Comparison of different anesthesia modalities during percutaneous kyphoplasty of osteoporotic vertebral compression fractures.

Local and general anesthesia are the main techniques used during percutaneous kyphoplasty (PKP); however, both are associated with adverse reactions. Monitored anesthesia with dexmedetomidine may be the appropriate sedative and analgesic technique. Few studies have compared monitored anesthesia with other anesthesia modalities during PKP. Our aim was to determine whether monitored anesthesia is an effective alternative anesthetic approach for PKP. One hundred sixty-five patients undergoing PKP for osteoporotic vertebral compression fractures (OVCFs) were recruited from a single center in this prospective, non-randomized controlled study. PKP was performed under local anesthesia with ropivacaine (n = 55), monitored anesthesia with dexmedetomidine (n = 55), and general anesthesia with sufentanil/propofol/sevoflurane (n = 55). Perioperative pain was assessed using a visual analogue score (VAS). Hemodynamic variables, operative time, adverse effects, and perioperative satisfaction were recorded. The mean arterial pressure (MAP), heart rate, VAS, and operative time during monitored anesthesia were significantly lower than local anesthesia. Compared with general anesthesia, monitored anesthesia led to less adverse anesthetic effects. Monitored anesthesia had the highest perioperative satisfaction and the lowest VAS 2 h postoperatively; however, the monitored anesthesia group had the lowest MAP and heart rate 2 h postoperatively. Based on better sedation and analgesia, monitored anesthesia with dexmedetomidine achieved better patient cooperation, a shorter operative time, and lower adverse events during PKP; however, the MAP and heart rate in the monitored anesthesia group should be closely observed after surgery.

Neohesperidin suppresses IgE-mediated anaphylactic reactions and mast cell activation via Lyn-PLC-Ca2+ pathway.

Mast cells play an essential role in IgE-FcεR1-mediated allergic diseases. Citrus aurantium is a prolific source of flavonoids with various biological activities, including anti-inflammatory, antioxidant, and anti-tumor efficacies. Neohesperidin is a novel flavonoid isolated from the leaves of C. aurantium. In this study, the anti-allergic and anti-inflammatory potentials of neohesperidin were investigated along with its molecular mechanism. The anti-anaphylactic activity of neohesperidin was evaluated through hind paw extravasation study in mice. Calcium imaging was used to assess intracellular Ca2+ mobilization. The levels of cytokines and chemokines were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. Neohesperidin suppressed IgE-induced mast cell activations, including degranulation and secretion of cytokines and eicosanoids through inhibiting phosphorylation of Lyn kinase. Neohesperidin inhibited the release of histamine and other proinflammatory cytokines through a mast cell-dependent passive cutaneous anaphylaxis animal model. Histological studies demonstrated that neohesperidin substantially inhibited IgE-induced cellular infiltration and attenuated mast cell activation in skin tissue. In conclusion, our study revealed that neohesperidin could inhibit allergic responses in vivo and in vitro, and the molecule may be regarded as a novel agent for preventing mast cell-immediate and delayed allergic diseases.

The anti-anaphylactoid effects of hydroxysafflor yellow A on the suppression of mast cell Ca2+ influx and degranulation.

BACKGROUND: Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cell mediators, especially histamine and lipid mediators. Non-IgE-mediated anaphylaxis can occur because of the direct activation of mast cells. Hydroxysafflor yellow A (HSYA) is the main chemical component of safflower (Carthamus tinctorius) and has been reported to have pharmacological activities. However, the anti-anaphylactoid effect of HSYA has not yet been investigated. PURPOSE: The aims of this study were to evaluate the anti-anaphylactoid activity of HSYA in vivo and to investigate the underlying mechanism in vitro. METHODS: The anti-anaphylactoid activity of HSYA was evaluated in a mouse model of hindpaw extravasation. Calcium imaging was used to assess intracellular Ca2+ mobilization. The levels of cytokines and chemokines released by stimulated mast cells were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. RESULTS: HSYA markedly inhibited mast cell degranulation by suppressing the activation of intracellular Ca2+ mobilization and preventing the release of cytokines and chemokines from mast cells in a dose-dependent manner via the PKC-PLCγ-IP3R signaling pathway. CONCLUSION: In summary, HSYA has anti-anaphylactoid pharmacological activity, which makes it a potential candidate for the development of a novel agent to suppress drug-induced anaphylactoid reactions.

Activation of STAT3 is involved in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptors in rats.

Pretreatment with electroacupuncture (EA) attenuates cerebral ischemic injury through the endocannabinoid system, although the molecular mechanisms mediate this neuroprotection are unknown. It is well-known that signal transducer and activator of transcription 3 (STAT3) plays an essential role in cell survival and proliferation. Therefore, we investigated whether STAT3 is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after transient focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MACO) for 120 min. The expression of pSTAT3(Ser727), which is necessary for STAT3 activation, was examined in the ipsilateral ischemic penumbra. Infarct volumes and neurological scores were evaluated at 72 h after MACO in the presence or absence of the STAT3 inhibitor peptide (PpYLKTK). Neuronal apoptosis and the Bax/Bcl-2 ratio were also evaluated 24h after reperfusion. Our results showed that EA pretreatment significantly enhanced neuronal expression of pSTAT3(Ser727) in the ischemic penumbra 6h after reperfusion. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and decreased the Bax/Bcl-2 ratio following reperfusion. The beneficial effects of EA were attenuated by PpYLKTK administered 30 min before MACO, and PpYLKTK effectively reversed the increase in pSTAT3(Ser727) expression. Furthermore, CB1R antagonist or CB1R knockdown with siRNA blocked the elevation of pSTAT3(Ser727) expression by EA pretreatment, whereas the two CB1R agonists increased STAT3 activation. In conclusion, EA pretreatment enhances STAT3 activation via CB1R to protect against cerebral ischemia, suggesting that STAT3 activation may be a novel target for stroke intervention.

NDRG2 is involved in anti-apoptosis induced by electroacupuncture pretreatment after focal cerebral ischemia in rats.

OBJECTIVE: We first reported that electroacupuncture (EA) pretreatment at the Baihui acupoint (GV20) induces ischemic tolerance. Our recent study demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) expression was up-regulated following transient focal cerebral ischemia. Therefore, we investigated whether NDRG2 was involved in the ischemic tolerance induced by EA pretreatment in rats. METHODS: Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 120 minutes in male Sprague-Dawley rats. The neurobehavioral score, infarction volume, and extent of neuronal apoptosis were evaluated at 24 hours after reperfusion. The expression of NDRG2 in the brain was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, and immunofluorescent staining. RESULTS: Electroacupuncture pretreatment decreased infarction volume and improved neurologic scores at 24 hours after reperfusion. Double immunofluorescence revealed that NDRG2 expression in astrocytes was suppressed in the EA group at 24 hours after reperfusion, and that NDRG2 protein expression was weak in the nucleus and strong in the cytoplasm of the EA group, but strong in the nucleus of the MCAO group. Triple immunofluorescent staining for terminal deoxynucleotidyl transferase nick-end labeling (TUNEL), NDRG2, and 4',6-diamidino-2-phenylindole (DAPI) showed that NDRG2 co-localised with apoptotic cells. Moreover, the number of apoptotic cells decreased with the attenuation of NDRG2 expression in the EA group compared to the MCAO group. CONCLUSION: Our results indicated that NDRG2 is involved in anti-apoptosis induced by EA pretreatment after focal cerebral ischemia in rats. N-Myc downstream-regulated gene 2 was involved in EA pretreatment-induced cerebral ischemic tolerance. These findings may be important for our understanding of the cellular signaling pathways induced by EA pretreatment.