Browsing by Publisher "ELSEVIER GMBH, URBAN & FISCHER VERLAG"

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    Propolis from Turkey induces apoptosis through activating caspases in human breast carcinoma cell lines
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Vatansever, HS; Sorkun, K; Gurhan, SID; Ozdal-Kurt, F; Turkoz, E; Gencay, O; Salih, B
    Propolis is a sticky substance that is collected from plants by honeybees that has anti-mutagenic and anti-carcinogenic properties with biological and therapeutic effects The target of this study was to investigate the anti apoptotic effect of propolis extracts (PE) on the caspase pathway in the human breast cell line MCF 7 in culture Seven different propolis extracts, numbered PE 1-7, produced in their natural ecological environment, were collected from the Hacettepe University Beytepe Campus area in Ankara, Turkey Individual extracts at 0 5, 0 25, 0 125 and 0 063 mg/ml were incubated with MCF 7 cells during 2 days culture Cell growth and cytotoxicity were measured colorimetrically by MTT assay Apoptotic cell death was determined by the TUNEL method (terminal deoxynucleotidyltransferase-biotin nick end labelling) and caspase activity was investigated by immunocytochemistry using antibodies directed against caspase 6, caspase 8 and caspase 9 The results showed that the PE 5 and 6 extracts at 0 125 mg/ml dilution induced apoptosis in association with increased number of TUNEL positive cells MTT results showed that cultures exposed to the same extracts and at the same dilution experienced better cell growth compared to those cultures exposed to the other extracts Immunpositivity for all caspases was detected after treatment with all the extracts and at all dilutions, with stronger immunoreactivity for caspase 6 than caspases 8 and 9 Caspase 6 labelling was especially strong in PE 5 and PE 6 We conclude that propolis may have anti-tumour effects by increasing apoptosis through the caspase pathway Such propolis extracts may be important economically and allow development of a relatively inexpensive cancer treatment (C) 2009 Elsevier GmbH All rights reserved
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    Regressing amphibian tail as a model for the cadherin/β-catenin complex disruption and glycosylation alteration during epithelial apoptosis
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Sahin, M; Balcan, E
    Epidermis is one of the many tissues that are resorbed during metamorphosis in the regressing tail of amphibian tadpoles. Apoptotic mechanisms play an important rote in this process. In this study, loss of intercellular contacts and alterations in plasma membrane glycosylation were observed during apoptosis. The cadherin/beta-catenin complex represents one of the major adhesive systems in multiple epithelial. tissues. Here, we analysed the fate of cadherin/beta-catenin complex and alterations of plasma membrane glycoconjugate compositions in apoptotic epithelial cells. Our results showed that the cadherin molecules were cleaved into extracellular and beta-catenin associated cytosolic domains by an intracellular mechanism. However, the extracellular domains were probably removed completely by matrix metalloproteinases. Lectin histochemistry studies suggested that mannose and alpha(2 --> 6) linked (but not alpha(2 --> 3) linked) sialic acids were major sugar motifs in plasma membranes of apoptotic tadpole epithelial cells. Although previous studies indicated reduced levels of sialic acid residues during apoptosis, elevated Sambucus nigra agglutinin (SNA) reactivity might be due to the degradation of high molecular weight glycoproteins (probably including cadherin) that masked the SNA-binding residues of the plasma membrane prior to apoptosis. (C) 2008 Elsevier GmbH. All rights reserved.
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    Characterization of osteoblasts derived from bone marrow stromal cells in a modified cell culture system
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Deliloglu-Gurhan, SI; Vatansever, HS; Ozdal-Kurt, F; Tuglu, I
    Bone marrow is a complex tissue composed of hematopoietic and stromal. stem cells with the potential to differentiate into adipogenic, fibroblastic, reticular, osteogenic and chondrogenic lineages. Identification of differentiation markers during transformation of stromal cells into osteoblasts in a time-dependent manner may be informative for cell-based tissue engineering. Therefore, we investigated the effects of osteogenic medium (OM) on the proliferation and differentiation of rat bone marrow stromal. cells (BMSCs). BMSCs from adult mate rat tibia and femur were collected and cultured in alpha-MEM medium with 10% fetal bovine serum, penicillin, streptomycin and gentamycin. After three days of culture, the medium covering the adherent cells in culture was changed to OM containing dexamethasone, Na-beta-glycerophosphate and ascorbic acid. As a control., cell. culture was also continued in the original. medium for the same time period. Differentiated osteoblast cells were collected after 7, 10, 14, 21 and 30 days of culture, fixed with 4% paraformaldehyde and their immunolabelling for osteoblast markers osteonectin (ON) and osteocalcin (OC) was assessed using an indirect immunoperoxidase technique. Immunoabelling of ON and OC was detectable from day 10 of culture, began to increase on day 14, and increased steadily through to day 21. Labelling was highest on day 30 and was more intense in cells cultured with OM compared to the culture without OM. The control cells cultured in the absence of OM produced negligible levels of both markers. In conclusion, our culture system facilitated differentiation of BMSCs into osteoblasts featuring osteoblast markers, and these cells may be useful in autologous bone implant for the treatment of bone wound heating. (C) 2005 Elsevier GmbH. All rights reserved.
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    Changes in distribution patterns of integrins in endometrium in copper T380 intrauterine device users
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Oruç, S; Vatansever, HS; Karaer, Ö; Eskicioglu, F; Narlikuyu, B
    Intrauterine contraception is the most cost-effective reversible method of contraception today, but its mechanism of action is not well understood. Our objective was to investigate immunohistochemical. distribution patterns of xv, x3, beta 1 integrins in women using a copper T380 intrauterine device (IUD) for different periods of time to obtain insight into the rote of integrins in intrauterine contraception. Endometrial biopsies were obtained from patients using T Cu380A IUD in follicular and luteat phases and in menopausal women grouped according to the period of time of IUD use (group 1: < 3 year, and group 2: >= 3 years). Each group consisted of 10 patients, with a total number of 60 patients. Labelling intensity of at integrins, except for beta 1 which increased in the follicular phase, were decreased in women who used IUD for >= 3 years when compared with group 1 in the follicular and luteat phases and in the menopause. We conclude that long-term use of IUD affects integrin expression in endometrium not only in follicular and luteat phases of premenopausal women but also in postmenopausal women. Copper IUD can inhibit binding of integrins to the extracellular matrix and it may cause inhibition of the implantation stage, which is crucial for pregnancy. (c) 2005 Elsevier GmbH. All rights reserved.
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    Biological effects of tolerable level chronic boron intake on transcription factors
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Boyacioglu, SO; Korkmaz, M; Kahraman, E; Yildirim, H; Bora, S; Ataman, OY
    The mechanism of boron effect on human transcription and translation has not been fully understood. In the current study it was aimed to reveal the role of boron on the expression of certain transcription factors that play key roles in many cellular pathways on human subjects chronically exposed to low amounts of boron. The boron concentrations in drinking water samples were 1.57 +/- 0.06 mg/l for boron group while the corresponding value for the control group was 0.016 +/- 0.002 mg/l. RNA isolation was performed using PAX gene RNA kit on the blood samples from the subjects. The RNA was then reverse transcribed into cDNA and analyzed using the Human Transcription Factors RT2 Profiler (TM) PCR Arrays. While the boron amount in urine was detected as 3.56 +/- 1.47 mg/day in the boron group, it was 0.72 +/- 0.30 mg/day in the control group. Daily boron intake of the boron and control groups were calculated to be 6.98 +/- 3.39 and 1.18 +/- 0.41 mg/day, respectively. The expression levels of the transcription factor genes were compared between the boron and control groups and no statistically significant difference was detected (P > 0.05). The data suggest that boron, intake at 6.98 +/- 3.39 mg/day, which is the dose at which beneficial effects might be seen, does not result in toxicity at molecular level since the expression levels of transcription factors are not changed. Although boron intake over this level will seem to increase RNA synthesis, further examination of the topic is needed using new molecular epidemiological data. (C) 2016 Elsevier GmbH. All rights reserved.
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    Investigation of BRAF mutation analysis with different technical platforms in metastatic melanoma
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Sener, E; Yildirim, P; Tan, A; Gokoz, O; Tezel, GG
    In metastatic melanoma, the detection of somatic mutations in the BRAF gene is crucial regarding patient selection for targeted therapy. Several screening methods have been developed to identify BRAF gene mutations. In this study, our objective was to evaluate the detection of the BRAF V600 mutations using two molecular methods, real-time polymerase chain (real-time PCR) assay and pyrosequencing, and immunohistochemistry (IHC), and to compare the results of these different technical platforms. This study included 98 patients diagnosed with metastatic melanoma at the Hacettepe University, Department of Pathology between 2002 and 2014. BRAF mutation analysis was tested with real-time PCR, pyrosequencing and IHC methods. The results of all three tests were compared with a reference test, and the sensitivity, specificity rates and kappa coefficient values were analysed for each test. We successfully analysed BRAF mutations using all three methods in 92 patients. According to our findings, the pyrosequencing method had the highest kappa value regarding the determination of BRAF V600 mutations. The kappa values were at almost perfect agreement levels in pyrosequencing and realtime PCR assay (kappa coefficient for pyrosequencing = 0.895 (95% CI: 0.795-0.995); kappa coefficient for real-time PCR=0.871 (95% CI: 0.761-0.981). The kappa value was at a substantial agreement level in the IHC analysis (kappa coefficient = 0.776 (95% CI: 0.629-0.923). According to our results, we found that real-time PCR and pyrosequencing methods were equally excellent in determination of BRAF V600 mutations. The IHC method, which is commonly used in routine pathology practice, can also be safely used as a screening test for determination of BRAF V600 mutations. (C) 2017 Elsevier GmbH. All rights reserved.
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    Histophysiological effects of fluid resuscitation on heart, lung and brain tissues in rats with hypovolemia
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Ekerbicer, N; Inan, S; Tarakci, F; Cilaker, S; Ozbek, M
    The efficacy of using colloids and crystalloids in the treatment of hypovolemia still remains controversial. An important aspect in treating hypovolemia is to re-establish normal tissue hemodynamics after fluid resuscitation. Production of nitric oxide (NO) or growth factors such as transforming growth factor beta (TGF-beta) has been identified as a key mechanism in physiological and pathological processes in the different systems. This study was designed to investigate the histophysiological effects of resuscitation with different plasma substitutes on the heart, lung and brain tissues following acute blood toss in mate Sprague-Dawley rats weighing 250-280 g (n = 30). After anesthesia with sodium pentobarbital, the left femoral. vein and artery were cannulated for the administration of volume expanders and for direct measurement of arterial pressure and heart rate. Twenty rats were bled (5ml/10min) and infused (5ml/10min) with one of four randomly selected solutions, (a) human albumin, (b) gelatin (Gelofusine), (c) dextran-70 (Macrodex); or (d) physiological saline (0.9% isotonic saline). Five control rats were bled without infusion. Tissue samples were taken and fixed in 10% formalin solution, then processed for embedding in paraffin wax. Sections were cut and stained with hematoxylin and eosin. Indirect immunohistochemical labelling was performed to reveal binding of primary antibodies against endothelial. nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and TGF-beta. Mild immunoreactivity of eNOS was observed in endothelial cells of vessels in brain, heart and tung tissues. Increased immunoreactivities of eNOS, iNOS and TGF-beta were observed in the non-fluid resuscitated group in these organs; mild, moderate, moderate and strong immunoreactivities were seen in the albumin, gelatin, physiological saline and dextran-70 treated groups, respectively. Immunoreactivities of iNOS and TGF-beta in the non-fluid resuscitated group were increased significantly, in comparison to the other groups, apart from the dextran-70 treated group. The results of this study show that gelatin solution and physiological saline may be of use after acute blood loss, and dextran-70 is not the preferred resuscitation fluid in the early stages of acute blood loss. It was concluded that albumin solution is the preferred fluid for resuscitation. (c) 2006 Elsevier GmbH. All rights reserved.
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    Effects of chronic amiodarone treatment on rat testis
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Özkaya, AK; Dilber, E; Gürgen, SG; Kutlu, Ö; Cansu, A; Gedik, Y
    Amiodarone is a potent agent used to treat tachyarrhythmias, which are especially refractory to other medications, in both adults and children. Although widely used as an antiarrhythmic drug, amiodarone causes many serious adverse effects that limit its use. This study investigated the possible morphological and apoptotic effects of amiodarone on rat testes. Amiodarone was administered to male Sprague-Dawley rats at doses of 20 or 200 mg/kg/day for 14 days. A histopathological examination of testicular tissue revealed the presence of inflammatory cells in the seminiferous tubule lumen together with swelling and vacuolization in the cytoplasm of some spermatogonia; these effects occured in a dose-dependent manner. Immunohistochemical staining showed evidence of apoptosis, including caspase-3, caspase-9, Bax and increased DNA fragmentation was detected via a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. In conclusion, the results show that chronic amiodarone treatment causes dose dependent degenerative and apoptotic effects on rat testes. (C) 2016 Elsevier GmbH. All rights reserved.
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    Histopathological and ultrastructural effects of Losartan on embryonic rat kidney
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Akil, I; Inan, S; Gurcu, B; Nazikoglu, A; Ozbilgin, K; Muftuoglu, S
    The aim of our study was to investigate the histopathological, immunohistochemical and ultrastructural effects of Losartan (a selective angiotensin II type-1 receptor blocker) on renal development in rats. Twelve pregnant rats were divided into control and experimental groups. In the experimental group, Losartan (10mg/kg/day) was given via nasogastric tube, between the sixth day of implantation and time of sacrifice on embryonic days 18 and 20. All formalin-fixed, paraffin wax-embedded renal tissue sections were stained with hematoxylin and eosin or labelled for binding of primary antibodies against transforming growth factor-it (TGF-beta 1,-2,-3) using an avidin-biotin-peroxidase method. For electron microscopic examination, samples were fixed with glutaraldehyde and osmium tetroxide and embedded in araldite. Glomerular basement membrane (GBM) thickness was measured and compared using an unpaired t-test. Angiotensin II type-1 receptor antagonism by Losartan inhibited renal growth and delayed nephron maturation. Increased immunoreactivity of TGF-beta's was observed in developing nephron precursors and interstitial cells in the experimental group. Electron microscopical examination showed that thickening of the GBM was normal in the control group but an irregular thickening was seen in the experimental group (p < 0.001). It was also seen that epithelial cells of developing tubules underwent apoptosis in the experimental group. Thus, renal development in rats seems to depend on an intact renin-angiotensin system. (c) 2005 Elsevier GmbH. All rights reserved.
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    The effects of Gemcitabine and Vinorelbine on inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) distribution of MCF-7 breast cancer cells
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Zeybek, ND; Inan, S; Ekerbicer, N; Vatansever, HS; Karakaya, J; Muftuoglu, SF
    Gemcitabine, which induces S-phase arrest, and Vinorelbine, which arrests microtubule organization, are two agents that have demonstrate preferred anti-tumor activity. Nitric oxide acts in diverse functions including anti-tumor and anti-pathogenic activities. In this study, we aimed to examine the distribution of immunoreactivities of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in cells of the MCF-7 breast cancer cell line in response to treatment with Gemcitabine (G), Vinorelbine (V) and combination of Gemcitabine and Vinorelbine (G+V). The distributions of iNOS and eNOS were determined by using indirect immunoperoxidase or immunofluorescence methods and ELISA. Cells incubated with G, V and G+V for 24, 48 and 72 h were immunolabelled with anti-eNOS and anti-iNOS primary antibodies. Apoptosis was determined by TUNEL assay. A significant increase of eNOS immunolabelling on MCF-7 cells treated with G and G+V was observed. Apoptotic cells were also detected in G, V and G+V treated MCF-7 cells. The immunolabelling of iNOS was detected in all groups but this immunoreactivity was not different among the groups. In conclusion, while G treatment, induced S-phase arrest, triggered the NOS pathway after treatment of MCF-7 cells, V treatment, arrested microtubule organization and did not change the NOS pathway. Detection of increased eNOS immunolabelling and apoptosis after G treatment of MCF-7 cells could be important to the treatment of human breast cancer. (C) 2009 Elsevier GmbH. All rights reserved.
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    Analysis of transferred keratinocyte-like cells derived from mouse embryonic stem cells on experimental surgical skin wounds of mouse
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Vatansever, HS; Uluer, ET; Aydede, H; Ozbilgin, MK
    Autologous/allogenic skin grafts constituted from differentiated adult or embryonic stem cells can be used in treatment of skin disorders. In our study we aimed to differentiate keratinocytes from mouse embryonic stem cells and the transfer of viable keratinocyte-like cells to a model of surgical skin wound of mouse. Embryoid bodies, derived from mouse embryonic stem cells, were cultured on basement membrane matrix with added BMP-4 for 10 days. The identification of differentiated keratinocyte-like cells was done by detection of cytokeratin-8 and cytokeratin-14 localization using an indirect immunoperoxidase technique and transmission electron microscopy evaluation. Distribution of BrdU, cytokeratin-8 and cytokeratin-14 were evaluated using an indirect immunoperoxidase technique from the experimental (dressing including BrdU labelled cells applied after the surgical wound was created on mouse), control (only the surgical wound was created on mouse) and sham (only the dressing applied after the surgical wound was created on mouse) in groups after 3, 5 and 7 days. Immunohistochemically and ultrastructurally, cells derived from mouse embryonic stem cells were similar to differentiated keratinocyte-like cells. Differentiated keratinocyte-like cells were demonstrated by positive BrdU, cytokeratin-8 and cytokeratin-14 staining after transfer to the wound area. In the experimental group wound healing was better after transferring differentiated keratinocytes when compared to the sham and control groups. In vivo continuity and usability of derived cells are very important issues. In wound repair mechanisms, keratinocyte-like cells could provide positive effects during the wound healing and could be used in clinical treatments of wound repair process. (C) 2012 Elsevier GmbH. All rights reserved.
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    Significance of tyrosine kinase activity on malign transformation of ovarian tumors
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Zeren, T; Inan, S; Vatansever, HS; Ekerbicer, N; Sayhan, S
    Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are members of the polypeptide growth factor family. The epidermal growth factor-receptor (EGF-R) is a receptor tyrosine kinase of the ErbB family. Many types of cancer, including ovarian cancer, display enhanced EGF-R immunoreactivity on their cell surface membranes. Also, an increase in TGF-alpha synthesis and secretion usually occurs in human carcinoma cell lines. In this study, we compared the immunoreactivities of TGF-alpha and EGF-R in ovarian tumors and related immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumor and serous-mucinous adenocarcinoma of the ovary (n = 10 each) were stained with hematoxylin-eosin and labeled for binding of primary antibodies against TGF-alpha and EGF-R using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare immunohistochemical labeling intensities. Increased immunoreactivity of EGF-R and moderate immunoreactivity of TGF-alpha was detected in adenocarcinomas. There was no significant difference in the immunoreactivity of TGF-alpha among the histologic types of ovarian tumors. The results of this study support the hypothesis that EGF-R may be a more useful marker than TGF-alpha in epithelial ovarian tumors. (c) 2007 Elsevier GmbH. All. rights reserved.
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    Histopathological and ultrastructural effects of glycolic acid on rat skin
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Inan, S; Oztukcan, S; Vatansever, S; Ermertcan, AT; Zeybek, D; Oksal, A; Giray, G; Muftuoglu, S
    Use of alpha hydroxy acids (AHA) to ameliorate specific dermatological, problems with keratinization has become fairly widespread. The aim of this study was to evaluate the effects of the AHA derivative of glycolic acid, applied in different dosages, on rat skin using tight and electron microscopy. Skin biopsies were taken from the dorsal side of rats (n = 16) and at the end of each week after applying solutions containing AHA: week 1, 8% (n = 5); week 2, 50% (n = 5); week 3, 70% (n = 6). The skin samples were fixed in 10% formalin for histology and 2.5% glutaraldehyde solution for electron microscopy and processed using routine protocols. Histological sections were stained with hematoxylin and eosin (H-E), Masson's trichrome and were also Labelled for binding of a primary antibody against collagen I using the avidin-biotin-peroxidase method. The epidermal thicknesses were measured and the fibroblast count of the dermis was taken and the results compared using the statistical ANOVA test. Semi-thin sections were stained with toluidine blue-azure II solution and ultrathin sections were contrasted with uranyl acetate and lead citrate. Histochemical and immunohistochemical observations demonstrated that AHA treatment resulted in statistically significant increased thickness of the epidermis and an increase in numbers of active fibroblasts and in the amount of dense collagen, especially at higher dosages of AHA. Ultrastructural examination of rat skin from AHA-treated groups showed cytoplasmic vacuolization in epidermal keratinocytes, intercellular dysjunctions, and increased quantities of organized bundles of collagen fibers in the dermis. The use of AHA in appropriate dosages has been found to play an important role in the treatment of specific skin disorders, however, the harmful effects of use of AHAs at higher concentrations should not be ignored. We conclude that alpha hydroxyl acids have a wide spectrum of use in the field of dermatology but, due to side-effects, their use, dosage, and time frame should be restricted to the advice of dermatologists. (C) 2006 Elsevier GmbH. All rights reserved.
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    Boron intake, osteocalcin polymorphism and serum level in postmenopausal osteoporosis
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Boyacioglu, O; Orenay-Boyacioglu, S; Yildirim, H; Korkmaz, M
    The relationship between daily boron intake and osteocalcin-mediated osteoporosis was studied in boron-exposed postmenopausal women. It is known that boron and osteocalcin are important in bone metabolism, however the effect of boron in bone metabolism has not been fully discovered. The study was performed on 53 postmenopausal women aged 55-60 living in parts of Balikesir, Turkey, where the subjects are naturally exposed to high (>= 1 mg/L) or low (< 1 mg/L) boron concentration in drinking water. 24-h urine samples were collected from all participants and creatinine clearance was detected. Boron intake levels of the subjects whose clearance levels were between 80-124 mL/min were measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) in urine samples. Serum osteocalcin levels of the subjects were measured by osteocalcin enzyme-linked immunosorbent assay (ELISA) kit. Osteocalcin polymorphism rs1800247 was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum osteocalcin levels in boron-exposed postmenopausal women were significantly higher than that of control group (P <= 0.05) and the correlation between the serum osteocalcin level and rs1800247 polymorphism was not significant in both groups (P > 0.05). The differences in the distribution of osteocalcin genotypes and alleles in postmenopausal women were not significant between the boron exposed and the control groups (P > 0.05). Serum osteocalcin level in the CC genotype was significantly higher compared to the TC genotype in boron-exposed group (P <= 0.05). Our study suggests that daily boron intake of 1 mg/L may affect bone metabolism in postmenopausal women positively.
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    Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility
    (ELSEVIER GMBH, URBAN & FISCHER VERLAG) Vatansever, HS; Lacin, S; Ozbilgin, MK
    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 Bc1-2, 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. White 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. (c) 2005 Elsevier GmbH. All rights reserved.