ABSTRACT
AIMS: Reactive oxygen species play a role in the signal transduction of beta-adrenergic receptors. We investigated whether an antioxidant (tocopherol) can reduce the effect of terbutaline in beta-2-adrenergic receptor (ß2-AR)-regulated smooth muscles. MAIN METHODS: Contractility of the tissues from nonpregnant (trachea) and 22-day-pregnant (myometrium and cervix) rats was investigated in an isolated organ bath. The tracheal and uterine ß2-AR expressions were increased by 17-beta-estradiol valerate (E2) and progesterone (P4), respectively. The accumulation of cyclic-AMP (cAMP), and the total oxidant (TOS) and total antioxidant status (TAS) were also measured. The oxidative stress index (OSI) was defined as the ratio of TOS and TAS. KEY FINDINGS: Terbutaline (10(-10)-10(-5)M) decreased the contractions in the nontreated and the P4-pretreated myometria, but tocopherol (10(-7)M) did not alter these actions. Terbutaline (10(-6)M) increased the cervical resistance both in the nontreated and in the P4-treated samples, while tocopherol reduced this action only in the P4-treated cervices. Terbutaline (10(-9)-10(-4)M) reduced the tracheal tones both in the nontreated and in the E2-treated tissues, while tocopherol reduced these effects. The changes in the intracellular cAMP levels of the tissues were in harmony with the isolated organ results. The OSI was highest in the trachea and lowest in the pregnant myometrium. SIGNIFICANCE: A higher OSI is linked to a higher tocopherol sensitivity of beta-mimetic-induced relaxation. Our results suggest that the antiasthmatic effect of beta-mimetics may worsen, while their tocolytic effect may remain unchanged during parallel tocopherol administration.
Subject(s)
Muscle, Smooth/metabolism , Oxidative Stress/physiology , Reproductive Physiological Phenomena/drug effects , Respiratory System/drug effects , Terbutaline/antagonists & inhibitors , Tocopherols/pharmacology , Analysis of Variance , Animals , Antioxidants/metabolism , Blotting, Western , Cyclic AMP/metabolism , Female , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth/drug effects , Oxidants/metabolism , Oxidative Stress/drug effects , Pregnancy , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction , Receptors, Adrenergic, beta-2/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Terbutaline/pharmacologyABSTRACT
The production of spherical crystals has recently gained great attention due to the fact that the crystal habit (form, surface, size, etc.) can be modified during the crystallization process. Spherical crystals of ASA were developed by non-typical and typical spherical crystallization techniques. The non-typical spherical crystallization process (conventional stirred tank method) resulted in few monocrystals and non-spherical crystal agglomerates. The typical spherical crystallization process was carried out by the three solvent-system (ethanol-water-carbon tetrachloride). The products were qualified by morphological study, NIR investigation, salicylic acid content, dissolution rate, studies on flowability, compactibility, cohesivity and tablettability. The results demonstrate that only typical spherical crystallization can be recommended for the production of spherical crystals of ASA. Only product made by this technique shows excellent flow properties and favourable compactibility, cohesiveness and tablettability values.
