Vascular graft infection by Staphylococcus aureus: efficacy of cefazolin, teicoplanin and vancomycin prophylaxis protocols in a rat model.

OBJECTIVES: Prophylactic efficiencies of cefazolin, teicoplanin and vancomycin in a dacron graft infection model caused by methicillin-susceptible (MSSA) or -resistant Staphylococcus aureus (MRSA) were investigated. DESIGN: Prospective, randomized, controlled animal study. MATERIALS AND METHODS: Infections were established subcutaneously in the back of rats by implantation of Dacron prostheses followed by topical inoculation onto grafts of MSSA or MRSA. Experimental groups were as follows: Uncontaminated group (control), MSSA- or MRSA-contaminated and untreated groups, MSSA- or MRSA-contaminated groups treated with cefazolin, teicoplanin or vancomycin by one of three regimens (one day, two days, or three days regimen). Grafts were removed 7 days after the implantation and evaluated by using sonication and quantitative blood agar culture. RESULTS: Contaminated groups demonstrated graft infections. Cefazolin, teicoplanin and vancomycin profoundly prevented the graft infections in MSSA- or MRSA-contaminated groups. For each antibiotic regimen, the most effective prevention was achieved by the drugs given as three days regimen. For MSSA and MRSA, the order of the effectiveness was as follows: teicoplanin>vancomycin>cefazolin. CONCLUSION: As a prophylactic agent, teicoplanin seems to be more effective than vancomycin and cefazolin against vascular graft infections caused by MSSA and MRSA in rats.     

Effect of Seminal Plasma Fractions on Stallion Sperm Survival after Cooled Storage

This study aimed to evaluate stallion sperm survival after 24 h of cooled storage in the presence of seminal plasma (SP) derived from the sperm‐rich fractions (SRF) or sperm‐poor fractions(SPF) of the ejaculate, without SP, or in the presence of SP from other stallions. Ejaculates were collected from four stallions using an automated phantom, which separated the semen into five cups. Centrifuged and washed spermatozoa from cup 2 (SRF) were mixed with skim milk extender to a concentration of 100 × 10⁶ sperm/ml and then 1:1 (v/v) with SP from the stallion's own or another stallions’ second (SP‐SRF) or last cup (SP‐SPF). Skim milk extender (K) and skim milk extender supplemented with modified Tyrode's medium (KMT) were used as control treatments. After a 24‐h storage period in a transport container, spermatozoa were evaluated for motion characteristics and plasma membrane integrity by calcein acetoxymethyl (AM)/propidium iodide staining. The percentage of spermatozoa with intact plasma membranes after storage was lower in SP‐SRF than in SP‐SPF, and the highest in K (P < 0.05). Progressive motility (PMOT) was lower for sperm stored in SP‐SRF than for sperm stored in SP‐SPF (P < 0.05), but there was no significant difference in total motility (TMOT). Sperm stored in KMT (P < 0.05) registered the highest TMOT and PMOT percentages. Osmolarity was significantly higher and pH lower in K than in KMT or SP. Treatment with SP‐SPF from three stallions benefited the PMOT of sperm from one stallion. These preliminary findings suggest that SP from SRFs may be more harmful during storage than SP from SPFs. Removal of SP improves sperm survival in KMT extender, and exchanging SP between stallions seems to influence sperm survival.     

Clinical and immunological effects of azithromycin in Behçet''s disease

Background: The aim of this study was to evaluate the effects of azithromycin on mucocutaneous manifestations, oral health and immune response in Behçet's disease (BD). Methods: Eight BD patients with active mucocutaneous symptoms were treated with azithromycin for 4 weeks. Oral health, clinical manifestations and in vitro interleukin (IL)‐12, interferon (IFN)‐γ, IL‐10 and monocyte chemotactic protein (MCP)‐1 responses were evaluated before and after treatment. Results: The number of folliculitic lesions, healing time of oral ulcers and scores of plaque indexes (PLIs) were lower after azithromycin treatment (P < 0.05). Scores of PLIs correlated positively with the healing time of oral ulcers (P = 0.02). Although a trend towards increased stimulated IL‐10 responses with azithromycin was observed, no statistically significant difference was found. Stimulated and unstimulated MCP‐1, IFN‐γ and IL‐12 responses were similar before and after treatment (P > 0.05). Conclusion: Azithromycin was observed to be effective in decreasing folliculitic lesions and fastening the healing time of oral ulcers in BD.     

Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis

Oxidative stress is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). To assess whether there are relationships between oxidative stress and antioxidant enzymes in the development of NASH, we investigated oxidative stress by measuring serum malondialdehyde (MDA) and nitric oxide (NO) and antioxidant status by measuring serum glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD). The study included 18 patients (13 men, 5 women; mean age 42 yr) with biopsy proven NASH and 16 healthy volunteers (10 men, 6 women; mean age 38 yr). Serum levels of MDA, NO, GSH, GSH-Px, GR and SOD were determined by spectrophotometric methods. Serum levels (mean +/- SD) of MDA (6.7 +/- 1.6 vs 2.8 +/- 1.7 nmol/ml, p 0.0001), NO (135 +/- 28 vs 113 +/- 35 mmol/L, p 0.04), GSH (919 +/- 137 vs 770 +/- 128 mmol/L, p 0.003) were increased in patients with NASH vs controls. Serum levels of GSH-Px (1063 +/- 152 vs 1000 +/- 94 U/L) and GR (47 +/- 22 vs 40 +/- 21 U/L) were not singnificantly different in the patients vs controls. However, the serum level of SOD (1.24 +/- 0.32 vs 1.51 +/- 0.37 U/ml, p: 0.04) was significantly decreased. Impaired antioxidant defense mechanisms may be an important factor in the pathogenesis of NASH. Treatment approaches that affect the antioxidant enzymes may be beneficial in patients with NASH.     

Determination of serum bile acids routinely may prevent delay in diagnosis of total parenteral nutrition-induced cholestasis

BACKGROUND/PURPOSE: Early diagnosis of development of cholestasis is a current major problem for patients receiving total parenteral nutrition (TPN). Conventional tests for hepatic function such as serum transaminases and alkaline phosphatase do not often reflect simultaneously histopathologic changes of the liver. The aim of this study is to find out the relationships between conventional hepatic function tests, total serum bile acid concentrations (TSBA), and the histopathologic changes in the liver during TPN administration in rats. METHODS: Forty Albino rats were divided into four experimental groups, each consisting of 10 rats, as follows: control group (C), 0.9% saline for 14 days; T7 group, TPN for 7 days; T14 group, TPN for 14 days; T7O7 group, TPN for 7 days and then 0.9% saline for the next 7 days. All solutions were administered by infusion through intraperitoneal catheter in two equal doses. During the experiment, rats also maintained on rat chow and water ad libitum. Levels of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, and TSBA were measured. Liver was evaluated histopathologically by light microscope and then Morphological Cholestasis Index (MCI) was calculated. RESULTS: Cholestasis was present in all experimental groups except control. Levels of transaminases and alkaline phosphatase were not correlated with the histopathologic changes (P > .05), but TSBA concentrations were correlated with MCI in all groups (P< .01). TSBA concentrations and MCI in all groups also were correlated with the duration of exposure with TPN (P< .01). CONCLUSIONS: Measurement of TSBA seems to be more sensitive in early diagnosis of TPN-induced cholestasis. Therefore, periodical determination of TSBA during TPN administration can be done routinely.     

Antiangiogenic treatment with endostatin inhibits progression of AML in vivo.

Increased vessel density in the bone marrow of patients with acute myeloid leukemia as well as elevated expression of proangiogenic factors by leukemic cells implies a central role of angiogenesis in hematological malignancies. Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis that has shown therapeutic activity in solid tumors in various preclinical models. Using microencapsulation technology, we studied the therapeutic effect of ES in AML. While ES had no effect on proliferation of M1 murine leukemic cells in vitro, ES producing microbeads significantly inhibited growth of subcutaneous chloromas in SCID mice as compared to controls. In a leukemia model using M1 cells the concomitant treatment of mice with ES microbeads prolonged median survival significantly. Histological analysis revealed a decreased microvessel density and a reduced number of CD31-positive single cells, putatively endothelial progenitor cells, in the bone marrow of treated animals. Taken together, ES has inhibitory effects on neo-angiogenesis in the bone marrow and on progression of leukemia in vivo. These experiments suggest a possible therapeutic role of antiangiogenic gene therapy with ES in AML.     

Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats

Carvacrol is a dietary polyphenol from Lamiaceae plants that has been shown to possess a wide range of biological activities including antioxidant and antitumor effects. This study aimed to investigate its anti-inflammatory and antioxidant effects on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Forty-nine rats were randomly assigned to four treatment and three control groups. Over 60 days, MNNG (200 mg/kg BW) was orally applied to animals of groups 1–5 while the rats in groups 2–5 also received different doses of carvacrol (10, 25, 50, and 100 mg/kg BW, respectively) until the end of the experiment. Group 6 rats were treated with 100 mg/kg BW carvacrol and no MNNG whereas group 7 was the control group without any treatment. After the euthanasia of all rats, the inflammatory cytokines and oxidative stress parameters were assessed in the blood and tissues. The expression of caspase 9, Bax, and Bcl-2 proteins in the stomach tissues were investigated through histopathological examinations. Statistically significant differences were observed in the body weight, oxidative stress, and inflammation parameters of groups 1 to 6 compared to group 7 (p ≤ 0.001). Animals in MNNG groups 2 and 3 treated with the low dose carvacrol (10 and 25 mg/kg BW) showed significantly reduced oxidative stress, inflammation, and apoptotic effect compared to animals of the MNNG groups receiving increased doses of carvacrol (50 and 100 mg/kg BW) or no carvacrol. Rats exposed to MNNG exhibited gastric cancer cells in several areas. In the MNNG group receiving 100 mg/kg BW carvacrol, the inflammatory cell infiltration was observed in gastric mucosal and submucosal areas whereas MNNG rats supplemented with 10 and 25 mg/kg BW carvacrol showed no pathological alterations of the gastric cells. The results of this study indicate that significant antioxidant and anti-inflammatory effects induced by carvacrol at doses of 10 and 25 mg/kg BW interfered with gastric carcinogenesis induced by MNNG in Wistar rats as well as provide hepatoprotection. However, high doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis.