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Microcirculation has great importance in eye and testicular tissue and is necessary to have adequate and appropriate amount of angiogenesis. It is known that high levels of Vascular Endothelial Growth Factor (VEGF) trigger uncontrolled angiogenesis, whereas inadequate VEGF can lead to decreased tissue perfusion and oxygenation. The aim of this study was to investigate effects of VEGF in testicular and ocular tissues in both non-diabetic and diabetic rats treated by statin. Atorvastatin (10 mg/kg daily given by orally gavage) was administered for two weeks. Diabetes was induced by streptozotocin, (STZ, 45 mg/kg/ip) in diabetic group's rats. Two weeks later from STZ injection, atorvastatin treatment was initiated in diabetic group. VEGF levels were measured by using ELISA. The VEGF levels were decreased in vitrous, ocular and testicular tissues of all statin-administered rats. In diabetic group VEGF levels were found to be decreased in testicular tissue and increased in ocular tissues., Conclusion: Statin use decreased in VEGF levels of testicular and ocular tissues in diabetic and non-diabetic rats. Statin treatment (anti-VEGF effect) had a protective effect in the development of diabetic retinopathy, yet statins may have a negative impact on tissues that depend on microcirculation by reducing VEGF levels. Further research is needed for statins' microcellular effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Diabetes and insulin resistance frequently cause liver damage. Diabetes also causes reduction in liver and blood IGF-1 levels. We investigated the relation between liver damage and IGF-1 levels in diabetic rats. Fourteen Wistar albino rats were divided into control and diabetic groups. Diabetes was induced by streptozotocin. Rats were sacrificed for biochemical and histologic examinations 2 weeks after streptozotocin injection. Serum and liver IGF-1 levels were decreased, liver malondialdehyde (MDA) levels were increased, glutathione peroxidase (GPx) enzymes activities were decreased and serum alanine aminotransferase (ALT) levels were increased in diabetic group. Microscopic examination of liver revealed that normal tissue organization was disrupted in streptozotocin-induced diabetic rats. There was a strongly positive correlation between blood glucose levels and liver injury, and blood and liver IGF-1 levels. There was a strongly negative correlation between blood IGF-1 levels and hepatic injury. Our results suggest that reduction of blood IGF-1 levels correlates with hepatic injury and circulating IGF-1 levels may have predictive value for determining hepatic damage that results from diabetes. In addition, circulating IGF-1 levels are correlated with glutathione levels and the oxidative stress status of diabetic rat liver.

Gemcitabine, which induces S-phase arrest, and Vinorelbine, which arrests microtubule organization, are two agents that have demonstrate preferred anti-tumor activity. Nitric oxide acts in diverse functions including anti-tumor and anti-pathogenic activities. In this study, we aimed to examine the distribution of immunoreactivities of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in cells of the MCF-7 breast cancer cell line in response to treatment with Gemcitabine (G), Vinorelbine (V) and combination of Gemcitabine and Vinorelbine (G+V). The distributions of iNOS and eNOS were determined by using indirect immunoperoxidase or immunofluorescence methods and ELISA. Cells incubated with G, V and G+V for 24, 48 and 72h were immunolabelled with anti-eNOS and anti-iNOS primary antibodies. Apoptosis was determined by TUNEL assay. A significant increase of eNOS immunolabelling on MCF-7 cells treated with G and G+V was observed. Apoptotic cells were also detected in G, V and G+V treated MCF-7 cells. The immunolabelling of iNOS was detected in all groups but this immunoreactivity was not different among the groups. In conclusion, while G treatment, induced S-phase arrest, triggered the NOS pathway after treatment of MCF-7 cells, V treatment, arrested microtubule organization and did not change the NOS pathway. Detection of increased eNOS immunolabelling and apoptosis after G treatment of MCF-7 cells could be important to the treatment of human breast cancer., (Copyright © 2009 Elsevier GmbH. All rights reserved.)

In treatment of hypovolemia it is important to reestablish normal tissue hemodynamics after fluid resuscitation. Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) have been identified as important in many physiological and pathological processes. In this study, we aimed to investigate the histo-physiological effects of VEGF, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1) in resuscitation with different plasma substitutes on lung tissues after acute hemorrhage in rats. Male Sprague-Dawley rats (n=25) were used in this study. The left femoral vein and artery were cannulated for the administration of volume expanders and for direct measurement of mean arterial blood pressure (MAP) (Power-Lab) and heart rate (HR). Fifteen rats were bled (5 ml/10 min) and infused (5 ml/5 min) with one of three randomly selected fluids: (a) dextran-70 (Macrodex); (b) gelatin (Gelofusine); or (c) physiological saline (PS, 0.9% isotonic saline) solutions. Five rats were bled and none were infused (hypovolemia group) and five rats were untreated as the control group. At the end of the experiment, rats were sacrificed and lung tissues were removed for routine processing and paraffin wax embedding. Sections of tissue were stained with hematoxylin and eosin (H&E) and selected blocks were then prepared for indirect immunohistochemical labeling for anti-VEGF, anti-VEGFR-1 and anti-VEGFR-2 primary antibodies. It was observed that both MAP and HR decreased parallel to blood withdrawn in this time interval. The MAP and HR were restored in the following periods. In the control rats, positive immunoreactivity of VEGF and its receptors (VEGFR-1 and VEGFR-2) were detected in respiratory epithelial cells, respiratory and vascular smooth muscle cells, alveolar cells and endothelial cells. While strong immunoreactivities of VEGF and VEGFR-1 were observed in the hypovolemia group, only moderate immunoreactivity of VEGFR-2 was seen in this group. Moderately strong immunolabeling of VEGF and VEGFR-1 were observed in the dextran-70, gelatin and PS resuscitated groups, whereas only weak immunolabeling of VEGFR-2 was observed in these groups. In summary, the vascular protecting effects of these factors were observed with fluid resuscitation, contributing to the pathophysiological changes seen in hypovolemia.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are members of the polypeptide growth factor family. The epidermal growth factor-receptor (EGF-R) is a receptor tyrosine kinase of the ErbB family. Many types of cancer, including ovarian cancer, display enhanced EGF-R immunoreactivity on their cell surface membranes. Also, an increase in TGF-alpha synthesis and secretion usually occurs in human carcinoma cell lines. In this study, we compared the immunoreactivities of TGF-alpha and EGF-R in ovarian tumors and related immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumor and serous-mucinous adenocarcinoma of the ovary (n=10 each) were stained with hematoxylin-eosin and labeled for binding of primary antibodies against TGF-alpha and EGF-R using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare immunohistochemical labeling intensities. Increased immunoreactivity of EGF-R and moderate immunoreactivity of TGF-alpha was detected in adenocarcinomas. There was no significant difference in the immunoreactivity of TGF-alpha among the histologic types of ovarian tumors. The results of this study support the hypothesis that EGF-R may be a more useful marker than TGF-alpha in epithelial ovarian tumors.

The efficacy of using colloids and crystalloids in the treatment of hypovolemia still remains controversial. An important aspect in treating hypovolemia is to re-establish normal tissue hemodynamics after fluid resuscitation. Production of nitric oxide (NO) or growth factors such as transforming growth factor beta (TGF-beta) has been identified as a key mechanism in physiological and pathological processes in the different systems. This study was designed to investigate the histophysiological effects of resuscitation with different plasma substitutes on the heart, lung and brain tissues following acute blood loss in male Sprague-Dawley rats weighing 250-280g (n=30). After anesthesia with sodium pentobarbital, the left femoral vein and artery were cannulated for the administration of volume expanders and for direct measurement of arterial pressure and heart rate. Twenty rats were bled (5ml/10min) and infused (5ml/10min) with one of four randomly selected solutions, (a) human albumin, (b) gelatin (Gelofusine), (c) dextran-70 (Macrodex); or (d) physiological saline (0.9% isotonic saline). Five control rats were bled without infusion. Tissue samples were taken and fixed in 10% formalin solution, then processed for embedding in paraffin wax. Sections were cut and stained with hematoxylin and eosin. Indirect immunohistochemical labelling was performed to reveal binding of primary antibodies against endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and TGF-beta. Mild immunoreactivity of eNOS was observed in endothelial cells of vessels in brain, heart and lung tissues. Increased immunoreactivities of eNOS, iNOS and TGF-beta were observed in the non-fluid resuscitated group in these organs; mild, moderate, moderate and strong immunoreactivities were seen in the albumin, gelatin, physiological saline and dextran-70 treated groups, respectively. Immunoreactivities of iNOS and TGF-beta in the non-fluid resuscitated group were increased significantly, in comparison to the other groups, apart from the dextran-70 treated group. The results of this study show that gelatin solution and physiological saline may be of use after acute blood loss, and dextran-70 is not the preferred resuscitation fluid in the early stages of acute blood loss. It was concluded that albumin solution is the preferred fluid for resuscitation.

The asymmetrical breakdown of the blood-brain barrier (BBB) was studied in female rats. Paw preference was assessed by a food reaching test. Adrenaline-induced hypertension was used to destroy the BBB, which was evaluated using triphenyltetrazolium (TTC) staining of the brain slices just after giving adrenaline for 30 s. In normal rats, the whole brain sections exhibited complete staining with TTC. After adrenaline infusion for 30 s, there were large unstained areas in the left brain in right-pawed animals, and vice versa in left-pawed animals. Similar results were obtained in seizure-induced breakdown of BBB. These results were explained by an asymmetric cerebral blood flow depending upon the paw preference in rats. It was suggested that this new method and the results are consistent with contralateral motor control that may be important in determining the dominant cerebral hemisphere in animals.

A short episode of ischemia induced by coronary artery occlusion can precondition the myocardium against arrhythmia. The factors that have the potential to protect the myocardium from subsequent ischemia and reperfusion are controversial. In this study, the preconditioning-like effects of adrenaline were investigated in both anesthetized and conscious rats. Adrenaline 0.1 and 0.5 mg/kg or saline was administered 10 min before coronary occlusion in conscious and anesthetized rats. The 0.5 mg/kg dose of adrenaline decreased the total duration of arrhythmia in both models. The incidence of ventricular fibrillation decreased and survival rate increased only in conscious rats administered 0.5 mg/kg adrenaline. As a result, it is suggested that exogenous administration of adrenaline before coronary ligation may precondition and protect the heart against arrhythmia.

The relationship between serum total testosterone (T) concentration and fluid intelligence (nonverbal, spatial) was studied in consistently right-handed men with successful (S) or unsuccessful educational levels (NS). Hand preference was assessed by the Edinburgh Handedness Inventory. Nonverbal intelligence was measured by Cattell's Culture Fair Intelligence Test. Serum T level was determined using chemiluminescence enzyme-immunoassay on hormone autoanalyzer. There was no significant difference between the mean T levels of the S subjects and NS subjects, although S-men tended to have higher T levels than NS-men. The mean IQ was found to be significantly higher in S-men than NS-men. In the total sample (S + NS men), the correlation between T to IQ was best described by a polynomial regression (3rd order), exhibiting an inverse U-shaped regression. In S-men, the relationship between T and IQ was best described by a polynomial regression equation of the 3rd order; however, the relationship was not U-shaped, but rather a positive correlation (low T: low IQ and high T high IQ). In NS-men, there was an inverse U-shaped correlation between T and IQ (low and very high T: low IQ and moderate T: high IQ). The present data suggest that (i) very low and very high serum T concentrations may be disadvantageous, (ii) moderate T levels may be advantageous for general fluid intelligence, and (iii) a prewired cerebral organization may be essential for the T effects on cognitive abilities.