Ketamine, a dissociative anesthetic, produces an increase in heart rate and blood pressure, but the precise mechanism of the cardiovascular stimulating affects of ketamine is not understood clearly. Clonidine, an antihypertensive agent, is an alpha-2 agonist that appears to act primarily on the CNS, where it apparently produces a decrease in the sympathetic outflow from the brain. Prazosin is antihypertensive agent that appears to evert its vasodilator action through the blockade of postsynaptic alpha-1 receptors. In order to investigate the effects of clonidine and prazosin on the heart rate and blood pressure increased by ketamine, ketamine was administered intravenously following administration of clonidine or prazosin in conscious patients. The results were as follows : 1) Intravenous ketamine (2 mg/kg) produced significant increases in heart rate and blood pressure by as much as 25%. 2) Intravenous clonidine (1.25 ug/kg) produced a decrease in the heart rate by 5 beats per minute and decreased blood pressure significantly. 3) In the clonidine pretreated group (1.25 ug/kg, lV), intravenous ketamine (2 mg/kg/kg, lV) produced significant increases in the heart rate and blood pressure without attenuation with clonidine 4) In the prasosin pretreated group (2 mg/kg~70 kg, PO), ketamine (2 mg/kg, lV) produced increases the in heart rate and blood pressure without attenuation with prasosin. From the above results, it was inferred that the action site of the cardiovascular stimulating effect of ketamine isn't a postsynaptic alpha-1 receptor and is different from the action site of clonidine.
Blood Pressure* ; Brain ; Clonidine* ; Heart Rate* ; Heart* ; Humans ; Ketamine* ; Prazosin*

BACKGROUND: The development of new drugs or alternative therapies effective against methicillin-resistant Staphylococcus aureus (MRSA) is of great importance, and various natural anti-MRSA products are good candidates for combination therapies. We evaluated the antibacterial activities of a Phellinus baumii ethyl acetate extract (PBEAE) and its synergistic effects with beta-lactams against MRSA. METHODS: The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the PBEAE. The PBEAE synergistic effects were determined by evaluating the MICs of anti-staphylococcal antibiotic mixtures, with or without PBEAE. Anti-MRSA synergistic bactericidal effects of the PBEAE and beta-lactams were assessed by time-killing assay. An ELISA was used to determine the effect of the PBEAE on penicillin binding protein (PBP)2a production. RESULTS: The MICs and MBCs of PBEAE against MRSA were 256-512 and 1,024-2,048 microg/mL, respectively. The PBEAE significantly reduced MICs of all beta-lactams tested, including oxacillin, cefazolin, cefepime, and penicillin. However, the PBEAE had little or no effect on the activity of non-beta-lactams. Time-killing assays showed that the synergistic effects of two beta-lactams (oxacillin and cefazolin) with the PBEAE were bactericidal in nature (Deltalog10 colony forming unit/mL at 24 hr: 2.34-2.87 and 2.10-3.04, respectively). The PBEAE induced a dose-dependent decrease in PBP2a production by MRSA, suggesting that the inhibition of PBP2a production was a major synergistic mechanism between the beta-lactams and the PBEAE. CONCLUSIONS: PBEAE can enhance the efficacy of beta-lactams for combined therapy in patients infected with MRSA.
Acetates/chemistry ; Agaricales/*chemistry/metabolism ; Anti-Infective Agents/chemistry/*pharmacology ; Drug Synergism ; Enzyme-Linked Immunosorbent Assay ; Methicillin-Resistant Staphylococcus aureus/*drug effects/metabolism ; Microbial Sensitivity Tests ; Penicillin-Binding Proteins/analysis/metabolism ; Plant Extracts/chemistry/*pharmacology ; beta-Lactams/*pharmacology

Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 microg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 microM), N omega-Nitro-L-arginine methyl ester hydrochloride (100 microM), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (10 microM), ryanodine (10 microM) and phentolamine (10 microM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 microM). Furthermore, the beta-adrenergic receptor antagonist, propranolol (10 microM), abolished SAWF-induced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via a-adrenergic receptors and sarcoplasmic reticulum Ca2+ ATPase.
Animals ; Baths ; Calcium-Transporting ATPases ; Carbamates ; Chenopodiaceae ; Contracts ; Gastrointestinal Diseases ; Gastrointestinal Motility ; Herbal Medicine ; Indoles ; Muscle, Smooth ; Muscles ; Organometallic Compounds ; Orientation ; Oxadiazoles ; Phentolamine ; Propranolol ; Pyloric Antrum ; Quinoxalines ; Rats ; Ryanodine ; Sarcoplasmic Reticulum ; Tetrodotoxin ; Water

The basidiomycete Laetiporus sulphureus var. miniatus belongs to the Aphyllophorales, Polyporaceae, and grows on the needleleaf tree. The fruiting bodies of Laetiporus species are known to produce N-methylated tyramine derivatives, polysaccharides, and various lanostane triterpenoids. As part of our ongoing effort to discover biologically active compounds from wood-rotting fungi, an anti-inflammatory triterpene, LSM-H7, has been isolated from the fruiting body of L. sulphureus var. miniatus and identified as acetyl eburicoic acid. LSM-H7 dose-dependently inhibited the NO production in RAW 264.7 cells without any cytotoxicity at the tested concentrations. Furthermore it suppressed the production of proinflammatory cytokines, mainly inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha, when compared with glyceraldehyde 3-phosphate dehydrogenase. These data suggest that LSM-H7 is a crucial component for the anti-inflammatory activity of L. sulphureus var. miniatus.
Basidiomycota ; Cyclooxygenase 2 ; Cytokines ; Fruit ; Fungi ; Glyceraldehyde 3-Phosphate ; Inflammation* ; Interleukin-6 ; Interleukins ; Macrophages* ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Oxidoreductases ; Polyporaceae ; Polyporales ; Polysaccharides ; Trees ; Tumor Necrosis Factor-alpha ; Tyramine

BACKGROUND: This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules (18microgram once daily) with a ipratropium metered dose inhaler (2 puffs of 20microgram q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). METHOD: After the initial screening assessment and a two-week run-in period, patients received either tiotropium 18microgram once daily or ipratropium 40microgram four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. RESULT: In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted FEV1 of 42 (12)% were analyzed. The trough FEV1 response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. CONCLUSION: This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.
Adult* ; Albuterol ; Bronchodilator Agents ; Capsules ; Forced Expiratory Volume ; Humans ; Inhalation ; Ipratropium* ; Lung ; Mass Screening ; Metered Dose Inhalers ; Outcome Assessment (Health Care) ; Peak Expiratory Flow Rate ; Pulmonary Disease, Chronic Obstructive* ; Surveys and Questionnaires ; Vital Capacity ; Tiotropium Bromide