Expression of angiogenic growth factors in canine squamous cell cancers.

Skin and subcutaneous tissue tumors are the most common neoplasms in dogs. The most common sites of origin in dogs include digits, skin and the oral cavity including cheek and retromandibular area. We investigated canine squamous cell carcinoma (SCC) samples from 15 dogs and classified them histopathologically according to the degree of differentiation. bFGF, VEGF-C, TGF-ß, PDGF-A, PDGF-C and PDGFR-α expressions were assessed using immunohistochemistry to determine the roles of growth factors during SCC. We found that TGF-ß1 immunolabeling was elevated significantly compared to healthy controls in SCC originating from nailbeds, while expression of other growth factors did not change significantly. Our findings might explain the role of TGF-ß1 in the infiltrative and malignant behavior of SCC originating from nailbeds.

Late effects of cutaneous 3-methylcholanthrene exposure on DNA damage-related pleiotropic growth factors and oxidative stress markers in mice.

BACKGROUND: Skin is the body's first defence against direct exposure to variety of chemicals. Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (3-MC) are common in polluted urban air and have a potential of producing harmful effects. Moreover, their late effects can occur months or years after exposure. OBJECTIVES: We aimed to investigate the long-term effects of 3-MC induced dermal toxicity on the expression of markers of apoptosis, pleiotropic cytokines, and oxidative stress and to determine the protective effect of cisplatin. METHODS: Groups were designed as control (group 1), 3-MC applied (group 2) and 3-MC+cisplatin applied mice (group 3). Cutaneous expressions of TGFß, PDGFA, PDGFC, bFGF, PDGFRα, USP28, and Ki67 were evaluated with qPCR. Total oxidant (TOS), total antioxidant (TAS) and oxidative stress index (OSI) values were determined in liver and kidney tissues. RESULTS: The expression levels of TGFß, PDGFRα, USP-28, Ki67, and PDGFA were decreased significantly in MC applied groups. Renal TAS levels were significantly lower in group-3. Liver and kidney OSI values were increased in both groups 2 and 3. CONCLUSION: The results indicated that low dose 3-MC caused oxidative stress and downregulated apoptotic and cytokine markers in the long term and cisplatin had no ameliorative effects on this degeneration processes (Tab. 3, Fig. 3, Ref. 32). Text in PDF www.elis.sk.

Significance of Angiogenic Growth Factors in Bovine Ocular Squamous Cell Carcinoma.

Bovine ocular squamous cell carcinoma (BOSCC) is the most common and economically significant neoplasm of the eye in cattle. This study investigated the role of angiogenic growth factors in the pathogenesis of BOSCC. Eighteen cases of BOSCC were classified histopathologically according to the degree of differentiation. Normal upper and lower eyelids and third eyelids collected from the right and left eyes of six healthy cattle aged 1-3 years, that had been presented for slaughter to abattoirs, served as controls. Transcription of genes encoding the angiogenic growth factors vascular endothelial growth factor-C (VEGF-C), basic fibroblast growth factor (bFGF), platelet-derived growth factor-C (PDGF-C) and platelet-derived growth factor receptor-α (PDGFR-α) was determined by quantitative real-time polymerase chain reaction (RT-PCR) in tissue obtained from paraffin wax blocks. Immunohistochemistry (IHC) was utilized to detect intensity of expression and tissue distribution of these growth factors. IHC results revealed that bFGF and PDGF-C were elevated significantly (P >0.05) and VEGF-C expression was decreased in BOSCC compared with healthy control tissue. PDGR-α expression was elevated; however, the difference, compared with control tissues, was not significant. RT-PCR results showed an inverse relationship to the results of IHC; where protein levels were elevated their corresponding mRNA levels were decreased or vice-versa. Angiogenic regulators therefore appear to play a role in the pathogenesis of BOSCC.

Periostin alters transcriptional profile in a rat model of isoproterenol-induced cardiotoxicity.

Periostin is an extracellular matrix protein from the fasciclin family that guides cellular trafficking and extracellular matrix organization. Periostin stimulates mature cardiomyocytes to reenter the cell cycle. The molecular mechanism behind such stimulation remains to be explored. A DNA microarray technology constituting 30,429 gene-level probe sets was utilized to investigate effects of recombinant murine periostin peptide on the gene expression pattern in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1) control group, (2) only periostin applied group, (3) ISO cardiotoxicity group, and (4) ISO + periostin group. The experiment was continued for 28 days, and rats were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that periostin significantly altered the expression of at least ±2-fold of 2474 genes in the ISO + periostin group compared to the ISO cardiotoxicity group of which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway analysis indicated that multiple pathway networks were affected by periostin, with predominant changes occurring in the expression of genes involved in oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-α NF-κB signaling pathways. These findings indicate that periostin alters gene expression profile in the ISO-induced myocardial injury and modulates local myocardial inflammation, possibly mitigating inflammation through TNF-α NF-κB signaling pathway along with a decreased Casp7 activity and apoptotic cell death.

Periostin normalizes levels of cardiac markers in rats with experimental isoproterenol cardiotoxicity.

BACKGROUND: Although the molecular mechanism of cardiac healing is not fully understood, myocardial infarction is one of the most usual diagnoses in hospitalized patients in industrialized nations while periostin has been recently suggested to have a potential in tissue repairing following myocardial ischemia. OBJECTIVES: To investigate the effects of periostin on the levels of selected cardiac parameters (cardiac troponin I and T, creatine kinase and creatine kinase isoenzyme-MB), antioxidant/lipid peroxidation parameters (superoxide dismutase, catalase, and malondialdehyde), hepatic parameters (alkaline phosphatase, lactate dehydrogenase, aspartate and alanine transaminases) as well as lipids (total cholesterol, triglyceride, high, low and very­low­density lipoproteins) in a rat model of isoproterenol---induced myocardial injury. METHODS: A total of 84 male rats were grouped into saline (Group I), periostin (Group II), isoproterenol (Group III) and isoproterenol+periostin (Group IV) groups (n = 21). Isoproterenol (85 mg/kg/day) and periostin groups were both injected intraperitoneally (1 µg/kg). RESULTS: Our results revealed that periostin has a positive reducing effect on the levels of analysed parameters especially on cardiac troponins and creatine kinases on days 7 and 28 of the recovery period following the induced experimental heart damage in rats. CONCLUSION: It is concluded that periostin could have a potential to increase the rate of myocardial recovery after myocardial infarction (Tab. 5, Ref. 28).

Levels of hormones and cytokines associated with growth in Honamli and native hair goats.

This study was designed to assess alterations of hormone and cytokine levels associated with growth period during puberty in Honamli goats which were identified as a new goat breed and had one of the highest meat production potential among the other goat breeds in Turkey. Honamli goats are originated from native hair goats, so parallel studies of sampling and analyzing were conducted also in native hair goats which have moderate meat production. Blood serum samples of Honamli (n=90) and native hair goats (n=90) were obtained from the pure herds in Korkuteli and Ka districts of Anatolia. Concentrations of growth hormone (GH), myostatin (MSTN), insulin-like growth factor (IGF), growth hormone releasing hormone (GHRH), growth hormone releasing peptide (GHRP), leptin, transforming growth factor-betal (TGF-ß1) and vascular endothelial cell growth factor (VEGF) levels were measured by ELISA in each breed in the age groups of 4, 8 and 12 months. The present results indicate interesting correlations among the age groups and all the examined hormone and cytokine parameters exhibited significant (P<0.05 and P<0.001) differences. The parameters investigated were usually begun to increase after 4 months of age in the both breeds and sexes. Therefore, this paper supported the view that the beginning of hormonal alterations of goats could occur at 4th month of age. The results reported here emphasize the primary role played by GH, MSTN, IGF-1, leptin, GHRH, GHRP, TGF-ßi and VEGF in the first year growth period of goats.

Phosphodiesterase type 5 inhibition attenuates cyclosporine A induced nephrotoxicity in mice.

We investigated the renal protective effects of phophodiesterase type 5 (PDE5) inhibitors in mice with cyclosporine A (CyA; a calcineurin phosphatase inhibitor) induced nephrotoxicity. Fifty male mice were divided into five groups of 10. Group 1 received no treatment, group 2 received only saline orally, group 3 received 30 mg/kg/day CyA by subcutaneous injection, group 4 received only 30 mg/kg/day vardenafil orally, and group 5 received 30 mg/kg/day CyA by subcutaneous injection and 30 mg/kg/day vardenafil orally. At 28 days, platelet-derived growth factor A (PDGF-A) and C (PDGF-C), transforming growth factor-beta 1 (TGF-ß1), cyclo-oxygenase 1 and 2 (COX-1 and COX-2), and P glycoprotein (Pgp) expression levels were measured in the renal tissues. In addition, expressions of COX-1 and COX-2 genes were determined using real-time PCR. PDE5 inhibitor administration ameliorated decreased PDGF-A and C, TGF-ß1, COX-1 and -2, and Pgp expression levels by modulation of cyclic guanosine monophosphate (cGMP) activity in kidneys. The relative expressions of COX-1 and COX-2 genes to GAPDH revealed that the maximum increase was obtained in the group treated with CyA and vardenafil for both COX-1 and COX-2 genes. Our study revealed that long term oral treatment with vardenafil protects kidneys from CyA induced nephrotoxicity. We showed that long term oral treatment with PDE5 prevents pathological kidney changes caused by CyA induced nephrotoxicity.

Levels of antioxidant substances, acute phase response and lipid peroxidation in the left and right abomasum displacement in cows.

The aim of the present study was to assess metabolic changes occurring in Holstein cows with left or right abomasal displacement. Total sialic acid (TSA) values of the left abomasal displacement (LDA) group were elevated significantly (p < 0.0001) as compared to the controls. In the LDA group, serum ceruloplasmin (CPN) and aspartate transaminase (AST) levels were increased significantly (p < 0.0001) as well. Compared to the control group, serum glutathione (GSH) level was decreased significantly in both LDA and right abomasal displacement (RDA) groups (p < 0.0001). Among the clinical examination parameters, rumen contraction rates were decreased in both LDA and RDA groups significantly (p < 0.0001). These results suggest that inflammatory and oxidative parameters might have taken part in the pathogenesis of abomasal displacement. In this regard, anti-cytokine and anti-oxidant therapies developed in human medicine may also play a potential therapeutic role in the fatty liver and abomasal displacement in cattle.

The effect of kefir on glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) levels in mice with colonic abnormal crypt formation (ACF) induced by azoxymethane (AOM).

In this study we investigated the effect of kefir on the levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) in the liver, stomach, spleen and colon of mice with colonic aberrant crypts formed by azoxymethane (AOM). Thirty 12 weeks old Swiss Albino mice averaging 31.5 g weight were used as experimental animals. The mice were separated into 3 groups. The first group was the control group, second group was the AOM and third group was the AOM+kefir group. We applied AOM to the second and third groups. Mice were fed ad libitum by laboratory rodent chow during the experiment period. Water was given to the first and second groups and third group received only kefir diluted with water (50%). AOM was injected subcutaneously to the second and third groups for 7 weeks (two times a week, 5 mg/kg). Six weeks after the final AOM treatment the animals were sacrificed and liver, stomach, spleen and colon samples were collected from all the groups. MDA level demonstrated an increase only in stomach for the third group (p < 0.001), while an elevation was observed for all of the four organs for the second group (spleen p < 0.001, liver p < 0.001, colon p < 0.01). GSH level showed an increase in the second group at stomach (p < 0.01) and colon (p < 0.001), while in the third group, a small increase was determined only at the colon (p < 0.05). NO level increased at all of the organs in the second group (spleen, liver, colon p < 0.001, stomach p < 0.05), but only at liver and colon in the third group 3 (p < 0.001). In conclusion these results showed that kefir plays an antioxidant role.