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Biomedical subjects

A Bozkurt

Publications and source records attributed to A Bozkurt.

At least 55 records · Page 3Linked to original sources
PubMed1999

CYP2C19 genotype does not represent a genetic predisposition in idiopathic systemic lupus erythematosus.

BACKGROUND: The aetiology of systemic lupus erythematosus (SLE) is still unknown. In several cases, however, chemicals or drugs were identified as aetiological agents and associations with certain phenotypes of drug metabolising enzymes have been reported. The purpose of this study was to discover if there is an association between CYP2C19 polymorphism and susceptibility to SLE. METHODS: Racemic mephenytoin (100 mg orally) was given to healthy volunteers (n = 161) and SLE patients (n = 37) and then S-mephenytoin and R-mephenytoin were determined in eight hour urine samples. A 10 ml blood sample was obtained from healthy volunteers (n = 80) and SLE patients (n = 69) for genotypic assay. Each blood sample was tested for the detection of CYP2C19*1 and CYP2C19*2 (formerly wt and m1 respectively) by oligonucleotide ligation assay. RESULTS: The ratio of S/R-mephenytoin ranged from < 0.1 to 1.293 in healthy subjects and from < 0.1 to 1.067 in SLE patients. PM phenotype was observed in 2 of 37 patients with idiopathic SLE (5.4%) and 6 of 161 healthy subjects (3.7%). There were no significant differences in the frequency of PM phenotypes between the groups (Fisher's exact test, p = 0.64) or in the frequency distribution profiles of ratios of S-mephenytoin to R-mephenytoin. No significant differences in distribution of overall genotypes and in allele frequencies were observed between the two groups. No significant relation was found between clinical features and the overall genotype. CONCLUSION: The results of this study indicate that CYP2C19 genotype does not represent a genetic predisposition in idiopathic SLE patients.

Adult↗
PubMed1999

Penetration of topical, oral, and combined administered ofloxacin into the subretinal fluid.

AIMS: To assess the subretinal fluid (SRF) levels of ofloxacin following topical, oral or combined administration. METHODS: 31 patients undergoing conventional retinal reattachment surgery were randomly assigned to three groups. Nine patients received topical ofloxacin, 11 patients received oral ofloxacin, and the other 11 patients received combined administration. Collected SRF samples were analysed for drug level by using high performance liquid chromatography. RESULTS: SRF drug levels after oral and combined administration were significantly higher than that after topical administration (p=0.0002 and p=0.0002, respectively) while there was no significant difference between oral and combined administration (p=0.0844). CONCLUSIONS: Ocular bioavailability of ofloxacin in SRF after oral and combined administration is equivalent. The addition of oral ofloxacin to topical therapy increased drug SRF penetration sixfold.

Administration, Oral↗
PubMed1999

Ofloxacin levels after intravitreal injection. Effects of trauma and inflammation.

PURPOSE: This study was carried out to get an insight into the ofloxacin elimination after intravitreal injection in rabbits. We also studied the effects of trauma and inflammation on the vitreous ofloxacin levels after intravitreal injection of ofloxacin. METHODS: A penetrating eye injury in the right eye was inflicted on 24 rabbits and another 12 animals were used as control. A standardized intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in half of the traumatized eyes. Ofloxacin (200 microg/0.1 ml) was injected into the midvitreous cavity of both traumatized and control right eyes, and samples were obtained at 2, 8, 24 and 48 h after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. RESULTS: Vitreous levels of ofloxacin were above the MIC(90) at 2 and 8 h in all groups for most of the common microorganisms causing endophthalmitis and also at 24 h in traumatized-infected eyes. At the second hour, the mean vitreous concentrations of ofloxacin both in traumatized and traumatized-infected eyes were lower than that in the control eyes (p < 0.05). At 8 h, the mean vitreous concentrations of ofloxacin in the traumatized and in the traumatized-infected eyes were higher than that in the control eyes (p < 0.05). At 24 h, the mean ofloxacin concentration was higher in the traumatized-infected eyes than that in control (p < 0.01) and traumatized eyes (p < 0.05), and also higher in the traumatized eyes than that in the control eyes (p < 0.05). The mean ofloxacin concentrations in the traumatized and traumatized-infected eyes were significantly higher (p < 0.01) than those in the controls at 48 h. The elimination half-life of ofloxacin in the control eyes was 5.65 h and trauma and inflammation prolonged the half-life to 9.47 and 9. 72 h, respectively. CONCLUSION: Clearance of ofloxacin is fast and appears to be reduced by trauma and inflammation. Therapeutic drug levels in traumatized-infected eyes were maintained up to 24 h. This may be an important pharmacokinetic advantage in treating endophthalmitis unless the dose used has local toxicity and allows a longer dose interval when the dose is repeated.

Animals↗
PubMed1999

Role of nitric oxide in indomethacin-induced gastric mucosal dysfunction in the rat.

The present study was undertaken to explore the role of nitric oxide (NO) in the pathogenesis of experimental non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy. We assessed the role of NO inhibition and donation in indomethacin-induced gastric mucosal dysfunction. The stomach was perfused with vehicle (control) for 20 min, followed by indomethacin (10 mg ml-1 in 1 25 % sodium bicarbonate, pH 8 4) for 120 min. NG-nitro-L-arginine methyl ester (L-NAME, 5 and 10 mg kg-1, I.V. bolus), L-arginine, D-arginine (100 mg kg-1 I.V. bolus, 10 mg kg-1 h-1, 2 h infusion) and the NO donor glyceryl trinitrate (GTN) were given at the same time (20, 40 and 80 microg kg-1 min-1, 15 min infusion) as perfusion with indomethacin was started. Epithelial permeability was quantified by measuring blood-to-lumen clearance of 51Cr-labelled EDTA. Indomethacin caused a 20-fold increase in 51Cr-EDTA leakage compared with that of the control group. Treatment with L-NAME or L-arginine did not affect the indomethacin-induced alterations in mucosal permeability. Administration of GTN (20 microg kg-1 min-1) significantly reduced the indomethacin-induced mucosal dysfunction. By contrast, higher doses of GTN (80 microg kg-1 min-1) exacerbated epithelial dysfunction induced by indomethacin. Elevated levels of carbonyls and myeloperoxidase (MPO) observed after indomethacin administration were significantly reduced, to the control values, when GTN (20 microg kg-1 min-1) was administered along with indomethacin. These data suggest that NO from exogenous sources can exert a dual action on the integrity of the gastric mucosa challenged by indomethacin. Low doses of GTN can prevent mucosal dysfunction induced by indomethacin, while higher doses of GTN may exacerbate the increases in epithelial permeability.

Animals↗
PubMed1999

Penetration of ofloxacin and ciprofloxacin in aqueous humor after topical administration.

BACKGROUND AND OBJECTIVE: To compare the aqueous humor levels of 0.3% ofloxacin and 0.3% ciprofloxacin containing eyedrops in patients with healthy cornea. PATIENTS AND METHODS: Fifty patients with cataract were randomly assigned to have 0.3% ofloxacin containing eyedrop (25 patients) or 0.3% ciprofloxacin containing eyedrop (25 patients). Both drugs were repetitively instilled to each patient for 6 hours before the surgery. Aqueous samples were collected after penetrating the anterior chamber during cataract extraction and assayed by high-performance liquid chromatography method. RESULTS: The aqueous humor level of ofloxacin (1.43 +/- 0.26 microg/ml, mean +/- SEM) was significantly higher than that of ciprofloxacin (0.35 +/- 0.07 microg/ml) following the topical application (P < .0002). CONCLUSION: Aqueous humor penetration of topical ofloxacin is about 4 times higher than that of topical ciprofloxacin when the drugs are applied as described above.

Administration, Topical↗
PubMed1999

Penetration of topical ciprofloxacin by presoaked medicated soft contact lenses.

PURPOSE: To assess the penetration of topical ciprofloxacin by a presoaked medicated disposable soft contact lens without topical drop administration. METHODS: Disposable soft contact lenses were presoaked in 0.3% topical ciprofloxacin (Ciloxan, Alcon Laboratories, Fort Worth,TX) for 10-12 hours. Presoaked lenses were placed on the eyes of patients with senile cataracts for 3 hours in group A, 5-6 hours in group B, and 8-12 hours in group C prior to their scheduled lens extraction surgery. Aqueous humor samples were drawn by paracentesis during the operation. Ciprofloxacin concentrations were determined by high pressure liquid chromatography-fluorescence detection. RESULTS: The mean ciprofloxacin concentration was 2.70 +/- 0.98 microg/mL in group A, 1.22 +/- 1.0 microg/mL in group B, and 0.5 +/- 0.2 microg/mL in group C. CONCLUSIONS: Penetration of topical ciprofloxacin is enhanced through a presoaked disposable soft contact lens, and at 3 hours therapeutic levels are obtained. Significant levels of ciprofloxacin are retained through 8-12 hours. This mode of treatment may increase patient compliance compared to frequent topical drop administration, and as a consequence, assure efficient treatment of keratitis, at least for the first 3 hours.

Administration, Topical↗
PubMed1998

Optimization of mobile phase in the separation of beta-blockers by HPLC.

Beta-blockers are generally determined using high-performance liquid chromatography (HPLC). Previous HPLC separations of beta-blockers have often required a mobile phase containing three components; acetonitrile or methanol to control the retention; buffer to control the ionic strength and pH of the mobile phase; ion-pairing reagent to provide adequate retention of beta-blockers or organic amines as masking agent to reduce peak tailing. Due to the complexity of the mobile phases employed, development of these assays can be a laborious process. Additionally, alkyl sulphonates and organic amines dramatically reduces the life-time reduction of silica based C18 columns. The results of this study demonstrated that the addition of tested alkyl sulphonates and organic amines is not essential for an adequate separation of beta-blockers. In this study, we developed a simple HPLC method for the simultaneous separation of model beta-blockers, atenolol, practolol, metoprolol, oxprenolol and propranolol. Atenolol, practolol, metoprolol, oxprenolol and propranolol adequately separated with high peak symmetries using a mobile phase consisted of methanol/acetonitrile/phosphate buffer (10 mM, pH 3.0) (15:15:70, v/v/v). By altering only the fraction of methanol with respect to acetonitrile, method development becomes a more efficient separation. Furthermore, atenolol, practolol, metoprolol, oxprenolol and propranolol can be detected up to 0.25, 5, 10, 50 and 10 ng ml(-1). In this publication, we present the simultaneous separation of beta-blockers having a wide range of polarity. It is proposed that this new mobile phase, consisting only acetonitrile, methanol and phosphate buffer can be used for the analysis of the several beta-blockers presently in doping control analysis as well as others.

Acetonitriles↗
PubMed1998

Adenosine protects against indomethacin-induced gastric damage in rats.

This study examines the putative gastroprotective effect of adenosine on indomethacin-induced gastric lesions and the possible mechanisms involved. After 24 hr of starvation, the rats were treated either with indomethacin (Indo; 25 mg/kg, subcutaneously) alone or adenosine + Indo (Ado; 7.5 mg/kg, subcutaneously, three times a day), or the vehicle (5% NaHCO3, subcutaneously). The length of hemorrhagic lesions in the stomachs was expressed as the lesion index. The tissue-associated myeloperoxidase (MPO) activity and protein oxidation were measured in gastric tissue samples. Formation of reactive oxygen species in gastric tissues was measured by using luminol- and lucigenin-enhanced chemiluminescence. In other groups of rats, gastric mucosal permeability and gastric acid output were performed following the same treatment regimens. The gastric mucosal permeability was measured by determination of [51Cr]EDTA clearance in a perfused stomach preparation and gastric acid secretion studies were performed following pylorus ligation. The lesion index, the increase in lucigenin-enhanced chemiluminescence, and the increase in gastric mucosal permeability in Indo-treated rats were reversed by Ado pretreatment. Ado pretreatment also prevented the increase in gastric acid output and gastric volume in Indo-treated rats. Thus, these findings implicate that exogenous adenosine has a protective role on indomethacin-induced gastric lesions, possibly by inhibiting gastric hyperacidity and reactive oxygen formation and by preventing disruption of the mucosal integrity.

Adenosine↗
PubMed1998

Penetration of ofloxacin in human aqueous and vitreous humors following oral and topical administration.

PURPOSE: To determine aqueous and vitreous humor ofloxacin levels following oral and topical application of ofloxacin in patients with noninflamed cornea and intact crystalline lens, and to compare the drug levels provided by each route. MATERIALS AND METHODS: Twenty-six patients undergoing pars plana vitrectomy for various ocular pathologies were divided into two groups. Fourteen patients received two drops of 0.3% ophthalmic solution of ofloxacin every 30 minutes for 3 hours and every 60 minutes for the next 3 hours, and 12 patients received a single oral dose of 400 mg ofloxacin 8 hours before surgery. The aqueous and vitreous humor samples were simultaneously collected after oral or topical administration during pars plana vitrectomy to assess penetration of the drug. Samples were assayed for ofloxacin concentrations by a previously described method using high-performance liquid chromatography. RESULTS: The aqueous and vitreous humor levels of ofloxacin were 1.54 +/- 0.27 microg/mL (mean +/- standard error) and 1.77 +/- 0.24 microg/mL after oral and 1.44 +/- 0.24 microg/mL and 0.37 +/- 0.05 microg/mL after topical ofloxacin administration, respectively. Aqueous humor levels were not statistically different following oral or topical administration (P > 0.8). However, vitreous level of the drug after oral administration was significantly higher than that after topical administration (P < 0.001). CONCLUSION: Ocular bioavailability of ofloxacin in aqueous humor after oral and topical administration is similar when the drug is applied as described. Penetration of ofloxacin into vitreous humor is less than that into aqueous humor following topical application. The aqueous humor levels of ofloxacin via both routes and the vitreous level of the drug after oral route exceed the minimum inhibitory concentrations for certain bacterial species that frequently cause intraocular infection.

Administration, Oral↗
PubMed1998

Comparison of aqueous humour and vitreous humour levels of two 0.3% ciprofloxacin eyedrops.

BACKGROUND: Two ophthalmic solutions of 0.3% ciprofloxacin eyedrops are available in Turkey: Ciloxan and Siprogut. The objective of this study was to compare the concentrations of drug produced by the two products in the aqueous humour and vitreous humour after local administration. METHODS: Twenty-one patients undergoing primary vitreoretinal surgery received either Ciloxan (10 patients) or Siprogut (11 patients). Six hours before surgery, two drops of solution were instilled onto the operative eye. Drops were then instilled every 30 minutes for the first 3 hours and then hourly for the next 3 hours. Aqueous and vitreous samples were collected 30 minutes after administration of the last dose and were assayed for ciprofloxacin concentration by means of high-performance liquid chromatography with fluorometric detection. RESULTS: The mean aqueous humour concentrations of Ciloxan and Siprogut were 0.36 (standard error of the mean [SEM] 0.09) microgram/mL and 0.44 (SEM 0.17) microgram/mL respectively. The corresponding vitreous humour concentrations were 0.21 (SEM 0.05) microgram/mL and 0.22 (SEM 0.06) microgram/mL. Neither of these differences was statistically significant. The aqueous and vitreous levels of both products exceeded the minimum inhibitory concentrations for certain bacterial species that frequently cause intraocular infections. INTERPRETATION: Our results show that the ocular bioavailability of Ciloxan and Siprogut after local administration is equivalent. Penetration of ciprofloxacin into the vitreous humour seems to be poorer than that into the aqueous humour.

Adult↗
PubMed1997

Pathways mediating CRF-induced inhibition of gastric emptying in rats.

The corticotrophin-releasing factor (CRF) is shown to be released during stress suggesting that CRF has a physiological role in the mediation of central nervous system (CNS) response to stress, including an inhibitory effect on gastric emptying. In the present study, we have examined the pathways by which intracerebroventricularly (i.c.v.) administered CRF and central CRF activation during stress alter the gastric emptying rate of saline (0.14 M), acid (50 mM), peptone (4.5%) and peptone after preload. The emptying rates of all these test meals were significantly (p < 0.05-0.001) delayed with increasing doses of i.c.v. CRF (0.001, 0.003, 0.01, 0.1, 0.3 and 1 nmol/10 microl), when compared with their i.c.v. saline-treated controls. The 1-nmol dose of CRF inhibited the emptying of acid, peptone and peptone after a preload by 43.8%, 64.1% and 81.1%, respectively. Twenty-minute swim stress delayed gastric emptying rate of saline, acid and peptone solutions significantly (p < 0.001) and the CRF receptor antagonist, alpha-helical CRF (8 nmol/10 microl, i.c.v.), applied before the swim stress, abolished the inhibitory effect of stress on the emptying rate of these solutions. Acute intragastric administration of capsaicin (2 mg/rat) and systemic capsaicin (125 mg kg(-1)) treatment facilitated the gastric emptying rate of acid, peptone and peptone after preload significantly, almost abolishing the inhibitory effect of central CRF (p < 0.001). However, either capsaicin treatment had no effect on stress-induced inhibition of the gastric emptying of none of the solutions, except peptone after a preload. Our findings demonstrate that the gastric inhibitory response induced by swimming as a stress-producing stimulus is mediated by the endogenous release of CRF. They also suggest that CRF exerts its CNS actions on the gastrointestinal tract via vago-vagal, capsaicin-sensitive pathways, probably involving the central cholecystokinin (CCK) mechanisms.

Animals↗
PubMed1997

The hydroxylation of omeprazole correlates with S-mephenytoin and proguanil metabolism.

OBJECTIVES: This pharmacogenetic study was aimed at studying the pattern of oxidation of omeprazole in a Turkish population and testing whether omeprazole metabolism cosegregates with the genetically determined metabolism of mephenytoin and proguanil in Turkish subjects. METHODS: The hydroxylation of omeprazole was measured in 116 unrelated healthy Turkish subjects after administration of a single oral dose of omeprazole (20 mg), using the ratio of omeprazole to 5-hydroxyomeprazole in plasma 3 h after dosing. To 31 subjects, who were phenotyped with omeprazole, mephenytoin (100 mg, p.o.) or proguanil (200 mg, p.o.) were administered at least 1 week apart. The S/R ratio of mephenytoin and the ratio of proguanil to cycloguanil were determined from an 8-h urine collection. RESULTS: Based on the distribution of the log (omeprazole/hydroxyomeprazole) values and using the antimode value of 0.8, the frequency of poor metabolizers of omeprazole was estimated to be 7.7% (95% confidence interval 3-18%) which was similar to that in the other Caucasian populations (P = 0.54, Fisher's exact test). Three poor metabolizers of omeprazole were also classified as poor metabolizers of both mephenytoin and proguanil and no misclassification occurred with three phenotyping methods. All three methods separated poor or extensive metabolizer phenotypes with complete concordance. The ratio of omeprazole to hydroxyomeprazole correlated with the S/R ratio of mephenytoin and the ratio of proguanil to cycloguanil. CONCLUSION: These results support the hypothesis that the oxidative metabolism of three different drugs may be catalyzed by the same cytochrome P450 enzyme.

Adult↗
PubMed1997

Determination of ofloxacin in human aqueous humour by high-performance liquid chromatography with fluorescence detection.

A reversed-phase high-performance liquid chromatographic method is described for the determination of ofloxacin in human aqueous humour; the method involves fluorescence detection (excitation at 290 nm; emission at 500 nm) after direct injection of samples. The method utilized a 100 mm x 8 mm i.d. cartridge column packed with 4 microns Novapak C18 with a mobile phase methanol-acetonitrile-0.4 M citric acid (3:1:10, v/v/v) and a flow rate of 1 ml min-1 at ambient temperature. The retention times for the internal standard pipemidic acid and for ofloxacin were 4.82 and 7.32 min respectively. The mean recovery (+/- ISD) from human aqueous humour was 103.24 +/- 4.45% for ofloxacin at 1 microgram ml-1 (n = 6). The within-day and day-to-day RSDs at 0.1 microgram ml-1 and 1 microgram ml-1 were less than 6.71% (n = 6) and the lower limit of reliable determination corresponding to a signal-to-noise ratio of 2.5:1 was 20 ng ml-1. The assay was shown to be suitable for measuring ofloxacin levels in human aqueous humour samples after topical, oral and intravenous administration.

Anti-Infective Agents↗
PubMed1997

Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms.

Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin-(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.

Animals↗
PubMed1996

Inhibitory effects of gastrin releasing peptide on gastric emptying in rats.

Gastrin-releasing peptide (GRP) has a wide range of biological actions, including stimulation of the frequency of antral contractions and delaying gastric emptying. The present study was designed to evaluate the role of GRP in the control of gastric emptying of liquid test meals in the rat. The emptying of methyl cellulose given by gavage to fasted rats, or of saline given via the fistula to conscious gastric fistula rats was not influenced by the GRP antagonists, NC-8-89 (Leu13-psi-(CH2NH)-Leu14-bombesin) and 2258U89 ((de-NH2)Phe19, D-Ala24, D-Pro26 psi (CH2NH)Phe27(-GRP (19-27)), at 2 mg/kg, s.c. However, both antagonists (0.02, 0.2 and 2 mg/kg) reversed the inhibitory effect of HCI on gastric emptying in gastric fistula rats (P < 0.05-0.001). When peptone was administered after a preload, but not otherwise, the inhibition of emptying was also partly reversed by both antagonists at all doses used (P < 0.05-0.001). Interestingly, the delay in the emptying of hyperosmolal saline compared to saline, was enhanced at a dose of 0.2 mg/kg of both antagonists (P < 0.05 and P < 0.01). Food intake did not change significantly with the two lower doses of antagonists, but was decreased by the highest dose of NC 8-89. We conclude that GRP specifically inhibits gastric emptying of acid and peptone solutions in the conscious rat.

Animals↗
PubMed1996

The effect of acute ligation of the rabbit appendix on antioxidant enzymes.

The role of oxygen free radicals (OFR) in the pathogenesis of many diseases is known. This experimental study was planned to investigate the role of OFR in acute abdominal inflammation. In this study, 20 adult rabbits were used. They were divided into two groups with 10 rabbits in each. In the study group, blood samples were taken from peripheral and mesenteric veins and then their appendices were ligated; after 24 h, blood samples were taken again and the appendices were resected. The same procedures were carried out in the control group, except for ligation of the appendices. Superoxide dismutase,catalase and glutathione peroxidase (GPX) activities were measured in all blood samples. The activities of catalase and GPX were increased postoperatively in peripheral and mesenteric blood samples in the experimental group. The catalase activity was increased in the control group. These results suggest that OFR increased sufficiently to activate the enzymatic defense system in acute appendicitis.

Acute Disease↗