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1.
Biol Trace Elem Res ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38687421

ABSTRACT

Cataract, characterized by the opacification of the lens, is the leading cause of reversible blindness and visual impairment globally. The study aims to investigate the role of trace elements such as Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn in the development and severity of cataract. Elements were quantified by inductively coupled plasma mass spectrometry in blood and aqueous humor of 32 cataract cases and 27 controls living in the Latium region, Italy. The association between element concentration in blood and aqueous humor and cataract severity, gender, and age of subjects were also assessed. Results showed Cr levels significantly elevated in both blood and aqueous humor of cataract cases, with concentrations that increased with cataract severity. In addition, blood Pb levels were significantly higher in older cases and positively correlated with the age of cataract cases, while blood Co and Cu levels negatively correlated with cataract severity, suggesting changes in the levels of these elements. In conclusion, this study provides evidence of the involvement of specific elements in cataract development and severity, and the findings highlighted important avenues for future research. Understanding the biological mechanism underlying element-induced cataract may contribute to preventing cataractogenesis and providing targeted interventions.

2.
Toxics ; 12(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38250988

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal neoplasm, and it has an average 5-year survival rate of less than 10%. Although the factors that influence PDAC development remain unclear, exposure to toxic metals or the imbalance in essential elements may have a role in PDAC-associated metabolic pathways. METHODS: This study determined the concentrations of Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se and Zn in whole blood, cancer and non-cancer tissues of patients affected by PDAC, and compared them with levels in healthy controls using inductively coupled plasma mass spectrometry. RESULTS: Results of the whole blood showed significantly higher levels of Cr, Cu and Cu/Zn ratio in PDAC patients compared to the controls. In addition, the concentrations of Cu, Se, Fe and Zn significantly increased in cancer tissue compared to the healthy counterparts. CONCLUSIONS: This study revealed evidence of altered metal levels in the blood and pancreatic tissues of PDAC patients with respect to healthy controls. These changes may contribute to multiple mechanisms involved in metal-induced carcinogenesis, including oxidative stress, DNA damage, genetic alteration, decreased antioxidant barriers and inflammatory responses. Thus, the analysis of metals can be used in the diagnosis and monitoring of PDAC neoplasms.

3.
Sci Total Environ ; 905: 167103, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37717768

ABSTRACT

This study assesses the potential impacts on human health of volcanic ash emitted during the 2021 Tajogaite eruption (La Palma Island, Spain). Ash samples were physically and chemically characterized and leaching tests (with deionized water and acidic solution) were performed according to the IVHHN protocols to elucidate i) the leachable elements that may affect water quality and represent a potential threat for livestock and humans through drinking water supply; and ii) the bioaccessible fraction of toxicants able to be solubilized from ash surfaces if ashes are incidentally ingested by children. The most abundant readily water-soluble compounds were SO4, F, Cl, Na, Ca, Ba, Mg, and Zn. Fluoride and chloride (up to 1085 and 1347 mg/kg) showed higher values in distal ash samples than closer ones. The potential F availability assessed from water leachates may suggest important environmental and health implications. In addition, long-term health hazard due to a long-term weathering of tephra deposits should be possible as confirmed by the greater amount of F extracted by acidic solution. Concentration of other trace elements (e.g., As, V, Mn, Mo, Cr, Fe, Se, Ti, Pb) were low compared to global medians and within the range globally assessed. Indicative calculation of hazard for water supply showed that F concentration may exceed both the recommended value (1 mg/L) for irrigation purpose and the health-based drinking water limits of 1.5 mg/L (for humans) and 2 mg/L (for livestock). If the predicted concentrations in water were compared with the toxicologically dose, F showed a potential health-risk for children through drinking water. The indicative health-risk characterization via accidental ash ingestion showed that the direct exposure does not represent a primary source of F daily intake for children. This important outcome confirmed F as element with the greatest health threat during Tajogaite 2021 eruption.


Subject(s)
Drinking Water , Volcanic Eruptions , Humans , Coal Ash/chemistry , Environmental Monitoring , Spain , Public Health
4.
Animals (Basel) ; 13(4)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36830437

ABSTRACT

There is strong scientific evidence that exposure to environmental contaminants, such as heavy metal(loid)s (HMs), can impair female reproductive function. Pets, such as cats and dogs, who share the same habitat as humans, may be particularly useful sentinel models for detecting HMs in the ovary. In the present study, we compared the concentration of essential (Ems; Cu, Fe, Mn, Se, and Zn) and non-essential metal(loid)s (NEMs; Al, As, Cd, and Pb) in the ovarian tissues of free-ranging queens and bitches of different ages living in industrialized/highly polluted (south group) and non-polluted (north group) urban areas of the island of Sardinia, Italy. The results showed that both EMs and NEMs were present at detectable concentrations in feline and canine ovaries and their levels varied according to geographical areas and animal age. Among the EMs, Cu was found elevated in older queens and bitches inhabiting the southern area. Cadmium and lead were higher in feline and canine ovaries of older animals from the south compared to those living in the north. In addition, Cd and Pb concentrations increased in individuals of both species living in the south. These findings showed new perspectives for the use of pets as early warning sentinels of environmental pollution by HMs and for the risk of human exposure within a "One Health" approach. Pets may help to study the link between exposure to metals and female reproductive disturbances in mammals.

5.
Environ Geochem Health ; 44(7): 1949-1970, 2022 Jul.
Article in English | MEDLINE | ID: mdl-33438150

ABSTRACT

The study deals with the analyses of springs and wells at the base of Montepugliano Hill that represents the SE edge of the wide carbonate Matese massif (Campania, southern Italy). At the base of the hill, from west to east and for almost one kilometre, cold springs HCO3-Ca type (Grassano springs, ~ 4.5 m3/s; TDS: about 0.45 g/L) pass to hypothermal, HCO3-Ca type, sulphurous and CO2-rich springs (~ 1 m3/s with TDS > 1 g/L). Some of the latter are widely used in Telese Spa and Centro Relax Spa. Chemical and isotopic analyses carried out for this study support the hypothesis that all these waters (mineral and non-mineral) have the same catchment area, which is located in the Matese massif. As regards the sulphurous springs, they receive both meteoric waters infiltration and uprising of deeper waters rich in endogenous CO2 and H2S gases through important faults systems. Far from these faults, the chemistry of groundwater is scarcely (or not at all) affected by these deep fluid enrichment processes. This scheme is very significant; in fact, when very important groundwater resources are present, it is possible to use both mineral waters in Spa and, in areas far from the faults, those not yet mineralized. Finally, at Montepugliano Hill, in the final stage of the flow path, groundwater is also affected by change in the microbiome: this could provide a basis for comparison between various mineral waters.


Subject(s)
Groundwater , Microbiota , Mineral Waters , Carbon Dioxide/analysis , Environmental Monitoring , Groundwater/chemistry , Mineral Waters/analysis , Water Wells
6.
Sci Rep ; 11(1): 9898, 2021 05 10.
Article in English | MEDLINE | ID: mdl-33972598

ABSTRACT

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.


Subject(s)
Child Behavior Disorders/diagnosis , Environmental Pollutants/adverse effects , Metals, Heavy/adverse effects , Neurotoxicity Syndromes/diagnosis , Child , Child Behavior/drug effects , Child Behavior Disorders/blood , Child Behavior Disorders/chemically induced , Child Behavior Disorders/urine , Cross-Sectional Studies , Environmental Exposure/adverse effects , Environmental Pollutants/analysis , Environmental Pollution/adverse effects , Humans , Italy , Male , Metals, Heavy/analysis , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/urine
7.
Chemosphere ; 271: 129514, 2021 May.
Article in English | MEDLINE | ID: mdl-33434828

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease that quickly leads to death. This paper addressed the issue of whether the levels of trace elements in sputum samples are suitable biomarkers for IPF disease. The sputum Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn concentrations were measured by sector field inductively coupled plasma mass spectrometry in populations sampled in Sardinia Island (Italy) including 31 patients with IPF, 31 patients with other lung-related diseases and 30 age- and gender-matched healthy controls. Risk factors in the disease as gender, age, severity and duration of the disease were assessed. Results showed that IPF patients had significantly increased sputum levels of Cd, Cr, Cu and Pb respect to controls. In males, but not in females, sputum levels of Cd, Cr and Cu were significantly higher in IPF cases respect to controls. In addition, Cr and Pb were increased in male patients with IPF compared to male patients with other lung diseases. Regarding Zn, it was found higher with the more serious stage of disease. Moreover, the ratios Cu/Zn, Fe/Mn and Cu/Mn were significantly increased in IPF patients and in non-IPF patients than in control subjects. These data showed clear increases in the concentration of some trace elements in sputum from patients with IPF and patients with other lung-related diseases that may contribute to the injury. The non-invasiveness of the sputum analysis is beneficial for its use as biomarker of trace element status in diseased patients for both the researcher and the clinic.


Subject(s)
Idiopathic Pulmonary Fibrosis , Trace Elements , Biomarkers , Female , Humans , Italy , Male , Sputum/chemistry , Trace Elements/analysis
8.
Neurol Sci ; 42(2): 531-537, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33280067

ABSTRACT

The present review represents an update about the knowledge of the possible role of Cadmium (Cd) in amyotrophic lateral sclerosis (ALS) initiation and its progression. ALS is a neurodegenerative disease that occurs in adulthood; its etiology is unknown and leads to death within a few years from its appearance. Among the various possible causes that can favor the development of the disease, heavy metals cannot be excluded. Cadmium is a heavy metal that does not play a biological role, but its neurotoxicity is well known. Numerous in vitro studies on cell and animal models confirm the toxicity of the metal on the nervous system, but these data are not accompanied by an epidemiological evidence, and, thus, an unclear correlation between Cd and the onset of the disease can be pointed out. On the other hand, a possible multifactorial and synergic mechanism in which Cd may have a role can explain the ALS onset. More efforts in new clinical, biochemical, and epidemiological studies are necessary to better elucidate the involvement of Cd in this lethal disease.


Subject(s)
Amyotrophic Lateral Sclerosis , Neurodegenerative Diseases , Amyotrophic Lateral Sclerosis/chemically induced , Amyotrophic Lateral Sclerosis/epidemiology , Animals , Cadmium/toxicity
9.
Neurotoxicology ; 81: 80-88, 2020 12.
Article in English | MEDLINE | ID: mdl-32941938

ABSTRACT

Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Central Nervous System/drug effects , Environmental Pollutants/adverse effects , Lead Poisoning, Nervous System , Lead/adverse effects , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/epidemiology , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Central Nervous System/metabolism , Central Nervous System/pathology , Central Nervous System/physiopathology , DNA-Binding Proteins/metabolism , Disease Progression , Environmental Exposure/adverse effects , Gene-Environment Interaction , Humans , Lead Poisoning, Nervous System/diagnosis , Lead Poisoning, Nervous System/epidemiology , Lead Poisoning, Nervous System/metabolism , Lead Poisoning, Nervous System/physiopathology , Protein Aggregates , Protein Aggregation, Pathological , Risk Assessment , Risk Factors
10.
J Trace Elem Med Biol ; 61: 126560, 2020 May 22.
Article in English | MEDLINE | ID: mdl-32485500

ABSTRACT

BACKGROUND: Primary open angle glaucoma (POAG) is the most common form of chronic, progressive optic neuropathies characterized by slow degeneration of the retinal ganglion cells and their axons, resulting in visual field loss. Risk factors for this disease are elevated intraocular pressure (IOP), increased age, European and African ethnicity, family history, myopia and decreased corneal thickness. In addition, studies indicated that levels of trace elements are also significantly related to the POAG. METHOD: The association between toxic and essential elements and POAG was explored in a population-based case-control study in the Sardinia Island (Italy). The aqueous humor levels of Al, Cd, Cu, Fe, Hg, Mn, Ni, Pb and Zn were measured in 25 POAG patients compared to 20 age- and gender-matched healthy controls by sector field inductively coupled mass spectrometry. Risk factors as gender, age and increased IOP were also explored. RESULTS: The concentrations of Fe, Hg and Zn were significantly higher in POAG patients than in control subjects, showing these elements as possible determinants in POAG development or degeneration. Other findings were the increased Cu and Fe levels in glaucomatous patients with age less than 70 years. Levels of Ni were found elevated in POAG females. Mercury accumulated more in POAG females, in patients over 70 years and in those with higher levels of IOP in the left eye. Moreover, the positive associations CuFe and Mn-Zn may indicate synergistic effects of elements. CONCLUSIONS: Altogether, these findings suggested a multifactorial role in the risk for POAG disease. The present study documented the levels of trace elements in aqueous humor of Sardinian POAG patients for the first time.

11.
Invest New Drugs ; 38(3): 634-649, 2020 06.
Article in English | MEDLINE | ID: mdl-31240514

ABSTRACT

Cutaneous melanoma, the most aggressive form of skin cancer, is characterized by activating BRAF mutations. Despite the initial success of selective BRAF inhibitors, only few patients exhibited complete responses, whereas many showed disease progression. Melanoma is one of the few types of cancer in which p53 is not frequently mutated, but p53 inactivation can be indirectly achieved by a stable activation of MDM2 induced by a deletion in CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) locus, encoding for p16INK4A and p14ARF, two tumor suppressor genes. In this study, we tested the efficacy of the previously synthesized tetra-substituted pyrrole derivatives, 8 g, 8 h and 8i, in melanoma cell lines, and we compared the effects of the most active of these, the 8i compound, with that exerted by Nutlin 3, a well-known inhibitor of p53-MDM2 interaction. The obtained results showed that 8i potentiates the inhibitory effect of Nutlin 3 and the combined use of 8i and Nutlin 3 triggers apoptosis and significantly impairs melanoma viability. Finally, the 8i compound reduces p53-MDM2 interaction and induces p53-HSP90 complex formation, suggesting that the observed raise in p53 transcriptional activity could be mediated by HSP90. Because the main feature of melanoma is the resistance to most chemotherapeutics, our studies suggest that the 8i tetra-substituted pyrrole derivative, restoring p53 functions and its transcriptional activities, may have potential application, at least as adjuvant, in the treatment of human melanoma.


Subject(s)
Pyrroles/pharmacology , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p16/metabolism , HSP90 Heat-Shock Proteins/metabolism , Humans , Imidazoles/metabolism , Melanoma , Mutation/drug effects , Piperazines/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , Transcription, Genetic/drug effects , Tumor Suppressor Protein p14ARF/metabolism , Tumor Suppressor Protein p53/genetics , Melanoma, Cutaneous Malignant
12.
Environ Health ; 18(1): 67, 2019 07 19.
Article in English | MEDLINE | ID: mdl-31324194

ABSTRACT

BACKGROUND: Metal exposure is a public health hazard due to neurocognitive effects starting in early life. Poor socio-economic status, adverse home and family environment can enhance the neurodevelopmental toxicity due to chemical exposure. Disadvantaged socio-economic conditions are generally higher in environmentally impacted areas although the combined effect of these two factors has not been sufficiently studied. METHODS: The effect of co-exposure to neurotoxic metals including arsenic, cadmium, manganese, mercury, lead, selenium, and to socio-economic stressors was assessed in a group of 299 children aged 6-12 years, residing at incremental distance from industrial emissions in Taranto, Italy. Exposure was assessed with biological monitoring and the distance between the home address and the exposure point source. Children's cognitive functions were examined using the Wechsler Intelligence Scale for Children (WISC) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear mixed models were chosen to assess the association between metal exposure, socio-economic status and neurocognitive outcomes. RESULTS: Urinary arsenic, cadmium and hair manganese resulted inversely related to the distance from the industrial emission source (ß - 0.04; 95% CI -0.06, - 0.01; ß - 0.02; 95% CI -0.05, - 0.001; ß - 0.02 95% CI -0.05, - 0.003) while the WISC intellectual quotient and its sub-scores (except processing speed index) showed a positive association with distance. Blood lead and urinary cadmium were negatively associated with the IQ total score and all sub-scores, although not reaching the significance level. Hair manganese and blood lead was positively associated with the CANTAB between errors of spatial working memory (ß 2.2; 95% CI 0.3, 3.9) and the reaction time of stop signal task (ß 0.05; 95% CI 0.02, 0.1) respectively. All the other CANTAB neurocognitive tests did not show to be significantly influenced by metal exposure. The highest socio-economic status showed about five points intellectual quotient more than the lowest level on average (ß 4.8; 95% CI 0.3, 9.6); the interaction term between blood lead and the socio-economic status showed a significant negative impact of lead on working memory at the lowest socio-economic status level (ß - 4.0; 95% CI -6.9, - 1.1). CONCLUSIONS: Metal exposure and the distance from industrial emission was associated with negative cognitive impacts in these children. Lead exposure had neurocognitive effect even at very low levels of blood lead concentration when socio-economic status is low, and this should further address the importance and prioritize preventive and regulatory interventions.


Subject(s)
Air Pollutants/adverse effects , Arsenic/adverse effects , Cognition/drug effects , Environmental Exposure/adverse effects , Metals, Heavy/adverse effects , Child , Female , Humans , Italy , Male , Neuropsychological Tests , Socioeconomic Factors
13.
J Microbiol ; 57(6): 498-508, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31054137

ABSTRACT

Outer membrane vesicles (OMVs) are nanostructures of 20-200 nm diameter deriving from the surface of several Gram-negative bacteria. OMVs are emerging as shuttles involved in several mechanisms of communication and environmental adaptation. In this work, OMVs were isolated and characterized from Novosphingobium sp. PP1Y, a Gram-negative non-pathogenic microorganism lacking LPS on the outer membrane surface and whose genome was sequenced and annotated. Scanning electron microscopy performed on samples obtained from a culture in minimal medium highlighted the presence of PP1Y cells embedded in an extracellular matrix rich in vesicular structures. OMVs were collected from the exhausted growth medium during the mid-exponential phase, and purified by ultracentrifugation on a sucrose gradient. Atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis showed that purified PP1Y OMVs had a spherical morphology with a diameter of ca. 150 nm and were homogenous in size and shape. Moreover, proteomic and fatty acid analysis of purified OMVs revealed a specific biochemical "fingerprint", suggesting interesting details concerning their biogenesis and physiological role. Moreover, these extracellular nanostructures do not appear to be cytotoxic on HaCaT cell line, thus paving the way to their future use as novel drug delivery systems.


Subject(s)
Bacterial Outer Membrane Proteins/metabolism , Cell Membrane/metabolism , Secretory Vesicles/chemistry , Secretory Vesicles/enzymology , Sphingomonadaceae/metabolism , Bacterial Outer Membrane Proteins/isolation & purification , Cell Line , Cell Survival/drug effects , Exocytosis , Fatty Acids/analysis , Humans , Keratinocytes/drug effects , Microscopy, Electron, Scanning , Nanoparticles , Peptide Hydrolases/metabolism , Proteomics/methods , Sphingomonadaceae/cytology
14.
ACS Med Chem Lett ; 10(4): 601-605, 2019 Apr 11.
Article in English | MEDLINE | ID: mdl-30996803

ABSTRACT

JMJD3 is a member of the KDM6 subfamily and catalyzes the demethylation of lysine 27 on histone H3 (H3K27). This protein was identified as a useful tool in understanding the role of epigenetics in inflammatory conditions and in cancer as well. Guided by a virtual fragment screening approach, we identified the benzoxazole scaffold as a new hit suitable for the development of tighter JMJD3 inhibitors. Compounds were synthesized by a microwave-assisted one-pot reaction under catalyst and solvent-free conditions. Among these, compound 8 presented the highest inhibitory activity (IC50 = 1.22 ± 0.22 µM) in accordance with molecular modeling calculations. Moreover, 8 induced the cycle arrest in S-phase on A375 melanoma cells.

15.
Biol Trace Elem Res ; 190(1): 1-10, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30215191

ABSTRACT

Systemic sclerosis (SSc) is a multisystem connective tissue disease; exogenous factors-including heavy metals-may have a role in the disease pathogenesis. In this context, a study on the quantification of Al, Cd, Hg, and Pb in blood and urine of 27 SSc patients and 30 controls was carried out. Main findings were that Al was significantly depleted in blood and increased in urine of SSc patients respect to controls; and Pb was found slightly increased in blood and significantly decreased in SSc group. In addition, higher Hg levels in urine were found in SSc subjects with the higher severity of the disease. Females showed the most marked differences in the levels of blood Al, blood Pb, and urine Cd between patients and controls. Smoking, hobby, ingestion of contaminated food, job exposure may contribute to the bodily levels of Al, Hg, Pb in SSc patients. The results indicated that low, chronic, and multiple exposures to heavy metals-also through habits, diet, and environment-may influence the risk for SSc.


Subject(s)
Metals, Heavy/blood , Metals, Heavy/urine , Scleroderma, Systemic/blood , Scleroderma, Systemic/urine , Adult , Aged , Aluminum/blood , Aluminum/urine , Cadmium/blood , Cadmium/urine , Female , Humans , Lead/blood , Lead/urine , Male , Mercury/blood , Mercury/urine , Middle Aged , Risk Factors
16.
Eur J Med Chem ; 152: 253-263, 2018 May 25.
Article in English | MEDLINE | ID: mdl-29730188

ABSTRACT

Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC50 on MCF7 cell lines, thus validating IVS in lead repurposing.


Subject(s)
Drug Discovery , Molecular Docking Simulation , Receptor, ErbB-4/antagonists & inhibitors , Small Molecule Libraries/pharmacology , Sulfonamides/pharmacology , Cell Cycle Checkpoints/drug effects , Dose-Response Relationship, Drug , Humans , MCF-7 Cells , Molecular Structure , Receptor, ErbB-4/metabolism , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Tumor Cells, Cultured , Benzenesulfonamides
17.
Environ Sci Pollut Res Int ; 25(9): 8404-8414, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29307065

ABSTRACT

Metals in bones of 72 subjects lived between the twelfth and eighteenth century AC and collected in four Sardinian (Italian insular region) burial sites (Alghero, Bisarcio, Geridu, and Sassari) were determined and used as biomarkers to evaluate diet and potential social-environmental differences. Concentrations of Ba, Ca, Cd, Cu, Hg, Pb, Sr, and Zn were quantified in different types of compact bone (femur, fibula, humerus, radius, tibia, ulna) by sector field inductively coupled plasma mass spectrometry previous acidic digestion and differences among the various burial sites, centuries, types of bone, gender, and age were explored by univariate and multivariate analyses. Results indicated differences between sites in terms of diet: Bisarcio (inland village) had increased ratios of Ba/Ca and Zn/Ca due to higher incidence of vegetables, cereals, and animal foods in the diet; Geridu (coastal village) showed increased Sr/Ca ratio indicating foods of plant and marine origin that were predominant; Alghero (coastal site) and Sassari (inland site) displayed prevalently a mixed diet reflecting a higher economy and food imports. In addition, these latter sites showed increased levels of Hg/Ca (fish, drugs, cosmetics) and Pb/Ca (coins, utensils, pipeline for water). In conclusion, the elemental Ba/Ca, Sr/Ca, and Zn/Ca ratios were indicative of provenance and diet, while Hg/Ca and Pb/Ca ratios were associated to various forms of environmental exposure.


Subject(s)
Barium/chemistry , Environmental Exposure/analysis , Mercury/analysis , Metals/analysis , Animals , Bone and Bones , Diet , Environmental Monitoring/methods , Fishes , Humans , Islands , Italy , Middle Aged , Nutritional Status
18.
Chemosphere ; 197: 457-466, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29366958

ABSTRACT

An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder. Aim of our research is to investigate the possible role of heavy metals in the severity of the disease. In this study, by the use of plasma mass (ICP-MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al, Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and controls; moreover we divided the patients in two groups for disease severity and analyzed the difference among the groups, in order to study a possible involvement of metals in the severity of the damage. Our results suggest a protective role of Selenium, involved in protective antioxidant mechanisms, and a risk factor in the case of presence of Lead in blood. The levels of the other metals are not easy to interpret, because these may be due to life style and for essential metals a consequence of the disease condition, not a cause.


Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , Environmental Exposure/statistics & numerical data , Trace Elements/blood , Adult , Amyotrophic Lateral Sclerosis/epidemiology , Female , Hair , Humans , Male , Mercury/metabolism , Metals, Heavy/metabolism , Middle Aged , Selenium/metabolism
19.
Neurol Sci ; 38(9): 1609-1615, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28601974

ABSTRACT

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.


Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , Trace Elements/analysis , Age Factors , Amyotrophic Lateral Sclerosis/epidemiology , Biomarkers/analysis , Biomarkers/blood , Biomarkers/urine , Disease Progression , Female , Hair/chemistry , Humans , Italy , Male , Mass Spectrometry , Middle Aged , ROC Curve , Risk
20.
J Trace Elem Med Biol ; 43: 3-8, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27769745

ABSTRACT

Mercury is a heavy metal that causes serious health problems in exposed subjects. The most toxic form, i.e., methylmercury (MeHg), is mostly excreted through human hair. Numerous analytical methods are available for total Hg analysis in human hair, including cold vapour atomic fluorescence spectrometry (CV-AFS), inductively coupled plasma mass spectrometry (ICP-MS) and thermal decomposition amalgamation atomic absorption spectrometry (TDA-AAS). The aim of the study was to compare the TDA-AAS with the ICP-MS in the Hg quantification in human hair. After the washing procedure to minimize the external contamination, from each hair sample two aliquots were taken; the first was used for direct analysis of Hg by TDA-AAS and the second was digested for Hg determination by the ICP-MS. Results indicated that the two data sets were fully comparable (median; TDA-AAS, 475ngg-1; ICP-MS, 437ngg-1) and were not statistically different (Mann-Whitney test; p=0.44). The two techniques presented results with a good coefficient of correlation (r=0.94) despite different operative ranges and method limits. Both techniques satisfied internal performance requirements and the parameters for method validation resulting sensitive, precise and reliable. Finally, the use of the TDA-AAS can be considered instead of the ICP-MS in hair analysis in order to reduce sample manipulation with minor risk of contamination, less time consuming due to the absence of the digestion step and cheaper analyses.


Subject(s)
Gold/chemistry , Hair/chemistry , Mass Spectrometry/methods , Mercury/analysis , Spectrophotometry, Atomic/methods , Humans
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