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Curcumin has numerous anti-carcinogenic properties, but low bioavailability prevents its use in chemotherapeutic applications. One strategy for circumventing this problem has been the creation of synthetic analogues. We tested the efficacy of an analogue known as GO-Y030 in human breast and pancreatic cancer cells. We compared the impact of curcumin and GO-Y030 on the breast cancer cell line MDA-MB-231 and pancreatic cancer cell lines, PANC-1, HPAC and BXPC-3. Both compounds reduced cell viability and induced apoptosis, but GO-Y030 was substantially more potent. We also demonstrated that GO-Y030 was capable of interfering with STAT3, a persistently activated transcription factor in many cancer types. GO-Y030 inhibited STAT3 phosphorylation and transcriptional activity whereas comparable dosages of curcumin had little or no effect. These results indicate that GO-Y030 is a potent inhibitor of cell viability and STAT3 activation, and may thus have potential as a therapeutic agent for cancers expressing high levels of activated STAT3.

Organophosphorus insecticides, as Chlorpyrifos (CPF), are widely used in agriculture and against household pests; these compounds receive an increasing consideration as potential endocrine disrupters. The aim of the present study was to examine the potential short- and long-term effects of CPF on thyroid and adrenal glands in CD1 mice following exposure at dose levels not inducing brain acetyl cholinesterase (AchE) inhibition, during gestational and/or postnatal vulnerable phases. Pregnant dams were treated with 0, 3, 6 mg/kg bw/day of CPF on gestational days 15-18. After delivery, pups were treated subcutaneously on postnatal days (PND) 11-14 with: 0, 1, 3 mg/kg bw/day of CPF. Serum thyroxin (T4), thyroid and adrenals histology and histomorphometry were evaluated in dams and in F1 mice. In dams at 6 mg/kg, decreased T4 levels and increased cell height in thyroid were observed, and adrenal histology showed a slightly increased vacuolization in the X-zone. In the F1, short-term morphological modifications (reduced follicular size at PND 2) and long-term morphological (increased necrotic follicular cells) and biochemical alterations (reduced serum T4 levels) were found at PND 150 with an apparent higher vulnerability of males. For the first time these results indicate that CPF exposure at dose levels not inducing brain AchE inhibition causes thyroid alterations in dams and in F1 CD1 mice. Thyroid may be a sensitive target to CPF developmental exposure possibly leading to long-term effects on thyroid function. Because thyroid plays a pivotal role in mammalian development, these findings can be relevant to humans.

A study of the optical transmission of low-loss W1.5 photonic crystal waveguides built on silicon membranes and operating at telecom wavelengths is presented. The feasibility of performing all-optical switching is demonstrated for W1.5 waveguides coupled with L3 cavities, systems amenable for incorporation in on-chip devices. Switching of waveguide transmission is achieved by means of optical excitation of free carriers using a 2.5 ns pump laser. Experimental results are reproduced by finite-difference time-domain simulations which model the response of the finite system and band structure calculations describing the infinite, ideal one.

Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

Background/aims: In end-stage renal disease (ESRD), hyperhomocysteinemia is a common finding associated with increased cardiovascular risk. However, the pathogenic role of homocysteine is still unclear. In vitro studies show that thiol redox status affects endothelial cell functions. We therefore investigated the possible association between homocysteinemia and plasma thiol redox status in ESRD patients., Methods: Total plasma homocysteine (Hcy), cysteine (Cys) and free thiols (SH) were measured both before and after a dialytic session in 54 ESRD patients receiving (n = 15) or not receiving (n = 39) folate supplementation, and 17 control subjects., Results: High predialysis levels of both Hcy and Cys were found to be negatively correlated with low SH levels both in supplemented (r = -0.680, p < 0.01 and r = -0.624, p < 0.02, respectively) and unsupplemented (r = -0.698, p < 0.001 and r = -0.445, p < 0.01, respectively) patients. Following dialysis, SH values returned to normal and the above correlations were no longer appreciable., Conclusion: A strong, folate therapy-insensitive association between homocysteinemia and plasma free thiol levels was found in ESRD patients. These results support a role for oxidative stress in ESRD-related hyperhomocysteinemia and suggest the plasma thiol redox status alteration as a possible pathogenic mechanism underlying the cardiovascular toxicity of hyperhomocysteinemia in these patients., ((c) 2008 S. Karger AG, Basel)

The use of whole body vibration (WBV) training is becoming more widespread both among athletes and the general public for improving muscle performance. The biological and mechanical effects of WBV are not completely understood and numerous contraindications, that can be identified while obtaining the patient's clinical history, must be taken into consideration. Nephrolithiasis, which often remains asymptomatic for an indefinite time, is not reported in the medical literature as a contraindication to WBV. This paper reports a case of significant morbidity following one session of WBV training in a patient with asymptomatic nephroli-thiasis.

Context: In Italy, the surveillance of congenital hypothyroidism (CH) is performed by the Italian National Registry of Infants with CH (INRICH). Up to now, about 3600 infants with CH are recorded in the INRICH, and a high number of twins are included., Objective: Our objective was to estimate the risk of CH in multiple and single deliveries and to compare neonatal features of CH twins with twins from the general population., Design: The Italian population of CH infants recorded in the INRICH from 1989-2000 was investigated., Results: A more than 3-fold higher frequency of twins was found in the CH population than in the general population, and for the first time, it was possible to estimate the CH incidence in multiple (10.1 in 10,000) and single deliveries (3.2 in 10,000 live births). Significantly higher frequencies of in situ gland as well as lower TSH mean level at screening were found in twin than in singleton CH babies. The concordance rate for permanent CH was very low (4.3%) and due to only three concordant couples. However, a high recurrence risk for CH was estimated in siblings of affected babies recorded in the INRICH, including twins considered as siblings., Conclusions: The high CH incidence observed in twins is worthy of interest for the high number of induced pregnancies in Italy as well as in other Western countries. Moreover, the low concordance rate for CH among twins together with a high recurrence risk for the disease among siblings indicates that environmental risk factors may act as a trigger on a susceptible genetic background in the etiology of the disease.

To evaluate the effect of ammonium persulphate (AP) inhalation on NANC inhibitory (i-NANC) neurotransmitters of guinea pig airways, we exposed eight guinea pigs to AP (1 mg/m3), by aerosol inhalation for 30 minutes daily for three weeks. Control animals inhaled saline aerosol. After the last exposure, the isolated trachea was mounted in an organ bath and electrically stimulated in the presence of hyoscine, piperoxane and propranolol. The i-NANC responses were evaluated as decreases in intraluminal pressure and expressed as area under the curve (AUC, Pa x seconds). The isolated tracheae were treated with a-chymotrypsin, L-NAME, zinc protoporphyrin IX and ODQ, that inhibit the production or action of the single neurotransmitters, like peptides, NO and CO. In the exposed individuals, the NANC relaxations were below 50%, as compared to controls (P < 0.01). NO and CO were the neurotransmitters responsible for all the i-NANC responses, in similar proportions either in exposed individuals or in controls. In conclusion, ammonium persulphate exposure impairs the i-NANC control of airway tone without specifically affecting any neurotransmitter.

Recent epidemiological studies provide a clear evidence that hyperuricemia is associated with hypertension, coronary heart disease, left ventricular hypertrophy and progression of renal disease. Aim of our study was to assess the effect of low dosage of recombinant urate oxidase on hyperuricemia in renal failure patients that already receiving allopurinol. Our study group consisted of 43 renal failure patients, 23 women and 20 men. The mean age was 74 years (range 36-90 years). The following variables were studied on admission: serum creatinine, blood urea nitrogen and serum uric acid. Intravenous rasburicase was administered at a dose of 0.02 mg/kg/day on 3 consecutive days in patients with serum uric acid between 8-10 mg/dl, on 5 consecutive days in patients with serum uric acid between 10-15 mg/dl and on 7 consecutive days in patients with serum uric acid > 15 mg/dl. Uric acid levels were assayed after 48 hours and 7 days after rasburicase treatment. Mean values of uric acid levels after 48 hours were 2.47 mg/dl (+/- 1.58) in men and 2.77 mg/dl (+/- 2.24) in woman, where'as mean values of uric acid levels after 7 days were 4.45 mg/dl (+/- 2.0) in men and 5.75 mg/dl (+/- 1.9) in woman. No significant relationship were found between uric acid and creatinine as before as well after therapy. There were no side effects in all patients included in the study. After 7 days, the rasburicase therapy showed more antihyperuricemic effect in men (59%) than in women (46%).

Background: Oxidative stress (OS) is considered to play a major role in the development of end-stage renal disease (ESRD) complications. However, conflicting and inconsistent data have been reported on OS in ESRD patients. Our aim was to investigate the reliability of the most popular non-enzymatic plasma OS biomarkers in ESRD., Methods: Vitamins A (VitA), E and C (VitC), uric acid, plasma antioxidant and ferric-reducing potential (PAP and PRP), thiols (SH), malondialdehyde (MDA) and lipid hydroperoxides (HPO) were determined before and after dialysis in plasma from 33 ESRD patients on hemodialysis, hemodiafiltration or peritoneal dialysis and 20 control subjects., Results: In ESRD patients, high PRP and normal PAP values were positively correlated with VitC levels. After dialysis, PRP levels decreased, while unchanged PAP levels correlated positively with high VitA and transiently recovered SH values. All patients showed high levels of both MDA and cholesterol-normalized HPO. However, while the former significantly decreased after dialysis, the latter were unaffected by treatment. Paradoxical correlations of MDA with both VitA and HPO were found., Conclusions: Plasma PRP and MDA levels may be dramatically affected by both uremia and dialysis; their use in ESRD patients may therefore lead to OS misevaluation and should be avoided. More reliable results can be obtained using physiologically relevant OS functional tests, such as PAP, and early biomarkers of OS damage, such as SH and HPO.

Cardiac calcifications are a frequent finding in hemodialysis for chronic renal failure. Several factors may play a role in the intimal and medial calcification of coronary arteries such as age and some known atherogenetic factors. In addition, Fetuin-A has been proposed as a protective agent through solubilization of calcium phosphate salt. Fetuin-A is also a marker of inflammatory-nutritional state, and its changes could be an expression of this condition. The aim of this cross-sectional study is to evaluate the relative importance of risk factors of calcifications with special regard to Fetuin-A. The study was conducted with 132 hemodialysis patients. They were subjected to multislice computed tomography for evaluation of calcium deposits in the heart. In addition, the patients were sampled for evaluation of calcium-phosphate parameters, lipid profile, nutritional and inflammatory markers, and also Fetuin-A. There was a wide variability of the extent of calcium deposits expressed as Agatston score, with only 9.3% of patients without calcifications. Age, hemodialysis age, sex, calcium-phosphate parameters, and lipid profile were important risk factors, together with nutritional and inflammatory status of the patients. An inverse correlation between coronary calcium score and Fetuin-A emerged from a multiple regression analysis. However, there was no significant difference in serum Fetuin-A among different grades of calcium score. By dividing the patients in tertiles of serum Fetuin-A, an association between low levels of Fetuin-A and high calcification score was found. Fetuin-A as dependent variable was strictly linked to prealbumin serum levels. In addition, there was a clear link between cardiac calcification scores and inflammatory-nutritional markers. Serum calcium and treatment with calcitriol emerged as predictive variables of coronary score.Fetuin-A could be involved in the process of calcification both in the case of markedly low serum levels, due to decreased prevention of calcium phosphate precipitation, and also as a marker of inflammation, a well-known risk factor of atherogenesis. Treatment with intravenous calcitriol could marginally enhance cardiac calcifications, probably through its hypercalcemic effect.

Background: Treatment with folic acid and vitamin B12 appears to be effective in lowering total plasma homocysteine (tHcy) concentrations, but whether vitamin B12 alone lowers tHcy in patients with normal vitamin B12 status is unknown. The aims of the present study were to explore the effect of individual supplementation with folic acid or vitamin B12 on tHcy concentrations in hemodialysis (HD) patients and to compare changes in tHcy concentrations with MTHFR genotype., Methods: We recruited 200 HD patients (119 men) from the "Umberto I" Hospital (Frosinone, Italy) and the Dialysis Unit of University Hospital "Tor Vergata". These patients were randomized blindly into 2 groups of 100 each. Unfortunately, during the study, 36 patients in the first group and 16 in the second group died. The first group was treated initially with vitamin B12 for 2 months and with folic acid for a following 2 months. The second group was treated initially with folic acid and then with vitamin B12. Samples were drawn before administration of either, after the first and second periods, and again 2 months after treatment., Results: The concentrations of tHcy decreased in both groups after the consecutive vitamin therapies, and the decrease was genotype-dependent. The decrease was greater for the T/T genotype (P <0.05) and was more significant when the treatment was started with folic acid (P <0.01)., Conclusion: The alternating vitamin treatment demonstrated for the first time the importance of folate therapy and the secondary contribution of vitamin B12 in lowering tHcy in HD patients.

In the present work, the oligochaete Lumbriculus variegatus was exposed for 56 d to lake sediment spiked with 4-nonylphenol (4-NP), which is a breakdown product of alkylphenol polyethoxylates, an important class of nonionic surfactants. During the exposure period, the content of 4-NP was determined in the oligochaetes, sediment, overlying water, and pore water in order to monitor the distribution of the 4-NP in the compartments of the test system. Concentration of 4-NP in L. variegatus increased linearly over the course of the test, with an uptake rate coefficient of 1.9 x 10(-2) (+/- 0.2 x 10(-2); [g carbon/(g lipid x h)]). No steady state was reached at the end of the exposure period, suggesting that the elimination of 4-NP by the organism was negligible. Ingested sediments played an important role in the accumulation of 4-NP in L. variegatus, which may achieve very high 4-NP body concentrations. The 56-d biota sediment accumulation factor (BSAF) was 24 +/- 7 g carbon/g lipid. L. variegatus also was exposed to 4-NP-contaminated field sediment, and field oligochaetes and sediments were collected for 4-NP pollution assessment in aquatic ecosystem. The 4-NP uptake with natural sediment was in accordance with that measured with spiked sediments, suggesting that the bioavailability of sediment-associated 4-NP for L. variegatus was not affected by 4-NP sediment concentration and abiotic sediment characteristics. The BSAFs measured in field oligochaetes, ranging from 39 to 55 g carbon/g lipid, was relatively higher than the bioaccumulation factor measured in laboratory tests. The results suggest that 4-NP concentration can reach high levels in benthic oligochaetes; this can be an important way of exposure for their pelagic predators.

The refractoriness of T cells to the interferon-gamma (IFN-gamma)/signal transducer and activator of transcription 1 (STAT1) pathway, which shields them from the antiproliferative effect of IFN-gamma, is attributed mainly to down-regulation of the IFN-gammaR2 signaling chain. However, the mechanisms responsible for this down-regulation are unclear. Here we show that iron uptake mediated by the transferrin receptor (TfR) delivers a signal that leads to IFN-gammaR2 internalization and thus plays an essential role in attenuating activation of the IFN-gamma/STAT1 pathway in human T lymphocytes. The effect of iron on IFN-gammaR2 internalization was specific as it did not affect expression of the IFN-gammaR1 binding chain. Deferoxamine (DFO), an iron-chelating agent, up-regulated IFN-gammaR2 surface expression and reinstated IFN-gamma/STAT1 activation in proliferating T lymphocytes. Resistance of malignant T cells to the antiproliferative effect of IFN-gamma in vitro was abrogated by addition of DFO. Conversely, iron inhibited IFN-gamma-induced apoptosis in malignant T cells in serum-free conditions. In combination but not individually, DFO and IFN-gamma strongly inhibited growth of human malignant T cells in an in vivo severe combined immunodeficient (SCID) mouse model. These data provide valuable insights for novel therapeutic approaches aimed at reinstating the IFN-gamma/STAT1 apoptotic signaling pathway in autoreactive or neoplastic T cells by means of iron chelation.

Heavy metal biosorption onto solid wastes from olive oil production plants, olive pomace, has been investigated. Acid-base properties of the active sites of olive pomace were determined by potentiometric titrations and represented by a continuous model accounting for two main kinds of active sites. Competition among protons and heavy metals in solution was considered by performing biosorption tests at different equilibrium pH with single (Cu and Cd) and binary metal systems (Cu-Cd). Both Langmuir extensions and non-ideal competitive adsorption models (NICA models) can be used to represent experimental data of Cu and Cd biosorption in single metal systems at different equilibrium pH. Nevertheless only NICA models, accounting for site heterogeneity and non-ideal adsorption of the different species simultaneously present in solution, can adequately simulate the competition among Cu and Cd in binary metal systems by using the parameters fitted to single system data.

HFR-ON LINE (double chamber HDF with reinfusion of ultrafiltrate regenerated through a charcoal-resin cartridge) is a novel method which combines the processes of diffusion, convection, and adsorbance. We have investigated the effect of such a treatment on the homocysteine (Hcy) levels in ten patients with a mean Hcy level of 57.6 micromol/L (range 24.1-119.7 micromol/L). We have measured the Hcy, folate, and vitamin B12 predialysis and postdialysis, and in the ultrafiltrate precartridge and postcartridge at 10, 120, and 240 min. The mean Hcy levels were 57.6 and 35.3 micromol/L (range 9.9-80.3 micromol/L) (P = 0.005) predialysis and postdialysis, respectively, while folate and vitamin B12 were unchanged. Precartridge and postcartridge Hcy levels were 11.6 vs. 2.5 micromol/L (P = 0.005), 9.3 vs. 3.9 micromol/L (P = 0.005), and 7.7 vs. 4.6 micro mol/L (P = 0.012) at the three time points considered, while folate and vitamin B12 were essentially undetectable. These preliminary data, which need confirmation in a long-term study, seem to indicate that HFR-ON LINE is able to reduce Hcy levels not only through a likely reduction of uremic toxins, but also through an actual removal of Hcy by adsorbance onto the charcoal-resin cartridge.

A readily applicable method based on extraction by aqueous non-ionic surfactant solutions (Tween 80) and RP-HPLC coupled to fluorescence detection, has been developed for the simultaneous determination of the phenolic endocrine disrupting chemicals (EDCs) nonylphenol (NP), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate (NP2EO) and bisphenol A (BPA) in environmental solid matrices. Clean up of sample extracts was performed on Si-C18 solid phase extraction (SPE) cartridges. The overall Tween 80 extraction-SPE-RP-HPLC procedure was validated for accuracy and precision by analyzing sediment samples spiked with known amounts of EDCs. Recoveries for NP, NP1EO, NP2EO and BPA and limits of detection are in agreement with conventional extraction methods. The developed methodology was successfully applied to the analysis of target compounds in Italian river sediments, river suspended matter and benthonic macroinvertebrate organisms (oligochaetes Lumbriculus variegatus). Results confirmed that this relatively simple procedure performed satisfactorily in the determination of phenolic EDCs in environmental solid matrices of different complexity and that it can be a suitable alternative method to conventional systems even for routine analyses.

The human CC chemokine CCL16, a liver-expressed chemokine, enhances the killing activity of mouse peritoneal macrophages by triggering their expression of tumor necrosis factor alpha (TNF-alpha) and Fas ligand. Macrophages also respond to CCL16 by enhancing their production of monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted chemokines, and interleukin (IL)-1 beta, TNF-alpha, and IL-12. The effect of CCL16 is almost as strong as that of lipopolysaccharide and interferon-gamma, two of the best macrophage activators. Moreover, CCL16-activated macrophages overexpress membrane CD80, CD86, and CD40 costimulatory molecules and extensively phagocytose tumor cell debris. On exposure to such debris, they activate a strong, tumor-specific, cytolytic response in virgin T cells. Furthermore, cytolytic T cells generated in the presence of CCL16 display a higher cytotoxicity and activate caspase-8 in tumor target cells. This ability to activate caspase-8 depends on their overexpression of TNF-alpha and Fas ligand induced by CCL16. These data reveal a new function for CCL16 in the immune-response scenario. CCL16 significantly enhances the effector and the antigen-presenting function of macrophages and augments T cell lytic activity.

The ability of insulin-like growth factor-1 (IGF-1) to regulate surface expression of the interferon-gamma receptor 2 (IFN-gamma R2) transducing chain and activation of IFN-gamma-induced signal transducer and activator of transcription-1 (STAT-1) in human T cells was analyzed. We show that, especially in the absence of serum (which contains IGF-1), IGF-1 down-regulated surface expression of the IFN-gamma R2 chain and inhibited both IFN-gamma-dependent STAT-1 activation and apoptosis in T-cell lines ST4, Jurkat, and Molt-4. IFN-gamma R2 down-regulation resulted from its enhanced internalization since IGF-1 completely restored the uptake of anti-IFN-gamma R2 monoclonal antibody (mAb) in serum-deprived T-cell lines. When the interaction between IGF-1 and its receptor was blocked by anti-IGF-1R mAb, enhancement of IFN-gamma R2 surface expression, STAT-1 activation, and reinstatement of IFN-gamma-induced apoptosis were observed. Enhanced expression of IFN-gamma R2 was also observed in phytohemagglutinin (PHA)-activated T lymphoblasts cultured in the presence of anti-IGF-1R mAb, whereas IGF-1 or anti-IGF-1R mAb did not modify the high IFN-gamma R2 expression in B and myeloid cell lines. Both IGF-1 and anti-IGF-1R mAb did not modify the constitutive expression of IFN-gamma R2 mRNA in T cells as well as the high IFN-gamma R1 binding chain surface expression in T, B, and myeloid cells. These data indicate that IGF-1 plays a critical role in the desensitization of IFN-gamma/STAT-1 signaling in T lymphocytes by delivering a signal for IFN-gamma R2 internalization.

Postpartum thyroiditis (PPT) is characterized by a rapid evolution and recovery of euthyroidism. Therefore, it can represent a good model to study early cytokine fluctuations in autoimmune thyroid diseases. TGFbeta1 is an immunosuppressive cytokine, as it inhibits T and B cell proliferation, natural killer cell cytotoxic activity, and the generation of T cell cytotoxicity. The aim of this study was to assess serum concentrations of TGFbeta1 during pregnancy and to study possible serum fluctuations of this cytokine during the different phases of PPT. Thyroid biochemical pattern, antithyroid autoantibodies (ATA), and total and active TGFbeta1 (aTGFbeta1) serum concentrations were evaluated in 63 pregnant women. Thirty-four of them were ATA(+), and 29 were ATA(-). Twenty of the 34 ATA(+) women were followed in the postpartum year. Nine of these 20 women developed PPT; 11 remained euthyroid. All of the PPT women became euthyroid during the follow-up. Our results showed 1) detectable serum levels of aTGFbeta1 in 50% of ATA(+) pregnant women, suggesting that the presence of autoantibodies may characterize a favorable condition for TGFbeta1 activation; and 2) decreased total TGFbeta1 and increased aTGFbeta1 serum levels during the active phase of PPT in ATA(+) women. This seems to suggest that inflammation may be responsible for TGFbeta1 activation and autoantibody increase because of antigen release. Although further studies of women with persistent hypothyroidism after the postpartum year are needed, the possibility that the enhanced activation of TGFbeta1 may contribute to resolution of thyroid inflammation postpartum cannot be excluded.

Some activities on marine sediments, such as escavation of the bottom, search for hydrocarbons, deposit of sands on beaches, and harbour dredging or works are considered. These activities may cause the release of pathogens or chemical contaminants in waters used for recreational, rearing or fishery activities, so representing a threat to human health.

In the last decade a high frequency of other congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in the population of CH infants detected in Italy between 1991 and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of screening, treatment, and follow-up of CH adhere to the Italian National Registry of infants with CH. In this study a high prevalence of additional CM (8.4%), more than 4-fold higher than that reported in the Italian population (1-2%), was found in the population of CH infants. Cardiac anomalies represented the most frequent malformations associated with CH, with a prevalence of 5.5%. However, a significant association between CH and anomalies of nervous system, eyes, and multiple CM was also observed. In conclusion, the significantly higher frequency of extrathyroidal congenital malformations reported in the CH infants than in the general population represents a further argument supporting the role of a genetic component in the etiology of CH. Investigations of the molecular mechanisms underlying developmental events of formation of thyroid and other organs represent critical steps in the knowledge of CH etiology.

The authors describe the characteristics of a rare hemoglobin mutant found in a young female. She carries the aminoacid replacement of Hb-Hinsdale:beta139(H17)ASN-->Lys, which was identified at molecular level. This case, clinically and hematologically symptomless, is identical, but genetically independent, to the cases first described in an American family.

Maternal and child health represents one of the most relevant fields of interest in public health and particular attention is given to congenital pathologies. In Italy, the incidence of congenital hypothyroidism (CH) is 1:3200 live birth. CH is diagnosed at birth by neonatal thyroid screening. This allows a precocious onset of substitutive therapy which avoids severe psychomotor deficits in infants with CH. Moreover, the newborn screening program have permitted to identify transient disorders of thyroid function in newborns. These are essentially due to neonatal, maternal and environmental risk factors, especially iodine deficiency. The National Register (NR) of infants with CH was established in 1987. The aim of the NR is to provide disease surveillance and to monitor efficiency and effectiveness of neonatal screening. Furthermore, the NR represents an useful tool for developing epidemiological studies to identify possible environmental and/or familial risk factors of CH.

On the basis of data collected in the National Register of infants with congenital hypothyroidism (CH), a mean incidence of 1 case of CH to 3200 live births has been estimated in Italy. Nevertheless a higher incidence (> 1:2000) than national mean value has been observed in several districts of our country. The aim of this study was to verify a possible occurrence of transient hypothyroidism (TH) in these areas. Results of our study showed that the proportion of infants with thyroid in situ was significantly higher in the areas with very high CH incidence than in the remaining parts of the country. Also serum TSH levels at confirmation showed a less severe hypothyroidism in infants of these areas when compared with the other CH infants. Furthermore, preliminary results of diagnosis reevaluation showed 58% of TH in the areas with CH incidence > 1:2000. Lower percentages of TH have been observed in the other areas in relation to the decreasing of CH incidence. Most of the high CH incidence areas are historically affected by iodine deficiency. This observation supports the hypothesis that iodine deficiency can contribute to the occurrence of transient disorders of thyroid function in our population and stresses the need of promoting diffusion of an adequate iodine prophylaxis.

Recent studies reported the role of several trace elements in health and disease. The role of iodine deficiency in thyroid dysfunction is well known. Also the selenium deficiency has been reported to be correlated to thyroid dysfunctions. In fact, although the major role of selenium is related to the glutathione peroxidase system, which protects cellular structures from oxidative damages, selenium plays also an important role in thyroid hormone metabolism as an essential component of the three deiodinase. These regulate inter-conversion of active and inactive forms of iodothyronines. Several studies have been carried out to establish the role of combined selenium and iodine deficiency. This review aims to provide information on the relationship between selenium and iodine intake and thyroid function. Furthermore, the state of art on the effects of the combined deficiency of selenium and iodine is also provided.

We report on the case of a 32 years old man submitted to right eye enucleation twelve years before for a choroidal melanoma. We observe a metastases located in the left adrenal gland. The blood-tests, the TAC of the abdomen did not show other localizations, while during laparotomy were discovered metastases in the pancreas and in the omentum. In this case, the age of tumor's development, the age of clinical manifestation, the period between the enucleation and the appearance of the metastases and their localization are exceptions to the normal biological behaviour of the choroidal melanoma.

The Authors report two cases of central nervous system complications after retrobulbar block. These complications have a 0.044% incidence in 4500 subsequent cases of retrobulbar blockade studied from 1981 to 1990. The Authors attribute the respiratory arrest and coma to direct access of the anesthetic to the central nervous system along the subdural space in the optic nerve sheath.

The Streptococci, isolated from 500 mucus-pharyngeal tampons, have been tested, for a group identification, by means of four different techniques in order to value the specificity and reliability in comparison with more traditional and, sometimes, more complex tests; such as Maxted and Lancefield. The most suitable method for routine researchers of microbiology laboratories is the one based on the extraction, by means of enzyme obtained from Streptomyces Griseus, of streptococci antigens before starting their serum identification, possible for A-B-C-D-F-G groups (Streptex). On the contrary, the method based on the links of group-specific antibodies with the A protein of the surface of Staphylococci Cowan I, has resulted more defective because Streptococci D and F cannot be grouped, and less specific because of frequent co-agglutinations.

A patient with acquired intestinal malabsorption developed a motor-sensory polyneuropathy with a recurrent remittent course, normal CSF and reduced motor and sensory conduction velocities. Nerve biopsy showed axonal changes. Serum DL-alpha-tocopherol was abnormally low. Six months supplementation with vitamin E was followed by normalization of DL-alpha-tocopherol serum levels and clinical and electrophysiological improvement.