IFN-beta reverses the lipopolysaccharide-induced proteome modifications in treated astrocytes.

Astrocytes have a key role in the pathogenesis of several diseases, including multiple sclerosis, and are proposed as a possible target for immunotherapy. Our earlier study reported that astrocytes treated with IFN-beta modified their biomechanical properties possibly due to changes in the expression of the proteins involved in cytoskeleton organization and other important physiological processes. To gain insight into the mechanism underlying IFN-beta action during inflammation, we stimulated astrocytes with LPS, a bacterial wall component used as a model for both in vitro and in vivo immunological stimulation of microglia and astrocytes. We showed that IFN-beta reverses the effects of LPS on the proteome of astrocytes. To better examine this result, we performed a proteomic analysis of astrocytes treated with LPS or LPS plus IFN-beta. Treatment with LPS caused increases both in a series of proteins mainly involved in cytoskeletal changes and in protein degradation, as well as protective enzymes like superoxide dismutase. IFN-beta reverses LPS effects on astrocyte proteome, supporting its protective role during inflammatory insults.

Age-related pelvic floor modifications and prolapse risk factors in postmenopausal women.

OBJECTIVE: Genital prolapse is frequent in postmenopausal women; it describes the loss of support to the pelvic organs, resulting in a herniation of these into the vaginal channel. This problem affects 50% of parous women, and at least 50% of all women develop a mild form of genital prolapse after pregnancy. METHODS: An extensive literature review from 1990 to 2008 was performed on prolapse etiology and its risk factors; analyzing the data, we reviewed the genetic and biological aspects, age-related prolapse, biological tissue modifications, surgical problems, pelvic musculature modifications, and neuropathy. RESULTS: Data suggested that aging, pelvic trauma, and surgery evoke tissue denervation and devascularization, anatomic alterations, and increased degradation of collagen; all of these may lead to a decrease in mechanical strength and predispose an individual to prolapse. It has been demonstrated that there is a reduction in protein content and estrogens in uterosacral ligaments, in the vagina, and in the parametrium of women with prolapse. This is a possible explanation for why many surgical procedures to correct prolapse fail and recurrences after surgical correction are frequent. CONCLUSIONS: Even if the etiology of pelvic prolapse is poorly defined and multifactorial, aging risk factors, such as biomechanical abnormalities in connective tissue composition, hormonal deficiency, and irregular tissue metabolism, are nonmodifiable and therefore largely stated in clinical practice. Regardless of future developments, based on the reported findings, prolapse therapy will be more influenced by genetics, biological pelvic changes, changes in tissue homeostasis, and topical hormones, rather than general pelvic corrective surgical anatomy.

An outlook on ovarian cancer and borderline ovarian tumors: focus on genomic and proteomic findings.

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches.

Biomechanical and proteomic analysis of INF- beta-treated astrocytes.

Astrocytes have a key role in the pathogenesis of several diseases including multiple sclerosis and were proposed as the designed target for immunotherapy. In this study we used atomic force microscopy (AFM) and proteomics methods to analyse and correlate the modifications induced in the viscoleastic properties of astrocytes to the changes induced in protein expression after interferon- beta (IFN-beta) treatment. Our results indicated that IFN-beta treatment resulted in a significant decrease in the Young's modulus, a measure of cell elasticity, in comparison with control cells. The molecular mechanisms that trigger these changes were investigated by 2DE (two-dimensional electrophoresis) and confocal analyses and confirmed by western blotting. Altered proteins were found to be involved in cytoskeleton organization and other important physiological processes.

Closure versus non-closure of the visceral peritoneum (VP) in patients with gestational hypertension--an observational analysis.

INTRODUCTION: Caesarean section (CS) is one of the most frequently performed surgical procedures worldwide. Surgical variants include closure and non-closure of the peritoneum: in case of non-suturing the visceral peritoneum (VP), abnormal fluid collections such as blood clots may lead to formation of a hematoperitoneum. MATERIAL AND METHODS: In this retrospective, observational study we reviewed 1848 patients with gestational hypertension (GH) undergoing repeat and primary CS performed by non-closure of the visceral peritoneum (VP). RESULTS: Six of these patients had major early post-CS complications: 5 patients experienced hypovolaemic shock that required urgent operative intervention. Four patients underwent repeat laparotomy and one patient was treated by laparoscopy. CONCLUSION: As an early major post-CS complication, hematoperitoneum occurs in cases with poor haemostasis and/or with haemodynamic disorders such as GH. A decrease in blood pressure (BP) during CS caused by spinal/epidural anaesthesia and the following BP increase in GH patients may favour bleeding complications. Closure of the VP may facilitate early detection of a subperitoneal hematoma. In contrast, hematoperitoneum may develop in cases of non-closure of the VP followed by hypovolemic shock. Early and aggressive intervention results in excellent prognosis of this complication.

Effects of visceral peritoneal closure on scar formation at cesarean delivery.

OBJECTIVE: To determine the effect of closure or non-closure of the visceral peritoneum at cesarean delivery on uterine scar formation assessed at repeat cesarean delivery. METHODS: Women undergoing initial cesarean delivery were allocated into 2 groups: group 1 underwent visceral peritoneal closure, while in group 2 the visceral peritoneum was not closed. At repeat cesarean delivery 4 specimens from the initial uterine scar were collected and assessed by light microscopy and scanning electron microscopy. RESULTS: In group 1, 57% of women had adhesions compared with 20.6% in group 2 (P<0.05). Light microscopy revealed reactive mesothelial hyperplasia (51.8% vs 13.7%), submesothelial fibrosis (48.1% vs 6.8%), and neoangiogenesis of mesothelial stroma (44.4% vs 12%) in group 1 and group 2 patients, respectively (P<0.05). Scanning electron microscopy showed more patients with pericytes on the surface of microvessels in group 1 compared with group 2 (26.3+/-1.4 vs 11.5+/-1.1 patients; P<0.05). CONCLUSION: Closure of the visceral peritoneum at cesarean delivery may produce an inflammatory reaction and adhesions, evidenced by reactive and regenerative mesothelial hyperplasia and submesothelial fibrosis.

Endometriosis management: workflow on genomics and proteomics and future biomolecular pharmacotherapy.

BACKGROUND: Endometriosis is an estrogen-dependent disease, associated with pelvic pain and infertility, with still limited knowledge of the pathogenesis, pathophysiology of related infertility and evolution. OBJECTIVE: To investigate proteogenomic approaches and new trends of endometriosis treatment. METHODS: A literature search was carried out for all articles on endometriosis related to immune system, and to non-hormonal, antiangiogenic and experimental therapies. RESULTS/CONCLUSIONS: Classic endometriosis pharmacotherapy is represented by GnRH agonists, oral contraceptives and Type II progesterone receptor ligands. New proteomic and genomic technologies could help to clarify the aetiology of endometriosis and promise the rapid identification of a new generation of drugs with a specific molecular target, with the aim to ameliorate the patients' quality of life.

Hormonal carcinogenesis and socio-biological development factors in endometrial cancer: a clinical review.

OBJECTIVE: Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries and the eighth leading cause of cancer death in women; it typically arises in the sixth or seventh decade of life. The aim of this review was to evaluate possible roles of genetic and socio-biological factors in type I endometrial cancer, largely confined to pre- and perimenopausal women, with a history of estrogen exposure and/or endometrial hyperplasia. METHODS: An extensive literature review, from 1990 to 2007 was performed on modifiable risk factors for type I endometrial cancer. Additionally, carcinogenesis mechanisms, biomarker and hormonal and biomolecular approaches to cancer detection, progression and monitoring and socio-biological factors were reviewed. RESULTS: Several socio-biological and lifestyle characteristics, such as hormone replacement therapy, glycemic index, obesity, alcohol use, antipsychotic medication, melatonin, physical activity and variants in hormone metabolism genes have been identified as risk factors for developing endometrial cancer of type I, the majority of which are associated with excess estrogens causing continued stimulation of the endometrium. There is a genetic link to non-polyposis colorectal cancer syndrome, but association of endometrial cancer risk to other genetic polymorphisms has yielded conflicting results. CONCLUSIONS: Many factors linked to hormonal imbalance, such as obesity, weight change, body size, alcohol, hyper-androgenic states, glycemic index and antidepressant agents, influence the endometrial cancer risk, central to which are endogenous and exogenous estrogen hyperstimulation of the endometrium. Conversely, smoking cigarettes, diet, physical activity and melatonin production seem to reduce the risk of cancer development. Other external factors fit well with the unopposed estrogen theory, but more studies are needed to investigate modifiable and added risk factors for endometrial cancer.

Abdominopelvic tuberculosis in gynaecology: laparoscopical and new laboratory findings.

INTRODUCTION: Tuberculosis (TB) is a rare curable infective disease, caused mainly by Mycobacterium tuberculosis, which in abdominopelvic (AP) localisation, can mimic a disseminated carcinomatosis. Symptoms of AP-TB are non-specific, so diagnosis is difficult and elusive as the affected patients have normal chest X-ray and elevated levels of CA125. Female ultrasonographic features of AP-TB mimic peritoneal carcinomatosis, and the computed tomography has also been suggested to be helpful, but the final diagnosis was reached by histology and serology. AIM OF THE STUDY: To propose the validity of the combination of laparoscopy (LPS), histopathology and enzyme-linked immuno-spot (ELIspot) in the diagnosis of AP-TB. METHODS: In the last two years, we had six women with suspect of AP-TB, who, after the routine exams, were referred for a diagnostic LPS that revealed turbid-free fluid in pelvis or ascites (collected for serology), multiple peritoneal and/or bowel tubercles (randomly sampled), fibrous bands, adhesions, hyperaemic and oedematous bowel loops. RESULTS: LPS diagnosis was confirmed by intra-LPS biopsy of nodules and histological examination of specimens: epithelioid granulomas with central caseous necrosis in five patients (83.3%) and a non-caseating granulomatous inflammation in the last one. An outer layer of epithelioid histiocytes and Langhans cells was present in all patients. Using the ELIspot technique performed on free fluids, the final diagnosis of TB was made in all patients. CONCLUSIONS: Even if gynaecological LPS appearance of the peritoneum can mimic other conditions, ELIspot and histopathological exam can confirm the suspect of AP-TB.

Ovarian cancer biomarkers: a focus on genomic and proteomic findings.

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers; several studies, analyzing clinical data and pathological features on ovarian cancers, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomarker discovery, but their validity should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management.Therefore, considerable interest lies in identifying molecular prognostic biomarkers and protein indicators to guide treatment decisions and clinical follow up; the current state of knowledge about the potential clinical value of gene expression profiling in ovarian cancer is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian tumors, identifying different subtypes of ovarian cancer and identifying cancer likely to be responsive to therapy.In this elaborate we discuss the use of novel molecules, discovered by proteomics and genomics approaches, as potential protein biomarkers in the management of ovarian cancer, to improve the anticancer therapy for malignant ovarian tumors and to monitor the clinical follow up.