The longitudinal biomonitoring of residents living near the waste incinerator of Turin: Polycyclic Aromatic Hydrocarbon metabolites after three years from the plant start-up.

The waste-to-energy (WTE) incinerator plant located in the Turin area (Italy) started to recover energy from the combustion of municipal solid waste in 2013. A health surveillance program was implemented to evaluate the potential health effects on the population living near the plant. This program included a longitudinal biomonitoring to evaluate temporal changes of some environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs), in residents living in areas near the Turin incinerator (exposed group, E) compared to those observed in subjects living far from the plant (not exposed group, NE). Ten monohydroxy-PAHs (OH-PAHs), consisting in the principal metabolites of naphthalene, fluorine, phenanthrene, and pyrene, were analyzed in urines collected from the E and NE subjects after one (T1) and three years (T2) of plant activity and compared with those determined in the same cohort established before the plant start-up (T0). Spearman correlation analysis was undertaken to explore possible associations between OH-PAHs and personal characteristics, lifestyle variables, and dietary habits. A linear mixed model (LMM) approach was applied to determine temporal trends of OH-PAHs observed in the E and NE subjects and to evaluate possible differences in trend between the two groups. Temporal trends of OH-PAHs determined by LMM analysis demonstrated that, at all times, the E group had concentrations lower than those assessed in the NE group, all other conditions being equal. Moreover, no increase in OH-PAH concentrations was observed at T1 and T2 either in E or in NE group. Significant positive correlations were found between all OH-PAHs and smoking habits. Regarding variables associated to outdoor PAH exposure, residence near high traffic roads and daily time in traffic road was positively correlated with 1-hydroxynaphthalene and 1-hydroxypyrene, respectively. In conclusion, no impact of the WTE plant on exposure to PAHs was observed on the population living near the plant.

Biomonitoring of the adult population living near the waste incinerator of Turin: Serum concentrations of PCDDs, PCDFs, and PCBs after three years from the plant start-up.

In September 2013 a waste-to-energy (WTE) incinerator located in the Turin area (Piedmont, Northern Italy) started to produce energy by the incineration of municipal solid wastes. The plant, one of the largest WTE incinerator in Europe, burns up to 490,000 tons of waste per year. A health surveillance program was implemented in order to evaluate the potential health effects on the population living near the plant. This program included a biomonitoring study aimed at assessing levels of several environmental contaminants including, among others, PCDDs, PCDFs, and PCBs. Before the WTE incinerator start-up (T0), a group of 85 subjects (41 "exposed" and 44 "not exposed" subjects) was randomly selected for enrollment by the local health units among individuals aged 36-50 years who had been living in the same area for at least five years prior to the study. Subjects were balanced by exposure area, sex and five-year age classes. As from the study design, the same cohort was re-evaluated after three years of incinerator activity (T2). A parallel study was conducted on a group of 12 farmers living and/or working in farms located in an area in the range of 5 km around the incinerator. Results of this study did not evidence any impact of the WTE plant on human exposure to PCDDs, PCDFs, and PCBs. In fact, no significant differences were found in the concentrations of PCDDs + PCDFs, DL-PCBs, and NDL-PCBs measured in the population group residing near the plant after three years of activity (T2) with respect to the control group. A significant decrease of serum concentrations of all the analytes was observed at T2 in both groups compared to T0. Serum concentrations of PCDDs, PCDFs, and PCBs in the group of farmers were higher than those observed in the adult population under study.

Defibrotide: properties and clinical use of an old/new drug.

The drug named defibrotide (DFT) has been studied for many years. It has been shown to possess many activities: profibrinolytic, antithrombotic-thrombolytic, antiischemic (heart, liver, kidney, skin, brain), antishock, antiatherosclerotic, antirejection and anti-angiogenic. The previously displayed activities, as antithrombotic, profibrinolytic and anti-inflammatory, suggested its use in vascular disorders, as in the treatment of peripheral obliterative arterial disease and in thrombophlebitis. Some years after, the use of DFT in hepatic veno-occlusive disease has been also proposed. Even if DFT was considered for long time a multi-target drug, now it could be considered on the whole as a drug able to protect endothelium against activation. The present work reviews the more important experimental and clinical studies performed to detect DFT effects.

Polychlorinated dibenzodioxins, dibenzofurans, and biphenyls in fresh water fish from Campania Region, southern Italy.

Twenty-eight fish muscle specimens from the main water bodies of the Campania Region were analyzed in our laboratory. On average, results showed a low contamination by PCDDs+PCDFs and a relatively more important presence of DL-PCBs. All specimens were compliant with EU regulatory maximum levels. Cumulative PCDD+PCDF+DL-PCB concentrations (TEQ(TOT)) were comprised in the range 0.223-11.4 pgWHO(97)-TEQ g(-1) fresh weight (fw). DL-PCB contribution to TEQ(TOT) was on average greater than 86% (range, 50.2-97.1%). The cumulative concentrations of 30 non-dioxin-like PCB congeners (Σ(30)(NDL-PCBs)) and of the six indicators (Σ(6)(NDL-PCBs)) were respectively in the ranges 3.30-515 and 1.30-195 ng g(-1) fw. The hybrid clustering approach adopted to analyze the sample-specific congener profiles indentified the main analytical patterns present in the database and, in particular, two main diverse exposure macro-areas that seem to exist north and south of the city of Naples. The distribution of PCDD and PCDF congeners among different species showed significant variations from chub (Leuciscus cephalus), characterized by a higher proportion of low-chlorinated congeners (e.g. 2,3,7,8-T(4)CDD), to eel (Anguilla anguilla), whose contamination consisted mainly of highly chlorinated congeners (e.g. O(8)CDD). To have a more complete perspective in relation to the contaminants present in the environment, the study suggestion is to use benthic as well as pelagic species to obtain an integrated characterization of fish tissue contamination.

Cellfood™ improves respiratory metabolism of endothelial cells and inhibits hypoxia-induced reactive oxygen species (ros) generation.

Endothelial mitochondria, the major site of ATP generation, modulate the intracellular dynamics of reactive oxygen species (ROS), which, in turn, control endothelial function. Adequate oxygen (O(2)) supply is required by endothelial cells (EC). Both hypoxia and hyperoxia may favor the overproduction of ROS leading to oxidative stress, mitochondrial damage and endothelial dysfunction. We investigated the capability and mechanisms of Cellfood™ (CF), an antioxidant compound, to modulate O(2) availability and mitochondrial respiratory metabolism and to regulate ROS generated by hypoxia in EC in vitro. Human umbilical vein endothelial cells (HUVEC) and ECV-304 were evaluated for the O(2) consumption using a Clark's electrode. The O(2) consumption rate rose, during the first minutes after CF addition and was associated with increase in mitochondrial oxidative capacity and good cell viability. Similar behaviours were observed when EC were exposed to CF for up to 8 days. The O(2) consumption increased and was accompanied by both intracellular rise of ATP and maintainment of LDH concentration. Hypoxia-induced ROS generation was significantly inhibited by CF, through the up-regulated expression of MnSOD, an anti-oxidant responsible for mitochondrial function preservation. The EC hypoxic response is mediated by the hypoxia master regulator HIF-1alpha whose activation was attenuated by CF, in concomitance with MnSOD up-regulation. Our results suggest a role for CF in improoving respiratory metabolism and in activating anti-oxidant mechanisms in EC, thus preserving endothelial function.

Periodate oxidized ATP (oATP) reduces hyperalgesia in mice: involvement of P2X7 receptors and implications for therapy.

Some inflammatory mediators play an important role not only in the pathogenesis of the inflammatory pain, but also in that of neuropathic and visceral pain. We previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7 receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in humans. We also show that mice lacking P2X7 receptors (KO) are resistant to hyperalgesic thermal stimuli following the induction of arthritic, neuropathic and visceral pain. Local (injection into the right hind paw) pre-treatment with oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in wild type mice. In addition, KO mice are not insensitive to intraplantar treatment with ATP. Our data suggest that, even if oATP is able to inhibit purinoceptors different from P2X7, the latter are the more important involved in pain transmission.

Rats desensitized by capsaicin alter their food intake regulation especially at cold ambient temperature.

Adult rats were treated subcutaneously for 10 days with capsaicin, and their food intake and body weight were recorded for almost 6 weeks after stopping the treatment. The animals were exposed to different ambient temperatures: Ta (22, 32, 35, 10 and 22 degrees C). In the capsaicin-treated group a persistent increase in food intake and a reduction of body weight were observed when the animals were exposed to the lowest Ta of 10 degrees C. Starting from this temperature, food intake remained significantly higher than in controls until the end of the experiment at a Ta of 22 degrees C. The discrepancy between body weight increase and food intake especially at low temperature (10 degrees C) suggests that capsaicin could prevent suppression of food intake through the mediation of capsaicin-sensitive vagal afferent fibers by activation of cold-temperature-sensitive receptors.

Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.

SETTING: An Argentinean reference hospital specialising in infectious diseases. OBJECTIVE: To assess the outcomes of all human immunodeficiency virus (HIV) negative multidrug-resistant tuberculosis (MDR-TB) patients referred to or diagnosed at Hospital Muñiz. DESIGN: Clinical study for the period 1996-1999, with follow-up until June 2002. RESULTS: One hundred and forty-one adult patients (52.5% female) with resistance to two to seven drugs were studied. Fifty patients (35.5%) had not been treated previously. The most frequently used second-line drugs were 5-F-quinolones, cycloserine and ethionamide in susceptibility based individually tailored three- to five-drug regimens. Hospital admission was associated with treatment success. Forty-five episodes of severe toxicity occurred. Treatment was successful in 51.8% of cases, but follow-up of 73 patients yielded 11.9% relapse. The mortality rate was 19.1% and default was 19.9%. Logistic regression analysis was statistically significant for treatment success in relation to patient admission, residence and resistance pattern. CONCLUSION: The burden of MDR-TB in this setting--prolonged infection, treatment cost and difficulties, low rates of cure and treatment adherence and high rates of fatality and relapse--can be improved by strengthening TB control programme activities and fighting against poverty and HIV/AIDS.

Effect of somatostatin on beta-endorphin release in rat experimental chronic inflammation.

The aim of the present study was to investigate the effect of somatostatin administration in arthritic rats. Inflammation was induced by daily interplantar injection of 100 microl of Freund's complete adjuvant into the left hind paw of the rat. Arthritis developed 20 days following the first injection and was stable in the inoculate paw. Arthritic rats were treated interplantarly with somatostatin (5 or 10 microg) or with indomethacin (100 microg) daily for 14 days. Inflammatory response was studied at 12 h, 7 and 14 days following drug administration. The effect of somatostatin was determined by local (into popliteal lymph nodes) and systemic production of beta-endorphin. Our results showed that somatostatin treatment significantly increased beta-endorphin levels in the blood and lymphocytes from popliteal lymph nodes. Greater efficiency was seen when 5 microg instead of 10 microg of somatostatin was used. A significant decrease of absolute leukocytosis was observed at the 14th day following somatostatin administration. Moreover, a significant reduction of plasmatic beta-globulins at 12 h and the 7th day and of plasmatic alpha2-globulins at the 14th day was observed after the beginning of somatostatin treatment.

Resveratrol, a natural stilbene in grapes and wine, enhances intraphagocytosis in human promonocytes: a co-factor in antiinflammatory and anticancer chemopreventive activity.

Trans-resveratrol, a natural stilbene present in wine and grapes, has been studied mainly for its antiinflammatory and anticancer activities. In this study the activity of resveratrol on proliferative immunological parameters (differentiation, apoptosis, phagocytosis and intracellular killing) was studied using a U937 human promonocytic cell line in comparison with another polyphenol, quercetin. After incubation of the pathogen, Candida albicans, intracellular killing by macrophage-like cells was decreased by quercetin and resveratrol 10 microM but was enhanced by resveratrol 1 microM after 20 h of treatment. Phagocytosis rate, expressed as phagocytosis frequency, (i.e., percentage number of phagocytosing cells/total cells) at 20 h was highest with resveratrol 10 microM and was higher with quercetin 10 microM than with resveratrol 1 microM. The phagocytosis index exhibited the same trend. While both polyphenols demonstrated cytostatic activity on U937 growth, a prointraphagocytic effect for resveratrol 10 microM-treated cells at 10 min, resveratrol 1 microM-treated cells at 20 h and resveratrol 10 microM-treated cells at 48 h was observed. Morphological examination with optic microscopy demonstrated both apoptotic and differentiating cells, even after 10 min treatment. Resveratrol-induced apoptosis (following 4 h treatment) was confirmed by flow cytometry at concentrations as low as 1 microM and 100 nM in the assay for detection of membrane phosphatidylserine. Resveratrol- or quercetin-treated, but unstimulated cells, did not produce tumor necrosis factor-alpha protein. As phosphatidylserine externalization triggers specific recognition by monocytes and macrophages, removal of intact apoptotic cells is important a) in cell population selection and differentiation for antiblastic therapy, and b) in preventing the release of toxic inflammatory substances such as reactive oxygen substances and proteolytic enzymes by dying cells. This observation suggests that wine polyphenols, at the same concentrations as those found in plasma after moderate wine consumption, are important cofactors in antiinfective, antiinflammatory and anticancer nonspecific immune reactions.

RANTES and MCP-1 chemokine plasma levels in chronic renal transplant dysfunction and chronic renal failure.

OBJECTIVES: Procedures to diagnose renal allograft rejection depend on detection of graft dysfunction due to the presence of mononuclear leukocytic infiltrates. DESIGN AND METHODS: In our study, we pursued an immunodiagnostic approach utilizing an ELISA method on plasma samples to monitor patients waiting to undergo transplantation in order to evidence prognostic developments in renal transplantation and, at least, to diagnose renal chronic transplant dysfunction. We analyzed blood levels of two chemokines, RANTES and MCP-1, which are normally overexpressed locally in renal chronic rejection. RESULTS: Our results showed that patients affected by chronic renal failure (and waiting for kidney transplant), as well as kidney-grafted patients affected by chronic transplant dysfunction, had plasma levels of RANTES significantly higher than those of controls (patients without acute or chronic pathologies). CONCLUSIONS: Our data suggest a simple method to evaluate the plasmatic presence of RANTES, which could be involved in longterm kidney graft failure.

Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium.

BACKGROUND: Resveratrol is a phytoalexin present in red wine. It has been shown to protect LDL from peroxidative degradation. OBJECTIVE: In consideration of the low plasma concentration of orally adsorbed resveratrol (which is insufficient for antioxidant protection of LDL), we studied another effect of the compound. DESIGN: Because resveratrol is a tyrosine kinase inhibitor like other members of the tyrphostin family, we hypothesized that it has the ability to modify intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression by stimulated endothelial cells. We studied the ability of resveratrol to inhibit such adhesion molecule expression and to block the adhesion of monocytes and granulocytes to endothelial cells. RESULTS: We showed that resveratrol, at concentrations as low as 1 micromol/L and 100 nmol/L, significantly inhibited ICAM-1 and VCAM-1 expression by tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells and lipopolysaccharide-stimulated human saphenous vein endothelial cells (HSVEC), respectively. In addition, we showed that resveratrol induced a significant inhibition in the adhesion of U937 monocytoid cells to lipopolysaccharide-stimulated HSVEC. Such inhibition was comparable with that obtained when anti-VCAM-1 monoclonal antibody was used instead of resveratrol. Resveratrol also significantly inhibited the adhesion of neutrophils to TNF-alpha-stimulated NIH/3T3 ICAM-1-transfected cells, whereas neutrophils activated by formyl-methionyl-leucyl-phenylalanine did not significantly modify adhesion to NIH/3T3 ICAM-1-transfected cells. CONCLUSIONS: Our results indicate activity of resveratrol on endothelial cells and a new interpretation of an effect independent of its antioxidant function.

Protection by L-2-oxothiazolidine-4-carboxylic acid of hydrogen peroxide-induced CD3zeta and CD16zeta chain down-regulation in human peripheral blood lymphocytes and lymphokine-activated killer cells.

We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [in the form of Procysteine, kindly donated by Transcend Therapeutics] could protect peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells from CD3zeta and CD16zeta chain down-regulation induced by H2O2 produced by lipopolysaccharide (LPS)-activated autologous monocytes. OTC is known to enhance glutathione production in cells in which glutathione was depleted by reactive oxygen species. Our data showed that OTC induced a significant increase in CD3zeta and CD16zeta chain expression in peripheral blood lymphocytes and LAK cells, respectively, pretreated for 12 hr at 37 degrees. Moreover, OTC significantly protected peripheral blood lymphocytes and LAK against decreased zeta chain expression induced by lipopolysaccharide-activated monocytes or the addition of H2O2 to the culture medium. Our experiments thus suggested that alterations in signal-transducing molecules, such as decreased CD3zeta and CD16zeta expression observed in cytotoxic T lymphocytes and LAK cells in response to oxidative stress, could be prevented by the use of OTC.

CD4+ and CD8+ T cell subset distribution in the blood of small-bowel-grafted rats: modification during graft-versus-host disease.

We studied the modifications of blood T cell distribution following small-bowel allografting in rats under different experimental conditions. Group 1: ACI (RT1a) rats were used as small-bowel donors for ACI x Wistar (RT1y) F1 hybrid rats (WAF1) in which graft-versus-host disease (GVHD) developed. Group 2: WAF1 rats were used as small-bowel donors to ACI rats which developed rejection. Group 3: WAF1 rats received small bowel from ACI rats hyperimmunized for 10 days (by grafting them with WAF1 skin) and GVHD developed. Group 4: Wistar rats received small bowel from ACI rats hyperimmunized for 10 days (by Wistar skin) and bidirectional GVHD and rejection were assured. A second set of the same groups which were continuously administered with cyclosporine (15 mg/kg per day s.c. for 15 consecutive days) was also studied. Recipient peripheral blood lymphocytes, obtained at 7 and 15 days following small-bowel transplantation, were stained with monoclonal antibodies anti-rat CD4 and CD8 and then analyzed in an automated flow cytometer. A significant major reduction of CD4+/CD8+ T cell ratios was shown in rats that developed simultaneous GVHD and rejection with respect to ungrafted rats.

Intracerebroventricular injection of capsaicin or substance P provokes the micturition reflex in the rat.

Acute intracerebroventricular injection of 25 micrograms capsaicin or 40 micrograms substance P in isotonic saline elicited approximately similar effects on the micturition reflex, but capsaicin had twice as much effect as substance P. This effect is specific, since acute intracerebroventricular injection of isotonic saline did not produce the micturition reflex. It can be hypothesized that capsaicin and substance P may act on the brain micturition centers directly or by mediation of neuropeptides such as tachykinins, but other hypotheses are also made.