A geo-chemo-mechanical study of a highly polluted marine system (Taranto, Italy) for the enhancement of the conceptual site model.

The paper presents the results of the analysis of the geo-chemo-mechanical data gathered through an innovative multidisciplinary investigation campaign in the Mar Piccolo basin, a heavily polluted marine bay aside the town of Taranto (Southern Italy). The basin is part of an area declared at high environmental risk by the Italian government. The cutting-edge approach to the environmental characterization of the site was promoted by the Special Commissioner for urgent measures of reclamation, environmental improvements and redevelopment of Taranto and involved experts from several research fields, who cooperated to gather a new insight into the origin, distribution, mobility and fate of the contaminants within the basin. The investigation campaign was designed to implement advanced research methodologies and testing strategies. Differently from traditional investigation campaigns, aimed solely at the assessment of the contamination state within sediments lying in the top layers, the new campaign provided an interpretation of the geo-chemo-mechanical properties and state of the sediments forming the deposit at the seafloor. The integrated, multidisciplinary and holistic approach, that considered geotechnical engineering, electrical and electronical engineering, geological, sedimentological, mineralogical, hydraulic engineering, hydrological, chemical, geochemical, biological fields, supported a comprehensive understanding of the influence of the contamination on the hydro-mechanical properties of the sediments, which need to be accounted for in the selection and design of the risk mitigation measures. The findings of the research represent the input ingredients of the conceptual model of the site, premise to model the evolutionary contamination scenarios within the basin, of guidance for the environmental risk management. The study testifies the importance of the cooperative approach among researchers of different fields to fulfil the interpretation of complex polluted eco-systems.

Proximate, fatty acids and metals in edible marine bivalves from Italian market: Beneficial and risk for consumers health.

Seafood is recognized as a healthy food choice due to high contents of essential nutrients, including polyunsaturated fatty acids (PUFAs) of the n-3 family. However, seafood is often contaminated by toxic compounds, which have adverse effects on human health. The aim of this study was to provide information about the percentage of edible part, condition index and the benefit and risk for human consumers health associated to the consumption of eight bivalve species (Flexopecten glaber, Mimachlamys varia, Modiolus barbatus, Mytilus galloprovincialis, Ostrea edulis, Ruditapes philippinarum, Solen marginatus and Venus verrucosa) of high commercial value, purchased from Taranto local fish markets. High percentage of edibility and condition index were found in all analysed species. The relatively high protein content, low levels of lipid and high percentage of healthy n-3 PUFAs make M. varia, O. edulis, S. marginatus, M. galloprovincialis, M. barbatus more suitable for benefit to consumers. Provisional tolerable weekly intake and hazard index calculated on the basis of trace metals in edible tissues, indicated specific recommendations for a responsible daily consumption of shellfish. For the most part of studied species, the estimated balance between beneficial and risk for consumers recommend a daily portion (RDP) lesser of 60 g/person/day than M. galloprovincialis, O. edulis and R. philippinarum (≥60 g/person/day). Careful risk-benefit considerations should promote seafood consumption while minimizing exposure to toxic contaminants.

Mode of action of trabectedin in myxoid liposarcomas.

To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respectively of type I, II and III. FUS-CHOP binding to the promoters of some target genes such as Pentraxin 3 or Fibronectin 1, assessed by chromatin immunoprecipitation, was strongly reduced in the tumor 24 h after the first or the third weekly dose of trabectedin, indicating that the drug at therapeutic doses causes a detachment of the FUS-CHOP chimera from its target promoters as previously shown in vitro. Moreover, the higher sensitivity of MRCL types I and II appears to be related to a more prolonged block of the transactivating activity of the fusion protein. Doxorubicin did not affect the binding of FUS-CHOP to target promoters. Histologically, the response to trabectedin in ML017 and ML015 was associated with a marked depletion of non-lipogenic tumoral cells and vascular component, as well as lipidic maturation as confirmed by PPARγ2 expression in western Blot. By contrast, in ML004 no major changes either in the cellularity or in the amount of mature were found, and consistently PPARγ2 was null. In conclusion, the data support the view that the selective mechanism of action of trabectedin in MRCL is specific and related to its ability to cause a functional inactivation of the oncogenic chimera with consequent derepression of the adypocytic differentiation.

Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents.

Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBPα and ß, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin.

Mercury and methylmercury contamination in Mytilus galloprovincialis from Taranto Gulf (Ionian Sea, Southern Italy): risk evaluation for consumers.

Total mercury (THg) and methylmercury (Me-Hg) concentrations were determined in mussels (Mytilus galloprovincialis) from 10 stations located in the Mar Piccolo of Taranto (Ionian Sea, Taranto Gulf) an important semi-enclosed basin in Italy, devoted to mussel culture activities. The obtained results show that THg and Me-Hg concentrations ranged from 0.236 to 0.559 µg g(-1) d.w. and from 0.066 to 0.155 µg g(-1) d.w., respectively. Consequently, the Me-Hg/THg ratios ranged from 17% to 49%. The dietary intake of THg and Me-Hg were studied among children and adults from Taranto (Southern Italy). The estimated weekly intake for THg and Me-Hg was below the Provisional Tolerable Weekly Intake (PTWI) established by European Food Safety Autority (EFSA) for all sampled mussels, though their consumption provides a THg intake in children near the PTWI.

Lipoid proteinosis: case report and review of the literature.

Lipoid proteinosis is a rare autosomal recessive disorder, characterized histologically by infiltration of periodic acid Schiff-positive hyaline material into the skin, upper aerodigestive tract, and internal organs. Classical clinical features include skin scarring, beaded eyelid papules, and laryngeal infiltration leading to hoarseness. Moreover, the infiltrates in the tongue and its frenulum limit lingual movements and cause speech difficulties. Usually, the hoarse voice is present at birth or in early infancy, as the first manifestation. In more severe cases, diffuse infiltration of the pharynx and larynx might cause respiratory distress, at times requiring tracheostomy. The disorder has recently been shown to result from loss-of-function mutations in the extracellular matrix protein 1 gene on chromosome 1q21. The function of the protein extracellular matrix protein 1 gene is still unclear, although an important role in skin physiology and homeostasis has been hypothesized. In this report, the case is described of a 6-year-old girl with lipoid proteinosis. Histopathological examination of a laryngeal biopsy specimen showed massive deposits of eosinophilic, periodic acid Schiff-positive, and diastase resistant material in the lamina propria corroborating the clinical diagnosis of lipoid proteinosis. Molecular analyses in this patient also confirmed the clinical diagnosis. The proposita was a compound heterozygote for a new small rearrangement (543de1TG/ins15) in exon 6, and a nonsense mutation (Arg243Stop) in exon 7. Together with previously documented mutations in the extracellular matrix protein 1 gene, this study supports the hypothesis that exons 6 and 7 are the most common sites for extracellular matrix protein 1 gene mutations in lipoid proteinosis.

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin.

Trace elements in organs and tissues of striped dolphins (Stenella coeruleoalba) from the Mediterranean sea (Southern Italy).

The distribution of metals (Cd, Cu, Zn, Fe, Cr, Pb and Sn) were investigated in various tissues and organs obtained from striped dolphins (Stenella coeruleoalba) stranded along the Apulian coasts (Southern Italy) during April-July 1991. Metals were determined by atomic absorption spectrophotometry. Metal concentrations were generally high in the liver, and low in brain and melon. Some metals showed organ-specific accumulations: copper, tin and zinc exhibited high concentrations in liver, the highest cadmium concentration was observed in kidney. Pathological, microbiological and parasitological surveys were performed on the animals. It was not possible to relate dolphin death to a specific cause, or to contaminants; however, the accumulation of metals may contribute to certain pathological alterations.

Speciation of butyltin compounds in marine sediments with headspace solid phase microextraction and gas chromatography mass spectrometry.

A method for the determination of organotin compounds (monobutyl = MBT, dibutyl = DBT, and tributyltin = TBT) in marine sediments by headspace Solid Phase Microextraction (SPME) has been developed. The analytical procedure involved 1) extraction of TBT, DBT and MBT from sediments with HCl and methanol mixture, 2) in situ derivatization with sodium tetraethylborate and 3) headspace SPME extraction using a fiber coated with poly(dimethylsiloxane). The derivatized organotin compounds were desorbed into the splitless injector and simultaneously analyzed by gas chromatography - mass spectrometry. The analytical method was optimized with respect to derivatization reaction and extraction conditions. The detection limits obtained for MBT, DBT and TBT ranged from 730 to 969 pg/g as Sn dry weight. Linear calibration curves were obtained for all analytes in the range of 30-1000 ng/L as Sn. Analysis of a standard reference sediment (CRM 462) demonstrates the suitability of this method for the determination of butyltin compounds in marine sediments. The application to the determination of TBT, DBT and MBT in a coastal marine sediment is shown.

Tissue distribution of metals in striped dolphins (Stenella coeruleoalba) from the Apulian coasts, southern Italy.

Tissue distributions of metals (mercury, lead, cadmium, zinc, copper, iron, manganese) were determined in six specimens of striped dolphins (Stenella coeruleoalba, Meyen) stranded on the Apulian coasts (Southern Italy) between February and June 1987. Methyl mercury and selenium were also determined in the liver samples. The liver accumulated the highest concentrations of metals, except for cadmium and chromium. Metal levels were higher than those found in dolphins living in the Atlantic, but lower than those recorded in the same species from the French Mediterranean coasts. Necroscopic surveys found that all specimens were affected by haemorrhagic gastritis, but the cause was not clear. While it was not possible to related the death of dolphins to a specific cause, or to contaminants, the accumulation of metals is likely to contribute to the health of the organism and represents a risk factor for dolphins.