Pharmacokinetic and pharmacodynamic parameters were established for the enantiomers of the 2-arylpropionic acid (APA) nonsteroidal anti-inflammatory drug (NSAID), ketoprofen (KTP). Each enantiomer was administered separately (1.5 mg/kg) and in a racemic mixture (3 mg/kg) intravenously (i.v.) to a group of eight sheep in a four-way, four-period cross-over study using a tissue cage model of inflammation. Plasma disposition of each KTP enantiomer was similar following separate administration of the pure compounds compared to administration of the racemic mixture. S(+)KTP volume of distribution (Vd(area)) was higher and clearance (ClB) faster than those of R(-)KTP. S(+) and R(-)KTP achieved relatively low concentrations in exudate and transudate. Unidirectional limited chiral inversion of R(-) to S(+)KTP was demonstrated. After R(-)KTP administration S(+)KTP was detected in plasma, but not in either exudate or transudate. Pharmacokinetic/pharmacodynamic (PK/PD) modelling of the data could not be undertaken following R(-)KTP administration because of chiral inversion to S(+)KTP, but the pharmacodynamic parameters, calculated maximum effect (Emax), concentration producing 50% effect (EC50), Hill's coefficient (N), rate constant of elimination of drug effect from the compartment (KeO) and mean equilibration half-life (t1/2KeO) were determined for S(+)KTP after administration of the racemic mixture as well as the pure compound.

Background: Work-related stress is a potential cardiovascular risk factor, but the underlying mechanism is not fully explained. The autonomic nervous system control of cardiac function might play a specific role; therefore, monitoring the QT interval in the electrocardiogram can highlight an autonomic imbalance induced by occupational stressors. The aim of our study was to explore the QT interval parameters as early indicators of imbalance of the autonomic cardiac function in relation to work-related stress. Methods: During 2015–2016 annual workplace health surveillance, we measured work-related stress in 484 workers of a logistic support company using the Health and Safety Executive (HSE) tool. We assessed the frequency-corrected QT (QTc) interval and the QT index (QTi) on the electrocardiogram of each participant, and collected demographic and clinical data. We compared the QTc values by the four Karasek’s categories (active/passive jobs, low/high strain job), and by job support (present/lacking), and conducted multivariate analysis to adjust for possible confounders. Results: The results of the multivariate regression analysis showed that QTc was prolonged among workers operating at a specific site where stress level was found to be elevated. Regular physical activity showed a beneficial effect against QTc prolongation. We did not observe an effect on QTc length by the cross-combined Karasek’s categories of job control, job demand, and job support. Conclusions: Our study suggests subclinical effects of conditions associated with work-related stress on the autonomic regulation of cardiac function. Further research is warranted to elucidate the combined effect of work organization and lifestyle factors on autonomic cardiac function.

The pathophysiology of exercise-induced hypoxaemia in elite athletes is still unclear but several studies indicate that a diffusion limitation, which could be explained by an interstitial pulmonary oedema, is a major contributing factor. Stress failure would induce a haemodynamical interstitial oedema with inflammatory reaction and release of mediators like histamine. Histamine release was found to be correlated with the hypoxaemia in elite athletes. If stress failure is involved, inhalation of pulmonary vasodilatators such as nitric oxide during exercise in athletes should induce an inhibition of the histamine release and a reversal of the hypoxaemia. Nine male endurance-trained young athletes performed two randomized exercise tests: one without and the other with 15 p.p.m. of inhaled NO. Measurements of histamine release and arterial blood gas analysis were performed at rest and at 50, 75 and 100% VO2max. At rest, inhaled NO induced a decrease in PaO2 and an increase in (Ai-a)DO2 suggesting increased perfusion of units with low V(A)/Q. During exercise, NO inhalation suppressed the histamine release observed without NO and induced a moderation in the decrease in PaO2 and the increase in (Ai-a)DO2 observed between 75 and 100% of VO2max (P < 0.005). In conclusion, this study showed that NO inhalation inhibited exercise-induced histamine release in highly trained athletes, but we were unable to confirm the suppression of exercise-induced hypoxaemia (EIH). An unexpected result was that inhaled NO seemed to have a marked effect on arterial oxygenation in highly trained-athletes, by disturbing gas exchanges.

Abstract

Linear feedback shift registers (LFSRs) are common structures in many application fields, including cryptography, digital broadcasting and communication. Highthroughput requirements need highly parallel implementations, usually accomplished in state of the art system on chips (SoCs) with application specific coprocessors. Although this approach achieves the required performance, it rapidly shows lack of flexibility when those devices are proposed, as an example, for multi-standard modems or for security applications in which run-time update can provide added value. This paper shows the implementation of parallel LFSR-based applications on an embedded adaptive DSP featuring a Pipelined Configurable Gate Array (PiCoGA). With respect to standard embedded FPGAs, pipelined devices usually provide better performance, e.g. in terms of speed, but they commonly show the undeniable drawback of additional design constraints. As a test-case, we consider the implementation of the 32-bit CRC used in the Ethernet standard that achieves on the target architecture up to 25Gbit/sec throughput, with a parallel LFSR processing 128 bit at time, which is comparable to the performance offered by some ASIC devices.