Could soluble minerals be hazardous to human health? Evidence from fibrous epsomite.

From a toxicological point of view, particulates and fibres with high solubility in water and/or in biological environments have not been considered in detail and the knowledge to date in this area is very scarce. In this study, the water-soluble natural epsomite fibres from Perticara Mine (Italy) were investigated using SEM-EDS, XRPD, ICP-AES and alpha spectrometry measurements which were combined and integrated to characterise the fibres' morphology, crystal chemistry and mineralogy. The morphological and morphometric results showed that most of the fibres are of inhalable size (Dae 5.09 µm) and can be potentially adsorbed from all parts of the respiratory tract. Chemical analysis reveals significant amounts of toxic elements (As, Co, Fe, Mn, Ni, Sr, Ti, Zn) and surprisingly high contents of radioactive isotopes (210Po and 228Th) in epsomite crystals, making the inhalation of these fibres potentially hazardous to human health. Through this study, we want to focus on soluble minerals, such as epsomite, which can be present in both natural and anthropic environments and have never been considered from the point of view of their potential hazard.

Hepatotoxicity caused by mebendazole in a patient with Gilbert's syndrome.

WHAT IS KNOWN AND OBJECTIVE: Mebendazole (MBZ) is a broad-spectrum antihelminthic agent of the benzimidazole type. Although MBZ has been reported to cause hepatic injury, case reports of severe hepatic injury are very rare. We report a case of severe hepatitis after administration of MBZ in a patient with Gilbert's syndrome affected by pinworms infestation. CASE SUMMARY: Differently from other cases of hepatitis due to MBZ reported in the scientific literature, our patient received standard doses of MBZ for a short period of time. After 18 days from the start of therapy, he developed hepatomegaly, and increases in hepatic enzymes and bilirubin. Hepatic enzymes returned to normal over the following 5 weeks. WHAT IS NEW AND CONCLUSION: This is the first case report of important liver injury after administration of MBZ in a patient with Gilbert's syndrome. We suspected that a diminished hepatic glucuronidation of MBZ due to the reduced activity of the glucuronosyltransferase enzyme in our patient could have caused an increase in unconjugated toxic metabolites of MBZ and the consequent liver damage.

Essential and toxic elements in honeys consumed in Italy.

The aim of this study was to determine the levels of iron (Fe), manganese (Mn), chromium (Cr), copper (Cu), zinc (Zn), mercury (Hg), cadmium (Cd) and lead (Pb) in several types of honey purchased from the local consumer markets in Central Italy by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Lead and Cd were also determined by Atomic Absorption Spectrometry with graphite tube atomization (AAS-GTA). The degree of humidity, sugar content, pH, free acidity, combined acidity (lactones) and total acidity were also measured. These elements were found to be present in honeys in various proportions depending upon (1) area foraged by bees, (2) flower type visited for the collection of nectar, and (3) quality of water in the vicinity of the hive. The honeys consumed in Italy were of good quality, but not completely free of heavy metal contamination. Compared with established recommended daily intakes, heavy metals or trace element concentrations in samples investigated, however, do not pose any serious concern to human health.

Applicability of an in vitro gastrointestinal digestion method to evaluation of toxic elements bioaccessibility from algae for human consumption.

This study aimed to investigate the bioaccessibility of toxic elements, including aluminum (Al), arsenic (As), nickel (Ni), cadmium (Cd), and lead (Pb) in five commercial algae consumed by humans in Italy. The degree of bioaccessibility of these elements may have important implications for human health. Simulation of gastrointestinal tract (GIT) digestion was divided into three stages through use of synthetic saliva, gastric, and bile-pancreas solutions. After pre-treatment with a saliva solution, seaweed samples underwent one of the following treatments: (1) simulated gastric digestion only or (2) simulated complete GIT digestion (gastric digestion followed by bile-pancreas digestion). The bioaccessibility of these toxic elements ranged from approximately 5% to 73% and from 4% to 77% in gastric and GIT digestion, respectively. The bioaccessibility of Al and Pb is poor (5-15%), As and Ni were fairly (40-55%), while Cd displayed a high bioaccessibility. No significant differences in toxic elements mobility was found between samples that only underwent gastric digestion compared to those that underwent a complete GIT digestion.

210Polonium bioaccessibility assessment in algae for human consumption: An in vitro gastrointestinal digestion method.

The occurrence and mobility of natural radioactive element as 210Polonium (210Po) in 13 commercial algae consumed in Italy by humans were determined because the effects on human health need to take into account the bioavailability of these elements. The simulation of gastrointestinal (GIT) digestion was divided into three stages and was accomplished using three different artificial solutions: saliva, gastric, and synthetic bile-pancreas solution. The same sample was treated in two different ways: a) only gastric digestion and b) complete GIT digestion (gastric digestion followed by bile-pancreas solution). The difference between Po gastric mobility with respect to that found for GIT digestion was not significant; in fact, Po mobility exhibited a mean value 17.2 ± 15.1% and 19.5 ± 11.5% for gastric and GIT digestion, respectively.

Radioactivity measurements and dosimetric evaluation in meat of wild birds.

The aim of this study was to determine the background activity concentration of natural radionuclides and 137Cesium (Cs) in meat of 14 migratory birds originating from central and northern Europe. This meat is largely consumed by the Italian population. 40K, 210Pb, and 137Cs were determined by gamma spectrometry and 210Po by alpha spectrometry. The mean 40K activity concentration detected was 490 ± 117 Bq/kgdw. In all the samples, 210Pb was below the limit of detection (LOD), and therefore it was not possible to calculate the ratio 210Po/210Pb. The 210Po activity concentration ranged between 0.11 ± 0.02 Bq/kgdw and 6.2 ± 0.93 Bq/kgdw with a mean value of 1.03 ± 1.75 Bq/kgdw. The 137Cs activity concentration was not detectable or near LOD except in two samples with 45 ± 0.7 Bq/kgdw (wood pigeon, from Italy) and 139.1 ± 1.9 Bq/kgdw (woodcock, from Sweden). The effective dose of 210Po ingested by consumption of wild birds meat accounts for only 0.01-0.6% of natural radiation exposure in Italy. These data indicate that the meat analyzed was safe.

Application of an in vitro digestion model for 210Po bioaccessibility assessment in seafood.

This study aims to investigate the bioaccessibility of 210Po in seafood and the impact of food preparation on this radionuclide. Polonium bioaccessibility is the fraction of 210Po mobilised from food matrices into digestive extractants when applying an in vitro digestion model. The degree of bioaccessibility of 210Po in food has important implications for estimating ingestion doses from this radionuclide. The simulation of gastrointestinal digestion was divided into three stages through the use of synthetic saliva, gastric and bile-pancreas solutions. Following pre-treatment with a saliva solution, raw and cooked seafood samples underwent one of the following treatments: (a) simulated gastric digestion only or (b) simulated complete gastrointestinal digestion (gastric digestion followed by bile-pancreas digestion). No significant difference (P > 0.05) in 210Po mobility was found between samples that underwent gastric digestion compared to those that only underwent gastro-intestinal digestion. However, a significant difference (P < 0.05) in 210Po bioaccessibility was found between raw and cooked seafood undergoing both gastric and gastro-intestinal digestion.

Essential and toxic elements in meat of wild birds.

Essential and toxic elements were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES), mass spectrometry (MS), and atomic absorption (AS) in meat of 14 migratory birds originating from central and northern Europe to provide baseline data regarding game meat consumed in central Italy. In all samples analyzed, cobalt (Co) and chromium (Cr) (total) levels were <0.326 mg/kgww. For nonessential or toxic elements, arsenic (As), barium (Ba), cadmium (Cd), stannous (Sn), thallium (Tl), tellurium (Te), titanium (Ti), cerium (Ce), lantanium (La), and uranium (U) concentrations were <0.326 mg/kgww, thorium (Th) <1.63 mg/kgww, and mercury (Hg) <0.0163 mg/kgww. When detectable, lead (Pb) concentrations always exceeded maximal admissible levels for metal (0.1 mg/kg ww) established by the European Commission for meat. These findings indicate that elevated Pb concentrations in game ingested by humans may be a cause for concern.

Vulvar Melanoma Associated with Lichen Sclerosus in a Child: Case Report and Literature Review.

The authors describe the sixth pediatric case to date of primary vulvar melanoma associated with lichen sclerosus and propose a practical management for such a rare cancer.

Essential and toxic elements in clays for pharmaceutical and cosmetic use.

Essential and toxic elements (Al, Si, P, S, K, Ca, Ti, Mn, Fe, Ni, Cu, Zn, As, Br, Rb, Sr, Ba, Cd, Ce, Nd, Pb, U, Th, and La) were determined by energy-dispersive polarized x-ray fluorescence spectrometry (EDPXRF) in 15 samples of clay materials for pharmaceutical and cosmetic use. The investigated samples were grouped according to their mineralogical composition determined by x-ray powder diffraction (XRPD). Samples consisting of smectites showed the lowest content of K, Zn, La, Ce, Nd, Pb, Ti, and Th and highest quantity of Sr, Br, and U. The sample containing smectite and kaolinite displayed the lowest content of Ca, Fe, Mn, Cu, Ni, and Sr and highest amount of Al, Si, Ba, Zn, As, La, Ce, Pb, and Th. Samples composed of illite demonstrated minimal amounts of Br and maximal content of K, Rb, Ti, and Fe. In all samples analyzed, Cd and Hg levels were below 2 mg/kg.

Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives.

STATs are transcription factors acting as intracellular signaling after stimulation with cytokines, growth factors and hormones. STAT5 is also constitutively active in many forms of cancers, including chronic myelogenous leukemia, acute lymphoblastic leukemia and Hodgkin's lymphoma. Recently, literature reported that the neuroleptic drug pimozide inhibits STAT5 phosphorylation inducing apoptosis in CML cells. We undertook an investigation from pimozide structure, obtaining simple derivatives with cytotoxic and STAT5-inhibitory activity, two of them markedly more potent than pimozide.

From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: synthesis and biological evaluation of valproic esters of 3'-C-methyladenosine.

We synthesized a series of serum-stable covalently linked drugs derived from 3'-C-methyladenosine (3'-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3'-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2',5'-bis-O-valproyl-3'-C-methyladenosine (A160) and 5'-O-valproyl-3'-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting features as an RR inhibitor. It inhibited RR activity by competing with ATP as an allosteric effector and concomitantly reduced the intracellular deoxyribonucleoside triphosphate (dNTP) pools. A167 represents a novel lead compound, which in contrast to previously used RR nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases.

Chemical characterization of baby food consumed in Italy.

In this study, a total of 30 elements (essential and non-essential or toxic) were determined in 25 foods consumed in Italy by children aged 0-6 months and produced in Europe. Inductively Coupled Plasma-Atomic Emission Spectrometry and Inductively Coupled Plasma-Mass Spectrometry were used as measurement techniques for the elements of interest. The estimated intakes for one-year-old infants were compared with risk estimators and nutritional requirements. Data indicate that commercially available baby food in Italy provides an excellent contribution for Mn, Cu, Fe, Zn, Ca, K, and P, covering up to approximately 70% of the adequate intake (AI) for an infant aged 6-12 months. The intake of detectable toxic elements was always below the safety limit: even the most concentrated toxic elements never exceeded about 86% of the Provisional Tolerable Weekly Intake (PTWI). This result indicates that the analyzed baby food is of good quality and does not pose risks to children's health.

Oxidative Stress as a Target for Non-Pharmacological Intervention in MAFLD: Could There Be a Role for EVOO?

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.

The new iodoacetamidobenzofuran derivative TR120 decreases STAT5 expression and induces antitumor effects in imatinib-sensitive and imatinib-resistant BCR-ABL-expressing leukemia cells.

The identification of novel compounds modulating the expression/activity of molecular targets downstream to BCR-ABL could be a new approach in the treatment of chronic myeloid leukemias (CMLs) resistant to imatinib or other BCR-ABL-targeted molecules. Recently, we synthesized a new class of substituted 2-(3,4,5-trimethoxybenzoyl)-2-N,N-dimethylamino-benzo[b]furans, and among these 3-iodoacetylamino-6-methoxybenzofuran-2-yl(3,5-trimethoxyphenyl)methanone (TR120) showed marked cytotoxic activity in BCR-ABL-expressing cells. Interestingly, TR120 was more potent than imatinib in cell growth inhibition and apoptosis induction in both BCR-ABL-expressing K562 and KCL22 cells. Moreover, it showed antitumor activity in imatinib-resistant K562-R and KCL22-R cells at concentrations similar to those active in the respective sensitive cells. Further, TR120 induced a marked decrease in signal transducer and activator of transcription 5 (STAT5) expression in K562 cells. Consistent with this effect, it determined a block of cells in the G0-G1 phase of the cell cycle, a decrease in the level of cyclin D1, and a reduction in Bcl-xL expression; however, it did not cause modifications in the Bcl-2 level. Of interest, TR120 had synergistic effects when used in combination with imatinib in both sensitive and resistant cells. Considering that STAT5 is a BCR-ABL molecular target that plays a key role in the pathogenesis of CML as well as in BCR-ABL-mediated resistance to apoptosis, TR120 could potentially be a useful novel agent in the treatment of imatinib-resistant CML.

Nrf2-Mediated Pathway Activated by Prunus spinosa L. (Rosaceae) Fruit Extract: Bioinformatics Analyses and Experimental Validation.

In our previous studies, Prunus spinosa fruit (PSF) ethanol extract was showed to exert antioxidant, antimicrobial, anti-inflammatory and wound healing activities. In the present study, an integrated bioinformatics analysis combined with experimental validation was carried out to investigate the biological mechanism(s) that are responsible for the reported PSF beneficial effects as an antioxidant during a pro-inflammatory TLR4 insult. Bioinformatics analysis using miRNet 2.0 was carried out to address which biological process(es) the extract could be involved in. In addition, Chemprop was employed to identify the key targets of nuclear receptor (NR) signaling and stress response (SR) pathways potentially modulated. The miRNet analysis suggested that the PSF extract mostly activates the biological process of cellular senescence. The Chemprop analysis predicted three possible targets for nine phytochemicals found in the extract: (i) ARE signaling, (ii) mitochondrial membrane potential (MMP) and (iii) p53 SR pathways. The PSF extract antioxidant effect was also experimentally validated in vitro using the human monocyte U937 cell line. Our findings showed that Nrf2 is modulated by the extract with a consequent reduction of the oxidative stress level. This was confirmed by a strong decrease in the amount of reactive oxygen species (ROS) observed in the PSF-treated cells subjected to lipopolysaccharide (LPS) (6 h treatment, 1 µg/mL). No visible effects were observed on p53 and MMP modulation.

Assessment of the release of metals from cigarette butts into the environment.

Cigarette butts are known to contain toxic metals which pose a potential threat to the environment and human health. The seriousness of this threat is largely determined by the leachability of these toxic metals when the butts are exposed to aqueous solutions in the environment. The aims of this study were to determine the presence and mobility of toxic and non-toxic elements found in discarded cigarette butts; to relate this mobility to two different contact situations with leaching liquids: tumbling and trampling (batch test) and percolation in a static position (column test); and finally, to verify possible variations in solubility by simulating different environmental systems. Five leachants with different pH values were used to simulate various environmental conditions The concentrations of the solubilized metals were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS). CH3COOH pH 2.5 showed the greatest capacity to dissolve many elements. On the contrary, weakly acidic or alkaline environments did not favor the leachability of the elements. The best extraction capacity of the column with respect to the batch is statistically significant (p <0.05) for the elements Al, Fe, Ni and Zn, while the batch for P, Si, S. Pb, Cd, As were not detectable in cigarette butts, while Hg had an average concentration of 0.0502 µg/g. However, Hg was < LOD in all different leachants.

The Perceptions and Needs of Practitioners Working to Promote Smart Decarceration.

The social work Grand Challenge to Promote Smart Decarceration's aim is to address the high rates of incarceration in the United States. PURPOSE: Yet very little is known about criminal justice practitioners in the U.S. METHOD: In this exploratory study. Practitioners in correctional facilities (n = 38), responded to an online survey asking them about their perceptions of the services they provide and to identify their professional needs working within these settings. RESULTS: Findings include the need for people who are incarcerated to have access to treatment for substance use, behavioral/mental health, and trauma-related issues. In addition, they reported the need for service coordination with agencies based in their home communities. Furthermore, the participants reported that they need more training and support on these topics in order to provide effective services to their clients. DISCUSSION: Implications for practice, research, and policy are discussed, including strategies to address all levels of primary, secondary, and tertiary prevention.

Bioaccessibility assessment of stable elements and 210Po in food.

Element bioaccessibility consists of the fraction of the element that is mobilized from food matrices into digestive extractants. The degree of bioaccessibility of a toxic metal is a fundamental consideration in estimating its bioavailability. In addition, gaining a better understanding of the essential elements released into the gastro intestinal fluids allows a more thorough assessment of the health benefits of food matrices in the field of nutrition science. In the present study, an in vitro digestion model simulating gastro-intestinal digestion (GID) was used to investigate the bioaccessibility of stable elements in mixed leaf salad and 210Po in various foods (meat, seafood, vegetables). The simulation was carried out over three phases: after a pre-treatment with a saliva solution, raw and cooked seafood samples were subjected to a complete simulated gastrointestinal digestion (gastric digestion followed by bile-pancreas digestion). The 210Po bioaccessibility was found to range from 16.2±9.39% to 62.8±17.7% and from 6.26±2.15% to 67.5±13.1% for raw and cooked food respectively. Moreover, bioaccessibility could not be determined for As, Cd, Ce, Co, Cr, Hg, La, Pb, Sb, Sn, Te, Th, Tl, Ti, U. It proved to be poor (1-16%) for Al, Fe and S; fair (40-50%) for Cu, P, and Si; and high (>50%) for Ba, Ca, K, Mg, Mn, Ni, Rb, Sr, Zn. The results show that bioaccessibility varies according to the chemical form of the element in the food as well as the matrix composition.

Nutritional, antioxidant and sensory properties of functional beef burgers formulated with chia seeds and goji puree, before and after in vitro digestion.

The addition of chia seeds and goji puree (2.5 and/or 5%) was evaluated in terms of their effects on the fatty acid profile, lipid peroxidation, total phenols and antioxidant capacity of cooked beef burgers. In comparison to control burgers, polyunsaturated fatty acids doubled or tripled in samples containing chia seeds; polyphenols and antioxidant capacities (ORAC, ABTS, DPPH) increased up to 70% and malondialdehyde values were reduced up to 50% in burgers formulated with both ingredients. Polyphenols, antioxidant capacity and lipid peroxidation were also assessed after in vitro digestion. A marked increase of polyphenol bioaccessibility and antioxidant capacity was observed for all samples, but also malondialdehyde values were increased after digestion, especially in samples containing 5% chia seeds. Finally, hedonistic tests were conducted on young (18-30 years), adult (31-60 years) and elderly (>60 years) subjects and the burgers resulted acceptable by all groups, appointing to their potential application as functional burgers.