Application value of dexmedetomidine in anesthesia for elderly patients undergoing radical colon cancer surgery

BACKGROUND Colon cancer presents a substantial risk to the well-being of elderly people worldwide.With advancements in medical technology,surgical treatment has become the primary approach for managing colon cancer patients.However,due to age-related physiological changes,especially a decline in cognitive function,older patients are more susceptible to the effects of surgery and anesthesia,increasing the relative risk of postoperative cognitive dysfunction(POCD).There-fore,in the surgical treatment of elderly patients with colon cancer,it is of pa-ramount importance to select an appropriate anesthetic approach to reduce the occurrence of POCD,protect brain function,and improve surgical success rates.METHODS One hundred and seventeen patients with colon cancer who underwent elective surgery under general anesthesia were selected and divided into two groups:A and B.Group A received Dex before anesthesia induction,and B group received an equivalent amount of normal saline.Changes in the mini-mental state exami-nation,regional cerebral oxygen saturation(rSO2),bispectral index,glucose uptake rate(GluER),lactate production rate(LacPR),serum S100βand neuron-specific enolase(NSE),POCD,and adverse anesthesia reactions were compared between the two groups.RESULTS Surgical duration,duration of anesthesia,and intraoperative blood loss were comparable between the two groups(P>0.05).The overall dosage of anesthetic drugs used in group A,including propofol and remifentanil,was significantly lower than that used in group B(P<0.05).Group A exhibited higher rSO2 values at the time of endotracheal intubation,30 min after the start of surgery,and immediately after extubation,higher GluER values and lower LacPR values at the time of endotra-cheal intubation,30 min after the start of surgery,immediately after extubation,and 5 min after extubation(P<0.05).Group A exhibited lower levels of serum S100βand NSE 24 h postoperatively and a lower incidence of cognitive dysfunction on the 1st and 5th postoperative days(P<0.05).CONCLUSION The use of Dex in elderly patients undergoing radical colon cancer surgery helps maintain rSO2 Levels and reduce cerebral metabolic levels and the incidence of anesthesia-and surgery-induced cognitive dysfunction.

Respiratory complications of propofol,sevoflurane,and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years:a randomized trial

Objective To evaluate the effect of propofol,sevoflurane,and dexmedetomidine on respiratory complications inchildren undergoing fiberoptic bronchoscopy(FOB).Methods This double-blind randomized clinical trial was conductedamong 120 children aged 1 month to 3 years undergoing FOB.The patients were randomized into 3 groups(n=40)foranesthesia induction with sevoflurane inhalation,1 mg/kg propofol,or 1μg/kg dexmedetomidine before bronchoscopy,andthe changes in hemodynamic parameters,sedation level,and respiratory complications during and after the procedure wereassessed.Results The patients'heart rate during bronchoscopy was significantly lower and the mean arterial blood pressuresignificantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P<0.05).Cough duringbronchoscopy did not occur in any of the cases in propofol group,while the highest frequency of cough was recorded indexmedetomidine group.The incidence of laryngospasm in the propofol group(12.5%)was significantly lower than those insevoflurane and dexmedetomidine groups(30%and 32.5%,respectively)(P<0.05).Conclusion Sevoflurane and propofol aresafe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve bettersedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

Comparative observation of the effectiveness and safety of remimazolam besylate versus dexmedetomidine in gastrointestinal surgery in obese patients

BACKGROUND Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients.Thus,a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety.AIM To compared the effectiveness and safety of remimazolam besylate versus dexmedetomidine(DEX)in gastrointestinal surgery in obese patients.METHODS The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023,comprising 30 patients who received DEX intervention(control group)and 30 patients who received remimazolam besylate intervention(research group).Heart rate(HR),respiratory rate(RR),mean arterial pressure(MAP),blood oxygen saturation(SpO_(2)),safety(nausea and vomiting,bradycardia,hypotension,and apnea),anesthesia and examination indices[induction time,anesthesia recovery time,and postanesthesia care unit(PACU)discharge time],sedation effect(Ramsay Sedation Scale),and postoperative pain visual analog scale were comparatively analyzed before anesthesia(T0),during anesthesia(T1),and after anesthesia(T2).RESULTS At T1,the research group showed significantly smaller changes in HR,RR,MAP,and SpO_(2) than the control group,with a significantly lower adverse reaction rate and shorter induction,anesthesia recovery,and PACU discharge times.Additionally,the intra-and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group.CONCLUSION Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.

Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway

BACKGROUND Diabetes is often associated with gastrointestinal dysfunctions,which can lead to hypoglycemia.Dexmedetomidine(DEX)is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function.AIM To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction.METHODS Sedation/anesthesia scores and vital signs of streptozotocin(STZ)-induced diabetic mice under DEX sedation were observed.Diabetic mice were divided into saline and DEX groups.After injecting sedatives intraperitoneally,tight junctions(TJs)and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function.The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion.In vitro,high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ intervention.Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions.RESULTS MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice,with the DEX group displaying decreased MMP23B levels.Diabetes-mediated TJ disruption,increased intestinal mucosal permeability,and systemic inflammation in wild-type mice might be reversed by DEX.In Caco-2 cells,MMP23B was associated with increased reactive oxygen species accumulation,mitochondrial membrane potential depolarization,and TJ disruption.CONCLUSION DEX reduces MMP23B,which may potentially contribute to STZ-induced intestinal barrier dysfunction,affecting TJ modification through mitochondrial dysfunction.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients

BACKGROUND Dexmedetomidine and propofol are two sedatives used for long-term sedation.It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation.AIM To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury.METHODS Patients who underwent mechanical ventilation for>72 h were randomly assigned to receive sedation with dexmedetomidine or propofol.The Richmond Agitation and Sedation Scale(RASS)was used to evaluate sedation effects,with a target range of-3 to 0.The primary outcomes were serum levels of S100-βand neuron-specific enolase(NSE)every 24 h.The secondary outcomes were remifentanil dosage,the proportion of patients requiring rescue sedation,and the time and frequency of RASS scores within the target range.RESULTS A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group,respectively.Baseline data were comparable between groups.No significant differences were identified between groups within the median duration of study drug infusion[52.0(IQR:36.0-73.5)h vs 53.0(IQR:37.0-72.0)h,P=0.958],the median dose of remifentanil[4.5(IQR:4.0-5.0)μg/kg/h vs 4.6(IQR:4.0-5.0)μg/kg/h,P=0.395],the median percentage of time in the target RASS range without rescue sedation[85.6%(IQR:65.8%-96.6%)vs 86.7%(IQR:72.3%-95.3),P=0.592],and the median frequency within the target RASS range without rescue sedation[72.2%(60.8%-91.7%)vs 73.3%(60.0%-100.0%),P=0.880].The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance(69.2%vs 50.8%,P=0.045).Serum S100-βand NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation,respectively(all P<0.05).CONCLUSION Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Impact of dexmedetomidine-assisted anesthesia in elderly patients undergoing radical resection of colon cancer

BACKGROUND Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy.However,due to the physiological charac-teristics of elderly patients,the safety of perioperative anesthesia needs special attention.As anα2-adrenergic receptor agonist,dexmedetomidine(Dex)has attracted much attention from anesthesiologists due to its stabilizing effect on heart rate and blood pressure,inhibitory effect on inflammation,and sedative and analgesic effects.Its application in general anesthesia may have a positive impact on the quality of anesthesia and postoperative recovery in elderly patients undergoing radical resection of colon cancer.METHODS A total of 165 colon cancer patients who underwent radical surgery for colon cancer under general anesthesia at Qingdao University Affiliated Haici Hospital,Qingdao,China were recruited and divided into two groups:A and B.In group A,Dex was administered 30 min before surgery,while group B received an equivalent amount of normal saline.The hemodynamic changes,pulmonary compliance,airway pressure,inflammatory factors,confusion assessment method scores,Ramsay Sedation-Agitation Scale scores,and cellular immune function indicators were compared between the two groups.RESULTS Group A showed less intraoperative hemodynamic fluctuations,better pulmonary compliance,and lower airway resistance compared with group B.Twelve hours after the surgery,the serum levels of TLR-2,TLR-4,IL-6,and TNF-αin group A were significantly lower than those of group B(P<0.05).After extubation,the Ramsay Sedation-Agitation Scale score of group A patients was significantly higher than that of group B patients,indicating a higher level of sedation.The incidence of delirium was significantly lower in group A than in group B(P<0.05).CONCLUSION The use of Dex as an adjunct to general anesthesia for radical surgery in elderly patients with colon cancer results in better effectiveness of anesthesia.

Intraplantar Injection of Monosodium Iodoacetate Produces Hyperalgesia in Rats and the Mechanism Underlying the Effect

Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect. Methods: Adult male Wistar rats were used in the experiment. 1) MIA was injected subcutaneously into the right hindpaw of rats, the low, medium, and high doses of MIA were 0.11, 0.33, and 1 mg, respectively, then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 4 hours after MIA injection were measured. 2) Capsazepine (TRPV1 antagonist, 30 μg) was injected subcutaneously into the right hindpaw of rats at 2 hours after intraplantar injection of MIA (1 mg), then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 1 hour after capsazepine injection were measured. Results: 1) The paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing decreased after intraplantar injection of MIA in rats and the effect lasted for at least 4 hours. 2) The MIA-induced reduction in paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing were significantly alleviated after intraplantar injection of capsazepine in rats. Conclusion: Intraplantar injection of MIA can produce thermal pain, mechanical pain, and spontaneous pain for more than 4 hours, which may be due to the TRPV1 activation caused by MIA.

Comparison of the efficacy and safety of sedation between dexmedetomidine-remifentanil and propofol-remifentanil during endoscopic submucosal dissection

AIM: To compare the efficacy and safety of sedation protocols for endoscopic submucosal dissection(ESD) between dexmedetomidine-remifentanil and propofolremifentanil.METHODS: Fifty-nine patients scheduled for ESD were randomly allocated into a dexmedetomidineremifentanil(DR) group or a propofol-remifentanil(PR) group. To control patient anxiety, dexmedetomidine or propofol was infused to maintain a score of 4-5 on the Modified Observer's Assessment of Alertness/Sedation scale. Remifentanil was infused continuously at a rate of 6 μg/kg per hour in both groups. The ease of advancing the scope into the throat, gastric motility grading, and satisfaction of the endoscopist and patient were assessed. Hemodynamic variables and hypoxemic events were compared to evaluate patient safety.RESULTS: Demographic data were comparable between the groups. The hemodynamic variables and pulse oximetry values were stable during the procedure in both groups despite a lower heart rate in the DR group. No oxygen desaturation events occurred in either group. Although advancing the scope into the throat was easier in the PR group("very easy" 24.1% vs 56.7%, P = 0.010), gastric motility was moresuppressed in the DR group("no + mild" 96.6% vs 73.3%, P = 0.013). The endoscopists felt that the procedure was more favorable in the DR group("very good + good" 100% vs 86.7%, P = 0.042), whereas patient satisfaction scores were comparable between the groups. En bloc resection was performed 100% of the time in both groups, and the complete resection rate was 94.4% in the DR group and 100% in the PR group(P = 0.477). CONCLUSION: The efficacy and safety of dexmedetomidine and remifentanil were comparable to propofol and remifentanil during ESD. However, the endoscopists favored dexmedetomidine perhaps due to lower gastric motility.

Dexmedetomidine Alleviates Pulmonary Edema by Upregulating AQP1 and AQP5 Expression in Rats with Acute Lung Injury Induced by Lipopolysaccharide

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide （LPS）. Male Wistar rats were randomly divided into five groups： normal saline control （NS） group, receiving intravenous 0.9% normal saline （5 mL/kg）; LPS group, receiving intravenous LPS （10 mg/kg）; small-dose dexmedetomidine （S） group, treated with a small dose of dexmedetomidine （0.5 μg·kg^-1·h^-1）; medium-dose dexmedetomidine （M） group, treated with a medium dose of dexmedetomidine （2.5 μg·kg^-1·h^-1）; high-dose dexmedetomidine （H） group, treated with a high dose of dexmedetomidine （5μg·kg^-1·h^-1）. The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the hmgs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio （W/D）. The levels of tumor necrosis factor-alpha （TNF-α） and interleukin-1β （IL-1β） in the lung tissues were assessed by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of aquaporin-1 （AQP1） and aquaporin-5 （AQP5） were detected by RT-PCR, immunohistochemistry, and Western blot- ting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group （P〈0.01）. The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group （P〈0.01）. Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

BACKGROUND: Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture(CLP) model in rats. METHODS: After CLP, 48 Wistar rats were randomly allocated into four groups:(1) CLP group;(2) small-dose treatment group(2.5 g·kg^(-1)·h^(-1));(3) medium-dose treatment group(5.0 g·kg^(-1)·h^(-1)); and(4) large-dose treatment group(10.0 g·kg^(-1)·h^(-1)). HLA-DR and plasma cytokine(IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure(MAP), heart rate(HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS: The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups(DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels(P_(group)=0.0202) and increased IL-6 production, which was increased at 3 h(P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR(P<0.001) while maintaining MAP(P_(group)=0.1238), and remarkably improving lactate(P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively.CONCLUSION: Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dosedependently.

Analgesic action of suspended moxibustion in rats with chronic visceral hyperalgesia correlates with enkephalins in the spinal cord

Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu （ST25） and Shangjuxu （ST37） once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.

Mild moxibustion at Tianshu (ST 25) decreases expression of prokineticin-1 and prokineticin receptor-1 in colon tissue of rats with chronic visceral hyperalgesia

Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu （ST 25） decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.

Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 ~tg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 ~tg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spon- taneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100~ and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry （http：//www.chictr.org. cn/） （registration number： ChiCTR-IPR- 16008113）.

Dexmedetomidine attenuates traumatic brain injury: action pathway and mechanisms

Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 days） post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.

Neurotoxicity of intrathecal injections of dexmedetomidine into the rat spinal dorsal horn

To investigate the neurotoxicity of intrathecal injections of dexmedetomidine,Sprague-Dawley rats were intrathecally injected with dexmedetomidine at doses of 0.75,1.50 and 3.00μg/kg into the spinal dorsal horn.We found that c-Fos expression in the rat spinal dorsal horn peaked at 7 hours following the 3.00μg/kg dexmedetomidine injection,while the levels of c-Fos expression following 0.75 and 1.50μg/kg dexmedetomidine were similar to those in the spinal dorsal horn of normal rats. At 48 hours following administration,the level of c-Fos expression was similar to normal levels.In addition,the intrathecal injections of dexmedetomidine increased paw withdrawal mechanical thresholds and prolonged thermal tail flick latencies.These results indicate that dexmedetomidine has pronounced antinociceptive effects.However,dexmedetomidine appears to have neurotoxic effects in the spinal cord because it increased c-Fos expression in the spinal dorsal horn within 7 hours following administration.

Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury

Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin（30 or 60 mg/kg） was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1（Trpv1） and transient receptor potential ankyrin 1（Trpa1） in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.

Effects of Intraoperative Administration of Dexmedetomidine on the Percentage of T-Lymphocyte Subsets and Natural Killer Cells in Patients with Colorectal Cancer

Study Objective: To observe the effect of dexmedetomidine (DEX) on T-lymphocyte subsets and natural killer (NK) cells in the peripheral blood of perioperative patients with colorectal cancer. Design: A random double-blind control clinical study. Setting: A university hospital. Patients: Forty patients with colorectal cancer, ASA I-П. Interventions: All patients were randomly divided into a DEX group (n = 20) and a control group (n = 20). Before induction of anesthesia, epidural catheters were placed in the L1-L2 or T12-L1 intervertebral spaces. The DEX group received 1 μg/kg of DEX (200 μg/50 ml) intravenously for 15 min prior to the surgery, which was then infused at a rate of 0.5 μg/kg/h until 30 min before the end of the surgery. The control group received an intravenous infusion of saline (50 ml) instead of DEX during the same periods as the DEX group. All patients received routine anesthesia and postoperative analgesia. Measurements: Blood samples from all patients were collected at the following time points: before anesthesia (T0), 24 h after surgery (T1), 48 h after surgery (T2) and 72 h after surgery (T3). Changes in T-lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and NK cells were determined by flow cytometry. Main Results: Compared with the control group, the percentages of CD3+ and CD4+ cells and the CD4+/CD8+ ratio in the DEX group increased significantly from T1 to T3

Dexmedetomidine Attenuates High Glucose-induced HK-2 Epithelial-mesenchymal Transition by Inhibiting AKT and ERK

Objective To explore the protective effects of dexmedetomidine(Dex)against high glucose-induced epithelial-mesenchymal transition in HK-2 cells and relevant mechanisms.Methods HK-2 cells were exposed to either glucose or glucose+Dex for 6 h.The production of ROS,morphology of HK-2 cells,and cell cycle were detected.Moreover,the expression of AKT,p-AKT,ERK,pERK,PI3 K,E-Cadherin,Claudin-1,andα-SMA were determined and compared between HK-2 cells exposed to glucose and those exposed to both glucose and Dex with or without PI3 K/AKT pathway inhibitor LY294002 and ERK pathway inhibitor U0126.Results Compared with HK-2 cells exposed to high level of glucose,the HK-2 cells exposed to both high level of glucose and Dex showed:(1)lower level of ROS production;(2)cell morphology was complete;(3)more cells in G1 phase;(4)lower expression of p-AKT,p-ERK andα-SMA,higher expression of ECadherin and Claudin-1.PI3 K/AKT inhibitor LY294002 and ERK inhibitor U0126 decreased the expression of p-AKT,p-ERK andα-SMA,and increased the expression of E-Cadherin and Claudin-1.Conclusion Dex can attenuate high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK.

Effects of dexmedetomidine and dexketoprofen on the conduction block of rat sciatic nerve

Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative,anxiolytic,and analgesic effects.Dexketoprofen,which is used as an analgesic,is a nonselective nonsteroidal anti-inflammatory drug (NSAID).The use of dexmedetomidine and dexketoprofen as adjuvants to local anesthetics for the peripheral nerve is gradually increasing.In this study,we aimed to investigate the effects of different doses of dexmedetomidine and dexketoprofen on conduction block of rat sciatic nerve.The isolated sciatic nerve from adult rats was transferred to a nerve chamber.The compound action potentials (CAPs) were recorded from stimulated nerve with electrophysiological methods.Dexmedetomidine (n = 8) and dexketoprofen (n = 8) were administered in the chamber with cumulative concentrations of 10–9 to 10–5 M,and the CAPs were recorded for 5 and 10 minutes.The CAP parameters were calculated.Both dexmedetomidine and dexketoprofen significantly depressed all CAP parameters in a dose-dependent manner compared with the control group,i.e.,the group in which rats did not receive treatment.CAP parameters showed there was no significant difference in nerve conduction inhibition between dexmedetomidine and dexketoprofen.Higher doses of dexmedetomidine suppressed the conduction in the fast-conducting fibers;however,dexketoprofen was found to suppress the conduction in the slow-conducting fibers in a time-dependent manner and suppress the conduction in the medium- and slow-conducting fibers in a dose-dependent manner.These findings suggest that dexmedetomidine and dexketoprofen exhibit better anesthetic effects on peripheral nerve through different ways of action.The experimental procedures were approved by the Necmettin Erbakan University on January 30,2013 (approval No.2013-024).