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Broderick G.A.,U.S. Department of Agriculture | Colombini S.,University degli Studi
EAAP Scientific Series | Year: 2010

Rates of ruminal protein degradation are required in most of the current nutritional models; however, protein degradation in the rumen is very complex and difficult to measure reliably using simple in vitro and in situ methods. In vitro assays based on using mixed ruminal organisms in which microbial N incorporation is quantified or in which microbial growth is inhibited have proven to be the most robust for estimating rate and extent of protein degradation. Use of gas production to estimate N incorporation or release has become widely adopted. Recent developments have allowed study of the time course of protein breakdown so degradation rates can be determined. The inhibitor in vitro procedure has been useful in a number of applications but is limited to short term incubations of 4 to 6 h. Also, this assay has not been widely adapted beyond the laboratory where it was developed, possibly because it requires large numbers of assays for ammonia and total AA. Under some conditions, extents of protein hydrolysis obtained using several different cell-free proteases have been correlated to extents of in situ degradation but, thus far, cell-free proteases have not proven completely reliable for predicting rates of ruminal protein degradation. Future research might be directed toward identifying how protein degradation activities of cell-free proteases differ from that of the proteases elaborated by mixed ruminal organisms.


Novotna A.,Krajska nemocnice Pardubice | Mares J.,Neurologicka Klinika | Ratcliffe S.,MAC UK Neuroscience Ltd | Novakova I.,MS Centrum | And 12 more authors.
European Journal of Neurology | Year: 2011

Background: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. Methods: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase. Results: Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of nabiximols (P=0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of nabiximols. Conclusions: The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment. Click to view the accompanying paper in this issue. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.


Lai S.,University degli Studi
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2010

Cardiovascular mortality and morbidity are higher in patients with chronic renal disease than in the general population. Patients with chronic renal disease are in the highest risk group for thromboembolic disease and many clinical trials have demonstrated the greater safety and efficacy of low-molecular-weight heparin (LMWH) versus unfractionated heparin (UFH). LMWH is cleared only by the kidneys while UFH is cleared by the renal and hepatic routes. Furthermore, LMWH has a significant accumulative effect in patients with impaired renal function (creatinine clearance <30 mL/min). The aim of this study was to evaluate the risk of bleeding when LMWH is used as an anticoagulant in hemodialysis or for treatment of acute thromboembolic disease in patients with renal failure. Twenty-one adult patients were enrolled, 13 with end-stage renal disease requiring chronic hemodialysis and 6 with acute thromboembolic disease and severe renal insufficiency (creatinine clearance <30 mL/min). Group A consisted of 13 patients receiving LMWH (enoxaparin 60 IU/kg/day) for preventing thrombosis of the extracorporeal dialysis circuit. Group B consisted of 8 patients with acute thromboembolic disease receiving LMWH (enoxaparin 60 IU/kg/day). In all patients anti-Xa activity was measured by a chromogenic assay (HEMONOX). In the first group 2 blood samples were taken during the dialysis session (2-4 hours) and a third sample after the end of the session up to 48 hours following enoxaparin injection; in the second group a blood sample was taken 4 days after the start of LMWH treatment, 2 hours after its daily administration. In group A, all dialysis sessions were performed with no minor or major bleeding. Anti-Xa activity was highest 2 hours after the start and remained above 100 seconds after the end of the session, while 44 hours after injection, at the start of the next dialysis session, it was low or absent (<100 seconds). In the second group there were 2 major bleeding episodes, 2 minor bleeding episodes, 1 prolonged time to hemostasis after needle removal, and 2 bleeding episodes at the vascular access site (central venous catheter). Anti-Xa activity was consistently higher than 200 seconds (therapeutic target range:100-200 seconds) and showed interindividual variability (in 2 patients the anti-Xa time was more than 900 seconds), indicating a high risk of bleeding. LMWH seems to be as effective and safe as UFH in terms of bleeding complications and in preventing extracorporeal circuit thrombosis in patients on hemodialysis. Our results indicate that it is preferable to avoid invasive procedures for 12 hours following a dialysis session performed with LMWH anticoagulation because the anticoagulant effect lasted at least 4 hours after its injection. These data suggest that in patients with acute thromboembolic events and severe renal insufficiency, standard anticoagulation with LMWH is not recommended because of an increased risk of major and minor bleeding.


Lupi C.,University of Rome La Sapienza | Dell'Era A.,University degli Studi | Pasquali M.,University of Rome La Sapienza
International Journal of Hydrogen Energy | Year: 2014

In this study Ni-Co alloys have been activated during hydrogen electrochemical production by adding Mo ions into the alkaline electrolyte. After dissolving different amounts of sodium molybdate in the Na(OH) electrolyte, Ni-Co alloys were used as cathodes for hydrogen evolution reaction. Afterwards a comparison between hydrogen overvoltage measured on Ni-Co alloys with and without in situ activation has been made. The in situ activation clearly shows an improvement of electrocatalytic properties of Ni-Co alloys for hydrogen evolution reaction. Depending on the alloy the best conditions are reached with different amounts of sodium molybdate in the electrolyte. The values of exchange current density for Ni-Co alloys without Mo, are an average of about 4.1 10-6 A/cm2, while by using in situ activation, these values are about 3.5·10-4 A/cm2. Therefore, exchange current density presents a value nearly one hundred-fold higher when molybdate ions are present in solution. Moreover, two Tafel slope values have been determined for HER on Ni-Co alloys with and without Mo in situ activation. Those Tafel slope values are different, so as their range of both overvoltage and current density, probably highlighting a different kinetic mechanism. © 2013, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights.


Pronzato P.,Oncologia Medica | Cortesi E.,University degli Studi | van der Rijt C.C.,Erasmus University Rotterdam | Bols A.,Az St. Jan | And 5 more authors.
Oncologist | Year: 2010

Purpose. To evaluate the effects of epoetin alfa on patient- reported outcomes (PROs) in patients with breast cancer receiving myelotoxic chemotherapy. Materials and Methods. Women with hemoglobin concentrations ≤12.0 g/dl and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-3 were randomized 1:1 to receive epoetin alfa (10,000 IU 3 times weekly) or best standard care (BSC) during chemotherapy. The primary endpoint was the change from baseline in the total anemia subscale assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire after 12 weeks of treatment. The fatigue and nonfatigue subscales from the FACT An, the Cancer Linear Analog Scale (CLAS), hemoglobin changes, ECOG PS score, tumor response, overall survival, and safety also were evaluated. Results. Of 223 patients randomized, 216 constituted the modified intent-to-treat population. Percentage changes in the total anemia subscale of the FACT-An were significantly different between epoetin alfa treatment (14.2%) and BSC (-0.5%; p =.002), favoring epoetin alfa; so were changes in the FACT-An fatigue subscale (epoetin alfa, 17.5%; BSC, -0.9%; p =.003) and nonfatigue subscale (epoetin alfa, 8.8%; BSC, 0.2%; p =.008). Similar results were observed with the CLAS. Hemoglobin concentrations >12 g/dl were more common with epoetin alfa (62.0%) than with BSC (27.6%). Tumor response, ECOG PS score, 12-month survival rate, and the incidence of serious treatmentemergent adverse events were similar between groups. Conclusion. Early intervention with epoetin alfa was well tolerated and improved anemia-related PROs in patients with breast cancer receiving myelotoxic chemotherapy. © AlphaMed Press.

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