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Background: Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers. Methods: Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate. Results: Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1-42.1) v 6.7 (3.9-10.4) v 4.2 (2.4-11.3) v 6.1 (4.5-7.6) ng/ml, p=0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11(1.4-8.0) v 0.14 (0.1-0.2) µg/µl, p=0.0002). Conclusion: MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers. [ABSTRACT FROM AUTHOR]

Background: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect bronchoconstrictor.Study Objectives: We studied the validity of isotonic saline solution (0.9%) inhalation as a means to induce sputum by comparing it to hypertonic saline solution (4.5%) inhalation.Patients: Sixteen patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion.Methods: Subjects underwent sputum induction twice at 1-week intervals. Saline solution (hypertonic or isotonic) was inhaled for three periods of 5 min. The parameters assessed in sputum samples were cell counts, sodium, eosinophil cationic protein (ECP), and albumin concentrations, osmolality, and pro-matrix metalloproteinase (MMP)-9 activity by zymography.Results: The maximal fall in peak expiratory flow during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p < 0.01). Each subject produced analyzable sputum on both visits. There were no statistically significant differences in total and differential sputum cell counts, and the reproducibility coefficients were high for eosinophils and neutrophils when comparing the two methods. Likewise, sputum levels of ECP and albumin as well as sputum pro-MMP-9 activity were not different between the two methods, and were highly reproducible as shown by high intraclass coefficients (Ri) of correlation (0.72, 0.74, and 0.77 for ECP, albumin, and pro-MMP-9, respectively). Sputum sodium concentrations and osmolality were higher after inhalation of hypertonic saline solution (p < 0.05).Conclusion: In patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion, inducing sputum by isotonic or hypertonic saline solution inhalation leads to comparable results in eosinophil and neutrophil cell counts and fluid phase mediators/proteins. [ABSTRACT FROM AUTHOR]

Lea fage influences the level of activity and the decay rate of the enzymes nitrate reductase (NR: E.C. 1.6.6.1) and glucose‐6‐phosphate dehydrogenase (G6PD; E.C. 1.1.1.49) extracted with and without protein in the extraction media. Such influence was determined in three plant species: corn (Zea mays L.), oats (Arena sativa L.), and tobacco (Nicotiana tabacum L.). Leaves of different ages were obtained from plants of various ages, or by removal of leaf blades from different positions on a single shoot. NR activity (per g fresh weight) declined as leaves of these plant species became older, especially when extraction was effected with conventional media (i.e. without added protein). The instability of NR in these extracts increased as leaves became older. Decay of NR in vitro was exponential with time. Addition of protein [3 %(w/v) casein or bovine serum albumin] to extraction media markedly increased the level of NR activity and its stability, especially in older leaves of all three plant species. Addition of protein did not affect the level of G6PD extracted from corn leaf blades, but slightly enhanced its activity in extracts from the oldest leaf blade of oats. G6PD activity also declined as leaf blades of corn and oats became older. [ABSTRACT FROM AUTHOR]

Background: Mechanisms that preclude lung metastasis are still barely understood. The possible consequences of allergic airways inflammation on cancer dissemination were studied in a mouse model of breast cancer.Methods: Balb/c mice were immunized and daily exposed to ovalbumin (OVA) from day 21. They were subcutaneously injected with 4T1 mammary tumor cells on day 45 and sacrificed on day 67. Lung metastases were measured by biophotonic imaging (IVIS® 200 Imaging System) and histological measurement of tumor area (Cytomine software). Effects of CCL11 were assessed in vivo by intratracheal instillations of recCCL11 and in vitro using Boyden chambers. CCR3 expression on cell surface was assessed by flow cytometry.Results: The extent of tumor metastases was significantly higher in lungs of OVA-exposed mice and increased levels of CCL11 expression were measured after OVA exposure. Migration of 4T1 cells and neutrophils was stimulated in vitro and in vivo by recCCL11. 4T1 cells and neutrophils express CCR3 as shown by flow cytometry and a selective CCR3 antagonist (SB-297006) inhibited the induction of 4T1 cells migration and proliferation in response to recCCL11.Conclusions: Allergic inflammation generated by exposure to allergens triggers the implantation of metastatic cells from primary breast tumor into lung tissues plausibly in a CCL11-CCR3-dependent manner. This indicates that asthma related inflammation in lungs might be a risk factor for lung metastasis in breast cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The onset of posttransplant diabetes mellitus (PTDM) among kidney recipients is associated with an increased risk of graft failure and death. Minimizing the risk of PTDM is a priority for long-term improvement in survival rates. We sought to evaluate the prevalence of PTDM and impaired fasting glucose (IFG) among a population of kidney transplant recipients to identify the risk factors and to evaluate graft and patient survivals. Methods: We analyzed 250 consecutive Caucasian patients who received kidney allografts in our center between May 2000 and December 2005, with a median follow-up of 32 months (range, 1–78 months). Results: We observed altered glucose metabolism in 17% of patients; specifically, the prevalences of PTDM and IFG were 12.2% and 4.8%, respectively. Patients who developed PTDM or IFG were overweight (BMI, 26.4 ± 3.4 and 28.1 ± 3.4 kg/m2, respectively), whereas the normal glucose (NG) group''s BMI was 23.8 ± 3.5 kg/m2 (P = .002 and P = .004, respectively). Prevalence of acute rejection was higher in the PTDM and IFG patients compared with the NG patients (60.7%, 63.6%, and 32.1%, respectively; P = .006; P < .04), while no difference was observed in terms of graft and patient overall survival. Conclusion: In our series of patients, we showed that being overweight represents a major risk factor for the development of PTDM, which results in an increased acute rejection rate. These results confirmed the importance of appropriate weight control among patients undergoing kidney transplantation, which should also be strictly monitored for all risk factors associated with the development of impaired glucose metabolism. [Copyright &y& Elsevier]

This article discusses the surveillance and management of branch duct intraductal papillary-mucinous neoplasms (BD-IPMNs) in a real-life cohort of patients at an Italian level III center. The authors propose discontinuing follow-up after 5 years of stability in certain patient groups. The study found that the risk of malignant transformation, surgery, and death related to BD-IPMN without worrisome features or high-risk stigmata is low, particularly after 5 years of follow-up. However, the incidence and mortality of pancreatic cancer related to BD-IPMN are not negligible, emphasizing the importance of continued surveillance in some cases. [Extracted from the article]

The eastern slope of Mt. Etna is characterised by shallow seismicity originating from normal-oblique faulting, Timpe Fault System, related to WNW-ESE regional extension. Recent research has demonstrated that in the fault population of Mt. Etna's eastern flank the minimum earthquake magnitude that will have a ground rupture effect is ca. 2.5. This system is characterised by high frequency seismic activity, due to thinned seismogenic crustal layer. This characteristic, together with the high density of the fault segments, does not always for identification of the segments responsible for the earthquake. The earthquakes, affecting the medium-lower eastern flank, have been historically reconstructed by macroseismic analysis and reported in a macroseismic database, and in recent decades by instrumental seismic registration, which provide the seismological parameters capable of evaluating focal mechanism, hypocentre and relative algorithms related to geometric parameters which control the growth of fault segments. In this paper, we present a methodology to evaluate the age of the rapid exhumation of the free-face fault plane of the NNW-SSE oriented normal fault segment named S. Tecla (Timpe Fault System). It consists of the measurement of the thalli species (Lichenometry method) in order to evaluate the parameters which characterise their growth. The seismic history of the S. Tecla Fault indicates eight certain events from 1865 to 2005 with 3.4 ÷ 4.7 Magnitude (De Guidi et al., 2012 and reference therein). We found evidence of two different recent rapid vertical deformation events at the base of the S. Tecla fault escarpment, the oldest 20 m long and 0.25 m in height, and the youngest with a 0.02 m high nude surface exposed. We have observed that there are thalli of Xanthoparmelia conspersa (Ehrh. Ex Ach.) Hale, colonizing part of the nude surface on the escarpment. The results highlight that the oldest thalli was dated at 43.7 years old, showing that rapid vertical deformation generated the surface where the thalli, after 4 years, took root. The displacement of this surface could be related to the seismic events occurring on 3rd August 1973 (3.8 M) in S. M. Ammalati area probably accompanied by intense post seismic deformation. The second and last event could be attributable to a 3.1 M seismic event occurring on 25th September 2014 (ISIDe, 2016). [ABSTRACT FROM AUTHOR]

Since its first description, ADAMTS14 has been considered as an aminoprocollagen peptidase based on its high similarity with ADAMTS3 and ADAMTS2. As its importance for procollagen processing was never experimentally demonstrated in vivo , we generated Adamts14 -deficient mice. They are healthy, fertile and display normal aminoprocollagen processing. They were further crossed with Adamts2 -deficient mice to evaluate potential functional redundancies between these two highly related enzymes. Initial characterizations made on young Adamts2-Adamts14 -deficient animals showed the same phenotype as that of Adamts2 -deficient mice, with no further reduction of procollagen processing and no significant aggravation of the structural alterations of collagen fibrils. However, when evaluated at older age, Adamts2-Adamts14 -deficient mice surprisingly displayed epidermal lesions, appearing in 2 month-old males and later in some females, and then worsening rapidly. Immunohistological evaluations of skin sections around the lesions revealed thickening of the epidermis, hypercellularity in the dermis and extensive infiltration by immune cells. Additional investigations, performed on young mice before the formation of the initial lesions, revealed that the primary cause of the phenotype was not related to alterations of the epidermal barrier but was rather the result of an abnormal activation and differentiation of T lymphocytes towards a Th1 profile. However, the primary molecular defect probably does not reside in the immune system itself since irradiated Adamts2-Adamts14 -deficient mice grafted with WT immune cells still developed lesions. While originally created to better characterize the common and specific functions of ADAMTS2 and ADAMTS14 in extracellular matrix and connective tissues homeostasis, the Adamts2-Adamts14 -deficient mice revealed an unexpected but significant role of ADAMTS in the regulation of immune system, possibly through a cross-talk involving mesenchymal cells and the TGFβ pathways. [ABSTRACT FROM AUTHOR]

Although contamination and invasive species are two of the most relevant anthropogenic drivers affecting ecosystems, their joint impact on the environment has been poorly investigated. Glyphosate, directly or indirectly, contaminates freshwater systems which in turn may be invaded by the golden mussel Limnoperna fortunei . Under laboratory conditions, we studied the combined effect of technical-grade glyphosate, Roundup Max ® and Glifosato Atanor ® , in scenarios with and without L. fortunei, on phytoplankton from Salto Grande Reservoir (Uruguay River, Argentina). We expected that the effects of the interaction on phytoplankton and water quality would vary with the form of herbicide applied. The assay was conducted for 14 days (Tf) using 3-L bottles as experimental units. Eight treatments were performed in triplicate: C: Control; M: mussel; G: technical-grade glyphosate acid; R: Roundup Max ® ; A: Glifosato Atanor ® ; MG: mussel + technical-grade glyphosate acid, MA: mussel + Glifosato Atanor ® and MR: mussel + Roundup Max ® . The active ingredient was applied at 6 ppm. The dissipation of glyphosate in water was 1.5–2.6 times higher in presence of mussels. Treatments G and A showed an increase in phytoplankton abundance, mainly the cyanobacteria Microcystis spp. wich rised to 289% and 639% at Tf, respectively, relative to their values at Ti. Roundup Max ® limited the growth of Microcystis spp., as its abundance decreased 59% relative to Ti. L. fortunei reduced phytoplankton abundances at Tf. Evenness increased significantly in M, MG, MR and MA, while it decreased in G, R and A relative to C. The interaction of factors produced a significant synergistic increase in periphyton; periphytic chlorophyll a concentration was 0.81 ± 0.02 μg cm −2 for MR; 0.09 ± 0.02 μg cm −2 for MA and 0.02 ± 0.01 μg cm −2 for MG. Limnoperna fortunei appeared as the driving force in the interaction. The assay described here allows for the rapid assessment of the impact of these types of agents on freshwater. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis. The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17. CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferonγ and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein. In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD. Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1α in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. By contrast, we report here that mice conditionally deficient for Hif1α in myeloid cells display enhanced sensitivity to the development of airway allergy to experimental allergens and house-dust mite antigens. We support that upon allergen exposure, MyD88-dependent upregulation of Hif1α boosts the expression of the immunosuppressive cytokine interleukin (IL)-10 by lung interstitial macrophages (IMs). Hif1α-dependent IL-10 secretion is required for IMs to block allergen-induced dendritic cell activation and consequently for preventing the development of allergen-specific T-helper cell responses upon allergen exposure. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1α possesses immunoregulatory functions implicated in the prevention of airway allergy. [ABSTRACT FROM AUTHOR]

Abstract: A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions. [Copyright &y& Elsevier]