BACKGROUND: Zaprinast is an inhibitor of phosphodiesterase 5, 6 and 9. Phosphodiesterase inhibitors could produce anti-nociceptive effects by promoting the accumulation of cGMP. We hypothesized that intrathecal zaprinast could attenuate the allodynia induced by chronic constriction injury of the sciatic nerve in rat. METHODS: Sprague-Dawley rats were prepared with four loose ligations of the left sciatic nerve just proximal to the trifurcation into the sural, peroneal and tibial nerve branches. Tactile allodynia was measured by applying von Frey filaments to the lesioned hindpaw. The thresholds for the withdrawal responses were assessed. Zaprinast (3-100microg) was administered intrathecally by the direct lumbar puncture method to obtain the dose-response curve and the 50% effective dose (ED50). Measurements were taken before and 15, 30, 45, 60, 90, 120, and 180 min after the intrathecal doses of zaprinast. The side effects were also observed. RESULTS: Intrathecal zaprinast resulted in a dose-dependent antiallodynic effect. The maximal effects occurred within 15-30 min and then they gradually decreased down to the baseline level over time in all the groups. There was a dose dependent increase in the magnitude and duration of the effect. The ED50 value was 17.4microg (95% confidence intervals; 14.7-20.5microg). No severe motor weakness or sedation was observed in any of the rats. CONCLUSIONS: Intrathecally administered zaprinast produced a dose-dependent antiallodynic effect in the chronic constriction injury neuropathic pain model. These findings suggest that spinal phosphodiesterase 5, 6 and 9 may play an important role in the modulation of neuropathic pain.
Animals ; Constriction ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Hyperalgesia ; Ligation ; Neuralgia ; Organic Chemicals ; Phosphodiesterase Inhibitors ; Purinones ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; Spinal Puncture ; Tibial Nerve

PURPOSE: This study is to assess the pharmacologic effects of ethanol and its metabolite, acetaldehyde on potassium channels of the corpus cavernosal smooth muscle of the rabbit. MATERIALS AND METHODS: Cavernosal strips from New Zealand white rabbits were harvested and pharmacophysiologic organ bath studies were executed. In equilibrium state after incubation, zaprinast (PDE5 inhibitor) induced relaxations were monitored in strips precontracted with phenylephrine (PE, 10(-4)M). The inhibitory effects of ethanol and acetaldehyde (2, 20, 40, 80 mmol) on zaprinast-induced relaxations were recorded. Pinacidil (K(ATP) channel opener) and phloretin (BK channel opener) were tested to reverse the inhibitory effects of ethanol and acetaldehyde on zaprinast-induced relaxations. RESULTS: Both ethanol and acetaldehyde inhibited the zaprinast-induced relaxations in a dosedependent manner (p<0.05). Both pinacidil and phloretin abolished the inhibition by both ethanol and acetaldehyde (p<0.05). Ethanol and acetaldehyde inhibits cavernosal relaxation, possibly through BK channels and K(ATP) channels. CONCLUSIONS: These results suggest that ethanol and its metabolite may affect the corpus cavernosal smooth muscle directly and lead to consequent erectile dysfunction. Furthermolecular and electrophysiological studies will help reveal the underlying mechanisms to which this process occurs.
Acetaldehyde ; Baths ; Erectile Dysfunction ; Ethanol ; Large-Conductance Calcium-Activated Potassium Channels ; Male ; Muscle, Smooth ; Penis ; Phenylephrine ; Phloretin ; Pinacidil ; Potassium Channels ; Purinones ; Rabbits ; Relaxation

BACKGROUNDNitric oxide (NO) is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that nitric oxide may induce the expression of heat shock protein 72 (HSP72) which may protect the heart against ischemia.

METHODSRabbits were given intravenous saline or S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, or Zaprinast, an inhibitor of cyclic guanosine monophosphate (GMP)-phosphodiesterase, which may increase myocardial cyclic GMP content. Twenty-four hours later, the rabbits were either sampled to measure HSP72, or induced with a 30-minute coronary occlusion followed by a 120-minute reperfusion, and then the infarct size was measured. Meanwhile, chelerythrine (CHE, an inhibitor of protein kinase C) was given intravenously 5 minutes before SNAP injection and the effect on HSP72 expression and infarct size was determined.

RESULTSTwenty-four hours after pretreatment, immunoblotting showed HSP72 expression increased in the SNAP group compared with control groups, and this was blocked by CHE. Myocardial infarct size in the SNAP group was smaller than that of the control group ((32.4 +/- 5.8)% vs (51.1 +/- 4.7)%, P < 0.05). Pretreated with CHE abolished the infarct size-limiting effect of SNAP ((46.0 +/- 5.1)%). Pretreatment with Zaprinast neither induced HSP72 expression nor reduced infarct size ((55.4 +/- 5.4)%).

CONCLUSIONNO induced HSP72 expression and a delayed protection to the heart via the activities of protein kinase C by a cyclic GMP-independent pathway.

Animals ; Benzophenanthridines ; pharmacology ; Cyclic GMP ; metabolism ; HSP72 Heat-Shock Proteins ; biosynthesis ; Hemodynamics ; Male ; Myocardial Infarction ; metabolism ; physiopathology ; prevention & control ; Myocardial Ischemia ; metabolism ; physiopathology ; prevention & control ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; Protein Kinase C ; metabolism ; Purinones ; pharmacology ; Rabbits ; S-Nitroso-N-Acetylpenicillamine ; pharmacology

PURPOSE: Methylxanthines are commonly used to treat apnea of prematurity. Recent studies have reported that caffeine therapy reduces the rate of bronchopulmonary dysplasia (BPD) and improves the rate of survival in preterm infant without neurodevelopmental disabilities. This study was performed to compare the effects on apnea episodes, adverse effects and morbidity between the caffeine and theophylline groups. METHODS: A retrospective study was performed in 143 infants born at less than 33 weeks of gestation and treated with caffeine (n=54) or theophylline (n=89) from 2011 to 2012. The baseline characteristics of mothers and their infants were examined. The number of apnea events before and after treatment, the duration of respiratory support, and the rate of re-intubation were compared. Furthermore, adverse effects, clinical course, and morbidities such as BPD and periventricular leukomalacia were compared before discharge. RESULTS: There were no significant differences in the baseline characteristics. Theophylline and caffeine appeared to have similar short-term therapeutic advantages on apnea of prematurity in mean apnea rate after first two weeks of treatment. However, there were no statistically significant differences in the duration of respiratory support, rate of re-intubation, clinical course, and morbidity between the two groups. Adverse effects, indicated by feeding intolerance were lower in the caffeine group. CONCLUSION: Caffeine was as effective as theophylline in the short-term for reducing apnea in preterm babies and was better tolerated and was easier to administer. A prospective randomized study is needed to confirm the effect of caffeine on the lone-term neurodevelopmental outcome in prematurity.
Apnea* ; Bronchopulmonary Dysplasia ; Caffeine* ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Leukomalacia, Periventricular ; Mothers ; Pregnancy ; Retrospective Studies ; Theophylline*

OBJECTIVETo compare the effect of Acanthopanacis senticosi injection, theophylline and caffeine on human sperm mobility in vitro.

METHODSWe incubated the sperm aseptically obtained by masturbation from 12 asthenospermia men and treated by swim-up technique in Acanthopanacis senticosi injection (10 g/L), theophylline (3 mmol/L) and caffeine (7 mmol/L) respectively, and detected various sperm parameters with the computer-assisted sperm analysis (CASA) system at 0 h, 1 h and 3 h.

RESULTSAcanthopanacis senticosi injection significantly increased sperm motility, the percentage of progressive motile sperm, straight line velocity (VSL) and curvilinear velocity (VCL) as compared with theophylline and caffeine (P < 0.05).

CONCLUSIONAcanthopanacis senticosi injection can activate the mobility of human sperm in vitro.

Caffeine ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Eleutherococcus ; chemistry ; Humans ; In Vitro Techniques ; Male ; Sperm Motility ; drug effects ; Theophylline ; pharmacology

Evidence for the existence of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective A-1 adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of A-2 adenosine receptor. N6-(L-2-phenylisopropyl)-adenosine (PIA) almost unselectively activates both A-1 and A-2 adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenyl-xanthine (DPX) were performed. Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature. Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function. Systemic administration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA. Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of, CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine. These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.
Adenosine* ; Adenosine-5'-(N-ethylcarboxamide) ; Aldosterone ; Blood Pressure ; Caffeine ; Creatinine ; Diuresis ; Diuretics ; Epinephrine ; Heart Rate ; Kidney ; Motor Activity ; Norepinephrine ; Osmolar Concentration ; Plasma ; Receptors, Purinergic P1 ; Renin ; Theophylline ; Water

AIMTo establish a HPLC method for determining five major metabolites of caffeine in the urine, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (1X), 1-methyluric acid (1U), 1,7-dimethyluric acid (17U) and 1,7-dimethylxanthine (17X) and assess the activity of cytochrome P-450 CYP2A6.

METHODSThe contents of five major metabolites of caffeine in the urine were determined by RP-HPLC method. Frequency distribution histogram was drawn by calculating the 17U/(AFMU + 1X + 1U + 17X + 17U) and then evaluated the activity of CYP2A6.

RESULTSThe frequency distribution histograms of CYP2A6 approximately indicated three distinct groups, the cut of point is 0.23 between fast metabolizer and intermediate type. And the cut of point is 0.15 between slow metabolizer and intermediate type.

CONCLUSIONThe method is simple and rapid, suitable for the determination of metabolites of caffeine in urine. The method can be used to assay the activity of CYP2A6.

Adult ; Aryl Hydrocarbon Hydroxylases ; metabolism ; Caffeine ; metabolism ; urine ; Chromatography, High Pressure Liquid ; methods ; Cytochrome P-450 CYP2A6 ; Female ; Humans ; Male ; Mixed Function Oxygenases ; metabolism ; Theophylline ; urine ; Uracil ; analogs & derivatives ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

Preparation of theophylline microcapsule by the coacervation - phase seperation method. Theophylline microcapsule has been prepared by coacervation - phase seperation, using ethyl cellulose as the coating material. Ethyl cellulose sustanined significally the release of theophylline from microcapsule. Microcapsule has been used for preparation of theophylline sustained - release tablet.
Theophylline ; Capsules

The theophylline microcapsule has been prepared by spray-drying technique, using ethyl cellulose as the coating material. Ethyl cellulose sustained significally the release of theophylline from microcapsule has been used for preparation of theophylline sustained-released tablet.
Theophylline ; Capsules

No abstract available.
Asthma* ; Theophylline*