phase, we studied the chiroptical properties of both enantiomers and we assigned their absolute configuration by 1H-NMR (nuclear magnetic resonance). Lastly, we measured the IC50 values of both enantiomers against both the PDE4D catalytic domain and the long PDE4D3 isoform. Results strongly support the notion that GEBR-32a inhibits the PDE4D enzyme by interacting with both the catalytic pocket and the regulatory domains.

A glance into psychiatric comorbidity in adolescents with anorexia nervosa.

BACKGROUND: Eating disorders display several psychiatric comorbidities. The aim of this study was to describe these comorbidities in a group of adolescent patients with anorexia nervosa or OSFED (Other Specified Feedind or Eating Disorder). We have evaluated the comorbidity both with a clinical interview (categorical comorbidities) and with a self-report interview (dimensional comorbidities) in order to compare the two profiles. METHODS: The study was carried out at the Division of Child and Adolescent Psychiatry (eating disorder service for developmental age) of the Luigi Vanvitelli University of Campania (ex Second University of Naples). Data were collected retrospectively from chart review, routinely gathered during the clinical assessment. RESULTS: Seventy-two subjects constituted the sample, 62 (86.1%) were female and 10 (13.9%) male. The most frequent categorical comorbidities were social anxiety disorder (SS: 38; 52.8%), Depression disorder (SS: 30; 41.7%) and generalized anxiety disorder (SS: 14; 19.4%). The mean scores at dimensional questionnaires were 15.5 (SD: 10.7) for the depression (Children Depression Inventory) and 34.8 (SD: 28.3) for social anxiety (Liebowitz Social Anxiety Scale). CONCLUSIONS: Data analysis showed that social anxiety and depression were the most common categorical comorbidities in young patients with eating disorders. However, comparing the data from the clinical interview with those of the self-interviews revealed that patients well recognize social anxiety symptoms, but tend to deny depressive ones.

Epidemiological pattern of bullying using a multi-assessment approach: Results from the Bullying and Youth Mental Health Naples Study (BYMHNS).

BACKGROUND: Bullying is a widespread phenomenon that has captured attention from mental health researchers. Several studies have assessed bullying prevalence with some methodological concerns. OBJECTIVES: Preliminary, we analyzed the psychometric properties of two bullying scales for victimization (the multidimensional peer victimization scale - MPVS) and for perpetration (the bully subscale of the Illinois bully scale - IBS-B); then, we estimated bullying prevalence; finally, we evaluated the effect of gender and classroom on the phenomenon. PARTICIPANTS AND SETTING: 2959 students from the metropolitan city of Naples constituted the sample. METHODS: Data collection was obtained using a multi-assessment approach that included both single-item questions and intensity scales in order to compare the two methods. RESULTS: The two scales resulted valid and showed good reliability. The MPVS displayed a 1-factor second order model. The IBS-B had a mono-factorial structure. Both showed full invariance for gender and classroom. Prevalence of victimization was 37% whereas that for perpetration was 21%. As expected we obtained several bullying prevalence results depending on the specificity of questions and in particular repetitiveness of episodes. There was a good correspondence between results of single-item questions and multi-item scales. Finally results demonstrated several differences for gender and classroom attended. CONCLUSION: In this epidemiological study the multi-assessment approach identified different but complementary features of bullying phenomena. The use of the two measurement approaches allowed us to obtain more precise and exhaustive information on bullying prevalence and compare it with previous findings.

Glycated fibroblast growth factor-2 is quickly produced in vitro upon low-millimolar glucose treatment and detected in vivo in diabetic mice.

Angiogenesis impairment in hyperglycemic patients represents a leading cause of severe vascular complications of both type-1 and -2 diabetes mellitus (DM). Angiogenesis dysfunction in DM is related to glycemic control; however, molecular mechanisms involved are still unclear. Fibroblast growth factor-2 (FGF-2) is a potent angiogenic factor and, according to previous evidence, may represent a key target of molecular modifications triggered by high-sugar exposure. Therefore, the purpose of this study was to investigate whether short incubation with hyperglycemic levels of glucose affected FGF-2 and whether glucose-modified FGF-2 was detectable in vivo. Biochemical analyses carried out with SDS-PAGE, fluorescence emission, mass-spectrometry, immunoblot, and competitive ELISA experiments demonstrated that human FGF-2 undergoes a rapid and specific glycation upon 12.5-50 mm glucose exposure. In addition, FGF-2 exposed for 30 min to 12.5 mm glucose lost mitogenic and chemotactic activity in a time- and dose-dependent manner. Under similar conditions, binding affinity to FGF receptor 1 was dramatically reduced by 20-fold, as well as FGF receptor 1 and ERK-1/2 phosphorylation, and FGF-2 lost about 45% of angiogenic activity in two different in vivo angiogenic (Matrigel and chorioallantoic-membrane) assays. Such glucose-induced modification was specific, because other angiogenic growth factors, namely platelet-derived growth factor BB and placental-derived growth factor were not significantly or markedly less modified. Finally, for the first time, glycated-FGF-2 was detected in vivo, in tissues from hyperglycemic nonobese diabetic mice, in significantly higher amounts than in normoglycemic mice. In conclusion, hyperglycemic levels of glucose may strongly affect FGF-2 structure and impair its angiogenic features, and endogenous glycated-FGF-2 is present in diabetic mice, indicating a novel pathogenetic mechanism underlying angiogenesis defects in DM.

Heterodimerization of FGF-receptor 1 and PDGF-receptor-alpha: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells.

Previous evidence has shown that platelet-derived growth factor-BB (PDGF-BB) and fibroblast growth factor-2 (FGF-2) directly interact with high affinity, leading to potent reciprocal inhibitory effects on bovine endothelial cells and rat vascular smooth muscle cells. In this study, we report that PDGF-BB inhibits a series of FGF-2-induced events, such as proliferation of human umbilical vein endothelial cells (HUVECs), FGF-2 cellular internalization, phosphorylation of intracellular signaling factors including p38, rac1/cdc42, MKK4, and MKK3/6, and phosphorylation of FGF-receptor 1 (FGF-R1). PDGF-receptor-alpha (PDGF-Ralpha) was found to mediate PDGF-BB inhibitory effects because its neutralization fully restored FGF-2 mitogenic activity and internalization. Additional biochemical analyses, coimmunoprecipitation experiments, and FRET analysis showed that FGF-R1 and PDGF-Ralpha directly interact in vitro and in vivo and that this interaction is somehow increased in the presence of the corresponding ligands FGF-2 and PDGF-BB. These results suggest that FGF-R1/PDGF-Ralpha heterodimerization may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control endothelial cell function.

Identification of a novel domain of fibroblast growth factor 2 controlling its angiogenic properties.

Fibroblast growth factor 2 (FGF-2) is a potent factor modulating the activity of many cell types. Its dimerization and binding to high affinity receptors are considered to be necessary steps to induce FGF receptor phosphorylation and signaling activation. A structural analysis was carried out and a region encompassing residues 48-58 of human FGF-2 was identified, as potentially involved in FGF-2 dimerization. A peptide (FREG-48-58) derived from this region strongly and specifically inhibited FGF-2 induced proliferation and migration of primary bovine aorta endothelial cells (BAEC) in vitro, and markedly reduced FGF-2-dependent angiogenesis in two distinct in vivo assays. To further investigate the role of region 48-58, a polyclonal antibody raised against FREG-(48-58) was tested and was found to block FGF-2 action in vitro. Human FGF-2 has three histidine residues, one falling within the region 48-58. Chemical modification of histidine residues blocked FGF-2 activity and FREG-(48-58) inhibitory effect in vitro, indicating that histidine residues, in particular the one within FREG-(48-58) region, play a crucial role in the observed activity. Additional experiments showed that FREG-(48-58) specifically interacted with FGF-2, impaired FGF-2-interaction with itself, with heparin and with FGF receptor 1, and inhibited FGF-2-induced receptor phosphorylation and FGF-2 internalization. These data indicate for the first time that region 48-58 of FGF-2 is a functional domain controlling FGF-2 activity.

Platelet-derived growth factor-BB and basic fibroblast growth factor directly interact in vitro with high affinity.

Platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) are potent growth factors active on many cell types. The present study indicates that they directly interact in vitro. The interaction was investigated with overlay experiments, surface plasmon resonance experiments, and solid-phase immunoassays by immobilizing one factor or the other and by steady-state fluorescence analysis. The interaction observed was specific, dose-dependent, and saturable, and the bFGF/PDGF-BB binding stoichiometry was found to be 2:1. K(D)(1) for the first step equilibrium and the overall K(D) values were found to be in the nanomolar and in the picomolar range, respectively. Basic FGF/PDGF-BB interaction was strongly reduced as a function of time of PDGF-BB proteolysis. Furthermore, docking analysis suggested that the PDGF-BB region interacting with bFGF may overlap, at least in part, with the PDGF-BB receptor-binding site. This hypothesis was supported by surface plasmon resonance experiments showing that an anti-PDGF-BB antibody, known to inhibit PDGF-BB binding with its receptor, strongly reduced bFGF/PDGF-BB interaction, whereas a control antibody was ineffective. According to these data, the observed bFGF.PDGF-BB complex formation might explain, at least in part, previous observations showing that PDGF-BB chemotactic and mitogenic activity on smooth muscle cells are strongly inhibited in the presence of bFGF.