BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of beta-amyloid peptide (Abeta) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Abeta1-42 until evaluation) effectively blocked Abeta1-42-induced impairment in passive avoidance performance, and Abeta1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1alpha in the hippocampus. In addition, it alleviated the Abeta1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1beta in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.
Eleutherococcus* ; Acetylcholine ; Administration, Oral ; Alzheimer Disease* ; Amyloid ; Animals ; Brain ; Glial Fibrillary Acidic Protein ; Hippocampus ; Interleukins ; Malondialdehyde ; Mice* ; Plaque, Amyloid

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of beta-amyloid peptide (Abeta) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Abeta1-42 until evaluation) effectively blocked Abeta1-42-induced impairment in passive avoidance performance, and Abeta1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1alpha in the hippocampus. In addition, it alleviated the Abeta1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1beta in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.
Eleutherococcus* ; Acetylcholine ; Administration, Oral ; Alzheimer Disease* ; Amyloid ; Animals ; Brain ; Glial Fibrillary Acidic Protein ; Hippocampus ; Interleukins ; Malondialdehyde ; Mice* ; Plaque, Amyloid

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*

BACKGROUND: Although recent studies have demonstrated that infusion of L-arginine reduces myocardial necrotic area during prolonged ischemia, its effects on transient postischemic myocardial dysfunction(myocardial stunning) and microvascular dyfunction(vascular stunning) are not well known. To investigate whether intravenous administration of L-arginine, physiological nitric oxide(NO) precursor, during reperfusion would attenuate postischemic myocardial dysfunction and microvascular dysfunction, 15 open-chest dogs were studied. METHODS: In 15 pentobarbital anesthesized open-chest dogs, left circumflex coronary artery was occluded for 20 minutes and was followed by a reperfusion for 60 minutes. L-Arginine(30mg/kg)(L-arginine group, n=8) or saline(control group, n=7) was given intravenously by a bolus 1 minute before reperfusion and was followed by a continuous infusion(10mg/kg/min) for 30 minutes during reperfusion. Before coronary occlusion and 60 minutes after reperfusion, coronary blood flow(CBF) and coronary vascular resistance(CVR) wre measured after intracoronary injection of each of acetylcholine(0.01/kg) and adenosine(1.5/kg), and reactive hyperemia with coronary occlusion(RH20) for 20 seconds was measured. Myocardial segment thickening in the area of ischemia-reperfusion was measured using 2D-echocardiography. The echocardiographic images were digitized and analyzed by cardiac image analyzer. RESULTS: The results obtained 60 minutes after reperfusion were as follows. 1) CBF was decreased by 41% in L-arginine group vs 30.1% in control group(p < 0.05) and CVR was increased by 83.9% in L-arginine group vs 19.3% in control group after 60 minutes of reperfusion, compared with pre-occlusion baseline values. 2) Percent change of CBF was decreased in control group(acetylcholine by 25.8%, adenosine by 29.2%, RH20 by 39.8%), while it was increased in L-arginine group(acetylcholine by 60%, adenosine by 22%, RH20 by 26.7%). Percent change of CVR was increased in control group(acetylcholine by 10.5%, adenosine by 6.9%, RH20 by 21%), but it was decreased in L-arginine group(acetylcholine by 10%, adenosine by 6.6%, RH20 by 1.6%). Increase of CBF and decrease of CVR were significant on acetylcholine and RH20 between control group and L-arginine group. 3) Fraction of myocardial segment thickening was significantly decreased in L-arginine group(by 80%) compared with control group(by 61.7%, p < 0.05). CONCLUSIONS: The finding that L-arginine depressed post-ischemic myocardial contractil function suggests that systemic infusion of L-arginine has unfavorable effect on myocardial stunning. In contrast, the finding that L-arginine improved CBF and CVR with acetylcholine and adenosine and reactive hyperemia indicates that L-arginine may exert a beneficial effect on vascular stunning. These results suggest that L-arginine may have independent effects on myocardial stunning and vascular stunning.
Acetylcholine ; Adenosine ; Administration, Intravenous ; Animals ; Arginine* ; Coronary Occlusion ; Coronary Vessels ; Dogs* ; Echocardiography ; Hyperemia ; Ischemia ; Myocardial Reperfusion ; Myocardial Stunning ; Nitric Oxide ; Pentobarbital ; Reperfusion

Overactive bladder (OAB) is characterized by urgency, with or without urge incontinence, and is usually accompanied by an increased micturition frequency and nocturia in the absence of other identifiable metabolic or pathologic conditions affecting the lower urinary tract. Although OAB is a common, distressing condition, a large number of patients remain untreated. The antimuscarinic drug medication, in conjugation with behavioral therapy such as bladder training, remains the first-line management of patients with OAB. Drugs used to treat OAB affect the nerve and function of the detrusor muscle, causing the detrusor muscle to relax and thus reduce the frequency and intensity of contractions of the bladder. These drugs work by blocking the binding of neurotransmitters called acetylcholine to specific sites of the bladder muscle. The binding of neurotransmitters to the receptor sites causes a sequence of changes that result in muscle contractions. Blocking this binding prevents the contraction of the bladder. Adverse events, such as dry mouth, dry eyes, constipation and headache can occur in all antimuscarinic drugs. In addition, intravesical injection can be used for patients who do not respond to oral medication.
Acetylcholine ; Administration, Intravesical ; Constipation ; Headache ; Humans ; Mouth ; Muscle Contraction ; Neurotransmitter Agents ; Nocturia ; Urinary Bladder ; Urinary Bladder, Overactive* ; Urinary Incontinence, Urge ; Urinary Tract ; Urination

We performed a randomized, prospective study to evaluate the effect of intraoperative, intracameral carbachol or acetylcholine on early postoperative intraocular pressure(IOP) after extracapsular cataract extraction(ECCE) and posterior chamber lens(PCL) implantation. Fifty-six eyes of 56 patients scheduled for routine ECCE and PCL implantation were randomly assigned into three groups: (1)carbachol infusion (19 eyes) (2) acetylcholine infusion (15 eyes) (3)balanced salt solution (BSS) infusion (control, 22 eyes). We compared the preoperative IOP, early postoperative IOP, postoperative 24 hours IOP and postoperative 1 week IOP. In the measurement of early postoperative IOP, IOP was measured at least twice at 3, 6 or 9 hours postoperatively. There was no significant difference in IOP between the three groups preoperatively, at postoperative 3 hours, and 1 week. At postoperative 6 hours, both the carbachol infusion group and acetylcholine infusion group were significantly different from the BSS infusion group. At postoperative 9 and 24 hours, only carbachol infusion group had a significant difference from BSS infusion group in suppression of postoperative IOP increase. Our results suggest that intraoperative, intracameral administration of carbachol or acetylcholine prevents early postoperative IOP increase, and that carbachol has a more lasting effect.
Acetylcholine/administration & dosage/*pharmacology ; Adult ; Aged ; Anterior Chamber/drug effects ; Carbachol/administration & dosage/*pharmacology ; Cataract Extraction/*adverse effects ; Female ; Humans ; Intraocular Pressure/*drug effects ; Lenses, Intraocular ; Male ; Middle Aged ; Ocular Hypertension/etiology/*prevention & control ; Postoperative Complications ; Prospective Studies

Hypertension is associated with endothelial dysfunction and increased cardiovascular risk. Caveolin-1 regulates nitric oxide (NO) signaling by modulating endothelial nitric oxide synthase (eNOS). The purpose of this study was to examine whether HMG-CoA reductase inhibitor improves impaired endothelial function of the aorta in spontaneous hypertensive rat (SHR) and to determine the underlying mechanisms involved. Eight-week-old male SHR were assigned to either a control group (CON, n=11) or a rosuvastatin group (ROS, n=12), rosuvastatin (10 mg/kg/day) administered for eight weeks. Abdominal aortic rings were prepared and responses to acetylcholine (10-9-10-4 M) were determined in vitro. To evaluate the potential role of NO and caveolin-1, we examined the plasma activity of NOx, eNOS, phosphorylated-eNOS and expression of caveolin-1. The relaxation in response to acetylcholine was significantly enhanced in ROS compared to CON. Expression of eNOS RNA was unchanged, whereas NOx level and phosphorylated-eNOS at serine-1177 was increased accompanied with depressed level of caveolin-1 in ROS. We conclude that 3-Hydroxy-3-methylglutaryl Coenzyme-A (HMG-CoA) reductase inhibitor can improve impaired endothelial dysfunction in SHR, and its underlying mechanisms are associated with increased NO production. Furthermore, HMG-CoA reductase inhibitor can activate the eNOS by phosphorylation related to decreased caveolin-1 abundance. These results imply the therapeutic strategies for the high blood pressure-associated endothelial dysfunction through modifying caveolin status.
Acetylcholine/metabolism ; Animals ; Aorta/metabolism/physiopathology ; Blood Pressure/drug effects ; Caveolin 1/*metabolism ; Down-Regulation ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Fluorobenzenes/administration & dosage/*pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*pharmacology ; Hypertension/enzymology/metabolism/*physiopathology ; Male ; Nitric Oxide/blood ; Nitric Oxide Synthase Type III/*metabolism ; Phosphorylation ; Pyrimidines/administration & dosage/*pharmacology ; Rats ; Rats, Inbred SHR ; Sulfonamides/administration & dosage/*pharmacology ; Vasodilation/drug effects

OBJECTIVETo understand the mechanism of effect of conditioned immune response in curing bronchial asthma.

METHODSAn experimental asthma modal was produced on healthy BALB/C mice (female, 4 - 6 weeks old) by sensitization and stimulation with ovalbumin (OV A). Totally 105 mice were divided into 7 groups randomly with 15 in each and treated differently: in group CIR(1), noise was used as conditioned stimulus (CS) and budesonide and salbutamol as unconditioned stimulus (UCS) respectively, a conditioned immune response model of mice with asthma was established by the combination of CS and UCS 7 times (7 days), then the mice were given CS only, and the combination were given once a week for 20 weeks. In group CIR(2) saccharin (SAC) was taken as CS, and the other treatments were the same as the group CIR(1). In the group of conventional therapy, the mice were given inhalation of nebulized budesonide and salbutamol only for 20 weeks. In the group of lower dose conventional therapy, the mice were given nebulized inhalation of budesonide and salbutamol for the first 7 days, then once a week for 20 weeks. In the noise group the mice were given noise only everyday for 20 weeks. In SAC group the mice were treated with SAC only everyday for 20 weeks. In the blank control group the mice were treated with placebo for 20 weeks. The mice in all the groups were stimulated with OVA once a day. The mice in the healthy control group were given PBS inhalation for 20 weeks. After 20 weeks therapy, the bronchoalveolar lavage fluid (BALF) was taken for eosinophils (EOS) counting. The spleens were taken to obtain CD4(+)T lymphocytes and the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7), IL-4, IFN-gamma and IL-17 were detected by flow cytometry.

RESULTS(1) The percent of EOS of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that of blank control (P < 0.01), and there was no significant difference among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). (2) The expression of nAChRalpha7, IL-4 and IL-17 of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that in blank control group, IFN-gamma was much higher (P < 0.01), and no significant difference was found among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). There was a positive correlation between nAChRalpha7 and IL-4 (r = 0.76, P < 0.01), nAChRalpha7 and IL-17 (r = 0.46, P < 0.01). There was a negative correlation between nAChRalpha7 and IFN-gamma (r = 0.69, P < 0.01). (3) In the groups treated with lower dose of conventional therapy, noise, SAC and blank control, the epithelial tissue of airway were much thicker, the lumens were much narrower, and inflammatory cells and collagen fibers were much more than in the healthy control group, and after therapy, the inflammation in groups CIR(1), CIR(2) and conventional therapy was significantly improved.

CONCLUSIONThe conditioned immune response models established by both noise and SAC as CS and budesonide and salbutamol as UCS can downregulate nAChRalpha7 on CD4(+)T lymphocytes, regulate the function of CD4(+)T lymphocytes, and achieve the same therapeutic efficacy in treatment of asthma.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; immunology ; Budesonide ; therapeutic use ; CD4-Positive T-Lymphocytes ; immunology ; metabolism ; Female ; Gene Expression Regulation ; Mice ; Mice, Inbred BALB C ; Receptors, Nicotinic ; metabolism ; alpha7 Nicotinic Acetylcholine Receptor

OBJECTIVETo observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury.

METHODThe synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process.

RESULTACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus.

CONCLUSIONThe synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.

Acetylcholine ; metabolism ; Animals ; Choline ; metabolism ; Extracellular Fluid ; drug effects ; metabolism ; Hippocampus ; cytology ; Male ; Neurotransmitter Agents ; metabolism ; Perfusion ; Prefrontal Cortex ; cytology ; Rats ; Rats, Sprague-Dawley ; Sodium Azide ; administration & dosage ; pharmacology ; Time Factors

In 1938 Cerletti described a method of producing convulsions by eleetricity and began its use in the treatment of schizophrenias. In avoider to avoid fractures or dislocation and to diminish the risk, convulsion may be modified by means of drugs which inhibit the action of acetylcholine at neuro-muscular junctions and often the muscular contractions combining ultra short acting barbiturate especially thiopental sodium. Since ultra short acting barbiturat, like thiopental, require postanesthesia supervision of the patient for up to an hour, the recentlyintroduced ultrashort-acting nonbarbiturate anesthetic agent, propanidid, was investigated for comparison with thiopental sodium. One hundred psychiatric patients under the diognosis of involutional melancholia, manic depressive psychosis, schizophrenia and neurotic depression, divided into two equal groups, were subjected to electroconvulsive therapy by thiopental-succinylcholine (Group 1) and propanidid-succinyl choline (Group 2). In our study, there were no definite change in blood pressure and heart rate after electroconvulsive therapy in both group. Duration of apnea in Group 2 averaged 63 seconds longer than in Group 1, but awakening and ambulation averaged 5 minutes and 40 minutes shorter than in Group 1. Complications after E.C.T. were minimal and not significant different between two groups.
Acetylcholine ; Anesthesia, General* ; Apnea ; Bipolar Disorder ; Blood Pressure ; Choline ; Depressive Disorder ; Depressive Disorder, Major ; Dislocations ; Electroconvulsive Therapy ; Heart Rate ; Humans ; Muscle Contraction ; Organization and Administration ; Propanidid ; Schizophrenia ; Seizures ; Thiopental ; Walking