GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling

Background/objectives: A better understanding of adipose tissue biology is crucial to tackle insulin resistance and eventually coronary heart disease and diabetes, leading causes of morbidity and mortality worldwide. GALNT2, a GalNAc-transferase, positively modulates insulin signaling in human liver cells by down-regulating ENPP1, an insulin signaling inhibitor. GALNT2 expression is increased in adipose tissue of obese as compared to that of non-obese individuals. Whether this association is secondary to a GALNT2-insulin sensitizing effect exerted also in adipocytes is unknown. We then investigated in mouse 3T3-L1 adipocytes the GALNT2 effect on adipogenesis, insulin signaling and expression levels of both Enpp1 and 72 adipogenesis-related genes. Methods: Stable over-expressing GALNT2 and GFP preadipocytes (T 0 ) were generated. Adipogenesis was induced with (R+) or without (R−) rosiglitazone and investigated after 15 days (T 15 ). Lipid accumulation (by Oil Red-O staining) and intracellular triglycerides (by fluorimetric assay) were measured. Lipid droplets (LD) measures were analyzed at confocal microscope. Gene expression was assessed by RT-PCR and insulin-induced insulin receptor (IR), IRS1, JNK and AKT phosphorylation by Western blot. Results: Lipid accumulation, triglycerides and LD measures progressively increased from T 0 to T 15 R- and furthermore to T 15 R+. Such increases were significantly higher in GALNT2 than in GFP cells so that, as compared to T 15 R+GFP, T 15 R- GALNT2 cells showed similar (intracellular lipid and triglycerides accumulation) or even higher (LD measures, p < 0.01) values. In GALNT2 preadipocytes, insulin-induced IR, IRS1 and AKT activation was higher than that in GFP cells. GALNT2 effect was totally abolished during adipocyte maturation and completely reversed at late stage maturation. Such GALNT2 effect trajectory was paralleled by coordinated changes in the expression of Enpp1 and adipocyte-maturation key genes. Conclusions: GALNT2 is a novel modulator of adipogenesis and related cellular phenotypes, thus becoming a potential target for tackling the obesity epidemics and its devastating sequelae

Myrtucommulone from Myrtus communis exhibits potent anti-inflammatory effectiveness in vivo.

Myrtucommulone a nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis), has been reported to suppress the biosynthesis of eicosanoids by inhibition of 5-lipoxygenase and cyclooxygenase-1 in vitro and to inhibit the release of elastase and the formation of reactive oxygen species in activated polymorphonuclear leukocytes. Here, in view of the ability of MC to suppress typical proinflammatory cellular responses in vitro, we have investigated the effects of MC in in vivo models of inflammation. MC was administered to mice intraperitoneally, and paw edema and pleurisy were induced by the subplantar and intrapleural injection of carrageenan, respectively. MC (0.5, 1.5, and 4.5 mg/kg i.p.) reduced the development of mouse carrageenan-induced paw edema in a dose-dependent manner. Moreover, MC (4.5 mg/kg i.p. 30 min before and after carrageenan) exerted anti-inflammatory effects in the pleurisy model. In particular, 4 h after carrageenan injection in the pleurisy model, MC reduced: 1) the exudate volume and leukocyte numbers; 2) lung injury (histological analysis) and neutrophil infiltration (myeloperoxidase activity); 3) the lung intercellular adhesion molecule-1 and P-selectin immunohistochemical localization; 4) the cytokine levels (tumor necrosis factor-α and interleukin-1 β in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B 4, but not prostaglandin E2, levels in the pleural exudates; and 6) lung peroxidation (thiobarbituric acid-reactant substance) and nitrotyrosine and poly (ADP-ribose) immunostaining. In conclusion, our results demonstrate that MC exerts potent anti-inflammatory effects in vivo and offer a novel therapeutic approach for the management of acute inflammation. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics

A retrospective analysis focusing on a group of patients with dual diagnosis treated by both mental health and substance use services

OBJECTIVE: To highlight which demographic, familial, premorbid, clinical, therapeutic, rehabilitative, and assistance factors were related to dual diagnosis, which, in psychiatry, means the co-occurrence of both mental disorder and substance use in the same patient. METHODS: Our sample (N=145) was chosen from all outpatients with a dual diagnosis treated from January 1, 2012 to July 31, 2012 by both the Mental Health Service and the Substance Use Service of Modena and Castelfranco Emilia, Italy. Patients who dropped out during the study period were excluded. Demographic data and variables related to familial and premorbid history, clinical course, rehabilitative programs, social support and nursing care, and outcome complications were collected. The patients' clinical and functioning conditions during the study period were evaluated. RESULTS: Our patients were mostly men suffering from a cluster B personality disorder. Substance use was significantly more likely to precede psychiatric disease (P<0.001), and 60% of the sample presented a positive familial history for psychiatric or addiction disease or premorbid traumatic factors. The onset age of substance use was related to the period of psychiatric treatment follow-up (P<0.001) and the time spent in rehabilitative facilities (P<0.05), which, in turn, was correlated with personality disorder diagnosis (P<0.05). Complications, which presented in 67% of patients, were related to the high number of psychiatric hospitalizations (P<0.05) and professionals involved in each patient's treatment (P<0.05). Males more frequently presented familial, health, and social complications, whereas females more frequently presented self-threatening behavior (P<0.005). CONCLUSION: It was concluded that the course of dual diagnosis may be chronic, severe, and disabling, requiring many long-term therapeutic and rehabilitative programs to manage various disabilities

Does degradation from selective logging and illegal activities differently impact forest resources? A case study in Ghana

Degradation, a reduction of the ecosystem’s capacity to supply goods and services, is widespread in tropical forests and mainly caused by human disturbance. To maintain the full range of forest ecosystem services and support the development of effective conservation policies, we must understand the overall impact of degradation on different forest resources. This research investigates the response to disturbance of forest structure using several indicators: soil carbon content, arboreal richness and biodiversity, functional composition (guild and wood density), and productivity. We drew upon large field and remote sensing datasets from different forest types in Ghana, characterized by varied protection status, to investigate impacts of selective logging, and of illegal land use and resources extraction, which are the main disturbance causes in West Africa. Results indicate that functional composition and the overall number of species are less affected by degradation, while forest structure, soil carbon content and species abundance are seriously impacted, with resources distribution reflecting the protection level of the areas. Remote sensing analysis showed an increase in productivity in the last three decades, with higher resiliency to change in drier forest types, and stronger productivity correlation with solar radiation in the short dry season. The study region is affected by growing anthropogenic pressure on natural resources and by an increased climate variability: possible interactions of disturbance with climate are also discussed, together with the urgency to reduce degradation in order to preserve the full range of ecosystem functions

An Inquiry-Based Approach to a Pedagogical Laboratory for Primary School Teacher Education

In questo articolo vengono presentati e di- scussi alcuni risultati relativi alla sperimen- tazione di due esperienze di didattica laboratoriale della fisica, una basata su me- todi di indagine scientifica e l’altra su meto- dologie didattiche più “tradizionali”, svolte durante l’A.A. 2014-15 con studenti del CdL in Scienze della Formazione Primaria del- l’Università di Palermo. I dati, analizzati tra- mite metodi quantitativi, sono stati ricavati dalla somministrazione prima, durante e do- po le attività laboratoriali, di un questionario finalizzato a comprendere gli stili di insegna- mento preferiti dagli studenti, la motivazio- ne di questi all’apprendimento/insegna- mento delle scienze e le loro idee sulle dif- ficoltà che un insegnante di scuola prima- ria/dell’infanzia incontra nel progettare e sperimentare in classe attività didattiche di tipo scientifico. Dopo una breve descrizione dei metodi di analisi utilizzati, i risultati della sperimentazione vengono discussi e commentati.In this paper we discuss some results of the trial of two pedagogical physics workshops, held during the academic year 2014-15 with students of the Undergraduate Program for Elementary/ Kindergarten Teacher Education at the University of Palermo. One of the workshops was Inquiry Based, while the other was performed by using “traditional” teaching methods. The data, analyzed by using quantitative methods, were obtained by the administration before, during and after the workshop activities of a questionnaire aimed at understanding what are the teaching styles preferred by students, the student motivation in learning and teaching science, and their ideas about the difficulties a teacher meets when designing and trialing with real pupils science-based pedagogical activities. After a short description of the analysis methods we used in our study, the results of the trial are discussed and commented

A long-lasting quiescence phase of the eruptive variable V1118 Ori

V1118 Ori is an eruptive variable belonging to the EXor class of Pre-Main Sequence stars whose episodic outbursts are attributed to disk accretion events. Since 2006, V1118 Ori is in the longest quiescence stage ever observed between two subsequent outbursts of its recent history. We present near-infrared photometry of V1118 Ori carried out during the last eight years, along with a complete spectroscopic coverage from 0.35 to 2.5 um. A longterm sampling of V1118 Ori in quiescence has never been done, hence we can benefit from the current circumstance to determine the lowest values (i.e. the zeroes) of the parameters to be used as a reference for evaluating the physical changes typical of more active phases. A quiescence mass accretion rate between 1--3 $\times$ 10$^{-9}$ M_{\sun} yr$^{-1}$ can be derived and the difference with previous determinations is discussed. From line emission and IR colors analysis a visual extinction of 1-2 mag is consistently derived, confirming that V1118 Ori (at least in quiescence) is a low-extinction T Tauri star with a bolometric luminosity of about 2.1 L_{\sun}. An anti-correlation exists between the equivalent width of the emission lines and the underlying continuum. We searched the literature for evaluating whether or not such a behaviour is a common feature of the whole class. The anti-correlation is clearly recognizable for all the available EXors in the optical range (H$\beta$ and H$\alpha$ lines), while it is not as much evident in the infrared (Pa$\beta$ and Br$\gamma$ lines). The observed anti-correlation supports the accretion-driven mechanism as the most likely to account for continuum variations.Comment: 6 figures, 5 tables, accepted on Ap

Protective role of PI3-kinase-Akt-eNOS signalling pathway in intestinal injury associated with splanchnic artery occlusion shock.

Background and purpose: Endothelial NO synthase (eNOS) is a dynamic enzyme tightly controlled by co- and post-translational lipid modifications, phosphorylation and regulated by protein-protein interactions. Here we have pharmacologically modulated the activation of eNOS, at different post-translational levels, to assess the role of eNOS-derived NO and of these regulatory mechanisms in intestinal injury associated with splanchnic artery occlusion (SAO) shock. Experimental approach: SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk for 45 min followed by 30 min of reperfusion. During ischemia, 15 min prior to reperfusion, mice were given geldanamycin, an inhibitor of hsp90 recruitment to eNOS, or LY-294002 an inhibitor of phosphatidylinositol 3-kinase (PI3K), an enzyme that initiates Akt-catalysed phosphorylation of eNOS on Ser 1179. After 30 min of reperfusion, samples of ileum were taken for histological examination or for biochemical studies. Key results: Either LY-294002 or geldanamycin reversed the increased activation of eNOS and Akt observed following SAO shock. These molecular effects were mirrored in vivo by an exacerbation of the intestinal damage. Histological damage also correlated with neutrophil infiltration, assessed as myeloperoxidase activity, and with an increased expression of the adhesion proteins: ICAM-I, VCAM, P-selectin and E-selectin. Conclusions and implications: Overall these results suggest that activation of the Akt pathway in ischemic regions of reperfused ileum is a protective event, triggered in order to protect the intestinal tissue from damage induced by ischaemia/reperfusion through a fine tuning of the endothelial NO pathway. © 2007 Nature Publishing Group All rights reserved

Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-gamma

Leukotrienes (LT) and prostaglandins (PG) are proinflammatory mediators generated by the conversion of arachidonic acid via 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways. It has long been proposed that the inhibition of the 5-LO could enhance the COX pathway leading to an increased PG generation. We have found that in in vitro models of inflammation, such as mice-elicited peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon- γ (IFN-γ), the deletion of the gene encoding for 5-LO or the enzyme activity inhibition corresponded to a negative modulation of the COX pathway. Moreover, exogenously added LTC4, but not LTD4, LTE 4, and LTB4, was able to increase PG production in stimulated cells from 5-LO wild-type and knockout mice. LTC4 was not able to induce COX-2 expression by itself but rather potentiated the action of LPS/IFN-γ through the extracellular signal-regulated kinase-1/2 activation, as demonstrated by the use of a specific mitogen-activated protein kinase (MAPK) kinase inhibitor. The LT-induced increase in PG generation, as well as MAPK activation, was dependent by a specific ligand-receptor interaction, as demonstrated by the use of a cys-LT1 receptor antagonist, although also a direct action of the antagonist used, on PG generation, cannot be excluded. Thus, the balance between COX and 5-LO metabolites could be of great importance in controlling macrophage functions and consequently, inflammation and tumor promotion

Comparative Bioavailability Study of Two 81 mg Coated Tablet Formulations of Acetylsalicylic Acid in Fasting Healthy Volunteers

Introduction: Low-dose acetylsalicylic acid is used as antithrombotic agent and the enteric-coated formulations are widely used to minimize the gastrointestinal side effects. Aim: To compare the bioavailability of two acetylsalicylic acid formulations (Ecasil-81®, 81 mg coated tablet) in fasting healthy volunteers. Methods: Healthy volunteers (n=16) were recruited to a monocentric, open label, randomized, two-way crossover pharmacokinetic study, with seven days washout period between the treatments. They received a single 81 mg oral dose of a test (new formulation) or a standard reference formulation of acetylsalicylic acid (Ecasil-81®) after about 8 h fasting. Blood samples were collected over a period of 36 h. The salicylic acid plasma concentration was evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Noncompartmental pharmacokinetic analysis was performed using the WinNonlin program. Results: The maximum plasma concentration (Cmax) of salicylic acid was 5433 and 5719 ng/mL reached in 3.66 and 4.02 h (tmax) for the test and the reference formulation, respectively. The 90% confidence interval of the ratios of geometric means of Cmax and area under curve of plasma concentration until the last concentration observed (AUC0- last) were within the interval 80-125%. Conclusion: The new acetylsalicylic acid formulation has a bioavailability equivalent to the reference formulation for the rate and the extent of absorption

Leg ulcer and osteomyelitis due to methicillin-susceptible Staphylococcus aureus infection after fracture repair treatment: a case highlighting the potential role of prostaglandin E₁ vasodilator

Prostaglandins appear to reduce biofilm formation and chronicization of infections, and stimulate a rapid and effective clearance of infecting micro-organisms. We report a case of recovery from methicillin-susceptible Staphylococcus aureus (MSSA) osteomyelitis after multidisciplinary management with antibiotics, anti-thrombotics and prostaglandin E1 (PGE1) vasodilator, in a patient with tibial plateau fracture repaired with internal fixation devices. A 47-year-old HIV-negative male with chronic ulcer on the proximal third of the left leg was admitted to the Orthopaedic Unit of the Orestano Clinic in Palermo, Italy, for suspected osteomyelitis. A biopsy of the skin ulcer and blood cultures were performed and resulted positive for MSSA. Labelled leukocyte scintigraphy confirmed osteomyelitis. No clinical improvement was observed after combined antibiotic treatment with rifampicin plus trimethoprim-sulfamethoxazole. The patient underwent a 4-day therapeutic cycle: PGE1 (alprostadil 60 mg/day IV) combined with nadroparin calcium plus gentamicin, followed by treatment with aminaftone plus sulodexide plus levofloxacin. At discharge, the patient's painful symptoms had completely resolved and the ulcer had cicatrized; recovery from osteomyelitis was confirmed by scintigraphy. This treatment protocol including PGE1 may result in a significant improvement in quality of life and functional status of patients with a reduction in direct and indirect costs and economic benefit for the National Health Service