Serum tumor necrosis factor-alpha and interleukin-2 concentrations in newly diagnosed ERBB2 (HER2/neu) positive breast cancer patients

Aim: Cytokines have been associated with symptoms and adverse outcomes in breast cancer. Overexpression of ERBB2 (c-erb-b2; formerly HER2/neu), which is a member of the epidermal growth receptor family, is associated with involvement of lymph nodes, large tumor size, high grade, steroid receptor negativity, aneuploidy, high proliferation rate, and low overall survival in breast cancer. The aim of the study was to examine whether ERBB2 amplification has any effect on circulating levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) in breast cancer patients

Connective tissue alterations in women with pelvic organ prolapse and urinary incontinence

Background. Alterations in collagen synthesis and metabolism have previously been reported in patients with pelvic organ prolapse (POP) and/or urodynamic stress incontinence (USI). Since urinary incontinence does not always associate with POP, the objective of this study was to examine connective tissues from patients with USI plus POP, and patients with prolapse only. Methods. Biopsies from the uterosacral ligaments were obtained during the operation from POP patients (n = 28), and from continent women (control group, n = 12) who underwent surgery for other benign reasons. POP patients were classified following urodynamic tests and symptom questionnaire with respect to the presence (n = 14) or absence (n = 14) of USI. N-terminal propepticles of collagen (PINP and PIIINP), TGF-beta and leptin were measured in plasma. Hydroxyproline and glycosaminoglycan (GAGs) concentrations and total hexosaminidase activity were measured in tissue samples. Histological sections were prepared using Masson's trichrome technique, and digitised solutions were used for imaging provided by Soft Imaging System GmBh. Statistical evaluations were made by the Kruskal-Wallis test. Results. A significant decrease in hydroxyproline content was found in USI + POP women in comparison to controls (p < 0.05). In contrast, histopathological examination revealed an increased density of collagen in USI+POP patients. Hexosaminidase activity was decreased in both groups with POP, but no change in the amount of GAGs was observed. Markers of collagen synthesis (PINP, PIIINP), and factors related to the collagen synthesis (TGF-beta, leptin) remained unaltered. Conclusion. Our biochemical and morphological findings suggest a different organisation of collagen fibres in tissues of patients with USI + POP, when compared with both the controls and the POP patients

Acute effects of estradiol and of diethylstilbestrol: Pro- or antioxidant potential?

This study was aimed to examine the effects of a single high dose of natural and synthetic estrogens on the antioxidant defense enzymes in liver and blood. Female Wistar albino rats, four to six months old, were divided into three groups, and received either i.p. injections of diethylstilbestrol (DES; 150 mg kg(-1) b.w.) or s.c. injections of estradiol (E-2; 25 mg kg(-1) b.w.), and the third group (control) was injected the solvent. Animals were killed under light ether anesthesia three hours after injection. Cu-Zn superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) enzyme activities and fluorometric malondialdehyde (MDA) determination were performed in liver tissue homogenates and in blood. Acute estradiol injection caused a significant increase in both MDA levels and GPx activity in liver tissue when compared to the controls, (p < 0.05 and p < 0.02; respectively). Changes in both enzyme activities and MDA concentration were unremarkable following acute DES injection. In blood, only Cu-Zn SOD activity was significantly altered in blood following E-2 injection. Although the significance of alteration in GPx activity remains unclear, it is most likely related to enhanced generation of lipoperoxides. A significant increase in MDA concentrations in liver tissue is indicative of pro-oxidative damage rather than an antioxidant action by E-2

Coadministration of melatonin and estradiol in rats: Effects on oxidant status

This study was designed to investigate the effects of melatonin and estradiol (E2) on lipid peroxidation and antioxidant defense enzymes in blood and liver tissue when administered in vivo. Wistar albino rats were divided into three experimental groups and treated with either estradiol (25 mg/kg bw, s.c.), melatonin (i. p.), or melatonin plus E2, whereas control animals had diluent injections only. Melatonin was given 10 mg/kg bw x 2 intraperitoneally 30 min before and 60 min after E2 treatment to the melatonin plus E2 group. Animals were sacrificed three hours after the estradiol injection, and their blood and liver tissues were prepared for biochemical analyses. Tissue malondialdehyde (MDA) levels and antioxidant enzyme activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) - were determined in the postmitochondrial fraction, and the results were compared. Estradiol injection caused significant increases in both MDA levels and GPx activity in liver. When melatonin was administered in combination with E2, the effect of estradiol on MDA levels was abolished. A significant decrement in SOD activity occurred in melatonin-treated animals. GPx activity in the blood of E2 plus melatonin-injected animals was significantly higher than those in control animals. Melatonin-treated animals exhibited relatively lower levels of SOD activity than those from the control and E2 plus melatonin groups. This indicates that estradiol could exert oxidant action resulting in an increment in tissue malondialdehyde levels. Enhanced activity of GPx in both liver and blood following melatonin injection may indicate the contribution of this neurohormone on the antioxidant defense

Advanced oxidation protein products in obese women: its relation to insulin resistance and resistin

Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus (TZDM). Resistin, an adipocyte-secreted hormone, is thought to take a part in the development of insulin resistance and T2DM. The aim of this study was to characterise the changes in circulating levels of resistin and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in diabetic and prediabetic obese patients and to explore their relationship to insulin resistance. Attempts were also made to see whether resistin levels are related to the degree of oxidative stress, as determined by the measurement of advanced oxidation protein products (AOPPs). The study groups consisted of obese diabetic (BMI: 30-42 kg/m(2), n=28) and prediabetic (BMI: 29-41 kg/m(2), n=23) women. Fourteen healthy women, with BMI in the range 21.5-25.5 kg/m2, were taken as controls. Serum levels of TNF-alpha, IL-6, resistin, glucose, insulin and AOPPs were measured. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Diabetic and prediabetic obese patients had increases in serum resistin and TNF-a levels (P < 0.01 and P < 0.001, respectively). IL-6 levels in diabetic patients were significantly higher than in prediabetics (P < 0.05). AOPP levels were also significantly higher in diabetics than prediabetics and controls (P < 0.05 and P < 0.001, respectively); and positively correlated with blood glucose. Insulin was significantly associated with circulating resistin and TNF-a. The development of insulin resistance may contribute to the elevation of circulating resistin or vice versa. Determination of AOPPs may be helpful for monitoring the impaired glucose metabolism in obesity