Akif Ciftcioglu

Clinical pregnancy after uterus transplantation

OBJECTIVE To present the first clinical pregnancy after uterus transplantation. DESIGN Case study. SETTING Tertiary center. PATIENT(S) A 23-year-old Mayer-Rokitansky-Kuster-Hauser syndrome patient with previous vaginal reconstruction and uterus transplantation. INTERVENTION(S) Eighteen months after the transplant, the endometrium was prepared for transfer of the thawed embryos. MAIN OUTCOME MEASURE(S) Implantation of embryo in an allografted human uterus. RESULT(S) The first ET cycle with one day 3 thawed embryo resulted in a biochemical pregnancy. The second ET cycle resulted in a clinical pregnancy confirmed with transvaginal ultrasound visualization of an intrauterine gestational sac with decidualization. CONCLUSION(S) We have presented the first clinical pregnancy in a patient with absolute uterine infertility after uterus allotransplantation. Although the real success is the delivery of a healthy near-term baby, this clinical pregnancy is a great step forward and a proof of concept that the implantation phase works.

Varicocele-Induced Testicular Dysfunction May Be Associated with Disruption of Blood-Testis Barrier

The objective of this study was to examine E-cadherin and α-catenin expression at the junctions between adjacent Sertoli cells in testicular specimens from patients with varicocele in order to determine the presence of a possible link between blood-testis barrier and pathophysiology of varicocele. A total of 51 testicular biopsies were obtained from 28 infertile men with unilateral or bilateral varicocele. Twenty-three patients had bilateral and 5 had unilateral varicocele, Grade I varicocele was detected in 30 (59%), grade II in 15 (29%) and grade III in 6 (12%) patients. Abnormal expression of E-cadherin and α-catenin at the junctions between adjacent Sertoli cells was demonstrated in 100% and 90% of the patients with varicocele, respectively. In those with grade I-III varicocele, the mean E-cadherin and α-catenin expression were 7.6 ± 11.4 and 39 ± 36; 7.6 ± 0.0 and 49 ± 30; 8.3 ± 9.3 and 58 ± 33, respectively, but the difference was not significant. Reduced E-cadherin and α-catenin expression at the junctions between adjacent Sertoli cells may be associated with disruption of blood-testis barrier in varicocele.

Reduced E-cadherin and α-catenin Expressions Have No Prognostic Role in Bladder Carcinoma

In various human cancers, dysfunction of the E-cad-herin-catenin complex is associated with a decrease in cellular and tissue differentiation, and with higher invasive and metastatic potentials. The objective of this study was to investigate E-cadherin and α-catenin expression in superficial noninvasive papillary TCC and invasive TCC, and correlate these results with pathological and clinical parameters. We have used immunohistochemistry to localize Ecadherin and α-catenin in 56 formalin-fixed, paraffin-embedded tissue blocks from 41 patients with superficial bladder cancer and 15 with invasive bladder cancer. The 46 male and 10 female patients had a mean age of 67 years, with range of 40 to 82 years. The mean follow-up time was 33.4 (range 5–120) months. Tumor grade 1:2:3 ratios were 5:32:19. In superficial bladder tumor, abnormal expression of E-cadherin and a-catenin was demonstrated in 37 and 71% of the tumors, respectively. In advanced bladder tumor, abnormal expression of E-cadherin and a-catenin was demonstrated in 80 and 100% of the tumors, respectively. Differences in expression of E-cadherin and α-catenin could be discerned between superficial and advanced bladder tumors (p=0.004, p=0.024, respectively). However, the association between E-cadherin and α-catenin expression and tumor grade was not statistically significant (p>0.05). In addition, the expression of E-cadherin and α-catenin did not correlate with tumor number and size (p>0.05). We have demonstrated that abnormal expression of E-cadherin and/or α-catenin occurs in more than 85% of bladder carcinomas and correlates significantly only with advanced stage. Nevertheless, these observations need to be confirmed in larger prospective clinical studies.

Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure.

The aim of this study was to clarify the possible protective effect of astaxanthin (ASX) on the retina in rats with elevated intraocular pressure (EIOP). Rats were randomly divided into two groups which received olive oil or 5mg/kg/day ASX for a period of 8 weeks. Elevated intraocular pressure was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. At the end of the experimental period, neuroprotective effect of ASX was determined via electrophysiological measurements of visual evoked potentials (VEP) and rats were subsequently sacrificed to obtain enucleated globes which were divided into four groups including control, ASX treated, EIOP, EIOP+ASX treated. Retinoprotective properties of ASX were determined by evaluating retinal apoptosis, protein carbonyl levels and nitric oxide synthase-2 (NOS-2) expression. Latencies of all VEP components were significantly prolonged in EIOP and returned to control levels following ASX administration. When compared to controls, EIOP significantly increased retinal protein oxidation which returned to baseline levels in ASX treated EIOP group. NOS-2 expression determined by Western blot analysis and immunohistochemical staining was significantly greater in rats with EIOP compared to ASX and control groups. Retinal TUNEL staining showed apoptosis in all EIOP groups; however ASX treatment significantly decreased the percent of apoptotic cells when compared to non treated ocular hypertensive controls. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of ASX in ocular hypertension.

The potential role of inducible nitric oxide synthase (iNOS) activity in the testicular dysfunction associated with varicocele: an experimental study.

Nitric oxide (NO) has been reported to be increased in the spermatic veins of men affected by varicocele. The aim of the present study was to determine whether iNOS (inducible nitric oxide synthase) has a role in testicular dysfunction associated with varicocele, immunohistochemistry analyze was used to study iNOS activity in testis of adolescent rats with experimental left varicoceles. Rats were randomly divided into three groups. The first group consisted of rats undergoing partial ligation of left renal vein (n:12). The second group consisted of rats undergoing a sham operation (n:6) and, the third group referred to as control rats (n:7). Immunohistochemistry slides were evaluated by counting the number of positive cells and expressed as percents (% iNOS activity). We found that iNOS was predominantly expressed in the cytoplasm of Leydig cells in each group and only a small amount of iNOS was expressed in Sertoli cells. There were significant differences in % iNOS activity between both testes of varicocele group and both of testes control group(p < 0.01), but no significant differences were noted between other groups (p > 0.05). Because of iNOS activity was markedly increased in the Leydig cells of varicocele bearing rats, we suggest that iNOS activity may play a role in the testicular dysfunction associated with varicocele during adolescence.

Corneal protein nitration in experimental uveitis

Increased expression of inducible nitric oxide synthase (NOS-2) in inflammatory diseases like uveitis suggests that it contributes to the observed pathological state. The aim of this study was to evaluate corneal expression of NOS-2 and corneal protein nitration in a rat model of uveitis. A single injection of intravitreal lipopolysaccharide was used to induce uveitis. Corneal proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by Coomassie blue staining. Expression of NOS-2 and nitrotyrosine (NO2Tyr) formation were determined via immunohistochemistry and Western blot analysis. Total nitrate/nitrite levels in the vitreous were measured by spectral analysis via the Griess reagent. Immunohistochemical analysis revealed increased corneal NOS-2 and NO2Tyr immunoreactivity in rats with uveitis compared with controls. NOS-2 and NO2Tyr immunoreactivity was observed in and around basal cells in the corneal epithelium. Western blot analysis of corneal lysates showed multiple nitrated protein bands in uveitic rats. Spectrophotometric measurement of total nitrate/nitrite levels in the vitreous affirmed significantly increased levels of nitric oxide generation in uveitis (126 ±2.63 μM/mg protein) compared with controls (65 ±6.57 μM/mg protein). The presented data suggests that extensive formation of protein nitration and reactive nitrogen species in the cornea contributes to tissue destruction in uveitis. Hence, selective inhibition of NOS-2 may prevent long-term complications and lead to an improvement in the management of uveitis.

RELATIONSHIP BETWEEN MAST CELL AND INOS EXPRESSION IN TESTICULAR TISSUE ASSOCIATED WITH INFERTILITY

The objective of this study was to investigate mast cells and iNOS expression in testis tissue, and to correlate these results with spermatogenetic disorders. A total of 136 testicular biopsies were obtained from the testes of 80 patients with infertility. Their age ranged from 21 to 45 years. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. In each section, all interstitial fields were evaluated for the total number of mast cells as well as the total number of Leydig cells. The number of mast cells per Leydig cell was calculated and recorded as mast cell index. Immunohistochemical iNOS staining was evaluated semiquantitatively according to intensity and the proportion of the stained cells. There was a significant increase of the mast cell index in all groups with testicular disorder compared with normal spermatogenesis group (p < 0.05). Increase of the index was in the order of hypospermatogenesis, maturation arrest and SCO, and index of SCO group was especially higher, i.e., more than twice than other groups. iNOS score was significantly higher in the SCO group than in the men with normal spermatogenesis, hypospermatogenesis, and maturation arrest (p < 0.05). Finally, a significant statistical correlation was found between the iNOS score and mast cells index (r = 0,758, p = 0,001). Increase of mast cell index was observed in the groups of infertile testis, and high expression of iNOS in Leydig cells was associated with the highest mast cell index in SCO, the lesion with the most severe damage of the germ cell.

Inhibition of neutral sphingomyelinase decreases elevated levels of inducible nitric oxide synthase and apoptotic cell death in ocular hypertensive rats

Endoplasmic reticulum (ER) stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS2) have been implicated in the pathogenesis of neuronal retinal cell death in ocular hypertension. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression, hence this study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on retinal NOS2 levels, ER stress, apoptosis and visual evoked potentials (VEPs) in a rat model of elevated intraocular pressure (EIOP). NOS2 expression and retinal protein nitration were significantly greater in EIOP and significantly decreased with N-SMase inhibition. A significant increase was observed in retinal ER stress markers pPERK, CHOP and GRP78 in EIOP, which were not significantly altered by N-SMase inhibition. Retinal TUNEL staining showed increased apoptosis in all EIOP groups; however N-SMase inhibition significantly decreased the percent of apoptotic cells in EIOP. Caspase-3, -8 and -9 activities were significantly increased in EIOP and returned to baseline levels following N-SMase inhibition. Latencies of all VEP components were significantly prolonged in EIOP and shortened following N-SMase inhibition. Data confirm the role of nitrative injury in EIOP and highlight the protective effect of N-SMase inhibition in EIOP via down-regulation of NOS2 levels and nitrative stress.

Sex cord tumour of the adult testis.

Sex cord stromal tumors are rare and accountfor approximately 6% of all testicularneoplasms. We report a case of sex cord tumorcomposed of granulosa cells and Sertoli cellsin the adult testis.

The Relationship Between Ischemia Time and Mucous Secretion in Vaginal Reconstruction With the Jejunal Free Flap: An Experimental Study on the Rat Jejunum.

AbstractJejunum flap for reconstruction of the vagina provides a durable, stable coverage; patent tube passage; and natural esthetic appearance. However, excessive mucous secretion is a major drawback of the technique.We have recently presented our cases in which strict 3-hour ischemia with lower mucus secretion was applied. However, a quantitative analysis of goblet cells of the jejunum subjected to ischemia and ischemia-reperfusion injury on an animal model has not been reported to support this argument.Because goblet cells are responsible for the production and the maintenance of the mucous blanket, we aimed to determine whether goblet cell numbers decrease after ischemia and ischemia-reperfusion injury.This study was conducted on 3 groups of 10 animals. We applied to the rat jejunum only ischemia in group 1, one hour of ischemia followed by reperfusion in group 2, and 2 hours of ischemia followed by reperfusion in group 3. Histological samples taken from the jejunum exposed to ischemia and ischemia-reperfusion injury were evaluated in terms of goblet cell numbers, inflammation, apoptotic bodies, and necrosis.Goblet cell numbers significantly decreased in the group of animals exposed to ischemia and exposed to ischemia-reperfusion injury. We think that mucus hypersecretion of the jejenum can be limited by applying a longer period of ischemia time during free flap transfer in vaginal reconstruction.