Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine (10⁻¹⁰–10⁻³ M) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside (10⁻¹⁰–10⁻³ M) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.
Acetylcholine ; Administration, Oral ; Amlodipine ; Animals ; Aorta ; Aralia* ; Blood Pressure ; Ethanol* ; Hypertension ; Lipid Peroxidation ; Malondialdehyde ; Nitroprusside ; Norepinephrine ; Organ Size ; Plasma ; Rats ; Rats, Inbred SHR*

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non-sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
Administration, Intravenous ; Administration, Oral ; Analgesia ; Analgesics, Non-Narcotic ; Anticonvulsants ; Antidepressive Agents ; Calcium ; Carbamazepine ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Hiccup ; Long-Term Potentiation ; Molecular Mechanisms of Pharmacological Action ; N-Methylaspartate ; Nausea ; Nefopam* ; Neuralgia* ; Neurotransmitter Agents ; Nociceptive Pain ; Norepinephrine ; Shivering ; Sleep Stages ; Sodium Channels ; Sweat ; Sweating ; Tachycardia

Clinical study of modified Ganmai Dazao decoction in the treatment of yang deficiency climacteric depression and observe the effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with yang deficiency climacteric depression. 86 cases were randomly divided into treatment group treated with modified Ganmai Dazao decoction and control group treated with Deanxit. The curative effect was evaluated with Hamilton's depressive scale (HAMD) and pittsburgh sleep quality scale (PSQI) before and at the end of the two and four weeks of the treatment, the serum levels of serotonin (5-HT), norepinephrine (NE), estradiol (E2), follicle stimulating hormone (FSH), luteotropic hormone (LH) were detected before and after the four weeks of the treatment The results showed that the total effective power of treatment group was 88.4% and the total effective power of control group was 81.4% after four weeks interference, with insignificant difference between the two groups. After two and four weeks of the treatment, the score of HAMD decreased remarkably in both groups (P < 0.01), with insignificant difference between the two groups in same phase. After two and four weeks of the treatment, the total score of PSQI decreased remarkably in both groups (P < 0.05), with significant difference between the two groups after four weeks (P < 0.01). After four weeks of treatment, the serum levels of 5-HT and NE increased (P < 0.01), with insignificant difference between the groups. After four weeks of treatment, the serum levels of E2 increased obviously (P < 0.05), the levels of FSH decreased obviously (P < 0.05), the levels of LH decreased insignificant, with insignificant difference between two groups. This study indicates that modified Ganmai Dazao decoction has obvious therapeutic effects in the treatment of climacteric depression, and showed equivalent efficacy with Deanxit, and modified Ganmai Dazao decoction has better effect on improving the sleep quality in patients than Deanxit, the effect of improved clinical symptoms may be through adjusted levels of 5-HT, NE, E2, FSH and LH of climacteric depression.
Adult ; Depression ; blood ; drug therapy ; etiology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Menopause ; drug effects ; psychology ; Middle Aged ; Neurosecretory Systems ; drug effects ; metabolism ; Norepinephrine ; blood ; Phytotherapy ; Serotonin ; blood

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.
Animals ; Antidepressive Agents ; administration & dosage ; pharmacology ; Coumaric Acids ; administration & dosage ; pharmacology ; Depression ; chemically induced ; complications ; metabolism ; physiopathology ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Frontal Lobe ; metabolism ; Hippocampus ; metabolism ; Hyperalgesia ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Nitric Oxide ; metabolism ; Norepinephrine ; metabolism ; Pain ; chemically induced ; complications ; metabolism ; physiopathology ; Pain Measurement ; Random Allocation ; Reserpine ; adverse effects ; Serotonin ; metabolism ; Superoxide Dismutase ; metabolism ; Swimming ; physiology

OBJECTIVE: Duloxetine hydrochloride is a selective serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor. It is approved for effective treatment for major depressive disorder. The pharmacokinetics (PK) of duloxetine has been studied, but few pharmacokinetics properties in Chinese subjects are available. This study explored the dose proportionality and determined duloxetine levels in human plasma by comparing the PK properties after administration of single or multiple doses in healthy volunteers. METHODS: Thirty-six subjects were divided randomly into three groups and received a single dose of 15, 30, or 60 mg duloxetine. Those who received 30 mg continued on to the multiple-dose phase and received 30 mg daily for 7 days. Liquid chromatography/mass spectroscopy was applied to determine concentrations. The PK properties were calculated and included maximum plasma concentration (Cmax), time when maximum plasma concentration was reached (Tmax), time when half-maximum plasma concentration was reached (t1/2), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t), mean concentration levels (AUC0-infinity), and apparent total clearance of the drug from plasma after oral administration (CL/F). RESULTS: The standard calibration curve was linear in the concentration range 0.11-112 ng/ml (r>0.992). Linear PK properties were found at doses of 15-60 mg. The Cmax and AUC were proportional to dose, but the Tmax and t1/2 did not increase with increasing dose. CONCLUSION: No significant differences in the PK parameters were found among the three groups during the single-dose phase. The AUC and Cmax were greater in the multiple-dose phase, indicating duloxetine accumulation following multiple-dose administration.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Calibration ; Depressive Disorder, Major ; Humans ; Norepinephrine ; Plasma ; Serotonin ; Spectrum Analysis ; Tablets, Enteric-Coated ; Thiophenes ; Duloxetine Hydrochloride

OBJECTIVETo explore the clinical effect of low dose pituitrin in children with septic shock.

METHODSA total of 48 pediatric cases with septic shock, in whom 6 hours, conventional treatment could not reverse shock from January 2008 to December 2010, were selected for this study. The patients were divided into two groups randomly (completely random design) (control group 24, remedial group 24). The conventional treatment included antibiotics/fluid resuscitation/correcting acid-base imbalance, glucocorticoid, organ (heart/lung) support, dopamine 1 - 15 µg/(kg·min) and norepinephrine 0.5 - 2 µg/(kg·min) pumped in continuously in the control group. In initial 6 hours the same treatment was given to the remedial group, while low dose pituitrin (0.01 - 0.03 U/min) was pumped additionally during the rest of time. The therapeutic effect on correcting shock was evaluated in both groups.

RESULTSThe total effective rate was 76.2% in the remedial group and 40.0% in the control group; the mortality was 33.3% and 60% respectively. The difference between both groups was significant (P = 0.025).

CONCLUSIONLow dose pituitrin could improve the clinical effect significantly in children with septic shock in whom 6 hours conventional treatment failed to correct shock, shorten the total periods of treatment, and decrease mortality.

Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Norepinephrine ; therapeutic use ; Pituitary Hormones, Posterior ; administration & dosage ; therapeutic use ; Shock, Septic ; drug therapy ; Treatment Outcome ; Vasoconstrictor Agents ; therapeutic use

The purpose of this study is to investigate whether the combination of green tea extract (GTE) and L-theanine has an anxiolytic effect by oral administration through behavioral tests and neurtransmitters (or hormone) anaylses. Four week oral administration of GTE (24 mg/kg), L-theanine (4 mg/kg) or their combination showed anxiety-reducing effects determined by increasing numbers of head-dips in a hole board test and reducing retention time in a rota-rod test without changing spontaneous locomotor activity. Biochemical analyses indicated that the test materials decreased dopamine (DA), noradrenaline (NA), corticosterone (CS) and increased serotonin (5-HT) levels in brain cortex, hippocampus, and striatum, which suggests a possible mechanism of previous behavioral tests. Although the synergistic effects of GTE and L-theanine combination were not observed on the behavioral test, its effects on neurotransmitters (NA, CS) were synergistic and comparable to diazepam (2 mg/kg i.p.) with much less muscle relaxation side effect. Therefore, a combination of GTE and L-theanine may be useful as a functional food ingredient having an anxiolytic effect.
Administration, Oral ; Anti-Anxiety Agents ; Brain ; Corticosterone ; Diazepam ; Dopamine ; Functional Food ; Hippocampus ; Motor Activity ; Muscle Relaxation ; Neurotransmitter Agents ; Norepinephrine ; Retention (Psychology) ; Serotonin ; Tea

Although numerous studies have validated the efficacy of intracoronary shunt on reducing left ventricular dysfunction during off-pump coronary artery bypass surgery (OPCAB), there is lack of evidence supporting its role on right ventricular (RV) function during right coronary artery (RCA) revascularization. Therefore, we studied the effect of intracoronary shunt during grafting of dominant RCA without visible collateral supply on global RV function using thermodilution method. Forty patients scheduled for multivessel OPCAB with right dominant coronary circulation without collateral supply confirmed by angiography were randomized to RCA revascularization either with a shunt (n=20) or soft snare occlusion (n=20). RV ejection fraction (RVEF) was recorded at baseline, during RCA grafting, and 15 min after reperfusion. Corresponding RV stroke work index (RVSWI) was calculated. RVEF and RVSWI decreased significantly during RCA grafting and returned to baseline values after reperfusion in both groups without any significant differences between the groups. Intracoronary shunt did not exert any beneficial effect on global RV function during RCA grafting, even in the absence of visible collateral supply. Regarding the possibility of graft failure by intracoronary shunt-induced endothelial damage, routine use of intracoronary shunt during RCA grafting is not recommended in patients with preserved biventricular function.
Aged ; Blood Pressure ; *Collateral Circulation ; Coronary Artery Bypass, Off-Pump/*methods ; Coronary Artery Disease/physiopathology/*surgery ; *Coronary Circulation ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Norepinephrine/administration & dosage ; Prospective Studies ; Stroke Volume ; Sympathomimetics/administration & dosage ; Thermodilution ; *Ventricular Function, Right

The aim of this study is to investigate the effect of isosorbide-5-mononitrate (ISMN) on the electric field stimulation induced sympathetic purinergic vasoconstriction of the rabbit saphenous arterial rings. Isometric vasoconstrictive responses to electric field stimulation and to exogenous noradrenaline and adenosine triphosphate were recorded. We found that the vasoconstrictive responses to electric field stimulation (15 V, 1 ms pulse duration, 2 - 16 Hz) were frequency-dependant in the rabbit saphenous arterial rings, and abolished by tetrodotoxin (0.1 micromol x L(-1)). The alpha1-adrenoceptor antagonist prazosin (1 micromol x L(-1)) did not affect the vascular responses to the electric field stimulation (2 -8 Hz). After a combination treatment with both alpha,beta-meATP (3 micromol x L(-1), desensitizing P2X1 receptors) and prazosin (1 micromol x L(-1)), the vasoconstrictive responses to electric field stimulation were abolished. When the arterial preparation was treated with ISMN (one preparation was exposed to only one concentration of ISMN), ISMN at 0.1 mmol x L(-1) significantly inhibited the vasoconstriction induced by electric stimulation at 8 Hz, 0.3 and 1.0 mmol x L(-1) significantly inhibited the vasoconstrictive responses to electric stimulation at 2 - 16 Hz. The highest concentration of ISMN (1.0 mmol x L(-1)) reduced the vasoconstrictive responses by 46% (2 Hz), 47% (4 Hz), 34% (8 Hz) and 22% (16 Hz), separately. ISMN (0.3 and 1.0 mmol x L(-1)) did not affect the vascular responses to exogenous noradrenaline (0.01-100 micromol x L(-1)) and adenosine triphosphate (1 mmol x L(-1)). It is reasonable to suggest that ISMN inhibits the purinergic vasoconstriction induced by sympathetic nerve stimulation via a prejunctional mechanism.
Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Adrenergic alpha-Antagonists ; pharmacology ; Animals ; Arteries ; drug effects ; Delayed-Action Preparations ; Electric Stimulation ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacology ; Male ; Norepinephrine ; pharmacology ; Prazosin ; pharmacology ; Purinergic P2 Receptor Agonists ; Rabbits ; Receptors, Purinergic P2X ; Vasoconstriction ; drug effects

OBJECTIVETo investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock.

METHODSEighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected.

RESULTSBefore anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal.

CONCLUSIONSThe first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.

APACHE ; Adult ; Aged ; Blood Transfusion ; Cardiotonic Agents ; administration & dosage ; Combined Modality Therapy ; Dopamine ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Kidney ; drug effects ; physiopathology ; Male ; Middle Aged ; Norepinephrine ; administration & dosage ; Retrospective Studies ; Shock, Septic ; physiopathology ; therapy ; Vasoconstrictor Agents ; administration & dosage