Curcumin protects against NMDA-induced toxicity: A possible role for NR2A subunit

PURPOSE. Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDAinduced excitotoxicity in primary retinal cultures. This study was conducted to further characterize curcumin neuroprotective ability and analyze its effects on NMDA receptor (NMDAr). METHODS. NMDAr modifications were analyzed in primary retinal cell cultures using immunocytochemistry, whole-cell patch-clamp recording and western blot analysis. Cell death was evaluated with the TUNEL assay in primary retinal and hippocampal cultures. Optical fluorometric recordings with Fura 2-AM were used to monitor [Ca 2ϩ ] i . RESULTS. Curcumin dose-and time-dependently protected both retinal and hippocampal neurons against NMDA-induced cell death, confirming its anti-excitotoxic property. In primary retinal cultures, in line with the observed reduction of NMDAinduced [Ca 2ϩ ] i rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current after curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with kinetics closely correlated to time-course of neuroprotection and decrease in [Ca 2ϩ ] i . The relation between neuroprotection and NR2A level increase was also in line with the observation that curcumin neuroprotection required protein synthesis. Electrophysiology confirmed an increased activity of NR2A-containing NMDAr at the plasma membrane level. CONCLUSIONS. These results confirm the neuroprotective activity of curcumin against NMDA toxicity, possibly related to an increased level of NR2A, and encourage further studies for a possible therapeutic use of curcumin based on neuromodulation of NMDArs. (Invest Ophthalmol Vis Sci

An experimental study of the behaviour of two rockfills accounting for the effects of degree of saturation

Rockfill dams have become more and more recognized for their safety, economy and adaptability to widely varying site conditions. As a contribution to the understanding of the main factors affecting the rockfill behaviour, the paper reports and discusses experimental data on several aspects relevant to the interpretation and analysis of their in-situ response. The experimental programme involved three series of oedometric tests on specimens of two different gravels having the same grading, reconstituted at the same initial relative density. Experimental observations on rockfills compressibility are presented and discussed: attention is paid to the role of degree of saturation (Sr) through the analysis of “driest”, “fully saturated” conditions, and the transition from one to the other. Grain crushing tests on dry and saturated soil particles are also reported. Grain size distributions of the specimens, both after compaction and after the oedometer tests, are compared in the paper. The results show that the effect of Sr cannot be overlooked in the mechanical characterization of the material, especially in rockfill/stress conditions prone to crushin

Riscrittura e attualizzazione dei testi germanici medievali

Raccolta di saggi sui processi di riscrittura e attualizzazione dei testi appartenenti alle tradizioni Germaniche medievali.Collection of essays on different forms of presenting medieval Germanic texts to a modern readership: literary rewritings, musical adaptations, translations etc

Riscrittura e attualizzazione dei testi germanici medievali

Discussione delle questioni terminologiche relative ai processi di riscrittura e traduzione, tenendo conto del ruolo del filologo nello studio di questi fenomeni.Discussion of terminological issues regarding rewriting and translation, with particular attention to the role of the philologist in the study of these phenomena

Mine haul road maintenance management systems

In surface mining operations, ultra-heavy trucks operate on haul road networks which are typically from 10-40km in length. These road networks are often not optimally designed and maintained and as a result, identifying and remediating road functional defects is problematic. Most surface mine operators agree good roads are desirable, but find it difficult to translate this into an effective road maintenance system. This paper presents a haul road maintenance management system which utilises an assessment of rolling resistance based on a functional performance evaluation of a haul road, together with mine haul truck operating cost models to derive the optimal frequency of road maintenance. A typical application is presented which illustrates the potential of the technique to manage maintenance as and where needed with resultant reduction in total road user costs and an improvement in service provided for the road user

Analisi real world sull’utilizzo di rifaximina 200 mg nella Regione Campania

Introduction: Since its approval in Italy in 1987, rifaximin has been licensed in over 30 countries for the treatment of a wide range gastrointestinal diseases. The aim of the study was to analyze the real world use of rifaximin 200 mg in the Campania region. Methods: An observation retrospective study was conducted analysing the prescriptions of rifaximin received by the subjects ≥18 years old resident in the Campania Region. For each user the first rifaximin prescription in 2019 was defined as index date. All the prescriptions during the 12 months following the index date were analyzed. The subjects were categorized according to the number of packages/year received (1-4, 5-12, 13-24, >24). Results: 231,207 subjects received at least one package/year of rifaximin 200 mg with a prevalence of use of 4.9% and a total annual expenditure of 9.2 million euros. The 73.9% of users received 1-4 packages/year, 16.4% between 5-12 packages/year and 7.7% between 13-24 packages/year. The 2.0% of the users received more than 24 packages/year with an incidence on total expenditure equal to 14.8% (5% is due to those who received more than 40 packages/year). Discussion: About two thirds of rifaximin users received no more than three packages, presumably for the treatment of the infectious gastroenteritis or diarrheal syndromes, while 24% received 5-24 packages/year probably for the relapsing chronic intestinal pathologies. The 15% of the expenditure and consumption is related to subjects receiving more than 24 packages/year, probably due to the treatment of chronic liver diseases. Conclusions: The use of rifaximin 200 mg should be further investigated in different recurrent chronic diseases, especially to verify which schemes and dosages are used in real life compared to those tested in clinical trials

Remifentanil effects on respiratory drive and timing during pressure support ventilation and neurally adjusted ventilatory assist

We assessed the effects of varying doses of remifentanil on respiratory drive and timing in patients receiving Pressure Support Ventilation (PSV) and Neurally Adjusted Ventilatory Assist (NAVA). Four incrementing remifentanil doses were randomly administered to thirteen intubated patients (0.03, 0.05, 0.08, and 0.1\u3bcg\ub7Kg 121\ub7min 121) during both PSV and NAVA. We measured the patient's (Ti/Ttotneu) and ventilator (Ti/Ttotmec) duty cycle, the Electrical Activity of the Diaphragm (EAdi), the inspiratory (Delaytrinsp) and expiratory (Delaytrexp) trigger delays and the Asynchrony Index (AI). Increasing doses of remifentanil did not modify EAdi, regardless the ventilatory mode. In comparison to baseline, remifentanil infusion >0.05\u3bcg/Kg 121/min 121produced a significant reduction of Ti/Ttotneuand Ti/Ttotmecby prolonging the expiratory time. Delaytrinspand Delaytrexpwere significantly shorter in NAVA, respect to PSV. AI was not influenced by the different doses of remifentanil, but it was significantly lower during NAVA, compared to PSV. In conclusion remifentanil did not affect the respiratory drive, but only respiratory timing, without differences between modes

The Role of New Morphological Parameters Provided by the BC 6800 Plus Analyzer in the Early Diagnosis of Sepsis

Background: Late diagnosis of sepsis is associated with adverse consequences and high mortality rate. The aim of this study was to evaluate the diagnostic value of hematologic research parameters, that reflect the cell morphology of blood cells, available on the BC 6800 plus automated analyzer (Mindray) for the early detection of sepsis. Materials and methods: A complete blood count (CBC) was performed by Mindray BC 6800 Plus Analyzer in 327 patients (223 with a confirmed diagnosis of sepsis following sepsis-3 criteria, 104 without sepsis), admitted at the Intensive Care Unit of the Novara's Hospital (Italy) and in 56 patients with localized infection. Results: In univariate logistic regression, age, Hb, RDW, MO#, NMR, NeuX, NeuY, NeuZ, LymX, MonX, MonY, MonZ were associated with sepsis (p < 0.005). In multivariate analysis, only RDW, NeuX, NeuY, NeuZ, MonX and MonZ were found to be independent predictors of sepsis (p < 0.005). Morphological research parameters are confirmed to be predictors of sepsis even when analyzing the group with localized infection. Conclusions: In addition to already established biomarkers and basic CBC parameters, new morphological cell parameters can be a valuable aid in the early diagnosis of sepsis at no additional cost

gc) Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease.

The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut-derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy-proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of 51Cr-ethylene diamine tetraacetate ( 51Cr-EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens-1 (ZO-1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P &lt; 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH. Conclusions: Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition. Copyright © 2009 by the American Association for the Study of Liver Diseases