Objective It has been shown that ketamine attenuates cytokine production and release induced by endotoxin. The purpose of this study was to investigate the effects of diazepam and ketamine on inflammatory responses during early stage of burn. Methods BALB/C male mice weighing 20-25 g were randomly divided into 5 groups : (1) normal control group (n = 10); (2) burn control group received Ⅲ degree bums covering 15%-20% of the body surface (n = 10); (3) D-K group received intramuscular diazepam 0.4mg?kg-1 and ketamine 10 mg?kg-1 ( n = 10); (4) D + K pretreatment group received D + K 15 min before burn ( n = 10) and (5) D + K post-treatment group received D + K 15 min after burn ( n = 10) . Four hours after burn or anesthesia (D + K) the animals were sacrificed and blood was collected for determination of serum TNF-?, IL-1? and IL-10 concentrations (ELISA) and peritoneal macrophages were isolated for detection of glucocorticoid receptor (GR) by Western blotting. In addition peritoneal macrophages isolated from normal animals (group 1) and bum animals (group 2) were cultured with diazepam-ketamine for 1 h befor detection of GR.Results Serum TNF-?, IL-1? and IL-10 levels in group 2 were significantly higher than those in group 1. In group 4 and 5 serum TNF-?, IL-l? and IL-10 levels were significantly lower than those in group 2. In group 4 only serum IL-10 level whereas both serum IL-1? and IL-10 levels in group 5 were significantly higher than those in group 1. GR of peritoneal macrophage was significantly down regulated 4 h after bum (group 2) as compared with group 1. The level of GR in group 4 was significantly higher than that in group 2 but not significantly different from that in group 1; whereas the GR level in group 5 was significantly higher than that in group 2 but lower than that in group 1 and 4. There was no significant difference in GR expression after macrophages were cultured in vitro with diazepam and ketamine between normal or bum groups. Conclusion Diazepam-ketamine pretreatment can suppress cytokine release induced by severe bum. The expression of GR in peritoneal macrophages is significantly reduced by bum. Diazepam-ketamine given before or after bum can suppress the inflammatory response but have no direct effect on peritoneal macrophages.

Dual material gate SOI MOSFET with asymmetrical halo can suppress short channel effect and increase carriers transport efficiency. The analytical model of its subthreshold drain current is derived based on the explicit solution of two-dimensional Poisson's equation in the depletion region. The model takes into consideration the channel length modulation effect and the contribution of the back channel current component. Its validation is verified by comparision with two dimensional device simulator MEDICI.

People departure from the treatment, prevention and health care purposes, intermittently or continuously excessive use of drugs with dependence, will cause serious mental and physical damage, while serious social harm.Opioids are the most commonly abused drug, abusers by taking an excess number of pills orally or by crushing the pills, followed by smoking, snorting, or injecting the new altered formulation to get euphoric.The escalating abuse of opioids has recently spawned the development of novel drug formulations resistant to various methods of tampering and misuse.This article discusses available opioids that include abuse-deterrent mechanisms as well as such agents currently in development.

Acute Disease ; Autonomic Nervous System Diseases ; Child ; Humans ; Male

Adult ; Female ; Gas Poisoning ; drug therapy ; Glycoproteins ; therapeutic use ; Humans ; Male ; Middle Aged ; Quinuclidines ; therapeutic use ; Treatment Outcome ; Young Adult

Animals ; Drug Tolerance ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Morphine ; Phosphorylation ; Rats ; Signal Transduction

Objective As estrogen increases visceral hypersensitivity induced by water avoidance stress in female rats,further experiment was designed to determine whether the influence of estrogen involves NR2B.Methods Healthy adult female Wistar rats were bilaterally ovariectomized,and then housed individually.Implantation of cannula into lateral cerebroventricle and electrodes into the abdominal muscle had been done.After 5 days recovery,rats with abnormal behavior and ehctromyography were excluded,finally a total of 48 rats were eligible,and were equipped for abdominal muscle electromyography and submitted to water avoidance stress(WAS).Visceromotor response(VMR)to 20,40,60 and 80 mmHg colorectal distension(CRD)was recorded in rats intracerebroventricular-infused with either 17β-estradiol,normal saline,AP5(NMDA receptor-antagonist)or Ro25-6981(NR2B antagonist).NR2B mRNA in anterior cingulate cortex or dorsal root ganglia were compared by real-time PCR between the rats treated with 17β-estradioI and that with normal saline.Results Bilaterally ovarieetomized rats treated with 17β-estradiol,exhibited more visceral hypersensitivity after WAS than that with normal saline on 40,60 and 80 mmHg CRD(P=0.039,P=0.033,P=O.001).The VMR on 40 and 60 mmHg CRD in 17β-estradiol treated group was not significantly different from that in 17β-estradiol plus Ro25-6981 treated group.Whilst,significant differences of VMR were noted between 17β-estradiol treated group and 17β-estradiol plus Ro25-6981 treated group on 80 mmHg CRD,17β-estradiol treated group and 17β-estradiol plus AP5 treated group on 60,80 nmmHg CRD,respectively.17β-estradiol increased NR2BmRNA in anterior cingulate cortex(0.57±0.41 vs 0.21±0.13,P=0.048),but not in dorsal root ganglia(0.35±0.45 vs 0.38±0.31,P=0.465). Stress-induced visceral hypersensitivity in the hormonally-restored visceral hyper-responsiveness of bilaterally ovariectomized rats was antagonized by AP5 or Ro25-6981.Conclusions Estrogen may be mediated through NR2B activation to enhance visceral sensitivity in female stressed rats,that probably related with the increased expression of NR2B mRNA in anterior cingulate cortex.

BACKGROUND:It has been reported that treatment with granulocyte-colony stimulating factor (G-CSF) increases the abundance of circulating CD34+ cells in rats. Data from the study, more important, suggested that mobilized by G-CSF may enhance rapid reendothelization and reduce neointimal formation after vascular injury.OBJECTIVE: To evaluate whether BM-derived CD34+ cells could enhance rapid reendothelization and reduce neointimal formation after balloon-injured carotid artery in an intact rat model.DESIGN: Randomized control animal study.SETTING: Nanjing First Hospital Affiliated to Nanjing Medical University.MATERIALS: The experiment was carried out in Nanjing First Hospital from December 2005 to April 2006. A total of 40 male Sprague-Dawley rats, weighing 200-250 g and of SPF grade, were purchased from National Rodent Laboratory Animal Resources, Shanghai Branch. The recombinant human G-CSF was purchased from Qilu Pharmaceutical. The 2F Fogarty arterial embolectomy catheters were purchased from Edwards Lifesciences. Anti-human CD34 and anti-human CD45 were purchased from Multi Sciences.METHODS: SD rats were divided randomly into treated group (n =20) and control group (n =20). Subcutaneous injection of recombinant human G-CSF (100 μg/kg/day) once daily for 8 days for treated group. Control group as treated with subcutaneous injection of saline. Five days after initiation of G-CSF treatment or saline, the rats were anesthetized by intraperitoneal injection with ketamine. The left common carotid artery was exposed through a midline incision of the ventral side of the neck. A 2F Fogarty arterial embolectomy catheter was inserted through the external carotid artery,inflated with 200 μL air, and passed 3 times along the length of the segment, which was defined proximally by the carotid bifurcation and distally by the edge of the omohyoid muscle. After removal of the catheter, the proximal ligature of the external carotid artery was tied off. ① An average of 1 mL venous blood per rat was collected for enumeration of the white blood wells (WBCs) and CD34+ cells before and 5 days after initiating G-CSF or saline treatment. ② Ten rats in each group were killed with overdose ketamine at 14 and 28 days after balloon injury and left common carotid arteries were harvested. The luminal surface of carotid arteries (n =5, each group) was exposed to calculate the reendothelialized area, which was manually traced with software (Image ProPlus). Reendothelialized area = non-stained with Evans blue area/the total area of balloon-injuried. The cross sections of carotid arteries (n =5, each group) were stained with hematoxylin and eosin (HE) and calculated intima-to-media area ratio (I/M) with software (Image ProPlus) to assess the extent of neointimal thickening. ③ To evaluate the extent of reendothelialization of arteries injury, sections were stained with CD31 and vWF by immunohistochemistry analysis.MAIN OUTCOME MEASURES: ① The number of WBCs and CD34+ cells; ② the extent of reendothelialization of arteries injury; ③ the extent of neointimal hyperplasia (I/M); ④ CD31 + and vWF+ endothelial cells.RESULTS: A total of 40 rats were involved in the final analysis. ① The number of WBCs and CD34+ cells: After 5 days of treatment, the number of WBCs in the treated rats increased more than 2.7-fold compared with control group [(27.60±2.45) ×109 L-1, (10.11±1.81) ×109 L-1, P ＜ 0.01], CD34+ cells increased more than 12.2-fold compared with control group (38.31×107 L-1, 3.14×107 L-1, P ＜ 0.01). ② The extent of reendothelialization: At 14 and 28 days after balloon injury,carotid artery of reendothelialization in the treated group were (68.3±8.3)％ and (97.6±4.1)％, superior than the control group (33.8±6.3)％ and (76.1±5.2)％ (P ＜ 0.01). ③ The extent of neointimal hyperplasia: At 14 and 28 days after balloon injury, the neointima-media (I/M) ratios in the treated rats were 0.39±0.11 and 0.45±0.09, less than the control group 0.87±0.15,1.26±0.16 (P ＜ 0.01). A highly significant inhibition of neointimal hyperplasia was observed in the treated group. ④ CD31+ and vWF+ endothelial cells: At 28 days after injury, sections from G-CSF treated group showed almost complete and continuous monolayer of CD31 and vWF positive cells.In contrast, a patchy and interrupted CD31 and vWF positive cells were found lining the lumen of control group.CONCLUSION:Treatment with G-CSF significantly increases the number of CD34+ cells and accelerates the rate of reendothelialization of injured vessels, leading to marked inhibition of neointimal formation after vascular injury in rats.

Objective To observe the effect of rosuvastatin on serum hs-CRP,IL-18 levels in patients with acute myocardial infarction.Methods By randomized,double-blind,controlled study,102 patients with acute myocardial infarction were randomly divided into the treatment group(rosuvastatin 10mg/d,continuous medication 14d) and the control group(not used rosuvastatin,other treatment and care were same with the treatment group).Before treatment,24h after treatment,after 2 months of follow-up,the serum hs-CRP and IL-18 levels were detected and compared.Results After treatment,the serum hsCRP level increased and then decreased,24h after treatment,the serum hsCRP level of the treatment group increased to (15.54 ±2.51) mg/L,which was significantly lower than the control group (19.26 ±.2.92) mg/L (t =4.65,all P ＜ 0.05).2 months after treatment,the serum hs-CRP levels of the two groups were decreased to (3.21 ± 1.39) mg/L and (7.67 ± 2.07) mg/L,the difference was statistically significant (t =5.54,4.63,all P ＜ 0.05).After treatment,the serum IL-18 level decreased,24h after treatment,the serum IL-18 level ofthe treatment group decreased to (29.13 ±6.34)pg/L,which was significandy lower than the control group (33.01 ± 7.34) pg/L(t =3.59,P ＜ 0.05).2 months after treatment,serum IL-18 levels of the two groups were decreased to (27.52 ± 5.33) pg/L and (32.01 ± 6.24) pg/L,the difference was statistically significant (t =3.87,3.28,P ＜0.05).Conclusion Rosuvastatin can significantly reduce the serum hsCRP and IL-18 levels in patients with acute coronary syndrome,it has better anti-inflammatory effect and can be used as a new therapeutic target for acute myocardial infarction.