In vitro studies have demonstrated that free fatty acids (FFA) may enhance oxidative stress. In contrast, no in vivo studies have addressed such a relationship. This four-part study aims at investigating the association between FFA and oxidative stress in healthy volunteers. The following experimental procedures were carried out: 1) determination and simple correlations among fasting plasma FFA, glucose, insulin, plasma thiobarbituric acid-reactive substance (TBARS), the ratio of reduced glutathione (GSH) to oxidized GSH, and lipid hydroperoxide (n = 30); 2) time-dependent effect of FFA on plasma TBARS concentrations and GSH/oxidized GSH ratio (n = 10); 3) dose-dependent effect of FFA on plasma TBARS concentrations (n = 9); and 4) relationship among plasma FFA concentrations, plasma TBARS concentrations, and insulin action (n = 11). The results demonstrate that fasting plasma FFA concentrations correlated with fasting plasma TBARS concentrations (r = 0.65; P < 0.001) and lipid hydroperoxide (r = 0.79; P < 0.001). The correlation between plasma FFA and TBARS remained significant even after adjustment for age, sex, body mass index, and fasting and 2-h plasma glucose concentrations (r = 0.43; P < 0.01). In the time-dependent study, plasma TBARS concentrations increased with the rise in plasma FFA concentrations. In the dose-response study, a progressive increase in fasting plasma FFA concentrations was achieved by varying the Intralipid infusion rate, which also caused plasma TBARS concentrations to increase progressively until they reached a plateau between the last two infusion rates (0.3 and 0.4 mL/min). A euglycemic hyperinsulinemic glucose clamp (insulin infusion rate, 10.2 pmol/kg min for 360 min) was also performed. Simultaneous 10% Intralipid (0.4 mL/min) infusion significantly enhanced plasma TBARS concentrations and inhibited insulin-stimulated whole body glucose disposal (WBGD). GSH infusion (15 mg/min for 360 min) had opposite effects on plasma TBARS concentrations and WBGD. A combined infusion of 10% Intralipid and GSH was associated with a stimulation of WBGD with a magnitude midway between that of 10% Intralipid and GSH infused separately. In conclusion, fasting plasma FFA seems to enhances oxidative stress, which might contribute to the disruptive effects of plasma FFA on insulin-mediated glucose uptake.

A controlled, parallel group study of the analgesic efficacy of flupirtine maleate, was compared against diclofenac sodium in 40 orthopaedic patients with post-operative pain. Clinically, both drugs were of equal analgesic efficacy. A mathematical model has been developed, however, to evaluate the speed, intensity and duration of the analgesic effect and provides data which significantly favour flupirtine maleate in the treatment of these patients.

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A box model to simulate mass transfer inside deep street canyons and with atmospheric flow above is introduced and discussed. Two ideal deep street canyons with aspect ratios of 3 and 5 (the aspect ratio being the ratio between building height and street width H/W ) are considered. This range of aspect ratios, found in many densely populated historical centres in Mediterranean cities as well as in other cities around the world, potentially creates high air pollutant concentration levels. Our model is based on a combination of analytical solutions and computation fluid dynamics (CFD) simulations using carbon monoxide (CO) as a tracer pollutant. The analytical part of the model is based on mass transfer velocity concepts while CFD simulations are used both for a preliminary validation of the physical hypothesis underlying the model (steady-state simulations) and to evaluate the concentration pattern with time (transient or wash-out simulations). Wash-out simulation curves were fitted by model curves, and mass transfer velocities were evaluated through a best-fitting procedure. Upon introducing into the model the contribution of traffic-produced turbulence, the modelled CO concentration levels became comparable with those obtained in real-world monitoring campaigns. The mass transfer rate between the canyon and the above atmosphere was then expressed in terms of an overall mass transfer velocity, which directly allows the evaluation of the mass transfer rate between the bottom volume of the canyon (pedestrian level) with the above atmosphere. Overall mass transfer velocities are reported as a function of the operating conditions studied (H/W = 3-5 and wind speeds = 2-8 m s −1 ). Finally, a simple expression is reported for determining pollutant concentrations at the pedestrian level based on the overall mass transfer velocity defined.

It is not known whether iron depletion before pegylated IFN or combination treatment improves sustained virological response (SVR) rate in patients with chronic hepatitis C, despite its use in clinical practice in this setting. We aimed to investigate whether blood letting improves the efficacy (SVR) and tolerability of PEG-IFNalpha2b + Ribavirin in chronic hepatitis C patients. Patients with chronic hepatitis C and ferritin >100 ng/mL were randomized to: (1) repeated phlebotomies to obtain a ferritin level <50 ng/mL followed by pegylated-Interferon alpha2b + ribavirin (active arm); or (2) pegylated-Interferon alpha2b + ribavirin (control arm). Primary endpoint was SVR rate, secondary endpoint was frequency of clinical and laboratory grade 3-4 adverse events. Thirty-three patients were enrolled in the study (19 in active arm, 14 in control arm). The 19 patients in the active arm underwent a median of 5 phlebotomies (range: 1-9) to achieve the targeted ferritin (<50 ng/mL). Phlebotomies significantly reduced ferritin, iron, transferrin saturation, aspartate aminotransferase, alanine aminotransferase, and hemoglobin levels. Platelet count significantly increased, whereas HCV-RNA levels remained unchanged. After antiviral therapy overall SVR was 31.6% in active arm and 21.4% in control arm (P = 0.698). Considering only the 18 patients who were naive to antiviral therapy, SVR was 60% in active arm versus 25% in control arm (P = 0.188). Tolerability, drug dose reduction or withdrawal were similar in the two arms. In conclusion phlebotomies do not increase the overall efficacy of antiviral therapy. However, the strong trend to higher SVR in naive patients undergoing phlebotomies warrants further investigation.