ANALISI DEL METABOLISMO GLUCIDICO IN PAZIENTI CIRROTICI SOTTOPOSTI A TRAPIANTO EPATICO: RUOLO DELLA SECREZIONE BETA CELLULARE E DELL'INSULINORESISTENZA.

Impaired glucose metabolism is frequently described in cirrhotic patients. The pathogenesis of diabetes mellitus (DM) in this population is complex and not precisely known. Insulin resistance (IR) plays a central role in the glucose metabolism disturbance and it has been speculated that genetic and environmental factors and some etiologic agents in liver disease impair insulin secretion. Aim of the study: evaluate \u3b2 cell secretion and insulin sensitivity in a cohort of cirrhotic patients undergoing liver transplantation (LT). 107 cirrhotic patients (31 female e 76 male) were evaluated before LT. The patients who underwent LT were evaluated 3, 6, 12 months after surgery. To evaluate insulin resistance HOMA-IR was used. To assess the \u3b2 cell secretion, a state-of-art modelling of glucose/C-peptide curves during OGTT was used. Two outputs were provided: dynamic evaluation (1st phase) and proportional evaluation (2nd phase). Before LT the prevalence of DM and prediabetes (pre DM) were 50.5% and 31.8 % respectively. DM patients showed a lower insulin secretion (both 1st and 2nd phase) and tended to have higher HOMA-IR when compared to pre DM and non DM subjects. After LT glucose metabolism improved (impaired glucose metabolism: 6 months 61.1%, 12 months 65.6%). HOMA-IR was decreased (pre LT: 5.48\ub15.14, 3 months post LT: 2.17\ub11.62, 6 months post LT: 2.28\ub11.44, 12 months post LT: 2.36\ub11.73 P=0.0017). No differences in \u3b2 cell secretion was found. When the population who underwent LT was divided in 2 groups according to the improvement or not of glucose metabolism, higher insulin secretion was found in improved subjects (2nd phase). No differences in HOMA-IR, age, duration of hepatic disease, family history of type 2 DM, immunosuppressive therapy were observed. In conclusion IR and reduced insulin secretion was observed in cirrhotic diabetic patients. After LT an improved glucose metabolism was observed. Insulin sensitivity was increased in all patients and higher \u3b2 cell secretion was observed only in subjects with improved glucose metabolism

Momentum distribution of liquid helium

We have obtained the one--body density matrix and the momentum distribution $n(p)$ of liquid $^4$He at $T=3D0^o$K from Diffusion Monte Carlo (DMC) simulations, using trial functions optimized via the Euler Monte Carlo (EMC) method. We find a condensate fraction smaller than in previous calculations. Though we do not explicitly include long--range correlations in our calculations, we get a momentum distribution at long wavelength which is compatible with the presence of long--range correlations in the exact wave function. We have also studied $^3$He, using fixed--node DMC, with nodes and trial functions provided by the EMC. In particular, we analyze the momentum distribution $n(p)$ with respect to the discontinuity $Z$ as well as the singular behavior, at the Fermi surface. We also show that an approximate factorization of the one-body density matrix $\rho(r)\simeq \rho_0(r)\rho_B(r)$ holds, with $\rho_0(r)$ and $\rho_B(r)$ respectively the density matrix of the ideal Fermi gas and the density matrix of a Bose $^3$He.Comment: 10 pages, REVTeX, 12 figure

Amyposomes, a nanotechnological chaperone with anti-amyloidogenic activity

Aim: the effect of liposomes bi-functionalized with phosphatidic acid and with a synthetic peptide derived from human apolipoprotein e has been evaluated on the aggregation features of different amyloidogenic proteins: human amyloid β1–40 (aβ1–40), transthyretin (ttR) variant s52P, human β2microglobulin (β2m) variants ΔN6 and D76N, serum amyloid a (saa). Methods: the formation of fibrillar aggregates of the proteins was investigated by thioflavint fluorescence assay and validated by atomic Force Microscopy. Results: the results show that liposomes are preventing the transition of non-aggregated forms to the fibrillar state, with stronger effects on aβ1–40, β2m ΔN6 and saa. liposomes also induce disaggregation of the amyloid aggregates of all the proteins investigated, with stronger effects on aβ1–40, β2 D76N and ttR. sPR assays show that liposomes bind aβ1–40 and saa aggregates with high affinity (KD in the nanomolar range) whereas binding to ttR aggregates showed a lower affinity (KD in the micromolar range). aggregates of β2m variants showed both high and low affinity binding sites. computed structural analysis of protein fibrillar aggregates and considerations on the multidentate features of liposomes allow to speculate a common mechanism of action, based on binding the β-stranded peptide regions responsible for the amyloid formation. Conclusion: thus, multifunctional liposomes perform as pharmacological chaperones with anti-amyloidogenic activity, with a promising potential for the treatment of a number of protein-misfolding diseases

Students’ satisfaction and teaching efficiency of university offer

This study analyses the factors affecting students’ satisfaction with university experience, focusing on the aspects characterising the teaching efficiency of educational offer. For this purpose, organisation of teaching activities, available information, teaching materials, and other facilities offered to students to make their learning experience more successful, are considered as indicators of teaching efficiency. Our interest in this topic is justified by the importance that students’ satisfaction assumes, not only as indicator of the quality of educational services but also for its relationship with overall life satisfaction and subjective well-being. A structural equation model with latent variables is estimated by using survey and administrative data of the University of Pisa. Main findings seem to show that teaching efficiency has a positive effect on satisfaction and suggest that whenever it is inadequate, or at least, considered as such, students are less satisfied for their university experience. The effects of other factors on students’ satisfaction such as studies organisation, social capital and internship experience are also discussed

Nanotechnology advances towards development of targeted-treatment for obesity

Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modifcation or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specifcity and unsustainable weight loss efects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side efects, and enhanced efcacy. These efects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbiditie

Differential scanning calorimetry of erythrocyte reconstituted membrane

The thermal properties of biomembranes examined by d\uedfferential calorimetry mimic the properties of b\uedlayers formed from their isolated lipids or from synthetic lipids. In this study we have analyzed, by differential scanning calorimetry (DSC), the thermal behaviour of lipids extracted from bovine erythrocyte and of their reconst\uedtuted mixtures. Membrane lipids were extracted from blood samples of 11 cows and separated in the three components: cholesterol, phospholipids and glycolipids. Phospholipid and glycolipid classes were determined by thin layer chromatography. Lipids from erythrocyte membrane of different animals (at controlled diet), at a given time, were pooled together at a proportional amount like in the original membranes. DSC was performed on aqueous buffer dispersions (pH 7.4) of the average lipid components but, \uedn some cases, the sample contained lipids \uedsolated from one animal. Average phospholipid sample exhibited two phase transitions: the first at 24 - 26 \ub0C and the second at about 38 \ub0C. Some scans of phosphol\uedpids from one animal show only the first trans\uedt\uedon which occurs between 23.1 and 25.4 \ub0C whereas the second phase transition, when occurring, is at very different temperatures (32.4 - 38.1 \ub0C). For all average glycolipid samples one transition was observed at about 35 \ub0C. Mixtures of cholesterol and phospholipids show only one broad transition. In these m\uedxtures the transition temperature is close to that of the second transition of phospholipid samples. Some correlations between the transition temperatures and the amounts of different phospholipids in the samples have been tested but it seems important to consider the fatty acid composition of the studied m\uedxtures to account for the different levels of saturated and unsaturated fatty acids