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Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20 mg/kg. Groups 3 and 4 received 100 mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p = 0.000) and HSP-70 (p = 0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p = 0.017), HSP-70 (p = 0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury.

Leishmaniasis is a neglected tropical disease caused by obligate intracellular protozoan Leishmania parasites. Especially cutaneous form of leishmaniasis has an increasing importance in Turkey because of immigration. The aims of this study that is supported by the Scientific and Technological Research Council of Turkey (TUBITAK project number 213S149) are to produce Leishmania infantum and L.tropica activated C kinase receptor (LACK) gene based DNA and protein vaccines and to investigate the effectiveness of these vaccines by prime-boost method alone and combined with two adjuvants in-vivo on mice model. Methodological steps in this study are to culture L.infantum and L.tropica promastigotes in NNN medium, total genomic DNA isolation from culture, cloning activated C kinase receptor (LACK) gene with specific primers, ligation of PCR product into plasmid, amplifying recombinant plasmid in competent cells, producing endotoxin free DNA vaccine, producing endotoxin free LACK recombinant protein, combining DNA and protein vaccines with MPL-SE and CpG-ODN adjuvants and to investigate the effectiveness of this vaccines in-vivo on mice model. As a result L.infantum and L.tropica LACK gene based DNA and protein vaccines was produced and ready to immunization. Th-1 and Th-2 immunologic responses are going to be investigated after two week intervals three time vaccination against L.tropica and L.infantum infections on BALB/c mice. Copyright © 2016 by The American Association of Immunologists, Inc

Introduction To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes. Methods The experiments were performed in Sprague Dawley rats using a hot-plate device. Streptozotocin (STZ) was administered to the rats after taking control measurements. Rats with a blood glucose level of 240 mg/dL or above in the blood specimen obtained from the tail vein 3 days after STZ administration were considered as being diabetic. Three weeks after STZ administration, the hot-plate test was performed. Compared with the control measurements, rats that exhibited >20% decrease in the second hot-plate test measurements were considered to have developed neuropathy. Drugs [mirtazapine, naloxone (opioidergic antagonist), metergoline (serotonergic antagonist), and BRL44408 (adrenergic antagonist)] and drug combinations were administered to those rats that developed neuropathy. After administrating the drugs or drug combinations, the third hot-plate test was performed. Results Mirtazapine at doses of 10 and 15 mg/kg exhibited a significant antinociceptive effect. Naloxone, metergoline, or BRL44408 alone did not cause an antinociceptive effect. However, combinations of these drugs with mirtazapine (15 mg/kg) significantly decreased the antinociceptive effect of mirtazapine. Conclusion It is suggested that mirtazapine has a significant antinociceptive effect in diabetic neuropathy and that opioidergic, serotonergic, and adrenergic systems have roles to play in this effect.

Preliminary clinical studies of testosterone therapy in male patients with coronary artery disease obtained promising results. However, little is known about the in vitro effects of testosterone in human isolated arteries. We investigated the effect of testosterone on contractile tone of human isolated radial artery (RA). Testosterone was added (0.1 – 300 µM ) cumulatively to organ baths after precontraction with KCl (45 mM) and phenylephrine (PE, 10 µM). Testosterone-induced relaxations were tested in the presence of the cyclooxygenase inhibitor indomethacin (10 µM), nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM), non-selective large conductance Ca2+-activated and voltage-sensitive K+ channel inhibitor tetraethylammonium (TEA, 1 mM), ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 10 µM), and voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM). Testosterone produced relaxation in human RA (Emax: 53.03 ± 2.76% and 66.83 ± 1.97% of KCl and PE-induced contraction, respectively). Except for GLI, the relaxation to testosterone is affected by neither K+ channel inhibitors (TEA, BaCl2, and 4-AP), L-NAME, nor indomethacin. We report for the first time that supraphysiological concentrations of testosterone induces relaxation in RA. This response may occur in part via ATP-sensitive K+ channel opening action. Keywords:: human radial artery, testosterone, vasodilation, potassium channel

Objective: Diabetes mellitus causes a decrease in cardiac output, arterial blood pressure, and heart rate. In this study, we aimed to investigate, at the molecular level, the effect of nitric oxide synthase (NOS) on heart pathology in type 1 diabetes and look at the therapeutic effect of pentoxifylline on this pathology., Objective: Diabetes mellitus causes a decrease in cardiac output, arterial blood pressure, and heart rate. In this study, we aimed to investigate, at the molecular level, the effect of nitric oxide synthase (NOS) on heart pathology in type 1 diabetes and look at the therapeutic effect of pentoxifylline on this pathology. Methods: In this experimental study, 50 Wistar albino male rats were used. The rats were divided into 5 groups: group C, control; group D, only diabetes; group D+PI and D+PII, diabetes + pentoxifylline; group P, only pentoxifylline. Group D+PI rats received 50 mg/kg/day pentoxifylline over two months. However, group D+PII rats received saline in the first month and 50 mg/kg/day of pentoxifylline over the following month. At the end of two months, NOS expressions in heart tissue were assessed through immunohistochemistry analysis. The data were compared by one-way ANOVA. Results: At the end of the experiments, there was increased cytoplasmic vacuolization, myofibrillar loss, cytoplasmic eosinophilia, and degeneration of cardiomyocytes; nNOS and iNOS expressions in group D decreased compared with that in group C. In group D+PI and group D+PII, nNOS and iNOS expressions improved compared with group D. Conclusion: As a result, we found that diabetes, a known chronic disease, causes serious damage in heart tissue. NOS plays a role in this damage, and pentoxifylline aided in improving nNOS and iNOS expression in this damage

p Dexmedetomidine (DEX) is a new methylol derivative with high affinity to 2-adrenergic receptors. It causes analgesia and sympatholysis, and has sedative, anxiolytic, and hypnotic effects. The use of DEX and its affinity to 2-adrenergic eceptors in the body should not only be limited to sedation and nesthesia, because 2-adrenergic receptors are scattered hroughout the body. In 1948, Ahlquist et al1 first reported and subtypes of adrenergic receptors that were activated by noradrenalin, the mediator of sympathetic nervous system stimulation in mammals. In light of this preliminary report, numerous studies were performed on this topic and, in 1973, 1 and 2 subtypes of -adrenergic receptors were determined.2 In subsequent investigations, gene studies were developed, and 3 subtypes, called aA, 1B, and 1c, or 1-adrenergic receptors2 and 4 subtypes, called 2A, 2B, 2C, and 2D, for 2-adrenergic receptors were isolated.3,4 Studies perormed on isolated organ samples from several experimental anmals showed that both subtypes of -adrenergic receptors are present in postsynaptic membranes in many animal species, including rabbits and guinea pigs; 1-adrenergic receptors are domnant.5 In contrast, 2-adrenergic receptors were reported to be enser only in a number of tissues, such as human saphenous vein6 and femoral vein tissue.7 Experimental findings show that localization of -adrenergic receptor subtypes can differ among species nd vessel segments, so the responses that occur after activation of hese receptors vary.

Mineral trioxide aggregate (MTA) is being advocated for vital pulp therapy. In the case of direct pulp capping, hemorrhage control is an important step on success, but little is known about the effect of MTA on pulpal bleeding. In addition, there has been a lack of information on the effect of MTA on smooth muscle contraction, such as can occur in the blood vessels of dental pulp. The present study assessed the vascular effects of MTA, using the rat aortic ring preparations as a tissue model. MTA (100–500 mg) induced dose–dependent contraction in rat thoracic aorta. The contractile effect of MTA was blocked by calcium channel blocker nifedipine (1 μM). These data suggest that the vasoconstrictor property of MTA is related to calcium influx and it may allow proper control of hemorrhage which is critical for the success of any pulp-capping treatment.

Objective: To investigate the direct effects of dexmedetomidine (DEX) on isolated human internal mammary artery (IMA). Design: In vitro experimental study. Setting: Cardiovascular Pharmacology Laboratory, Department of Pharmacology, Gulhane School of Medicine, Ankara, Turkey. Participants: IMA segments were obtained from 18 patients undergoing coronary artery bypass surgery. Interventions: The response in IMA was recorded isometrically by a force displacement transducer in isolated organ baths. DEX-induced contractions were tested in the presence of the α2-adrenoceptor antagonist yohimbine (10−7 mol/L) and the α1-adrenoceptor antagonist prazosin (10−8 M). The effect of DEX (10−7, 10−6, and 10−5 mol/L) on phenylephrine (10−9-3 × 10−4 mol/L)-induced contactions was also tested. Measurement and Main Results: DEX (10−9 mol/L-3 × 10−5 mol/L) caused contraction in IMA segments. The contraction at lower concentrations of DEX (10−9 mol/L-3 × 10−7 mol/L) was attenuated by yohimbine (10−7 mol/L), whereas prazosin (10−8 mol/L) attenuated the contractions at higher concentrations of DEX (10−6 mol/L-3 × 10−5 mol/L). Incubation of IMA segments with high concentrations of DEX (10−6 mol/L and 10−5 mol/L) caused an inhibition of phenylephrine (10−9 mol/L-3 × 10−4 mol/L)-induced contraction. Conclusion: These data suggest that DEX causes contraction by activating α2-adrenoceptors at lower concentrations, but it may also activate α1-adrenoceptors at higher concentrations in IMA. The action of DEX on phenylephrine-induced contraction may be related to an α1-adrenoceptor antagonistic effect produced via partial α1-adrenoceptor agonistic action.

To determine the myocardial and vascular effects of remifentanil and fentanyl in human atria and saphenous veins.In vitro, prospective with repeated measures.University research laboratory.The direct effects of remifentanil and fentanyl on the electrical stimulation-induced contraction of nonfailing human atrium and saphenous veins contracted with 5-hydroxytryptamine were studied.In human atrial trabeculae, cumulative (10(-9)-10(-5) mol/L) added remifentanil had no effect on contractile force, compared with untreated muscles (p0.05). The force of contraction was significantly less than control values with concentrations of fentanyl ranging from 10(-8) to 10(-5) mol/L (p0.05). At the highest concentration (10(-5) mol/L), the inhibition by fentanyl of the electrical stimulation-induced contraction was 40.6% +/- 6.32%. In human saphenous vein strips preconstricted with 5-hydroxytryptamine, remifentanil (10(-8)-10(-5) mol/L) and fentanyl (10(-8)-10(-5) mol/L) produced "concentration-dependent" relaxation when compared with the control contraction value (p0.05). The IC(50) was similar with remifentanil and fentanyl and the E(max) of fentanyl was significantly higher than remifentanil (p0.05). The venodilatory effects of remifentanil and fentanyl were similar on veins with or without endothelium (p0.05).Remifentanil has no direct effect on the contraction of myocardium. Fentanyl inhibits the electrical stimulation-induced contraction in human right atrial muscles in vitro. Remifentanil and fentanyl produce "concentration-dependent" relaxation in human saphenous vein strips independent from the endothelium.