The psychophysiological stress response in psoriasis and rheumatoid arthritis.

BACKGROUND: Psychosocial stress can be a risk factor for the maintenance and exacerbation of chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis (RA). OBJECTIVES: To gain insight into the specificity of the psychophysiological stress response during chronic inflammation, we assessed autonomic and neuroendocrine responses to stress in different chronic inflammatory diseases. METHODS: Thirty patients with psoriasis (nine women, mean age 58·5 years ± 12·4), 34 patients with RA (16 women, mean age 60·8 years ± 9·2) and 25 healthy controls (16 women, mean age 55·6 years ± 8·7) underwent a standardized psychosocial stress task (Trier Social Stress Test). Salivary levels of α-amylase and cortisol and self-reported tension levels were measured before and after the stress test. RESULTS: The cortisol response to stress was heightened in patients with psoriasis compared with patients with RA and healthy controls, whereas there were no differences in the autonomic and self-reported measures. CONCLUSIONS: The altered neuroendocrine stress response in patients with psoriasis suggests that stressful events might have different physiological consequences for specific patient groups with chronic inflammatory conditions, possibly adversely affecting disease status.

Evaluation of RAD51C as cancer susceptibility gene in a large breast-ovarian cancer patient population referred for genetic testing.

Despite extensive analysis of the BRCA1 and BRCA2 genes, germline mutations are detected in <20% of families with a presumed genetic predisposition for breast and ovarian cancer. Recent literature reported RAD51C as a new breast cancer susceptibility gene. In this study, we report the analysis of 410 patients from 351 unrelated pedigrees. All were referred for genetic testing and we selected families with at least one reported case of ovarian cancer in which BRCA1&2 mutations were previously ruled out. We analyzed the coding exons, intron-exons boundaries, and UTRs of RAD51C. Our mutation analysis did not reveal any unequivocal deleterious mutation. In total 12 unique sequence variations were identified of which two were novel. Our study and others suggest a low prevalence of RAD51C mutations with an exception for some founder populations. This observation is in favor of the rare allele hypothesis in the debate over the nature of the genetic contribution to individual susceptibility to breast and ovarian cancer and further genome-wide studies in high risk families are warranted.

How stress gets under the skin: cortisol and stress reactivity in psoriasis.

BACKGROUND: Psychological stressors might contribute to the severity of chronic inflammatory diseases such as psoriasis by dysregulating hypothalamic-pituitary-adrenal (HPA) axis activity. OBJECTIVES: To evaluate the role of cortisol, a key component of the HPA axis, in reaction to psychological stress in patients with psoriasis. METHODS: Serum cortisol, clinical indicators of disease severity (Psoriasis Area and Severity Index) and self-report measures of daily stressors were measured monthly for 6 months in 62 patients with psoriasis. RESULTS: In addition to the previous findings in this sample showing that peak levels of daily stressors predicted an increase in disease severity a month later, the peak levels of daily stressors were also significantly associated with a lower cortisol level. Moreover, patients who persistently experienced higher levels of daily stressors had lower mean cortisol levels than patients who experienced lower levels of daily stressors. CONCLUSIONS: Results suggest that daily stressors influence disease outcome in patients with psoriasis by affecting cortisol levels at moments of high stress. Furthermore, patients with persistently high levels of stressors seem to have a specific psychophysiological profile of lowered cortisol levels and may be particularly vulnerable to the influence of stressors on their psoriasis.

Role of retinal slip in the prediction of target motion during smooth and saccadic pursuit.

Visual tracking of moving targets requires the combination of smooth pursuit eye movements with catch-up saccades. In primates, catch-up saccades usually take place only during pursuit initiation because pursuit gain is close to unity. This contrasts with the lower and more variable gain of smooth pursuit in cats, where smooth eye movements are intermingled with catch-up saccades during steady-state pursuit. In this paper, we studied in detail the role of retinal slip in the prediction of target motion during smooth and saccadic pursuit in the cat. We found that the typical pattern of pursuit in the cat was a combination of smooth eye movements with saccades. During smooth pursuit initiation, there was a correlation between peak eye acceleration and target velocity. During pursuit maintenance, eye velocity oscillated at approximately 3 Hz around a steady-state value. The average gain of smooth pursuit was approximately 0.5. Trained cats were able to continue pursuing in the absence of a visible target, suggesting a role of the prediction of future target motion in this species. The analysis of catch-up saccades showed that the smooth-pursuit motor command is added to the saccadic command during catch-up saccades and that both position error and retinal slip are taken into account in their programming. The influence of retinal slip on catch-up saccades showed that prediction about future target motion is used in the programming of catch-up saccades. Altogether, these results suggest that pursuit systems in primates and cats are qualitatively similar, with a lower average gain in the cat and that prediction affects both saccades and smooth eye movements during pursuit.

Activity of mesencephalic vertical burst neurons during saccades and smooth pursuit.

The activity of vertical burst neurons (BNs) was recorded in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF-BNs) and in the interstitial nucleus of Cajal (NIC-BNs) in head-restrained cats while performing saccades or smooth pursuit. BNs emitted a high-frequency burst of action potentials before and during vertical saccades. On average, these bursts led saccade onset by 14 +/- 4 ms (mean +/- SD, n = 23), and this value was in the range of latencies ( approximately 5-15 ms) of medium-lead burst neurons (MLBNs). All NIC-BNs (n = 15) had a downward preferred direction, whereas riMLF-BNs showed either a downward (n = 3) or an upward (n = 5) preferred direction. We found significant correlations between saccade and burst parameters in all BNs: vertical amplitude was correlated with the number of spikes, maximum vertical velocity with maximum of the spike density, and saccade duration with burst duration. A correlation was also found between instantaneous vertical velocity and neuronal activity during saccades. During fixation, all riMLF-BNs and approximately 50% of NIC-BNs (7/15) were silent. Among NIC-BNs active during fixation (8/15), only two cells had an activity correlated with the eye position in the orbit. During smooth pursuit, most riMLF-BNs were silent (7/8), but all NIC-BNs showed an activity that was significantly correlated with the eye velocity. This activity was unaltered during temporary disappearance of the visual target, demonstrating that it was not visual in origin. For a given neuron, its ON-direction during smooth pursuit and saccades remained identical. The activity of NIC-BNs during both saccades and smooth pursuit can be described by a nonlinear exponential function using the velocity of the eye as independent variable. We suggest that riMLF-BNs, which were not active during smooth pursuit, are vertical MLBNs responsible for the generation of vertical saccades. Because NIC-BNs discharged during both saccades and pursuit, they cannot be regarded as MLBNs as usually defined. NIC-BNs could, however, be the site of convergence of both the saccadic and smooth pursuit signals at the premotoneuronal level. Alternatively, NIC-BNs could participate in the integration of eye velocity to eye position signals and represent input neurons to a common integrator.

Arterial vasomotion: effect of flow and evidence of nonlinear dynamics.

Vasomotion has been studied on segments of rat mesenteric and femoral arteries perfused in vitro. We have investigated 1) the effect of perfusion flow on the characteristics of vasomotion and 2) the nature and patterns of vasomotion. We have found that perfusion flow is not a control parameter that contributes to the genesis of vasomotion but that it affects, in most cases only slightly, the frequency and amplitude of vasomotion. We have found evidence that vasomotion is low-dimensional chaotic. The correlation dimension ranged between 2 and 4, and the average Lyapunov's coefficient was approximately 0.1. A great variety of vasomotion patterns was observed with features that are typical of nonlinear deterministic systems: regular and irregular vasomotion, quasiperiodicity, period doubling and higher-order periods, intermittency, mixed modes, and bursting activity. Vasomotion patterns appeared occasionally to be highly sensitive to perturbations in perfusion flow, which also supported the existence of nonlinear dynamics. Finally, entrainment (phase locking) was observed when arteries were perfused with oscillatory flow with frequency in the neighborhood of the frequency of vasomotion.

Simplification of the quasiperiodic route to chaos in agonist-induced vasomotion by iterative circle maps.

We have shown that the patterns of vasomotion induced by histamine in isolated rabbit ear resistance arteries can be described in terms of iterative circle maps that model the dynamics of coupled nonlinear oscillators. Cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase pump, consistently transformed chaotic behavior into characteristic periodic oscillations known as mixed-mode responses, which consist of mixtures of large- and small-amplitude excursions and represent frequency-locked states. Quasiperiodicity, which reflects the interaction of oscillators with incommensurate frequencies, was also observed, although in a smaller number of experiments. The patterns of mixed-mode complexes found at different CPA concentrations allowed the derivation of firing numbers, i.e., number of large oscillations/sum of number of small and large oscillations, and the sequences in which they emerged conformed to Farey arithmetic. Two-dimensional return maps derived by Poincaré section of phase space representations of the dynamics were used to compute the mean number of rotations per iteration on the circle, i.e., the winding number. Plots of winding number against firing number revealed a devil's staircase-type structure. Experiments with verapamil, a voltage-operated L-type Ca(2+)-channel antagonist, confirmed that influx of extracellular Ca2+ was essential to sustain chaos, quasiperiodicity, and mixed-mode responses. Nonlinear coupling between cytosolic and membrane events in rabbit ear arteries thus results in a self-organized dynamics that collapses to that predicted by the theory of simple circle maps.