Nur Çakar

In vitro and in vivo studies of ibuprofen-loaded biodegradable alginate beads

The irritation effects of ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), were evaluated on mouse gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. The ionotropic gelation method was used to prepare controlled release alginate beads of ibuprofen. The influence of various formulation factors on the encapsulation efficiency, as in vitro drug release and micromeritic properties, was investigated. Other variables included the alginate concentration, percentage drug loading and stirring speed during the microencapsulation process. Scanning electron micrographs of alginate beads loaded with ibuprofen showed rough surface morphology and particle sizes in the range of 1.15 ± 0.4–3.15 ± 0.6 mm. The yield of microspheres, as collected after drying, was generally 80–90%. Formulation code H showing t50% value of 3.5 h was chosen for in vivo trials because of the appropriate drug release properties. For in vivo trials, free ibuprofen (100 mg kg−1), blank and ibuprofen (100 mg kg−1) loaded alginate beads (formulation code H) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six mice orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of ibuprofen in alginate beads prevented the gastric lesions.

The preventive effect of heparin on stricture formation after caustic esophageal burns

BACKGROUND/PURPOSE Preventing thrombus formation after caustic esophageal ingestion has been proposed to have beneficial effects. Therefore, an experimental study was carried out to investigate the effects of heparin on the esophagus after caustic burns. METHODS Caustic esophageal burns were produced in rats by irrigation with 50% NaOH as described by Liu. Rats were divided into four groups as follows: group A, animals with esophageal burns, received placebo and underwent autopsy 48 hours after caustic injury; group B, animals with esophageal burns, received subcutaneous heparin treatment and underwent autopsy 48 hours after caustic injury; group C, animals with esophageal burns, received placebo and underwent autopsy 28 days after caustic injury; group D, animals with esophageal burns, received subcutaneous heparin treatment for 7 days and underwent autopsy 28 days after caustic injury. Histopathologic evaluation was performed in all groups, and collagen content of esophageal sections was analyzed by determination of hydroxyproline levels. RESULTS Submucosal vascular thrombosis was encountered in all group A animals but the submucosal venules and arterioles were patent in most of group B animals. Esophageal strictures did not develop in any of group D animals, although varying degree of esophageal stenoses were encountered in all animals of group C. The circumferences of the burned segment have been narrowed to 3+/-1 mm in group C rats. There was obvious collagen deposition in submucosa, and epithelial regeneration was not complete in group C rats. Submucosa and epithelial integrity seemed normal in group D animals. Hydroxyproline contents in group D were significantly lower compared with group C (P < .05). CONCLUSIONS Heparin has ameliorating effects on stricture formation after caustic esophageal burn. Those effects may occur through possible anticoagulant, antithrombotic, and endothelial protective effects, and modifying effects of heparin on wound healing.

In vitro growth stimulatory and in vivo wound healing studies on cycloartane-type saponins of Astragalus genus

AIM OF THE STUDY The present study was undertaken to evaluate the wound healing effects of the four chief saponins of Astragalus species [cycloastragenol (CA), astragaloside IV (AG), cyclocephaloside I (CCI) and cyclocanthoside E (CCE)]. MATERIAL AND METHODS Effects of cell viability and proliferation of the isolated compounds were evaluated by the MTT assay on human keratinocyte. The wound healing activity was studied by using in vitro wound healing, proliferation and migration scratch assay. In order to see in vivo effectiveness of the compounds, an animal study with Sprague-Dawley male rats at the age of 12 weeks was carried out, and then the main histological outcomes were investigated to observe reepithelization, neovascularization, and presence of inflammatory cells, granulation tissue amount and maturation. RESULTS All the compounds increased both fibroblast proliferation and migration, but the effects were much superior for CA at 1 ng/ml concentration. Among the compounds, based on the histological findings, 5% CA preparation was found to be the most remarkable in vivo wound healing agent showing greater cell density, more regularly organized dermis and more newly formed blood vessels. CONCLUSION Results of this study indicate that the cycloartane-type saponins are the principal constituents responsible for wound healing activities of the roots of Astragalus species substantiating its use in traditional medicine.

The effect of taurine on mesenteric blood flow and organ injury in sepsis

Summary.Endotoxin decreases mesenteric blood flow and inflicts organ injury via free radicals. We investigated whether taurine, an endogenous antioxidant and vasodilator, could attenuate the deleterious effects of endotoxin in a mouse model of sepsis. Swiss albino mice were allocated into four groups and treated either with taurine (150 mg/kg, i.p. at 0th, 8th, 16th h) or its solvent sterile saline (NaCl 0.9%, w/v) while E. coli endotoxin (20 mg/kg, i.p.) or its solvent saline were also given at 8th h. At 24th h the animals were anaesthetized and the mesenteric blood flow was measured by using perivascular ultrasonic Doppler-flowmeter. The animals were then exsanguinated, the spleen, liver, and kidneys were isolated for histopathological examination. Thiobarbituric acid-reacting substances (TBARS), glutathione, and myeloperoxidase activity were determined in the liver samples. Endotoxin significantly decreased the mesenteric blood flow and glutathione levels in liver while TBARS and myeloperoxidase activity were increased. However, taurine did not block the deleterious effects of endotoxin nor it did attenuate the histopathological injury. Therefore, we concluded that endotoxin-induced organ injury via free radicals is resistant to blockade by taurine.

Effect of Trimetazidine on Retinal Ischemia/Reperfusion Injury in Rats

Purpose: To investigate the effect of trimetazidine (TMZ), an antioxidant agent, on the ischemia/reperfusion (I/R) injury in rat retina histopathologically. Methods: The retinal I/R model was carried out by the 4-vessel occlusion method on Wistar albino rats. Twenty-one rats were divided into 7 groups, each comprising 3 rats. The animals in groups 1, 2 and 3 underwent 30 min of ischemia + 4 h of reperfusion and were treated by the administration of saline, TMZ before reperfusion and TMZ before ischemia, respectively. The animals in groups 4, 5 and 6 underwent 90 min of ischemia + 4 h of reperfusion and were treated in the same way as those in groups 1, 2 and 3, respectively. The 7th group was sham operated. Results: Thirty and 90 min of ischemia followed by 4 h of reperfusion induced retinal injury in the rat retina. Histopathologically, the inner plexiform and inner nuclear layers were the most affected parts. TMZ was able to reduce almost all retinal I/R damage when administered before ischemia. A cytoprotective effect of TMZ was partly observed in those animals which were treated before reperfusion. Conclusion: TMZ seemed to have a protective effect against retinal I/R injury in rats.

The effect of low amniotic pressure without oligohydramnios on fetal lung development in a rabbit model

OBJECTIVE Our purpose was to examine fetal lung development in reduced intraamniotic pressure without amniotic fluid loss. STUDY DESIGN A circular portion of uterine wall measuring 1 cm in diameter was excised while the chorionic and amniotic membranes were left intact at the twenty-third day of gestation in New Zealand White rabbits. The chorionic and amniotic membranes herniated spontaneously through the defect. RESULTS Amniotic pressure was significantly reduced after herniation. Lung weight/body weight ratios at term were significantly reduced in experimental fetuses compared with controls. Residual amniotic fluid volumes at term did not differ. Histopathologic examination of lung specimens showed that fetal lungs had not matured in the experimental group as fully as in the control group. CONCLUSION This experimental study demonstrated that low amniotic pressure impaired fetal lung development, even without oligohydramnios.

An immunohistochemical evaluation of cell adhesion molecules in human dental pulp after tooth preparation and application of temporary luting cements

OBJECTIVE The aim of this study was to determine if temporary luting cements used with provisional restorations alter the expression of cell adhesion molecules (CAMs) in human dental pulp. STUDY DESIGN Twenty-five healthy human premolars and third molars scheduled to be extracted for orthodontic reasons were randomly assigned to 5 experimental groups. Group 1 included untreated teeth as negative control. In groups 2-5, provisional crowns were cemented to the prepared teeth with either eugenol-containing or eugenol-free temporary cement and extracted 24 or 48 h after the treatment. Expression ratio and staining intensity of CAMs, including E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule 1 (PECAM-1), was investigated in the pulp samples. The assessment of immunohistochemical reactions was performed by 2 independent observers using a semiquantitative scale. RESULTS Significant reductions were recorded in the expression ratio and/or the staining intensity of E-selectin, ICAM-1, and VCAM-1 in samples removed 48 h after treatment with eugenol-containing cement compared with intact teeth. This reduction was significant only for ICAM-1 for 48-h eugenol-free samples. Moreover, the eugenol-free cement group indicated considerably higher E-selectin, ICAM-1, and VCAM-1 expression compared with the eugenol-containing group (P < .005) 48 h after the application. The PECAM-1 reactivity was similar for all of the experimental groups. CONCLUSION Application of temporary luting cements after tooth preparation for full crown causes alterations in the expression of endothelial CAMs in the dental pulp.

Transient intrauterine hypotension: effect on newborn rat brain.

Intrauterine perfusion failure can cause cerebral malformations. We investigated the effect of transient maternal hypotension on newborn rat brain by inducing hypovolemic hypotension for 2.5 h during early embryonic day 7 (E7) or late (E15) gestation in pregnant rats. We found an increase in the number of TUNEL-positive cells within the periventricular germinative matrix in pups subjected to early gestational hypotension and within the cerebral cortex in those subjected to late gestational hypotension in comparison to sham control animals. These results suggest that episodic maternal hypovolemic hypotension may affect the fetal brain, and apoptotic mechanisms may mediate this effect.

Prenatal Diagnosis of Hemoglobinopathies in Hacettepe University, Turkey

Between 1983 and 2008, prenatal diagnostic procedures for identifying hemoglobinopathies were performed in 947 at-risk fetuses. Seventy-six percent of the fetuses were at risk for β-thalassemia major and 16% for sickle cell anemia; only a small percentage (7%) were at risk for compound heterozygosity of β-thalassemia and an abnormal hemoglobin of the β chain. The results of the study showed that β gene mutations in hemoglobinopathies have a very broad spectrum. Seven hundred and thirty of the 947 fetuses examined using the DNA technique showed 88 different combinations of 27 different mutations. Although the number of fetuses evaluated was far below the desired target, the termination of 261 affected fetuses provided both psychological and economic relief for the parents and was economically beneficial for the country in the long term.

Prenatal Diagnosis of Hemoglobinopathies in Turkey: Hacettepe Experience

Prenatal diagnosis of hemoglobinopathies was performed in 250 fetuses at risk for hemoglobinopathies. The main diagnostic procedures were in vitro hemoglobin synthesis analysis in fetal blood and analysis of DNA obtained from chorionic villus samples. Sixty-six percent of the fetuses were at risk for beta thalassemia major and 28% for sickle cell anemia. Beta thalassemia mutations were heterogenous, and 51 fetuses examined by the DNA technique were found to be at risk for at least 20 different combinations.