Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D06103 (Theophylline)
 2,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with "serious apnea" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, "specific" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.
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PMID:Physiologic changes induced by theophylline in the treatment of apnea in preterm infants. 2 92

Sympathoadrenal activity was studied in 13 young piglets during hypoxia. The piglets were anaesthetized with chloralose/urethane, tracheostomized, paralyzed with gallamine and artificially ventilated. A femoral artery catheter was inserted and used for blood sampling. The piglets were challenged with 6 min of 6% CO2, 10 min of 12% O2 and 6 min of 6% O2 before and after theophylline (an adenosine receptor antagonist) treatment 20 mg/kg (n = 9) or saline (n = 4). Plasma samples were obtained before, during and after each hypercapnic or hypoxic period and analysed for their content of noradrenaline, adrenaline and neuropeptide Y. Hypercapnia with 6% CO2 and moderate hypoxia with 12% O2 did not lead to any significant increase of either noradrenaline (NA), adrenaline (A) or neuropeptide Y (NPY). However, severe hypoxia with 6% O2 increased the NA level from 30 to 66 nmol/l; the A level from 1 to 28 nmol/l and NPY from 140 to 213 pmol/l. After treatment with theophylline the baseline NA increased from 27 to 40 nmol/l, A rom 1.5 to 4.0 and NPY concentration from 65 to 171 pmol/l. Theophylline moderately enhanced the release of NPY, NA and A during the 12% O2 challenge. However, during the severe hypoxia (6%), the increase of NA (from 49 to 333 nmol/l), A (from 8 to 214 nmol/l) and NPY (from 184 to 385 pmol/l) showed considerably enhancement after the theophylline treatment. The results obtained before and after saline were similar showing that the duration of the experiments per se did not change the baseline levels or the effect of the challenges on NA, A or NPY levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y and catecholamine release in the piglet during hypoxia: enhancement by theophylline. 130 59

Hypoxic, hypercapnic acidosis (HHA) decreases tension and enhances fatigue in hamster diaphragm in vitro. We hypothesized that theophylline would decrease the harmful effect of HHA. Hamster diaphragm strips were studied in Krebs solution aerated with 21% O2 and 12% CO2. The force-frequency responses and the tension and relaxation of brief, submaximal contractions were studied. Mild fatigue was produced by a series of 45 submaximal contractions, after which recovery of force was followed for 15 min. Theophylline (0.55 mM) was added at the time of exposure to HHA (early theophylline) in half the strips and at the end of the fatigue run (late theophylline) in the others. In contrast to our hypothesis, early theophylline had a limited effect on force production in unfatigued HHA diaphragm strips and resulted in lower force production in the recovery period. Late theophylline improved force in the recovery period for low-frequency contractions. Thus the effect of theophylline in the setting of HHA depended on the time it was added and was beneficial only if added after the muscle stopped contracting.
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PMID:The effect of theophylline on hypoxic, hypercapnic hamster diaphragm muscle in vitro. 202 50

Theophylline improves diaphragmatic contractility of the respiratory muscles both in isolated muscle preparations, as well as in animals and normal human beings. Furthermore, theophylline restores diaphragmatic fatigue and prevents fatigue of the diaphragm when given prophylactically. Finally, it was recently shown that theophylline improves diaphragmatic function in COPD patients, all of whom were CO2 retainers (PaCO2 53 +/- 3 mm Hg) and hypoxemic (PaO2 57 +/- 8 mm Hg). Patients improved transdiaphragmatic pressure and were less susceptible to fatigue. Presently the mechanisms of action of theophylline regarding its effects on diaphragmatic function are not fully elucidated. Experimental evidence, however, suggests that theophylline may have an effect on transmembrane calcium movements by blocking adenosine receptors.
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PMID:Effect of theophylline on respiratory muscle function. 241 Feb 4

Net Cl- absorption by Amphiuma small intestine is electrogenic but associated with the secretion of HCO3-. To define the mechanisms of Cl- entry into the enterocytes the initial rate of uptake of 36Cl into isolated segments of small intestine was measured. Luminal extracellular space was measured using [3H]inulin. Cl- influx was saturable with a Km of 5.3 mM. When the mucosal medium Cl- concentration was 20 mM influx was linear for 5 min. Cl- influx in 5 min (JiCl) was not reduced by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid added to the serosal medium, although the Cl- current was abolished. Hence the luminal membrane was the barrier to Cl- uptake. Monovalent anions blocked Cl- influx in the order I- = SCN- = NO3- greater than Br- greater than F-. Anoxia and dinitrophenol reduced JiCl 33 and 71%, respectively. Substitution of medium Na+ with choline or N-methyl glucamine reduced JiCl 60-70%. Removal of medium K+ reduced influx 51%. After medium Na+ and K+ were both replaced influx was stimulated upon reexposure to (Na+ + K+); Na+ alone did not stimulate. JiCl was reduced 34% by furosemide. Neither amiloride nor SITS in the mucosal medium altered influx. JiCl was reduced by replacement of the HCO3- -CO2 buffer with either phosphate or N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid and by exposure to acetazolamide. Theophylline reduced influx 60%, whereas the Ca ionophore A23187 reduced net Cl- absorption and lowered JiCl by 17%. Norepinephrine (10(-5) M) in the serosal bathing medium stimulated Cl- influx 51%. These results indicate that Cl- influx into the intestinal mucosa occurs by a Na+- and, possibly, K+-dependent pathway. Cl- entry is under adrenergic influence.
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PMID:Characteristics of chloride ion influx in Amphiuma small intestine. 253 36

Chronic hyperglycemia has been shown to induce a decrease in beta cell sensitivity to a subsequent glucose challenge. Calcium is a necessary cofactor in the insulin secretory process and glucose elevates cytoplasmic levels. This study was designed to study whether chronic exposure to different extracellular calcium and glucose concentrations would affect the islets' subsequent response to regulatory stimuli. Islets were isolated and cultured in TC 199 plus 10% beta calf serum, glucose (5.5 or 27.5 mM) and calcium (0.5, 2.5 or 4.0 mM) for 48 h. Following culture, the islets were harvested and incubated a second time in the presence of glucose and/or arginine, theophylline, and trifluoperazine (TFP). Some islets were used for insulin content, protein synthesis studies and/or CO2 production from labelled glucose. Islets cultured in a normal glucose environment with low or normal calcium concentration maintained the capacity to respond to a subsequent glucose or arginine challenge. However, islets cultured in a high glucose or high calcium medium failed to respond to a second glucose or arginine stimulus. Theophylline stimulated insulin secretion from both glucose-sensitive and non-sensitive islets, while trifluoperazine inhibited glucose-stimulated insulin secretion in previously sensitive islets and increased insulin secretion in previously non-sensitive islets. The different culture conditions did not alter insulin content, protein synthesis or glucose conversion to labelled CO2. We conclude that chronic exposure to high glucose decreases beta cell responsiveness to glucose and amino acids. Increased extracellular calcium augmented this response. However, the beta cell remained sensitive to theophylline-induced insulin secretion, while TFP paradoxically increased insulin secretion in the glucose-insensitive beta cells. Protein synthesis and glucose oxidation were not affected by culture conditions. Thus we suggest that the glucose-induced desensitization of the beta cells may be due to alterations in the calcium-dependent release mechanism.
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PMID:Beta cell desensitization to glucose induced by hyperglycemia is augmented by increased calcium. 269 Dec 17

Submerged rat hippocampal slices were exposed to hypoxic medium prepared with 95% N2/5% CO2. The population spikes recorded from CA1 cell layer were completely blocked within a range of 5-10 min. The adenosine antagonist theophylline (100 microM) delayed and partially prevented the hypoxia-induced depression. Increasing concentrations of the more potent adenosine antagonist 8-phenyltheophylline (8-PT; 0.1, 1, 10 microM) resulted in progressively less hypoxia-induced depression. The antidromically elicited afterpotentials recorded in the absence of synaptic transmission in low calcium, high magnesium medium were blocked within 8 min of hypoxia. Theophylline (100 microM) and 8-PT (10 microM) delayed to a similar extent the hypoxia-induced depression of the first afterpotential but did not prevent its complete depression.
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PMID:Adenosine antagonists delay hypoxia-induced depression of neuronal activity in hippocampal brain slice. 276 71

Although both methacholine (MCh)- and A23187-induced sweat secretion are known to be strictly dependent on extracellular Ca2+, the role of intracellular calcium concentration ([Ca2+]i) in eccrine sweating has not been clarified. Partially purified eccrine secretory cells were prepared from 400 to 600 isolated secretory coils of monkey sweat glands by serial collagenase digestion and Percoll gradient centrifugation. The quin2 method was used for semiquantitative determination of [Ca2+]i, MCh increased [Ca2+]i in a dose-dependent, reversible, and pharmacologically specific manner (from the resting [Ca2+]i of 80-320 nM) but failed to increase [Ca2+]i in a Ca2+-free medium. A23187 (10(-7) M) increased [Ca2+]i to approximately 900 nM. Theophylline (TH), isoproterenol (ISO), and forskolin (FK) had no effect on the resting [Ca2+]i but, in combination, attenuated the effect of subsequently added MCh and A23187. A23187 at 10(-7) M failed to stimulate sweat secretion or CO2 production in vitro from the quin2-loaded intact isolated sweat glands and dispersed sweat secretory cells, respectively. The observed dissociation between the increase in [Ca2+] may suggest either that MCh stimulation induces some unknown excitatory signal in addition to a rise in [Ca2+] or that A23187-induced Ca2+ influx into the secretory cells is much lower in undissociated sweat glands.
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PMID:Relationship between quin2-determined cytosolic [Ca2+] and sweat secretion. 283 26

In an effort to characterize significant neonatal apnea and evaluate the nursing diagnosis of apnea, apnea type and frequency were determined in 27 infants by continuous computer recording of heart rate, respiratory impedance, end-tidal CO2, and either or both transcutaneous oxygen and pulse oximetry. Of the 1,266 recorded apneas, 46% were central, 44% were mixed, and 10% were obstructive. Mixed apnea was associated with a longer mean duration and greater mean decrease in heart rate than central apnea. Apnea duration was positively correlated with both a decrease in heart rate and oxygen saturation (P less than .001), and a lower baseline saturation was associated with a greater decrease in oxygen saturation during apnea (P = .002). Theophylline therapy had no effect on apnea duration or oxygen desaturation but resulted in a decrease in the mean heart rate decrease associated with apnea. Overall, nurses diagnosed 54% of all apneic episodes and were significantly poorer at detecting mixed and obstructive events. Nursing detection of apnea improved with increasing apnea duration and was always associated with a greater decrease in heart rate. Nurses diagnosed significantly fewer mixed apnea following theophylline therapy. Improved monitoring techniques, particularly for mixed and obstructive apnea, are essential to increase apnea detection in the nursery.
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PMID:Neonatal apnea: diagnosis by nurse versus computer. 318 50

Six normal male subjects, ages 28-40 years, were studied on separate days during increasing infusions with adenosine, 40-120 micrograms kg-1 min-1, before and during infusions of two xanthine derivatives, theophylline (mean plasma concentration 9 mg l-1) and enprofylline (mean plasma concentration 3 mg l-1). The study was double-blind, randomized, placebo controlled. Cardio-respiratory variables were measured non-invasively. Adenosine by itself increased heart rate (P less than 0.05), skin temperature (P less than 0.05), resting minute ventilation (P less than 0.01) and decreased estimated Pa, CO2 (P less than 0.01). Compared with placebo enprofylline increased heart rate (P less than 0.05) and shifted the heart rate and ventilation dose-response curves of adenosine upwards (P less than 0.05 and P less than 0.02, respectively). Theophylline did not by itself affect heart rate but significantly (P less than 0.05) reduced the heart rate response to adenosine. Compared with placebo theophylline caused a small increase in minute ventilation (P less than 0.05) and flattened the dose-response curves of the effects of adenosine on ventilation (P less than 0.01) and Pa, CO2 (P less than 0.01). Theophylline also reduced abdominal and chest discomfort caused by adenosine permitting significantly (P less than 0.05) higher infusion rates of adenosine. These findings suggest that, with equipotent bronchodilating plasma concentrations, theophylline can inhibit while enprofylline augments some cardio-respiratory stimulant effects of infused adenosine in man.
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PMID:Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio-respiratory stimulation of infused adenosine in man. 342 50


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