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We previously showed a prolonged inhibition of current-induced vasodilation (CIV) after a single oral high dose of aspirin. In this study, we tested the hypothesis of platelet involvement in CIV. Nine healthy volunteers took 75 mg aspirin/day, 98 mg of clopidogrel bisulfate/day, or placebo for 4 days. CIV was induced by two consecutive 1-min anodal current applications (0.08 mA/[cm.sup.2]) through deionized water with a 10-min interval. CIV was measured with laser Doppler flowmetry and expressed as a percentage of baseline cutaneous vascular conductance: %[C.sub.b]. In a second experiment in 10 volunteers, aspirin and placebo were given as in experiment 1, but a 26-h delay from the last aspirin intake elapsed before ACh iontophoresis and postocclusive hyperemia were studied in parallel to CIV. In experiment 1, the means [+ or -] SE amplitude of CIV was 822 [+ or -] 314, 313 [+ or -] 144, and 746 [+ or -] 397% [C.sub.b] with placebo, aspirin (P < 0.05 from placebo and clopidogrel), and clopidogrel (NS from placebo), respectively. In experiment 2, CIV impairment with aspirin was confirmed: CIV amplitudes were 300 [+ or -] 99, and 916 [+ or -] 528%[C.sub.b] under aspirin and placebo, respectively (P < 0.05), whereas vasodilation to ACh iontophoresis (322 [+ or -] 74 and 365 [+ or -] 104%Cb) and peak postocclusive hyperemia (491 [+ or -] 137 and 661 [+ or -] 248%Cb) were not different between aspirin and placebo, respectively. Low-dose aspirin, even 26 h after oral administration, impairs CIV, while ACh-mediated vasodilation and postocclusive hyperemia are preserved. If platelets are involved in the neurovascular mechanism triggered by galvanic current application in humans, it is likely to occur through the cyclooxygenase but not the ADP pathway. microcirculation; axon reflex; platelets; skin

We previously reported that forearm vasodilation to a delivered all-at-once over 5 min or a 1-min repeated monopolar anodal 0.10-mA current application is aspirin sensitive and that a single high-dose aspirin exerts a long-lived effect in the former case. We hypothesized that 1) in the latter case, the effect of aspirin would also be long lived and 2) the time required to resupply nerve endings with unblocked cyclooxygenase through axonal transport could explain this phenomenon. We studied the time course for the recovery of vasodilation to repeated current application after placebo or 1-g aspirin treatment. We then searched for a difference at a proximal vs. distal site in the recovery of the response. Aspirin abolished current-induced vasodilation at 2 h, 10 h, and 3 days, with a progressive recovery thereafter, but no difference between distal and proximal site was observed for the recovery of the response. This suggests that, although neural cyclooxygenase could participate in the response, the time course of aspirin inhibition of current-induced cutaneous vasodilation is not due to the time required through neural transport to resupply nerve endings with unblocked proteins. skin blood flow; laser Doppler; prostaglandin; iontophoresis; axonal transport

Assumed to rely on an axon reflex, the current-induced vasodilation (CIV) interferes with the microvascular response to iontophoretic drug delivery. Mechanisms resulting in CIV are likely different at the anode and at the cathode. While studies have been conducted to understand anodal CIV, little information is available on cathodal CIV. The present study investigates CIV observed following 0.1-mA cathodal applications on forearms of healthy volunteers and the possible mechanisms involved. Results are expressed in percentage of the cutaneous heat-induced maximal vascular conductance [%MVC (means ± SE)]. 1) The amplitude of CIV was proportional to the duration of cathodal currents for periods of «1 min: r = 0.99. 2) Two current applications of 10 s, with 10-min interstimulation interval, induced a higher peak value of CIV (79.1 ± 8.6% MVC) than the one obtained with all-at-once 20-s current application (39.5 ± 4.3% MVC, P « 0.05). This amplified vascular response due to segmental application was observed for all tested interstimulation intervals (up to 40 min). 3) Two hours and 3 days following pretreatment with 1-g oral aspirin, the CIV observed following cathodal application, as well as the difference of cathodal CIV amplitude between all-at-once and segmented applications, were reduced. These findings suggest a role of prostaglandins, not only released from endothelial or smooth muscle cells, as direct vasodilator and/or as a sensitizer. Thus aspirin pretreatment could be used to decrease CIV resulting from all-at-once and repeated cathodal application and facilitate the study of the specific vascular effect induced by the drug delivered. [ABSTRACT FROM AUTHOR]

Objectives: The present study examined the relationship between medical student fatigue with psychological variables: emotional intelligence (EI), sense of coherence (SoC) (comprehensibility, manageability, and meaningfulness), quality of life (QoL), stress, and satisfaction with studying medicine., Material and Methods: The sample consisted of 566 medical students from the Medical University of Gdańsk, Poland. The instruments used were the Chalder Fatigue Scale , Schutte Self Report Emotional Intelligence Test , Sense of Coherence Questionnaire , and a questionnaire designed by the authors, comprised questions relating to the quality of life, stress levels, and satisfaction with studying medicine., Results: The results show that fatigue was negatively related to the ability to use emotions effectively in the management of one's activities (EI), 1 aspect of SoC - a level of comprehensibility, QoL, and satisfaction with studying medicine. Fatigue is positively related to the ability to recognize, understand, and control emotions (EI) and stress connected with studying medicine., Conclusions: The outcomes of the study afford a better understanding of the relation- ship between selected variables in the field of individual differences in the context of fatigue in the medical student population. It may help medical educators and authorities to have a better understanding of the phenomenon of building resilience and increasing abilities to cope with the negative effects of chronic stress such as fatigue in the population of medical students. Early recognition of specific psychological features in medical stu- dents, such as misunderstanding emotions and their perception of environments as unstructured, would make it possible to prepare early support and development programmes. Int J Occup Med Environ Health. 2023;36(4):517-25., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Objectives: The purpose of the study was to investigate the relation between system values during medical education and styles of success in the medical career., Material and Methods: The participants were first examined when they applied to the medical school. Questionnaires were given to these students each academic year. Medical doctors who had participated in the first phase of the study completed a questionnaire 4 years after their graduation, too. The baseline questionnaire measured the system values. The follow-up questionnaire included measures of quality of life, work stress and burnout, satisfaction with medicine as a career and professional competency., Results: The identified 3 groups of students representing 3 types of careers had been different regarding their preferred terminal values and instrumental values. Out of 3 groups, 2 presented a high risk of burnout. What is more the life goals (terminal values) are relatively stable, but preferable modes of behavior (instrumental values) are likely to change. The most important differences between students who may suffer from burnout later as doctors and those who are at a lower risk are e.g., family security, freedom, happiness, mature love, self-respect, social recognition and wisdom., Conclusions: The Rokeach Value Survey may be applied to identify specific tendencies in the development of medical career. The obtained results may be used by the medical school admission officers as well as resident selection committees in order to identify candidates who may be at risk of professional difficulties. Authors can identify during medical education which student will be at risk of professional burnout after studies. Thus there could be a selection of interventions directed toward differentiated groups of students, e.g.: supplying them with proper coping vs. guiding them, to increase life satisfaction and productivity. Int J Occup Med Environ Health 2018;31(6):823-835., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: The goal of this paper is to verify the correlations between adaptive and maladaptive perfectionism and the selected demographic and job characteristics vs. professional burnout among medical laboratory scientists in Poland., Material and Methods: The study group consisted of 166 laboratory scientists. The Polish Adaptive and Maladaptive Perfectionism Questionnaire (Szczucka) was used for testing perfectionism. The Oldenburg Burnout Inventory was used for examining burnout syndrome., Results: Adaptive perfectionism was positively and maladaptive perfectionism was negatively correlated with both aspects of professional burnout: the disengagement from work and exhaustion. What is more, maladaptive perfectionism was correlated negatively with age and work experience. People in relationships have a higher level of disengagement and a higher level of exhaustion than single ones. The results of hierarchical regression analyses have revealed, after having controlled selected demographic and job factors, that a significant predictor of disengagement is the high level of adaptive perfectionism and low level of maladaptive perfectionism. In addition, a significant predictor of high level of exhaustion is the low level of maladaptive perfectionism., Conclusions: Professional burnout among medical laboratory scientists is of a specific nature. The "healthier" perfectionism they reveal, the higher level of burnout they present. In this profession, lower risk of burnout is represented by those who are characterized by the lack of confidence in the quality of their actions and a negative reaction to their own imperfections associated with imposed social obligation to be perfect. The individuals pursuing their internal high standards experience burnout faster. Med Pr 2018;69(3):253-260., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

The goal of the paper is to describe the extent to which medical students and professionals are vulnerable to extreme stress. A select review of existing literature on this area has been undertaken, using the English-language online databases EBSCO, Medline and PubMed. The search has identified 36 citations relating to 6324 medical students and 28,285 medical staff (physicians, residents, nurses). The review indicates that merely beginning medical studies is a risk factor for stress, and that medical professionals, who are vulnerable to extreme work stress, say that they do not receive enough support from their co-workers. They are also often notably impulsive, introverted, neurotic and perfectionist, with low emotional intelligence and agreeableness, as well as low and external locus of control. Additionally, from longitudinal studies we have been able to identify psychological factors underpinning admission to a medical university that may be useful for predicting future stress in medical career. The results of this study may be taken into account when organizing psychological intervention programs targeted at educating future medical professionals. It seems that early identification of people at risk could reduce the impact of stress related to medical career and enhance the somatic and mental health of medical professionals., (Copyright 27 Mar, 2018 Equinox Publishing.)

Background: The stress associated with the physician's work is generally acknowledged and is related to well-being and life satisfaction. The presented study was designed to extract the role of coping strategies in identifying differentiated styles of success in a medical career during medical education., Methods: The participants were examined when they applied to medical school and each subsequent academic year. The final study took place four years after graduation. The baseline questionnaire measured coping strategies. The follow-up questionnaire consisted of measures of: quality of life, work stress and burnout, satisfaction with medicine as a career, and professional competency., Results: Based on coping strategies assessed during admission and preclinical years of medical study, some aspects of success in the participants' future medical career can be predicted. Students who take action and deal directly with a problem, neither accept resignation, nor reduce tension by expressing feelings would most probably resist future burnout. However, despite the fact that they obtain the highest quality of life or earn the highest income they would be, at the same time, the least satisfied with chosen career, as well as being more likely to be characterised by a low level of competence., Conclusions: Assessment of coping strategies at the beginning of medical education could be taken into consideration as an instrument to diagnose a specific trend in physicians' career development.

Background: Sense of coherence is related to well-being, stress and life satisfaction among medical students and physicians. The purpose of the study was to investigate relation between sense of coherence during medical education and styles of success in the medical career., Methods: The participants were first examined when they applied to medical school in 1999. Questionnaires were given to these students each academic year from 2000 to 2005. Also, 54 medical doctors who had participated in the first phase of the study completed a questionnaire in 2009, four years after graduation. The baseline questionnaire measured the sense of coherence. The follow-up questionnaire included measures of quality of life, work stress and burnout, satisfaction with medicine as a career, and professional competency., Results: Medical students with the highest sense of coherence later have the highest quality of life and income, and are the least overwhelmed by work stress, but they also show the least satisfaction with medicine as a career and a low level of professional competence., Conclusions: Antonovsky's SOC-29 questionnaire can be used to identify specific tendencies in the development of the medical career. Our results may be useful to medical school admissions officers and resident selection committees, in order to identify candidates at risk for failure.

The eukaryotic initiation factor 4E-binding protein-2 (4E-BP2) is a repressor of cap-dependent mRNA translation and a major downstream effector of the mammalian target of rapamycin (mTOR) implicated in hippocampal long-term synaptic plasticity and memory. Yet, synaptic mechanisms regulated by 4E-BP2 translational repression remain unknown. Combining knock-out mice, whole-cell recordings, spine analysis, and translation profiling, we found that 4E-BP2 deletion selectively upregulated synthesis of glutamate receptor subunits GluA1 and GluA2, facilitating AMPA receptor (AMPAR)-mediated synaptic transmission and affecting translation-dependent chemically induced late long-term potentiation (cL-LTP). In 4E-BP2 knock-out (4E-BP2(-/-)) mice, evoked and miniature EPSCs were increased, an effect mimicked by short-hairpin RNA knockdown of 4E-BP2 in wild-type mice, indicating that 4E-BP2 level regulates basal transmission at mature hippocampal AMPAR-containing synapses. Remarkably, in 4E-BP2(-/-) mice, the AMPA to NMDA receptor (NMDAR) EPSC ratio was increased, without affecting NMDAR-mediated EPSCs. The enhanced AMPAR function concurred with increased spine density and decreased length resulting from greater proportion of regular spines and less filopodia in 4E-BP2(-/-) mice. Polysome profiling revealed that translation of GluA1 and GluA2 subunits, but not GluN1 or GluN2A/B, was selectively increased in 4E-BP2(-/-) hippocampi, consistent with unaltered I-V relation of EPSCs mediated by GluA1/GluA2 heteromers. Finally, translation-dependent cL-LTP of unitary EPSCs was also affected in 4E-BP2(-/-) mice, lowering induction threshold and removing mTOR signaling requirement while impairing induction by normal stimulation. Thus, translational control through 4E-BP2 represents a unique mechanism for selective regulation of AMPAR synthesis, synaptic function, and long-term plasticity, important for hippocampal-dependent memory processes.

Aim: Our study investigated the styles of success in the medical career in young physicians, in comparison with the same subjects examined 4-10 years earlier., Methods: The participants were first studied when they applied to the medical university (1999). Questionnaires were sent to all students each year (2000-2005). Fifty-four medical doctors participated in the first phase of the study completed a questionnaire four years after graduation. The current questionnaire included measures of burnout, satisfaction with medicine as a career, quality of life (QOL) and postgraduate examination results. Previous questionnaires had included measures of academic achievement, depression and anxiety., Results: We can describe three different styles of success, which can be predicted during medical education. Physicians with the best professional competence have the lowest income. However, physicians with the lowest professional competence gain the highest income. Those with the highest QOL (general well-being and life satisfaction) have the lowest professional stress and vulnerability to burnout. Anxiety and academic achievement (during the second and fourth year of study) are the significant predictors of specific style belonging., Conclusions: Our results may be useful to medical school admissions and resident selection committees to identify candidates at risk for less satisfaction or less competence.

The two members of the Staufen family of RNA-binding proteins, Stau1 and Stau2, are present in distinct ribonucleoprotein complexes and associate with different mRNAs. Stau1 is required for protein synthesis-dependent long-term potentiation (L-LTP) in hippocampal pyramidal cells. However, the role of Stau2 in synaptic plasticity remains unexplored. We found that unlike Stau1, Stau2 is not required for L-LTP. In contrast, Stau2, but not Stau1, is necessary for DHPG-induced protein synthesis-dependent long-term depression (mGluR-LTD). While Stau2 is involved in early development of spines, its down-regulation does not alter spine morphology or spontaneous miniature synaptic activity in older cultures where LTD occurs. In addition, Stau2, but not Stau1, knockdown reduces the dendritic localization of Map1b mRNA, a specific transcript involved in mGluR-LTD. Moreover, mGluR stimulation with DHPG induces Map1b, but not Map2, mRNA dissociation from mRNA granules containing Stau2 and the ribosomal protein P0. This dissociation was not observed in cells in which Stau2 was depleted. Finally, Stau2 knockdown reduces basal Map1b protein expression in dendrites and prevents DHPG-induced increases in dendritic Map1b protein level. We suggest a role for Stau2 in the generation and regulation of Map1b mRNA containing granules that are required for mGluR-LTD.

Background: Systemic review of predictors of success in medical career is an important tool to recognize the indicators of proper training., Aim: To determine psychological factors that predict success in a medical career. The success is defined as professional competence, satisfaction with medicine as a career, occupational stress and burnout and quality of life (QOF)., Methods: Part I (1999-2005), medical students were examined each subsequent year, beginning with admission. Assessment included academic achievement (high school final examination results, entrance exam results, academic results during medical school) and psychological characteristics (sense of coherence (SOC), depression, anxiety, coping styles, value system and need for social approval). Part II (2008-2009), the same participants completed an Internet survey 4 years after graduation. Results of the postgraduate medical exam were taken under consideration., Results: Academic achievement predicts only professional competence. Coping styles are significant indicators of satisfaction with medicine as a career. SOC, while assessed with anxiety and depression during studies, enabled us to recognize future QOF of medical graduates. Professional stress is not predictable to such an extent as other success indicators., Conclusions: There are significant psychological qualities useful to draw the outline of the future job and life performance of medical graduates.

Hebbian long-term potentiation (LTP) develops at specific synapses onto hippocampal CA1 oriens/alveus interneurons (OA-INs), suggesting selective regulation of distinct input pathways. Afferent-specific properties at interneuron synapses have been characterized extensively in CA3 stratum lucidum cells, but given interneuron diversity these rules of transmission and plasticity may not hold in other interneuron types. Here, we used paired recordings and demonstrate that CA2/3 pyramidal cell (PC) feedforward and CA1 PC feedback synapses onto OA-INs show distinct AMPA receptor rectification and Ca(2+) permeability, short-term plasticity and mGluR2/3-mediated inhibition. Only feedback synapses undergo Hebbian LTP. OA-IN firing during repeated synaptic stimulation displays onset-transient or late-persistent responses consistent with activation of feedforward and feedback inputs, respectively. Input-output functions are preserved after theta-burst stimulation, but late-persistent responses selectively show mGluR1-dependent long-term increases. Thus, cell type- and afferent-specific rules of transmission and plasticity underlie distinct OA-IN input-output functions, providing selective long-term regulation in feedback inhibitory networks.

Although it is known that noradrenaline (NA) powerfully controls spinal motor networks, few data are available regarding the noradrenergic (NAergic) modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of NAergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of NA and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. NA increases the motoneuron excitability partly via the inhibition of a K(IR) like current. Methoxamine (alpha(1)), clonidine (alpha(2)) and isoproterenol (beta) differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (alpha(1)), yohimbine (alpha(2)) and propranolol (beta). We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by NA, methoxamine and isoproterenol. On the other hand, NA, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic alpha(1) and beta receptor activation. Our data thus show that the NAergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord.

In the present study, we investigated the modulation of short-term depression (STD) at synapses between sensory afferents and rat motoneurons by serotonin, dopamine and noradrenaline. STD was elicited with trains of 15 stimuli at 1, 5 and 10 Hz and investigated using whole-cell voltage-clamp recordings from identified motoneurons in the neonatal rat spinal cord in vitro. STD was differentially modulated by the amines. Dopamine was effective at all stimulation frequencies, whereas serotonin affected STD only during 5 and 10 Hz stimulus trains and noradrenaline during 1 and 5 Hz trains. Dopamine and serotonin homogenized the degree of depression observed with the different stimulation modalities, in contrast to noradrenaline, which amplified the rate differences. The different modulatory profiles observed with the amines were partly due to GABAergic interneuron activity. In the presence of GABA(A) and GABA(B) receptor antagonists, the rate and/or kinetics of STD did not vary with the stimulation frequency in contrast to the control condition, and noradrenaline failed to alter either synaptic amplitude or STD, suggesting indirect actions. Dopamine and serotonin strongly decreased STD and converted depression to facilitation at 5 and 10 Hz during the blockade of the GABAergic receptors in 50% of the neurons tested. Altogether, these results show that STD expressed at sensorimotor synapses in the neonatal rat not only is a function of the frequency of afferent firing but also closely depends on the neuromodulatory state of these connections, with a major contribution from GABAergic transmission.

We study the dynamics of skin laser Doppler flowmetry signals giving a peripheral view of the cardiovascular system. The analysis of Hölder exponents reveals that the experimental signals are weakly multifractal for young healthy subjects at rest. We implement the same analysis on data generated by a standard theoretical model of the cardiovascular system based on nonlinear coupled oscillators with linear couplings and fluctuations. We show that the theoretical model, although it captures basic features of the dynamics, is not complex enough to reflect the multifractal irregularities of microvascular mechanisms.

There is now strong evidence that an endothelium-derived hyperpolarizing factor (EDHF), other than nitric oxide (NO) or prostaglandin (PG), exists for dilating arteries and arterioles. In vitro studies on isolated vessels pointed out a role for EDHF as a back-up mechanism when the NO pathway is impaired, but there was a lack of in vivo studies showing a functional role for EDHF. Ageing has pronounced effects on vascular function and particularly on endothelium-dependent relaxation, providing a novel situation in which to assess the contributions of EDHF. The purpose of the present study was thus to determine if, in vivo, there was a functional role for EDHF as a back-up mechanism in the cutaneous microcirculation in the ageing process. We investigated in vivo the contribution of each endothelial factor (NO, PG and EDHF) in the cutaneous vasodilatation induced by iontophoretic delivery of acetylcholine and local pressure application in young adult (6-7 months) and old (22-25 months) mice, using pharmacological inhibitors. The cutaneous vasodilator responses induced by acetylcholine and local pressure application were dependent upon NO and PG pathways in young adult mice, whereas they were EDHF-dependent in old mice. EDHF appears to serve as a back-up mechanism when ageing reaches pathological states in terms of the ability for NO and PG to relax cutaneous microvessels, allowing for persistent cutaneous vasodilatator responses in old mice. However, as a back-up mechanism, EDHF did not completely restore cutaneous vasodilatation, since endothelial responses were reduced in old mice compared to young adult mice.

Laser Doppler flowmetry signals give information about many physiological activities of the cardiovascular system. The activities manifest themselves in rhythmic cycles. In order to explore these activities during the reactive hyperemia phenomenon, a novel time-frequency method, called the S-transform, based on a scalable Gaussian wavelet, is applied. The goal is to have a deeper understanding of reactive hyperemia. This paper focuses on the evaluation of the different activities between a rest signal and an hyperemia signal, both acquired simultaneously on the two forearms of healthy subjects. The results show that after the release of the occlusion, the myogenic, neurogenic, and endothelial related activities clearly increase on the forearm where the occlusion took place. Then, they return progressively to their basal level. However, on the rest forearm, no increase is noted for the three activities. The mechanisms that take place during reactive hyperemia are, therefore, local. The S-transform proves to be a suited time-frequency method, in order to analyze laser Doppler signal underlying mechanisms.

Pressure-induced vasodilation, a neurovascular mechanism relying on the interaction between mechanosensitive C-fibers and vessels, allows skin blood flow to increase in response to locally nonnociceptive applied pressure that in turn may protect against pressure ulcers. We expected that severe neuropathy would dramatically affect pressure-induced vasodilation in diabetic mice, and we aimed to determine whether pressure-induced vasodilation alteration could be reversed in 8-week diabetic mice. Control and diabetic mice received no treatment or sorbinil, an aldose reductase inhibitor, or alagebrium, an advanced glycation end product breaker, the last 2 weeks of diabetes. Laser Doppler flowmetry was used to evaluate pressure-induced vasodilation and endothelium-dependent vasodilation after iontophoretic delivery of acetylcholine (ACh). We assessed the nervous function with measurements of motor nerve conduction velocity (MNCV) as well as the C-fiber-mediated nociception threshold. Pressure-induced vasodilation, endothelial response, C-fiber threshold, and MNCV were all altered in 8-week diabetic mice. None of the treatments had a significant effect on MNCV. Although sorbinil and alagebrium both restored ACh-dependent vasodilation, sorbinil was the sole treatment to restore the C-fiber threshold as well as pressure-induced vasodilation development. Therefore, the inhibition of aldose reductase pathway by sorbinil improved vascular and C-fiber functions that allow pressure-induced vasodilation restoration that could limit neuropathic diabetic cutaneous pressure ulcers.

Conventional signal processing typically involves frequency selective techniques which are highly inadequate for nonstationary signals. In this paper, we present an approach to perform time-frequency selective processing of laser Doppler flowmetry (LDF) signals using the S-transform. The approach is motivated by the excellent localization, in both time and frequency, afforded by the wavelet basis functions. Suitably chosen Gaussian wavelet functions are used to characterize the subspace of signals that have a given localized time-frequency support, thus enabling a time-frequency partitioning of signals. In this paper, the goal is to study the influence of various pharmacological substances taken by the oral way (celecobix (Celebrex), indomethacin (Indocid) and placebo) on the physiological activity behaviour. The results show that no statistical differences are observed in the energy computed from the time-frequency representation of LDF signals, for the myogenic, neurogenic and endothelial related metabolic activities between Celebrex and placebo, and Indocid and placebo. The work therefore proves that these drugs do not affect these physiological activities. For future physiological studies, there will therefore be no need to exclude patients having taken cyclo-oxygenase 1 inhibitions.

It is generally acknowledged that cutaneous vasodilatation in response to monopolar galvanic current application would result from an axon reflex in primary afferent fibers and the neurogenic inflammation resulting from neuropeptide release. Previous studies suggested participation of prostaglandin (PG) in anodal current-induced cutaneous vasodilatation. Thus the inducible cyclooxygenase (COX) isoform (COX-2), assumed to play a key role in inflammation, should be involved in the synthesis of the PG that is released. Skin blood flow (SkBF) variations induced by 5 min of 0.1-mA monopolar anodal current application were evaluated with laser-Doppler flowmetry on the forearm of healthy volunteers treated with indomethacin (COX-1 and COX-2 inhibitor), celecoxib (COX-2 inhibitor), or placebo. SkBF was indexed as cutaneous vascular conductance (CVC), expressed as percentage of heat-induced maximal CVC (%MVC). Urinalyses were performed to test celecoxib treatment efficiency. No difference was found in CVC values at rest: 14.3 +/- 4.0, 11.9 +/- 3.2, and 10.9 +/- 2.0% MVC after indomethacin, celecoxib, and placebo treatment, respectively. At 10 min after the onset of anodal current application, CVC values were 22.2 +/- 4.9% MVC (not significantly different from rest) with indomethacin, 85.7 +/- 15.3% MVC (P < 0.001 vs. rest) with celecoxib, and 70.4 +/- 13.1% MVC (P < 0.001 vs. rest) with placebo. Celecoxib significantly depressed the urinary prostacyclin metabolite 6-keto-PGF(1alpha) (P < 0.05 vs. placebo). Indomethacin, but not celecoxib, significantly inhibited the anodal current-induced vasodilatation. Thus, although they are assumed to result from an axon reflex in primary afferent fibers and neurogenic inflammation, these results suggest that the early anodal current-induced vasodilatation is mainly dependent on COX-1-induced PG synthesis.

When using iontophoresis, the 'non-specific' vasodilatation (NSV) that is observed as a result of C-fibre excitation is generally attributed to the local accumulation of protons under the anode. NSV following prolonged 100-microA anodal current application only appears after the current is stopped. Break excitation alone does not explain the delayed onset of this vasodilatation. We hypothesised that this delay could result from an anodal block and thus, that a minimal intensity would be required to achieve hyperpolarisation of primary afferent fibres (mainly C-fibres). Using laser Doppler flowmetry, cutaneous blood flow was recorded in the forearms of 8 healthy volunteers 2 min before current application, during the application and 20 min after stopping the monopolar anodal current. In protocol 1, after 2.5 min of current application at an intensity of 100 microA, the intensity was abruptly decreased to 0-80 microA for a second 2.5-min period. The onset of vasodilatation was only delayed at intensities >30 microA during this second period. In protocol 2, re-application of the current after a 50-second interruption (expected to allow for the occurrence of an axon reflex) did not interfere with the onset of vasodilatation. Thus: (1) the minimal intensity interfering with the axon reflex is far lower than that reported for C-fibre blockade in isolated nerves; (2) the results suggest that current application does not directly interfere with the vasodilator mechanisms induced by the axon reflex at the level of smooth muscle cells., (Copyright 2004 S. Karger AG, Basel)

1 Acetyl salicyclic acid (aspirin) irreversibly blocks cyclo-oxygenase (COX). This effect is short-lived in endothelial or smooth muscle cells due to resynthesis but long-lived in platelets devoid of synthesis ability. Aspirin blocks the anodal current-induced vasodilatation, suggesting participation by prostaglandin (PG). We analysed the time course of the effect of aspirin as an indirect indicator of the origin of the PG possibly involved in anodal current-induced vasodilatation. 2 In healthy volunteers, vasodilatation, estimated from the peak cutaneous vascular conductance (CVC(peak)), was recorded in the forearm during and in the 20 min following 5 min, 0.10 mA transcutaneous anodal current application, using deionized water as a vehicle. CVC(peak) was normalized to 44 degrees C heat-induced maximal vasodilatation and expressed in per cent values. Experiments were performed before and at 2 and 10 h, 3, 7, 10 and 14 days after blinded 1-g aspirin or placebo treatment. 3 CVC(peak) (mean+/-s.d.mean) after aspirin vs placebo was 13.6+/-14.5 vs 65.0+/-32.1 (P<0.05) 14.7+/-4.2 vs 87.5+/-31.9 (P<0.05), 18.1+/-10.2 vs 71.6+/-26.8 (P<0.05), 42.5+/-23.4 vs 73.3+/-26.8 (non significant, NS), 60.2+/-24.3 vs 75.2+/-26.9 (NS), 52.1+/-18.5 vs 67.9+/-32.1 (NS) at 2 and 10 h and at days 3, 7, 10 and 14 respectively. 4 Aspirin inhibition of anodal current-induced vasodilatation persists long after endothelial and smooth muscle cyclo-oxygenases are assumed to be restored. This suggests that the PG involved in this response are not endothelial- or smooth muscle-derived. The underlying mechanism of this unexpected long-lived inhibition of vasodilatation by single high dose aspirin remains to be studied.