Biomedical subjects

H Guven

Publications and source records attributed to H Guven.

35 records · Page 2Linked to original sources

PubMed1998

Circadian rhythmicity in serotonin-induced acute gastric mucosal injury in rats.

Time-dependent patterns in the susceptibility of the rat gastric mucosa to ulcerogenic stimuli involving stress or chemical injury have been described. The purpose of this study was to evaluate whether serotonin (5-HT)-induced gastric mucosal injury is produced in a circadian fashion in the rat model. In fasted Wistar rats (adapted for 3 weeks to a standard 12-h light-dark cycle), 5-HT administered subcutaneously (20 mg/kg, 4 h before autopsy) produced gastric mucosal injury. The stomachs were removed and the ulcers were scored for intensity, using a scale of 0-4. In studies performed at 4-h intervals, beginning 1 h after lights-on, most of the mucosal injury occurred at 2000 h, i.e. early in the dark phase. Likewise, serum corticosterone levels were also found to be high at the same time period. The time of 2000 h is approximately determined to be the beginning of the rats' active period. These results suggest that the extent of acute 5-HT-induced gastric mucosal injury varies with the time of day and that elevations in corticosterone concentrations might be responsible for the 5-HT-induced gastric mucosal injury.

Acute Disease↗

PubMed1998

The effects of 4-aminopyridine and Bay K 8644 on verapamil-induced cardiovascular toxicity in anesthetized rats.

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.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1997

The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model.

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.

Amrinone↗

PubMed1997

Relationship between high serum digoxin levels and toxicity.

A retrospective study of 1,269 patients on digoxin was done to determine the relationship between serum digoxin levels of 3.0 ng/ml or higher and clinical toxicity. Of 1,269 patients, 58 (4.6%) had digoxin serum levels of 3.0 ng/ml or higher. Clinical evidence of digoxin toxicity was present in only 11 of these patients and premature blood sampling accounted for the high levels in 10 other nontoxic patients. None of the patients with clinical toxicity died. The other 37 patients tolerated the high digoxin levels without exhibiting toxic effect. Low cardiac output, concomitant use of other drugs, and impaired renal function increased the serum digoxin levels in patients with and without clinical toxicity. Appropriate therapeutic digoxin level monitoring and confirmatory laboratory-clinical relationship may have important influences on these results. Additional work on further definition of "toxic" digoxin levels needs to be performed.

Adult↗

PubMed1996

The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats.

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.

Amrinone↗

PubMed1996

Multiple-dose activated charcoal in an accidental vancomycin overdose.

BACKGROUND: Multiple-dose activated charcoal may enhance the enterocapillary clearance of vancomycin. CASE REPORT: A 17-day-old female neonate born with congenital meningomyelocele and Arnold-Chiari malformation was iatrogenically overdosed with a 500 mg intravenous bolus of vancomycin during a shunt operation. The Red Man's Syndrome developed within minutes, characterized by sudden hypotension, skin rash and cyanosis. Serum vancomycin level at one hour after the injection was 165.7 micrograms/mL, as measured by an enzyme immunoassay method (EMIT). Multiple dose activated charcoal, 1 g/kg, was first given five hours after injection, and continued every four hours for 12 doses. The half-life of vancomycin during charcoal administration was calculated to be 9.4 h or less than the reported 13.4-33.7 h half-life in normal neonates. The neonate's renal function tests and brainstem auditory responses remained normal. CONCLUSIONS: Gastrointestinal dialysis with multiple-dose activated charcoal without cathartics appeared to shorten the elimination half-life of vancomycin.

Anti-Bacterial Agents↗

PubMed1995

Elevation of breath ethanol measurements by metered-dose inhalers.

STUDY OBJECTIVE: Metered-dose inhalers (MDIs) may contain as much as 38% ethanol. We evaluated the effects of ethanol-containing MDIs on breath alcohol testing. DESIGN: Prospective, single-blind, crossover, controlled study. PARTICIPANTS: Three healthy male volunteers 29 to 36 years old. INTERVENTION: We studied three brands: Tornalate, (38% ethanol), Bronkometer, (30% ethanol), and Alupent, (0% ethanol). The effects of each MDI on breath and blood ethanol measurements were evaluated separately. Two puffs of each brand of MDI were administered. Breath ethanol measurements were obtained at baseline and .25, .5, 1, 2, 3, 5, and 10 minutes after MDI use. Blood ethanol measurements were obtained at baseline and 1 and 10 minutes after MDI use. RESULTS: Overall, Tornalate had the highest breath ethanol readings, with a mean ethanol level of 189 mg/dL recorded just after MDI use. Breath ethanol levels subsequently decreased rapidly over time. Mean breath ethanol concentrations were lower after the use of Bronkometer and undetectable after the use of Alupent. Blood ethanol levels were undetectable at all times tested. CONCLUSION: MDIs may cause elevations of breath alcohol above the legal criteria for intoxication. These effects are transient and may be prevented by a 10-minute interval between the use of an MDI and breath alcohol testing.

Administration, Inhalation↗

PubMed1995

Adsorption of botulinum toxin to activated charcoal with a mouse bioassay.

STUDY OBJECTIVE: We evaluated the effectiveness of activated charcoal (AC) in adsorbing Clostridium botulinum type A toxin using a mouse bioassay. DESIGN: Prospective, blinded, randomized, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: One hundred forty Swiss/Webster ND-4 strain mice. INTERVENTION: Food contaminated with type A botulinum toxin was homogenized in a phosphate/gel buffer (pH 6.2). The concentrate was diluted by factors of 1:10, 1:50, and 1:100. AC was added to aliquots of the dilutions to a 20% final concentration. The samples were centrifuged, supernatant was removed, and separate groups of mice were injected intraperitoneally with .5 mL of each dilution (those treated with AC and controls untreated with AC). The animals were then observed over 5 days for signs of botulism. RESULTS: None of the 60 animals injected intraperitoneally with dilutions treated with AC was observed to have any signs of botulism. In contrast, deaths were observed in 10 of 20, 9 of 20 and 4 of 20 mice injected with untreated dilutions of 1:100, 1:50, and 1:10, respectively (P < .004). CONCLUSION: In this model, treatment of botulinum toxin with AC before administration resulted in greatly reduced morbidity and mortality.

Adsorption↗

PubMed1995

Prevention of oral dichlorvos toxicity by different activated charcoal products in mice.

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.

Administration, Oral↗

PubMed1995

Urginea maritima (squill) toxicity.

A 55 year-old female ingested two bulbs of Urginea maritime (squill) plant as a folk remedy for her arthritic pains. Her past history was significant for Hashimoto thyroiditis and she was hypothyroid upon presentation. Subsequent effects resembling those seen with cardiac glycoside intoxication included nausea, vomiting, seizures, hyperkalemia, atrioventricular block and ventricular arrhythmias resembling digitalis toxicity. A serum digoxin level by an enzyme immunoassay method was 1.59 ng/mL. Despite supportive treatment and pacing, the patient expired from ventricular arrhythmias 30 h after ingestion. Squill has been recognized since antiquity for the clinical toxicity of its cardiac glycosides, but this appears to be the first report of a fatality since 1966.

Digoxin↗

PubMed1994

In vitro adsorption of dichlorvos and parathion by activated charcoal.

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.

Adsorption↗

PubMed1994

The effects of theophylline on serum alprazolam levels.

Theophylline and benzodiazepines are frequently combined in clinical practice. Because of a number of case reports about antagonism of benzodiazepine-induced sedation by theophylline, we investigated serum alprazolam levels in a convenient sample of pulmonary medicine inpatients receiving theophylline and no theophylline. One mg of alprazolam was given daily for seven days to 6 patients receiving theophylline and 7 patients not receiving theophylline treatment. On days 2 through 7, trough serum alprazolam levels were measured. On day 7, blood samples were collected before (0 hour), and at 3, 6, 9 and 12 hours after alprazolam administration. In patients receiving theophylline, serum trough alprazolam levels were significantly lower during each day of the study. In patients receiving no theophylline, serum alprazolam levels were in the therapeutic range, except for two patients who had high alprazolam levels. In this small study, serum alprazolam levels were found to be consistently below the therapeutic range in patients receiving chronic theophylline treatment. Previously reported antagonism of anxiolytic effects of benzodiazepines by theophylline is probably due to the lower serum benzodiazepine levels in these patients.

Adult↗

PubMed1994

Gentamicin excretion and uptake from breast milk by nursing infants.

OBJECTIVE: To investigate the excretion of gentamicin into human breast milk and resulting serum gentamicin levels in nursing newborn infants. METHODS: Women delivered by cesarean received gentamicin, 240 mg/day (80 mg intramuscularly three times a day) for 5 days postpartum. On day 4, maternal serum samples were collected 1 and 7 hours after gentamicin administration. Milk samples were collected 1, 3, 5, and 7 hours following administration. The infants were fed 1 hour after gentamicin administration, and serum samples were collected from the newborns 1 hour later. The concentrations of gentamicin were measured by a fluorescence polarization immunoassay. RESULTS: The mean (+/- standard deviation) maternal serum gentamicin levels at 1 and 7 hours were 3.94 +/- 1.12 and 1.02 +/- 0.78 microgram/mL, respectively. Milk gentamicin levels were: 0.42 +/- 0.26, 0.48 +/- 0.17, 0.49 +/- 0.17, and 0.41 +/- 0.25 microgram/mL at 1, 3, 5, and 7 hours, respectively. The mean milk:plasma gentamicin ratios were 0.11 and 0.44 at 1 and 7 hours, respectively. The correlation between maternal peak serum levels and milk levels was not statistically significant (P > .05). Detectable (above 0.27 microgram/mL) gentamicin levels were found in five of the ten newborn serum samples, with a mean level of 0.41 +/- 0.05 microgram/mL. CONCLUSION: Gentamicin is transferred into breast milk, and half of nursing newborn infants have detectable serum gentamicin levels.

Adult↗

PubMed1993

Age-related digoxin-alprazolam interaction.

A case report of dramatic increases in serum digoxin levels after alprazolam administration prompted our investigation. Twelve inpatients receiving long-term digoxin (0.25 mg daily) randomly received oral administration of either 1.0 or 0.5 mg alprazolam per day for 7 days. In each dosage group, three patients were older than and three were younger than 65 years of age. The area under the concentration-time curve for serum digoxin increased significantly in patients receiving 1 mg alprazolam daily, and this increase was more pronounced in patients older than 65 years of age. Clinical digoxin toxicity developed in one elderly patient who was receiving 1 mg/day alprazolam.

Aged↗

PubMedDate not supplied

The prokinetic effect of domperidone in gallbladder--not upon dopaminergic receptors.

The mechanism of the contractile effect of domperidone on gallbladder smooth muscle has been investigated by using an in-vivo and an in-vitro model. In the in-vivo part of the study 14 healthy males were administered 20 mg domperidone or two placebo tablets orally and gallbladder emptying was measured by ultrasonography. The reduction in the gallbladder volume was significant compared to the placebo at 45 and 55 min. In the in-vitro part of the study, the gallbladder strips isolated from guinea pigs were field stimulated and 10(-6)-10(-4) M concentrations of dopamine were administered before electrical field stimulation (EFS) was repeated. Dopamine exerted no significant effect upon the contractions obtained by EFS. The effect of dopamine and domperidone under basal conditions were also explored. Under basal conditions, dopamine neither contracted nor relaxed the gallbladder muscle between 10(-6) and 10(-4) M concentrations when added directly to the organ bath. Besides, a significant contraction was observed with 10(-4) M concentration of domperidone whereas 10(-7), 10(-6) and 10(-5) M concentrations exerted no effect. This effect of domperidone was thought to be nonspecific but inhibited by 10(-6) M atropine, 10(-5) M pirenzepine and abolished by 10(-6) M tetrodotoxin. In summary, domperidone produces a modest contraction in human gallbladder. This effect does not seem to occur upon dopaminergic receptors in guinea pig models.

Adult↗

PubMedDate not supplied

A comparison of digoxin concentration--time curves before and after open-heart surgery.

The effects of open heart surgery on serum digoxin concentration--time curves were investigated in 10 cardiac patients receiving 0.25 mg/day digoxin. Blood samples were obtained from the patients immediately before and 1, 2, 3, 5, 8, 16 and 24 h after digoxin administration, both before open-heart surgery and 7 days after surgery. Serum digoxin concentrations, determined by fluorescence polarization immuno-assay, significantly (P < 0.05) increased after surgery, as did the maximum serum concentrations and the areas under the concentration-time curves. After surgery there was a significant increase in the serum gamma-glutamyl transferase concentration and a significant reduction in the total protein concentration. A reduction of digoxin dose may be appropriate for patients who have undergone open-heart surgery.

Adult↗

PubMedDate not supplied

A comparison of the serum concentration time-curves of amikacin-administered patients before and after open heart surgery.

The effects of open heart surgery on amikacin concentration time-curves were investigated in eight patients who were scheduled for open heart surgery at a Thoracic and Cardiovascular Surgery Department. A 500 mg single dose of amikacin was administered parenterally to the volunteers pre- and postoperatively and the serum concentration time-curves were compared. Serum amikacin levels after pre-operative intramuscular (IM) administration did not reach therapeutic values. By comparison, preoperative and postoperative IM or intravenously (IV) administration resulted in therapeutic serum amikacin levels. It was concluded that IM administration preoperatively was not appropriate. Serum levels of amikacin were also shown to fall below therapeutic values 8 h after administration. It is recommended that dosing intervals with amikacin should not exceed 8 h.

Adult↗