Behavior of vascular endothelial growth factor and erythropoietin throughout the menstrual cycle in healthy women

OBJECTIVE: To evaluate any correlations between erythropoietin (EPO) and vascular endothelial growth factor (VEGF) levels in the serum and the menstrual fluid of healthy women during the different phases of the menstrual cycle. STUDY DESIGN: Blood samples from 25 healthy female volunteers were obtained for serum VEGF and EPO detection on the 1st, 7th, 14th, 21st and 25th days of the menstrual cycle. Menstrual fluid samples for VEGF and EPO detection were obtained on the 1st and 4th days of menstruation. RESULTS: Circulating VEGF levels were found to increase in a stage-dependent cyclic manner. The mean VEGF concentration in menstrual blood on the 1st day of the cycle was significantly higher than the mean plasma value and was reduced to a significant extent on the 4th day of the cycle. We found no significant changes in serum EPO levels. Mean EPO concentration detected in menstrual blood was comparable to those in serum blood either on the 1st or 4th day of the menstrual cycle. CONCLUSION: During menstruation, a local production of VEGF occurs independent of systemic production, thus sustaining angiogenic activity in autonomous, independent ways. Our findings demonstrate the presence of an "open compartment" that reflects the systemic pattern of EPO at the uterine level that allows us to speculate on different effects beyond the angiogenic action of EPO.     

A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells

OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.     

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer     

Multimodal study of pelvic splenosis: a rare cause of abdominal pain

We present a rare case of pelvic splenosis, in a 46-year-old man, with a previous history of partial splenectomy, complaining of nonspecific pain in the lower abdominal quadrants. Splenosis is a benign acquired condition, defined as a heterotopic autotransplantation of splenic tissue in other compartments of the body, caused by rupture of the splenic capsule following trauma or splenectomy. Splenosis is often asymptomatic and incidentally found and does not require treatment. Surgery is indicated only in patients presenting with symptoms or complications. In our case, the multimodal imaging study (ultrasound, MRI, CT, and scintigraphy) allowed a correct differential diagnosis without resorting to invasive procedures, susceptible to complications     

Evaluation of depression in patients with alzheimer's disease according to the location of medical care

The objective of the study was to assess the severity of depression and to assess the level of self-sufficiency of patients with Alzheimer's disease, with particular emphasis on the place of residence and level of education. The study covered 90 people diagnosed with Alzheimer's disease. All respondents were persons over 65?years of age and residents of cities with a population over one-hundred thousand. The research method based on this work is the author's own questionnaire, the Zung Self-Rating Depression Scale (ZSDS) about depression and the Karnofsky Performance Scale Index (KPSI) for assessment of a patient's self-sufficiency. Regardless of residence, patients with Alzheimer's disease displayed signs of mild or moderate depression (100% in social welfare homes and hospital patients and 60% in those with caregivers at home). Patients with Alzheimer's disease have an unsatisfactory salary in social-economic terms. In those with Alzheimer's disease, quality of life is best for those in family homes under the care of their immediate family. People with a vocational education were the largest group of people diagnosed with Alzheimer's. Patients at home and in the hospital had a higher level of physical activity, but most patients in the hospital needed regular medical care, as did patients in social welfare homes.     

Adenovirus 36 and Obesity: An Overview

There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed.