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Faecal contamination of the coastal sea poses widespread hazard to human and environmental health and is predicted to rise in response to global change and human pressure. For better management and risk reduction it is thus imperative to clarify and predict trends of faecal pollution over spatial and temporal scales, and to assess links with climate and other variables. Here, we investigated the spatio-temporal variation in the Faecal Indicator Bacteria (FIB) Escherichia coli and enterococci, over a time frame spanning 11 years (2011-2021) along a coastal area covering approximately 40 km and 59 bathing sites in the Marche region (Adriatic Sea, Italy), characterized by intense beach tourism, high riverine inputs, resident population, maritime traffic and industrial activities. Our analysis, that considers 5,183 measurements during the bathing season (April to October), shows that FIB abundance varied significantly among years. A general, although not significant, increase over time of both FIB was observed, mainly due to a general reduction of structural zeros (i.e., zeros originated from the actual absence of the response variable) over the examined time period. FIB abundances displayed their maxima and minima in different years according to the municipality, with overall peaks recorded in different months (May-June or September), whereas the lowest values were always observed in October. FIB levels were not significantly related neither to rainfalls nor to river discharge, but the activation of combined sewer overflows (CSOs), typically occurring after intense rainfall events, appeared as a necessary condition for the high faecal contamination levels. Considering climate change scenarios predicting significant increases in extreme weather events, our findings support the usefulness of analysing long-term trends to identify pollution sources, and the prioritization of control strategies to better manage the release of microbial pollutants from combined sewer overflows in coastal waters to reduce human risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The wine market has always faced the problem of fraud, including the addition of exogenous sugar solutions to grape musts to increase the final alcohol content. Since in some countries the practice of chaptalization is prohibited (except by adding concentrated must) it is necessary to broaden the analytical techniques that allow the identification of this type of fraud. The aim of this study was to define an NMR-based sugar profile of genuine grape must to set concentration limits for each sugar as parameters of authenticity. Glucose, fructose, together with eleven minor sugars were quantified in 82 genuine Italian grape musts, developing an analytical procedure based on highly selective chemical shift filters followed by TOCSY. Alongside the characteristic myo- and scyllo-inositol, significant contents of mannose, galactose, and trehalose were also found. Otherwise, maltose, rhamnose, arabinose, sucrose and lactose are present in lower concentrations and show great concentration variability., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Crustacean fisheries are gaining prominence globally amid a decline in finfish stocks. Some decapod crustacean species have experienced increased landings in response to shifting market demands and environmental dynamics. Notably, the caramote prawn ( Penaeus kerathurus -Forskål, 1775) in the northern Adriatic Sea, Geographical Sub Area (GSA) 17, has risen in both landings and economic importance in recent years. However, despite its significance, comprehensive information on fishery-dependent data, age, and growth in this region remains lacking. To address this gap, this study employs modal progression analysis and the ELEFAN approach, utilizing the "TropFishR" R package and newly developed functions, including bootstrapping procedures. These advancements aim to overcome issues identified in previous versions and enhance the accuracy and reliability of age and growth estimations. The study leverages one year of monthly length-frequency distributions (LFDs) collected from commercial bottom trawls in the northern Adriatic Sea. The results of the analysis confirm the presence of sexual dimorphism in the caramote prawn species, with females exhibiting faster growth rates compared to males. Additionally, the growth performance index supports this observation, further underscoring the importance of accounting for sexual dimorphism in growth modeling and fisheries management strategies. By contributing to a growing body of knowledge on the growth dynamics of the caramote prawn, this study provides valuable insights for sustainable fisheries management in the northern Adriatic Sea. Understanding the age and growth patterns of key crustacean species is essential for developing effective conservation measures and ensuring the long-term health and productivity of marine ecosystems. The findings of this study serve as a foundation for informed decision-making and proactive management practices aimed at preserving the ecological integrity and economic viability of crustacean fisheries in the region.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting., Research Design and Methods: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24., Results: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 ( p  = 0.0004) and 24 ( p  = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission ( p  = 0.002) and clinical >response rates ( p  = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy., Conclusion: This real-world study shows that UST effectively and safely treats patients with UC.

This study is based on assessing fecal indicator bacteria contamination along meteorological, hydrological and physical-chemical variables after high rainy events during the summer period. The study focused on four different coastal sites in the western and eastern Adriatic coast characterized by various geomorphological and hydrological features, levels of urbanization and anthropogenic pressures, with the aim of finding appropriate and effective solutions to ensure the safety and sustainability of tourism and public health. Detailed in-situ survey revealed a wide range of fecal indicator bacterial (FIB) across the different river mouths with concentrations of E. coli ranging from 165 to 6700 CFU 100 mL -1 . It was found that nitrogen compounds track microbial load and acted as tracers for fecal contaminants. Further, a modelling tool was also used to analyze the spatial and temporal distribution of fecal pollution at these coastal sites. The integrated monitoring through high frequent survey in river waters and modeling framework allowed for the estimation of fecal indicator bacterial load at the river mouth and examination of fecal pollutant dispersion in recreational waters, considering different scenarios of fecal dispersion along the coast. This study formed the basis of a robust decision support system aimed at improving the management of recreational areas and ensuring the protection of water bodies through efficient management of bathing areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients., Research Design and Methods: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF., Results: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment ( p  = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded., Conclusions: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

During the last decade vessel-position-recording devices, such as the Vessel Monitoring System and the Automatic Identification System, have increasingly given accurate spatial and quantitative information of industrial fisheries. On the other hand, small-scale fisheries (vessels below 12 m) remain untracked and largely unregulated even though they play an important socio-economic and cultural role in European waters and coastal communities and account for most of the total EU fishing fleet. The typically low-technological capacity of these small-scale fishing boats-for which space and power onboard are often limited-as well their reduced operative range encourage the development of efficient, low-cost, and low-burden tracking solutions. In this context, we designed a cost-effective and scalable prototypic architecture to gather and process positional data from small-scale vessels, making use of a LoRaWAN/cellular network. Data collected by our first installation are presented, as well as its preliminary processing. The emergence of a such low-cost and open-source technology coupled to artificial intelligence could open new opportunities for equipping small-scale vessels, collecting their trajectory data, and estimating their fishing effort (information which has historically not been present). It enables a new monitoring strategy that could effectively include small-scale fleets and support the design of new policies oriented to inform coastal resource and fisheries management.

The dataset presented in this article contains information about marine Area-Based Management Tools (ABMTs) used to assess their contribution to the United Nations 2030 Sustainable Development Goals. Following the scope of the analysis, ABMTs were identified by scrutinizing international and regional legal sources related to ocean management in the fields of marine conservation, fisheries, deep sea bed mining, underwater natural and cultural heritage, environmental conservation, and marine spatial planning. Legal sources were screened to depict the following characteristics of individual ABMTs: i) management objectives; ii) authorities responsible for delivering such objectives; iii) the system of management and planning entailed in the ABMT including the zoning type; and iv) the specific spatial scope and domain each ABMT refer to in vertical depth and horizontal domain. Data were generated through an internal expert elicitation. Experts, initially trained in the data analysis and related protocol, contributed to the data production because of their specific knowledge and experience in ocean management. This dataset represents a unique source of information for advancing research about monitoring and assessment of the achievement of sustainable development goals that encompasses different types of ABMTs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

In the Adriatic Sea, massive rainfall events are causing flooding of rivers and streams, with severe consequences on the environment. The consequent bacterial contamination of bathing water poses public health risks besides damaging tourism and the economy. This study was conducted in the framework of WATERCARE, an EU Interreg Italy-Croatia Project, which aims at reducing the impact of microbial contamination on Adriatic bathing water due to heavy rainfall events drained in the local sewage network and; enhancing the quality of local waters; and providing support for the decision-making processes regarding the management of bathing water in line with EU regulations. The study involved the development of an innovative water quality integrated system that helps meet these objectives. It consists of four components: a real time hydro-meteorological monitoring system; an autosampler to collect freshwater samples during and after significant rainfall events; a forecast system to simulate the dispersion of pollutants in seawater; and a real-time alert system that can predict the potential ecological risk from the microbial contamination of seawater. The system was developed and tested at a pilot site (Fano, Italy). These preliminary results will be used to develop guidelines for urban wastewater and coastal system quality assessments to contribute to develop policy actions and final governance decisions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Marine bioinvasions require integrating monitoring tools with other complementary strategies. In this study, we collected information about the invasive alien crab Callinectes sapidus in Italy, Croatia and Montenegro, by means of online questionnaires administered to recreational fishers (n = 797). Our records matched the current distribution of the species: C. sapidus resulted far more common in the Adriatic/Ionian than in the Tyrrhenian/Ligurian sector. Most respondents rated the species as 'occasional' or 'rare'. Moreover, the more C. sapidus was considered to be abundant, the more fishers tended to perceive it as a negative disturbance over fisheries and the environment. Our findings suggest that C. sapidus is more common than previously thought in most of the study area, and it could have reached the levels of a true invasions in the south-eastern Adriatic Sea. This experience demonstrates that online questionnaires can be appropriate tools to effectively engage stakeholders in alien species monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

One of the objectives of the BALMAS project was to conduct Port Baseline Biological Surveys of native and non-indigenous benthic flora in 12 Adriatic ports. Samples of macroalgae growing on vertical artificial substrates were collected in spring and autumn 2014 and/or 2015. A total number of 248 taxa, 152 Rhodophyta, 62 Chlorophyta, and 34 Ochrophyta, were identified. Of these, 13 were non-indigenous seaweeds, mainly filamentous macroalgae, that were probably introduced through hull fouling. Some of these taxa had already been described in the study areas, others were recorded for the first time, a few were no longer detected at sites where they had previously been recorded (e.g. Sargassum muticum). Some other NISS reported for the Adriatic Sea, were not collected at any sampling site (i.e. Caulerpa cylindracea, Codium fragile). Possible reasons for the absence of these species are discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Port baseline surveys (PBS) provide species inventories in and around ports, with a focus on non-indigenous species that may have been introduced by vessels, primarily via ballast water. PBS are an essential tool to support effective management strategies for non-indigenous as well as native harmful aquatic organisms and pathogens (HAOP). This paper describes the methodology of PBS that were conducted in 12 Adriatic ports. The PBS employed existing protocols that were adapted to meet the characteristics of the Adriatic sites. Their results are reported in several papers included in this special issue, each of which is devoted to a specific community. An overview of existing surveys protocols - which provide valuable support to decision-making and to design effective monitoring of non-indigenous species - is also supplied., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Climate change and biological invasions are rapidly reshuffling species distribution, restructuring the biological communities of many ecosystems worldwide. Tracking these transformations in the marine environment is crucial, but our understanding of climate change effects and invasive species dynamics is often hampered by the practical challenge of surveying large geographical areas. Here, we focus on the Mediterranean Sea, a hot spot for climate change and biological invasions to investigate recent spatiotemporal changes in fish abundances and distribution. To this end, we accessed the local ecological knowledge (LEK) of small-scale and recreational fishers, reconstructing the dynamics of fish perceived as "new" or increasing in different fishing areas. Over 500 fishers across 95 locations and nine different countries were interviewed, and semiquantitative information on yearly changes in species abundance was collected. Overall, 75 species were mentioned by the respondents, mostly warm-adapted species of both native and exotic origin. Respondents belonging to the same biogeographic sectors described coherent spatial and temporal patterns, and gradients along latitudinal and longitudinal axes were revealed. This information provides a more complete understanding of the shifting distribution of Mediterranean fishes and it also demonstrates that adequately structured LEK methodology might be applied successfully beyond the local scale, across national borders and jurisdictions. Acknowledging this potential through macroregional coordination could pave the way for future large-scale aggregations of individual observations, increasing our potential for integrated monitoring and conservation planning at the regional or even global level. This might help local communities to better understand, manage, and adapt to the ongoing biotic transformations driven by climate change and biological invaders., (© 2019 John Wiley & Sons Ltd.)

Objective: Arthritis is the most frequent extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). The coexistence of intestinal and articular inflammation advocates the need for a multidisciplinary management of patients with IBD-associated spondyloarthritis., Methods: Consecutive IBD patients were evaluated jointly by the gastroenterologist and the rheumatologist in a combined clinic. All the patients were assessed and screened for articular involvement, disease activity and health related quality of life. After the prescription of a shared treatment, patients with spondyloarthritis were followed up for 24 months., Results: Two hundred sixty-two IBD patients, including 80 who were classified as affected by spondyloarthritis according to the ASAS criteria, were included in the study. At baseline, patients with both IBD and spondyloarthritis showed worse quality of life in both the physical and mental domains. The multidisciplinary management provided a significant improvement of gastrointestinal and articular manifestations, as well as the health-related quality of life. Moreover, global and gastrointestinal-specific quality of life significantly correlated with articular disease activity., Conclusion: The multidisciplinary management significantly improves both articular and gastrointestinal disease activities and the quality of life of patients with IBD-associated spondyloarthritis. An appropriate screening strategy and the integrated management of these patients should be encouraged and employed in clinical practice., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

This two-year study evaluates the effects of new management strategies directed at helping the recovery of Adriatic cuttlefish populations. The ability of three specially developed artificial spawning devices-seagrass collectors (SC; deployed on artificial reefs), longline collectors (LC; deployed at mussel farms), and trap collectors (TC; delivered to 19 professional and 54 recreational trap fishermen together with a dedicated logbook)-to attract egg deposition was tested. All devices were provided with a polyethylene floating rope 8 mm in diameter that served as a collector for egg deposition. Total rope length was 1,440 m in SC (2,880 segments of 0.5 m), 250 m in LC (500 segments of 0.5 m), and 250 m in TC (10 m per trap). Although the sites where SC and LC were deployed were sheltered from the action of destructive fishing gears, heavy winter storms destroyed the SC after a year. Most recreational fishermen and none of the professional fishermen provided detailed information on percent egg coverage on their collectors. The collectors attached to the three devices proved highly suitable for cuttlefish spawning, collecting more than 500,000 eggs on 2,440 m of rope. The analysis of egg diameter distribution suggested three laying events during the spawning season. The logbook data showed that egg number peaked in June. The present approach, combining habitat reconstruction and participatory research, has the potential to contribute to the recovery of cuttlefish stocks in the framework of a broader management plan., Competing Interests: The authors have declared that no competing interests exist.

Objective: The early diagnosis of inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA/IBD) in patients affected by IBD represents a major topic in clinical practice; in particular, to date there are no available serum biomarkers revealing the presence of joint inflammation in these patients. Sclerostin (SOST), an antagonist of the Wnt/β-catenin pathway, and antisclerostin-immunoglobulin G (anti-SOST-IgG) have been recently studied in patients with ankylosing spondylitis (AS) as a putative marker of disease activity., Methods: SOST and anti-SOST-IgG serum levels were assayed in 125 patients with IBD, 85 with axial or peripheral SpA, and in control groups (patients with AS and rheumatoid arthritis, and healthy individuals). The diagnostic performance in discriminating the presence of SpA/IBD was assessed for both candidate biomarkers., Results: Patients affected by SpA/IBD with axial involvement displayed significantly lower levels of SOST and higher levels of anti-SOST-IgG compared to patients with only peripheral arthritis, IBD, and controls. Moreover, SOST and anti-SOST-IgG serum levels were inversely correlated and were associated with the duration of articular symptoms. Both biomarkers showed good accuracy in predicting the presence of axial SpA in patients with IBD., Conclusion: We demonstrated that in patients with IBD, SOST and anti-SOST-IgG might represent novel biomarkers to assess the presence of axial joint involvement. Moreover, the development of anti-SOST-IgG and the subsequent decrease of SOST serum levels could play a role in the pathogenesis of SpA/IBD.

Aim: To report adalimumab (Ada) efficacy on articular-gastrointestinal disease and health-related quality of life (HRQoL) in patients with enteropathic spondyloarthritis (ES)., Methods: A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes (PROs) of the HRQoL questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor (TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests: (1) Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) for articular activity; (2) Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and partial Mayo (pMayo) score for gastrointestinal symptoms and activity; and (3) Health Assessment Questionnaire (HAQ), Patient Global Assessment (PGA) and Short Form-36 health survey (SF-36) questionnaires for PROs of the HRQoL., Results: Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQoL scores, showed a significant improvement having been achieved at the earliest (6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES., Conclusion: Ada treatment, upon multidisciplinary (gastro-rheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQoL in patients affected by ES., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

This study provides a parasitological analysis of the elasmobranch species caught in the northern and central Adriatic Sea. Sixty-two marine leeches were recorded on 747 individuals of Raja clavata Linnaeus, 1758 (thornback ray), Myliobatis aquila Linnaeus, 1758 (common eagle ray), and Torpedo marmorata Risso, 1810 (marbled torpedo ray) caught in 56 hauls over a 5 yr period. All leeches were identified as Pontobdella muricata, which is a typical ectoparasite of benthic elasmobranchs. The prevalence of infection ranged from 7.11% on R. clavata to 12.00% on M. aquila. The intensity of infection, the preferential sites of attachment to the host, and the periodicity of infection were evaluated.

The implementation of the European Directive No 391/89, among the other news, introduced the obligation for the occupational physician to actively participate to the assessment of risks. The reduction of the incidence of "historical" professional pathologies and the arising of work-related disease is making the role of the occupational physician, in the survey and risk assessment, ever more important, especially in consideration of the physiological and biomechanical peculiar competences required. In addition, a correct risk assessment allows to optimise the valorisation of human resources. The occupational physician, in other terms, can not only protect the health of workers, but "save" jobs too. The survey carried out in a logistic unit of a large-scale distributors group, documented herein, can give evidence of that.

A biogenic and a pyrogenic amorphous silica were incubated in normal human plasma and compared on a per unit surface basis for their ability to split C5 molecules and yield small C5a peptides. Since C5a peptides induce selective chemotactic attraction of polymorphonuclear leukocytes (PMN), measurement of PMN-induced chemotaxis was used as an index of C5 activation. Though to a lesser extent than the crystalline forms, amorphous silicas can promote the cleavage of C5 protein and generation of C5a-like fragment. The biogenic silica, which differs from the pyrogenic variety in particle shape, level of contaminants, and degree of surface hydrophilicity, besides specific surface, induced a greater response. Both silicas activated C5 through a process which seems to involve multiple events similar to those induced by crystalline silica. C5 molecules are adsorbed and hydroxyl radicals are generated through Haber Weiss cycles catalyzed by the redox-active iron present at the particle surface either as trace impurities or chelated from plasma by silanol groups. In turn, these radicals convert native C5 to an oxidized C5-like form C5(H2O2). Finally, C5(H2O2) is cleaved by protease enzymatic action of plasma kallikrein activated by the same silica dusts, yielding a product, C5a(H2O2), having the same functional characteristic as C5a.

Background: Epidemiological studies revealed an unusually high incidence of malignant pleural mesothelioma in Biancavilla, a town in eastern Sicily located in a volcanic area. In the absence of occupational risk factors connected with asbestos inhalation, a nearby stone quarry, which has long been providing most of the local building materials (e.g. plaster), was suspected to be the source of mineral fibres. These fibres had never been studied before and were identified as fluoro-edenite., Objective: To investigate the ability of the fluoro-edenite fibres present in mineral dusts and house plaster to release hydroxyl radicals in vitro., Methods: After fibre characterisation and the determination of particulate specific surface, the ability of quarry rock dust and house plaster dust to generate hydroxyl radicals was measured in vitro using the deoxyribose degradation assay. Treatment with 1,3-dimethyl-2-thiourea (DMTU), a hydroxyl radical scavenger, or deferoxamine (DFX), an iron chelator, was performed to confirm hydroxyl radical production and study the role of iron. Crocidolite (UICC) was used as positive control., Results: The rocks were found to contain fibrous amphiboles, identified as fluoro-edenite, which are chemically similar to tremolite. All samples generated hydroxyl radicals, with rocks yielding consistently higher values than plaster. Treatment of the dusts with DMTU or DFX significantly reduced hydroxyl radical production by both samples. The type of biological reactivity observed with these fluoro-edenite fibres resembled that of asbestos fibres., Conclusions: The hydroxyl radicals generated by asbestos fibres have long been known to mediate inflammatory fibrosis of the lung and DNA damage that may ultimately result in lung carcinoma and mesothelioma.

The effects of the same form of crystalline silica variously modified were compared to investigate the mechanisms by which silica activates C5 molecules. After incubation in human plasma, silica generated C5a-type fragments that stimulated polymorphonuclear leukocyte chemotaxis. This activity was totally abolished when plasma, adsorbed with antiserum against C5a or thermally inactivated, was used. Pretreatment of plasma with deferoxamine, 1,3 dimethyl-2-thiourea, or aprotinin markedly inhibited or totally abolished C5 activation. Finally, a significant increase in kallikrein activity was detected after incubation of silica particles in plasma. The results seem to indicate that the activation of C5 by crystalline silica occurs through a complex mechanism: the redox-active iron possibly present at the silica surface catalyzes, via Haber-Weiss cycles, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same silica particles, yielding oxidized C5a with the same functional properties as C5a. The different types of the same form of silica exhibited different reactivity. Two separate properties of the dusts seem to contribute to C5 activation: the potential to release hydroxyl radicals and the extent of C5 adsorption at the surface. The degree of surface hydrophobicity/hydrophilicity appeared sufficient to explain the different responses., (Copyright 2002 Elsevier Science (USA).)

Background & Aims: The Na+/H+ exchanger is the main intracellular pH regulator in hepatic stellate cells (HSCs), and its activity is increased by platelet-derived growth factor (PDGF). Amiloride, an Na+/H+ exchange inhibitor, reduces PDGF-induced HSC proliferation, suggesting that the Na+/H+ exchanger plays a role in regulating HSC proliferative response. The aim of this study was to characterize the intracellular pathways mediating activation of the Na+/H+ exchanger by PDGF in HSCs., Methods: The activity of the Na+/H+ exchanger and HSC proliferation rate were evaluated under control condition and after incubation with PDGF in the absence or presence of specific inhibitors of the main intracellular pathways of signal transduction. Na+/H+ exchange protein expression was evaluated by means of Western blot., Results: PDGF induced a significant increase in the activity of the Na+/H+ exchanger without modifying protein expression. Inhibition of the calcium/calmodulin- and protein kinase C-dependent pathways resulted in a significant inhibition of both Na+/H+ exchange activity and of PDGF-induced HSC proliferation. The involvement of the two pathways was confirmed by showing that incubation of HSCs with both phorbol-12-myristate-13-acetate, a potent protein kinase C activator, and thapsigargin, which increases intracellular calcium levels, significantly increased both the Na+/H+ exchanger activity and HSC proliferation rate. Inhibition of the protein kinase A pathway did not modify either PDGF-induced Na+/H+ exchange activation or PDGF-induced HSC proliferation. On the contrary, inhibition of the mitogen-activated protein kinase- and of phosphatidylinositol 3-kinase-dependent pathways significantly reduced PDGF-induced HSC proliferation without affecting the activity of the Na+/H+ exchanger., Conclusions: Activation of the Na+/H+ exchanger by PDGF in HSCs is mediated by calcium/calmodulin- and protein kinase C-dependent pathways. PDGF-induced HSC proliferation is mediated by Na+/H+ exchange-dependent and -independent pathways.

Aspartate glucan, glycine glucan, and serine glucan obtained by reductive amination of oxalacetic acid, glyoxylic acid, and beta-hydroxypyruvic acid, respectively, with polyglucosamine were tested as chromatographic chelating media. Crosslinked glycine glucan exhibited high capacities for cobalt and copper, even in acidic solutions (pH 2.9). Breakthrough points for 10 mg/L solutions through 6.0 x 0.6 cm columns containing 200 mg of polymer were at 1.8 L for both ions; for 1 mg/L solutions, they were at 4.0 and 12.0 L for cobalt and copper, respectively. Crosslinked glycine glucan could remove microgram amounts of cobalt and copper from fluoride and chloride brines. Cobalt and copper could be separated by elution with 0.25M sulfuric acid.