Immunohistochemical investigation of endometrial leukocytes in implantation period in rats with streptozotosin-induced diabetes.

Our first aim was to determine the total leukocyte profile in implantation. Second aim was to detect the changes in uterine leukocyte profile in diabetes, a common accompanying disease. For this purpose 4 groups are formed with Wistar albino rats weighing 250-300 g. Two of the groups were non-diabetic and two of them were diabetic. One of the diabetic and one of the non-diabetic groups were left pregnant. Then uterus tissues of pregnant animals were removed in the 5th and 7th days of pregnancy together with tissues of other two non-pregnant groups. Tissues were analyzed immunohistochemically with antibodies CD45, CD3, CD4, CD8, CD56, CD68 and CD79a. It was revealed that pregnancy increased immune staining of CD68, CD3, CD45 and CD56 in endometrium. In addition it was observed that immune staining density of CD68, CD45 and CD56 decreased in diabetes. In the histopathological examination, significant degeneration was detected in the endometrium of diabetic rats. Diabetes could decrease leukocyte proportions in decidua in early pregnancy periods. Therefore immune cell therapies could be administrated in diabetes related problems of pregnancy.

Protective effect of ebselen on experimental testicular torsion and detorsion injury.

Ebselen is used as a drug in clinical trials against stroke, reperfusion injury with anti-atherosclerotic and renoprotective effects. The aim of this study is to investigate the protective effect of ebselen, on torsion/detorsion (T/D)-induced biochemical and histopathological changes in experimental testicular ischaemia/reperfusion injury. A total of 28 male Wistar Albino rats were divided into four groups: group 1(sham-operated group, n = 7), group 2(ebselen group, n = 7), group 3(torsion/detorsion + saline, n = 7) and group 4(T/D + 10 mg kg(-1) ebselen group, n = 7). The tissue homogenate samples were used for immediate nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase, catalase and glutathione measurement. Testes in all groups were evaluated for the biochemical assay and histopathological examinations. To evaluate spermatogenesis, Johnsen scoring system was used. Testicular tissue MDA and NO levels in group 3 were significantly higher than in group 1 and 4. In histological evaluation of the testicular tissues, ebselen administration improved tubular histology significantly compared with T/D group. Significant increase in histological score was observed in the testis of group 3 compared with group 1 and 2. Histological score in group 4 significantly decreased compared with group 3. Johnson score was significantly lower in T/D group compared with all other three groups, ebselen administration increased the score significantly compared with T/D group. Ebselen reduced oxidative biochemical and histopathological damage in our testicular T/D rat model.

Thrombin activatable fibrinolysis inhibitor : its role in slow coronary flow.

BACKGROUND: The slow coronary flow (SCF) phenomenon is characterized by slow progression of angiographic contrast medium in the coronary arteries in the absence of stenosis in the epicardial vessels. The pathophysiological mechanisms of SCF phenomenon remain uncertain. Several hypotheses, however, have been suggested for SCF phenomenon, including an early form of atherosclerosis, small vessel dysfunction, dilatation of coronary vessels, imbalance between vasoconstrictor and vasodilatory factors, platelet function disorder, and inflammation. Atherosclerosis and inflammation are the most accepted mechanisms for the pathogenesis of SCF. Thrombin activatable fibrinolysis inhibitor (TAFI) was described as a new inhibitor of fibrinolysis recently and plays an important role in coagulation and fibrinolysis. In previous studies, the role of TAFI was associated with inflammation and evolution of atherosclerosis in coronary artery disease. There are no data available about TAFI levels in patients with SCF phenomenon investigated by angiography. Our goal was to evaluate TAFI antigen (Ag) levels in patients with SCF and to determine the association of the TAFI Ag level with traditional cardiovascular risk factors in our study. METHODS: The study group constituted 41 patients with angiographically confirmed SCF and 46 patients with normal coronary flow as the control group. The TAFI Ag levels of each patient were determined. RESULTS: Between the control and study group, a statistical difference in the levels of TAFI Ag (p < 0.05) was observed. The TAFI Ag level was significantly higher in the SCF group than the control group (132.21 ± 21.14 versus 122.15 ± 21.59). CONCLUSION: We have demonstrated that TAFI might be a risk factor for the development of SCF independently of conventional cardiovascular risk factors. In addition, TAFI Ag levels were positively correlated with C-reactive protein (CRP) known as an acute phase reactant. Our findings support the reports of previous studies that increased TAFI levels may be associated with inflammation. Further large studies are required to evaluate the importance of TAFI antigen levels in relation to the development of SCF.

N-acetylcysteine prevents doxorubucine-induced cardiotoxicity in rats.

This study is designed to observe the effects of N-acetylcysteine (NAC) on doxorubucine-induced cardiac toxicity in rats both histologically and biochemically. Totally 32 rats divided equally into four groups were studied. The first group received only 200 mg/kg NAC intraperitoneal (i.p.) once every 24 h for 5 days (group 1); the second group received 20 mg/kg doxorubucine (DOX) i.p. single dose plus NAC 200 mg/kg i.p. once every 24 h for 5 days (group 2); the third group received DOX 20 mg/kg DOX i.p. single dose (group 3) and the fourth group, which is also the control group, received saline (group 4). Following 24 h of the final dose, blood samples were drawn from a portal vein and heart tissue were obtained. Tissue thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) levels were highest in the DOX group. In the DOX-treated rats, serum TBARS, NO, aspartate transaminase, lactate dehydrogenase and creatine kinase levels were highest when compared with other groups. Except for serum superoxide dismutase levels, all other parameters differed significantly between the DOX plus NAC group and the DOX group. In the DOX plus NAC group, general architecture was preserved better than the DOX group and myofibril loss was minimal compared with the DOX group. NAC demonstrated, both biochemically and histologically, to be effective in the prevention of DOX-induced cardiotoxicity in rat models. Evaluation of NAC's effect on DOX toxicity warrants further clinical trials on cancer patients.

Effects of ceftriaxone on ischemia/reperfusion injury in rat brain.

The aim of this study was to investigate the effect of ceftriaxone treatment against short-term global brain ischemia/reperfusion (I/R) injury in rats. The study was carried out on 30 Wistar-albino rats that were divided into three groups: control group (n=10), I/R group (n=10) and I/R-ceftriaxone group (n=10). Malondialdehyde (MDA) levels were significantly increased in the I/R group in comparison with the control group (p<0.001). MDA was significantly lower in the I/R-ceftriaxone group than in the I/R group (p<0.05). Superoxide dismutase activity was significantly decreased in the I/R group and increased in the I/R-ceftriaxone group as compared with the control group. Glutathione peroxidase activity was significantly decreased in the I/R group and increased in the I/R-ceftriaxone group as compared with the I/R group and the control. Histopathologically, ceftriaxone provided morphological improvement compared with the I/R group. We concluded that ceftriaxone has neuron-protective effects due to its antioxidant properties as shown by a decrease in MDA overproduction and histological improvement in brain tissue.

The protective effects of omega-3 fatty acid against toluene-induced neurotoxicity in prefrontal cortex of rats.

OBJECTIVE: Toluene is used as an organic solvent, and it has neurotoxic effects. Omega-3 is an essential fatty acid required for brain development. The aim of this study was to investigate the protective effects of omega-3 fatty acid against toluene-induced neurotoxicity in prefrontal cortex of rats. MATERIALS AND METHODS: A total of 21 male Wistar rats were divided into three groups with seven rats in each group. Rats in group I were the controls. Toluene was intraperitoneally injected into the rats of group II with a dose of 0.5 ml/kg. Rats in group III received omega-3 fatty acid with a dose of 0.4 g/kg/day while exposed to toluene. After 14 days, all the rats were killed by decapitation. Enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) were spectrophotometrically studied in the prefrontal cortex of rats. RESULTS: Enzymatic activities of SOD and GSH-Px were decreased, and MDA levels were significantly increased in rats treated with toluene compared with the controls. However, the increased SOD and decreased GSH-Px enzymatic activities and MDA levels were detected in the rats administered with omega-3 fatty acid while exposed to toluene. CONCLUSION: The results of this experimental study indicate that omega-3 fatty acid treatment can prevent toluene-induced neuronal damage in the prefrontal cortex of rats.

Effects of erdosteine on cyclosporin-A-induced nephrotoxicity.

AIM: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. MATERIALS AND METHODS: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. RESULTS: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. CONCLUSION: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.

Investigation of liposome formulation effects on rivastigmine transport through human colonic adenocarcinoma cell line (CACO-2).

Transportations of rivastigmine containing liposomes across Caco-2 cells were studied and in vitro test results were compared with in vivo results. MTT test was used for cell viability studies. Series of formulations were prepared containing rivastigmine which is used for the treatment of Alzheimer's disease. Characterization and stability studies for liposome formulations were performed. Encapsulation efficiencies of liposomes were 35.4%, 25.2% and 29.9% for rivastigmine, rivastigmine-sodium taurocholate, rivastigmine-dimethyl-beta-CD liposomes, respectively. In stability studies, particle size and size distribution, zeta potential, rivastigmine amounts were determined and shelf lives of liposomes were calculated. Penetration properties of rivastigmine through Caco-2 cells, dialysis membrane and kinetics of release from liposomes were determined. Permeability coefficients were calculated after diffusion studies. The highest value of % cumulative amount of rivastigmine passed through caco-2 cell cultures was found to be 87.2% for rivastigmine-sodium taurocholate solution and 12.8% for rivastigmine-sodium taurocholate liposome. The highest permeability coefficient value was obtained with sodium taurocholate liposomes for -0.75. Rivastigmine liposomes and solutions were also applied to animals. Acetyl choline esterase (AChE) activity was determined by the Ellman method on mice. %AChE inhibition values were calculated using blood and brain tissue samples. The physical appearances of the brains were investigated by TEM microscope. The highest value of AChE inhibition was observed for rivastigmine and sodium taurocholate liposomes. The histological investigations and observations also supported these results.

Antibodies neutralizing Nogo-A increase pan-cadherin expression and motor recovery following spinal cord injury in rats.

STUDY DESIGN: A rat model of spinal cord injury was used to test the hypothesis that Nogo-A monoclonal antibody (NEP1-40) promotes morphologic and functional recoveries of injured spinal cord. OBJECTIVE: Nogo-A is a myelin-associated neurite outgrowth inhibitory protein, which blocks elongation nerve fibers and limits neuronal regeneration after central nervous system injury. METHODS: Forty-four rats were utilized and allocated into control (vehicle) and NEP1-40-treated groups. In all animals, the spinal cord was hemi-transected at Th-10 and phosphate-buffered saline solution was immediately applied on the injured area in the control group. NEP1-40 solution was immediately applied on the hemi-transected area in the treatment group. Each group was subdivided into three subgroups according to the postsurgical day of killing (3, 8 and 21 days). The spinal cords were removed for analysis. RESULTS: Motor scores in the NEP1-40-treated groups were significantly higher than those in the vehicle groups both at 8 and 21 days post injury. Immunohistochemical staining for pan-cadherin, a marker of neuronal cell adhesion and axonal sprouting, revealed a significant increase in staining in the NEP1-40 treatment group at 8 and 21 days post injury. Transmission electron microscopical evaluation revealed degeneration of the myelin and loss of cytoarchitectural organization in the axons of controls. Better preservation and normal histologic features were observed in the NEP1-40-treated groups. CONCLUSION: We have demonstrated improved preservation of injured axons and significant pan-cadherin expression after NEP1-40 treatment after the spinal cord injury. Inhibition of Nogo-A may improve the capacity for neuronal regeneration after spinal cord injury.

Apoptosis and proliferation in gastric epithelium due to Helicobacter pylori: an immunohistochemical and ultrastructural study.

UNLABELLED: The effect of H. pylori infection on gastric epithelial cell apoptosis and proliferation is contradictory. Using immunohistochemistry and electron microscopy, this study sought to demonstrate gastric epithelial changes (ie, apoptosis and proliferation) due to chronic H. pylori infection. METHODS: Eighteen female 6- to 8-week old Swiss Albino mice were inoculated intragastrically with 3 doses of 10(9) CFU/mL H. pylori prepared in a Brucella Broth in 5 days. Nine others served as a control group. At the end of 28 weeks, tissue specimens from the gastric antrum were excised and examined immunohistochemically (epithelial growth factor for regeneration and Caspase-3 for apoptosis) and electron microscopically. Immunohistochemical assessment was performed using the indirect peroxidase-antiperoxidase method. RESULTS: In the H. pylori-infected group, EGF staining in gastric epithelium was found to be decreased significantly compared to that in control group (P < 0.001). Caspase-3 reactivity was commonly observed in surface epithelial cells and glandular epithelial cells in H. pylori-infected group and totally it was statistically significant compared to Caspase-3 staining in control group (P < 0.001). Electron micrograph images demonstrated numerous apoptotic cells with condensed chromatin. CONCLUSION: Chronic H. pylori infection of 28 weeks' duration increases apoptosis in gastric epithelium; however, increased apoptosis does not induce proliferation.