Everolimus and enteric-coated mycophenolate sodium Ab initio after liver transplantation: Midterm results

Background and aim. Everolimus (EVR) use in liver transplantation (OLT) has been prescribed with calcineurin inhibitors (CNIs), steroids, and monoclonal antibodies. The aim of our study was to evaluate the safety, feasibility, and impact on renal function of EVR ab initio, in combination with enteric-coated mycophenolate sodium (EC-MPS) without the use of induction treatment, steroids, or CNIs.Patients and methods. We retrospective analyzed nine consecutive patients who underwent OLT at our institution. The initial dose of EVR (1.5 mg/d) was adjusted to achieve trough levels of 8 to 12 ng/mL. EC-MPS introduced at 1080 mg/d was maintained at the same dose over time.Results. At a mean follow-up of 21.48 (standard deviation [SD] 1.4) months from OLT, 7/9 recipients were alive with stable graft function. The 2-year patient and graft survivals were 77%. One recipient died due to cerebral hemorrhage and one, lung failure. No clinical evidence of an acute rejection episode was observed. Mean estimated glomerular filtration rate value, according to the Modification of Diet in Renal Disease formula increased from 59.5 (SD 9.89) mL/min/1.73 m(2) at OLT to 100.2 (SD 47.5) mL/min/1.73 m(2) (P = .03) after 12 months and 98.71 (SD 33.74) mL/min/1.73 m(2) (P = .03) after 24 months' follow-up.Conclusion. A double immunosuppression therapy with EVR and EC-MPS ab initio seemed to be efficacions and safe, representing a valid alternative to CNIs to prevent renal failure after OLT

Discovery, activity and characterisation of an AA10 lytic polysaccharide oxygenase from the shipworm symbiont Teredinibacter turnerae

Background: The quest for novel enzymes for cellulosic biomass-degradation has recently been focussed on lytic polysaccharide monooxygenases (LPMOs/PMOs), Cu-containing proteins that catalyse the oxidative degradation of otherwise recalcitrant polysaccharides using O2 or H2O2 as a co-substrate. Results: Although classical saprotrophic fungi and bacteria have been a rich source of lytic polysaccharide monooxy genases (LPMOs), we were interested to see if LPMOs from less evident bio-environments could be discovered and assessed for their cellulolytic activity in a biofuel context. In this regard, the marine shipworm Lyrodus pedicellatus represents an interesting source of new enzymes, since it must digest wood particles ingested during its natural tunnel boring behaviour and plays host to a symbiotic bacterium, Teredinibacter turnerae, the genome of which has revealed a multitude of enzymes dedicated to biomass deconstruction. Here, we show that T. turnerae encodes a cellulose-active AA10 LPMO. The 3D structure, at 1.4 Å resolution, along with its EPR spectrum is distinct from other AA10 polysaccharide monooxygenases insofar as it displays a “histidine-brace” catalytic apparatus with changes to the surrounding coordination sphere of the copper. Furthermore, TtAA10A possesses a second, surface accessible, Cu site 14 Å from the classical catalytic centre. Activity measurements show that the LPMO oxidises cellulose and thereby signifcantly augments the rate of degradation of cellulosic biomass by classical glycoside hydrolases. Conclusion: Shipworms are wood-boring marine molluscs that can live on a diet of lignocellulose. Bacterial sym bionts of shipworms provide many of the enzymes needed for wood digestion. The shipworm symbiont T. turnerae produces one of the few LPMOs yet described from the marine environment, notably adding to the capability of shipworms to digest recalcitrant polysaccharides

Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One- and two-year outcomes

BACKGROUND. Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has been shown to provide effective immunosuppression for kidney, liver, lung, and small bowel transplantation. This drug combination was evaluated in pancreas transplant recipients. METHODS. Sixty consecutive pancreas transplants (30 simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone) were carried out under this protocol between July 2003 to January 2005. The mean follow-up was 22 months (range 17-33). RESULTS. One-year patient, pancreas, and kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%, respectively. The rejection rate was 30% (18/60), with four patients (7%) experiencing steroid-resistant rejection. Major infection occurred in three (5%) patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a herpes virus infection. One patient with cryptococcal meningitis was successfully treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic posttransplant lymphoproliferative disease was seen, which regressed with a temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum creatinine of the 30 simultaneous pancreas-kidney transplants at one year posttransplant was 1.37±0.33 mg/ml. The preexisting creatinine in pancreas after kidney transplants was not adversely affected by this immunosuppressive protocol. CONCLUSION. A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear. © 2006 Lippincott Williams & Wilkins, Inc

Development and tests of a new prototype detector for the XAFS beamline at Elettra Synchrotron in Trieste

The XAFS beamline at Elettra Synchrotron in Trieste combines X-ray absorption spectroscopy and X-ray diffraction to provide chemically specific structural information of materials. It operates in the energy range 2.4-27 keV by using a silicon double reflection Bragg monochromator. The fluorescence measurement is performed in place of the absorption spectroscopy when the sample transparency is too low for transmission measurements or the element to study is too diluted in the sample. We report on the development and on the preliminary tests of a new prototype detector based on Silicon Drift Detectors technology and the SIRIO ultra low noise front-end ASIC. The new system will be able to reduce drastically the time needed to perform fluorescence measurements, while keeping a short dead time and maintaining an adequate energy resolution to perform spectroscopy. The custom-made silicon sensor and the electronics are designed specifically for the beamline requirements.Comment: Proceeding of the 6YRM 12th-14th Oct 2015 - L'Aquila (Italy). Accepted for publication on Journal of Physics: Conference Serie

Commercial hemp seed oils: a multimethodological characterization

Nine commercial hemp seed oils from different countries were studied using a multimethodological approach to obtain information about their quality and chemical composition. Due to the lack of a specific regulation for hemp seed oils, quality parameters used in the case of olive oils (free acidity, peroxides number, spectrophotometer parameters) and anisidine number were measured and compared with those reported for extra virgin olive oil (EVOO). Free acidity and peroxides number showed a great variability, ranging from 0.4 to 17.24% and from 4.32 to 22.14 meqO2/kg, respectively, whereas the anisidine number ranged from 0.11 to 3.58. K232 value turned out to be generally below the limit reported for EVOO, whereas K270 and ΔK values were higher, with respect to EVOO limits, due to the high amount of tri-unsaturated fatty chains. Colorimetric analysis showed a peculiar curve trend that could represent the fingerprint of this product. Untargeted nuclear magnetic resonance methodology allowed to measure the amount of fatty chains, ω-6:ω-3 ratio, β-sitosterol, and aldehydes. The ω-6:ω-3 ratio turned out to be, in some cases, different from that reported on the bottle labels. Finally, lipoperoxidation assays were also carried out under different storage (light and temperature) and time exposure conditions, confirming that the exposure to direct light is the condition that interferes more with the product quality

Chemico-biological characterization of Torpedino Di Fondi® tomato fruits. A comparison with San Marzano cultivar at two ripeness stages

Torpedino di Fondi (TF) is a hybrid tomato landrace developed in Sicily and recently introduced in the south Lazio area along with the classical San Marzano (SM) cultivar. The present study aimed at characterizing TF tomatoes at both pink and red ripening stages, and at comparing them with traditional SM tomatoes. A multidisciplinary approach consisting of morphological, chemical (FT‐ICR MS, NMR, HPLC, and spectrophotometric methods), and biological (antioxidant and antifungal in vitro activity) analyses was applied. Morphological analysis confirmed the mini‐ San Marzano nature and the peculiar crunchy and solid consistency of TF fruits. Pink TF tomatoes displayed the highest content of hydrophilic antioxidants, like total polyphenols (0.192 mg/g), tannins (0.013 mg/g), flavonoids (0.204 mg/g), and chlorophylls a (0.344 mg/g) and b (0.161 mg/g), whereas red TF fruits were characterized by the highest levels of fructose (3000 mg/100 g), glucose (2000 mg/100 g), tryptophan (2.7 mg/100 g), phenylalanine (13 mg/100 g), alanine (25 mg/100 g), and total tri‐unsaturated fatty acids (13% mol). Red SM fruits revealed the greatest content of lipophilic antioxidants, with 1234 mg/g of total carotenoids. In agreement with phenolics content, TF cultivar showed the greatest antioxidant activity. Lastly, red TF inhibited Candida species (albicans, glabrata and krusei) growth

Cannabis sativa L. inflorescences from monoecious cultivars grown in central Italy: an untargeted chemical characterization from early flowering to ripening

The chemical composition of the inflorescences from four Cannabis sativa L. monoecious cultivars (Ferimon, Uso-31, Felina 32 and Fedora 17), recently introduced in the Lazio Region, was monitored over the season from June to September giving indications on their sensorial, pharmaceutical/nutraceutical proprieties. Both untargeted (NMR) and targeted (GC/MS, UHPLC, HPLC-PDA/FD and spectrophotometry) analyses were carried out to identify and quantify compounds of different classes (sugars, organic acids, amino acids, cannabinoids, terpenoids, phenols, tannins, flavonoids and biogenic amines). All cultivars in each harvesting period showed a THC content below the Italian legal limit, although in general THC content increased over the season. Citric acid, malic acid and glucose showed the highest content in the late flowering period, whereas the content of proline drastically decreased after June in all cultivars. Neophytadiene, nerolidol and chlorogenic acid were quantified only in Felina 32 cultivar, characterized also by a very high content of flavonoids, whereas alloaromadendrene and trans-cinnamic acid were detected only in Uso-31 cultivar. Naringenin and naringin were present only in Fedora 17 and Ferimon cultivars, respectively. Moreover, Ferimon had the highest concentration of biogenic amines, especially in July and August. Cadaverine was present in all cultivars but only in September. These results suggest that the chemical composition of Cannabis sativa L. inflorescences depends on the cultivar and on the harvesting period. Producers can use this information as a guide to obtain inflorescences with peculiar chemical characteristics according to the specific use

The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73532/1/j.1460-9568.2004.03612.x.pd