The purpose of this study was to evaluate in vitro the effects of hydrocortisone and aminophylline on adenosine diphosphate (ADP)-induced platelet aggregation in horses. Blood samples from 30 healthy Thoroughbred horses were collected by via jugular venipuncture to assess platelet aggregation. Platelet-rich and platelet-poor plasma were prepared from all samples by centrifugation and divided into three different aliquots. In the first aliquot, platelet aggregation was measured after platelet activation with 1 microM and 0.5 microM ADP (Group A). In the other two aliquots, the effect of a 10 min preincubation with hydrocortisone (Group B) or aminophylline (Group C) on ADP-induced aggregation at final ADP concentrations of 1 microM and 0.5 microM was observed. Platelet aggregation, recorded by an aggregometer, was evaluated by measuring the maximum degree of platelet aggregation and the initial velocities of platelet aggregation were obtained. Our results demonstrated the inhibitory effect of hydrocortisone and the induction effect of aminophylline on equine platelet responses in vitro.
Adenosine Diphosphate/pharmacology ; Aminophylline/*pharmacology ; Animals ; Anti-Inflammatory Agents/*pharmacology ; Female ; Horses/*physiology ; Hydrocortisone/*pharmacology ; Male ; Platelet Aggregation/*drug effects

OBJECTIVETo study the pharmacokinetic and pharmacodynamic features of different doses of aminophylline in very low birth weight (VLBW) infants with different postmenstrual ages, weights, and ages (in days).

METHODSA total of 40 VLBW infants with apnea were enrolled. After an intravenous loading dose of 5 mg/kg aminophylline, they were randomized into two groups with different maintenance doses of aminophylline (1 mg/kg and 2 mg/kg, once every 8 hours). Blood concentrations of aminophylline and liver and renal functions were monitored at 8 hours, 3 days, and 7 days after the loading dose. Attacks of apnea were documented. Pharmacokinetic data of aminophylline were compared between the two groups.

RESULTSThe steady-state plasma concentration of aminophylline and plasma clearance in the 2 mg/kg group were significantly higher than those in the 1 mg/kg group (P<0.05). However, the elimination half life was shorter in the 2 mg/kg group (P<0.05). Days of apnea attacks within 7 days after birth in the 2 mg/kg group were significantly fewer than in the 1 mg/kg group (P<0.05). Aminophylline plasma clearance was positively correlated with age (in days) after birth and postmenstrual age in both groups.

CONCLUSIONSIn VLBW infants, pharmacokinetics and pharmacodynamics are different when different maintenance doses of aminophylline are given. The maintenance dose of 2 mg/kg is associated with a better effect in the treatment of apnea. Postmenstrual age and age (in days) should be considered during the adjustment of dose, and routine blood concentration monitoring should be performed.

Aminophylline ; pharmacokinetics ; pharmacology ; Apnea ; drug therapy ; Female ; Humans ; Infant, Newborn ; Infant, Very Low Birth Weight ; Male

OBJECTIVE: To observe the effect of aminophylline on physiological and pathological changes in acute exposure to high altitude in rats. METHODS: A total of 21 male Wistar rats were randomly divided into a plain group (altitude 55 m), a high altitude hypoxia group (altitude 4 300 m), and a high altitude hypoxia plus aminophylline group. After 5 days, blood from orbital venous was collected for analyzing biochemical parameters. Blood from abdominal aorta was collected for analyzing the parameters of blood gas. The tissues of brain, lung, and kidney were dissected for pathological observation. RESULTS: Compared with the plain group, the parameters of LDH, ALP, Urea and cCl? in the hypoxia group or the aminophylline treatment group were significantly increased (P<0.01), while the parameters of ALB, Cr, SatO₂, Hb, Hct, PaCO₂, PaO₂2, BB and BE were significantly reduced (P<0.01). Compared with the hypoxia group, the parameters of Cr, pH, Hct, cNa⁺, cCl⁻ in the aminophylline treatment group were significantly increased (P<0.01), while AST, ALT, ALB, PaCO₂ and cK⁺ were significantly decreased (P<0.01 or P<0.05). Pathological results showed the brain, lung and liver tissues were obviously damaged in the hypoxia group compared with that in the plain group. These damages were significantly attenuated by aminophylline. CONCLUSION Aminophylline can improve blood gas and biochemical parameters in acute exposure to high altitude in rats. It can protect rat brain, lung and liver from the damage caused by acute high altitude, which may be related its effects on relaxation of bronchial smooth muscle and inhibition of inflammation.
Altitude ; Aminophylline ; pharmacology ; Animals ; Brain ; pathology ; Hypoxia ; blood ; physiopathology ; Liver ; pathology ; Lung ; pathology ; Male ; Rats ; Rats, Wistar

This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together.
Aminophylline/*antagonists & inhibitors/pharmacology ; Anesthetics, Intravenous/*antagonists & inhibitors/pharmacology ; Bronchodilator Agents/*antagonists & inhibitors/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; Endothelial Cells/*drug effects/metabolism ; Endothelium, Vascular/cytology ; Humans ; Lysophospholipids/pharmacology ; Microscopy, Confocal ; Propofol/*antagonists & inhibitors/pharmacology ; Umbilical Veins/cytology

OBJECTIVETo investigate the effect of caffeine citrate treatment on early pulmonary function in preterm infants with apnea.

METHODSForty preterm infants with apnea were randomly divided into aminophylline treatment group (20 infants) and caffeine citrate treatment group (20 infants). When the preterm infants experienced apnea after birth, they were given aminophylline or caffeine citrate in addition to assisted ventilation with continuous positive airway pressure (NCPAP). After drug discontinuation, pulmonary function was measured and compared between the two groups.

RESULTSAfter treatment, compared with the aminophylline treatment group, the caffeine citrate treatment group had significantly higher tidal volume, minute ventilation volume, ratio of time to peak tidal expiratory flow to total expiratory time, ratio of volume to peak tidal expiratory flow to total expiratory volume, peak expiratory flow, and breathing flow at 75%, 50%, and 25% of tidal volume (P<0.05). The caffeine citrate treatment group had a significantly shorter time of oxygen use and NCPAP support than the aminophylline treatment group (P<0.01). Compared with the aminophylline treatment group, the caffeine citrate treatment group had a significantly lower frequency of apnea attacks (P<0.01).

CONCLUSIONSIn the treatment of apnea in preterm infants, caffeine citrate can improve early pulmonary function and reduce the incidence of apnea.

Aminophylline ; therapeutic use ; Apnea ; drug therapy ; physiopathology ; Caffeine ; pharmacology ; therapeutic use ; Citrates ; pharmacology ; therapeutic use ; Continuous Positive Airway Pressure ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Lung ; drug effects ; physiopathology ; Male

OBJECTIVETo observe the effects of Bufei Jianpi Recipe (BJR) on the diaphragmatic neural discharge and the diaphragmatic muscle function in rats with chronic obstructive pulmonary disease (COPD).

METHODSRats were randomly divided into the normal control group, the model group, the high dose BJR group (9.68 g/kg x d(-1)), the medium dose BJR group (4.84 g/kg x d(-1)), the low dose BJR group (2.42 g/kg x d(-1)), and the aminophylline group (2.3 mg/kg x d(-1)). The stable phase COPD rat model was prepared using repeated smoke inhalations and bacterial infections. The high, medium, and low dose BJR and aminophylline was respectively administered to rats from the ninth week to the twentieth week. The sampling was taken. The lung function, diaphragmatic neural discharge time (Td), and diaphragmatic neural discharge interval (Tdi), diaphragmatic neural discharge range (Rd), diaphragmatic neural discharge area (Ad), expiratory time (Tex), inspiratory time (Tin), respiratory rate (RR), respiratory excursion (RE), respiratory area (RA), and diaphragmatic muscular tension and endurance were detected.

RESULTSCompared with the normal control group, the tidal volume (TV), peak expiratory flow (PEF), and 50% tidal volume expiratory flow (EF50) significantly decreased in the model group (P < 0.01). Td, Tdi, Tex, and Tin were significantly prolonged (P < 0. 05, P < 0.01). Ad, Rd, RR, RE, RA, diaphragmatic muscular tension and endurance significantly decreased (P < 0.05, P < 0.01). The ratio of type I and IIA diaphragmatic fibers significantly increased and type IIB significantly decreased (P < 0.01). The activity of ATP decreased and the activity of SDH increased (P < 0.01). The aforesaid indices were improved to different degrees in BJR groups, especially in the high dose BJR group and the medium dose BJR group (P < 0.05, P < 0.01).

CONCLUSIONSBJR could significantly improve the diaphragmatic neural discharge and the diaphragmatic muscle function. Its efficacy was better than that of aminophylline.

Aminophylline ; pharmacology ; Animals ; Diaphragm ; drug effects ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Phrenic Nerve ; drug effects ; physiopathology ; Phytotherapy ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; physiopathology ; Rats

The effects of Shenmai injection (SMI) and aminophylline on apoptosis of small airway smooth muscle cells (SASMC) and the Fas/FasL expression in rats with papain-induced emphysema were investigated. Rat emphysema model was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were detected by immunohistochemistry SABC and TUNEL assay at day 1, 3, 5, 7, 15, 30 after modeling, and the effect of SMI and aminophylline on them were observed. The results indicated that the Fas/FasL expression positive rate in SASMC was 2.31 +/- 0.55/1.28 +/- 0.47 respectively. After a single intratracheal instillation of papain, the expression of Fas/FasL positive rate in the placebo group was increased in a time-dependent manner. SMI could inhibit the expression of Fas/FasL, but aminophylline couldn't. The positive rate of apoptosis in the control group was 0.87 +/- 0.32. After a single intratracheal instillation of papain, the SASMC apoptosis positive rate in the placebo group was increased in a time-dependent manner. The SASMC apoptosis rate in all groups was declined after treatment with SMI, but the effect of aminophylline was not obvious. It was demonstrated that in the pathogenesis of emphysema Fas/FasL played an important role in the regulation of SASMC apoptosis. SMI influenced the expression of Fas/FasL and declined SASMC apoptosis by inhibiting the releasing of inflammatory media and played an important role in the therapy of emphysema.
Aminophylline ; pharmacology ; Animals ; Bronchi ; metabolism ; pathology ; Bronchodilator Agents ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; Emphysema ; genetics ; pathology ; Fas Ligand Protein ; Female ; Gene Expression ; drug effects ; Male ; Membrane Glycoproteins ; biosynthesis ; genetics ; Myocytes, Smooth Muscle ; pathology ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; fas Receptor ; biosynthesis ; genetics

OBJECTIVETo investigate the effect of Shenmai Injection (SMI) and aminophylline on small airway smooth muscle cell (SASMC) apoptosis and the Fas/FasL expression in the papain induced emphysema model rats.

METHODSEmphysema model in rat was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were examined by immunohistochemical SABC and TUNEL assay at 1, 3, 5, 7, 15 and 30 days after modelling, and the effect of SMI and aminophylline on them were observed.

RESULTSFas, FasL expressions in normal SASMC were very low with a positive rate of (2.31 +/- 0.05)% and (1.28 +/- 0.47)% respectively. After papain instillation, the positive rates increased along with the prolonging of instillation time. SMI showed an inhibition on SASMC Fas and FasL expression but aminophylline didn't show. SASMC apoptosis was very low in normal rats with a rate of (0.87 +/- 0.32)%, it also raised after papain instillation and increased progressively along with the instillation time. SMI treatment could lower the apoptosis rate but aminophylline couldn't.

CONCLUSIONFas and FasL participated the SASMC apoptosis modulation in emphysema formation. SMI shows a definite treatment effect on emphysema by influencing the Fas and FasL protein expression and reducing SASMC apoptosis through inhibiting the release of inflammatory mediator.

Aminophylline ; pharmacology ; Animals ; Apoptosis ; drug effects ; Bronchi ; metabolism ; pathology ; Cells, Cultured ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Emphysema ; metabolism ; pathology ; Fas Ligand Protein ; Female ; Male ; Membrane Glycoproteins ; biosynthesis ; metabolism ; Muscle, Smooth ; cytology ; metabolism ; Neuropeptides ; biosynthesis ; metabolism ; Papain ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Tumor Necrosis Factor ; fas Receptor

OBJECTIVE: To observe the role of aminophylline and simvastatin in preventing and curing chronic obstructive pulmonary disease (COPD), and to explore the underlying mechanisms based on airway inflammation and mucus hypersecretion.
 METHODS: The rat model of COPD was established by combination of cigarette smoking with intratracheal lipopolysaccharide (LPS) injection. Male SD rats were randomly divided into 4 groups (n=10 per group): a control group, a COPD group, an aminophylline group and a simvastatin group. The rats in the control group and the COPD group were treated with normal saline once a day via intragastric administration, while the rats in the aminophylline group and the simvastatin group were treated with aminophylline (5 g/L) and simvastatin (0.5 g/L) 1 mL/100 g once a day via intragastric administration, respectively. Pulmonary function and pathological changes in bronchus and lung were observed. The levels of IL-8, IL-17, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of TLR4 and mucin 5AC (MUC5AC) in bronchi and lung tissues were detected by real-time PCR and Western blot, respectively.
 RESULTS: Pulmonary function and the pathophysiologic changes in bronchi and lung tissues in the COPD rats were consistent with typical phenotype of COPD. Compared with the control group, lung function indexes were significantly attenuated in the COPD group, while the levels of IL-8, IL-17, and TNF-α in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly increased. Compared with the COPD group, lung function indexes were significantly increased in the aminophylline group and simvastatin group (P<0.01), while pulmonary pathological damages, the levels of IL-8, IL-17, and TNF-α in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly decreased (P<0.01). Compared with the aminophylline group, the peak expiratory flow as well as the levels of IL-8, IL-17, and TNF-α in the simvastatin group were elevated (P<0.05). There are no significant difference in the mRNA and protein levels of MUC5AC and TLR4 between the 2 groups (P﹥0.05).
 CONCLUSION Aminophylline and simvastatin can decrease IL-8, IL-17, and TNF-α levels in BALF and inhibit the expression of MUC5AC and TLR4 in airway and lung tissues in COPD rats, suggesting that they may have a preventive and therapeutic effect on COPD through reducing the airway inflammation and mucus hypersecretion.
Aminophylline ; pharmacology ; Animals ; Bronchi ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Cytokines ; chemistry ; Inflammation ; drug therapy ; Lipopolysaccharides ; Lung ; metabolism ; physiopathology ; Male ; Mucin 5AC ; metabolism ; Mucus ; metabolism ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology ; Smoke ; adverse effects ; Smoking ; adverse effects ; Toll-Like Receptor 4 ; metabolism

The aim of this study was to investigate whether and how phosphodiesterase (PDE) inhibitors modulate the proliferation, cell cycle and apoptosis in lymphoma cells. The effects of aminophylline (AM), a non-specific PDE inhibitor, on Raji cells were explored in vitro. MTT assay, light and transmission electron microscopy and annexin V staining were used to observe cell proliferation, morphologic changes and apoptosis rate in AM-treated cells, and FCM and RT-PCR techniques were adopted to detect the effect on cell cycle, the expression of cyclin B1 and Bcl-2 and mitochondrial transmembrane potential in AM-treated cells. The results showed that AM inhibited the growth of Raji cells in a concentration-dependent manner. Morphologic observations showed apoptosis changes in AM-treated cells, including cytoplamic shrinkage, cytoplasmic bubbling, karyopyknosis and nuclear fragmentation. FCM and RT-PCR detection showed that AM intervention increased the fraction of annexin V(+) cells, reduced the value of mitochondrial transmembrane potential, induced S phase arrest, and down-regulated the expression of Bcl-2 at both mRNA and protein level and cyclin B1 protein in a concentration-dependent manner. It is concluded that PDE inhibitor aminophylline may induce Raji cell growth inhibition, S phase arrest, apoptosis via down-regulation of Bcl-2 and reduction of mitochondrial transmembrane potential.
Aminophylline ; pharmacology ; Apoptosis ; drug effects ; Burkitt Lymphoma ; drug therapy ; genetics ; pathology ; Cell Division ; drug effects ; Cyclin B ; genetics ; metabolism ; Cyclin B1 ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Intracellular Membranes ; drug effects ; physiology ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Phosphodiesterase Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; drug effects ; genetics ; metabolism ; S Phase ; Tumor Cells, Cultured ; drug effects ; metabolism ; ultrastructure