Nese Lortlar

Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9

OBJECTIVE We sought to test if metformin could regress endometriotic explants in rats. STUDY DESIGN After inducing endometriotic implants and randomization of female Wistar albino rats, they were given 25 and 50 mg/kg/day of oral metformin in group A (n = 9) and B (n = 8), respectively, for 28 days. Group C (n = 9) was given saline as placebo. RESULTS Mean volume, weight, and histologic score of implants in groups A (P < .01, P < .05, and P < .05, respectively) and B (P < .01, P < .05, and P < .05, respectively) were significantly lower than in group C. The activity of superoxide dismutase and tissue inhibitor of metalloproteinase-2 staining in groups A (P < .05 and P < .01, respectively) and B (P < .01 and P < .01, respectively) was significantly higher than in the control group. Moreover, there were more significant reductions in implant levels of vascular endothelial growth factor and matrix metalloproteinase-9 in groups A (both P < .001) and B (both P < .001) than in group C. CONCLUSION Metformin causes regression of endometriotic implants in rats.

Environmental tobacco smoke exposure during intrauterine period promotes granulosa cell apoptosis: a prospective, randomized study

Objective: To evaluate the intrauterine effect of cigarette smoke on cell death and DNA damage in follicular cells of fetal ovarian tissue. Methods: A prospective, randomized study was conducted with 25 female wistar-albino rats. The rats were randomized to be exposed either to cigarette smoke or to room air, initiating from proestrous period and during pregnancy. Newborn female rats were categorized as Group 1 (n = 24) that had been exposed to cigarette smoke during intrauterine life and Group 2 (n = 7) that had been exposed to room air during intrauterine life. Bilateral ooferectomies were performed on the 2nd week of their life. TUNEL (in-situ Terminal Deoxynucleotidyl-Transferase Mediated dUTP-Nick-End Labeling) immunofluorescent staining and immunohistochemical analyses with caspase-3 were used for detection of DNA damage and apoptosis. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORE). Secondary outcomes were ovarian follicle counts and birth weights of newborn rats. Results: There was a significant increase of HSCORE and apoptotic index in Group 1. Increased immunofluorescent staining; evaluating DNA damage, with TUNEL method was observed in granulosa cells in Group 1. Conclusions: Intrauterine exposure to cigarette smoke diminishes ovarian reserve of female offspring, raising the concern about the generational impact of maternal smoking on ovarian function in the human.

Caspase-3 and VEGF immunopositivity in seminiferous tubule germ cells in cases of obstructive and non-obstructive azoospermia in smokers versus non-smokers

PurposeTo investigate immunostaining pattern of caspase-3, an apoptosis marker, and vascular endothelial growth factor (VEGF), an hypoxia marker in testis biopsy specimens collected either from smoking or non-smoking patients with azoospermia.MethodsTestis biopsy specimens were obtained from thirty seven non-smoker and thirty eight smoker patients. Using immunochemistry technique, caspase-3 and VEGF were evaluated in all intratubular spermatogenic and interstitial Leydig cells.Result(s)Caspase-3 expression was significantly increased in germ cells in maturation arrest specimens in smoker azoospermic patients. No statistically significant difference was present between smokers and non-smokers for caspase-3 expression in Sertoli cell. However, the VEGF immunopositive Leydig cells were statistically higher in smokers. There were no differences between groups in terms of germ cell immunopositivity.ConclusionOur results support the hypothesis that increased apoptosis contributes significantly to impaired spermatogenesis. We conjecture that germ cell apoptosis may be augmented by hypoxic microenvironments and environmental toxicants in smoking azoospermic men.

Effect of Preoperative Subcutaneous Platelet-Rich Plasma and Fibrin Glue Application on Skin Flap Survival

BackgroundThe aim of this study was to compare the effects of preoperative subcutaneous platelet-rich plasma and fibrin glue administration on skin flap survival.MethodsOne week before surgery; saline, platelet-rich plasma, fibrin glue, and thrombin solutions were applied under rat skin flap areas in Groups I, II, III, and IV, respectively. Unipedicled epigastric flaps were elevated in the first three groups but could not be elevated in Group IV because of preoperative abdominal skin necrosis. Necrotic area measurements, microangiography, and histological and immunohistochemical evaluations were performed.ResultsPlatelet-rich plasma reduced the percentage of necrotic area when compared to other groups. Histologically and microangiographically an increased number of arterioles were observed in the platelet-rich plasma group. Thrombin (when used alone) caused abdominal skin necrosis. Increased expression of VEGF and PDGF was found in all platelet-rich plasma-treated flaps. There was no significant difference between groups with respect to TGF-β3 staining intensity.ConclusionIn this study preoperative administration of platelet-rich plasma mimicked the pharmacological delay effect and enhanced flap survival. Individual use of thrombin was found to be unsuitable in flap surgery.Level of Evidence IThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) immunoreactivities in rat ovaries and uterine tubes after tubal ligation: a controlled immunohistochemical study

Objective To evaluate the effects of tubal ligation on ovarian and tubal tissues by means of immunohistochemical evaluation of two hypoxia related mediators: vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). Design Fourteen Sprague-Dawley female rats were divided into two groups: a tubal ligation (Pomeroy technique) was carried out on rats in group 1 (n = 7) whereas those in group 2 served as controls (n = 7). Salpingo-oophorectomy was performed in group 1 during the second oestrous period following tubal ligation. Rats in group 2 were submitted to a salpingo-oophorectomy, as well. VEGF and iNOS immunoreactivities in ovarian and tubal tissues were evaluated by means of immunohistochemistry. Immunohistochemical scores and number of antral follicles were compared. Results In the ovary, VEGF immunoreactivity was significantly more intense in the granulosa (p = 0.002) and the theca cells (p = 0.001) of rats in group 1 but, in ovarian medulla (p = 0.259) and germinal epithelium (p = 0.209), it was not significantly different from that of rats in group 2. The iNOS immunoreactivity in ovarian granulosa cells (p = 0.073) and germinal epithelial cells (p = 0.805) did not differ between the two groups. The cytoplasmic VEGF (p = 0.001) and iNOS (p = 0.017) immunoreactivities in the uterine tube, were significantly more intense in group 1. However, VEGF immunoreactivity in the lamina propria of the uterine tube (p = 0.209) was of similar intensity in both groups. Conclusion Tubal ligation may lead to supraphysiological hypoxia as evidenced by increased VEGF and iNOS immunoreactivities in ovarian and tubal tissues.

Adrenomedullin attenuates aortic cross-clamping–induced myocardial injury in rats

BACKGROUND In this study we investigate the effects of adrenomedullin on myocardial injury after ischemia-reperfusion (I/R) after abdominal aortic surgery. METHODS Thirty-two Wistar rats were randomized into 4 groups (n = 8) as follows: control group (sham laparotomy), the aortic I/R group, aortic I/R plus adrenomedullin group (underwent aortic I/R periods, and received a bolus intravenous injection of .05 μg/kg/min adrenomedullin), and the control plus adrenomedullin group. RESULTS Biochemical analysis showed that aortic I/R significantly increased (P < .05) the plasma levels of troponin-I and tumor necrosis factor-α, and the myocardial tissue levels of malondialdehyde, superoxide dismutase, catalase, and angiotensin II, whereas aortic I/R plus adrenomedullin significantly decreased these same factors (P < .05). Aortic I/R significantly increased (P < .05) myocardial tissue levels of nitric oxide whereas aortic I/R plus adrenomedullin significantly increased the same factor (P < .05). CONCLUSIONS These results indicate that adrenomedullin has protective effects against myocardial injury induced by abdominal aortic I/R in rats.

Caspase-9 expression is increased in endothelial cells of active Behçet's disease patients

Background  Behçets disease is a multisystem disease of unknown etiology. Caspase‐9 is responsible for initiating the caspase activation cascade during apoptosis. The aim of this study was to examine caspase‐9 expression in both endothelial and perivascular infiltrates of patients with active Behçets disease.

Effect of intraoperative platelet-rich plasma and fibrin glue application on skin flap survival.

Abstract The experiment was designed to compare the effect of intraoperative platelet-rich plasma (PRP) and fibrin glue application on skin flap survival. In this study, bilateral epigastric flaps were elevated in 24 rats. The right-side flaps were used as the control of the left-side flaps. Platelet-rich plasma, fibrin glue, and thrombin had been applied under the flap sites in groups 1, 2, and 3, respectively. Five days later, all flap pedicles were ligated. Necrotic area measurements, microangiography, and histologic and immunohistochemical evaluations were performed to compare the groups. Platelet-rich plasma reduced necrotic area percentages as compared with other groups. Histologically and microangiographically increased number of arterioles were observed in PRP groups. Thrombin when used alone increased flap necrosis. Vascular endothelial growth factor, platelet-derived growth factor, and transforming growth factor &bgr;3 primary antibody staining showed increased neovascularization and reepithelialization in all PRP-applied flaps. This study demonstrated that PRP, when applied intraoperatively under the skin flap, may enhance flap survival. Thrombin used alone was found to be unsuitable in flap surgery.

The protective effect of adrenomedullin on renal injury, in a model of abdominal aorta cross-clamping.

Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The aim of this study was to examine the effect of adrenomedullin (AM) on kidney injury induced by infrarenal abdominal aortic IR in rats. Thirty-two Wistar Albino rats were randomized into four groups (eight per group) as follows: Control group, IR group (120-minute ischemia and 120-minute reperfusion), IR + AM group (a bolus intravenously of 0.05 µg/kg/min AM), and control + AM group. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Immunohistological evaluation of the rat kidney tissues was also done. IR significantly increased (p < 0.05 vs control group) and AM significantly decreased (p < 0.05 vs. IR group) all of the biochemical parameters. Immunohistological evaluation showed that AM attenuated morphological changes as apoptosis associated with kidney injury. The results of this study indicate that AM attenuates both biochemically and immunohistopathologically kidney injury induced by aortic IR in rats.

Feasibility of demineralized bone matrix for craniomaxillofacial contour restoration.

Demineralized bone matrix (DBM) could be a good alternative for craniomaxillofacial contour restoration, especially in perialar, malar, temporal, and frontal regions. In this study, the histologic behavior of DBM was investigated in different tissue planes to determine its proper application plane for restoration of craniomaxillofacial contour deformities and defects. Forty Wistar rats were divided into 6 groups: (1) 0.3 mL of 0.9% saline was injected into the subperiosteal plane of the cranium, (2) 0.3 mL of DBM was implanted into the subperiosteal plane of the cranium, (3) 0.3 mL of 0.9% saline was injected into the subdermal plane on the left inguinal region, (4) 0.3 mL of DBM was implanted into the subdermal plane on the right inguinal region, (5) 0.3 mL of 0.9% saline was injected between the left external and internal oblique muscles, and (6) 0.3 mL of DBM was implanted between the right external and internal oblique muscles. At the 8th week half of the rats and at 16th week the remaining rats were killed in each group, and tissue samples were harvested. Histological and immunohistochemical evaluation revealed new bone tissue and bone marrow formation in all planes that DBM was given. Demineralized bone matrix can provide satisfactory results in craniomaxillofacial contour deformities including forehead, temporal, and malar augmentations, as well as mental and perialar augmentations and saddle nose corrections, with supraperiosteal or deep subcutaneous applications. However, superficial applications must be avoided because of the possibility of palpation, because it induces hard bone tissue formation in all tissue planes.