Natural Hexavalent Chromium in the Pollino Massif Groundwater (Southern Apennines, Italy): Occurrence, Geochemistry and Preliminary Remediation Tests by Means of Innovative Adsorbent Nanomaterials.

In this study Cr(tot), Cr(VI), major and trace elements were determined in groundwater of northern sector of the Pollino Massif (southern Italy). The investigated area is characterized by ophiolitic rocks consisting of metabasites, shales and calcschists and fractured serpentinites. Two main hydro-facies were observed, reflecting low temperature water-rock interaction. The Mg-HCO3 hydrofacies is due to the weathering of serpentinites, Ca-HCO3 groundwaters are linked to the interaction with calcschist and metabasites. High Cr(VI) concentrations were detected, exceeding the maximum admissible concentrations by Italian regulation, due to the release of Cr(III) from ophiolitic rocks into water and its oxidation to the hexavalent state. Remediation tests were carried out using two synthetized nanomaterials, Fe(0) and magnetite, characterized by a mean size lower than 50 nm. The experiments were conducted at fixed nanoparticles/Cr(VI) molar ratio and according to previous studies. In addition, the kinetic data were interpreted with a suitable mathematical model.

Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements.

In near infrared fluorescence-guided surgical oncology, it is challenging to distinguish healthy from cancerous tissue. One promising research avenue consists in the analysis of the exogenous fluorophores' lifetime, which are however in the (sub-)nanosecond range. We have integrated a single-photon pixel array, based on standard CMOS SPADs (single-photon avalanche diodes), in a compact, time-gated measurement system, named FluoCam. In vivo measurements were carried out with indocyanine green (ICG)-modified derivatives targeting the αvß 3 integrin, initially on a genetically engineered mouse model of melanoma injected with ICG conjugated with tetrameric cyclic pentapeptide (ICG-E[c(RGD f K)4]), then on mice carrying tumour xenografts of U87-MG (a human primary glioblastoma cell line) injected with monomeric ICG-c(RGD f K). Measurements on tumor, muscle and tail locations allowed us to demonstrate the feasibility of in vivo lifetime measurements with the FluoCam, to determine the characteristic lifetimes (around 500 ps) and subtle lifetime differences between bound and unbound ICG-modified fluorophores (10% level), as well as to estimate the available photon fluxes under realistic conditions.

The cytoprotective drug amifostine modifies both expression and activity of the pro-angiogenic factor VEGF-A.

BACKGROUND: Amifostine (WR-2721, delivered as Ethyol) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. Its mechanism of action is attributed to the free radical scavenging properties of its active dephosphorylated metabolite WR-1065. However, amifostine has also been described as a potent hypoxia-mimetic compound and as a strong p53 inducer; both effects are known to potently modulate vascular endothelial growth factor (VEGF-A) expression. The angiogenic properties of this drug have not been clearly defined. METHODS: Cancer cell lines and endothelial cells were used in culture and treated with Amifostine in order to study (i) the expression of angiogenesis related genes and proteins and (ii) the effects of the drug on VEGF-A induced in vitro angiogenesis. RESULTS: We demonstrated that the treatment of several human cancer cell lines with therapeutical doses of WR-1065 led to a strong induction of different VEGF-A mRNA isoforms independently of HIF-1alpha. VEGF-A induction by WR-1065 depends on the activation of the eIF2alpha/ATF4 pathway. This up-regulation of VEGF-A mRNA was accompanied by an increased secretion of VEGF-A proteins fully active in stimulating vascular endothelial cells (EC). Nevertheless, direct treatment of EC with amifostine impaired their ability to respond to exogenous VEGF-A, an effect that correlated to the down-regulation of VEGFR-2 expression, to the reduction in cell surface binding of VEGF-A and to the decreased phosphorylation of the downstream p42/44 kinases. CONCLUSIONS: Taken together, our results indicate that amifostine treatment modulates tumour angiogenesis by two apparently opposite mechanisms - the increased VEGF-A expression by tumour cells and the inhibition of EC capacity to respond to VEGF-A stimulation.

Lack of TSH inhibition by exogenous L-T4 in a patient with follicular thyroid carcinoma.

We report a case of a male patient thyroidectomized for follicular thyroid carcinoma and presenting extremely elevated serum thyrotropin levels under L-T4 suppressive therapy. Administration of L-T3 in increasing amounts resulted in a significant decrease of serum TSH levels. The nature of the possible molecular defects underlying this unusual condition and pitfalls arising from the failure of L-T4 therapy to inhibit TSH secretion in a patient in post-surgical follow-up for follicular carcinoma are discussed.

[The need for integrated care of patients with chronic nephropathies: the epidemiology of 'late referral']. / Epidemiologia dei bisogni di gestione integrata: il "late referral" in Nefrologia.

BACKGROUND: The recent need for information has prompted this collaboration between health system epidemiologists (Basilicata) and clinicians to compare models of 'local' epidemiology in the management of diseases. The referral of patients to a nephrologist represents a working hypothesis of research- intervention. METHODS: Analysis of renal registry (RR) and administrative databases (hospital discharge abstracts/HDA, ambulatory);ad hoc surveys. RESULTS: Patients on dialysis between 1994 and 1998 are 594, cumulative deaths are 190 (32%). Males and the elderly (age = 65 years) are associated with more than 50% and threefold increase in relative risk of death, and with a diabetic nephropathy of 60% vs other renal diseases. Of 570 patients alive in 1996, 442 are linked with 2,628 HAD. Comorbid conditions are underreported in the RR (the Charlson index has been computed using HDA). Of 66 new dialysis cases, 31 are referred to a nephrologist only 6 months before the start of dialysis (47%) (22% diabetics). Patients discharged with chronic nephropathies (CN) and diabetes are 21% of CN patients (5% of diabetics). Of 100 patients with pre-end stage renal disease and diabetes, only 11-14 are discharged from the nephrology ward. At the local level, 3 out of 4 patients with serum creatinine higher than 1.5 mg/dl are not referred to a nephrologist. The prevalence of CN may vary from 0.4% to more than 1%. CONCLUSIONS: While an improvement in health databases in the regions is underway, collaboration studies are essential for planning specific interventions for prevention and management of diabetic nephropathy to improve the use of resources in nephrology.

alpha2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity.

BACKGROUND: Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation. DESIGN: In this study, we investigated the effects of pre-treatment with an alpha2-adrenoceptor agonist, clonidine (2 microg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0. 001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100 microg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and in nonobese controls. RESULTS: During the control CRH + AVP test the ACTH but not the cortisol response was higher (P < 0.05) in obese A-BFD women than in controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadily and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group. CONCLUSIONS: This study shows that alpha2-adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH + AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.