Increased Expression of Fibroblast Activation Protein is Associated with Autophagy Dysregulation and Oxidative Stress in Obese Women with Uterine Fibroids.

Uterine fibroids (UF) represent an immense health burden throughout the world. Obesity is considered one of the risk factors for UF development; however, the underlying mechanisms remain largely unexplored. We investigated the effect of obesity on fibroblast activation and its association with inflammation, autophagy dysfunction, and oxidative stress in UF patients. Thirty-five pre-menopausal UF patients were included in this study and classified into non-obese group (BM1 ≤ 30 kg/m2, n = 15) and obese group (BMI > 30 kg/m2, n = 20). Tissue samples were collected from fibroids and adjacent normal myometrium. Our results showed increased expression of fibroblast activation protein (FAP) together with markers of autophagy, inflammation, and oxidative stress in UF patients, which were all more markedly upregulated in obese compared to non-obese patients. In addition, BMI was significantly positive correlated with FAP and autophagy markers. In conclusion, the results of the present study suggest that obesity-associated autophagy dysregulation together with increased FAP expression may increase the risk of UFs in obese women.

Environmental factors and apoptotic indices in patients with intrauterine growth retardation: a nested case-control study.

BACKGROUND: Egypt has one of the highest incidences of IUGR. The current study investigates the effect of heavy metals toxicity as risk factors of IUGR and determines the possible role of increased apoptosis in their pathogenesis. METHODS: This study was conducted in Assiut, Egypt, included 60 women diagnosed to have IUGR. We measured lead and cadmium levels in blood besides arsenic and cadmium levels in urine. Neonatal scalp hair sample were analyzed for arsenic content. Quantitative determination of human placental Bcl-2 and caspase-3 were performed. RESULTS: There are significantly higher levels of heavy metals and caspase-3 and lower levels of placental Bcl-2 in the IUGR group. The levels of heavy metals were positively correlated with caspase-3 while negatively correlated (except cadmium) with Bcl-2 levels. CONCLUSIONS: There is an alarming high level of heavy metals toxicity in Egypt that was positively correlated to IUGR. Increased placental apoptosis may be one of the possible mechanisms behind the effect.

Soluble Fas and gonadal hormones in infertile men with varicocele.

OBJECTIVE: To assess gonadal hormones in serum and semen as well as seminal antiapoptotic factor; soluble fibroblast associated (sFas) in infertile men associated with scrotal varicocele. DESIGN: Prospective. SETTING: Academic setting. PATIENTS: Eighty-eight males: fertile healthy controls (Gr1, n = 12), fertile normozoospermia with varicocele (Gr2, n = 31), and infertile oligoasthenozoospermia with varicocele (Gr3, n = 45). MAIN OUTCOME MEASURE(S): Serum and seminal gonadal hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone (T), in addition to seminal sFas. RESULTS: There were significant higher mean levels of serum FSH, serum, and seminal LH with significant lower seminal T levels in cases of Gr3 compared with Gr2. Mean seminal sFas in Gr3 were significantly higher than its levels in Gr1 and 2 (mean +/- SE 8.34 +/- 0.36 vs. 6.8 +/- 0.53 and 6.06 +/- 0.39 ng/mL, respectively). Nonsignificant differences between serum and seminal gonadal hormones were elicited between Gr2 and controls. Seminal sFas in various varicocele grades demonstrated nonsignificant differences. There were significant positive correlations between seminal sFas with serum FSH, serum LH, semen FSH, sperm abnormal forms percentage, and significant negative correlations with sperm concentration and sperm motility. CONCLUSION(S): sFas could play a role in germ cell apoptosis in varicocele-associated cases.

Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen that promotes angiogenesis, vascular hyperpermeability, and vasodilatation by autocrine mechanisms involving nitric oxide (NO). This study was undertaken to determine the potential role of VEGF in the pathogenesis of pleural effusions, and its relationship with tumour necrosis factor (TNF)-alpha and NO in the pleural fluid and serum of patients with tuberculous and malignant pleural effusions. METHODOLOGY: Pleural fluid and serum (SE) VEGF, TNF-alpha and NO levels were measured in 30 patients with exudative pleural effusion (15 with malignancies and 15 with tuberculosis). Control pleural fluid was obtained from 10 patients with transudative pleural effusion due to congestive heart failure and control serum samples were obtained from 10 healthy individuals. VEGF and TNF-alpha were measured by enzyme-linked immunosorbent assay and NO by a colorimetric method. Pleural biopsy, cytology or microbiological methods were used to make the final diagnosis. RESULTS: In patients with exudative pleural effusions, the mean pleural fluid and serum VEGF levels and their ratios (P < 0.0001 for all) and TNF-alpha levels (P < 0.01, P < 0.0001 and P < 0.05) were significantly elevated compared to those with transudative pleural effusion. In malignant effusions, pleural fluid and serum VEGF levels were significantly elevated (P < 0.001 and P < 0.0001) while pleural fluid, and serum levels and their ratios of TNF-alpha (P < 0.001, P < 0.01 and P < 0.05) were significantly lower than those in tuberculosis. NO levels did not distinguish between tuberculous and malignant effusions. CONCLUSIONS: In patients with malignant pleural effusions, levels of VEGF were significantly higher, while levels of TNF-alpha were significantly lower, than in patients with tuberculous effusions. In malignant pleural effusions, the elevated pleural fluid levels of VEGF and TNF-alpha are noteworthy. Our data support the hypothesis that blockade of VEGF, might benefit cancer patients with recurrent ascites or pleural fluid accumulation.