Cyclophosphamide suppresses spermatogenesis in the testis of mice through downregulation of miR-34b and miR-34c.

Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several organs, including the testes. In this study, we aimed to evaluate the effects of CP-induced testicular toxicity, using glial cell line-derived neurotrophic factor (GDNF), occludin and transforming growth factor beta 3 (TGF-ß3) primary antibodies, and miR-34b and miR-34c expressions. Eighteen young Balb/c male mice were divided into three groups. The control group received no treatment. The mice of CP group were injected 100 mg kg-1  day-1 CP for 5 days, and the same amount of saline was injected in the sham group. The animals were sacrificed 24 hr after the last injection. Immunohistochemical analysis of testicular tissues showed a decrease in both spermatogenic germ cell count and also GDNF, occludin expressions, but an increase in TGF-ß3 expression in the CP group compared to the others group. The expressions of miR-34b and miR-34c were examined by qPCR technique, a significant decrease was observed in tissue samples in the CP-treated group. The expression of GDNF, occludin and TGF-ß3 plays an important role in testicular injury caused by CP, and the decrease in the expression of miR-34b/c in tissue samples may be an important marker for the detection of testicular damage.

The effect of Resveratrol and Octreotide on peritoneal adhesions in a rat model.

INTRODUCTION: The aim of this study was to investigate the efficacy of resveratrol and octreotide, agents that are used to prevent intra-abdominal adhesions in experimental models, in preventing intraperitoneal adhesions when used alone or in combination. MATERIALS AND METHODS: The study employed 28 young female Wistar albino rats weighing 250-300 grams. An experimental adhesion model was created in each rat using serosal abrasion and peritoneal excision. They were divided into four groups, each comprising seven rats: Group 1, adhesion induction only; Group 2, resveratrol administration only; Group 3, octreotide administration only; and Group 4, administration of resveratrol and octreotide combination. The rats were monitored under appropriate conditions for 14 days and then underwent laparotomy. Macroscopic intensity and extensiveness of adhesions and microscopic changes in the granulation tissue (cellular intensity, reticular and collagen fibers, capillaries, elastic and smooth muscle fibers, fibrosis) were evaluated and graded. Kruskal-Wallis and Mann-Whitney U-test were used in statistical analysis and the level of statistical significance was established as p <0.05. RESULTS: There was no significant difference between the groups in terms of the intensity and extensiveness of macroscopic adhesions (p=0.377 and p=0.319). There was a statistically significant difference between the microscopic scores of the groups according to Zühlke's classification (p=0.026). The Bonferroni correction used to test for the differences revealed that the rats in Group 1 achieved significantly higher scores than the rats in Group 3 (p=0.016). CONCLUSION: Octreotide showed higher efficiency compared to the control group in microscopic classification; however, the two agents were not superior to each other or their combination was not superior in preventing intra-abdominal adhesions.

Jak-Stat signaling pathway may play a role in the pathogenesis of cholesteatoma.

PURPOSE: Jak-Stat signaling pathway is one of the major signal transduction cascades which regulates most of the cellular events such as cell proliferation, differentiation, cell migration and apoptosis. This study aims to determine the activity of Jak-Stat signaling pathway in the pathogenesis of cholesteatoma. MATERIALS AND METHODS: Cholesteatoma and skin samples were obtained from 10 patients who underwent tympanomastoidectomy for chronic otitis media with cholesteatoma. Immunohistochemical analysis of cholesteatoma and skin was performed using anti-Jak1, anti-Jak2, anti-Jak3, anti-Stat1, anti-Stat2, anti-Stat3, anti-Stat4 and anti-Stat5 antibodies. The immunoreactivities in cholesteatoma and skin were quantified using H-score measurement and statistical comparison was performed. RESULTS: Jak1, Jak2, Jak3, Stat1 and Stat3 immunoreactivities were not detected in cholesteatoma; in contrast to the skin (129.8; 226.7; 33.0; 66.4;115.9). In addition, when H-score measurements of Stat2, Stat4 and Stat5 immunoreactivities were compared between cholesteatoma (172.8; 166.7; 120.0) and skin (400.0; 284.9; 292.0), statistically significant differences were found (p<0.0001, p<0.0001, p<0.0001). CONCLUSIONS: A remarkable deficiency in the family members of Jak-Stat signaling pathway was demonstrated in cholesteatoma. Therefore, perturbations in Jak-Stat signaling pathway may play a role in the pathogenesis of cholesteatoma.

An Experimental Study of Radiation Effect on Normal Tissue: Analysis of HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 Expression.

OBJECTIVE: This study investigated whether or not the stress and hypoxia, which are the effects of radiation on normal vascular endothelium, leading to the release of HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 were related and the possibility of them stimulating angiogenesis. MATERIALS AND METHODS: Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1), and the second, third, and fourth groups were euthanized after 24 h (Group 2), 48 h (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Immunohistochemistry and light microscopy were used to investigate whether there would be an increase or not in the angiogenesis pathway by using the HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 antibodies. RESULTS: The HIF-1α antibody showed strong staining in Group 3, while the staining intensity was less in other groups. VEGF showed weak staining in Groups 1 and 4, while moderate staining in Group 2 and strong staining in Group 3 was observed. eIF2 showed strong staining in Groups 1 and 4. Groups 2 and 3 were stained weakly. In the present study, staining with TSP-1 was very strong in the samples belonging to Group 1, while other groups showed very weak staining. CONCLUSION: When normal tissue was exposed to radiation, the positively effective factors (HIF-1, VEGF, eIF2, and TIA-1) on the angiogenesis pathway were increased while the negative factor (TSP-1) was decreased. Radiation may initiate physiological angiogenesis in the normal tissue and accelerate healing in the damaged normal tissue. CONFLICT OF INTEREST: None declared.

Keratinocytes derived from embryonic stem cells induce wound healing in mice.

The skin plays an important role in defending the body against the environment. Treatments for burns and skin injuries that use autologous or allogenic skin grafts derived from adult or embryonic stem cells are promising. Embryonic stem cells are candidates for regenerative and reparative medicine. We investigated the utility of keratinocyte-like cells, which are differentiated from mouse embryonic stem cells, for wound healing using a mouse surgical wound model. Mice were allocated to the following groups: experimental, in which dressing and differentiated cells were applied after the surgical wound was created; control, in which only the surgical wound was created; sham, in which only the dressing was applied after the surgical wound was created; and untreated animal controls with healthy skin. Biopsies were taken from each group on days 3, 5 and 7 after cell transfer. Samples were fixed in formalin, then stained with Masson's trichrome and primary antibodies to interleukin-8 (IL-8), fibroblast growth factor-2 (FGF-2), monocyte chemoattractant protein-1 (MCP-1), collagen-1 and epidermal growth factor (EGF) using the indirect immunoperoxidase technique for light microscopy. Wound healing was faster in the experimental group compared to the sham and control groups. The experimental group exhibited increased expression of IL-8, FGF-2 and MCP-1 during early stages of wound healing (inflammation) and collagen-1 and EGF expression during late stages of wound healing (proliferation and remodeling). Keratinocytes derived from embryonic stem cells improved wound healing and influenced the wound healing stages.

Comparison of Patients With and Without Anterior Sector Venous Drainage in Right Lobe Liver Transplantation From Live Donors in Terms of Complications, Rejections, and Graft Survival: Single-Center Experience.

AIM: The issue of performing an anastomosis of the anterior sector veins to the vena cava in living donor liver transplantation is still controversial. We aimed to research whether there was any difference in terms of complications, rejections, and graft survival between patients with and without anterior sector venous drainage to the vena cava. PATIENTS AND METHODS: Patients were retrospectively investigated for demographic data and ratio of graft needed to available graft weight. Donors had volumetric calculations and middle hepatic vein anterior sector drainage documented in detail. RESULTS: Seventy-three donors with middle hepatic vein drainage were included. Thirty-five had anterior sector venous drainage performed and 38 patients did not have drainage procedures performed. The incidence of general complications was higher in the group without anterior sector drainage (78.3% and P = .002). Biloma linked to bile leaks were observed in 8 patients without drainage (72.8%) and 3 patients with drainage (27.2%). Late acute rejection occurring during follow up after transplantation was identified in 28 patients (11.6%). Of these, 1 (14.3%) had anterior sector drainage and 6 (85.7%) were in the patient group without drainage (P = .067). CONCLUSION: As a result of this study, for patients with grafts at the volume limit (graft weight to receiver weight ratio <0.8) and with congestion observed in the anterior sector after liver implantation and for patients with outflow problems identified on Doppler ultrasonography, anterior sector veins >5 mm should definitely be drained into the vena cava. Hence, both complication and rejection rates will reduce, and we can lengthen the graft, and thus patient, survival.

Survival Outcomes After Liver Transplantation in Elderly Patients: A Single-Center Retrospective Analysis.

AIM: This study aims to evaluate survival rates in elderly patients after liver transplantation (LT) and to analyze the factors associated with mortality. PATIENTS AND METHODS: Our study includes 535 patients over the age of 18 who had undergone LT in our clinic between June 2004 and January 2018. Data were collected prospectively and scanned retrospectively. Data concerning the patients' age, sex, LT indication, Child-Turcotte-Pugh score, Model for End-Stage Liver Disease score, presence of hepatocellular cancer (HCC), coexisting disease, LT types, and post-transplant survival were investigated. The patients were grouped under 2 categories (18-59 years of age and 60 years of age and over) and were compared in terms of their characteristics. In patients aged 60 and over, the causes of mortality and related factors were investigated. RESULTS: The study included 535 patients, 458 (85.6%) of whom were between 18 and 59 years of age and 77 (14.4%) were over 60 years of age. The median follow-up period was 86.7 (1 to 247) months. The elderly group's survival rate was significantly lower than that of the younger group (P = .002). In elderly patients, survival rates of 1, 3, 5, and 10 years were 67.4%, 56.4%, 53.8%, and 46.1%, respectively. CONCLUSION: In elderly patients, factors that increase post-LT mortality require thorough consideration. Equally important is the physiological status of the candidates for transplantation. Correct patient selection in the preoperative stage and good postoperative care can provide successful survival results in elderly patients.

Assessment of Effect of Intraperitoneal Tacrolimus on Liver Regeneration in Major (70%) Hepatectomy Model After Experimental Pringle Maneuver in Rats.

AIM: Small-for-size grafts have become more important, especially in living donor liver transplants. The Pringle maneuver, used to reduce blood loss, and the immunosuppressive medications used to prevent graft rejection in liver transplants have different side effects on liver regeneration. We researched the effect of situations where tacrolimus and the Pringle maneuver were applied or not on liver regeneration in rats with partial hepatectomy. MATERIAL AND METHODS: This study was completed with 35 Wistar Albino rats. The subjects were randomly divided into 5 groups: Group 1 had the abdomen opened and no other procedure was performed; Group 2 underwent a 70% hepatectomy; Group 3 underwent a 15-minute Pringle maneuver + 70% hepatectomy; Group 4 underwent a 70% hepatectomy + 5 days of 1 mg/kg/day intraperitoneal tacrolimus; and Group 5 underwent a 150 minute Pringle maneuver + 0% hepatectomy + 5 days of 1 mg/kg/day intraperitoneal tacrolimus. All rats were sacrificed on the seventh postoperative day, remaining liver tissue was weighed, and weight indices created. The remaining liver tissue was stained with phosphohistone H3 and the mitotic index calculated. RESULTS: The groups that underwent the Pringle maneuver, 70% hepatectomy, and tacrolimus administration were compared with the control group in terms of mitotic index and weight index, but no statistically significant differences were identified. CONCLUSION: Suppression of regeneration forms a risk after liver transplantation with small-volume grafts. As a result, research on the effect of tacrolimus combined with the Pringle maneuver is important, especially for transplantations using segmented liver grafts. In our study, we showed that the use of tacrolimus had no negative effect on liver regeneration.

The Analysis of Posthepatectomy Liver Failure Incidence and Risk Factors Among Right Liver Living Donors According to International Study Group of Liver Surgery Definition.

AIM: There is a well-known risk of the emergence of hepatic failure in living donor transplant cases on whom are performed a right donor hepatectomy (RDH). There are different prevalence ratios in literature on this phenomenon. In our study, we aim to depict the prevalence of hepatic failure and risk factors in our cases regarding the most recent description criteria related to hepatic failure. PATIENTS AND METHODS: We included right liver donor hepatectomy cases who fit the donor evaluation algorithm at the Dokuz Eylul University Liver Transplantation Unit between the period of June 2000 and September 2017. The patients were evaluated regarding preoperative data. Liver failure was defined according to the International Study Group of Liver Surgery (ISGLS) criteria. We also included statistical analysis of risk factors that are potentially related to liver failure. RESULTS: We included a total of 276 patients. In 27 (9.7%) patients, we observed posthepatectomy liver failure (PHLF). In 26 (9.4%) patients, we observed Grade A liver failure; in 1 (0.3%) patient, we observed Grade B liver failure. We did not observe any Grade C hepatic failure. In patients with hepatic failure, we observed a significantly longer period of hospitalization (P = .007). Old age (odds ratio = 1.065, 95% confidence interval, 1.135-29.108, P = .035) and preoperatory red blood cell (RBC) transfusion (odds ratio = 5.749, 95% confidence interval, 1.019-1.113, P = .005) were shown as independent risk factors for PHLF. CONCLUSION: Posthepatectomy liver failure is a vital complication of RDH. The risk can be decreased by careful selection of donor candidates. Elderly donor candidates and intraoperative RBC are independent risk factors for PHLF.

The Predictive Ability of the Glasgow Prognostic Score and Variants in Both Deceased Donor and Living Donor Liver Transplantation for Hepatocellular Cancer.

AIM: Liver transplantation (LT) is the most promising treatment method in hepatocellular cancer (HCC). Due to the shortage of organ donors and the possible risks associated with living donation, the selection of patients for LT is critical. The aim of this study is to investigate the predictive ability of the Glasgow Prognostic Score (GPS), modified GPS (mGPS), and hepatic GPS (hGPS) on prognoses in a patient group who underwent deceased donor LT (DDLT) or living-donor LT (LDLT) for HCC. PATIENTS AND METHODS: This study includes 62 DDLT and 55 LDLT patients who underwent LT for HCC between 1998 and 2016 in a single center. The study endpoints were recurrence, 0- to 1-year mortality, 0- to 3-year mortality, mortality, and overall survival (OS). RESULTS: The median follow-up time was 70.24 ± 48.47 months. GPS and hGPS positivity were found to be prognostic indicators of 0- to 3-year mortality and overall mortality in DDLT (P = .012, P = .006; P = .044 and P = .022 respectively). In the LDLT group, GPS was found to be effective in predicting 0- to 1-year and 0- to 3-year mortality (P = .045, P = .022 respectively); GPS and hGPS were also found to be effective in predicting overall mortality (P = .001 and P = .046 respectively). The OS was significantly longer in the GPS 0 group and hGPS 0 group compared to the GPS 1-2 and hGPS 1-2 group in both DDLT and LDLT. CONCLUSION: The findings of this study and the literature indicate that using GPS and hGPS is appropriate in selecting patients with HCC who are candidates for LT.

The Most Frequently Cited 100 Articles in Liver Transplantation Literature.

INTRODUCTION: We investigated the liver transplantation literature since 1975 and found the most frequently cited 100 articles and assessed the distribution of authors and journals of these articles. METHOD: Using the advanced mode of the Institute for Scientific Information (ISI) Web of Science (WOS) search engine, the words "SU = transplantation AND TI = liver OR SU = transplantation AND TS = liver" were used to scan articles and determine the most-cited 100 articles on July 18, 2016. RESULTS: From 1975 to date, it appears a total of 43,369 articles were published in the field of liver transplantation in the WOS. Although the most cited article had 677 citations, the least cited article had 180 citations. The mean citation number for the 100 articles was 252.31 ± 96.75. The mean annual citation number for the articles varied from 61.55 to 5 and the mean was 15.31 ± 8.63. The most cited article was by Feng et al "Characteristics Associated With Liver Graft Failure: The Concept of a Donor Risk Index" published in the American Journal of Transplantation (677 citations). CONCLUSION: Bibliometric analysis highlights the key topics and publications that have shaped the understanding and management of liver transplantation. According to our research, this is the first study to investigate articles with most citations in the field of liver transplantation. In our study the article with the most citations was cited 677 times, whereas the 100th article was cited 180 times with a mean citation number for the 100 articles of 252.31 ± 96.75.

Hepatic Artery Reconstruction With Autologous Inferior Mesenteric Artery Graft in Living Donor Liver Transplant Recipients.

INTRODUCTION: In living donor liver transplantation (LDLT), hepatic arterial continuity is crucial to avoid biliary leakage, biliary stricture, cholangitis, and graft and patient loss. Sometimes there exist factors making anastomosis difficult or even impossible. In these cases, a vascular graft may be needed to bridge the two arteries for revascularization. METHOD: Medical records of 297 patients who underwent LDLT between June 2000 and July 2016 at the Hepatopancreatobiliary Surgery and Liver Transplantation Unit of Dokuz Eylul University Hospital were reviewed retrospectively. Twenty-eight (9%) patients younger than the age of 18 were excluded from the study. The remaining 269 patients were included in the study. We analyzed data of patients who developed hepatic arterial complications during or after LDLT and underwent revascularization using autologous interposed inferior mesenteric artery (IMA) grafts. RESULTS: In 8 (2.9%) of the 269 patients who underwent LDLT and were included in the study, autologous interposed IMA grafts were used for the hepatic artery revascularization. All of the patients were males. Their mean age was 42 (range, 25-57). The mean duration of follow-up was 83.25 months (range, 3-144 months). One patient developed intraoperative hepatic arterial thrombosis (HAT) after autologus IMA reconstruction and this patient needed retransplantation. No arterial complications developed in the other 7 patients. CONCLUSION: Autologous interposed IMA graft could be used as an alternative vascular graft in hepatic artery revascularization to provide tension-free hepatic arterial continuity.

Complications in Donors Using Right Liver Graft: Analysis of 280 Consecutive Cases.

INTRODUCTION: Living donor liver transplantation (LDLT) is performed with increasing frequency worldwide due to the shortage of donated organs. It is a life-saving procedure for the recipient, but, on the other hand, a major surgical procedure for healthy donors and it may cause morbidity and even mortality. PATIENTS AND METHODS: This research was completed at Dokuz Eylül University Faculty of Medicine Hospital General Surgery Department Liver Transplant Unit and included 280 cases (4 with simultaneous liver and kidney transplants from living donors) who underwent donor right hepatectomy for LDLT from June 2000 to June 2016. We analyzed the data of patients retrospectively. RESULTS: Of 280 donor right hepatectomies for LDLT, 181 were male (M; 64.6%) and 99 were female (F; 35.4%) (M/F: 1.82). Mean donor age was 31.2 ± 0.9 years (range, 18-56). Mean donor monitoring duration was 45 ± 2.4 months (range, 3-192 months). Mean body mass index (BMI) was 24.28 ± 2.96 kg/m2 (range, 18.1-32.42 kg/m2). In our study 72 cases (25.7%) developed postoperative complications. There were 17 Clavien grade 3A, 1 grade 3B, and 5 grade 4A complications and also 1 death due to pulmonary embolism. CONCLUSION: Together with the increase in living donor surgery, the morbidity and mortality of these cases are becoming controversial. Full donor safety is only possible with appropriate donor choice requiring very detailed studies, a problem-free hepatectomy process, and close postoperative donor monitoring.

Long-term Results of Living Donors in Simultaneous Kidney and Liver Transplantations.

INTRODUCTION: Because of the shortage of organs available for transplantation, living related sequential transplantation with the use of liver and a kidney from the same donor has emerged as a reasonable therapeutic alternative. However, there is insufficient literature about the complications that living donors experience after simultaneous kidney and liver transplantations. METHODS: From December 2001 to October 2009, 5 living donors provided simultaneous donation of livers and kidneys and 1 living donor donated first her kidney and then her liver. Demographic data of the donors and information concerning the surgery and postoperative observation were collected prospectively. RESULTS: All of the donors were female. The median age was 27.5 (range, 19-36) years. Indications requiring the simultaneous transplantation of livers and kidneys were primary hyperoxaluria type 1 (PH1) in 5 potential recipients and cirrhosis due to chronic hepatitis B infection and idiopathic chronic renal insufficiency in 1 potential recipient. Four recipients underwent right hepatectomy (segments 5-8) and right nephrectomy; 1 recipient underwent left hepatectomy (segments 2-4) and right nephrectomy; and 1 recipient underwent left lobectomy (segments 2-3) and right nephrectomy. There were no complications except in 1 donor (postoperative ileus). No donor developed hypertension or microalbuminuria. CONCLUSIONS: With the right indications, appropriate preoperative evaluation, meticulous surgical technique, proper postoperative care, and long-term close monitoring to minimize morbidity and mortality risks, liver and kidney donation from the same donor can be considered for simultaneous kidney and liver transplantation.

Efficacy of right anterior sector drainage reconstruction in right-lobe live-donor transplantation.

BACKGROUND: Without including the middle hepatic vein (MHV) into right-lobe grafts, venous drainage of the anterior segment (AS) has always been a concern. The efficacy and the necessity of additional venous reconstruction in the AS for graft viability and function are still controversial. METHODS: Since February 2002, 57 right-lobe grafts were implanted into adult recipients. The mean graft to ideal recipient weight ratio (GRWR) was 1.3% (minimum: 0.8%, maximum 2.1%). All minor venous tributaries to the MHV less than 5 mm in diameter were ligated. The management of MHV tributaries was categorized into three groups: (A) no major tributaries (n = 33); (B) major tributaries ligated (n = 11); and (C) major tributaries reconstructed (n = 13). Reconstructions were established using vascular grafts (PTF, n = 8; cadaveric, n = 2) or joining with right hepatic vein orifice (n = 6). The groups were homogenous in age, gender, MELD (17 +/- 6, 16 +/- 4, 18 +/- 7), graft weight (817 +/- 181, 838 +/- 152, and 855 +/- 159 g), and graft/ideal liver weight ratio (0.54 +/- 0.12, 0.57 +/- 0.13, and 0.57 +/- 0.1, respectively). We investigated the volume of ascites, serum bilirubin, albumin, and liver enzyme levels and INR on postoperative day 4 (POD4) and POD21. RESULTS: Two patients died of MRSA sepsis on POD18 and POD23 (MELD: 24 and 28) after initial graft function. Their graft weights were 800 g and 980 g, and their volumes were 47% (group B) and 62% (group A) of the ideal liver mass of the recipients, respectively. One PTF and another cadaveric vascular graft were found occluded 4 and 7 days after implantation without any negative consequence. At 6-month follow-up, the remaining 55 patients were alive with primary liver grafts. Vascular reconstructions were patent except for 2 early occlusions. Among the 3 groups, no significant difference was found on POD4. Three weeks after transplantation, the mean AST level in the major ligation group (46.7 +/- 8.14) was significantly higher than in the minor ligatation group (29.6 +/- 8.6) but not in the major reconstruction group (33.7 +/- 3.7; P = .03 and P = .29). The mean albumin level was highest after minor ligation (3.2 +/- 0.18), which was significantly better than the major reconstruction (2.7 +/- 0.1) but not the major ligation (3.1 +/- 0.14) cohorts (P = .02 and P = .13). CONCLUSIONS: In this study of a limited number of cases, right-lobe liver grafts with GRWR of > or =1.1% displayed optimal graft function without additional venous reconstruction to the AS.

Calcitonin expression of high endothelial venules during lymphocyte migration in human pharyngeal tonsil.

The migration routes of lymphocytes through high endothelial venules (HEVs) of control and hypertrophic pharyngeal tonsil (HPT) tissue sections were investigated by immunohistochemistry using the expression of a hormone [calcitonin (CT)] and two calcium-dependent endothelial adhesion molecules (E-selectin and P-selectin), as well as electron microscopy. A marked increase in CT-specific staining was observed in the endothelial cells of HEV in the HPT group compared to the control group. Expressions of E-selectin and P-selectin on HEVs of control group were faint, when compared to the strong expression of these selectins on HEVs of HPT. Electron microscopically, we demonstrated that lymphocytes transmigrated through HEV and observed the close membranous contact between endothelial cells and lymphocytes during this process. We speculate that increasing CT during inflammation may be important for lymphocyte migration through the HEVs via controlling the expression of E-selectin and P-selectin.

Evaluation of Pregnancy Outcomes After Liver Transplantation.

Liver transplantation is increasing worldwide. Pregnancy after liver transplantation is considered to be well tolerated with favorable neonatal outcomes in cases of stable and sufficient graft function. In this study, our aim was to determine pregnancy and neonatal outcomes of patients after liver transplantation. Data for patients who had been followed-up by the liver transplantation clinic at the Dokuz Eylül University Medical Faculty Hospital, Turkey, between 2002 and 2016, and who had pregnancy after the transplantation were evaluated retrospectively. The earliest post-transplantation conception occurred after 22 months and the latest conception occurred after 108 months (mean, 55.4 months). Twenty-one pregnancies concluded with live births (100%). The mean birth week was 37.09. The earliest birth occurred at 27 weeks and the latest at 40 weeks. Mean birth weight was 2993 g (10th to 25th percentiles). No pregnancy-induced hypertension, pre-eclampsia, or gestational diabetes were observed in any patient. Five pregnancies concluded with premature birth. In conclusion, several complications may occur during pregnancy (such as hypertension or pre-eclampsia, etc) in patients with liver transplantation, but it seems that pregnancy has good effects on graft functions and the neonatal outcomes are favorable.

Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation.

OBJECTIVE: To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. STUDY DESIGN: Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. RESULTS: In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). CONCLUSION: COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium.

Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility.

Apoptosis has been shown to be an important regulator of endometrial function during the menstrual cycle and implantation. Recently, some possible implantation defects were identified in patients with unexplained infertility. In this study, we investigated the role of spontaneous apoptosis, which is regulated by death regulatory genes, such as Bcl-2, Bax, p53, and isoenzymes of nitric oxide synthases; eNOS and iNOS during the implantation window in women with unexplained infertility. Endometrial samples were evaluated from fertile (n=15) and unexplained-infertile women (n=15) during post-ovulatory 7th or 8th day of their menstrual cycles. Apoptotic cells were detected using the dUTP nick-end labelling assay and Bcl-2, Bax, p53, iNOS and eNOS were assessed immunohistochemically. Reduced apoptotic cells, weak immunoreactivity of p53 and strong immunoreactivity of Bcl-2 were observed in the unexplained-infertile group compared with the fertile group (p<0.001). Bax intensity was similar in both groups. While weak iNOS immunoreactivity was detected in both groups, moderately increased eNOS immunoreactivity was observed in infertile cases. Spontaneous apoptosis is reduced in the endometrium of unexplained-infertile women, and is associated with the changed Bcl-2:Bax ratio. This finding may be a contributing factor to defective implantation causing infertility in this group of patients.

Incidence of Late Acute Rejection in Living Donor Liver Transplant Patients, Risk Factors, and the Role of Immunosuppressive Drugs.

INTRODUCTION: Late acute rejection (LAR) is a clinical manifestation that occurs 6 months after liver transplantation, shows histopathologic features different from those of acute rejection, and is the cause of a high prevalence of morbidity and mortality. METHODS: In this study, hospital records of 211 living donor liver transplantation (LDLT) patients who underwent surgery in our clinic between June 2000 and February 2014 were reviewed retrospectively. The patients were ≥ 18 years old and were followed for ≥ 6 months. RESULTS: Of the 211 patients, 21 (9.9%; 16 males, 5 females) developed LAR. The mean age of the patients was 46 years (range, 33-58). The mean follow-up period was 61.2 months (range, 6-152) and the median time to development of LAR was 26.4 months (range, 7-77). In our study, patients who received cyclosporine and mycophenolate mofetil (MMF) treatment developed more LAR than did patients who received tacrolimus and MMF therapy (P = .05). In addition, the incidence of LAR in patients who underwent LDLT was significantly greater in the ABO-matched groups than in the ABO identical group (P = .028). CONCLUSIONS: Development of LAR and serious complications related to it can be avoided if liver transplant recipients are followed regularly and closely in outpatient clinics after transplantation.