Prevalence of clostridium difficile toxin in kidney transplant recipients.
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Biomedical subjects
Publications and source records attributed to S Apaydin.
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OBJECTIVE: To determine the effects of 4-aminopyridine and Bay K 8644 on mean arterial pressure and heart rate in an anesthetized rat model of verapamil toxicity. METHODS: The study was a randomized, controlled animal study. Rats were anesthetized and the carotid artery was cannulated for mean arterial pressure and heart rate measurements while both jugular veins were cannulated for drug administration. All animals were infused with verapamil (15 mg/kg/h i.v.) until 45-60% reduction of mean arterial pressure and 30% reduction of heart rate were observed. After verapamil, control animals were given normal saline solution and the other groups received 4-aminopyridine (1 and 2 mg/kg/h) or Bay K 8644 (0.3 and 0.6 mg/kg/h) for 60 minutes. RESULTS: While 4-aminopyridine (1 mg/kg/h i.v.) did not significantly increase mean arterial pressure (75.9 +/- 5.5%) when compared with the control group (64.3 +/- 5.1%, p > 0.05), 2 mg/kg/h i.v. of 4-aminopyridine improved mean arterial pressure within 40 minutes (87.4 +/- 6.6%, p < 0.05, 95% CI 66.4-108.6%). Because the 2 mg/kg/h 4-aminopyridine produced side effects including seizures, secretions, and fasciculations at 35 +/- 5 minutes, the infusion was stopped at that time. Only the 2 mg/kg/h 4-aminopyridine infusion increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 283.2-364.4). Bay K 8644 (0.3 and 0.6 mg/kg/h i.v.) significantly enhanced mean arterial pressure within 5 minutes (68.0 +/- 4.1% and 73.0 +/- 2.9%, respectively, p < 0.05), (95% CI 56.8-78.0% and 95% CI 64.9-81.1%, respectively) but no significant changes in mean arterial pressure were observed after 5 minutes. The 4-aminopyridine (2 mg/kg/h) increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 311.3-358.7). Bay K 8644 did not produce a significant effect on heart rate (p > 0.05). CONCLUSIONS: 4-Aminopyridine improved mean arterial pressure and heart rate in a dose-dependent fashion; however, the higher infusion rate (2 mg/kg/h) necessary to improve mean arterial pressure and heart rate resulted in convulsions and excessive secretions. The reversal effects of Bay K 8644 on mean arterial pressure were transient and did not affect heart rate.
Arachidonic acid (AA) and lysophosphatidic acid (LPA) are two important signaling molecules generated by the hydrolysis of membrane phospholipids by the action of phospholipase A2 (PLA2) enzymes. We have previously shown that arachidonic acid affects opioid receptor binding in a negative manner. In the present study, we have investigated the modulatory role of LPA on equilibrium binding of [3H]naloxone to rat brain opioid receptors. The preliminary data demonstrates that LPA at physiological concentrations (100-400 nM) was capable of modulating opioid receptor binding. 100 nM free lysophosphatidic acid concentration stimulates while 200 and 400 nM concentrations inhibit binding. This observation brings the possibility of a cross talking mechanism between opioid and LPA signaling pathways.
The aim of the present study was to compare the analgesic efficacy of piroxicam-FDDF (fast dissolving dosage form) with naproxen sodium, following bilateral removal of impacted third molars. A double-blind, randomized, crossover, analgesic trial was carried out on 40 patients undergoing surgical removal of one lower third molar at each visit. The analgesic efficacy of a single dose regimen of piroxicam-FDDF (40 mg, Feldene Flash, Pfizer, Turkey) was compared with naproxen sodium (550 mg, Anaprotab, Sanli, Turkey). Pain intensity was measured on a category-rating scale during the 8-h period after drug administration. Each patient evaluated the efficacy of the study medication at 15, 30, 45, 60, 90 and 120 min, and then hourly for up to 8 h of drug ingestion. Additional key efficacy measures were also determined (pain intensity difference [PID], sums of pain intensity difference [SPID], total pain relief [TOTPAR], peak pain relief, number of observations at which pain was half-relieved, overall evaluation of study medication effectiveness, and time to medication with a back-up analgesic). The data were analyzed by paired Student's t-test and one-way analysis of variance (ANOVA). Results are expressed as means +/- SEM, and p < 0.05 was taken as statistically significant. The PID and pain relief scores of the piroxicam-FDDF group were significantly greater than those for the naproxen sodium group at 15, 30, 45 and 60 min (p < 0.01). After 90 min to 8 h, no statistical significance was revealed among the two test groups (p > 0.05). The peak pain relief, maximal analgesic effect, SPID, TOTPAR values, adjusted mean number of observations with pain at least half-relieved, and the final overall evaluation records were all superior for piroxicam-FDDF (p < 0.05). The results of this study clearly show that the analgesic efficacy of piroxicam-FDDF is superior to naproxen sodium in the treatment of pain following oral surgery for the removal of impacted third molars.
Arachidonic acid effect on binding of [3H]naloxone to rat brain membranes were studied at opioid receptor subtype level. Arachidonic acid inhibited opioid receptor binding in a dose-dependent manner, both in the presence and absence of sodium. With blockage experiments it was shown that delta-opioid receptors were modulated by arachidonic acid to a greater extent than that of mu-opioid receptors. On the other hand, there was no significant difference in terms of IC50 values for arachidonic acid inhibition of [3H]naloxone binding at agonist and antagonist configuration of the receptor subtypes.
GR127935 (N-[methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2 ,4-oxadiazol-3-yl) [1, 1-biphenyl]-4-carboxamide hydrochloride) has been recently introduced as an experimental tool to antagonize 5-HT(1B/D) receptor-mediated functional responses. The compound indeed exhibits a very high affinity and selectivity for 5-HT(1B/D) binding sites and it antagonizes a number of 5-HT(1B/D) receptor-mediated responses. The present experiments were performed to investigate the selectivity of GR127935 against functional responses mediated by 5-HT1-like, 'orphan' 5-HT1-like (5-ht7?), 5-HT2, 5-HT3 or 5-HT4 receptors in several in vivo preparations. Intravenous (i.v.) treatment with GR127935 (300 microg x kg(-1)) potently antagonized decreases in total carotid blood flow as well as hypotensive responses induced by the 5-HT1-like receptor agonist sumatriptan in rabbits. I.v. bolus injections of GR127935 (up to 500 and/or 1500 microg x kg(-1)) did not significantly modify 5-HT-induced: (i) tachycardia in the pig (5-HT4 receptor-mediated) and cat ('orphan' 5-HT1-like or, perhaps, 5-ht7 receptor-mediated); (ii) depressor effects in the rat and cat ('orphan' 5-HT1-like or 5-ht7 receptor-mediated); (iii) von Bezold-Jarisch reflex in the rat or the early phase of the urinary bladder contraction in the cat (both 5-HT3 receptor-mediated). In contrast, high doses (500-1500 microg x kg(-1)) of GR127935 suppressed 5-HT-induced pressor responses in the rat and cat and urinary bladder contractions (secondary phase) in the cat as well as the DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride)-induced pressor responses in the rat, which are all mediated by 5-HT2A receptors. In conclusion, the present study demonstrates that GR127935 is a selective 5-HT(1B/D) receptor antagonist devoid of interactions at 'orphan' 5-HT1-like (5-ht7?), 5-HT3 and 5-HT4 receptors. However, GR127935 possesses a moderate 5-HT2A receptor blocking property, which is consistent with its binding profile (pKi: 7.4). Lastly, in view of the potent antagonist action of GR127935, the sumatriptan-induced hypotension in rabbits seems to be mediated by 5-HT(1B/D) receptors.
1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.
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A patient with end stage renal disease developed ischaemic skin necrosis and digital gangrene. He had diffuse arterial calcification associated with hyperparathyroidism secondary to renal failure. The patient received inappropriate cyclophosphamide therapy as he had been misdiagnosed as having an inflammatory vasculitis. This clinical picture, previously named "calciphylaxis" should come into the differential diagnosis of systemic vasculitis in a uraemic patient with hyperparathyroidism.
The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/ kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group (P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP. Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group (P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates (P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.
In this study we investigated the actions of SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl -9-(methylthio)-2H- naphth[2,3-b)-1,4-oxazine hydrogen malonate), previously classified and employed as a selective alpha 1-adrenoceptor agonist, in the rat isolated aorta assay. It was shown that, in addition to its alpha 1-adrenoceptor agonistic action, SDZ NVI-085 behaves as a competitive antagonist of 5-hydroxytryptamine (5-HT)-induced contraction of rat aorta (pKB = 8.13 +/- 0.08). The structurally related alpha 1-adrenoceptor agonist, SK & F 89748-A (l-1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine hydrochloride), produced inhibition of the 5-HT response only at the highest concentration tested (1 microM) with an associated pA2 value of 6.0 +/- 0.1. These findings suggest that the affinity of SDZ NVI-085 for 5-HT2 receptors is considerably higher than for alpha 1-adrenoceptors, which may have implications for its use as a pharmacological tool.
STUDY OBJECTIVE: To determine whether immediate treatment with oral activated charcoal (AC) products of differing surface areas prevents clinical toxicity of a lethal oral dose of dichlorvos in mice. DESIGN: An in vivo, prospective, randomized, placebo-controlled study using 75 male albino mice. INTERVENTIONS: Fasting mice were administered 57.5 mg/kg of a 0.55% dichlorvos solution via feeding tube. One minute later, groups of 15 mice each received 1 or 2 g/kg of Actidose-Aqua AC or 1 or 2 g/kg of Sigma AC or sterile water by feeding tube. In this way, all mice received 15 mL/kg of an AC suspension or sterile water. The animals were observed for 24 hours for seizures or death. RESULTS: In all treatment groups, mice were found to have significantly fewer seizures and deaths (P < .05) than the control group when compared by chi 2 and Fisher's exact tests. No statistical difference was found between the death and seizure rates when treatment groups were compared with each other. The group sizes were too small, however, to rule out significant type II error (beta > .2). CONCLUSION: In this in vivo mouse model, all AC products tested decreased the incidence of seizures and death. Further studies should be done to investigate the clinical effects of AC products with different surface areas.
1-Aroyl-4-substituted thiosemicarbazides were obtained by the addition of 4-(4-fluorobenzoylamino)benzoylhydrazine to methyl, ethyl, propyl, allyl, cyclohexyl, phenyl and phenethyl isothiocyanates. The structures of the synthesized compounds were confirmed using UV, IR, 1H-NMR (for compounds 4c, 4g) and mass (for compounds 4b, 4c, 4g) spectral methods together with elemental analyses. None of the synthesized compounds has been reported previously.
5-HT-induced acute gastric mucosal injury was assessed in rats by using 5HT1, 5HT2, 5HT3, 5HT4 or muscarinic receptor related drugs. Rats were treated with antagonists i.p. and 30 minutes later either vehicle, 5-HT (20 mg/kg) or other agonists were administered s.c. The stomachs were removed 4 hours after the last injection and mucosal integrity was assessed by light microscopy using a histological ulcer index (HUI). The HUI was found to be significantly increased following 5-HT administration (1.57 +/- 0.3) when compared with controls (0.14 +/- 0.1). 5HT1 agonist 5-carboxamidotryptamine (20 mg/kg) produced acute gastric erosion and increased the HUI (P < 0.05). The HUI in the animals receiving 5-HT1D agonist sumatriptan (7 mg/kg) was found to be 1.62 +/- 0.24. 5HT2 antagonist ketanserine (2.5-15 mg/kg), 5HT3 antagonist ondansetron (1-5 mg/kg), 5HT4 antagonist DAU 6285 (1-10 mg/kg) and atropine (1.5-30 mg/kg) exerted no effect whereas 5HT1/2 antagonist metitepine (0.05-0.5 mg/kg) caused a dose dependent inhibition of the effect of 5-HT. The results from this study demonstrate that 5-HT causes acute gastric mucosal injury and this injury is probably due to the activation of the 5-HT1D receptors.
Amikacin is usually administered to the patients during open heart surgery immediately after cardiopulmonary bypass (CPB) because the serum levels of this drug may decrease due to the volume overload and hemodilution caused by intravenously administered fluids (1.2-2 liters prime solution). We investigated whether this application of amikacin is necessary immediately after CPB. A total of ten patients from Dokuz Eylül University Hospital, Department of Thoracic and Cardiovascular Surgery, who were scheduled for open heart surgery were studied. Serum sodium, potassium, blood urea nitrogen and creatinine values of the patients were found to be within normal limits before the operation. Amikacin was administered to patients just before open heart surgery and 2 ml blood samples were collected from all patients 15 minutes after the drug administration, just before cardiopulmonary by-pass (CPB), at the 30th and 60th minutes of the CPB, after CPB and after the cessation of operation, 4 hours after drug administration. A significant decrease was observed between the values of 10 patients by ANOVA (p < 0.05). Serum amikacin values were found to be 9.80 +/- 0.96 micrograms/ml at the end of the operation, 4 hours after the drug administration. Since serum amikacin levels do not fall below the trough concentrations at the end of the fourth hour we conclude that it is unnecessary to repeat the dose at the end of the operation.
Accidental and suicidal ingestions of organophosphate compounds continue to be a common occurrence in Turkey. Activated charcoal administration without gastric emptying has been advocated as primary therapy in most acute poisoning cases, although some references do not recommend activated charcoal use in organophosphate poisoning. This study was performed to determine the in vitro adsorption of dimethyl dichlorovinyl phosphate (dichlorvos) and parathion by activated charcoal over a wide range of charcoal:organophosphate ratios (1:1, 2.5:1, 5:1, 10:1 and 20:1, g:g). The charcoal binding ability of dichlorvos and parathion were studied in both pH 1.2 and pH 7 environments. The supernatant was extracted with n-hexane and then analyzed by gas chromatography. Each incremental increase in charcoal dose increased the percent adsorption of dichlorvos and parathion. At the 20:1 ratio, 82.8 +/- 2.0/87.3 +/- 2.9% (pH 1.2/7.0) of dichlorvos and 59.3 +/- 4.5/64.5 +/- 6.1% (pH 1.2/7.0) of parathion were bound by activated charcoal. There were no significant differences in amounts of compound bound in the acid and neutral solutions. Large doses of activated charcoal effectively bind dichlorvos and parathion in vitro. In vivo research should be performed to determine activated charcoal's role in organophosphate poisoning cases.