Frequent methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene in pancreatic endocrine tumors

Molecular mechanisms contributing to the tumorigenesis of pancreatic endocrine tumors (PETs) are still not well understood. Allelic deletions at chromosome 22q12.3 were detected in about 30-60% of PETs, suggesting that inactivation of one or more tumor suppressor genes on this chromosomal arm is important for their pathogenesis. Because the putative tumor suppressor gene tissue inhibitor of metalloproteinase-3 (TIMP-3) has been located at 22q12.3, we undertook a genetic analysis of TIMP-3 to determine its role in the tumorigenesis of PETs. Single-strand conformational polymorphism analysis, methylation-specific PCR, RNA expression analysis, and immunohistochemistry of TIMP-3 were performed in 21 sporadic PETs. Thirteen of 21 PETs (62%) revealed TIMP-3 alterations, including promoter hypermethylation and homozygous deletion. The predominant TIMP-3 alteration was promoter hypermethylation, identified in 8 of 18 (44%) PETs. It was tumor-specific and corresponded to loss or strong reduction of TIMP-3 protein expression. Notably, 11 of 14 (79%) PETs with metastases had TIMP-3 alterations, compared with only 1 of 7 (14%) PETs without metastases (P < 0.02). These data suggest a possibly important role of TIMP-3 in the tumorigenesis of human PETs, especially in the development of metastases, which has to be further evaluated in large-scale studies.     

Cellular distribution, regulated expression, and functional role of the anorexigenic peptide, NUCB2/nesfatin-1, in the testis

Nesfatin-1, product of the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as anorectic hypothalamic neuropeptide, acting in a leptin-independent manner. In addition to its central role in the control of energy homeostasis, evidence has mounted recently that nesfatin-1 is also produced in peripheral metabolic tissues, such as pancreas, adipose, and gut. Moreover, nesfatin-1 has been shown to participate in the control of body functions gated by whole-body energy homeostasis, including puberty onset. Yet, whether, as is the case for other metabolic neuropeptides, NUCB2/nesfatin-1 participates in the direct control of gonadal function remains unexplored. We document here for the first time the expression of NUCB2 mRNA in rat, mouse, and human testes, where NUCB2/nesfatin-1 protein was identified in interstitial mature Leydig cells. Yet in rats, NUCB2/nesfatin-1 became expressed in Sertoli cells upon Leydig cell elimination and was also detected in Leydig cell progenitors. Although NUCB2 mRNA levels did not overtly change in rat testis during pubertal maturation and after short-term fasting, NUCB2/nesfatin-1 content significantly increased along the puberty-to-adult transition and was markedly suppressed after fasting. In addition, testicular NUCB2/nesfatin-1 expression was up-regulated by pituitary LH, because hypophysectomy decreased, whereas human choriogonadotropin (super-agonist of LH receptors) replacement enhanced, NUCB2/nesfatin-1 mRNA and peptide levels. Finally, nesfatin-1 increased human choriogonadotropin-stimulated testosterone secretion by rat testicular explants ex vivo. Our data are the first to disclose the presence and functional role of NUCB2/nesfatin-1 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues as well as by Leydig cell-derived factors. Our observations expand the reproductive dimension of nesfatin-1, which may operate directly at the testicular level to link energy homeostasis, puberty onset, and gonadal function.     

Serum prolidase activity,oxidative stress,and nitric oxide levels in patients with bladder cancer

Objectives

Prolidase is a member of the matrix metalloproteinase family. It plays a major role in collagen turnover, matrix remodeling and cell growth. Nitric oxide (NO) regulates many processes such as collagen synthesis and matrix remodeling. Thus, NO may augment angiogenesis, tumor invasion, and metastasis. The aim of this study was to investigate total antioxidant status (TAS), malondialdehyde (MDA) and NO levels in patients with bladder cancer and to determine their relationship with prolidase activity.

Design and methods

Thirty-five patients with bladder cancer and 32 controls were enrolled. Serum TAS, MDA, prolidase activity and NO levels were determined.

Results

Serum prolidase activity, NO levels and MDA levels were significantly higher in bladder cancer than controls (all, P < 0.05), while TAS levels were significantly lower (P < 0.05).

Conclusions

Our results show that increased prolidase seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in bladder cancer.

     

Penetrating Colon Injury: Experience of a Single Centre

Objective: Penetrating colonic injuries are amongst the most discussed intra-abdominal injuries because of the complexity of their management and the severe complications. Penetrating colonic injuries can be managed by either primary repair or diversion. There is a debate over which procedure has to be used under which circumstances. In this retrospective study we analyzed our experience to contribute to the answer.

Patients and methods: The records of patients with penetrating colonic injury between January 1995 and December 2006 at the General Surgery Department of Atatürk University School of Medicine, were reviewed retrospectively. Results: One hundred and forty-one patients were included in the study. Ten patients did not need any surgical treatment. Seventy-nine patients (56%) were treated without formation of a stoma and fifty-two patients (36.8%) with formation of a stoma. The overall complication rate was 50.3% (71 patients). The rate of septic complications was 33.3%.

Conclusion: There is an ongoing debate whether formation of a stoma is indicated in penetrating colonic injury or not. Our clinical experience showed that severe faecal contamination, shock at presentation, and high CIS grades are associated with increased postoperative complications and mortality. Therefore the treatment of penetrating colonic injury in the presence of these risk factors should be stoma formation rather than primary repair.     

An enhanced treatment effect can be expected from a higher serum thyroglobulin level after radioactive iodine therapy

Annals of Nuclear Medicine - The aim of this study was to investigate if increased serum thyroglobulin (Tg) levels after radioactive iodine (RAI) showed more therapeutic effects in patients with...     

Changes in retinal vessels related to varicocele: a pilot investigation

The aim of this study was to investigate whether retinal vasculature changes had occurred (retinal artery diameter, retinal vein diameter and artery/vein ratio) in patients with varicocele. This pilot study included 50 healthy subjects with any eye disease apart from slight refractive errors and 55 patients with varicocele. Retinal arteriolar and venular diameters were measured and summarised as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Retinal microvascular diameters and the arteriolar–to‐venular ratio (AVR) were assessed with a digital retinal camera. All measurements and calculations were performed using a computer‐based program. The mean CRAE value was 151.8 ± 3.6 μm in the study group and 150.4 ± 4.5 μm in the control group. Mean CRVE value was 209.4 ± 5.9 μm in the study group and 200.1 ± 8.7 μm in the control group. AVR was found 0.72 ± 0.02 in the study group and 0.75 ± 0.03 in the control group. There were significant differences between groups in terms of CRVE and AVR. There were no significant differences between groups in terms of CRAE. The results of this study showed that the patients with varicocele showed significant changes on retinal vascular diameter.     

A comparative analysis of arterial blood flow in unexplained infertility,tubal infertility and fertile groups

We aimed to compare ovarian (O), uterine (U) and spiral (S) artery (A) resistance of patients diagnosed as fertile, unexplained infertility (UI) and tubal factor infertility (TFI) in the peri-implantation period and independent from the impact of the treatment. UI (n?=?70), TFI (n?=?75) and fertile (n?=?72) patients’ ovarian, uterine and spiral artery pulsatility index (PI), resistance index (RI) and the endometrial thickness, serum estradiol and progesterone levels were compared. The specificity and sensitivity values were calculated according to determined cutoff values. Both TFI and control groups’ UA PI values were significantly lower than the UI group’s PI values. The highest UA RI values were found in UI group and the lowest values were in the control group. UI and TFI groups’ OA PI/RI values were significantly higher than the control group. Both the control and TFI groups’ SA PI/RI values were significantly lower than UI group’s PI/RI values. UI patients’ uterine and spiral arteries PI values >1.86 and >0.85, RI values >0.80 and >0.53 can be used as a valuable test showing reduced uterine perfusion. Ovarian artery PI values >0.96 and RI values >0.58 can be used as tests showing decreased ovarian perfusion in patients with TFI. In these patients, embryo cryopreservation can be considered.     

Turkish women's level of knowledge on and attitude toward sexual health

OBJECTIVE: Sexuality is a basic human function that can affect general well-being and overall life quality. The aim of this study was to assess the level of knowledge on and attitude toward sexuality of a subgroup of Turkish women. METHODS: A cross-sectional survey including 1007 women was carried out concurrently in gynecology and urology outpatient clinics of Gazi University Faculty of Medicine, Turkey, between January 2003 and December 2003. A self-created questionnaire for data collection was administered to the participants, which addressed questions concerning their sexual life, sexual problems and attitudes towards sexuality. Statistical package for the social sciences (SPSS) was used for the data analysis of the study (SPSS ver. 11.0 Inc. Chicago, IL, USA). RESULTS: The data included 1007 patients aged 14-77 (mean: 35.6 +/- 11.1). Among the women assessed, 90.2% were married, 79.8% were premenopausal and 77.1% were currently sexually active. 68.7% entered sexual intercourse 1-2 times per week, while 28.5% had an average of 3-4. 77.8% were aware of experiencing an orgasm and 74.7% had at least one orgasm. Only 21.4% of all women had an orgasm during each sexual intercourse. 2.2% of those who had never experienced an orgasm concurrently applied to a medical center. The average age of first intercourse was 21.3 +/- 4.1 years. CONCLUSIONS: Because there is no national data on sexual health in Turkey, analysis and evaluation of the severity of the problem, and alternatives for international comparisons are not possible. In our opinion, this study presents a valuable perception into the current sexual behavior of Turkish women.