Meltem Özgüner

Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury.

BACKGROUND/PURPOSE Intestinal ischemia-reperfusion (IIR) induced acute lung injury (ALI) has been documented. Kupffer cell blockage with gadolinium chloride (GdCl(3)) has been shown to attenuate IIR-induced ALI. However, the effects of splenic monocytes/macrophages on IIR-induced ALI has not been studied previously. In the current study, the authors aimed to investigate the role of splenectomy in IIR-induced ALI. METHODS Forty-eight rats were divided randomly into 6 groups as follows: SHAM, SHAM + KCB, SHAM + SPLN, IIR, IIR + KCB, IIR + SPLN. Two hours of ischemia and 1 hour of reperfusion has been applied by clipping the SMA. GdCl3 was given 24 hours before experiment. Splenectomy was done just before SMA clipping. Lung levels of tumor necrosis-factor (TNF), interleukin (IL)-6, myeloperoxidase (MPO), and malondialdehyde (MDA) were assayed biochemically. Lung leukosequestration was determined by counting PMNLs histologically. Kruskal-Wallis and Mann-Whitney U tests were done; P values less than.003 were considered significant. RESULTS Polimorphonuclear leukocyte (PMNL) counts and biochemical parameters in the IIR group were significantly higher than the other groups (P <.003). When compared with IIR group, PMNL counts and biochemical parameters were significantly decreased in the IIR+KCB and IIR+SPLN groups, respectively (P <.003). However, they were still significantly higher than their sham-operated controls (P <.003). CONCLUSIONS This study documents that splenectomy attenuates ALI as well as Kupffer cell blockage. Spleen, an important component of mononuclear phagocytic system as liver Kupffer cells, might play an important role in the IIR-induced ALI.

Investigation of biochemical and histopathological effects of Mentha piperitaLabiatae and Mentha spicata Labiatae on liver tissue in rats

The plant Mentha piperita, or peppermint, is commonly used in the treatment of loss of appetite, common cold, bronchitis, sinusitis, fever, nausea and vomiting, and indigestion as a herbal agent. In this study, we aimed to investigate biochemical and histological effects of M. piperita Labiatae, growing in the Yenisar Bademli town of Isparta city, and Mentha spicata Labiatae, growing in the Anamas high plateau of the Yenisar Bademli town, on the rat liver tissue. Forty-eight male Wistar albino rats weighing 200-250 g were used for this study. Rats were divided into four groups of 12 animals: Group I received no herbal tea (control group); Group II received 20 g/L M. piperita tea; Group III received 20 g/L M. spicata tea; and Group IV received 40 g/L M. spicata tea. Herbal teas were prepared daily and provided at all times to the rats during 30 days as drinking water. Liver function tests, including aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) activities were measured. To evaluate liver antioxidant defences, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), cata lase (CAT) and thiobarbituric acid reactive substance (TBARS) activities were determined in the homogenates of liver tissue. In addition, liver tissues were submitted for histopathologic examination. AST and ALT activities were increased in Group II, Group III and Group IV gradually when compared with the control group. The difference between Group II and the control group was not statistically significant (P > 0.016). Increases in AST and ALT activities of Group III and Group IV were statistically significant when compared with the control group. SOD, GSH-Px and CAT activities were increased in Group II when compared with the control group but the difference was not statistically significant (P > 0.016). However, SOD, GSH-Px activities and the TBARS level were significantly increased, and CAT activity was significantly decreased in Group III when compared with the control group. In Group IV, while SOD, GSH-Px and CAT activities were decreased, the TBARS level was increased as compared with the control group (P < 0.0016). Histopathological evaluation of experimental groups revealed a mild to severe degree of hepatic damage when compared to the control group. In Group II, there was only minimal hepatocytes degeneration. In Groups III and IV, there were granular or ballooning hepatocyte degeneration and necrosis, sinusoidal and central vein dilatation. It was concluded that lipid peroxidation and hepatic damage occurs after M. piperita and M. spicata administration in rat liver and the damage seems to be dose dependent.

Ovarian toxicity in rats caused by methidathion and ameliorating effect of vitamins E and C

We have investigated the effect of subchronic administration of methidathion (MD) on ovary evaluated ameliorating effects of vitamins E and C against MD toxicity. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD + Vit group). MD and MD + Vit groups were given MD by gavage five days a week for four weeks at a dose level of 5 mg/kg/day by using corn oil as the vehicle. Serum malondialdehyde (MDA: an indicator of lipid peroxidation) concentration, serum activity of cholinesterase (ChE), and ovary histopathology were studied. The level of MDA increased significantly in the MD group compared with the control (P < 0.005). Serum MDA decreased significantly in the MD + Vit group compared with the MD group (P < 0.05). The activities of ChE decreased significantly both in the MD and MD + Vit groups compared with the controls ( P < 0.05). However, the decrease in the MD + Vit groups was less than in the MD group; the ChE activity in the MD + Vit group was significantly higher compared with MD group (P < 0.05). Number of ovarian follicles were significantly lower in the MD group compared to the controls (P < 0.05). Number of atretic follicles were significantly higher in the MD group than in the controls (P < 0.05). Follicle counts in MD + Vit group showed that all types of ovarian follicles were significantly higher, and a significant decrease in the number of atretic follicles compared with the MD group (P < 0.05). In conclusion, subchronic MD administration caused an ovarian damage, in addition, LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Treatment with vitamins E and C after the administration of MD reduced LPO and ovarian damage. Human & Experimental Toxicology (2007) 26 , 491—498

Evaluation of caspase-dependent apoptosis during methyl parathion-induced endometrial damage in rats: Ameliorating effect of Vitamins E and C.

The role of reactive oxygen species (ROS) in various diseases of the female reproductive tract has been shown, and oxidative stress is an important component of the mechanism of toxicity of OPIs. Methyl parathion (MPT) is one of the most widely used organophosphate insecticides (OPIs) in agriculture. The aim of the study was to elucidate the effect of subchronic MPT exposure on lipid peroxidation and serum activities of cholinesterase (ChE), and the protective effects of combination of antioxidant Vitamins E and C in rats. Additionally, histopathological and immunohistochemical changes in endometrium were aimed to be examined. Three groups of rats were used in the experiment. The first group was treated with 5mg/kg MPT; the second group was treated with 5mg/kg body weight MPT plus Vitamin E and Vitamin C (MPT+Vit); and the third group was given only corn oil (control). MPT and MPT+Vit groups were given MPT by gavage 5 days a week for 4 weeks at a dose level of 4mg/(kgday) by using corn oil as the vechicle. Vitamins E and C were injected at doses of 50mg/kg i.m. and 20mg/kg body weight i.p. Histopathological and immunohistochemical examinations for caspase-3 and caspase-9 were accomplished in the endometrium. The level of malondialdehyde (MDA) increased significantly in the MPT group compared with the control group (p<0.05). MDA significantly decreased in the MPT+Vit group compared with the MPT group (p<0.05). Administration of Vitamins E and C along with MPT significantly reduced the histopathological changes and the extent of apoptosis. In conclusion, subchronic MPT administration caused endometrial damage and that treatment with a combination of Vitamins E and C reduced endometrial damage caused by MPT.

Thrombotic effect of purposeful back-wall stitch for different suture locations and vessels in rats.

Many microsurgeons experience inadvertent back-wall stitch as a cause of immediate anastomotic failure. To investigate this factor as a possible cause of delayed arterial anastomotic failure that does not appear in the operation room, a purposeful back-wall stitch (PBWS) model of microarterial anastomosis was applied in various configurations on femoral and carotid arteries of rats. Carotid (n = 28) and femoral (n = 28) artery groups were equally divided into 4 different subgroups according to the type of PBWS. Control subgroups had no PBWS. Thirty-degree, 60-degree, and 90-degree subgroups had PBWS located at 30, 60, and 90 degrees, respectively. Patencies were assessed at 60 minutes and 24 hours. Immediate milking test demonstrated normal anterograde refilling in all anastomoses. PBWS increased thrombosis in femoral arteries, while it did not increase it in the carotid at either evaluation times. The only significant difference was between 90 degrees PBWS and the control subgroup irrespective of the vessel factor in 24 hours. Histologic examination supported absence of thrombosis, as suggested by surgical examination. This may show that small-sized arteries are more inclined to thrombosis compared with larger ones and the thrombosis risk increases as the inadvertent back-wall stitch is more centrally located. Contrary to general notion that the inadvertent back-wall stitch causes immediate thrombosis, thromboses later than 1 hour, and even patent anastomoses in 24 hours, were observed in femoral and carotid artery groups. This study suggests that the inadvertent back-wall stitch should also be considered as a possible cause of late anastomotic problems.

Evaluation of Cardiac Markers in Children Undergoing Hematopoietic Stem Cell Transplantation.

Early life‐threatening cardiotoxicity and cardiac death have been reported after hematopoietic stem cell transplantation (HSCT). The purpose of the current study was to evaluate cardiac toxicity of conventional chemotherapy followed by HSCT with cardiac markers: heart‐type fatty acid binding protein (H‐FABP), glycogen phosphorylase BB (GPBB), high sensitive C reactive protein (hsCRP) cardiac troponin I, (cTnI), creatine kinase MB (CK‐MB mass) and myoglobin.

The effects of unilateral testicular ischemia and hemicastration on contralateral testicular IGF-1 level, histology and lipid peroxidation

Hemicastration is followed by compansatoryhypertrophy whereas unilateral testiculartorsion is followed by atrophy in contralateraltesticle in rats. Insulin-likegrowth factor (IGF-1) has important roles intesticular paracrine and autocrine functions. Inthis study it was aimed to compare ischemicparameters and IGF-1levels in the contralateral testicle inunilateral spermatic cord ligation, testiculartorsion, and hemicastratron. 32 wistar ratswere equally altocated into sham,ligation, torsion, and hemicastration groups.In ligation group, right spermatic cord wasligated with 3/0 silk suture. In thetorsion group, right testis was tcrsed for720 degrees. In hemicastration group, rightorchiectomy was done. 48 hours later leftorchiectomy was done in all groups.Malondialdehyde (MDA) and IGF-1 levels weredetermined in the testicle. Average values ofthe groups werecompared with Anova followed by Dunnett T3multiple comparison tests. MDAlevels were significantly reduced in ligationand torsion groups (p < 0.05). This reductionwas more prominent in hemicastration group(p < 0.05). Contralateral testicular IGF-1levels in ligation and torsion groups were notdifferent compared with the sham group. Lefttesticular IGF-1 level in the hemicastrationgroup was decreased significantly comparedwith other groups (p < 0.05). Histological.changes evaluated. Contralateral Johnsenstesticular biopsy scores were significantlydecreased in all experimental groups but meantubular diameter was not changed in all groups.

Factors associated with bone marrow stem cell yield for pediatric allogeneic stem cell transplantation: The impact of donor characteristics.

The aim of this study was to investigate the effects of donor characteristics on CD34+ cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady‐state BM donors) and those who received G‐CSF for stem cell mobilization (G‐CSF‐primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donors leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+ cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+ cell yield in the harvest was 0.12×106/L (0.02‐0.21) in SS‐BM donors and 0.18×106/L (0.09‐0.67) in GP‐BM donors (P=.03). Median of CD34+ cell count given to recipients was 2.6×106/recipient body weight (1.3‐19.3) in SS‐BM yields and 3.8×106/recipient body weight (1.1‐10.2) in GP‐BM yields, respectively. Multiple regression analysis showed that donor height and pre‐G‐CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+ cell count especially for pediatric donors.

Thrombotic effect of purposeful back-wall stitch for end-to-side microarterial anastomosis in rats.

The accidental placement of a back-wall stitch is a mistake easily made by microsurgeons during an end-to-side (ETS) anastomosis, which is technically more difficult compared with an end-to-end (ETE) anastomosis. The thrombogenic effects of a back-wall stitch may aggravate the already existing turbulence and therefore thrombus-prone ETS anastomosis. We investigated this dangerous combination by applying a purposeful back-wall stitch model (PBWS) in an ETS microarterial anastomosis model in various configurations the rat carotid and femoral arteries. We performed femoral and carotid artery bypass grafts via two ETS anastomosis. Carotid (n=28) and femoral (n=28) artery groups were equally divided into four different subgroups according to PBWS placement: Control (no PBWS) and 30-degree, 60-degree, and 90-degree subgroups with PBWS located at 30, 60, and 90 degrees, respectively. We found that there were no significant patency differences with respect to vessel type, PBWS placement, or time of assessment. The results of our current study and previous studies demonstrate that a PBWS in the ETS anastomosis does not have a major effect on thrombus formation. We think that an inadvertent back-wall stitch in the ETS anastomosis may not be a significant cause of thrombosis alone but in combination with retained thrombogenic material into lumen can contribute to thrombus.

Angiopoietins in the bone marrow microenvironment of acute lymphoblastic leukemia.

Objective: Angiogenesis have implications in leukemia biology. Angiopoietin 1 (Ang 1) is an angiogenic cytokine which is essential in survival and proliferation of endothelial cells. Angiopoietin 2 (Ang 2) promotes dissociation of pericytes and increases vascular permeability and stromal derived factor 1 alpha (SDF 1α) which is a key player in stem cell traffic in the bone marrow (BM), has stimulating effects on angiogenesis as well. Here, we investigated the role of the leukemic BM microenvironment and specifically, the role of SDF 1α-CXCR4 and Ang 1/Ang 2–Tie 2 axes. Methods: Here, Ang 1, Ang 2, and SDF 1α levels were measured in the BM plasma and in supernatants of mesenchymal stem/stromal cells (MSCs) of patients with ALL and compared with those of healthy controls. Results: The results showed that at diagnosis, BM plasma levels of Ang 1 and SDF 1α were significantly low and Ang 2 was high when compared to control values. Remission induction was associated with an increase in Ang 1/Ang 2 ratio and SDF levels in BM plasma. Discussion: The results suggest that BM microenvironment and leukemic cell–stroma interaction influences the secretion of Ang 1, 2 and SDF 1α, thus, may affect both angiogenesis, homing and mobilization of leukemic blasts.