Berrin Avci

Comparative evaluation of apoptotic activity in photoreceptor cells after intravitreal injection of bevacizumab and pegaptanib sodium in rabbits.

PURPOSE To evaluate quantitatively the apoptotic activity after intravitreal injections of pegaptanib sodium and bevacizumab in the rabbit retina. METHODS Different doses of bevacizumab (0.25, 0.625, 1.25, and 2.5 mg) and pegaptanib sodium (0.15, 0.3, and 0.6 mg) were injected intravitreally in 48 rabbits. The eyes were enucleated at different times for early studies at day 14 and for late studies at 3 months after a single injection or at 3 months, with 1 injection in each of the 3 months (day 90). The time course and dose-response of photoreceptor cells in the rabbit retina after intravitreal injection of bevacizumab or pegaptanib sodium were examined by histologic analysis with hematoxylin and eosin (H&E) staining, caspase-3 and -9 immunostaining, and in situ terminal-deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments of paraffin-embedded sections. RESULTS No sign of retinal toxicity was seen in H&E stained histologic sections of eyes that had received bevacizumab or pegaptanib sodium. Nuclear DNA fragmentation in the outer retinal layers shown by the TUNEL method was evident in the high-dose groups (55.3% with 1.25 mg and 64.5% with 2.5 mg bevacizumab, and 48.5% with 0.6 mg pegaptanib sodium) at 14 days and also in the clinical dose groups (49.8% with three injections [1 each month] of 0.625 mg bevacizumab and 44.3% with 0.15 mg pegaptanib sodium) at 90 days. The ratios of TUNEL-positive cells in physiologic saline and the sham-control groups were 32.3% and 21%, respectively. CONCLUSIONS Intravitreal injection of bevacizumab and pegaptanib sodium caused a significant increase in apoptotic activity in rabbit photoreceptor cells. However, although bevacizumab caused increasing apoptotic activity at higher doses, similar dose-dependent adverse effects were not evident for pegaptanib sodium.

Pars plana vitrectomy and removal of the internal limiting membrane in the treatment of chronic macular oedema

BackgroundTo evaluate the results of pars plana vitrectomy with peeling of the internal limiting membrane (ILM) in eyes with chronic macular oedema.MethodsPPV with indocyanine green (ICG) assisted peeling of the ILM was performed in 33 eyes with diabetic (21 eyes) or non-diabetic (12 eyes) macular oedema. Postoperatively, resolution of macular oedema, improvement of visual acuity (VA) and complications were documented. The peeled membranes were submitted for light and transmission electron microscopic evaluation.ResultsThe mean follow-up time was 12.2 months. The macular oedema decreased or was resolved in 17 (81%) eyes in the diabetic group and in 11 (92%) eyes in the non-diabetic group. VA improved by at least 2 lines in 11 (52%) eyes in the diabetic group and in 7 (58%) eyes in the non-diabetic group. The difference between visual acuity improvements of the two groups was not statistically significant (P>0.05). However, in the diabetic group the difference of visual improvement between cystoid and diffuse type of macular oedema eyes was statistically significant (14% versus 71%, P=0.02). Light and transmission electron microscopy showed the presence of ILM in all specimens. During the follow-up period no recurrence of macular oedema or epiretinal membrane formation was observed.ConclusionPars plana vitrectomy with peeling of the ILM and epiretinal membrane leads to the resolution of macular oedema in the majority of eyes. This however, is not always associated with VA improvement. In diabetic eyes, cystoid type of macular oedema appears to be a poor prognostic factor for improved VA.

The effects of caspofungin and voriconazole in experimental Candida endophthalmitis.

Purpose: To evaluate the efficacy of newly developed antifungal agents caspofungin and voriconazole in Candida albicans endophthalmitis in rabbit eyes. Methods: Thirty New Zealand white rabbits were divided into four treatment groups and one control group. One eye of each rabbit was infected by inoculation of 1 × 104 CFU/ml of C. albicans. Seventy-two hours after the inoculation, caspofungin 100 μg/0.1 ml in group 1 (n = 6), voriconazole 50 μg/0.1 ml in group 2 (n = 6), amphotericin B 10 μg/0.1 ml in group 3 (n = 6), itraconazole 10 μg/0.1 ml in group 4 (n = 6), and 0.1 ml NaCl 0.9% in control group (n = 6) were injected into the vitreous cavity. Clinical and histopathologic examination scores and microbiological analysis of vitreous aspirates were compared. Results: There was statistically significant difference in the clinical scores, histopathologic scores, and mean CFU/ml between the treatment and control groups (p < 0.05). In caspofungin and voriconazole groups, histopathologic scores and mean CFU were lower than other treatment groups and control group. Conclusions: Intravitreal injection of caspofungin and voriconazole was effective against C. albicans endophthalmitis in this experimental rabbit model.

Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury

OBJECTIVE Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of trimetazidine (TMZ) and N-acetylcysteine (NAC), used alone or in combination, on oxidative stress, infarct size, and ischemia-reperfusion (IR)-induced cardiomyocyte apoptosis in a rat model of myocardial IR. METHODS AND RESULTS Myocardial IR was established by ligating an area under the left main coronary artery for 30 min followed by 3 h of reperfusion. Saline (1 ml/kg), NAC (50, 150 mg/kg), or TMZ (3, 5 mg/kg) was intravenously injected during the middle of the ischemic period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the S100b level, which is a marker of inflammation, and the malondialdehyde (MDA) level, which is a marker of oxidative stress. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by caspase-3 immunostaining and a TUNEL assay. TMZ and NAC, either alone or in combination, significantly reduced serum MDA levels, infarct area and apoptotic activity compared to those observed in saline group. Interestingly, the infarct area was more smaller in TMZ (3 and 5 mg/kg) injected groups (9.72 ± 1.3% and 9.96 ± 2.3%) than those observed in NAC (50 and 150 mg/kg) (16.1 ± 2.5% and 19.1 ± 2.14%) or TMZ (5 mg/kg)- NAC (150 mg/kg) combination groups (16.9 ± 1.6%). However, the apoptotic activity was reduced more significantly in the combination of TMZ (5 mg/kg)-NAC (50 mg/kg) compared to TMZ-only group. Neither TMZ or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and S100B levels. CONCLUSION Intravenous NAC and TMZ administration decreased oxidative stress, infarct area and apoptotic activity in a rat model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, TMZ treatment was more successful in reducing the infarct area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of TMZ and NAC may help to reduce IR injury.

A new surgical approach for indocyanine green-assisted internal limiting membrane peeling.

BACKGROUND AND OBJECTIVE The efficiency of indocyanine green (ICG) dye in the removal of the internal limiting membrane (ILM) with a fluid needle using passive aspiration was evaluated. PATIENTS AND METHODS Eighteen consecutive patients with diffuse diabetic macular edema were studied. After vitrectomy and total fluid-air exchange, 0.1 mL of ICG solution 0.25% was left in the macular area for 1 minute. Then the macular ILM was peeled with a specially designed tapered fluid needle using passive aspiration. RESULTS In 16 of the 18 eyes, the peeling procedure could be easily performed with a tapered fluid needle using passive aspiration. In 11 eyes, partial development of spontaneous ILM detachment prior to the peeling process was also observed. CONCLUSIONS ICG solution 0.25% appears to reduce the adhesive force of the ILM to the sensory retina, which makes the removal of the ILM much easier by passive aspiration with a fluid needle.

Effect of repeatedly given CDP-choline on cardiovascular and tissue injury in spinal shock conditions: investigation of the acute phase

Objectives The protective effect of CDP‐choline in spinal cord transection and the mediation of its cardiovascular effects were investigated.

Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind trial in a mouse model.

OBJECTIVE To determine whether tamoxifen (TMX) exposure causes a permanent decrease in ovarian reserve. MATERIAL AND METHODS A randomized controlled assessor-blind trial including 30 adult female inbred BALB/C mice. Fifteen mice in the TMX group were given a single 0.1-mg dose of TMX intraperitoneally. Fifteen mice in the control group were given a single dose of the vehicle at the same volume intraperitoneally. Two cycles later, blood samples were collected for determination of anti-Müllerian hormone (AMH) levels, and the mice were sacrificed. After gonadectomy, ovarian size was measured, and follicles were counted under light microscopy. RESULTS Median serum AMH levels were 6.53 and 6.14 ng/ml in the control and TMX groups, respectively (p=0.03). Ovarian size was significantly decreased in the TMX group. While the number of primordial (9 vs 8), primary (6 vs 3), and secondary (4.5 vs 5) follicles were similar, there were significantly fewer preantral (11.5 vs 6, p<0.01) and antral (2 vs 1, p: 0.03) follicles, as well as corpora lutea (6 vs 3, p: 0.04), in the TMX group than in the control group. The number of atretic (2.5 vs 5, p: 0.048) follicles was increased in the TMX group. CONCLUSION Tamoxifen administration leads to arrested growth of gonadotropin-sensitive follicles, while insensitive follicles can remain unaffected. TMX is merely an endocrine disruptor, and it does not cause a decrease in primordial follicle pool.

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas

STUDY QUESTİON Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? SUMMARY ANSWER Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. WHAT IS ALREADY KNOWN Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). LIMITATIONS, REASONS FOR CAUTION The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS OF THE FINDINGS The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. STUDY FUNDING/COMPETING INTEREST(S) No funding or competing interests to declare. TRIAL REGISTRATION NUMBER None.

Scheduling GnRH antagonist cycles by a short course of oral estradiol administration during early follicular phase: a comparative study with non-scheduled cycles

Abstract This hypothesis generating study investigated whether GnRH antagonist cycles can be scheduled by a short course of oral estradiol administration during the follicular phase without impairing treatment outcome. Thirty-five women who underwent follicular phase estrogen scheduling (ES) of GnRH antagonist cycles were retrospectively matched for age and number of prior failed cycles with 35 women who underwent unscheduled GnRH antagonist cycles. ES group was given 6 mg/day estradiol orally from cycle day 2 until (including) one day before the scheduled start of stimulation. Gonadotropins were started on cycle days 2–3 in the control group. Flexible GnRH antagonist protocol was employed in both groups. ES group received estradiol for a median of 5 days. Total gonadotropin consumption was similar but one more GnRH antagonist injection was required in the ES group. Endometrial thickness on the day of hCG injection was increased in the ES group (12 versus 10 mm, p < 0.01). Number of oocytes, metaphase II oocytes and transferred embryos were similar. Embryo implantation rates were 44.8% versus 34.4% (p = 0.3), and clinical pregnancy rates were 48.6% versus 37.1%, (p = 0.33) in the ES and control groups, respectively. All women in the ES group had oocyte retrieval and embryo transfer within the desired period.

Detrimental effects of endometriosis on oocyte morphology in intracytoplasmic sperm injection cycles: a retrospective cohort study

Abstract While an association can be addressed among endometriosis and subfertility, the causal relationship has not been elucidated yet. Impaired oocyte quality in endometriosis patients has been accused for the unsuccessful outcomes of assisted reproductive techniques. There are limited studies in literature evaluated association between endometriosis and oocyte morphology. We conducted this retrospective study to evaluate whether morphological abnormalities of oocytes are more common in women with endometriosis than women with diagnosis of male factor infertility as a source of healthy oocytes. Totally 1568 oocytes, 775 (49.4%) in endometriosis groups and 793 (50.6%) in control group were evaluated for morphological parameters before ICSI cycles. Abnormal oocyte morphology was detected in 352 (22.4%) of 1568 oocytes. Of the abnormal oocytes, 208 (59.1%) were in endometriosis group and 144 (40.9%) in control group (p < .001). The following dysmorphisms were significantly higher in oocytes retrieved from endometriosis group: dark cytoplasm; dark, large or thin zona pellucida; and flat or fragmented polar body (p <  .05 for all). When morphological parameters for oocytes of endometriosis patients evaluated, the oocyte defects has increased significantly in endometriosis patients. These findings are thought to be useful to clarify the subfertility in endometriosis patient, which needs to be confirmed with further studies.