Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.
Abstract. The aim of the present study was to evaluate the effect of a combination of dexmedetomidine and fentanyl on peripheral oxygen saturation (SpO 2 ) and hemodynamic stability in patients undergoing flexible bronchoscopy. One hundred patients undergoing elective flexible bronchoscopy were randomized into either a propofol-fentanyl group (PF group; n=50) or a dexmedetomidine-fentanyl group (DF group; n=50). SpO 2 values, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), patients' cough scores and discomfort scores as determined by patients and bronchoscopists, levels of sedation, number of times that additional lidocaine was required, elapsed time until recovery, and adverse events were recorded. The mean SpO 2 values in the DF group were significantly higher than those in the PF group (P<0.01), and HR, SBP and DBP were significantly lower in the DF group than in the PF group (P<0.05). There were no statistically significant differences between the two groups in terms of cough scores or discomfort scores, sedation levels, or number of times that additional lidocaine was required (P>0.05). Elapsed time until recovery in the DF group was significantly longer than in the PF group (P=0.002). The incidence of hypoxemia was significantly lower in the DF group than in the PF group (P= 0.027), but the incidence of bradycardia was significantly higher in the DF group than in the PF group (P= 0.037). Dexmedetomidine-fentanyl was superior to propofol-fentanyl in providing satisfactory SpO 2 . Furthermore, dexmedetomidine-fentanyl attenuated hemodynamic responses during bronchoscopy and maintained hemodynamic stability in the early stage of the procedure. IntroductionFlexible bronchoscopy is commonly used for the diagnosis and management of a variety of pulmonary diseases. However, it is an invasive procedure that can induce coughing, pain, dyspnea and other adverse effects (1,2). The use of sedatives not only can increase patients' safety and comfort (3) but also can make it easier for the bronchoscopist to perform the procedure and thus avoid extending its duration (4). In addition to alleviating the physiological response to airway irritation during the procedure (5), the proper sedatives should have a rapid onset and a short duration of action, in addition to allowing rapid recovery.Propofol, a non-opioid and nonbarbiturate sedative hypnotic agent, is frequently used in the induction and maintenance of anesthesia. The properties of rapid onset and offset of action and of smooth recovery (6) make propofol an appealing agent alone or in combination with an opioid for procedural sedation (7-10). However, dose-dependent respiratory depression and hypoxemia are possible, owing to interactions and synergism between sedatives and opioids (11-13).Dexmedetomidine, a highly selective α 2 -adrenoceptor agonist, has an affinity for α 2 -adrenoceptors that is 8-fold greater than that of clonidine (14). In addition to providing sedative and analgesic effects (15), dexmedetomidine can be applied generally duri...
Objective. Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis and increased cardiovascular risk. Angiogenic T cells (Tang), a specific T cell subset, have been identified and involved in the repair of damaged endothelium. This study aimed to analyze the Tang cell subsets in relation to disease specific features from SLE patients. Methods. Tang cell subsets were assessed in peripheral blood samples from 41 SLE patients and 22 healthy controls (HC) by flow cytometry on the basis of CD31 and CXCR4 expression on CD3+, CD4+, and CD8+ T cells. Results. The percentage of circulating CD8+CD31+CXCR4+ T cells (CD8+ Tang), but not CD3+CD31+CXCR4+ T cells (Tang) and CD4+CD31+CXCR4+ T cells (CD4+ Tang), in SLE was higher than HC. The percentages of Tang cell subsets in anti-dsDNA-positive SLE patients were significantly increased as compared to their negative counterparts and HC. Additionally, the levels of circulating Tang cell subsets were negatively correlated with age at sampling and at diagnosis, but not disease duration or disease activity. Conclusion. Anti-dsDNA-positivity may identify a group of SLE patients with increased Tang cell subsets and circulating CD8+ Tang cells may be viewed as a potentially useful biomarker of endothelial damage and cardiovascular risk in SLE.
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