Relaxant effects of different fractions from Tymus vulgaris on guinea-pig tracheal chains

In previous studies, the relaxant effect of Tymus vulgaris has been demonstrated on guinea pig tracheal chains. Therefore, in the present study, the relaxant effects of n-hexane, dichloromethane, methanol and aqueous fractions of Tymus vulgaris on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of each fraction (0.4, 0.8, 1.2 and 1.6 g%) in comparison to saline as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6 and 0.8 mM) were examined for their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 ìÌ methacholine (group 2, n = 7 for each group). In group 1, all concentrations of the n-hexane fraction and theophylline and three last concentrations (0.8, 1.2 and 1.6 g%) of dichloromethane and two higher concentrations (1.2 and 1.6 g%) of methanol fractions showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). In group 2, all concentrations of theophylline, n-hexane and dichloromethane fractions and three concentrations (0.8, 1.2 and 1.6 g%) of methanol and two higher concentrations (1.2 and 1.6 g%) of aqueous fractions showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). In addition, with group 1, the relaxant effect of all concentrations of all fractions except the n-hexane fraction, were significantly less than those of theophylline (p<0.05 to p<0.001). The n-hexane fraction showed higher relaxant effect than theophylline. The relaxant effect of all concentrations of the n-hexane fraction and the three last concentrations (0.8, 1.2 and 1.6 g%) of dichloromethane and aqueous fractions were significantly greater in group 2 than in group 1 (p<0.05 to p<0.001). There were significant positive correlations between the relaxant effects and concentrations for theophylline and all fractions (except aqueous fraction in group 1) in both groups, but a negative correlation for the aqueous fraction in group 1 (p<0.05 to p<0.001). These results showed a potent relaxant effect for n-hexane and weaker relaxant effect for other fractions from Tymus vulgaris on tracheal chains of guinea pigs.

Hypophagic and hypolocomotive effects of metachloro phenyl piperazine in rats treated with theophylline and caffeine

Long term intake of coffee is known to produce anxiety and suppression of appetite. 5- hydroxytryptamine [5-HT] acting via 5-HT-2C receptors elicits anorexia and anxiety. The present study is design to monitor metachloro phenyl piperazine [m-CPP] at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion in rats taking a solution of caffeine [a component of coffee and tea] or theophylline [a component of tea] as a sole source of water. We found that hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline but not in caffeine treated animals suggesting that long term intake of theophylline may, attenuate anorexiogenic and anxiogenic effects of 5-HT. A possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in people drinking coffee or tea discussed

Positive inotropic effect of Murraya koenigii (Linn.) Spreng extract on an isolated perfused frog heart.

Ethanolic extract of fresh leaves of M. koenigii (MKEE) showed a dose dependent positive inotropic effect on isolated frog heart. The responses to MKEE (62.5-1000 microg) were not affected in either way by theophylline, imidazole, propranolol and sildenafil. The change in potassium and sodium concentration did not alter MKEE-induced positive inotropic effect. Lignocaine did not alter the responses to MKEE significantly. Responses to MKEE were significantly inhibited when calcium concentration was reduced to half (from 1.58 to 0.79 mM) and were significantly potentiated when calcium concentration was doubled (from 1.58 to 3.16 mM). Verapamil was found to inhibit the responses significantly. The results suggest that M. koenigii induced positive inotropic effect possibly by increasing availability of calcium from extra cellular sites.

Preparation and characterization of theophylline-chitosan beads as an aapproach to colon delivery

Chitosan with excellent biodegradable and biocompatible characteristics has received attention as an oral drug delivery vehicle for controlled-release formulations. In this study an enteric-coated capsule containing theophylline-chitosan beads based on 2[3] factorial designs was prepared as a colon drug delivery system. The theophylline-chitosan gel beads were formulated by adding the drug-containing solution of chitosan into tripolyphosphate solutions, dropwise. The obtained beads were washed with water and freeze-dried before filling into the capsules. Eudragit[R] S100 was then used to enteric-coat the prepared capsules. Drug entrapment efficiency and the effects of different variables including: bead morphology, swelling behavior of the beads and the release behavior of the system on these parameters were investigated. Results showed that the highest and lowest swelling ratio is obtained at pH 4.5 and 7.2, respectively. These studies have shown that chitosan concentration and drug polymer weight ratio significantly affect the drug entrapment. Decreasing the drug solubility in external phase caused a significant increase in drug loading. External phase saturation with theophylline and tripolyphosphate, as well as decreasing temperature, have increased drug loading. Furthermore, the lowering of temperature had a significant effect on bead's hardness. The release of theophylline from freeze-dried beads filled in enteric-coated capsules was also investigated. Release of theophylline was prolonged with saturation of both drug and tripolyphosphate in the external phase. Results showed that the release of theophylline from chitosan beads is possibly due to more than one mechanism, possibly dissolution, diffusion and relaxation of the polymer chains

Theophylline Increases the Uptake of Radioiodine by Mouse Thyroid

Diagnostic and therapeutic use of radioiodine in the management of thyroid disorders depends on the ability of thyroid cells to concentrate radioiodine, a process that is regulated by the intracellular increase in cAMP. We hypothesized that theophylline, a drug known to increase intracellular cAMP via inhibition of phosphodiesterase, could increase thyroidal radioiodine uptake. We tested this effect in vivo, using C57BL/6j mice, and in vitro, using Fisher rat thyroid (FRTL-5) cells. One mouse received 2.5mg theophylline i.p., whereas a control mouse received only saline. Twenty-hours after theophylline, mice were injected with 10mu Ci Na(125)I in 0.1 mL saline through the tail vein. Mean thyroidal (125)I activity was 3.3-fold higher in theophylline-treated mice than in their respective controls. Radioiodine uptake and intracellular cAMP production of FRTL-5 cells were increased by a relatively low concentration of theophylline (1mu M). Intracellular cAMP increased up to 30 min and then declined in response to 1mu M theophylline. Sera from theophylline-treated mice stimulated (125)I uptake and intracellular cAMP production by FRTL-5 cells. These findings show that theophylline can enhance radioiodine uptake by thyrocytes in vivo and in vitro. The in vitro effects of theophylline on both radioiodine uptake and cAMP production in a dose-dependent manner are consistent with an action mediated by phosphodiesterase inhibition.

Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors.

The aim of the present study was to investigate the role of phosphodiesterase (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline a nonspecific PDE inhibitor exerted dose dependent analgesic and anti-inflammatory effect against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated analgesic effect of rolipram but it failed to modulate the anti-inflammatory effect of PDE inhibitors. Present study suggests that PDE enzymes might be playing a role in nociceptive and inflammatory responses in animals.

Caracterización de los pacientes portadores de enfermedad pulmonar obstructiva crónica y su respuesta a ipratropio y teofilina / Characterization of chronic obstructive pulmonary disease patients and their response to ipratropium and theophylline

La respuesta clínica y funcional a dos broncodilatadores, bromuro de ipratropio y teofilina en enfermedad pulmonar obstructiva crónica fue evaluada en 62 pacientes, procedentes del programa de enfermedades bronquiales obstructivas del Instituto Nacional del Tórax. Conjuntamente se describen las características clínicas, radiológicas y de laboratorio de los 62 pacientes. El estudio duró 6 meses y los pacientes recibieron bromuro de ipratropio 40 mg 4 veces al día por vía inhalatoria o teofilina oral 200 mg 2 veces al día. Por distribución aleatoria se dividieron en dos series : ipratropio (n=30) y teofilina (n=32) realizándose cambio de terapia a los 3 meses. Los pacientes fueron sometidos mensualmente a un seguimiento clínico y funcional durante el tiempo de duración del estudio. Al final del período de tratamiento, la disnea mejoró solo durante el período con ipratropio (p<0,01), aunque no se apreció cambios significativos en la función pulmonar con ninguno de los dos medicamentos. Durante el período con ipratropio se presentó una menor frecuencia de reacciones adversas severas (p < 0,05)

Development of the insulin secretion mechanism in fetal and neonatal rat pancreatic B-cells: response to glucose, K+, theophylline, and carbamylcholine

We studied the development of the insulin secretion mechanism in the pancreas of fetal (19- and 21-day-old), neonatal (3-day-old), and adult (90-day-old) rats in response to stimulation with 8.3 or 16.7 mM glucose, 30 mM K + , 5 mM theophylline (Theo) and 200 µM carbamylcholine (Cch). No effect of glucose or high K + was observed on the pancreas from 19-day-old fetuses, whereas Theo and Cch significantly increased insulin secretion at this age (82 and 127 por cento above basal levels, respectively). High K + also failed to alter the insulin secretion in the pancreas from 21-day-old fetuses, whereas 8.3 mM and 16.7 mM glucose significantly stimulated insulin release by 41 and 54 percent above basal levels, respectively. Similar results were obtained with Theo and Cch. A more marked effect of glucose on insulin secretion was observed in the pancreas of 3-day-old rats, reaching 84 and 179 percent above basal levels with 8.3 mM and 16.7 mM glucose, respectively. At this age, both Theo and Cch increased insulin secretion to close to two-times basal levels. In islets from adult rats, 8.3 mM and 16.7 mM glucose, Theo, and Cch increased the insulin release by 104, 193, 318 and 396 percent above basal levels, respectively. These data indicate that pancreatic B-cells from 19-day-old fetuses were already sensitive to stimuli that use either cAMP or IP 3 and DAG as second messengers, but insensitive to stimuli such as glucose and high K + that induce membrane depolarization. The greater effect of glucose on insulin secretion during the neonatal period indicates that this period is crucial for the maturation of the glucose-sensing mechanism in B-cells

Teofilina en asma / Teophylline in asthma

La teofilina ha sido uno de los medicamentos más ampliamente utilizados e intensivamente estudiado para el tratamiento del asma. La teofilina es una xantina metilada, relacionada con las xantinas de la dieta, cafeína, y teobromina. Tradicionalmente utilizada como broncodilatador, su uso actual es predominante como medicamento de mantenimiento para el asma crónica. Para el tratamiento del asma aguda, la teofilina es menos efectiva que los ß-2 agonistas inhalados o inyectados y permanece como una importante medicación en el manejo de síntomas nocturnos refractarios a tratamietno antiinflamatorio; es también útil como manejo de primera línea en pacientes que no cumplen o sin apego al tratamiento antiinflamatorio inhalado. El beneficio y toxicidad de la teofilina está en estrecha relación a las concentraciones séricas, y óptimos beneficios se obtienen a concentraciones de 10µg/mL y la toxicidad es frecuente a concentraciones que exceden 20 µg/mL. El rango de eliminación varía entre individuos, pero generalmente permanece estable en el paciente, excepto cuando cursa con alteraciones fisiológicas o con interacciones medicamentosas. Su uso clínico requiere cuidadosas consideraciones, de las características de absorción, individualización de la dosis, guiada por las concentraciones séricas y educación al paciente sobre los potenciales efectos secundarios y de las interacciones con medicamentos. Recientemente, parece renovarse el entusiasmo por el uso de la teofilina para el tratamiento del asma por sus propiedades antiinflamatorias y efecto inmunomodulador

Effect of theophylline on diazepam and sodium valproate protection in pentylenetetrazole - kindled seizures in rats.

Theophylline is well known for its convulsant and proconvulsant action. Some experimental studies also suggest that theophylline and other methylxanthines may impair the protection of antiepileptic drugs. The interaction of theophylline and the antiepileptic drugs diazepam and sodium valproate was studied in pentylenetetrazole (PTZ) - kindled seizures in rats. Pretreatment with both diazepam 4 mg/kg and sodium valproate 300 mg/kg, i.p., showed protection against PTZ kindled seizures. Theophylline, 50 mg/kg, i.p., when given before the antiepileptic drugs, failed to reverse their protection. Since theophylline has an adenosine receptor antagonist activity which may be responsible for its convulsant potential, the results indicate non-involvement of adenosinergic mechanisms in the mechanisms of actions of these antiepileptic drugs.

Estudios biofarmacéuticos de productos similares de teofilina del mercado nacional / Biopharmaceutical studies of teophylline-like products at the national market

To perform in vitro release-dissolution studies of sustained release theophylline forms commercialized in Chile, 5 sustained release products were studied according to the specifications of the 7th supplement of the United States Pharmacopoeia Convention. Release and dissolution rates were compared with a rapid release aminophylline form. The identity, validation and active principle content of each product was also studied. All the studied forms complied with the quality requirements of the USP XII. The dissolution rate constants of the products at pH 6 ranged from 0.0583 to 0.2130, compared with 7.1 for the rapid release form. The dissolution of all products, except one, was pH dependent. These results underscore the need to systematically study the quality of pharmaceutical products considered similar, whose differences could have potential risks for patients

Plasma protein binding of theophylline in late pregnancy in rat.

A single bolus dose of theophylline (Th; 5 mg/kg) was administered through the abdominal catheter in nonpregnant and pregnant rats to measure unbound fraction (fu) of Th in pregnancy. After 90 min blood samples were collected. Plasma was extracted with a solvent system comprising chloroform and isopropyl alcohol (IPA) followed by iso-cratic HPLC analysis. Results showed an increase in unbound fraction of Th in late pregnancy.

Microalbuminuria, uric acid, uric acid clearance, gamma glutamyl transferase and cholesterol level in patients with chronic obstructive airway disease

This study was performed on thirty-two patients with chronic obstructive airway disease [COPD] subdivided into sixteen patients not receiving theophylline [group A] and sixteen patients taking regular theophylline [group B] and a control group of ten healthy individuals. Microalbuminuria was increased significantly in the patients compared with the controls, with the use of theophylline no significant difference was noted between group A and B. Serum gamma glutamyl transferase [GGT] was increased significantly in the patients compared with the controls and no difference was noted with the use of theophylline between groups A and B. Serum uric acid was increased significantly in the patients group compared with the controls. In the patients using aminophylline, it was significantly increased than patients not using theophylline. Serum uric acid clearance was increased significantly in the patients group as a whole compared with the controls. This increase was significantly higher in patients not using theophylline [group A] than patients using theophylline [group B]. Serum cholesterol was significantly increased in the patients group than the controls, this increase was more significant in the patients not using theophylline [group A] than patients using theophylline [group B]. Serum triglycerides, fasting blood sugar, serum creatinine and urea all showed no significant difference in the patients compared with the controls or with the use of theophylline. As regards the respiratory function, all patients with COPD showed a statistically significant decrease in all the studied parameters compared with the control and no significant difference was noted between the patients using theophylline [group B] and those not using theophylline [group A]. No correlation was found between microalbuminuria, uric acid clearance, cholesterol or respiratory functions in the study, while serum GGT was found to be correlated to cholesterol, but not by any other parameter

Antinociceptive effect of purine nucleotides

The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.

Empleo de la teofilina en pediatría / Therapy use of teophylline in children with asthma

La teofilina es uno de los medicamentos más antiguos utilizados para tratamiento del asma. En este artículo se resumen las indicaciones para su utilización en asma, y se concluye que las principales indicaciones son para asma crónica, particularmente nocturna, aunque se puede utilizar en crisis asmáticas agudas refractarias al manejo inicial con beta agonistas y esteroides

Asma y embarazo / Asthma and pregnancy

De los padecimientos que puede complicar el embarazo, el asma ocupa un lugar importante, ya que afecta hasta en 4 por ciento. Cuendo no se controla se compromete la oxigenación adecuada de la madre y del hijo. Según la intensidad del asma las manifestaciones clínicas pueden ser mínimas no aparentes o aparatosas que ameriten hospitalización, por esta razón además del parámetro clínico, es necesario que la paciente determine diariamente su flujo espiratorio máximo mediante un flujómetro portátil. Para el manejo farmacológico, se deben considerar los cambios fisiológicos que hay en la gestación, como la disminución de albúmina y ciertas proteínas que se unen al medicamento dando como resultado mayor fármaco libre activo, esto es particularmente importante como es el caso de teofilinas que además de lo anterior el aclaramiento de ésta se encuentra disminuido. Para fines prácticos se deben utilizar broncodilatadores beta dos solo por razón necesaria, prefiriendo la vía inhalada y en caso necesario el empleo de ciclo corto de esteroides. El manejo debe tener como objetivo el control de síntomas, evitar recaídas, función pulmonar lo más cercana a lo normal para lograr un estado satisfactorio del binomio madre-hijo