BackgroundThe area of Milazzo-Valle del Mela (Sicily, Italy) is considered at high risk of environmental crisis by regional authorities.ObjectiveTo measure oxidative-stress, DNA repair and detoxification genes in school children living near the industrial area and in age-matched controls.MethodsThe parent study was a biomonitoring investigation evaluating heavy metal urine levels in 226 children aged 12–14 years, living in the high risk area, and in 29 age-matched controls living 45 km far from the industrial site. In the present study 67 exposed adolescents and 29 controls were included. Samples were analyzed for urinary 8-hydroxydeoxyguanosine (8OHdG) levels, and gene expression of OGG1 (DNA repair gene), NQO1, ST13, and MT1A (detoxifying genes).ResultsUrinary cadmium was higher (p = 0.0004) in exposed [geometric mean, 0.46 µg/L; 25th–75th percentile: 0.3–0.56] than in control adolescents [geometric mean, 0.26 µg/L; 25th–75th percentile: 0.2–0.3]. Chromium was also significantly elevated in exposed [geometric mean, 1.52 µg/L; 25th–75th percentile: 1.19–1.93] compared with controls [geometric mean, 1.25 µg/L; 25th–75th percentile: 1.05–1.48; p = 0.02]. Urinary 8-OHdG concentration was greater in exposed than in controls (71.49 vs 61.87 µg/L, p = 0.02), and it was correlated with cadmium levels (r = 0.46, p < 0.0001), and with the combined exposure index (r = 0.43, p < 0.0001). Moreover, cadmium levels showed a robust correlation with OGG1 and MT1A gene expression levels (r = 0.44, p < 0.0001; r = 0.39, p < 0.0001, respectively). Finally, OGG1 and MT1A were over-expressed in adolescents from Milazzo-Valle del Mela area compared with controls (p = 0.0004; p < 0.0001, respectively).ConclusionsContinuous exposure at relatively low concentrations of heavy metals is associated with increased oxidative DNA damage and impaired expression of DNA repair and detoxification genes in adolescents.

In the Milazzo-Valle del Mela area, the presence of industrial plants and the oil refinery make local residents concerned for their health. For this reason, we evaluated the levels of heavy metals in 226 children aged 12–14 years, living in the 7 municipalities of the area. A control age-matched population (n = 29) living 45 km far from the industrial site was also enrolled. Arsenic, cadmium, chromium, mercury, nickel, and vanadium were analysed in 24 h urine samples, while lead concentration was evaluated in blood samples. A questionnaire regarding life style and risk perception was also administered. Adolescents from Milazzo-Valle del Mela had cadmium levels significantly higher compared to either controls  (P < 0.0001) or the reference values of the European Germany Environmental Survey (GerES-IV) and the American National Health and Nutrition Examination Survey (NHANES). Furthermore, children had higher perception of living in a high-risk environment. The present data, for the first time, clearly indicate that adolescents living in Milazzo-Valle del Mela have increased body concentration of cadmium, which may be harmful to human health. These results deserve particular attention by the local and regional government to initiate prevention programmes in this susceptible population.

This study, for the first time, suggests that increased Cd burden is associated with delayed onset of puberty in male adolescents and impaired testicular growth.

Cecal ligation and puncture (CLP) is an experimental polymicrobial sepsis induced systemic inflammation that leads to acute organ failure. Aim of our study was to evaluate the effects of SP600125, a specific c-Jun NH2-terminal kinase (JNK) inhibitor, to modulate the early and late steps of the inflammatory cascade in a murine model of CLP-induced sepsis. CB57BL/6J mice were subjected to CLP or sham operation. Animals were randomized to receive either SP600125 (15 mg/kg) or its vehicle intraperitoneally 1 hour after surgery and repeat treatment every 24 hours. To evaluate survival, a group of animals was monitored every 24 hours for 120 hours. Two other animals were sacrificed 4 or 18 hours after surgical procedures; lung and liver samples were collected for biomolecular and histopathologic analysis. The expression of p-JNK, p-ERK, TNF-α, HMGB-1, NF-κB, Ras, Rho, Caspase 3, Bcl-2, and Bax was evaluated in lung and liver samples; SP600125 improved survival, reduced CLP induced activation of JNK, NF-κB, TNF-α, and HMGB-1, inhibited proapoptotic pathway, preserved Bcl-2 expression, and reduced histologic damage in both lung and liver of septic mice. SP600125 protects against CLP induced sepsis by blocking JNK signalling; therefore, it can be considered a therapeutic approach in human sepsis.

Systemic administration of kainic acid causes inflammation and apoptosis in the brain, resulting in neuronal loss. Dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitors could represent a possible neuroprotective approach in preventing glutamate excitotoxicity. Consequently, we investigated the effects of a dual inhibitor of COX/5-LOX following intraperitoneal administration of kainic acid (KA, 10 mg/kg) in rats. Animals were randomized to receive either the dual inhibitor of COX/5-LOX (flavocoxid, 20 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) 30 min after KA administration. Sham brain injury rats were used as controls. We evaluated protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) and tumor necrosis factor alpha (TNF-α) as well as levels of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the hippocampus. Animals were also observed for monitoring behavioral changes according to Racine Scale. Finally, histological analysis and brain edema evaluation were carried out. Treatment with the dual inhibitor of COX/5-LOX decreased protein expression of p-ERK1/2 and TNF-α in hippocampus, markedly reduced MDA, LTB4 and PGE2 hippocampal levels, and also ameliorated brain edema. Histological analysis showed a reduction in cell damage in rats treated with the dual inhibitor of COX/5-LOX, particularly in hippocampal subregion CA3c. Moreover, flavocoxid significantly improved behavioral signs following kainic acid administration. Our results suggest that dual inhibition of COX/5-LOX by flavocoxid has neuroprotective effects during kainic acid-induced excitotoxicity.

Acute pancreatitis (AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis of AP is still not well understood. In recent years several papers have highlighted the cellular and molecular events of acute pancreatitis. Pancreatitis is initiated by activation of digestive enzymes within the acinar cells that are involved in autodigestion of the gland, followed by a massive infiltration of neutrophils and macrophages and release of inflammatory mediators, responsible for the local and systemic inflammatory response. The hallmark of AP is parenchymal cell necrosis that represents the cause of the high morbidity and mortality, so that new potential therapeutic approaches are indispensable for the treatment of patients at high risk of complications. However, not all factors that determine the onset and course of the disease have been explained. Aim of this article is to review the role of mitogen-activated protein kinases in pathogenesis of acute pancreatitis.

The aryl hydrocarbon receptor (AHR) mediates a variety of biological responses to ubiquitous dioxin and PCB dioxin-like. AHR together with ARNT, AHRR, represent a novel basic helix-loop-helix/PAS family of transcriptional regulators. Their interplay may affect the xenobiotic response. The aim of this study was to investigate, by histological, immunohistochemical investigations and western-blot analysis, the expression of AHR, ARNT and AHRR in liver of seabrem (Spaurus aurata) after exposure at different time to dioxin-like PCB126 in order to deep the knowledge about their specific role. The findings showed a significant increase of AHR and ARNT expression in juvenile fishes after 12 h than control group. The induction of AHR and ARNT is also significant at 24 and 72 hours compared to the control group. Furthemore, induction of AHRR expression has proved to increase both 12 h but this induction does not seem significant to 24 and 72 hours. The most important data of this work is that the induction of AHRR, when the action of the toxic persistence substances, as dioxin and PCB-126, it is not enough to reduce AHR signaling and thus its hyperactivation leads to toxic effects in seabrem (Spaurus aurata). All this confirms the importance of AHR ligands as new class of drugs that can be directed against severe disease such as cancer.

The mineral and geological historical collections reported here were part of the original collections of the Mineralogy Institute at the University of Messina, most of which date back to the 1880s. These historical collections, today hosted by the Earth Sciences Section of the Department of Mathematical and Computers Sciences, Physical Sciences and Earth Sciences at the University of Messina, comprise a thousand specimens of minerals, gemstones, ores, rocks, hundreds of topographic, geographical, and geological maps, mineralogical and geological models, and numerous original documents and instruments. They represent an essential geoscientific cultural heritage to preserve and valorize for future generations. The restoration and cataloging of this geoscientific naturalist heritage are necessary to make it accessible to scientists, students, tourists, and citizens worldwide. The preliminary results presented in this study are part of an ongoing project devoted to restoring, analyzing, and cataloging the mineral and geological historical collections of the University of Messina.