Adenosine ; administration & dosage ; therapeutic use ; Humans ; Myocardial Infarction ; drug therapy

Adenosine is well known as a safe and effective drug for the termination of paroxysmal supraventricular tachycardia (PSVT), and is also widely used for the termination of both narrow and wide QRS-complex tachycardia of unknown origin in the setting of hemodynamic stability. However, due to a shortening of atrial refractoriness, adenosine can facilitate the induction of atrial fibrillation. A life threatening tachycardia may result from a potential rapid conduction of the atrial fibrillation over an accessory pathway. A case of patient, where the intravenous administration of adenosine, during regular, narrow QRS tachycardia, was followed by atrial fibrillation with rapid conduction over a manifest accessory pathway, is reported.
Adenosine* ; Administration, Intravenous ; Atrial Fibrillation* ; Hemodynamics ; Humans ; Tachycardia ; Tachycardia, Supraventricular* ; Wolff-Parkinson-White Syndrome

Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As2O3) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAsIII) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As2O3 exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na+-K+ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As2O3 exposure. AST showed a significant protective effect against As2O3-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAsIII from natural sources or cancer therapy.
Adenosine Triphosphatases ; Administration, Oral ; Animals ; Arsenic ; Humans ; Kidney ; Leukemia, Promyelocytic, Acute ; Oxidative Stress ; Rats ; Rats, Wistar*

Aggressive intravenous and oral dual antiplatelet therapy has established primary percutaneous coronary intervention (PCI) as the standard of care for acute myocardial infarction. Clopidogrel is currently the thienopyridine of choice for dual antiplatelet therapy in patients treated with PCI. The dose regime and duration of therapy of clopidogrel has undergone multiple refinements. Recently, 2 novel third generation oral inhibitors of P2Y12 receptors, prasugrel and ticagrelor, have undergone clinical evaluation with promising results. This article is a non-exhaustive review of the literature, concentrating on the role of current and novel oral antiplatelet agents for acute myocardial infarction particularly highlighting the limitations and issues associated with clopidogrel use.
Adenosine ; administration & dosage ; analogs & derivatives ; Angioplasty, Balloon, Coronary ; Drug Therapy, Combination ; Electrocardiography ; Humans ; Myocardial Infarction ; drug therapy ; surgery ; Piperazines ; administration & dosage ; Platelet Aggregation Inhibitors ; administration & dosage ; Prasugrel Hydrochloride ; Thiophenes ; administration & dosage ; Ticlopidine ; administration & dosage ; analogs & derivatives

PURPOSE: Beraprost Sodium (BPS) is an orally stable prostacyclin (PGI2) analogue and exerts an inhibitory effect on platelet aggregation as well as a potent vasodilatory effect. We investigated the efficacy and safety of BPS in patients with erectile dysfunction (ED). MATERIALS AND METHODS: A total of 74, consecutive patients subjected to have impotence work-ups including history taking, penile duplex ultrasonography, pharmacological erection test, and cavernous nicotinamide adenosine dinucleotide phosphatase (NADPH) diaphorase staining. Sixty-six patients continuously received BPS for more than 4weeks (range 4-32 weeks, average 8.4+/-5.8 weeks), bid or tid (a total 80-120microgram/day) for long-term control of ED. Remaining 8 patients intermittently received 40-60microgram of BPS an hour prior to intercourse to obtain immediate erection for on-demand treatment. Sexual function was compared by analysis of an International Index of Erectile Function (IIEF) and general efficacy based on patient's subjective evaluation after treatment. RESULTS: IIEFs of all patients were significantly improved after BPS treatment for ED. Erectile function with IIEF question No. 3 and 4 were improved by 1.7+/-1.3 to 3.2+/-1.8 and 1.4+/-0.9 to 2.7+/-1.6, respectively (p<0.05). General efficacy of BPS was shown as full effect in 23%, moderate effect in 31%, mild effect in 26%, and no effect in 20% of the patients. Better sexual function including IIEF and general efficacy were observed in continuous treatment group than on-demand treatment group. Better result was also found in diabetics than non-diabetics (p<0.05) while no difference was observed among psychogenic, vasculogenic, and neurogenic group. The side effect of BPS was minimal; flushing in 8%, headache in 5%, indigestion in 4%, and insomnia in 1% of total patients. CONCLUSIONS: Oral BPS is a safe and effective agent to treat ED. It remains to be investigative, to determine desirable treatment method and to elucidate long term control of ED in association with oral BPS.
Adenosine ; Administration, Oral* ; Dyspepsia ; Epoprostenol ; Erectile Dysfunction* ; Flushing ; Headache ; Humans ; Male ; Niacinamide ; Platelet Aggregation ; Sleep Initiation and Maintenance Disorders ; Sodium* ; Ultrasonography

PURPOSE: Tribulus terrestris has been used as an aphrodisiac. However, little is known about the effects and mechanism of action of T. terrestris on penile erection. Therefore, the effect of a T. terrestris extract and the mechanism of action of the extract on relaxation of the corpus cavernosum (CC) were investigated. The erectogenic effects of an oral preparation of the extract were also assessed. MATERIALS AND METHODS: The relaxation effects and mechanism of action of the T. terrestris extract on rabbit CC were investigated in an organ bath. The intracavernous pressure (ICP) was calculated after oral administration of the extract for 1 month to evaluate whether the relaxation response of the CC shown in the organ bath occurred in vivo. Additionally, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in the CC by immunoassay. Smooth muscle relaxation was expressed as the percentage decrease in precontraction induced by phenylephrine. The ICP was also assessed in rats after oral administration of the extract for 1 month, and changes in concentrations of cGMP and cAMP were monitored. RESULTS: Concentration-dependent relaxation effects of the extract on the CC were detected in the organ bath study. Relaxation of the CC by the T. terrestris extract was inhibited in both an endothelium-removed group and an L-arginen methyl ester pretreatment group. The ICP measured after oral administration of the T. terrestris extract for 1 month was higher than that measured in the control group, and a significant increase in cAMP was observed in the T. terrestris extract group. CONCLUSIONS: The T. terrestris extract induced concentration-dependent relaxation of the CC in an organ bath. The mechanism included a reaction involving the nitric oxide/nitric oxide synthase pathway and endothelium of the CC. Moreover, in an in vivo study, the T. terrestris extract showed a significant concentration-dependent increase in ICP. Accordingly, the T. terrestris extract may improve erectile function.
Adenosine Monophosphate ; Administration, Oral ; Animals ; Baths ; Endothelium ; Guanosine Monophosphate ; Immunoassay ; Male ; Muscle, Smooth ; Penile Erection ; Phenylephrine ; Rats ; Relaxation ; Tribulus

OBJECTIVETo establish a method for determining nucleosides (adenoside and guanoside) in Siweilingzhi Mixture by HPCE.

METHODAdenoside and guanoside were separated within 25 min using an 20 mmol.L-1 borate buffer with 30 mmol.L-1 SDS and 5% Ethanol (adjusted to pH 10.0 with sodium hydroxide solution), with an operation voltage of 10 kV, temperature of 20 degrees C and a hydrodynamic injection time of 15 s. Seperations were carried out in a fused-silica capillary 75 microns id x 57 cm (effective length 50 cm) with peak detection by direct UV at 254 nm.

RESULTRegression equation of adenoside and that of guanoside were Y = 0.0705 + 0.01707X (r = 0.9995) and Y = 0.0232 + 0.01864X (r = 0.9999) respectively. The average recovery rate was 99.22% (RSD = 3.66%) and 104.3% (RSD = 1.91%) respectively. Nine samples were determined with the method.

CONCLUSIONThe method is simple, rapid and accurate with good repeatability and it can be used to determine nucleosides.

Adenosine ; analysis ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Electrophoresis, Capillary ; methods ; Fermentation ; Guanosine ; analysis ; Reishi ; chemistry

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.
Adenosine Triphosphate ; blood ; pharmacokinetics ; Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Biotransformation ; Cardiotonic Agents ; administration & dosage ; blood ; pharmacokinetics ; Creatine ; administration & dosage ; metabolism ; pharmacokinetics ; Erythrocytes ; metabolism ; Injections, Intravenous ; Male ; Phosphocreatine ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

We examined the antiallodynic interaction between gabapentin and adenosine A1 receptor agonist, N(6)-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA), in a rat model of nerve ligation injury. Rats were prepared with ligation of left L5-6 spinal nerves and intrathecal catheter implantation for drug administration. Mechanical allodynia was measured by applying von Frey filaments. Gabapentin and R-PIA were administered to obtain the dose-response curve and the 50% effective dose (ED50). Fractions of ED50s were administered concurrently to establish the ED50 of the drug combination. The drug interaction between gabapentin and R-PIA was analyzed using the isobolographic method. Adenosine A1 receptor antagonist was administered intrathecally to examine the reversal of the antiallodynic effect. Locomotor function changes were evaluated by rotarod testing. Intrathecal gabapentin and R-PIA and their combination produced a dose-dependent antagonism against mechanical allodynia without severe side effects. Intrathecal gabapentin synergistically enhanced the antiallodynic effect of R-PIA when coadministered. There were no significant changes in rotarod performance time, except gabapentin 300 microgram. In the combination group, the maximal antiallodynic effect was reversed by A1 adenosine receptor antagonist. These results suggest that activation of adenosine A1 receptors at the spinal level is required for the synergistic interaction on the mechanical allodynia.
Adenosine/administration & dosage/*analogs & derivatives ; Amines/*administration & dosage ; Animals ; Cyclohexanecarboxylic Acids/*administration & dosage ; Dose-Response Relationship, Drug ; Drug Synergism ; Drug Therapy, Combination ; Injections, Spinal ; Ligation ; Male ; Pain/*drug therapy ; Rats ; Rats, Sprague-Dawley ; Receptor, Adenosine A1/drug effects/physiology ; Spinal Nerves/*injuries ; Xanthines/pharmacology ; gamma-Aminobutyric Acid/*administration & dosage

PURPOSE: Adenosine triphosphate (ATP) from the urothelium acts as a sensory neurotransmitter and is augmented in many diseases, such as overactive bladder. We investigated the effects of intravesical instillation of oxybutynin on ATP-induced bladder overactivity to determine whether this effect is mediated by effects on urothelial muscarinic receptors. MATERIALS AND METHODS: Cystometry (at rate of 0.04 ml/min) was performed in female Sprague-Dawley rats (body weight 250 g) under urethane anesthesia (1.2 g/kg). After a 2-hour baseline period, protamine sulfate (10 mg/ml) was instilled for 1 hour, and then ATP (60 mM, pH 6.0) or a mixture of oxybutynin (10(-6) M) and ATP (60 mM, pH 6.0) was instilled intravesically. We performed experiments with 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) and methoctramine by the same methods. Cystometric parameters, such as the intercontraction interval (ICI), pressure threshold (PT), and maximal voiding pressure (MVP), were compared. RESULTS: With intravesical instillation of ATP after protamine sulfate treatment, the ICI was decreased compared with baseline (ICI: baseline, 487.1+/-64.8 s; protamine, 450.6+/-56.1 s; ATP, 229.7+/-35.3 s; p<0.05). Addition of oxybutynin, 4-DAMP, or methoctramine in the ATP solution did not significantly change the ICI compared with ATP solution alone (ICI: oxybutynin, 189.1+/-32.3 s; 4-DAMP, 161.1+/-22.8 s; methoctramine, 341.0+/-113.3 s; p>0.05). Intravesical instillation of ATP decreased MVP and PT significantly compared with baseline, but MVP and PT were not changed significantly with oxybutynin, 4-DAMP, or methoctramine compared with ATP. CONCLUSIONS: Bladder overactivity induced by intravesical instillation of ATP was not suppressed by intravesical instillation of antimuscarinics. Suppression of ATP-induced bladder overactivity by intravenous oxybutynin is not mediated by urothelial muscarinic receptors.
Adenosine ; Adenosine Triphosphate ; Administration, Intravesical ; Anesthesia ; Animals ; Diamines ; Female ; Humans ; Hydrogen-Ion Concentration ; Mandelic Acids ; Muscarinic Antagonists ; Neurotransmitter Agents ; Piperidines ; Polyphosphates ; Protamines ; Rats ; Rats, Sprague-Dawley ; Receptors, Muscarinic ; Urethane ; Urinary Bladder ; Urinary Bladder, Overactive ; Urothelium