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Background We compared the neuroprotective effects of Fingolimod (fng), a neuroprotective and anti-inflammatory drug, with that of magnesium sulfate (MgSO4), alone and in combination, in fetal rat whose mothers were exposed to endotoxin. Method Seven groups of pregnant rats (28 total) were evaluated at 0.8 gestation - Group1 - saline only; 2 - endotoxin only; 3 - endotoxin + MgSO4; 4 - endotoxin + fng; 5 - endotoxin + MgSO4 + fng; 6 - saline + fng; 7 - saline + MgSO4 + fng. Preterm labor was induced 4 h after intraperitoneal endotoxin administration. Fetal brain samples were examined immunohistochemically using S100 beta, IL-6, and IL-10. Results Endotoxin caused increased expression of S100 beta, IL-6, and IL-10. Compared with MgSO4 alone, combined treatment was associated with lower expression of IL-10, IL-6 and S100 beta. Conclusion Fng decreases inflammatory markers after in-utero exposure to endotoxin, has a synergistic effect combined with MgSO4, and may be a candidate neuroprotective drug for inflammation-induced preterm brain injury.

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We investigated the effects of artemisinin on doxorubicin (Dox) induced heart and liver pathology in rats. We divided 49 male rats into seven groups: group 1 was the untreated control. Dox was administered intraperitoneally to groups 2, 3 and 4 on day 1. Artemisinin was administered by gavage to groups 3 and 6 at a dose of 7 mg/kg, and to groups 4 and 7 at a dose of 35 mg/kg for 14 days. Group 5 was given only 0.9% NaCl orally for 14 days. At the end of the study, heart and liver samples were collected for histopathology and immunohistochemistry. Hyperemia and slight hemorrhages were observed in both livers and hearts of rats treated with Dox only. Significant increases in caspase-3, TNF-α, iNOS and NF-κB expression were observed in the myocardial cells and hepatocytes of group 2. Significant reductions in caspase-3, TNF-α, iNOS and NF-κB expression were observed in groups 3 and 4 following artemisinin treatment compared to group 2. Artemisinin may exert protective effects against Dox induced cardiotoxicity and hepatotoxicity in rats.

We investigated the effects of alpha lipoic acid (ALA) on blood and lung tissue exposed chronically to cigarette smoke (CS). Female Sprague-Dawley rats were divided into three groups. Group 1 was the control group (CON): fresh air was supplied twice daily and 0.1 ml physiological saline was given orally for 8 weeks. Group 2 was exposed to CS: 12 cigarettes were smoked daily at two sessions for 1 h and 0.1 ml saline was given orally for 8 weeks. Group 3 (CS + ALA) was exposed to 12 cigarettes daily in two sessions for 1 h and 100 mg/kg/day ALA was given orally for 8 weeks. DNA damage was assessed using comet analysis; oxidative damage was assessed using ischemia-modified albumin (IMA) from blood; and total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured in blood and lung tissue. Histopathological and immunohistochemical evaluation of hypoxia-inducible factor (HIF)-1α, and -2α, caspase-3, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) were conducted using lung tissue. The oxidative markers, TOS, OSI and IMA, and the comet analysis score were increased and the TAS level was decreased in the blood of the CS group compared to the CON group. IMA levels in blood, and TOS and OSI levels in the lung were decreased significantly in the CS + ALA group compared to the CS group. We observed increased septal wall thickness, marked and diffuse inflammatory reaction, emphysema, and necrotic cell debris in bronchial and bronchiolar lumens in the CS group. HIF-1α, HIF-2α, caspase-3 and FGF2 expressions were increased, while VEGF expression decreased in the lung tissues of the CS group compared to the CON group. ALA slightly ameliorated the damage caused by chronic exposure to CS in the lungs, but further investigation is needed to determine its possible protective effects at different dosages.

PubMedID: 29565181 We investigated the expression of bcl-2, estrogen receptor alpha (ER-alpha), caspase-3, -8, -9, proliferating cell nuclear antigen (PCNA) and Ki-67 in canine mammary carcinomas. We used 65 paraffin embedded and re-diagnosed archival canine mammary tumor samples to which we applied the routine streptavidin-biotin-peroxidase technique. Seventeen cases were re-diagnosed as tubulopapillary carcinoma, 31 were re-diagnosed as complex carcinoma and 17 were re-diagnosed as carcinosarcoma. Differences of expression of bcl-2 and PCNA were statistically significant according to tumor type. Differences in expression of ER-alpha, caspase-3, -8, -9 and Ki-67 were not statistically significant. Differences of expression of bcl-2 and PCNA were statistically significant compared to ER-alpha, caspase-3, -8, -9 and Ki-67 in carcinosarcomas. We report the prognostic significance of bcl-2 and PCNA expression in canine mammary carcinosarcomas. © 2018, © 2018 The Biological Stain Commission. 0193-NAP-13 Our study was supported by Scientific Projects Commission of University of Mehmet Akif Ersoy (Project no. 0193-NAP-13).

Endosulfan, a chlorinated hydrocarbon insecticide/acaricide, is a member of a cyclodiene sub-group of poisons to a wide variety of insects and mites. It is also toxic to humans and animals, but there is limited knowledge about endosulfan-related splenic and overall immunotoxicity. The aim of this study was to review pathological findings of endosulfan toxicity in the spleen and to examine potential protective effects of the anti-oxidant Vitamin C (Vit C). Here, after 6-week exposures, the spleens of New Zealand White rabbits were examined grossly and histopathologically and tissue caspase-3 activity was assessed immunohistochemically. Rabbits in four groups were used: Group END were given by oral gavage a sub-lethal dose of endosulfan (1 mg/kg) in corn oil daily for 6 weeks; Group END + C received the same dose of endosulfan daily and Vit C (20 mg/kg) every other day by gavage during this period; Group Vit C received oral corn oil daily and 20 mg/kg Vit C every other day; and Group OIL received corn oil daily for 6 weeks. Analyses of the tissues collected 1 week after the final dosing revealed lymphocyte depletion and necrosis in spleens of the hosts that received the pesticide (END only and END + C); hemorrhage and slight neutrophilic infiltration was also noted. Caspase-3 immunoreactivity was marked in lymphocytes in all spleens of rabbits in both END groups. Overall, these toxicities were mitigated by Vit C co-treatment; in END + C hosts, markedly decreased depletion of lymphocytes, inflammation and caspase-3 immunoreactivity were observed. However, even with mitigation, the level of toxicity present was still greater than any seen in the spleens of hosts that received OIL or Vit C alone. These results revealed endosulfan could cause toxicity in the rabbit spleen, characterized by depletion of lymphocytes, inflammation, necrosis and hemorrhage, and that this toxicity could begin to be mitigated by Vit C co-treatment.

To examine the pathological findings that occurred in the lens and cornea and biochemical findings in the lens of rats fed with corn syrup and the protective effects of alpha lipoic acid (ALA).Twenty-four rats were randomly divided into three groups. Group I served as the control group. Group II was used as the study group; the rats were treated with 30% corn sugar solution for 10 weeks. Group III was the treatment group. Corn syrup was given by the oral route to the rats during the study, and ALA (100 mg/kg) was added to the treatment 4 weeks after the study began. At the end of the experiment, central corneal thickness (CCT) was measured in all rats with an ultrasonic pachymeter. Then the right eyes of the rats were enucleated for histopathological examination of the cornea and lens. The left lenses were homogenized for biochemical analyses.The lenses of the rats treated with corn syrup revealed severe damage; many lens fibers appeared swollen and ruptured with large vacuoles near the lens epithelium. In addition, malondialdehyde (MDA) levels, a parameter of oxidative stress, increased but not significantly in Group II; however. ALA treatment decreased MDA levels significantly. Antioxidant enzyme and catalase (CAT) activities were significantly decreased in Group II, and ALA treatment increased these activities; however, the increase was not significant. Changes were observed in the cornea such as epithelial alterations, subepithelial vacuolizations, collagen fibers loss in the stromal layer, interruptions in the subepithelial basement membrane and central corneal thickening.Corn syrup can cause severe damage in rat lenses and corneas. However, ALA ameliorates the effect of corn syrup-related lesions on the cornea and lens.

Endosulfan is an insecticide that is composed of two stereoisomers: α- and β- endosulfan in an approximate ratio of 70:30. Owing to its widespread use, poisoning of both humans and animals is possible. We examined the toxic effects of endosulfan on New Zealand white rabbit kidneys. Rabbit kidneys were examined histopathologically and caspase-3 activity was detected using immunohistochemistry. Animals were divided into four groups: Group 1 was given a sublethal dose of endosulfan in corn oil by oral gavage daily for 6 weeks, Group 2 was given endosulfan + vitamin C during the same period, Group 3 was given corn oil daily and vitamin C on alternate days, Group 4 was given only corn oil daily throughout the experiment. By the end of experimental period, the concentration of α-endosulfan was greater than the β-endosulfan concentration in the kidneys of both of endosulfan treated groups (Groups 1 and 2). Decreased accumulation of α- and β-endosulfan was observed in Group 2, possibly because of the antioxidant effect of the vitamin C. Histopathological examination revealed hemorrhages, tubule cell necrosis, glomerular infiltration, glomerulosclerosis and proteinaceous material in the tubules, and Bowman spaces in the kidneys of Group 1. Caspase-3 reaction was stronger in Group 1 than in the other groups. Apoptotic activity was most frequent in proximal tubule cells. Endosulfan is toxic to rabbit kidneys. Vitamin C treatment reduced the accumulation of endosulfan in kidneys and reduced its toxicity.

In this study, three stillborn and five premature and blind calves from cows suffering from chronic nitrate poisoning were examined pathologically. The live calves were euthanized, due to a poor prognosis. Complete necropsy was performed on all the eight affected calves. Hydroperitoneum and ascites were the most predominant lesions in the stillborn calves. Edema and hemorrhage were observed in the lungs of all the calves. Hemorrhages were seen in the digestive systems of four calves. Blood samples were taken from five live calves and their mothers, and from two cows that had delivered stillborn or blind calves, for biochemical observations and measurement of methemoglobin levels. Blood values of five healthy cattle from a herd with no history of stillborn or blind calves were used as controls. Water and feed samples were taken from five different farms with a history of stillborn or blind calves and examined for nitrates. Nitrate and nitrite levels of feeds ranged from 154 to 480 and 1.5 to 20 ppm respect...