Immunohistochemical expression of hypoxia-inducible factor-1α in stromal cells of vaginal tissue in post-menopausal women with pelvic organ prolapse.

Background & objectives: Pelvic organ prolapse (POP) is a common medical condition that affects adult women of different ages. The support of a normal pelvic floor is the result of complex interactions between ligaments, muscles, connective tissue and vaginal walls. Hypoxia and oxidative stress can reduce protein synthesis in the pelvic muscles that may contribute to muscular atrophy. Hypoxia-inducible factor-1α (HIF-1α) is a transcriptional activator which, expressed in response to hypoxia, activates a number of genes involved in cellular response to hypoxia. However, a potential role of hypoxia and oxidative stress in pathogenesis of POP is not known. This study was aimed to compare the level of HIF-1α immunohistochemical expression in the vaginal stromal cells of postmenopausal women with and without POP. Methods: Samples of the vaginal tissue from 120 menopausal women were obtained during surgery, and immunohistochemical expression of HIF-1α was assessed. There were 60 women with POP while 60 women in the control group were without prolapse but with benign gynaecological diseases. Results: In post-menopausal women with prolapse, significant differences were observed in the number of HIF-1α-positive stromal cells in the vaginal tissue compared to the control group. There was a significant increase in the number of HIF-1α in the stromal cells of the vaginal tissue in women with prolapse. Interpretation & conclusions: Difference in expression of HIF-1α in stromal cells of the vaginal tissue in the post-menopausal women with and without POP suggests that prolonged hypoxia probably has an important role in the aetiopathogenesis of POP.

Influence of the grade and invasiveness of bladder cancer on disease course severity in patients with bladder tamponade resulting from a bleeding bladder cancer.

Introduction and Objectives: Urinary bladder tamponade is a common urological emergency, but it has so far been insufficiently researched. The aim of our study was to show the association between the characteristics of bladder cancer (grade and invasiveness) and disease course severity based on blood hemoglobin (Hgb) count at admission, the need for red blood cell transfusion (RBCT), and the length of hospitalization in patients suffering from bladder tamponade. Materials and Methods: A retrospective, cross-sectional study was conducted, namely, including 25 adult patients surgically treated for bladder tamponade resulting from a bleeding bladder cancer. Results: Patients with low-grade cancer had statistically significantly higher mean Hgb values at admission (101.14 ± 8.26 vs. 87.22 g/L ± 10.64 g/L, P = 0.005), as well as a lower mean number of received units of RBCT (0.71 ± 0.76 vs. 2.39 ± 1.46, P < 0.001) and a shorter hospitalization (2.43 ± 0.55 vs. 4.36 ± 1.04 days, P = 0.009) than those with high-grade cancer. Patients suffering from nonmuscle-invasive bladder cancer (NMIBC) had statistically significantly higher mean Hgb values at admission (96.69 ± 9.86 g/L vs. 81.22 ± 7.23 g/L, P = 0.001), as well as a lower mean number of received units of RBCT (1.31 ± 1.2 vs. 3 ± 1.41, P = 0.004) and a shorter hospitalization (3.31 ± 1.14 vs. 4.78 ± 0.97 days, P = 0.004) than those with muscle-invasive bladder cancer. Conclusion: Low-grade bladder cancer and NMIBC are associated with a milder clinical course of bladder tamponade.

First Croatian transvaginal laparoscopically assisted cholecystectomies.

BACKGROUND/AIMS: The aim of this study was to determine the feasibility and technical aspects of a new endoluminal surgical procedure: transvaginal laparoscopically assisted endoscopic cholecystectomy. METHODOLOGY: Three female patients underwent transvaginal laparoscopically assisted endoscopic cholecystectomy (aged 40, 61 and 33 years). Pneumoperitoneum was created through a 5mm supraumbilical incision. Through the posterior fornix of the vagina the second 10mm trocar, laparoscope and 5mm laparoscopic grasper were introduced. The gallbladder was dissected using standard 5mm laparoscopic grasper, hook, electrocoagulation and harmonic shears introduced supraumbilically. The dissected gallbladder was removed in a specimen retrieval bag. RESULTS: Transvaginal laparoscopically assisted endoscopic cholecystectomy was feasible in all patients. No intraoperative or postoperative complications were observed and there was no need for extra-umbilical skin incisions. Total operative time ranged between 60 and 75 minutes. Median length of hospital stay was 1 day. CONCLUSIONS: This was the first clinical application of transvaginal laparoscopically assisted cholecystectomy in Croatia. The initial clinical application of this technique in 3 female patients was feasible, effective and safe when performed by experienced laparoscopic surgeons using standard laparoscopic instruments.

Apoptotic and anti-apoptotic factors in early human mandible development.

The regulators of apoptosis Bcl-2, Bax, caspase-3, p53, and Hsp70 were analyzed immunohistochemically in the developing human mandible of eight human conceptuses from weeks 5 to 10 of gestation. During this period, all proteins displayed an increased pattern of expression in the mandible ectomesenchyme and in newly formed bone, except for caspase-3, which showed decreased expression in the ectomesenchyme, but appeared first in the ossification zone at the 7th wk of development. Simultaneously, the oral epithelium showed weak (p53) to strong (hsp70) expression of all proteins investigated, while in Meckel's cartilage cells, bcl-2 was expressed weakly and hsp70 was expressed moderately. Cells on the surface of the forming bone were predominantly bax positive, and only occasionally bcl-2 positive. Only a few cells on the surface and inside the bony spicules co-expressed bax and bcl-2. Terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick-end labelling (TUNEL)-positive cells were found to be apoptotic osteoblasts. The expression of all proteins investigated changed dynamically during early mandible development and the subsequent differentiation of Meckel's cartilage and bone. While interactions between those factors might be associated with the survival of Meckel's cartilage, in the ossification zone they might participate in the control of cell numbers, mineralization, and bone remodelling. Among many other factors, precise orchestration of pro- and anti-apoptotic factors contributes to normal mandible development.

The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome.

PURPOSE: To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". MATERIALS AND METHODS: 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). RESULTS: There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (χ²=2.7; p=0.100) and LMWH treated pregnancies (χ²=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (χ²=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. CONCLUSION: The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended.

Difference in expression of collagen type I and matrix metalloproteinase-1 in uterosacral ligaments of women with and without pelvic organ prolapse.

OBJECTIVE: To compare the expression of collagen type I and matrix metalloproteinase-1 (MMP-1) in uterosacral ligament biopsies from women with and without pelvic organ prolapse (POP). STUDY DESIGN: Uterosacral ligament biopsies were obtained from women with POP (n=46) and control subjects (n=49). Immunohistochemistry for collagen type I and MMP-1 was performed on formalin-fixed and paraffin-embedded sections. The two groups were matched for age, body mass index, parity and postmenopausal status. Statistical Package for the Social Sciences Version 13.0 was used for statistical analysis. RESULTS: The expression of collagen type I (p=0.034) and MMP-1 (p=0.038) differed between women with POP and control subjects. There was increased expression of MMP-1 and decreased expression of collagen type 1 in uterosacral ligaments of women with POP compared with control subjects. CONCLUSIONS: This difference indicates a possible relationship between POP and the immunohistochemical expression of collagen type I and MMP-1 in uterosacral ligaments.