Risperidone and ethyl pyruvate have protective effects against ketamine-induced cognitive impairments in mice.

OBJECTIVE: Ketamine, an N-methyl D-aspartic acid receptor antagonist drug, is reported to produce memory disruptions. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP), a pyruvic acid derivative, and risperidone, an atypical antipsychotic drug, against ketamine-induced cognitive disturbances. MATERIALS AND METHODS: A passive-avoidance test, a novel object recognition test, and a modified elevated plus maze test were used to assess memory functions. Hippocampal malondialdehyde (MDA) levels were measured to determine the oxidation levels. RESULTS: Ketamine applications produced memory deficits in all tests and insignificantly increased MDA levels, which were alleviated by risperidone, EP, and combination treatments. CONCLUSIONS: Increased oxidative stress and neurotransmission imbalance can be responsible for ketamine-induced memory disruptions. With its antioxidant effects, EP may be helpful to reduce cognitive impairments related to schizophrenia either alone or in combination with antipsychotics.

Economic burden of severe asthma in Turkey: a cost of illness study from payer perspective.

Summary: Objective. To estimate economic burden of severe asthma in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods. This cost of illness study was based on identification of per patient annual direct medical costs for the management of sever easthma in Turkey from payer perspective. Average per patient direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations and interventions, drug treatment and equipment, and co-morbidities/complications. Results. Based on total annual per patient costs calculated for outpatient admission ($ 177.91), laboratory and radiological tests ($ 82.32), hospitalizations/interventions ($ 1,154.55), drug treatment/equipment ($ 2,289.63) and co-morbidities ($ 665.39) cost items, total per patient annual direct medical costrelated to management of severe asthma was calculated to be $ 4,369.76 from payer perspective. Drug treatment/equipment (52.4%) was the main cost driver in the management of severe asthma in Turkey, as followed by hospitalizations/interventions (26.4%) and co-morbidities (15.2%). Conclusions. In conclusion, our findings indicate that managing patients with severe asthma pose a considerable burden to health economics in Turkey, with medications as the main cost driver.

The combined effect of rosuvastatin and ischemic pre- or post-conditioning on myocardial ischemia-reperfusion injury in rat heart.

OBJECTIVE: To investigate the combined effect of rosuvastatin and ischemic preconditioning or postconditioning on ischemia-reperfusion injury in in vivo rat heart. MATERIALS AND METHODS: Ninenty-six male adult Wistar rats were randomly assigned to eight groups: Sham group, ischemia-reperfusion, rosuvastatin preconditioning, rosuvastatin postconditioning, ischemic preconditioning, ischemic postconditioning, ischemic + pharmacologic preconditioning and ischemic + pharmacologic postconditioning groups. Blood samples were taken for creatine kinase evaluation at selected time points. Six rats in each group were separated for either infarct size assessment or immunohistochemical staining with Bcl-2 antibody. RESULTS: The staining with Bcl-2 was significantly lower in groups Sham, ischemic + pharmacologic preconditioning and ischemic + pharmacologic postconditioning groups which is well correlated with the decrease in infarct size for the same groups. The creatine kinase enzyme levels were also reduced to their lowest levels in ischemic + pharmacologic preconditioning and ischemic + pharmacologic postconditioning groups. CONCLUSIONS: These findings suggest that enriching the composition of reperfusate with rosuvastatin along with ischemic preconditioning or postconditioning procedures at the opposite sides of ischemia may interact synergistically for protecting ischemic myocardium from reperfusion injury. The combined application of rosuvastatin with ischemic preconditioning or ischemic postconditioning may provide a new therapeutic option in clinical interventions when compared to single treatment with ischemic and rosuvastatin preconditioning or postconditioning.

Investigating the effect of the poly(ADP-ribose) polymerase inhibitor 5-aminoisoquinolinone and the Na⁺-H⁺ exchanger inhibitor zoniporide on isolated perfused rat hearts during ischemia-reperfusion injury.

The goal of this study was to investigate whether the combination of the Poly(ADP-ribose) polymerase inhibitor 5-aminoisoquinolinone (5-AIQ) and the Na+-H+ exchanger inhibitor zoniporide (ZN) provides increased protection against ischemia-reperfusion (I/R) injury. Rats were separated into 5 groups (n=8): Group 1: Control group, Group 2: I/R, Group 3: 5-AIQ, Group 4: ZN and Group 5: Mix (5-AIQ+ZN). Isolated rat hearts were subjected to 30 min of global ischemia, followed by 120 min of reperfusion using Langendorff's apparatus. In groups 3, 4 and 5, 5-AIO (7.5 µM/L) and ZN (50 nM/L) were added to Tyrode Solution after a stabilization period. The level of lactate dehydrogenase (LDH) was determined in the sample perfusate. Myocardial infarct size was determined using the triphenyltetrazolium chloride method. Heart tissues were stored to determine the malondialdehyde (MDA) content, total oxidant status (TOS) and total antioxidant status (TAS). Compared to the 5-AIQ and ZN groups, there was no notable difference in the LDH, MDA, TOS, TAS and hemodynamic parameters of the 5-AIQ+ZN group, but myocardial infarct size decreased significantly, as determined by volume and weight measurements. These results show that the combined use of Zoniporide and 5-Aminoisoquinolinone provides increased protection against I/R injury by reducing myocardial infarct size.

Protective effect of ethyl pyruvate on liver injury in streptozotocin-induced diabetic rats.

BACKGROUND AND AIMS: Diabetes Mellitus, leading to an increase in oxidative stress, can cause liver damage. Our aim was to investigate the antioxidant effects of Ethyl Pyruvate (EP) on the liver tissue in diabetic rats. MATERIALS AND METHODS: Thirty-two Wistar albino rats were separated into four equal groups. Groups were assigned as follows: (1) Non-diabetic group; (2) EP-treated non-diabetic group; (3) diabetic group; and (4) EP-treated diabetic group. In order to induce diabetes mellitus, 45 mg/kg b.w. streptozotocin was administered intraperitoneally to the rats in groups 3 and 4. On the 3rd day, blood glucose was assessed. Rats with blood glucose levels higher than 300 mg/dl were considered to be diabetic. The EP solution was administered intraperitoneally at a dose of 50 mg/kg b.w. twice daily for 14 days to the rats in groups 2 and 4. The other rats were simultaneously given the same amount of Ringer's lactate solution intraperitoneally. Liver tissue was obtained for malondialdehyde (MDA) analyses and histopathological examination. RESULTS: In group 4, Total Antioxidant Status (TOS) and MDA levels were significantly lower as compared to group 3. Also, morphological abnormalities occurred in group 3 when compared with non-diabetic groups (groups 1 and 2), whereas the disorders resulting from diabetes improved significantly in group 4. CONCLUSIONS: These findings show that EP has protective effects against diabetes-induced liver injury.

Optical coherence tomographic assessment of diabetic macular edema: comparison with fluorescein angiographic and clinical findings.

PURPOSE: To compare the optical coherence tomographic (OCT) features with clinical and fluorescein angiographic (FA) findings in patients with diabetic retinopathy. METHODS: In a retrospective study ophthalmologic examination together with FA and OCT images were obtained from 195 eyes of 110 patients with different stages of diabetic retinopathy and OCT images were obtained from 40 eyes of 20 control subjects. Fluorescein leakage characteristics were organized into five groups: no leakage (1), focal (2), diffuse (3), combined focal+diffuse leakage (4) and cystoid (5). The Pearson correlation test was used to test the correlation between visual acuity and central foveal thickness and ANOVA was used for the statistical comparison between the groups. RESULTS: The OCT images demonstrated retinal swelling in 66.1% of eyes, cystoid macular edema (CME) in 11.8% of eyes, serous foveal detachment + swelling in 6.2% of eyes, serous foveal detachment+swelling+CME in 3.6% of eyes and normal foveal structure in 12.3% of eyes. The best-corrected visual acuity was significantly correlated with central foveal thickness (r:-0.528, p<0.01). There was 77% agreement between clinical examination and OCT results. CME was detected with OCT in 15.4% of eyes in our study, 40% of which was not detected with slit-lamp biomicroscopy and 63.3% of which was not evident in FA. None of the serous foveal detachments could be detected during slit-lamp biomicroscopy or FA. CONCLUSIONS: OCT-3 provided objective documentation of foveal structural changes in eyes with diabetic retinopathy. Best-corrected visual acuity provided a significant correlation with the retinal thickness at the central fovea. These results indicate that OCT can facilitate deciding on the treatment protocol (surgical or medical) and follow-up of diabetic patients, which is especially important in the early stages of diabetic maculopathy when the structural changes are not yet evident with slit-lamp biomicroscopy or angiographically.

Eosinophilic bronchitis as a cause of chronic cough.

Eosinophilic bronchitis is a recently described condition in patients with chronic cough, sputum eosinophilia, normal spirometry and no evidence of bronchial hyperreactivity. The aim of the study was to assess the causes of chronic cough and to identify the prevalence of eosinophilic bronchitis as a cause of chronic cough. Thirty-six patients [mean age 45.4 +/- 14.3 years (range 16-69 years), M/F: 4/32] with an isolated chronic cough lasting for more than 4 weeks were recruited from the outpatient clinic. In all patients, after a full history and physical examination, blood eosinophil count, eosinophilic cationic protein (ECP), serum total and specific IgE levels were measured. Spirometry, methacholine provocation test, skin prick tests, ear, nose and throat examination, induction of sputum and esophageal pH testing were performed. The mean duration of cough was 31.3 +/- 52.3 months. Sputum eosinophilia greater than 3% was present in 12 (33.3%) patients and they were diagnosed as eosinophilic bronchitis. Their induced sputum had a mean eosinophil count of 8.3% and a mean ECP level of 98.5 mg x l(-1), which were higher than the others (P=0.003, both). The diagnosis of the remaining patients were postnasal drip syndrome in eight, gastroesophageal reflux disease in eight, post-infectious cough in two and cough-variant asthma in one patient. In conclusion, eosinophilic bronchitis is an important cause of chronic cough and should be considered in the assessment of patients before regarding them as having idiopathic chronic cough.

Perlite exposure and 4-year change in lung function.

Perlite is a volcanic glass or amorphous aluminium silicate composed of 71-75% SiO(2). When heated to 800-1100 degrees C, it expands to form processed perlite, which has a low density, high surface area, and a low thermal conductivity. The objective was to determine the effect of perlite exposure on pulmonary function tests. Pulmonary function tests in conjunction with chest radiogram were carried out in 36 perlite-exposed workers and 22 unexposed office workers in 1992 and 1996. Respirable dust level exceeded permissible dust levels in work places in the 4 years under study. Transfer coefficient (K(CO)) decline was significant in nonsmoker perlite-exposed workers (n=9), and found to be 5.28+/-0.71 (predicted 4.32+/-0.11) and 3.84+/-0.96 (predicted 4.18+/-0.18) 1/min/mmHg, in 1992 and 1996, respectively (P<0.001). Both smoker perlite workers and office workers showed significant obstruction to airflow in small airways with respect to predicted values and 4-year change in transfer factor (T(L), CO) was significant. Although predicted, 12-year perlite exposure did not lead to a decrease in mean pulmonary function test parameters, there was a tendency to a decline in T(L), CO in the 4-year study period, which may be due to high perlite dust levels. As early effects of perlite dust exposure may not be detected by spirometric measurements alone, the transfer coefficient should be added to spirometry.

Potentiation of cisplatin-induced nephrotoxicity in rats by allopurinol.

Cisplatin (CDDP) is an effective chemotherapeutic agent used against various human malignancies. However, it induces nephrotoxicity, a severe side effect in which oxygen free radicals have been implicated to play an important role. The effect of allopurinol (Allp) given in a dose of 50 mg/kg subcutaneously (s.c.) for five days was examined on induced nephrotoxicity by a single dose of 5 mg/kg CDDP intraperitoneally (i.p.) in male wistar rats. Serum creatinine and blood urea nitrogen (BUN) concentrations were found significantly higher in the group given both Allp and CDDP than in the group given CDDP alone, p < 0.001, and histopathological examination showed more excessive degree of proximal tubular necrosis in the kidneys of animals given CDDP plus Allp than in those treated with CDDP alone. Increased renal lipid peroxidation, p < 0.001 associated with these pathological alterations suggested that oxidative stress may be involved in the potentiation of CDDP-induced nephrotoxicity by Allp.

Gentian violet solution for staining the anterior capsule.

PURPOSE: To evaluate the histopathological changes after injecting gentian violet solution into the anterior chamber of rats and to describe a technique that uses gentian violet to allow a clear view of the anterior capsule during continuous curvilinear capsulorhexis (CCC) in human eyes with white mature cataract. SETTING: Department of Ophthalmology, University of Dicle, Diyarbakir, Turkey. METHODS: In this masked, experimental study (first stage), 0.05 mL of gentian violet 0.01% or 0.001% solution or balanced salt solution (BSS) (control group) was injected into the anterior chamber of 30 eyes of 30 Wistar albino rats. One, 24, and 48 hours after injection, 4 eyes in each group and 2 eyes in the control group were enucleated, and histopathological examination was performed. In the second stage, these solutions were used for staining the anterior capsule in the 18 human eyes with white mature cataract. The success rate of CCC and intraoperative and postoperative complications were evaluated. RESULTS: Histopathological examination revealed no pathology in any group. A CCC was completed in all cases. No intraoperative or postoperative complications were observed in human eyes except mild corneal edema and mild inflammatory reaction in the anterior chamber that improved within 1 week. Mean follow-up was 3.4 months. Visualization of the anterior capsule was better with gentian violet 0.01% solution. CONCLUSIONS: Gentian violet solutions at 0.01% and 0.001% concentrations had no evident toxic effect that caused significant histopathological changes. The staining technique was practical and helped the surgeon visualize the anterior capsule. However, gentian violet may have adverse effects that lead to corneal edema.

Coronary artery bypass grafting in the conscious patient without endotracheal general anesthesia.

BACKGROUND: Over the past several years, considerable experience has accumulated in performing coronary anastomoses on the beating heart, and various aspects of minimally invasive approaches have been simplified. In an attempt to further simplify and decrease the "invasiveness" of this procedure, performing this operation without endotracheal general anesthesia was deemed feasible in certain subsets of patients. METHODS: Between October 1998 and June 1999, 5 patients underwent coronary artery bypass grafting without endotracheal general anesthesia, using high thoracic epidural block to construct extension grafts with a short segment of radial artery, between the in situ left or right internal thoracic arteries and the left anterior descending (n = 4) or right coronary arteries (n = 1). There were 2 female and 3 male patients, with a mean age of 67.4 +/- 8.3 years. RESULTS: The perioperative course of the patients was uneventful. There was no perioperative morbidity or mortality. No patient was converted to general anesthesia or to conventional operation. Control angiograms revealed patent anastomoses in all patients. In 1 patient, spasm of the radial artery graft was observed that was relieved 3 weeks later spontaneously. Mean length of hospital stay was 2.2 +/- 0.4 days. All patients were symptom free and returned to normal daily life at the first postoperative month. CONCLUSIONS: Our initial experience confirms the feasibility of performing coronary bypass grafting in the conscious patient without endotracheal general anesthesia.

Histopathological changes in the uterus of rats treated neonatally with clomiphene citrate.

Clomiphene citrate has estrogenic and teratogenic effects on the developing rat and human fetal genital tract. Clomiphene citrate was given subcutaneously to newly born rats by daily injections of 100 micrograms/kg and changes caused by clomiphene in female rats were investigated at 28 and 35 days. Depending upon the effect of clomiphene citrate, histopathological changes such as the observation of polygonal shaped nodular cells in the uterus epithelium and presence of erythrocytes in free nature in the stroma were considered as important findings.

Histopathological changes in the vagina of rats treated neonatally with clomiphene citrate.

Clomiphene citrate is a nonsteroid antiestrogen which is widely used in the therapy of receptor-positive estrogen for the induction of ovulation. Clomiphene citrate was given subcutaneously to newly born rats with daily injections of 100 mg/kg for 5 days. Changes caused by the clomiphene citrate in vaginas of female rats were investigated at 28 and 35 days. Depending upon the effect of the clomiphene citrate, histopathological changes such as papillary development at keratinization, increase in vaginal epithelium, and observation of polygonal shaped nodular cells in stroma were considered as important findings. It should be emphasised that clomiphene citrate used for induction of ovulation caused these abnormalities in the vagina of rats.