Tijen Kaya

A Placebo-Controlled Comparison of Effects of Repetitive Doses of Betamethasone and Dexamethasone on Lung Maturation and Lung, Liver, and Body Weights of Mouse Pups

The aim of this study was to compare in vivo effects of single and repetitive doses of betamethasone (BETA) and dexamethasone (DEX) administered to pregnant mice on lung maturation and lung, liver, and body weights (LLBW) of their pups. One hundred and eighty gravid Swiss albino mice were randomly assigned to 1 of 6 groups (n = 30) and administered either BETA, DEX, or saline as a single dose at 14 d gestation or repetitive doses twice daily at 14 and 15 d gestation. All the study groups were then divided into three sets (n = 10). The mice in the second sets were redivided into three subsets randomly (including four, three, and three mice). All gestations in the first sets were terminated at 16.5 d gestation to observe the neonatal breathing pattern (scale to 0–5; 5 is unlabored breathing) of male and female pups whereas other sets had normal delivery. The pups in first, second, and third sets were killed for evaluation in the first set after the evaluation of breathing pattern, in the subsets of second set on postnatal d 1, 3, and 5, and in the third set on postnatal d 90. We recorded maternal body weights at 0 and 16.5 d gestation, and LLBW, the lung/body weight ratio of pups, sex, and the amount of live and dead births per litter. Pups exposed to BETA and DEX had significantly lower maternal weight compared with the saline groups. The death litter size was significantly higher in pups exposed to repetitive doses of DEX than the other treatments. Sex had no significant effect on breathing score and LLBW. Pups exposed to repetitive doses of BETA and DEX presented a higher breathing score than the other groups. The breathing score was significantly higher with BETA than DEX after their repetitive use. The LLBW were significantly less in the treatment groups, especially in the group exposed to repetitive doses of DEX. In conclusion, repetitive doses of BETA and DEX lead to increased fetal lung maturation, but this may be at the expense of fetal and neonatal growth. DEX is less potent in accelerating lung maturation than BETA but it causes more reduction in fetal and neonatal growth.

The role of K(+) channels on the inhibitor effect of sevoflurane in pregnant rat myometrium.

UNLABELLED Volatile anesthetics and K(+) channel openers inhibit spontaneous contractions in myometrial smooth muscle. Volatile anesthetics modulate K(+) channel activity. We investigated the role of two K(+) channel blockers on the effect of sevoflurane in pregnant rat myometrium. Term pregnant rat uteri were excised, and cross-sectional myometrial strips were mounted for isometric force recording. Sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner. The maximal inhibition measured in amplitude and frequency of spontaneous myometrial contractions with sevoflurane (at 3 minimum alveolar anesthetic concentration) was 44.32% and 33.32% of control contractions, respectively. Tetraethylammonium (TEA) and glibenclamide, K(+) channel blockers, increased spontaneous myometrial contractions in a concentration-dependent manner. Sevoflurane responses were repeated at concentrations with no effect on spontaneous contractility of TEA, a Ca(2+)-activated K(+) channel blocker, and glibenclamide, an adenosine triphosphate-sensitive K(+) channel blocker, in myometrial strips. TEA (3.10(-4) M) caused a significant reduction in sevoflurane-induced inhibitor responses, but glibenclamide (10(-6) M) did not. Sevoflurane-induced maximal inhibition (at 3 minimum alveolar anesthetic concentration) on amplitude and frequency of spontaneous myometrial contractions in the presence of TEA (3.10(-4) M) was 31.85% and 22.33% of control contractions, respectively (P < 0.05). These results suggest that the in vitroapplication of sevoflurane inhibited the amplitude and frequency of spontaneous myometrial contractions in pregnant rats in a concentration-dependent manner. Such inhibition was reduced by TEA. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by TEA. IMPLICATIONS In this study, we found that sevoflurane causes significantly decreased myometrial contractile activity in pregnant rats. The inhibition of myometrial smooth muscle induced by sevoflurane seems to be mediated, at least in part, via activation of Ca(2+)-activated K(+) channels, because inhibition was reduced by tetraethylammonium.

Vasorelaxant effect of opioid analgesics on the isolated human radial artery

Background and objective: Arterial grafts are prone to vasospasm. Opioid analgesics are commonly used in the perioperative course of cardiac surgical procedures. Therefore, we investigated the direct effects of morphine, meperidine, fentanyl and remifentanil on the human radial artery. Methods: Radial artery segments, obtained from 20 patients, were precontracted with phenylephrine. Using the organ bath technique, the endothelium‐independent vasodilatation was tested in vitro by addition of cumulative concentrations of morphine, meperidine, fentanyl and remifentanil in separate organ baths, in the presence or absence of naloxone. Indomethacin and NG‐nitro‐l‐arginine methyl ester was added to all organ bath in order to determine the effects of prostaglandins and nitric oxide, respectively. Results: Morphine (10−8–10−4mol L−1), meperidine (10−10–10−6mol L−1), fentanyl (10−10–10−6mol L−1) and remifentanil (10−8–10−4mol L−1) caused a concentration‐dependent vasorelaxation in the human being artery rings. The relaxations in the presence of naloxane did not change. The maximal relaxant effects of meperidine and fentanyl were significantly greater than those of morphine and remifentanil (P < 0.05). Conclusions: These findings indicate that morphine, meperidine, fentanyl and remifentanil produce concentration‐dependent and endothelium‐independent relaxations in human being radial artery rings. Meperidine and fentanyl are more potent relaxant agents than morphine and remifentanil in the human being radial artery in vitro.

Inhibitor effect of omeprazole in isolated human myometrial smooth muscle

The aim of the present study was to investigate the effect of omeprazole, an H+-K+-ATPase inhibitor, in myometrial smooth muscle strips from women undergoing elective caesarean section at term. Isolated myometrial strips taken with informed consent were obtained from eight pregnant women undergoing elective caesarean section at term (not in labour) and mounted in organ baths for recording of isometric tension. We recorded the effect of increasing concentrations of omeprazole on spontaneous and Ca2+-induced contractions of myometrial smooth muscle and on contractions of myometrial smooth muscle pretreated with indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M). Omeprazole (10(-4)-10(-3) M) decreased the amplitude and frequency of spontaneous contractions in a time- and concentration-dependent manner in all myometrial smooth muscle isolated from pregnant women. The decrease in amplitude of contractions in myometrial smooth muscle reached statistical significance beginning from the concentration of 3 x 10(-4) M. Addition of indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M) in to the organ baths 30 min before did not change relaxation responses to omeprazole. When 8 mM Ca2+-precontracted in Ca2+-free medium myometrial smooth muscle were exposed to increasing concentrations of omeprazole (10(-5)-10(-3) M), omeprazole produced relaxation responses in a time- and concentration-dependent manner, reaching statistical significance at 10(-4) M. These results show: (1) omeprazole time- and concentration-dependently decreased spontaneous contractile activity in myometrial smooth muscle isolated from pregnant women, (2) omeprazole-induced relaxations was not influenced by indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME), suggesting that it is not mediated by cyclooxygenase products and nitric oxide, and (3) omeprazole brought about time- and concentration-dependently relaxation of myometrial smooth muscle precontracted by 8 mM Ca2+ in Ca2+-free medium. This effect of omeprazole may be due to blockade of the calcium channels.

Effect of magnesium sulfate, isradipine, and ritodrine on contractions of myometrium: pregnant human and rat

Background.  Magnesium sulfate, isradipine, and ritodrine are smooth muscle relaxants used for treating preterm labor. The aim of this study is to investigate the action profile of these drugs on the amplitude and frequency of spontaneous contractions of isolated myometrial strips of pregnant human and rat.

Effect of hypothyroidism on the NO/cGMP pathway of corpus cavernosum in rabbits.

INTRODUCTION The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. There is some evidence suggesting that hypothyroidism may be a cause of impotence. AIM We aimed to investigate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in hypothyroidism in an experimental rabbit model and compared hypothyroid rabbits with controls to evaluate the possible involvement of the NO/cGMP pathway. METHODS The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. The first group had hypothyroidism induced surgically by thyroidectomy for 6 weeks. The second group underwent a sham operation. RESULTS There was no significant change in the mean body weight of hypothyroid rabbits and controls. Triiodothyronine and thyroxine levels were significantly lower in hypothyroid rabbits. Plasma thyroid-stimulating hormone and prolactin levels were significantly higher in hypothyroid rabbits. Plasma total calcium and parathormone levels remained in the normal range in both groups. MAIN OUTCOME MEASURES Papaverine-induced concentration-dependent relaxations were similar in both groups. Carbachol-induced relaxation responses decreased in hypothyroid rabbits. There were significant differences between control and hypothyroid rabbits in frequency-dependent relaxations induced by electrical-field stimulation (EFS). YC-1-induced relaxation responses did not change significantly in hypothyroid rabbits. Concentration-dependent relaxations induced by diethylamine (DEA)/NO were similar in both groups. Amrinone-induced relaxation responses did not change significantly in hypothyroid rabbits. CONCLUSION Reductions of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on the decrease of released or synthesized NO from nitrergic nerves and endothelium.

Effects of nimesulide and pentoxifylline on decreased contractile responses in rat ileum with peritonitis.

The aim of this study was to determine the effects of nimesulide and pentoxifylline on the contractile effects of KCl, carbachol and substance P in the longitudinal muscle of rat ileum during peritonitis. Peritonitis was induced in rat ileum by cecal ligation and puncture. Thirty rats were operated on to induce peritonitis, 10 of which received nimesulide (5 mg/kg, subcutaneously) and 10 of which received pentoxifylline (25 mg/kg, subcutaneously) before the operation; 10 other rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, ileum segments were transferred to isolated organ baths and responses to KCl, carbachol and substance P were recorded. Emax values of KCl, carbachol and substance P were markedly lower (P<0.05), with no change in the pD2 values, in the peritonitis group than in the controls. Peritonitis-induced changes in the KCl, carbachol and substance P responses of ileum were significantly restored by nimesulide (P<0.05), but not by pentoxifylline. The improved contractile responses following nimesulide treatment indicate that products of cyclooxygenase-II may be, at least in part, responsible for the decreased contractile responses to KCl, carbachol and substance P in peritonitis.

Chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid and anthracene-9-carboxylic acid inhibit contractions of pregnant rat myometrium in vitro.

Objective: We compared in vitro relaxant effect of chloride channel modulators, such as 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and anthracene-9-carboxylate (9-AC), and β2-adrenergic agonists, such as ritodrine, in pregnant rat myometrium. Methods: Isolated myometrial strips were obtained from eight pregnant rats, and the strips were mounted in organ baths for recording isometric tension. The effects of 10-8-10-4 M ritodrine, 10-6-3 × 10-4 M NPPB, and 10-6-10-3 M 9-AC on spontaneous contractions were recorded. Results: Ritodrine (10-8-10-5 M) completely inhibited the amplitude and frequency of spontaneous contrations in myometrial strips isolated from pregnant rats in a concentration-dependent manner, but the relaxant effect of ritodrine at 10-4 M concentration resulted in tachyphylaxis. The chloride channel blocker NPPB (10-6-3 × 10-4 M) and the chloride transport inhibitor 9-AC (10-5-10-3 M) decreased the amplitude of spontaneous myometrial contractions in a concentration-dependent manner; the maximum inhibition produced by the highest tested concentration of each drug was 43.8% and 42.1% of the original degree of spontaneous contractions, respectively. The frequency of myometrial contractions was significantly inhibited by NPPB and 9-AC beginning with the concentration of 10-4 M. Conclusion: NPPB and 9-AC appear to be effective relaxants of pregnant rat myometrium. These effects of NPPB and 9-AC might be therapeutically advantageous in clinical management of preterm labor.

Investigation of the relaxant effects of propofol on ovalbumin-induced asthma in guinea pigs

Background and objective: Because the incidence of asthma appears to be increasing, the importance of proper perioperative management of individuals with asthma will also continue to increase. Although its mechanism of smooth muscle relaxation is unknown, propofol has been associated with less bronchoconstriction during anaesthetic induction. The aim of this study was to investigate the possible mechanism of these effects and the effects of propofol on the isolated trachea preparations from control and ovalbumin‐sensitized guinea pigs. Methods: Adult male guinea pigs, weighing 280‐330 g, were randomly allocated to two experimental groups, each consisting of 10 animals. Ten guinea pigs were sensitized by intramuscular injections of 0.30 mL of a 5% (w/v) ovalbumin/saline solution into each thigh (0.6 mL total) on days 1 and 4, whereas the remaining 10 served as controls receiving a total of 0.6 mL distilled water on days 1 and 4 as placebo. The isolated trachea preparations were mounted in tissue baths with modified Krebs‐Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. We tested the effects of propofol (10−7‐10−3 M) on resting tension and after precontraction with carbachol and histamine on isolated trachea preparations from control and ovalbumin‐sensitized guinea pigs. We also tested the effect of propofol on isolated trachea preparations precontracted with carbachol and histamine in the absence and presence of different inhibitors or antagonists. We investigated propofol responses in tracheal smooth muscle precontracted with CaCl2. Results: Propofol (10−7‐10−3 M) produced a concentration‐dependent relaxation of isolated tracheal preparations precontracted by carbachol (10−6 M) and histamine (10−6 M) in both groups. Preincubation with N(w)‐nitro l‐arginine methyl ester (3 × 10−5 M), indomethacin (10−5 M) or propranolol (10−4 M) did not produce a significant alteration on propofol‐induced relaxation responses (P > 0.05), while preincubation with tetraethylammonium (3 × 10−4 M) significantly decreased the propofol‐induced relaxation responses in both groups (P < 0.05). Propofol (10−7‐10−3 M) induced concentration‐dependently relaxations in isolated trachea rings precontracted with CaCl2 in both the control and ovalbumin‐sensitized groups. Conclusion: Propofol induced concentration‐dependent relaxations in precontracted, isolated trachea smooth muscle of guinea pigs in both the control and ovalbumin‐sensitized groups. These relaxations were independent of epithelial function and stimulation of &bgr; adrenergic receptors. Opened Ca2+‐sensitive K+ channels and inhibited L‐type Ca2+ channels can contribute to these relaxations.

In vitro effects of intravenous anesthetics on the sphincter of oddi strips of sheep

Background: Intravenous anesthetics are often used for conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi (SO) manometry. This study was designed to investigate the direct effects of some intravenous anesthetics on SO in sheep. Methods: In sheep SO rings, changes in isometric tension in response to cumulative concentrations of intravenous anesthetics were determined, and values for E_max (mean maximal inhibition) and pD₂ (i.e. the negative logarithm of the concentration for the half-maximal response, EC₅₀) were compared. Results: Meperidine (10^–7 to 3 × 10^–5M), fentanyl (10^–7 to 3 × 10^–5M), midazolam (10^–7 to 3 × 10^–5M) and propofol (10^–7 to 3 × 10^–4M) induced concentration-dependent relaxations on SO precontracted with carbachol (10^–6M). E_max and pD₂values following meperidine, fentanyl and midazolam administration were significantly greater than after propofol (p < 0.05). There were no significant differences in E_max and pD₂values for meperidine, fentanyl and midazolam. Conclusion: These results suggest that meperidine, fentanyl and midazolam are equipotent relaxants in the sheep SO in vitro. The relaxatory effect of propofol was 10 times less potent compared to the above agents, and it can be beneficial during SO manometry in controlled clinical human studies.