Clinical evaluation of antiviral combination treatment in cats with feline herpesvirus-1 infection.

Feline herpesvirus-1 (FHV-1) can cause lifelong problems such as rhinotracheitis and ocular disease due to latency and reactivation in affected cats. The particular effects of antiviral drugs have been separately investigated in previous studies for decades and little is known about the combination treatment in active FHV-1 infection. Therefore, we aimed to evaluate the effects of antiviral combination on clinical effectiveness in cats with naturally occurring FHV-1 infection. 28 cats suffering from clinical signs of sneezing, nasal congestion, conjunctivitis, and eye/nose discharge were involved in this study following FHV-1 DNA detection by PCR assay in oculo-oropharyngeal samples. The treatment protocol was as follows: oral famciclovir and L-lysine, ophthalmic acyclovir, and subcutaneous amoxicillin plus clavulanic acid. The symptoms improved each day and total recovery success rate was 80% reduction in clinical scores at the end of the treatment on day 10 (p<0.001). Additionally, PCR was found to be negative for FHV-1 DNA in 82.1% of the samples after the treatment. There were mild decreases in neutrophil and monocyte counts (p>0.05). The arginine to lysine ratio decreased in favour of lysine (p<0.01). As a result, the antiviral combination treatment with famciclovir, L-lysine and ophthalmic acyclovir, and antibacterial drug appears to be clinically effective for the treatment of naturally occurring active FHV-1 infection in cats. In addition, any adverse clinical effect has not been determined associated with the antiviral combination during the study.

Biochemical and histopathologic analysis of the effects of periodontitis on left ventricular heart tissues of rats.

BACKGROUND AND OBJECTIVE: Current epidemiological works have suggested that chronic infections, such as periodontitis, are associated with an increased risk of cardiovascular diseases, including hypertrophy and heart failure. However, mechanisms behind the association are not known. The aim of this study was to evaluate the effects of periodontitis on the serum lipid levels, inflammatory marker levels and left ventricular heart muscle tissues of rats. MATERIAL AND METHODS: Eighteen male Sprague-Dawley rats were randomly divided into two groups: control (without ligature) and experimental periodontitis (EP; ligatured). Periodontitis was induced by placing ligatures (3.0 silk) at a submarginal position of the lower first molar teeth for 5 wk. Serum samples were collected for biochemical studies (C-reactive protein, interleukin-1ß, tumor necrosis factor-α and serum lipids), after which the rats were killed and heart tissue samples were obtained for histopathological and immunological studies (nuclear factor kappa B and ß-myosin heavy chain). RESULTS: Significant increases in C-reactive protein and interleukin-1ß levels and no statistically significant increase in tumor necrosis factor-α level were observed in the EP group compared to the control group. In addition, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels were significantly higher in the EP group. Stereological and immunological findings showed that the number of nuclear factor kappa B-p65- and ß-myosin heavy chain-positive cardiomyocytes increased significantly in the left ventricular tissue samples of the rats with periodontitis. CONCLUSION: Early chronic phase effects of periodontitis on heart tissue are in the form of degenerative and hypotrophic changes. Prolonging the exposure to systemic inflammatory stress may increase the risk of occurrence of hypertrophic changes.

Melatonin prevents radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis.

BACKGROUND AND OBJECTIVE: The aim of this study was to analyze the biochemical and histochemical effects of radiation therapy and protective melatonin administration on periodontal tissues in rats with experimental periodontitis. MATERIAL AND METHODS: Sixty male Sprague Dawley rats were divided into six groups, as follows: control; experimental periodontitis (Ped); radiotherapy administration (Rt); experimental periodontitis and exposure to irradiation (Ped-Rt); radiotherapy and protective melatonin administration (Rt-Mel); and periodontitis, radiation therapy and protective melatonin administration (Ped-Rt-Mel). The rats were killed at the end of the experimental procedure, and the oxidative stress level and periodontal destruction were compared among the groups. RESULTS: The oxidative stress index and the levels of 8-hydroxy-2'-deoxyguanosine, malondialdehyde and C-terminal telopeptide of type I collagen were found to be significantly higher in the Ped-Rt group compared with the Ped group (p < 0.05), and the levels were lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). Alveolar bone destruction and attachment level were also significantly lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). CONCLUSION: It was found that radiotherapy increased oxidative stress, the periodontal attachment level and alveolar bone loss, and protective melatonin administration significantly reduced the oxidative parameters and prevented periodontal damage in irradiated rats with experimental periodontitis. Further research is needed regarding the use of systemic melatonin administration before radiation therapy.

Influence of experimental periodontitis on cardiac oxidative stress in rats: a biochemical and histomorphometric study.

BACKGROUND AND OBJECTIVE: The role of oxidative stress in the process of cardiac remodeling, hypertrophy and heart failure is a current topic. The purpose of this experimental study was to investigate the influences of periodontitis on levels of cardiac oxidative stress. MATERIAL AND METHODS: Twenty rats were separated into two groups: control and experimental periodontitis (EP). Periodontitis was induced by placing a 3.0 silk suture in the cervix of the left and right mandibular first molar teeth for 5 wk. At the end of the experiment, the animals were killed and blood samples and mandibular and ventricular cardiac tissue samples were collected. Levels of alveolar bone loss were determined using measurements performed on histological slices and radiographies. Left ventricular tissue 8-hydroxy-2'-deoxyguanosine, malonylaldehyde, glutathione peroxidase, total oxidant status, total antioxidant status (TAS) levels and serum paraoxonase-1 activity were evaluated biochemically. RESULTS: Measurements performed on the histological slices and radiographies demonstrated that applying the ligature caused obvious alveolar bone loss. Oxidative damage markers (malonylaldehyde, 8-hydroxy-2'-deoxyguanosine, oxidative stress index: total oxidant status/TAS) were significantly higher, and antioxidant markers (glutathione peroxidase, TAS) were statistically insignificantly higher, in the hearts of rats with EP when compared to the controls. In addition, reduced serum paraoxonase-1 activity was also detected in the EP group. CONCLUSION: The pronounced increase in cardiac oxidative stress caused by periodontitis was due to an excessive increase in the production of reactive oxygen species, rather than due to decreased antioxidant capacity. The results indicate that periodontitis-related cardiac oxidative stress might be one of the mechanisms that contribute to the pathological process that leads to heart failure.

Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan.

Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß), and also proliferation of monocyte chemotactic protein. In the present study, the potential effects of melatonin on proinflammatory cytokines, hematological values, and lymphoid tissues were investigated in diabetic rats. In the study, 36 male rats were randomly divided into 4 groups as follows: Control, Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was given to the Control and DM groups; melatonin was administered to the Mel and DM-Mel groups intraperitoneally. At the end of the study, all animals were sacrificed by drawing the blood from their hearts under deep anesthesia. Samples of the spleen, thymus, and lymph nodes were fixed in 10% formaldehyde for histologic analysis. Increases in proinflammatory serum cytokine concentrations, mast cells, and total white blood cell counts as well as tissue destruction in the lymphoid organs were determined in the DM group via biochemical, hematological, and histologic analyses. However, the findings for the DM-Mel group revealed decreases in serum IL-1ß concentration and mast cell densities, and destructions in lymphoid tissues by the melatonin administration. The present study suggests that melatonin treatment may control immune system regulation and inhibit the production of proinflammatory cytokines and tissue mast cell accumulation by preventing the destruction of lymphoid organs in the diabetic process.

Endothelin receptor inhibition with bosentan delays onset of liver injury in streptozotocin-induced diabetic condition.

BACKGROUND: This study was designed to investigate the protective effects of bosentan an orally active non-peptide mixed ETA/ETB receptor antagonist, on liver injury in streptozotocin-induced diabetic rats. METHODS: 24 Albino-Wistar rats were randomly divided into 4 groups: healthy (Group 1), diabetic (Group 2) (60 mg/kg of streptozotocin i.p.), diabetic treated with bosentan 50 mg/kg (Group 3) and diabetic treated with bosentan 100 mg/kg (Group 4). The treatment of bosentan was initiated after streptozocin injection and continued for 60 days. RESULTS: Liver from diabetic rats showed significant increase in malondialdehyde (MDA) level and significant decrease in glutathione (GSH), and superoxide dismutase (SOD) activity. Endothelin (ET-1), tumor necrosis factor (TNF-α) and transforming growth factor beta (TGF-ß) gene expression significantly increased in the diabetic groups in the rat liver tissue. Bosentan treatment showed a significant up-regulatory effect on ET-1, TNF-α and TGF-ß mRNA expression. Results from histopathological evaluation of the liver were in accordance with our biochemical and molecular results. CONCLUSIONS: These data provide clear evidence that bosentan treatment is associated with promising hepatoprotective effect against diabetes-induced liver damage via reduction of cell inflammation and oxidative damage. These data suggest that ET receptors may be an important actor in diabetes-related liver damage, and blockage of these receptors may become a target for preventing diabetic complications in the future.