Barbaros Sahin

Alteration of drug metabolizing enzymes in sulphite oxidase deficiency

The aim of this study was to investigate the possible effects of sulphite oxidase (SOX, E.C. 1.8.3.1) deficiency on xenobiotic metabolism. For this purpose, SOX deficiency was produced in rats by the administration of a low molybdenum diet with concurrent addition of 200 ppm tungsten to their drinking water. First, hepatic SOX activity in deficient groups was measured to confirm SOX deficiency. Then, aminopyrine N-demethylase, aniline 4-hydroxylase, aromatase, caffeine N-demethylase, cytochrome b5 reductase, erythromycin N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase, N-nitrosodimethylamine N-demethylase and penthoxyresorufin O-deethylase activities were determined to follow changes in the activity of drug metabolizing enzymes in SOX-deficient rats. Our results clearly demonstrated that SOX deficiency significantly elevated A4H, caffeine N-demethylase, erythromycin N-demethylase and N-nitrosodimethylamine N-demethylase activities while decreasing ethoxyresorufin O-deethylase and aromatase activities. These alterations in drug metabolizing enzymes can contribute to the varying susceptibility and response of sulphite-sensitive individuals to different drugs and/or therapeutics used for treatments.

Linezolid compared with vancomycin for the prevention of methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis vascular graft infection in rats: A randomized, controlled, experimental study

BACKGROUND Graft infections are severe complications of vascular surgery that may result in amputation or mortality. Staphylococci are the most frequent cause of vascular graft infections. OBJECTIVE In this study we assessed the prophylactic efficacy of linezolid in comparison with vancomycin in preventing prosthetic vascular graft infection due to methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). METHODS This randomized, controlled, experimental study using healthy adult (aged >5 months) male Wistar rats was conducted in the research laboratory of the Pamukkale University, Denizli, Turkey. The study consisted of an uncontaminated control group and 3 groups for both staphylococcal strains: a contaminated group that did not receive any antibiotic prophylaxis; a contaminated group that received preoperative intraperitoneal (IP) prophylaxis with vancomycin; and a contaminated group that received preoperative IP prophylaxis with linezolid. All rats received a vascular Dacron graft placed inside a subcutaneous pocket created on the right side of the median line. Sterile saline solution (1 mL), to which MRSA or MRSE at a concentration of 2 × 10(7) colony-forming units per milliliter had been added, was inoculated onto the graft surface using a tuberculin syringe to fill the pocket. The grafts were explanted 7 days after implantation and assessed by quantitative culture. RESULTS Seventy rats (mean [SD]weight, 323.7 [17.9]g; mean [SD]age, 5.98 [0.64] months) were evenly divided between the 7 groups. Statistical analysis of the quantitative graft culture suggested that both vancomycin and linezolid were effective in significantly inhibiting bacterial growth when compared with the untreated contaminated groups (all, P < 0.001). However, a statistically significant difference was not observed between the bacteria count in the vancomycin and linezolid prophylaxis groups. When a comparison was made between the bacterial growth in the contaminated control groups, MRSA had significantly greater affinity to the Dacron prostheses than MRSE (all, P < 0.001). CONCLUSION Our study found that linezolid was as effective as vancomycin in suppressing colony counts in MRSA- or MRSE-infected vascular Dacron grafts in rats.

Effectiveness of Palatal Mucosa Graft in Surgical Treatment of Sub-Glottic Stenosis

Objectives Mucosal free grafts may be successfully applied in many surgical interventions. This study aims at investigating the feasibility of palatal mucosa graft in sub-glottic field in an animal model. Methods This randomized prospective controlled study was conducted with an animal model. Sub-glottic inflammation was created in 15 adult rabbits in each group and sub-glottic stenosis surgery was applied thereafter. The rabbits in group 1 (control group) underwent segmental resection, partial cricoidectomy, and trachea-thyroid cartilage anastomosis; the rabbits in group 2 underwent segmental resection, cricoplasty, and crico-tracheal anastomosis using free buccal mucosa graft; and the rabbits in group 3 underwent segmental resection, cricoplasty, and crico-tracheal anastomosis using free palatal mucosa graft. Re-stenosis was evaluated after 42 days. Results The percentages of stenosis were 27%±20%, 40%±20%, and 34%±23% for group 1, 2, and 3, respectively and the difference was not statistically significant (P=0.29). Intensive and tight fibrosis was observed in 2 rabbits (13%) in group 1, in 5 rabbits (33%) in group 2, and in 3 rabbits (20%) in group 3. There was not a statistically significant difference between groups (P=0.41). Excessive inflammation was observed in 3 rabbits (20%) in group 1, in 7 rabbits (47%) in group 2, and 3 rabbits (20%) in group 3. There was no a statistically significant difference between groups although inflammation rate was higher in the rabbits which underwent buccal mucosa graft (P=0.18). Conclusion The surgical treatments applied with free mucosa graft reduced anastomosis tension through enabling anastomosis to the distal of cricoid instead of thyroid cartilage. Free palatal mucosa grafts may be used in sub-glottic field, one of the most challenging fields of trachea surgery, due to ease of application and rapid vascularization.

Effects of menopause, diabetes mellitus and steroid use on type I mesh-induced tissue reaction in a rat model.

OBJECTIVE To evaluate the effects of menopause, use of steroids, diabetes mellitus, and site of implantation on the tissue response to type I polypropylene mesh used in pelvic reconstructive surgery. STUDY DESIGN Forty mature female albino rats were used in the study. Inflammatory reaction and mesh-tissue detachment strength were studied in 4 different animal models; control (GI), menopause (GII), steroid+menopause (GIII), and diabetes mellitus+menopause (GIV) groups. Two pieces of 1cm×1cm type I macro porous polypropylene monofilament mesh were fixed over rectus abdominis muscle on both sides of the midline, and 0.5cm×0.5cm in size was placed into paravaginal area. Nine weeks later, implanted sling materials in the vaginal region and the right abdominal side were harvested with surrounding tissue for histopathologic examination, whereas the left sided meshes were used for the mechanical testing of detachment strength. RESULTS The mean detachment strengths in groups were, 595±274g for GI, 410±161g for GII, 610±202g for GIII, and 457±250g for GIV (p>0.008). Inflammatory process was more intense in menopause and DM+menopause groups for both abdominal and vaginal tissues (p<0.008). There was no difference between control and steroid+menopause groups, and DM+menopause and menopause groups (p>0.008). Comparison of tissue reaction caused by meshes in abdominal and vaginal area showed more intense granulocyte infiltration in abdominal region whereas more prominent inflammation and necrosis in the vaginal site (p<0.05). CONCLUSION The abdominal and vaginal region show differences in tissue reaction to type I mesh, and menopause was the most determining factor on the intensity of mesh induced inflammatory response.