The purpose of this study was to investigate the effects of α₂ adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α₂ adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α₂ adrenergic receptor.
Adrenergic alpha-2 Receptor Agonists/therapeutic use* ; Alcoholism/drug therapy* ; Animals ; Dexmedetomidine/therapeutic use* ; Hippocampus/metabolism* ; Male ; Norepinephrine ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2/metabolism* ; Substance Withdrawal Syndrome/drug therapy* ; Yohimbine/pharmacology*

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.
3,4-Dihydroxyphenylacetic Acid/pharmacology* ; Animals ; Antidepressive Agents/therapeutic use* ; Chromatography, Liquid ; Depression/drug therapy* ; Disease Models, Animal ; Dopamine ; Eosine Yellowish-(YS)/pharmacology* ; Hematoxylin/pharmacology* ; Hippocampus/metabolism* ; Homovanillic Acid/pharmacology* ; Hydroxyindoleacetic Acid/metabolism* ; Methoxyhydroxyphenylglycol/pharmacology* ; Monoamine Oxidase/metabolism* ; Neurotransmitter Agents/metabolism* ; Norepinephrine/pharmacology* ; Plant Extracts ; Rats ; Rehmannia/chemistry* ; Serotonin/metabolism* ; Serotonin Plasma Membrane Transport Proteins/pharmacology* ; Stress, Psychological/metabolism* ; Tandem Mass Spectrometry ; Tryptophan Hydroxylase/metabolism*

BACKGROUNDInconsistencies in the use of the vasoactive agent therapy to treat shock are found in previous studies. A descriptive study was proposed to investigate current use of vasoactive agents for patients with shock in Chinese intensive care settings.

METHODSA nationwide survey of physicians was conducted from August 17 to December 30, 2012. Physicians were asked to complete a questionnaire which focused on the selection of vasoactive agents, management in the use of vasopressor/inotropic therapy, monitoring protocols when using these agents, and demographic characteristics.

RESULTSThe response rate was 65.1% with physicians returning 586 valid questionnaires. Norepinephrine was the first choice of a vasopressor used to treat septic shock by 70.8% of respondents; 73.4% of respondents favored dopamine for hypovolemic shock; and 68.3% of respondents preferred dopamine for cardiogenic shock. Dobutamine was selected by 84.1%, 64.5%, and 60.6% of respondents for septic, hypovolemic, and cardiogenic shock, respectively. Vasodilator agents were prescribed by physicians in the management of cardiogenic shock (67.1%) rather than for septic (32.3%) and hypovolemic shock (6.5%). A significant number of physicians working in teaching hospitals were using vasoactive agents in an appropriate manner when compared to physicians in nonteaching hospitals.

CONCLUSIONSVasoactive agent use for treatment of shock is inconsistent according to self-report by Chinese intensive care physicians; however, the variation in use depends upon the form of shock being treated and the type of hospital; thus, corresponding educational programs about vasoactive agent use for shock management should be considered.

Data Collection ; Dobutamine ; therapeutic use ; Dopamine ; therapeutic use ; Humans ; Intensive Care Units ; statistics & numerical data ; Norepinephrine ; therapeutic use ; Shock ; drug therapy ; Shock, Cardiogenic ; drug therapy ; Shock, Septic ; drug therapy ; Surveys and Questionnaires ; Vasoconstrictor Agents ; therapeutic use ; Vasodilator Agents ; therapeutic use

OBJECTIVETo observe the clinical curative effect of Chinese medicine Bushen Huoxue Granule(补肾活血颗粒, BHG) on Parkinson's disease (PD) patients with depressive state.

METHODSSixty-two PD patients with depressive state were randomly assigned to two groups by using a random number table, 31 in each group. Madopar was given to all as the conventional treatment. The fluoxetine hydrochloride dispersible tablet was given to the patients in the control group and BHG was given to those in the treatment group. The therapeutic course for all was 12 weeks. Before and after treatment, Hamilton depression rating scale (HAMD) was applied to judge the curative effect, and the changes of cerebral neurotransmitters levels in the brain of patients were detected by encephalofluctuograph technique.

RESULTSThe scores of HAMD in the two groups were decreased markedly after 12-week treatment. It was lower in the treatment group than that in the control group with significant difference (P<0.01). The contents of norepinephrine (NE) and 5-serotonin (5-HT) in the PD patients were obviously lower than normal value. There was no significant difference between the two groups before treatment (P>0.05). The contents of NE and 5-HT were all increased in the two groups after treatment (P<0.05), with significant differences between the two groups (P<0.01).

CONCLUSIONBHG could increase the contents of NE and 5-HT in PD patients' brain to improve the depressive state of PD patients.

Aged ; Brain ; drug effects ; metabolism ; Depression ; complications ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Norepinephrine ; metabolism ; Parkinson Disease ; complications ; drug therapy ; Serotonin ; metabolism ; Treatment Outcome

OBJECTIVETo study the mechanism of warm-hot nature Chinese drugs (WHNCD) for promoting blood circulation and removing blood stasis (PBCRBS) for intervening model rats of cold coagulation and blood stasis syndrome (CCBSS).

METHODSCCBSS rat model was set up in outbred SD rats using ice water immersion method. Totally 300 successfully modeled CCBSS rats were randomly divided into 5 groups according to the principle of balance weight, 60 in each group. Contents of triothyrone (T3), tetraiodothyroine (T4), progesterone (P), 5-hydroxytryptamine (5-HT), and noradrenalin (NE) were paralleledly detected in all groups. Then rats in each group were subdivided into 6 subgroups as the model group, the curcuma group, the Ligsticum Chuanxiong group, the safflower group, the Rhizoma Corydalis group, and the Olibanumg group. Besides, 5 normal control groups were set up for 5 indices, 50 rats in total. We need 70 rats (7 groups) to finish observing 1 index, 350 rats in total for 5 indices. Except those in the model group and the normal control group, rats were administered with corresponding decoction at 20 g crude drugs/kg body weight by gastrogavage, 3 mL each time, once daily for 7 successive days. Equal volume of normal saline was given to rats in the normal control group and the model group. Contents of T3, T4, P, 5-HT, and NE were detected before treatment and 1 week after treatment.

RESULTSCompared with before treatment in the same group, T3 increased in the Ligsticum Chuanxiong group and the Olibanumg group, 5-HT increased in the Ligsticum Chuanxiong group, T4, NE, and P increased in all medicated groups (P < 0.05). Compared with the normal control group, contents of T3, T4, 5-HT, NE, and P in the model group decreased (P < 0.05). Compared with the model group, contents of T3, T4, 5-HT, and NE increased in each medicated group (P < 0.05). There was statistical difference in contents of P between the Ligsticum Chuanxiong group and the Olibanumg group (P < 0.05).

CONCLUSIONSWHNCD for PBCRBS had regulatory roles in serum contents of T3, T4, P, and NE in modeled rats of CCBSS. They could promote the thyroid gland-gonadal axis function, enhance the function of the endocrine system, which might be one of the pharmacodynamic mechanism of WHNCD for PBCRBS in intervening CCBSS.

Animals ; Blood Coagulation ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hot Temperature ; Medicine, Chinese Traditional ; Norepinephrine ; metabolism ; Progesterone ; metabolism ; Rats ; Serotonin ; metabolism

OBJECTIVETo investigate the influence of Yiqi Huatan Decoction (, YHD) on a model of depression in rats under different pathological conditions.

METHODSThirty-two male SD rats were randomly divided into 4 groups of 8: normal, model, YHD, and maprotiline. The model group, YHD group and maprotiline group used separate feeding and rats were exposed to chronic and unpredictable stress to build the depression model. From day 2, the YHD group and maprotiline group were respectively given YHD (7 g/kg) and maprotiline (10 mg/kg) by gastrogavage once daily. The normal and model groups were given the same volume of drinking water. The medication duration were 21 days. At the end of the experiment, the serum levels of copper and zinc were determined by atomic absorption spectroscopy, plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (COR) were detected by radioimmunoassay, and levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the hypothalamus were analysed by high performance liquid chromatography-eletricochemistry.

RESULTSCompared with the content of copper and zinc in the serum of rats in the normal group, serum copper levels in model rats were significantly increased and zinc content was significantly reduced (both P<0.05). Plasma concentrations of ACTH and COR in the model group were significantly increased compared with those in the normal group (P<0.05, P<0.01). The contents of NE, DA, and 5-HT in the hypothalamus of rats in the model group were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, the serum copper content and plasma concentrations of ACTH and COR were significantly decreased (all P<0.05); meanwhile, serum zinc content and hypothalamic contents of NE, DA, and 5-HT were significantly increased in rats of the YHD group (all P<0.05). The same effects were also shown in the maprotiline group except for 5-HT (all P<0.05)

CONCLUSIONThe pharmacological actions of YHD for depression might be related to improving trace-element anomalies, reversing endocrine dysfunction, and modulating the disorders of monoaminergic neurotransmitters.

Adrenocorticotropic Hormone ; blood ; Animals ; Behavior, Animal ; drug effects ; Copper ; blood ; Depression ; blood ; drug therapy ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hydrocortisone ; blood ; Hypothalamus ; drug effects ; metabolism ; Male ; Norepinephrine ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Zinc ; blood

BACKGROUNDAliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated.

METHODSMale Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups: angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, β adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed.

RESULTSThe plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats.

CONCLUSIONSAliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.

Amides ; pharmacology ; therapeutic use ; Animals ; Fumarates ; pharmacology ; therapeutic use ; Male ; Myocardial Infarction ; blood ; drug therapy ; Norepinephrine ; blood ; Rats ; Rats, Sprague-Dawley ; Renin ; antagonists & inhibitors ; Sympathetic Nervous System ; drug effects ; Tachycardia, Ventricular ; prevention & control

PURPOSE: Acute pancreatitis is one of the potentially lethal complications that occurs after cardiac surgery. We tried to identify risk factors for and the prognosis of acute pancreatitis after cardiac valve surgery with cardiopulmonary bypass. MATERIALS AND METHODS: We retrospectively analyzed a database of consecutive patients who underwent cardiac valve surgery with cardiopulmonary bypass between January 2005 and April 2010 at our institution. Patients were classified as having acute pancreatitis based on serum lipase concentration and clinical symptoms (lipase > or =180 U/L or > or =60 U/L with relevant symptoms). RESULTS: Of the 986 patients who underwent cardiac valve surgery with cardiopulmonary bypass, 58 (5.9%) patients developed post-operative pancreatitis. Post-operative hospital stay was significantly longer (29.7+/-45.6 days vs. 12.4+/-10.7 days, p=0.005) and in-hospital mortality rate was higher (15.5% vs. 2.0%, p<0.001) in patients with post-operative pancreatitis than those without. Hypertension, chronic kidney disease, and peri-operative use of norepinephrine were identified as independent risk factors for developing pancreatitis after cardiac valve surgery. CONCLUSION: We found that acute pancreatitis after cardiac valve surgery requires longer hospitalization and increases the in-hospital mortality rate. Clinicians should be aware that patients could develop pancreatitis after cardiac valve surgery, especially in patients with hypertension and chronic kidney disease treated with norepinephrine.
Acute Disease ; Adult ; Aged ; Cardiac Surgical Procedures/adverse effects ; Cardiopulmonary Bypass ; Female ; Heart Valve Diseases/*complications/*surgery ; Heart Valve Prosthesis Implantation/*adverse effects ; Humans ; Lipase/blood ; Male ; Middle Aged ; Multivariate Analysis ; Norepinephrine/therapeutic use ; Pancreatitis/*diagnosis/*etiology ; Postoperative Period ; Prognosis ; Retrospective Studies ; Risk Factors

PURPOSE: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. MATERIALS AND METHODS: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6x10-4 M levobupivacaine, 2x10-3 M ropivacaine, and 7x10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. RESULTS: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3x10-3 M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. CONCLUSION: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.
Amides/adverse effects ; Anesthetics, Local/*adverse effects ; Animals ; Bupivacaine/adverse effects/analogs & derivatives ; Emulsions/*chemistry/*therapeutic use ; Lipids/*chemistry ; Male ; Mepivacaine/adverse effects ; Norepinephrine/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Vasodilation/*drug effects

OBJECTIVETo study the effects of Jing'an Oral Liquid (JOL) on the central neurotransmitters of multiple tics (MT) children.

METHODSSixty MT children patients were randomly assigned to the treatment group and the control group, 30 cases in each group. Another 30 healthy children were recruited as the health group. JOL and Tiapride Tablet (TT) was respectively given to patients in the treatment group and the control group. The treatment course was 2 months. The levels of central neurotransmitters [dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), glutamic acid (GLU), aspartate (ASP), gamma-aminobutyric acid (GABA)] were measured using high performance liquid chromatography (HPLC) before and after treatment, and compared with the health group.

RESULTSCompared with the health group, the levels of 5-HT, HVA, GLU, and ASP significantly increased in the treatment group and the control group before treatment (P < 0.05), GABA significantly decreased (P < 0.05). Compared with before treatment in the same group, the levels 5-HT, HVA, and GLU significantly decreased in the treatment group (P < 0.05), while the levels of NE and GABA significantly increased (P < 0.05). The levels of DA, 5-HT, GLU, and ASP significantly decreased, while the levels of NE ang GABA significantly increased in the control group, showing statistical difference (P < 0.05). There was no statistical difference in each index between the treatment group and the control group before and after treatment (P > 0.05).

CONCLUSIONS(1) The imbalance of a variety of monoamines and amino acid neurotransmitters can lead to MT, especially in the changes of 5-HT, HVA, GLU, ASP, and GABA. (2) JOL can significantly reduce the levels of 5-HT, HVA, and GLU, and significantly increase the levels of NE and GABA, which might be its pharmacodynamic mechanisms for treating MT.

Child ; Dopamine ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Neurotransmitter Agents ; blood ; Norepinephrine ; blood ; Phytotherapy ; Serotonin ; blood ; Tiapride Hydrochloride ; therapeutic use ; Tourette Syndrome ; blood ; drug therapy