Hydrogeochemical and isotopic characterization of the Gioia Tauro coastal Plain (Calabria - southern Italy): A multidisciplinary approach for a focused management of vulnerable strategic systems.

This work pursues the hydro-geochemical and isotopic characterization of the complex groundwater system of the Gioia Tauro Plain, one of the most important industrialized and agricultural coastal areas of southern Italy. The anthropic pressure exposes the water resources at risk of depletion and quality degradation making the plain groundwater a system of high scientific and social interest. The plain is characterized by a shallow aquifer, mostly recharged by local rains and a deep aquifer apparently less influenced by local precipitation. Both aquifers are mainly Ca-HCO3 waters except for localized sectors where Na-HCO3, Na-Cl and Ca-SO4 waters are present. In deep aquifer, both prolonged interaction with sedimentary rocks, mainly deriving from the erosion of crystalline rocks, and direct cation exchange represent the primary factors controlling the formation of Na-HCO3 waters. Mixing processes between these waters and either connate brine and/or deep thermal waters contribute to the formation of isolated high salinity Na-Cl-rich waters. In shallow aquifer, inputs of N-rich sewage and agriculture-related contaminants, and SOx emissions in proximity of the harbor are responsible of the increasing nitrate and sulphate concentrations, respectively. The Cl/Br and NO3/Cl ratios highlight contamination mainly linked to agricultural activities and contribution of wastewater. Along the northern boundary, the warmest groundwater (Na-Cl[SO4]) were found close to a bend of the main strike-slip fault system, locally favouring the rising of B- and Li-rich deep waters, testifying the influence of geological-structural features on deep water circulation. Despite the high-water demand, a direct marine intrusion is localized in a very restricted area, where we observed an incipient groundwater-seawater mixing (seawater contribution ≤7 %). The qualitative and quantitative conditions of the shallow aquifer still have acceptable levels because of the relatively high recharge inflow. A reliable hydrogeochemical conceptual model, able to explain the compositional variability of the studied waters, is proposed.

Uterine myomas during pregnancy: a longitudinal sonographic study.

OBJECTIVE: To evaluate volumetric changes of uterine myomas (fibroids) during pregnancy. METHODS: This was an observational, longitudinal and prospective study of 38 consecutive Caucasian women with singleton pregnancies and a total of 42 uterine myomas, enrolled from a cohort of 1492 women who took part in our first-trimester Down syndrome screening program. Myoma volume was evaluated by ultrasound at 11-14, 20-22 and 32-34 weeks of gestation. RESULTS: Mean myoma volume increased significantly throughout pregnancy. Taking a volumetric change of > 10% between gestational periods to be an increase in size, 71.4% of uterine myomas increased in size between the first and second gestational periods, while this percentage was slightly lower (66.6%) between the second and third periods. Logistic regression analysis revealed that greater maternal age was correlated with a reduction/no change in overall myoma size and multiparity was correlated with a decrease/no change between the first and second trimesters, while a higher prepregnancy maternal body mass index (BMI) was correlated with a volumetric increase between the first and second trimesters and a decrease/no change between the second and third trimesters. CONCLUSIONS: Fibroids enlarge during pregnancy regardless of their initial size or local factors, and maternal age, prepregnancy BMI and parity are apparently correlated with these changes.

Heterotopic pregnancy: case report.

Heterotopic pregnancy is the simultaneus development of an intrauterine pregnancy and ectopic pregnancy. It is a potentially fatal condition and rarely occurrs in natural conception cycles. A high incidence of heterotopic pregnancy is reported in pregnancies following an assisted reproduction technique (ART) with embryo transfer in utero. We report the case of heterotopic pregnancy via ART in a 42-year-old primigravida. She presented with pelvic pain and intraabdominal fluid collection. She was treated with laparoscopic surgery. At present the intrauterine pregnancy is in normal evolution.

Laparoscopic management of adnexal masses in postmenopause.

The study included 64 postmenopausal women with adnexal masses. The selection criteria included menopausal status, an ultrasound scan indicating a benign mass and serum levels of CA-125 below the cutoff (35 U/ml). The results of the study confirm that the removal of a cystic mass in postmenopausal patients with laparoscopic surgery is a more valid and acceptable alternative to traditional surgery.

Ovarian endometriotic cyst in a patient with Ellis-van Creveld's syndrome: case report.

Ellis-van Creveld (EvC) syndrome, or chondroectodermal dysplasia, is a rare genetic disorder associated with chondrodysplasia, ectodermal dysplasia, polydactyly, and congenital cardiac malformations. The disorder is due to an autosomal-recessive mutation mapped to chromosome 4p16. It may occur with different phenotypes. The case of an ovarian endometriotic cyst in a patient suffering from EvC syndrome is reported.

Defective thyroglobulin synthesis in an experimental rat thyroid tumor: iodination and thyroid hormone synthesis in isolated tumor thyroglobulin.

Purified rat tumor thyroglobulin from the experimental rat thyroid tumor, line 1-1C2, was studied for its thyroid hormone content after in vivo and in vitro iodination and compared with normal and desialylated normal rat thyroglobulin. Tumor thyroglobulin had a very low sialic acid and iodine content; after in vivo iodination it contained only small amounts of triiodothyronine (T3) and no detectable thyroxine (T4). After in vitro iodination with 125I it showed a distribution of T3 and T4 very similar to that of normal and desialylated normal thyroglobulin iodinated in vitro. In vitro iodination dissociated tumor and desialylated normal thyroglobulin to a greater extent than normal thyroglobulin. Tumor tissue, on the other hand, showed considerable iodinating activity in the 105,000 X g pellet when studied with exogenous acceptors. These results are compatible with a role for sialic acid in the maturation and migration of thyroglobulin to the iodination site, rpovided that the intracellular distribution of the iodinating enzymes are normal.

Pharmacogenomics of neurodegenerative diseases.

Current knowledge of sporadic degenerative disorders suggests that, despite their multifactorial etiopathogenesis, genetics plays a primary role in orchestrating the pathological events, and even dramatically changes the disease phenotype from patient to patient. Genes may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the magnitude and severity of pathogenic processes or the response to drug treatment. The goal of pharmacogenomics is the application of this knowledge to elaborate more specific and effective treatments and to tailor therapies to individual patients according to their genetic profile. Here, we outline the leading theories on the etiopathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer disease, and we review the potential role of genetic variations, such as gene mutations and polymorphisms, in each context. We also suggest potential targets for new therapeutic approaches and variability factors for current treatments based on genotype features. Finally, we propose a few options of preventive therapeutic interventions in patients with a high genetic risk of disease.

Mutagenicity of methyl methanesulfonate and cyclophosphamide in resting and growing Saccharomyces cerevisiae D7 cells.

In order to evaluate the optimal experimental conditions and to identify the best growth phase for yeast genotoxicity studies, comparative experiments were performed with stationary and growing cells. Methyl methanesulfonate (MMS) and cyclophosphamide (CP) were used as chemical mutagens and strain D7 of Saccharomyces cerevisiae as detector of induced mitotic gene conversion (trp+ convertants) and point reverse mutation (ilv+ revertants) in log or stationary phase cells after either 4 or 16 h of treatment. The highest MMS-induced toxicity and genotoxicity were observed after 16 h of exposure in a suspension test with log phase cells, which is consistent with the greater permeability and sensitivity of growing yeast cells. The maximal induction of genetic effects and toxicity by CP was conversely obtained after 16 h of treatment in stationary phase cells. This may be ascribed to the greater ability of detoxication of growing cells as compared to resting cells. Our results suggest that in evaluating the mutagenicity of chemicals in yeast systems it is important to consider factors such as growth phase and exposure time.

Identification of a novel polymorphism in the fibronectin type II domain of the SEL1L gene and possible relation to the persistent hyperinsulinemic hypoglycemia of infancy.

SEL1L, a human gene located on chromosome 14q24.3-q31, is highly expressed in adult pancreas. It is proximal to D14S67 (IDDM11) a proposed type I diabetes susceptibility locus. Considering the organ specific expression of SEL1L, a fundamental role of SEL1L in pancreatic growth can be hypothesized. While screening for mutations in young diabetic patients, in children affected by persistent hyperinsulinemic hypoglycemia of infancy (PHHI), in patients with non-functional endocrine tumours and in over 100 control subjects, we identified a novel polymorphism (D162G) residing on the fourth exon of the gene. This exon encodes for the fibronectin type II domain and the nucleotide change involves a highly conserved amino acid. The D162G polymorphism induces a major change in the amino acid composition producing a possible disruptive role in collagen binding.

Control mechanisms of cell-mediated reactions.

One of the most relevant aspects of tumor adoptive immunotherapy is provided by clinical trails on transfer of cytotoxic cells (LAK and TIL). However, LAK cell therapy is effective in a small number (16-22%) of only certain tumors, while therapy with TIL cells is efficient in about 40% of melanomas. Several possibilities have been raised to explain the low efficacy of cytotoxic cells in tumor therapy, amongst which are the poor immunogenicity of tumor and tumor-induced immunodepression. Furthermore, the possibility that cytotoxic cells do not reach the tumor site in adequate numbers has to be considered. We have developed an experimental system to study the ability of antigen-specific T cells to reach the target antigen in the tissues. The results obtained demonstrate that gamma delta cells and IL-4 are required to allow tissue localization of antigen-specific alpha beta cells, thus indicating that their ability to exert certain effect or functions requires cooperation by other cells types. These results may be relevant to the understanding of the mechanisms leading to localization of immunologically active cells at a tumor site.

[Mesotheliomas among mechanics of the railways in Italy: a current problem]. / Mesoteliomi fra i meccanici delle ferrovie in Italia: un problema di attualità.

Asbestos has been used on rolling stock of the Italian Railways since the 1940's. From the 1950's to the 1970's it was used on a massive scale for the insulation of passenger carriages (up to more than 800 kg per carriage). About 10 years ago, a programme was began to remove asbestos from rolling stock and replace it with glass fibre. We must consider as exposed to the carcinogenic effects of asbestos all mechanics who, during the past years, worked at the Major Repair Workshops (MRW), at the Locomotive Depots (LD) of the State Railways, or in other state or private factories where railway rolling stock insulated with asbestos was built, checked, repaired or demolished, or where asbestos removal operations took place. It has been estimated that the total number of mechanics potentially exposed to asbestos since 1950 in the MRWs alone amounts to more than 25,000. There are about 750 workers presently employed at the Bologna MRW and it has been estimated that the entire cohort of this MRW from the beginning of the 1950's includes about 3,000 people (in excess). In 1986 the Bologna Institute of Oncology reported 6 cases of pleural mesothelioma at the Bologna MRW and 1 at the Rimini MRW. This was the first report of pleural mesotheliomas among railway mechanics in Italy. From 1986 up to the present, other cases of pleural mesothelioma have been recorded among mechanics working on railway rolling stock in the MRW's and in the LD's of the State Railways and in other factories.(ABSTRACT TRUNCATED AT 250 WORDS)

[The evaluation of the presumed mutagenic activity of barium nitrate]. / Valutazione della presunta attività mutagena del bario nitrato.

Barium nitrate, which is used in industry in the production of green signal lights, to remove gases from vacuum tubes, and in the production of barium oxide, was assayed to assess the possible mutagenic effects using both the Ames test (S. typhimurium TA 1535, TA 1537, TA 1538, TA 97a, TA 98, TA 100, TA 102c), with and without metabolic activation with the plate incorporation assay and pre-incubation assay methods, and using the mitotic crossing over test, the mitotic genic conversion test, and the retromutation test in Saccharomyces cerevisiae, D7 strain, with and without metabolic activation. In the experimental conditions of the study, at various gradually increasing concentrations, barium nitrate gave negative results.

[Mutagen activity of barium chloride in Salmonella typhimurium]. / Studio dell'attività mutagena del bario cloruro in Salmonella typhimurium.

Barium chloride, which is an important industrial chemical used in pigments, lacquers, dyes, glass and pesticide production, leather tanning and cloth dying, was tested on Salmonella typhimurium (TA 1535, TA 1537, TA 1538, TA 97, TA 98, TA 100) with the reverse mutation test, with and without metabolic activation, to assess its possible genotoxic effects and any possible action with respect to standard mutagens (sodium azide, 9-aminoacridine, 2-nitrofluorene, mitomycine-C, 2 aminoacridine). Using the platelet incorporation technique, barium chloride at various progressive concentrations gave negative results under the experimental conditions of the study.

Frizzled-1 is down-regulated in follicular thyroid tumours and modulates growth and invasiveness.

The mechanisms of follicular thyroid carcinoma (FTC) transformation and progression are not well understood. Previously, we detected LOH at 7q21 in all FTCs examined, indicating that loss of genetic material in that region is a common trait in these lesions. To analyse the effects of LOH on gene expression, we performed an analysis of the mRNA expression levels of six different genes, located at 7q21.1-7q21.3. A total of 23 lesions, including eight follicular hyperplasias (FHs), eight follicular adenomas (FAs), two FTCs and five papillary thyroid carcinomas (PTCs) were analysed. The Frizzled-1 (FZD-1) gene, located at 7q21.13, showed the lowest levels of mRNA expression. Down-regulation of FZD-1 expression was also confirmed in an independent series of 69 follicular neoplastic lesions compared to 25 PTCs, analysed by quantitative RT-PCR. In vitro studies showed that FZD-1 expression was also markedly reduced at both protein and mRNA levels in three FTC-derived cell lines (FRO, WRO and FTC-133), while it was normal in the three PTC-derived cell lines (Ca300, Ca301 and K1) examined. We demonstrated that over-expression of FZD-1 in 3 FTC-derived cells decreased invasiveness and proliferation rate, indicating a possible pathogenetic role. In addition, FZD-1 RNA interference in the PTC-derived cell line K1 increased invasiveness. Our data indicated that FZD-1 is involved in growth of follicular tumours and may be considered as a novel marker of this type of tumour.

Neonatal screening in Italy for congenital hypothyroidism and metabolic disorders: hyperphenylalaninemia, maple syrup urine disease and homocystinuria.

A multiple screening program to establish the frequency of congenital hypothyroidism (CH), phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria and hypertyrosinemia in endemic and sporadic goitrous regions of Italy is being carried out. Valine, methionine, leucine, isoleucine, tyrosine and phenylalanine, eluted from a single spot and separated by column chromatography, are measured, using whole blood adsorbed on filter paper. CH is detected by RIA assay of TSH eluted from dried blood spot. A cut-off of 100 microU/ml for TSH is used providing a recall rate of 0.38%. Out of 116,000 newborn infants screened for aminoacidopathies (since 1974), 16 PKU patients, 3 affected by MSUD, 2 homocystinuric babies have been detected. Out of 25,400 newborn infants screened for CH, 5 patients were affected by permanent CH and 29 by transient hyperthyrotropinemia. Thus PKU shows a frequency of 1:7,200 newborn infants, and permanent congenital hypothyroidism 1:5,080. The coordination of screening programs for congenital metabolic diseases in a single central unit allows:--the unification of the input of samples and output of data in a single data bank;--a minimization of the physical and psychological stress to the patients and their families;--and a more satisfactory cost/benefit ratio.

Immunoreactive trypsin on dried-blood spots as a possible neonatal test for cystic fibrosis. (I. Evaluation of the method and preliminary field trial).

A method for blood spot immunoreactive trypsin (IRT) determination suitable for neonatal mass screening, and the preliminary steps towards its large-scale application are described. The method showed a highly significant correlation between blood spot and plasma values, and a study of plasma reference values in a population of 1,050 newborn infants demonstrated a log-normal distribution with a mean IRT concentration of 238.3 ng/ml. The results and their implications for neonatal mass screening are discussed.

Receptors for fluoresceinated human thyroglobulin in peripheral blood lymphocytes.

Fluoresceinated human native and desialylated thyroglobulin were incubated with peripheral blood lymphocytes. 1% of the lymphocytes, in twenty samples from normal human blood donors, showed a bright granular fluorescence where neither the number nor pattern of fluorescence differed from lymphocytes from the blood of thyroiditis patients. Fluoresceinated albumin and gamma-globulin did not bind to the lymphocytes, and a 500-fold excess of native non-fluoresceinated thyroglobulin inhibited the binding and pre-incubation with anti-IgM serum abolished it. Binding with desialylated thyroglobulin was negligible, and the pattern of fluorescence was pale and uniform. Analysis by sucrose gradient centrifugation and double diffusion in agar gel showed that fluorescein dissociates thyroglobulin into 12S fragments and reduces its immunoreaction with autoantibodies. It can therefore be concluded that the 12S molecule produced by fluoresceination maintains its determinants for lymphocyte receptors, whereas further dissociation, as in desialylated fluoresceinated thyroglobulin, leads to a marked reduction in the binding with lymphocytes.

Immunological properties of Tg carbohydrates: enhancement of Tg immunoreaction by removal of sialic acid.

Immunoreaction of desialylated and native thyroglobulin was compared in sera of patients with anti-thyroglobulin antibodies by radioimmunoassay with 125I-labelled thyroglobulin. Two human thyroglobulins were iodinated both in vivo and by lactoperoxidase. After desialylation enhancement of immunoreaction was observed in several sera ranging from marginal to more than 100%. The effect was not due to iodination since it was reproducible with desialylated thyroglobulin labelled in vivo. In one serum (B.P.) a marked enhancement was only seen with one thyroglobulin suggesting that desialylation may unmask isoantigens of thyroglobulin. Glycopeptides prepared from human thyroglobulin inhibited the immunoreaction between native thyroglobulin and autoantisera. The results indicate that sialic acid masks antigenic determinants in human thyroglobulin and that carbohydrates might be the determinants involved in the process of autoimmunization.