BACKGROUNDThe authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 microg/kg and fentanyl 2 microg/kg by bolus injection on the cardiovascular intubation response in healthy children.

METHODSOne hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 microg/kg (Group R) and fentanyl 2 microg/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22,000 during the observation were recorded.

RESULTSThere were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22,000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R.

CONCLUSIONSWhen used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 microg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 microg/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.

Anesthetics, Intravenous ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Double-Blind Method ; Female ; Fentanyl ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Humans ; Intubation, Intratracheal ; adverse effects ; Male ; Piperidines ; pharmacology ; therapeutic use

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; physiology ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; metabolism ; Cyclins ; metabolism ; Flavonoids ; pharmacology ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; metabolism ; pathology ; Piperidines ; pharmacology ; therapeutic use ; Purines ; pharmacology ; therapeutic use ; Staurosporine ; analogs & derivatives ; pharmacology ; therapeutic use

The effects of effective part group on hyperlipidemia in animal were studied. The SD rats, hamsters and Kunming mouse were divided into blank group, model group. The positive control group and test group were fed with normal diet, blank and other groups were fed with high fat diet (mouse only a single intraperitoneal injection of egg yolk ). The corresponding concentration of solvent, simvastatin, effective part group of emulsion were given gavage once daily. The animal serum total cholesterol (TC) , triglyceride (TG) , low density lipoprotein (LDL) , high density lipoprotein (HDL) and liver TC, TG contents were determined to observe the effects of the effective fractions on blood lipid regulating function. Comparing with control group, the animial hyperlipidemia models of the SD rat (TC increase), mouse (TC, TG, LDL increase), hamsters ( TC, TG, LDL increase, HDL decrease) (P <0. 05, P < 0. 001) were successfully established. Piper longum effective part group could decrease the serum TC, TG, LDL (P <0.05, P < 0. 001) and liver TC, TG content, and elevate serum HDL levels (P <0.05, P <0.001). The golden hamster is ideal for hyperlipidemia model.
Alkaloids ; pharmacology ; therapeutic use ; Animals ; Benzodioxoles ; pharmacology ; therapeutic use ; Cholesterol ; blood ; metabolism ; Cricetinae ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Hyperlipidemias ; blood ; drug therapy ; metabolism ; Lipid Metabolism ; drug effects ; Lipoproteins, HDL ; blood ; metabolism ; Lipoproteins, LDL ; blood ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Piper ; chemistry ; Piperidines ; pharmacology ; therapeutic use ; Polyunsaturated Alkamides ; pharmacology ; therapeutic use ; Rats ; Triglycerides ; blood ; metabolism

Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.
Animals ; Anti-Asthmatic Agents ; pharmacology ; therapeutic use ; Asthma ; drug therapy ; Heterocyclic Compounds ; pharmacology ; Humans ; Phenylurea Compounds ; therapeutic use ; Piperidines ; pharmacology ; therapeutic use ; Pyridazines ; pharmacology ; Receptors, CCR1 ; antagonists & inhibitors ; Receptors, CCR3 ; antagonists & inhibitors ; Receptors, CCR4 ; antagonists & inhibitors ; Receptors, CXCR4 ; antagonists & inhibitors ; Receptors, Chemokine ; antagonists & inhibitors

PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult ; Aged ; Androstanols/adverse effects/pharmacology ; Anesthetics/adverse effects/pharmacology ; Anesthetics, Inhalation/adverse effects/*pharmacology ; Blood Pressure/drug effects ; Etomidate/adverse effects/pharmacology ; Female ; Heart/*drug effects ; Heart Rate/drug effects ; Humans ; Isoflurane/adverse effects/*analogs & derivatives/pharmacology ; Male ; Middle Aged ; Piperidines/adverse effects/*therapeutic use ; Protective Agents/adverse effects/*therapeutic use

Animals ; Cannabinoid Receptor Antagonists ; therapeutic use ; Cannabinoids ; pharmacology ; Fibrosis ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; metabolism ; therapy ; Piperidines ; therapeutic use ; Pyrazoles ; therapeutic use ; Receptor, Cannabinoid, CB1 ; metabolism ; Receptor, Cannabinoid, CB2 ; metabolism ; Receptors, Cannabinoid ; metabolism ; Scleroderma, Diffuse ; metabolism ; Signal Transduction ; drug effects ; Skin ; metabolism ; Smad Proteins ; metabolism ; Transforming Growth Factor beta1 ; metabolism

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 µg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.
Adult ; Aged ; Airway Extubation ; *Anesthesia Recovery Period ; Cough/drug therapy ; *Craniotomy/adverse effects ; Dexmedetomidine/*pharmacology/therapeutic use ; Double-Blind Method ; Female ; Hemodynamics/*drug effects ; Humans ; Male ; Middle Aged ; Piperidines/*pharmacology/therapeutic use ; Prospective Studies ; Reflex/*drug effects ; Respiratory System/blood supply/*drug effects/physiopathology ; Young Adult

OBJECTIVETo assess the role of p38 mitogen-activated protein kinases (p38MAPK) in the protective effect of remifentanil preconditioning (RPC) on hepatic ischemia-reperfusion injury in rats.

METHODSNinety-six male SD rats were randomly assigned into sham-operated group, ischemia-reperfusion group (I/R group), RPC group, and SB (an inhibitor of p38 MAPK) +RPC group. The rats were sacrificed at the end of reperfusion, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured. HE staining was used to observe the hepatic histopathological changes, and Western blotting was employed to examine p38MAPK and pp38MAPK protein expression. TUNEL staining was used to examine cell apoptosis in the liver tissues.

RESULTSCompared with sham-operated group, I/R group showed significantly increased serum levels of AST, ALT, TNF-α and IL-1β with obvious histopathological changes and cell apoptosis in the liver. RPC significantly decresed the elevated serum levels of AST, ALT, TNF-α and IL-1β and lessened hepatic histopathological changes, and caused reduced p38MAPK phosphorylation and hepatic cell apoptosis index. The protective effects of RPC were abolished by SB 203580 pretreatment.

CONCLUSIONRPC attenuates the production of inflammatory factors by activating p38MAPK signal pathway to improve hepatic ischemia-reperfusion injury, and these effects can be blocked by SB203580, a p38MAPK inhibitor.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Imidazoles ; pharmacology ; Interleukin-1beta ; blood ; Ischemia ; physiopathology ; Ischemic Preconditioning ; methods ; Liver ; blood supply ; MAP Kinase Signaling System ; Male ; Piperidines ; therapeutic use ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid ; agonists ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; blood ; p38 Mitogen-Activated Protein Kinases ; metabolism

PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.
Adenocarcinoma/drug therapy/*genetics ; Cell Line, Tumor ; Cetuximab/pharmacology ; Drug Resistance, Neoplasm/drug effects/*genetics ; Epidermal Growth Factor/metabolism/*pharmacology ; *Gene Rearrangement ; Hepatocyte Growth Factor/*pharmacology ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/*genetics ; MAP Kinase Signaling System ; *Mutation ; Niacinamide/analogs & derivatives/pharmacology ; Phenylurea Compounds/pharmacology ; Piperidines/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-ret/*antagonists & inhibitors/genetics ; Pyrroles/pharmacology ; Quinazolines/pharmacology ; RNA, Small Interfering/pharmacology ; Receptor, Epidermal Growth Factor/genetics/metabolism ; Signal Transduction/drug effects ; fms-Like Tyrosine Kinase 3/metabolism