Deniz Billur

Efficacy of platelet-rich fibrin matrix on viability of diced cartilage grafts in a rabbit model.

The objective of this study was to compare the viability of cartilage grafts embedded in platelet‐rich fibrin matrix (PRFM) wrapped with no material (bare diced cartilage grafts), oxidized methylcellulose (Surgicel), or acellular dermal tissue (AlloDerm).

Interplay Between Cytosolic Free Zn(2+) and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.

The Zn2+ in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO4 (extracellular exposure) or Zn2+ pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn2+ exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in ZnPO4- or ZnPT-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn2+-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during 1-μM ZnPT minute applications by using confocal microscopy. We also showed that 1-μM ZnPT incubation induced significant increases in the phosphorylation levels of GSK3β (Ser21 and Ser9), Akt (Ser473), and NFκB (Ser276 and Thr254) together with increased expression levels in ER stress proteins such as GRP78 and calregulin. Furthermore, a new key player at ER-mitochondria sites, promyelocytic leukemia protein (PML) level, was markedly increased in ZnPT-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn2+ can induce marked alterations in mitochondrion morphology as well as depolarization in mitochondrion membrane potential and changes in some cytosolic signaling proteins as well as a defect in ER-mitochondria cross talk.

The effects of levetiracetam on neural tube development in the early stage of chick embryos.

AIM This study aimed to investigate the effects of a new generation antiepileptic agent, levetiracetam, on the neural tube development in a chick embryo model that corresponds to the first month of vertebral development in mammals. MATERIAL AND METHODS Forty-five Atabey® breed fertilized chicken eggs with no specific pathogens were randomly divided into 5 groups. All of the eggs were incubated at 37.8±2°C and 60±5 % relative humidity in an incubator. Group A was control group. The other eggs were applied physiological saline and drugs at a volume of 10 μL by the in ovo method at the 28th hour of the incubation period. Group B was given distilled water; Group C, physiological saline; Group D, Levetiracetam (L8668) at a dose equivalent to the treatment dose for humans (10 mg/ kg), and Group E, Levetiracetam (L8668) at a dose of 10 times the treatment dose. The embryos in all of the groups were removed from the shells at the 48th hour and morphologically and histologically evaluated. RESULTS Of the 45 embryos incubated, neural tubes of 41 were closed and the embryos displayed normal development. CONCLUSION Levetiracetam, at a dose equivalent to human treatment dose and 10 times the treatment dose, was shown not to cause neural tube defects in chick embryos.

Metamizole Sodium Induces Neural Tube Defects in a Chick Embryo Model.

AIM The aim of this study was to investigate the effects of metamizole sodium on neural tube development in the early stage chick embryo model that complies with the first month of embryonic development in mammals. MATERIAL AND METHODS A total of 40 fertilized chicken eggs were divided into 4 equal groups. The eggs were incubated in the incubator at a temperature of 37.8±2°C with 60±5% humidity. Group A was the control, Group B was administered physiological saline, Group C was administered 30 mg/kg metamizole sodium (based on the therapeutic index range of it used in humans) and Group D was administered 90 mg/kg metamizole sodium. All embryos were removed from the egg at the 48th hour and morphologically and histologically examined. RESULTS Normal development was seen and the neural tube was closed in 17 embryos in Groups A and B. A neural tube defect was seen in 2 embryos in group A and in 1 embryo in group B. A neural tube closure defect was seen in all embryos in group C and 9 embryos in group D. There was 1 dead embryo in Group D. CONCLUSION Metamizole sodium was seen to produce a neural tube defect in the chicken embyro model.

The Effects of Local and Systemic Growth Hormone Treatment on Germ Cell Population and Fertility in an Experimental Unilateral Testicular Torsion and Orchiectomy Model

PURPOSE We evaluated the effects of local and systemic growth hormone on the germ cell population of the contralateral testes of pubertal rats subjected to unilateral testicular torsion and orchiectomy 24 hours later. MATERIALS AND METHODS A total of 40 male Wistar-Albino rats at age 3 weeks were divided into 5 groups. In the sham operated group the right testis was sutured and orchiectomy was performed 24 hours later. In groups 2 to 5 orchiectomy was performed 24 hours later following testicular torsion. In groups 3 and 4 unloaded and growth hormone loaded gelatin films, respectively, were sutured on the contralateral testes. In group 5 systemic growth hormone was administered for 7 days. Five weeks later each rat was cohabited with 2 female rats and the left testes were removed for evaluation. Mean seminiferous tubular diameter, mean testicular biopsy score and the mean haploid cell percentage were calculated. Mating studies were performed and fertility parameters were assayed. RESULTS Mean seminiferous tubular diameter, mean testicular biopsy score and the mean haploid cell percentage of the contralateral testes were significantly decreased in the control and gelatin groups compared with the other groups. There was no difference between the local and systemic growth hormone groups regarding the haploid cell percentage. There were no differences between the groups in mean fetus numbers, mating or fertility and fecundity indexes except in the gelatin group, in which the mean fetus number was significantly lower. CONCLUSIONS Fertility is not affected in rats after 24 hours of testicular torsion and orchiectomy, although there is germ cell injury and a decrease in the percent of haploid cells. Growth hormone administration resulted in the restoration of germ cell histology and an increase in the haploid cell percentage of the contralateral testes. Growth hormone may improve fertility after unilateral testicular torsion and orchiectomy.

Increase in pro-apoptotic Bax expression and decrease in anti-apoptotic Bcl-2 expression in newborns with necrotizing enterocolitis

BACKGROUND/AIM The aim of the present study was to find out if there is an increase in the expression of pro-apoptotic Bax and reduction in expression of anti-apoptotic Blc-2A1 in newborn intestines with necrotizing enterocolitis (NEC). MATERIALS AND METHODS We compared 8 consecutive newborn patients undergoing bowel resection for NEC with 8 neonates undergoing intestinal resection for ileal atresia. Histopathological evaluation of tissue injury and apoptosis was performed by using light microscopic examination and TUNEL method. The mRNA level of apoptotic (CASP3, CASP6, CASP7, Bax, BIRC2) and anti-apoptotic genes were evaluated by PCR array method. Protein expression was assessed by immunohistochemistry. RESULTS We compared 8 consecutive newborn patients undergoing bowel resection for NEC with 8 neonates undergoing intestinal resection for ileal atresia. Histopathological evaluation of tissue injury and apoptosis was performed by using light microscopic examination and TUNEL method. The mRNA level of apoptotic (CASP3, CASP6, CASP7, Bax, BIRC2) and anti-apoptotic genes were evaluated by PCR array method. Protein expression was assessed by immunohistochemistry. CONCLUSIONS Our data in humannewborns suggest that alteration of the balance between pro-apoptotic Bax expression and anti-apoptotic Bcl-2A1 expression in the site of injury is a possible mechanism in the pathogenesis of NEC.

Montelukast attenuates radioactive I131-induced pulmonary damage on rats

Abstract Purpose: Radioactive I131 (RAI) therapy is a standard method to ablate the remnant thyroidal tissue after total thyroidectomy and its metastases in differentiated thyroid carcinomas; however, I131 also accumulates in nonthyroidal tissue, which may cause adverse effects and limit the I131 dose required for treatment. We hypothesized that montelukast, a known agent with anti-inflammatory and anti-oxidant properties, would ameliorate the radiation-induced histopathological characteristics such as pneumonitis and fibrosis in rat lungs after RAI. Methods: Fifty female Wistar albino rats were randomly separated into five groups of 10. Group 1 was the control group; Group 2 was administered RAI only; Group 3 was administered RAI and montelukast, Group 4 was administered RAI after total thyroidectomy and Group 5 was administered RAI and montelukast after total thyroidectomy. All rats were sacrificed after 12 weeks and the lungs were evaluated in the histological examination to determine the degree of inflammation and fibrosis and for immunohistochemical (IHC) staining for tissue expression of IL-1, IL-6 and TNF-alpha and TGF-beta. Results: The RAI-administered groups, Group 2 and Group 4, were significantly different from the control group, however, the groups medicated with both RAI and montelukast, Group 3 and Group 5, were not significantly different from the control group. All histopathological and IHC parameters were significantly less in the groups administered with montelukast compared to the groups not administered with montelukast. Conclusions: The results of this study demonstrated the radioprotective effect of montelukast in the pulmonary system through histopathological and IHC examination.

Aging related functional and structural changes in the heart and aorta: MitoTEMPO improves aged-cardiovascular performance

&NA; Aging in humans represents declining in cardio‐protective systems, however its mechanisms are not known yet. We aimed to analyse how aging affects key mechanisms responsible for contractile dysfunction via comparing the improperly synchrony between electrical and mechanical activities in male aged‐rats (24‐month old) comparison to those of adult‐rats (6‐month old). We determined significantly increased systemic oxidative stress with decreased antioxidant capacity, clear insulin resistance and hypertrophy in aged‐rats with normal fasting blood glucose. We also determined significantly high level of reactive oxygen species, ROS production in fluorescent dye chloromethyl‐2′,7′‐dichlorodihydrofluoroscein diacetate (DCFDA) loaded isolated cardiomyocytes from aged‐rats, confirming the increased oxidative stress in these hearts. In situ electrocardiograms, ECGs presented significant prolongations in RR‐ and QT‐intervals in the aged‐rats. Invasive hemodynamic measurements demonstrated marked increases in the heart rate and mean arterial pressure and decreases in the ejection‐fraction and preload‐recruitable stroke‐work, together with depressed contraction and relaxation activities in aortic rings. In light and electron microscopy examinations in aged‐rats, significant increases in muscle fibre radius and amount of collagen fibres were detected in the heart as well as markedly flattened and partial local splitting in elastic lamellas in the aorta, besides irregularly clustered mitochondria and lysosomes around the myofilaments in cardiomyocytes. MitoTEMPO treatment of tissue samples and cardiomyocytes from aged‐rats for 1‐h induced significant structural improvements. In the second part of our study, we have shown that mitochondria‐targeted antioxidant MitoTEMPO antagonized all alterations in the heart samples as well as penylephrine‐induced contractile and acetylcholine‐induced relaxation responses of aged‐rat aortic rings. Overall, the present data strongly support the important role of mitochondrial oxidative stress in the development of aged‐related insufficiencies and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in aging‐associated complications. Highlights Building upon our recent work in which, we examined whether a mitochondria‐targeted antioxidant MitoTEMPO could prevent cardiovascular dysfunction in an aged‐rat model and we showed for the first time that;We monitored insulin resistance and systemic oxidative status with decreased antioxidant capacity in aged‐rats.We observed a significant prolongation in RR‐ and QT‐intervals in ECG recordings.We determined a direct protection against cellular ROS production in isolated cardiomyocytes.We showed that improvement of mitochondrial antioxidant capacity with MitoTEMPO, Overall, the present data strongly support the important role of mitochondrial oxidative stress in the development of aged‐related insufficiencies and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in aging‐associated complications.

Punica granatum L. Juice Attenuates Experimental Cerebral Vasospasm in the Rabbit Subarachnoid Hemorrhage Model: A Basilar Artery Morphometric Study and Apoptosis.

Background This study investigated the effect of Punica granatum L. (pomegranate) juice on the rabbit basilar artery in an experimental subarachnoid hemorrhage (SAH) model. Methods Eighteen adult male New Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH + treatment group (n = 6). Basilar artery diameter was measured with magnetic resonance angiography (MRA) in all groups at the beginning of the study. Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 30 ml/kg pomegranate juice via gastric gavage for 4 days after the SAH. The SAH group and SAH + treatment group underwent cerebral MRA after 72 hours. After a neurologic score assessment, all the animals were killed. The wall thickness and lumen area of the basilar artery were measured histometrically in all groups, and the apoptotic cell percentage in the artery was identified. The mean diameter of the basilar artery during MRA was measured. Results Pomegranate improved neurologic functions compared with the SAH group (p < 0.01). The mean basilar artery diameter on MRA in the SAH + treatment group was larger than in the SAH group and smaller than in the control group (p < 0.01 and p < 0.05, respectively). The mean vessel wall thickness value in the SAH + treatment group was lower than in the SAH group (p < 0.01), whereas there was no difference between the control and the SAH + treatment group (p > 0.05). The apoptotic cell rate in the SAH + treatment group was significantly lower than in the SAH group (p < 0.001). Evaluation of the basilar artery luminal area showed no difference between the three groups (p > 0.05). Discussion Pomegranate was shown to have a vasospasm‐ attenuating effect on the basilar artery in the rabbit SAH model for the first time in our study.