Cholesteryl Ester Transfer Protein (cetp) Expression Does Not Affect Glucose Homeostasis And Insulin Secretion: Studies In Human Cetp Transgenic Mice.

Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the exchange of triglycerides for esterified cholesterol between HDL and apoB-lipoproteins. Previous studies suggest that CETP may modify glucose metabolism in patients or cultured cells. In this study, we tested if stable CETP expression would impair glucose metabolism. We used human CETP transgenic mice and non-transgenic littermate controls (NTg), fed with control or high fat diet, as well as in dyslipidemic background and aging conditions. Assays included glucose and insulin tolerance tests, isolated islets insulin secretion, tissue glucose uptake and adipose tissue GLUT mRNA expression. CETP expression did not modify glucose or insulin tolerance in all tested conditions such as chow and high fat diet, adult and aged mice, normo and dyslipidemic backgrounds. Fasting and fed state plasma levels of insulin were not differ in CETP and NTg mice. Direct measurements of isolated pancreatic islet insulin secretion rates induced by glucose (11, 16.7 or 22 mM), KCl (40 mM), and leucine (10 mM) were similar in NTg and CETP mice, indicating that CETP expression did not affect β-cell function in vivo and ex vivo. Glucose uptake by insulin target tissues, measured in vivo using (3)H-2-deoxyglucose, showed that CETP expression had no effect on the glucose uptake in liver, muscle, perigonadal, perirenal, subcutaneous and brown adipose tissues. Accordingly, GLUT1 and GLUT4 mRNA in adipose tissue were not affected by CETP. In summary, by comparing the in vivo all-or-nothing CETP expressing mouse models, we demonstrated that CETP per se has no impact on the glucose tolerance and tissue uptake, global insulin sensitivity and beta cell insulin secretion rates.15

Apolipoprotein CIII overexpression exacerbates diet-induced obesity due to adipose tissue higher exogenous lipid uptake and retention and lower lipolysis rates

Hypertriglyceridemia is a common type of dyslipidemia found in obesity. However, it is not established whether primary hyperlipidemia can predispose to obesity. Evidences have suggested that proteins primarily related to plasma lipoprotein transport, such as apolipoprotein (apo) CIII and E, may significantly affect the process of body fat accumulation. We have previously observed an increased adiposity in response to a high fat diet (HFD) in mice overexpressing apoCIII. Here, we examined the potential mechanisms involved in this exacerbated response of apoCIII mice to the HFD. We measured body energy balance, tissue capacity to store exogenous lipids, lipogenesis and lipolysis rates in non-transgenic and apoCIII overexpressing mice fed a HFD during two months. Food intake, fat excretion and whole body CO2 production were similar in both groups. However, the adipose tissue mass (45 %) and leptin plasma levels (2-fold) were significantly greater in apoCIII mice. Lipogenesis rates were similar, while exogenous lipid retention was increased in perigonadal (2-fold) and brown adipose tissues (40 %) of apoCIII mice. In addition, adipocyte basal lipolysis (55 %) and in vivo lipolysis index (30 %) were significantly decreased in apoCIII mice. A fat tolerance test evidenced delayed plasma triglyceride clearance and greater transient availability of non-esterified fatty acids (NEFA) during the post-prandial state in the apoCIII mice plasma. Thus, apoCIII overexpression resulted in increased NEFA availability to adipose uptake and decreased adipocyte lipolysis, favoring lipid enlargement of adipose depots. We propose that plasma apoCIII levels represent a new risk factor for diet-induced obesity12CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informação2011/50400-0; 2011/51349-

A CFD study of a pMDI plume spray

Uncorrected proofAsthma is an inflammatory chronic disease characterized by airway obstructions disorders. The treatment is usually done by inhalation therapy, in which pressurized metered-dose inhalers (pMDIs) are preferred devices. The objective of this paper is to characterize and simulate a pMDI spray plume by introducing realistic factors through a computational fluid dynamics (CFD) study. Numerical simulations were performed with Fluent® software, by using a three-dimensional “testbox” for room environment representation. A salbutamol/HFA-134a formulation was used for characterization, whose properties taken as input for the CFD simulations. Spray droplets were considered to be composed by ethanol, salbutamol and HFA-134a. Propellant evaporation was taken into consideration, as well as, drag coefficient correction. Results showed an air temperature drop of 3.3 °C near the nozzle. Also, an increase in air velocity of 3.27 m/s was noticed. The CFD results seem to be in good agreement with Dunbar (1997) data on particle average velocity along the axial distance from the nozzle.National Funds-Portuguese Foundation for Science and Technology, under Strategic Project PEst-C/EME/UI4077/2011 and PEst-OE/EME/299UI0252/201

Are coffee silverskin extracts safe for topical use? An in vitro and in vivo approach

Recent changes in regulatory requirements and social views on animal testing have incremented the development of reliable alternative tests for predicting skin and ocular irritation potential of products based on new raw materials. In this regard, botanical ingredients used in cosmetic products are among those materials, and should be carefully reviewed concerning the potential presence of irritant constituents. In particular, cosmetic products used on the face, in vicinity of the eyes or that may come in contact with mucous membranes, should avoid botanical ingredients that contain, or are suspected to contain, such ingredients. In this study, we aimed to evaluate the effect of a new cosmetic ingredient, namely, coffee silverskin (CS), with an in vitro skin and ocular irritation assay using reconstructed human epidermis, EpiSkin™, and human corneal epithelial model, SkinEthics™ HCE, and an in vivo assay. Three different extracts of CS were evaluated. The histology of the models after extracts applications was analysed. The in vitro results demonstrated that extracts were not classified as irritant and the histological analyses proved that extracts did not affect both models structure. The content of caffeine, 5-hydroxymethyl furfural and chlorogenic acid was quantified after the epidermal assay. The in vivo test carried out with the most promising extract (hydroalcoholic) showed that, with respect to irritant effects, these extracts can be regarded as safe for topical application

Pancreatic lesions and metabolic aggravation are prevented by low doses of sitagliptin in a rat model of type 2 diabetes

Introduction: The management of type 2 diabetes is designed to reduce disease-related complications and improve long-term outcomes. Inhibition of dipeptidyl peptidase-4 (DPP-4) activity by sitagliptin has been shown to improve glycaemic control in patients with type 2 diabetes Mellitus (T2DM) by prolonging the actions of incretin hormones, but the real impact of low-dose sitagliptin treatment on cardiometabolic risk factors and pancreatic lesions is almost unknown. This study aimed to evaluate the effects of low doses of sitagliptin on cardiovascular risk factors and histological pancreas parameters in Zucker Diabetic Fatty rats (ZDF (fa/fa)) an animal model of T2DM. Materials and Methods: Twenty weeks old diabetic obese (fa/fa) ZDF male rats were treated with vehicle or sitagliptin (10 mg/kg BW/day) during 6 weeks (n=8 each). The following parameters were assessed: glycaemia, HbA1c, insulin, lipidic profile; blood pressure. Specimens for pancreatic histopathology were stained with haematoxylin-eosin and periodic-acid-Shiff, examined by light microscopy. Endocrine and exocrine pancreas was evaluated semiquantitatively concerning inflammatory infiltrate, fibrosis, vacuolization and congestion, and scored from 0 (absent) to 3 (severe and extensive damage). Results: Sitagliptin in diabetic obese ZDF rats promoted a positive effect on dysglycaemia, dyslipidaemia and prevented the increase of blood pressure. Endocrine and exocrine pancreas presented a reduction/amelioration of fibrosis severity, inflammatory infiltrate, intra-islet vacuolation, and congestion vs the vehicle-treated diabetic rats. Conclusion: Simultaneous improvement of a sustainable glycaemic profile and of pancreatic histopathological lesions supports the favorable cardiovascular risk profile and may prove beneficial in decreasing long-term complications of T2DM.The authors are very grateful to the support of Fundação Merck Sharp & Dohm

Kidney segmentation in 3D CT images using B-Spline Explicit Active Surfaces

In this manuscript, we propose to adapt the B-Spline Explicit Active Surfaces (BEAS) framework for semi-automatic kidney segmentation in computed tomography (CT) images. To study the best energy functional for kidney CT extraction, three different localized region-based energies were implemented within the BEAS framework, namely localized Chan-Vese, localized Yezzi, and signed localized Yezzi energies. Moreover, a novel gradient-based regularization term is proposed. The method was applied on 18 kidneys from 9 CT datasets, with different image properties. Several energy combinations were contrasted using surface-based comparison against ground truth meshes, assessing their accuracy and robustness against surface initialization. Overall, the hybrid energy functional combining the localized signed Yezzi energy with gradient-based regularization simultaneously showed the highest accuracy and the lowest sensitivity to the initialization. Volumetric analysis demonstrated the feasibility of the method from a clinical point of view, with similar reproducibility to manual observers.The authors acknowledge FCT - Fundação para a Ciência e a Tecnologia, Portugal, and the European Social Found, European Union, for funding support through the Programa Operacional Capital Humano (POCH) in the scope of the PhD grants SFRH/BD/93443/2013 (S. Queirós) and SFRH/BD/95438/2013 (P. Morais).info:eu-repo/semantics/publishedVersio

Alginate-lysozyme nanofibers hydrogels with improved rheological behavior, printability and biological properties for 3D bioprinting applications

In this study, alginate nanocomposite hydrogel bioinks reinforced with lysozyme nanofibers (LNFs) were developed. Alginate-LNF (A-LNF) suspensions with different LNF contents (1, 5 and 10 wt.%) were prepared and pre-crosslinked with 0.5% (w/v) CaCl2 to formulate A-LNF inks. These inks exhibit proper shear-thinning behavior and good recovery properties (~90%), with the pre-crosslinking step playing a crucial role. A-LNF fully crosslinked hydrogels (with 2% (w/v) CaCl2) that mimic 3D printing scaffolds were prepared, and it was observed that the addition of LNFs improved several properties of the hydrogels, such as the morphology, swelling and degradation profiles, and mechanical properties. All formulations are also noncytotoxic towards HaCaT cells. The printing parameters and 3D scaffold model were then optimized, with A-LNF inks showing improved printability. Selected A-LNF inks (A-LNF0 and A-LNF5) were loaded with HaCaT cells (cell density 2 × 106 cells mL-1), and the cell viability within the bioprinted scaffolds was evaluated for 1, 3 and 7 days, with scaffolds printed with the A-LNF5 bioink showing the highest values for 7 days (87.99 ± 1.28%). Hence, A-LNF bioinks exhibited improved rheological performance, printability and biological properties representing a good strategy to overcome the main limitations of alginate-based bioinks.publishe

Segmentation of kidney and renal collecting system on 3D computed tomography images

Surgical training for minimal invasive kidney interventions (MIKI) has huge importance within the urology field. Within this topic, simulate MIKI in a patient-specific virtual environment can be used for pre-operative planning using the real patient's anatomy, possibly resulting in a reduction of intra-operative medical complications. However, the validated VR simulators perform the training in a group of standard models and do not allow patient-specific training. For a patient-specific training, the standard simulator would need to be adapted using personalized models, which can be extracted from pre-operative images using segmentation strategies. To date, several methods have already been proposed to accurately segment the kidney in computed tomography (CT) images. However, most of these works focused on kidney segmentation only, neglecting the extraction of its internal compartments. In this work, we propose to adapt a coupled formulation of the B-Spline Explicit Active Surfaces (BEAS) framework to simultaneously segment the kidney and the renal collecting system (CS) from CT images. Moreover, from the difference of both kidney and CS segmentations, one is able to extract the renal parenchyma also. The segmentation process is guided by a new energy functional that combines both gradient and region-based energies. The method was evaluated in 10 kidneys from 5 CT datasets, with different image properties. Overall, the results demonstrate the accuracy of the proposed strategy, with a Dice overlap of 92.5%, 86.9% and 63.5%, and a point-to-surface error around 1.6 mm, 1.9 mm and 4 mm for the kidney, renal parenchyma and CS, respectively.NORTE-01-0145-FEDER0000I3, and NORTE-01-0145-FEDER-024300, supported by Northern Portugal Regional Operational Programme (Norte2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and also been funded by FEDER funds, through Competitiveness Factors Operational Programme (COMPETE), and by national funds, through the FCT-Fundacao para a Ciência e Tecnologia, under the scope of the project POCI-01-0145-FEDER-007038. The authors acknowledge FCT-Fundação para a Ciância e a Tecnologia, Portugal, and the European Social Found, European Union, for funding support through the Programa Operacional Capital Humano (POCH).info:eu-repo/semantics/publishedVersio