Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways

This study aimed to investigate the role and signaling pathways of β3-AR in myocardial ischemia/reperfusion (I/R) injury, which is one of the leading causes of death worldwide. 47 male rats were randomly divided into two main groups to evaluate infarct size and molecular parameters. Rats in both groups were randomly divided into 4 groups. Control (sham), I/R (30 min ischemia/120 min reperfusion), BRL37344 (BRL) (A) (5 µg/kg single-dose pre-treatment (preT) before I/R) and BRL (B) (5 µg/kg/day preT for 10 days before I/R). Infarct size was determined with triphenyltetrazolium chloride staining and analyzed with ImageJ program. The levels of AMPK, SIRT1, mTOR, and p70SK6 responsible for cellular energy and autophagy were evaluated by western blot. Infarct size increased in the I/R group (44.84 ± 1.47%) and reduced in the single-dose and 10-day BRL-treated groups (32.22 ± 1.57%, 29.65 ± 0.55%; respectively). AMPK and SIRT1 levels were decreased by I/R but improved in the treatment groups. While mTOR and p70S6K levels increased in the I/R group, they decreased with BRL preT. BRL preT protects the heart against I/R injury. These beneficial effects are mediated in part by activation of AMPK and SIRT1, inhibition of mTOR and p70S6K, and consequently protected autophagy.

Protective effects of dextromethorphan and tizanidine on ouabain-induced arrhythmias

The effects of the opioid agonist dextromethorphan and the alpha(2)-adrenoceptor agonist tizanidine on ouabain-induced cardiac arrhythmias were investigated in rats. Ouabain (10 mg/kg i.v.) elicited ventricular arrhythmias in all of the control rats. Administration of dextromethorphan (25 mg/kg i.v.) and tizanidine (0.1 mg/kg i.v.) 30 min before ouabain treatment significantly reduced the incidence of arrhythmias. We suggest that dextromethorphan and tizanidine showed these effects by decreasing excitatory amino acid (EAA) activity. It can be speculated that opioids and other EAA antagonists may have antiarrhythmic actions through both their central and peripheral effects as well. (C) 2002 Prous Science. All rights reserved

Comparison of the effects of specific and nonspecific inhibition of nitric oxide synthase on morphine analgesia, tolerance and dependence in mice

The effects of L-Canavanine, a selective inducible nitric oxide synthase (NOS) inhibitor and N-G-nitro-Larginine methyl ester (L-NAME), a nonselective NOS inhibitor, on pain threshold and morphine induced analgesia, tolerance and dependence in mice were investigated and compared. Morphine was administered by subcutaneous implantation of a pellet containing 40 mg free base and withdrawal was precipitated by intraperitoneal (i.p.) injection of naloxone (2 mg/kg). L-Canavanine (200 mg/kg, i.p.) did not affect the pain threshold, morphine-induced analgesia and the induction and expression phases of morphine tolerance and dependence. L-NAME (20 mg/kg, i.p.) significantly (p < 0.05) enhanced the pain threshold, potentiated morphine-induced analgesia and attenuated the expression phase of morphine dependence which has been characterized by withdrawal signs and body weight loss, but did not modify the induction phase of morphine tolerance and dependence. It is concluded that constitutive NOS isoforms which were inhibited by L-NAME may be involved specifically in the mechanisms of morphine induced analgesia, tolerance and dependence. (C) 2003 Elsevier Science Inc. All rights reserved

Composition of the essential oils of Angelica sylvestris L. var. sylvestris isolated from the fruits by different isolation techniques

Baser, K. Husnu Can/0000-0003-2710-0231; Ozek, Temel/0000-0003-4251-8783WOS: 000259509300007The essential oils of the fruits of Angelica sylvestris L.var.sylvestris (Umbelliferae) obtained using hydrodistillation (HD), nucrodistillation (MD) and micro-steam distillation-solid-phase microextraction (MSD-SPME) techniques were analyzed by GC and GUMS. The composition of the oils depended on the isolation method employed. alpha-Pinene (25.6%,36.2% and 9.2%, respectively), beta-phellandrene (9.1%, 9.9% and 3.2%), bornyl acetate (7.3%,4.3% and 6.9%), limonene (5.6%, 4.3% and 2.1%). myrcene (4.4%, 4.0% and 1.3%), camphene (3.9%, 4.7% and 1.2%), alpha-chamigrene (3.4%,4.4% and 9.1%) and beta-sesquiphellandrene (2.5%,3.8% and 8.7%) were found as the main constituents in the oils. p-Cresol (6.5%), epi-alpha-bisabolol (5.6%), (Z)-beta-farnesene (5.5%), naphthalene (4.4%), daucene (3.1%), amorpha-4,11-diene (3.1%) and gamma-muurolene (2.5%) were also among the main constituents of the oil isolated by MSD-SPME

Effects of different nitrogen doses on thymoquinone and fatty acid composition in seed oil of black cumin (Nigella sativa L.)

Black cumin, Nigella sativa L. belonging to Ranunculaceae, is a valuable medicinal plant because of the curative effects of seed and oil. Despite studies on black cumin, there are few studies on the effects of nitrogen on fatty acid composition, no records on thymoquinone yield, and the thymoquinone content of the seed oil. In this study, the effects of different nitrogen doses on the seed oil yield, thymoquinone ratio/yield, and fatty acid compositions were investigated. Field studies with nitrogen doses (0, 40, 60, 80, and 100 kg/ha) were studied using the randomized plot design. As a result of the research, nitrogen doses significantly affected the oil and thymoquinone yields while insignificant on the thymoquinone ratio. The highest oil yield with 501.6 kg/ha was obtained from 80 kg/ha of the nitrogen doses, while the highest thymoquinone yield with 10.24 kg/ha was obtained from the control plots. Thymoquinone yields were in the same statistical group with other nitrogen doses, except for means of 100 kg/ha nitrogen doses. Linoleic, oleic, and palmitic acids were major fatty acids of black cumin, and their variations were insignificant in nitrogen applications. The values of butyric, capric, and linolenic acids varied significantly in different nitrogen doses. As a result of the study, it was determined that the highest oil yield was obtained from 80 kg/ha nitrogen application. It has been determined that nitrogen doses above 60-80 kg/ha should be avoided for the seed oil and thymoquinone yields in black cumin

Lipid and essential oil constituents of Cota hamzaoglui (Asteraceae)

In the present work, lipids and essential oil constituents of endemic Cota hamzaoglui Özbek & Vural were investigated with GC-FID/MS techniques. The fatty acids fraction was isolated with liquid-liquid extraction from the herb with Folch method and then methylated with BF3 reagent. Linolenic, linoleic, oleic and hexadecanoic acids were found to be the main fatty acids. The unsaturated fatty acids (66.0%) prevailed upon saturated (33.6%) ones. The essential oil was characterized with high percentage of the fatty acids (34.7 %), alkanes (14.0 %) and aliphatic aldehydes (8.3 %). The present study is the first report on chemical composition of C. hamzaoglui lipids and essential oil

Therapeutic drug monitoring in Turkey: Experiences from Istanbul

Therapeutic drug monitoring (TDM) has assumed an important place in patient management in the last few decades. In this study, serum drug levels determined in 7759 specimens sent to the Department of Pharmacology and Clinical Pharmacology in 1994 and 1998 for TDM were retrospectively evaluated. Monitored drugs were carbamazepine, valproate, phenytoin, phenobarbital, digoxin, theophylline, and salicylate, The comparison of the results obtained for the relevant 2 years showed that there was a remarkable increase in the number of requests for TDM per year and in the rate of serum drug levels that were within therapeutic range. Serum antiepileptic drug level monitoring accounted for a major part of the data. Overall data suggest that the use of TDM in antiepileptic drugs is improving; conversely, digoxin and theophylline are still not being properly monitored. In this study, the results are discussed in the light of rational TDM criteria

Effects of valsartan on stress-induced changes of serum vascular endothelial growth factor and nitric oxide in mice

This study investigated the effects of renin- angiotensin system ( RAS) blockade on stress- induced changes of serum vascular endothelial growth factor ( VEGF) and nitric oxide ( NO) in mice. Chronic stress increased the serum NO levels significantly compared to control group ( p =.0172). Valsartan, an angiotensin II receptor antagonist, alone, did not make significant difference versus control group. In chronic stress + valsartan group, serum NO levels decreased nonsignificantly compared to chronic stress group. There was a nonsignificant increase in serum VEGF levels after chronic stress. Valsartan alone or with chronic stress did not significantly affect the serum VEGF levels. In conclusion, there was no correlation between NO and VEGF changes during the stress response. In this respect, there may be other mechanisms to explain the stress- induced NO increase