To reveal the characterization of interaction between Chinese and western medicinal injections, isothermal titration calorimetry (ITC) was applied to evaluating the interaction of Yiqi Fumai injection (YQFM, as mode drug) with epinephrine hydrochloride injection (YS) and 5% glucose injection (5% GS). The diversification of Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) were determined to judge the reaction types of colliquefaction procedures of different injections. Meanwhile, the fingerprints of YQFM before and after combined with the various injections were compared to validate the results. This work demonstrated that during the titration procedure of YQFM and YS, [ΔH] > T [ΔS] , that was to say the reaction was enthalpy-driving. And the reactive profile indicated that a great deal of heat gave out during the procedure. Obviously, chemical reactions happened and the internal component changed. On the other side, the reaction of YQFM combined with 5% GS was entropy-driving, because [ΔH] < T [ΔS]. The reactive profile showed there was only a little heat released. So non-chemical reactions happened and the major ingredients did not change. ITC could be applied to the evaluation on compatibility of other kinds of Chinese and western medicinal injection combination.
Calorimetry ; Drug Interactions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Entropy ; Epinephrine ; chemistry ; pharmacology ; Glucose ; chemistry ; pharmacology ; Injections ; Thermodynamics

Calcium ; metabolism ; Calcium Signaling ; Epinephrine ; pharmacology ; Hepatocytes ; drug effects ; metabolism ; Humans

The effect of dexamethasone (10(-5)M) and epinephrine (10(-6)M) on the biosynthesis of metallothionein (MT) in the perfused rat liver was investigated. MT synthesis was determined by measuring the incorporation of 14C-L-aspartic acid into liver MT fraction after the perfusion for five hours of isolated liver by artificial blood containing 14C-L-U-aspartic acid (0.2uci) with dexamethasone or epinephrine. MT was isolated by Sephadex G-75 column chromatography and DEAE Sephadex column chromatography. Incorporation of radioactive 14C into the MT fraction of perfused liver cytosol (9.0grams of liver) from dexamethasone treated, epinephrine treated and control groups were, respective1y, 0.72, 0.34 and 0.33% of total radioactivity infused. Total protein content in the MT fraction of liver perfused with dexamethasone and epinephrine were 0.80, 0.64mg/g liver compared to 0.52mg/g liver in the control. MT, a protein having a high content of cystein and metals is synthesized in the perfused rat liver and its induction is stimulated by dexamethasone, while epinephrine increased the accumulation of Zn in the MT fraction of the perfused rat liver. The present experiment confirms that MT synthesis and degradation are somewhat regulated by glucocorticoid hormone and epinephrine.
Animal ; Dexamethasone/pharmacology* ; Epinephrine/pharmacology* ; Female ; In Vitro ; Liver/drug effects ; Liver/metabolism* ; Metalloproteins/metabolism* ; Metallothionein/metabolism* ; Perfusion ; Rats ; Zinc/metabolism

The influence of thyroxine upon n the cardiac uptake of catecholamines was investigated in rabbits. A single injection of thyroxine(1.0m/kg) into rabbits did not affect the concentration of myocardial catecholamines. However, this dose of thyroxine greatly increased the cardiac uptake of catecholamine following injection of 2.0mg of norepinephrine as compared to that of untreated normal animals and it remained elevated for several hours. Similarly thyroxine also enhanced the accumulation of myocardial catecholamines following administration of dopa(60-80mg/kg) and epinephrine(1.0-1.5mg/kg).
Animal ; Catecholamines/metabolism* ; Epinephrine/metabolism ; Heart/drug effects* ; Male ; Myocardium/metabolism* ; Norepinephrine/metabolism ; Rabbits ; Thyroxine/pharmacology* ; Tritium

BACKGROUNDEpinephrine has been used as a first-choice vasopressor drug for cardiac arrest (CA) since 1974. However, the administration of epinephrine is controversial. This study aims to compare the effects of Shen-Fu injection (SFI) and epinephrine on resuscitation outcomes in a porcine model of prolonged CA.

METHODSVentricular fibrillation (VF) was electrically induced. After 8 minutes of untreated VF and 2 minutes of chest compressions, 24 pigs were randomly divided into 3 groups (n = 8 per group): central venous injection of SFI (SFI group), epinephrine (EPI group), or saline solution (SA group). The haemodynamic status and oxygen metabolism parameters, including cardiac output, mean arterial pressure, left ventricular dp/dtmax and negative dp/dtmax, oxygen delivery (DO2), and oxygen consumption (VO2), were calculated.

RESULTSSFI shortened the time to restoration of spontaneous circulation (ROSC) and decreased the number of shocks, similar to epinephrine. However, the mean arterial pressure, cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC. VO2 and ERO2 decreased after ROSC and then increased. VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC, while those were lowest in the EPI group among all groups.

CONCLUSIONSSFI shortened the time to ROSC and decreased the number of shocks, similar to epinephrine. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with epinephrine. SFI might be a potentially vasopressor drug for the treatment of CA.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Epinephrine ; administration & dosage ; pharmacology ; Heart Arrest ; drug therapy ; Injections, Intravenous ; Male ; Resuscitation ; methods ; Swine ; Treatment Outcome

Cells, Cultured ; Epinephrine ; adverse effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; ultrastructure ; Humans ; Laminaria ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Protective Agents ; pharmacology

OBJECTIVETo study the effects of catecholamines on human preadipocyte proliferation and differentiation.

METHODSCatecholamines (epinephrine, isoprenaline and noradrenaline) were added to the culture media of human preadipocytes. The proliferation of cells, the expression of GPDH and lipid droplet accumulation in cytoplasm were observed and recorded. The functions of alpha and beta receptors were examined with adding alpha and beta receptor blockers.

RESULTSEpinephrine and isoprenaline stimulated human preadipocyte proliferation and inhibited GPDH up-regulation during differentiation. The three types of catecholamines inhibited lipid accumulation in cell differentiation. The beta-adrenoceptors played a key role during the process.

CONCLUSIONHuman preadipocytes responded to catecholamine characteristically. The result would be applicable in the study of drugs for obesity.

Adipocytes ; cytology ; drug effects ; Catecholamines ; pharmacology ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Epinephrine ; pharmacology ; Humans ; Isoproterenol ; pharmacology ; Norepinephrine ; pharmacology ; Obesity ; drug therapy ; Receptors, Adrenergic, beta ; Up-Regulation

Perioperative unilateral mydriasis is a disturbing finding, which is suggestive of acute intracranial pathology during general anesthesia. In addition, the assessment of an abnormal neurological injury is limited during general anesthesia, with anisocoria requiring special consideration. The case of a 27 year old healthy male patient, with ipsilateral mydriasis found near the end of surgery of open reduction for left blow out fracture, was experienced. The patient's pupils were bilaterally equal four hours after uneventfully surgery. The possible causes of unilateral mydriasis include the effects of anesthetic agents, stellate ganglion block, impaired venous return from head and neck, an acute intracranial mass lesion or hemorrhagic event, direct eye trauma, pre-existing medical or surgical conditions (Adie's tonic pupil, artificial eye etc.) and inadvertent direct deposition of alpha-adrenergic or anticholinergic agents in the eye. The understanding and diagnosis of unusual mydriasis during general anesthesia requires knowledge of the autonomic nerve pathways and pharmacology of the eye. In this case, the myadriasis of the left eye was considered to have resulted from the absorption of 1:100.000 topical epinephrine infiltrated into the lower eyelid via episcleral vessels.
Absorption ; Adult ; Anesthesia, General ; Anesthetics ; Anisocoria ; Autonomic Pathways ; Cholinergic Antagonists ; Diagnosis ; Epinephrine ; Eye, Artificial ; Eyelids ; Head ; Humans ; Male ; Mydriasis* ; Neck ; Pathology ; Pharmacology ; Pupil ; Stellate Ganglion ; Tonic Pupil

OBJECTIVES: Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms. METHODS: Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA. RESULTS: Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited. CONCLUSIONS MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.
Animals ; Rats ; Adrenal Medulla ; Cell Transdifferentiation ; Chromaffin Cells ; Dexamethasone ; Epinephrine/pharmacology* ; Mammals ; Nerve Growth Factor ; Neurons ; Peripherins ; Protein Kinases ; Tyrosine 3-Monooxygenase

The purpose of this study was to elucidate the effects of fentanyl and morphine on the ability of epinephrine to induce arrhythmias in halothane-anesthetized dogs. Epinephrine was infused in progressively increasing doses from 0.5 ug/kg/min. Arrhythmogenic dose of epinephrine(ADE), defined as that induces 4 or more premature ventricular contractions within 15 s during 3 min iafusions of epinephrine, was determined before(control) and after pretreatment of either fentanyl(6 ug/kg i.v. plus 6 pg/kg/hr) or morphine(0.2mg/kg i.v. plus 0.2 mg/kg/hr). Blood pressure and heart rate were also measured immediately before(baseline), immediately after infusion of epinephrine. The results were as follows. l) Fentanyl and morphine increased ADE by 37%(2.19+/-0.49 to 3.00+/-0.44 ug/kg/min, p<0.01) and by 43%(2.50+/-0.60 to 3.58+/-0.93 ug/kg/min, p<0.05), respectively. 2) Percent increases in systolic blood pressure at control were similar to those after pretreatment with fentanyl or morphine in both groups, but systolic blood pressures at the time of arrhythmia after pretreatment were lower than those at control in fentanyl(p<0.05) and morphine group(NS). 3) Fentanyl and morphine decreased heart rate by 27%(127+/-8 to 93+/-6 beats/min, p<0.001) and by 13%(118+/-5 to 103+/-5 beats/min, p<0.05), respectively. These results suggest that fentanyl or morphine inhibits epinephrine induced arrhythmias during halothane-oxygen anesthesia. Thus, pretreatment of surgical patients, who were supposed to receive epinephrine during halothane anesthesia, with either fentanyl or morphine might be safe.
Anesthesia ; Anesthetics ; Animals ; Arrhythmias, Cardiac* ; Blood Pressure ; Dogs* ; Epinephrine* ; Fentanyl* ; Halothane* ; Heart ; Heart Rate ; Humans ; Morphine* ; Pharmacology ; Sympathetic Nervous System ; Ventricular Premature Complexes