Liver toxicity after treatment with gefitinib and anastrozole: drug-drug interactions through cytochrome p450?

No abstract availabl

The HMGB1/RAGE pro-inflammatory axis in the human placenta: Modulating effect of low molecular weight heparin

We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response

Discovering Neverland: São Tomé e Príncipe and the development of the agricultural heritage of a multi-ethnic population

The history of São Tomé and Príncipe (STP) shows that the development of the roças, agriculturally based structures of colonial time, form a heritage linked to STP’s human development. Different agricultural products have characterized the historical periods of migration, slavery, creolism, and gender emancipation up to the present day; agricultural products and ethnic contamination make STP unique with the culture-nature relationship providing a useful tool for a better understanding of its historical roots. The essay argues that STP’s sustainable development could be fostered through agro-food geographical indications (GIs), which directly link territories, peoples, and traditions. GIs could lead to improvements in the export price of some of STP’s cocoa and coffee and, at the same time, increasing the cultivation of a number of other crops, especially indigenous fruits. The breeding of inland species, such as São Tomé bees, could also foster a multi-faceted approach to territorial development, including eco-tourism

Osteoporosis and cardiovascular diseases’ cosegregation: epidemiological features

Life expectancy in Italy is estimated to rise to 77.9 and 84.4 years in next years. Increased life expectancy is associated with a greater frailty of elderly people and an increased prevalence of chronic and degenerative illnesses such as cardiovascular diseases and osteoporosis. The impact of osteoporotic hip fractures in Italy is very similar to that of acute myocardial infarction (AMI), and there is a need for further epidemiological investigations concerning both the pathologies, as well as for a better understanding of possible mechanisms of their cosegregation. Actually, calcium metabolism is involved both in the development of osteoporosis and in the raise of cardiovascular risk. We have reviewed the most recent publications concerning epidemiological trends of both osteoporosis and acute myocardial infarction (AMI), and also the trials addressing cosegregation of these pathologies. According to the publications examined, in the Italian population (both ³ 45 and > 65 years old), the number of hospitalizations following hip fracture and AMI are comparable. Both hip fractures and cardiovascular diseases represent in Italy a serious medical problem and a leading health cost driver, according to what has already been reported for many other Countries in the industrialized world, thus requiring a global clinical approach. Low calcium intake could represent one of the possible pathogenic paths underlining the association between hypertension and osteoporosis. Low calcium serum levels has been proved to enhance PTH and vitamin D3 production, which result in a remarkable lypogenesis performed by adypocites and switch on mechanisms leading to the raise of blood systolic pressure, the development of atherosclerotic plaques and cardiovascular events. Although many trials have suggested that bone mineral density may be included in the list of cardiovascular risk factors, more studies are needed in order to deeply investigate the causal relationships between calcium metabolism and cardiovascular diseases

A multi-service data management platform for scientific oceanographic products

Abstract. An efficient, secure and interoperable data platform solution has been developed in the TESSA project to provide fast navigation and access to the data stored in the data archive, as well as a standard-based metadata management support. The platform mainly targets scientific users and the situational sea awareness high-level services such as the decision support systems (DSS). These datasets are accessible through the following three main components: the Data Access Service (DAS), the Metadata Service and the Complex Data Analysis Module (CDAM). The DAS allows access to data stored in the archive by providing interfaces for different protocols and services for downloading, variables selection, data subsetting or map generation. Metadata Service is the heart of the information system of the TESSA products and completes the overall infrastructure for data and metadata management. This component enables data search and discovery and addresses interoperability by exploiting widely adopted standards for geospatial data. Finally, the CDAM represents the back-end of the TESSA DSS by performing on-demand complex data analysis tasks

D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans

The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene

Contributi alla flora vascolare di Toscana. VII (357-439)

New localities and/or confirmations concerning 83 specific and subspecific plant taxa of Tuscan vascular flora, belonging to 71 genera and 33 families are presented: Carpobrotus (Aizoaceae), Alternanthera (Amaranthaceae), Leucojum (Amaryllidaceae), Anacyclus, Andryala, Carduus, Centaurea, Cichorium, Erigeron, Helichrysum, Helminthotheca, Hieracium, Limbarda, Pilosella, Scolymus, Sonchus, Tagetes, Urospermum, Xanthium (Asteraceae), Mahonia (Berberidaceae), Myosotis (Boraginaceae), Biscutella, Ionopsidium, Raphanus, Rapistrum (Brassicaceae), Buxus (Buxaceae), Vaccaria (Caryophyllaceae), Cistus (Cistaceae), Calystegia, Cuscuta (Convolvulaceae), Cymodocea (Cymodoceaceae), Cyperus (Cyperaceae), Amorpha, Emerus, Lathyrus, Lotus, Ononis, Trifolium, Vicia (Fabaceae), Quercus (Fagaceae), Geranium (Geraniaceae), Myriophyllum (Haloragaceae), Malva (Malvaceae), Epipogium, Himantoglossum (Orchidaceae), Orobanche (Orobanchaceae), Osyris (Santalaceae), Oxalis (Oxalidaceae), Pinus (Pinaceae), Anisantha, Avellinia, Avena, Corynephorus, Crypsis, Cutandia, Elytrigia, Lolium, Panicum, Polypogon, Sporobolus (Poaceae), Rumex (Polygonaceae), Lysimachia (Primulaceae), Eranthis, Ranunculus (Ranunculaceae), Rubus (Rosaceae), Crucianella, Galium (Rubiaceae), Verbascum (Scrophulariaceae), Solanum (Solanaceae), Tamarix (Tamaricaceae), Viola (Violaceae). In the end, the conservation status of the units and eventual protection of the cited biotopes are discussed

BioClimate: a Science Gateway for Climate Change and Biodiversity research in the EUBrazilCloudConnect project

[EN] Climate and biodiversity systems are closely linked across a wide range of scales. To better understand the mutual interaction between climate change and biodiversity there is a strong need for multidisciplinary skills, scientific tools, and access to a large variety of heterogeneous, often distributed, data sources. Related to that, the EUBrazilCloudConnect project provides a user-oriented research environment built on top of a federated cloud infrastructure across Europe and Brazil, to serve key needs in different scientific domains, which is validated through a set of use cases. Among them, the most data-centric one is focused on climate change and biodiversity research. As part of this use case, the BioClimate Science Gateway has been implemented to provide end-users transparent access to (i) a highly integrated user-friendly environment, (ii) a large variety of data sources, and (iii) different analytics & visualization tools to serve a large spectrum of users needs and requirements. This paper presents a complete overview of BioClimate and the related scientific environment, in particular its Science Gateway, delivered to the end-user community at the end of the project.This work was supported by the EU FP7 EUBrazilCloudConnect Project (Grant Agreement 614048), and CNPq/Brazil (Grant Agreement no 490115/2013-6).Fiore, S.; Elia, D.; Blanquer Espert, I.; Brasileiro, FV.; Nuzzo, A.; Nassisi, P.; Rufino, LAA.... (2019). BioClimate: a Science Gateway for Climate Change and Biodiversity research in the EUBrazilCloudConnect project. Future Generation Computer Systems. 94:895-909. https://doi.org/10.1016/j.future.2017.11.034S8959099

Real-world impact of the introduction of chemo-immunotherapy in extended small cell lung cancer: a multicentric analysis

BackgroundRecent clinical trials demonstrated longer survival in extended small cell lung cancer (SCLC) patients treated with immunotherapy in addition to chemotherapy. However, the magnitude of benefit is modest and the impact in real-world setting has to be fully established.MethodsWe collected clinical data and radiological imaging of patients affected by extended or relapsing SCLC and consecutively treated according to clinical practice between 2016 and 2023. As primary end-point, we compared pre-defined outcome indicators before and after the introduction of chemo-immunotherapy (May 2020): 6-month and 12-month progression free survival (PFS) rate, 12-month and 18-month overall survival (OS). Among those who were treated after May 2020, patients who did not receive immunotherapy according to treating physician’s choice were included in the analysis to minimize clinical selection bias.ResultsThe analysis included 214 patients: 132 (61.7%) were treated in an Academic cancer center and 82 (38.3%) in two community hospitals; 104 were treated before May 2020. Median PFS of the overall study population was 4.8 months (95% confidence interval [95% CI]: 4.4-5.4), median OS was 7.1 months (95% CI: 6.3-7.7). Estimated PFS and OS were significantly longer in patients treated after May 2020 with hazard ratio (HR) for PFS and OS of 0.61 (95% CI: 0.46-0.81, p < 0.001) and 0.70 (95% CI: 0.52-0.93, p = 0.015), respectively. 6-month PFS rate increased from 27% to 40% (p = 0.04) while 12-months PFS raised from 1% to 11% (p = 0.003). 12-month and 18-month OS rate increased from 15% to 28% (p = 0.03) and from 2.1% to 12% (p = 0.009), respectively. After May 2020 the median number of hospitalization days per patient decreased significantly and the incidence of severe AEs was similar. Among patients treated with chemo-immunotherapy, the onset of immune-related AEs was associated with improved PFS and OS (HR 0.55, 95% CI: 0.35-0.89, p = 0.012 and HR 0.47, 95%CI 0.28-0.77, p = 0.002, respectively).ConclusionsThe real-world analysis shows a meaningful improvement of outcome indicators after the introduction of chemo-immunotherapy, with reduction of the duration of hospitalization, thus supporting the use of chemo-immunotherapy and the need for further biomarker research

Antidepressant activity of fingolimod in mice

Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed with face and pharmacological validity. Chronic treatment with fingolimod (3\ua0mg\ua0kg(-1), i.p., once a day for 4\ua0weeks) reduced the immobility time in the forced swim test (FST) in a large proportion of CUS mice. This treatment also caused anxiogenic-like effects in the social interaction test without affecting anxiety-like behavior in the elevated plus maze or spatial learning in the water maze. CUS mice showed reduced BDNF levels and enhanced HDAC2 levels in the hippocampus. These changes were reversed by fingolimod exclusively in mice that showed a behavioral response to the drug in the FST. Fingolimod treatment also enhanced H3 histone K14-acetylation and adult neurogenesis in the hippocampus of CUS mice. Fingolimod did not affect most of the parameters we have tested in unstressed control mice. The antidepressant-like activity of fingolimod was confirmed in mice chronically treated with corticosterone. These findings show for the first time that fingolimod exerts antidepressant-like effect acting in a "disease-dependent" manner, and raise the interesting possibility that the drug could relieve depressive symptoms in MS patients independently of its disease-modifying effect on MS