Lidocaine alleviates inflammation and pruritus in atopic dermatitis by blocking different population of sensory neurons.

BACKGROUND AND PURPOSE: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism. EXPERIMENTAL APPROACH: Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients. KEY RESULTS: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaV blocker that enters through pathologically activated large-pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV 1.8-expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1-positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. CONCLUSION AND IMPLICATIONS: NaV 1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti-inflammatory and anti-pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis.

Transcranial Doppler Ultrasound for Monitoring the Cerebral Hemodynamic Changes and Prognosticating Outcomes in Venoarterial Extracorporeal Membrane-Oxygenated Patients.

Objective: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support may have cerebral hemodynamic changes whose impact on patient outcome are not fully elucidated. This study aims to evaluate the correlation between cerebral hemodynamic changes and prognostic outcome in patients during VA-ECMO. Methods: Transcranial Doppler (TCD) ultrasound examination was performed to attain the systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), and pulsatility index (PI) of patients undergoing VA-ECMO. Cardiac ultrasound was also performed to assess the correlation between the left ventricular outflow tract velocity time integral (LVOT VTI), left ventricular ejection fraction (LVEF), and middle cerebral artery (MCA) with the systolic peak. Moreover, we assessed the predictive value of LVOT VTI and LVEF in patients with the systolic peak. Patients were divided into survival and death groups according to the 28-day survival period. Clinical data were compared between the two groups to investigate the effects of cerebral hemodynamic changes on the prognosis of VA-ECMO patients. Results: We found that the patient's LVOT VTI and LVEF had high predictive values for the systolic peak of the right middle cerebral artery. The initial LVEF, Vs, Vd and PI, and lactate level as well as the MODS incidence rate difference were significantly different between the survival and death groups. In addition, the results showed that the initial Vs value was an independent risk factor for the prognosis of patients undergoing VA-ECMO. Conclusions: Cerebral hemodynamic changes may occur in patients supported by VA-ECMO. In addition, a poor cerebral arterial pulsatile blood flow was closely correlated with an unfavorable outcome in these patients.

Phase difference in modulated signals of two orthogonally polarized outputs of a Nd:YAG microchip laser with anisotropic optical feedback.

We present an experimental observation of the output responses of a Nd:YAG microchip laser with an anisotropic external cavity under weak optical feedback. The feedback mirror is stationary during the experiments. A pair of acousto-optic modulators is used to produce a frequency shift in the feedback light with respect to the initial light. The laser output is a beat signal with 40 kHz modulation frequency and is separated into two orthogonal directions by a Wollaston prism. Phase differences between the two intensity curves are observed as the laser works in two orthogonal modes, and vary with the external birefringence element and the pump power. Theoretical analyses are given, and the simulated results are consistent with the experimental phenomena.