Carbonyl and oxidative stress in patients with breast cancer--is there a relation to the stage of the disease?

UNLABELLED: Oxidative and carbonyl stress may, on one hand, contribute to the progression of cancer, on the other hand, they may have some antiproliferative effects. We examined serum levels of AGEs (advanced glycation end-products), CML (carboxymethyllysine) and AOPP (advanced oxidation protein products) in 86 patients with breast cancer subdivided based on the clinical stage (TNM classification), histologic grading, expression of hormonal and C-erb B2 receptors and in 14 healthy age-matched women as controls. Breast cancer patients had higher serum concentrations of AGEs (325,581 +/- 66,037 vs. 271,322 +/- 34,826 AU, p < 0.01) even in the early stage of the disease; patients with advanced breast cancer (stage III and IV) had significantly higher both AGEs and AOPP (113.0 +/- 44.9 vs. 78.1 +/- 28.4 micromol/l, p < 0.05) levels, not only compared to controls, but also compared to stages I and II. Serum levels of AOPP were higher in patients having only weakly positive expression of C-erb 2/Her-neu compared to controls and the patients having the highest C-erb2/Her-neu expression. Serum concentrations of AGEs in patients with breast cancer correlated with the age and also with the serum concentration of AOPP. IN CONCLUSION: breast cancer patients had an early increase of AGEs (marker of the carbonyl stress) followed by further increase of AGEs and elevation of AOPP (marker of oxidative stress) in patients with progressive disease. As the clinical significance of these observations is currently uncertain further studies are clearly warranted, especially with respect to their potential therapeutic implications.

[Determination concentrations of tissue factor pathway inhibitor and their changes during estrogen replacement therapy]. / Stanovení hladin TFPI a jejich zmeny pri estrogenní substitucní terapii.

OBJECTIVE: The purpose of the present study was to determine changes of tissue factor pathway inhibitor (TFPI) as a biochemical risk factors of thromboembolism during the use of different administration methods of the early estrogen replacement therapy. DESIGN: Prospective randomized cross-over trial. SETTING: General Faculty Hospital Prague. METHODS: In a 12-week prospective, randomized, interventional, cross-over trial, estradiol was administered orally in a dose of 2 mg daily or transdermally in a dose of 0,05 mg daily. Forty-five healthy postmenopausal women were included into the study within 12 weeks after the hysterectomy and ovariectomy (surgical castration). Forty-one women completed the study and their data were analyzed. The average age was of 49 +/- 6 years. An enzymatic method (IMUBIND Total TFPI ELISA test) was employed for the determination of TFPI. RESULTS: After the oral therapy, the average value of TFPI decreased statistically significantly (p < 0.0001) from 87.5 +/- 39.1 ng/ml to 68 +/- 37.49 ng/ml. CONCLUSION: Statistically the oral therapy reduced significantly TFPI compared with the transdermal method of administration. In spite of the fact that these changes cannot be unambiguously considered as risky and that the zero change of D-dimers suggests that there was no activation of the coagulation cascade, we consider the neutral effect of the transdermal therapy as more beneficial. The lack of manifestations of the coagulation cascade activation demonstrates the safety of both administration forms of the estrogen replacement therapy in the case of the early administration.

[Changes in C-reactive protein levels induced by different application forms of estrogen replacement therapy]. / Vliv ruzných aplikacních forem estrogenní substitucní terapie na hladiny C-reaktivního proteinu.

BACKGROUND: C-reactive protein is one of the independent risk factors of cardiovascular diseases. The aim of study was to find changes of hsCRP levels during transdermal and oral application of estrogen replacement therapy. METHODS AND RESULTS: Two application ways were used for 12 weeks: oral estradiol 2 mg/day and transdermal estradiol 50 microg /day (7-day patches). 41 healthy women with average age 49 +/- 6 years were randomised into prospective cross-over designed study. The average level of hsCRP before therapy was 3.3 mg/l. Elevation on 4.8 mg/I after the oral therapy was significant (p = 0.05). Transdermal estrogene therapy did not induce any significant (p = 0.87) changes. Differences between oral and transdermal therapy were significant (p = 0.002). CONCLUSIONS: The transdermal application of the estrogene replacement therapy is more safety for a vessel wall from the view of hsCRP levels. Differences between transdermal and oral application way are apparent even in case of the early start of hormone replacement therapy.

[Effect of early onset of transdermal and oral estrogen therapy on the lipid profile: a prospective study with cross-over design]. / Vliv casne zahájené transdermální a perorální estrogenní substitucní terapie na lipidový profil--prospektivní studie s cross-over designem.

OBJECTIVE: The aim of study was to evaluate changes of lipid profil during different types of estrogen replacement therapy (ERT). DESIGN: Prospective randomized study. SETTING: 1st Faculty of Medicine and General Faculty Hospital Prague. METHODS: Two routes of administration were used for 12 weeks: oral estradiol 2 mg/day and transdermal estradiol 50 microg/day (7-day pathes). Forty five healthy women with average age 49 +/- 6 years were randomised into prospective cross-over designed study. Forty one women finished the study and were analysed. Blood collections were performed from veins on the beginning of study and during last week of each therapeutic interventions. Statistical results have counted by paired t-test. RESULTS: Total cholesterol levels were not changed. Triglycerides grew up from 1,39 +/- 0,9 mmol/l to 1.61 +/- 0.8 mmol/l (p = 0,004) after oral ERT. This results showed significant (p = 0.0001) differences between oral and transdermal application because of nonsignificant (p = 0.187) lowering trends after transdermal ERT. The elevation of HDL levels after oral ERT (from 1.85 +/- 0.39 mmol/l to 2.09 +/- 0.42 mmol/l, p = 0.0001) was significantly (p = 0.009) more favourable than after transdermal ERT (to 1.96 +/- 0.42 mmol/l, p = 0.029). Changes of LDL levels are also more favourable (p = 0.0001). LDL levels decreased after oral ET from 3.06 +/- 0.97 mmol/l to 2.52 +/- 0.71 mmol/l in comparison with the nonsignificant decline on 3.0 +/- 1.0 mmol/l after transdemal ERT. CONCLUSION: All data from lipid metabolism had more favourable changes after oral ET with the exception of triglycerides. Knowledge of the patient's lipid profile and it's changes after each type of estrogen applications enable doctors individualisation of hormone replacement therapy from this point of view.

Functional and morphological changes of the brain in rats exposed to intermittent hypobaric hypoxia after the repetitive magnesium administration.

Intermittent hypobaric hypoxia induces functional and morphological changes of the brain in 25-day-old rats. Administration of magnesium has partial pro-convulsion effect in hypoxia not exposed rats and it practically does not influence the excitability of cortical neurones in rats exposed to intermittent hypoxia. Magnesium administration decreases the number of NADPH-diaphorase neurones in rats exposed to hypoxia in all studied areas of the hippocampus and dentate gyrus. In control rats this effect was only in CA1, CA3 and in the ventral blade of the dentate gyrus. Increased concentration of magnesium in cells of the hypoxia exposed rats after the repeated magnesium administration was found.

Platelet adhesion to fibrinogen, fibrin monomer, and fibrin protofibrils in flowing blood -- the effect of fibrinogen immobilization and fibrin formation.

Platelet fibrin(ogen) adhesive interactions were investigated in whole citrated blood using the rectangular perfusion chamber at wall shear rates of 300 and 1600 s(-1) with regard to the amount and structure of immobilized protein. Only single platelets adhered to adsorbed fibrinogen at both low and high surface fibrinogen concentrations and at 1600 s(-1) almost no adhesion was observed. When using spray-immobilized protein, platelet adhesion was significantly higher than to adsorbed protein. Conversion of adsorbed fibrinogen to fibrin monomer resulted in the formation of pronounced platelets aggregates and with the elevation of wall shear rate 50% decrease of adhesion took place. Degree of platelet adhesion to fibrin monomer was significantly influenced by immobilized protein concentration at both shear rates. However, the morphology (small and dense platelet aggregates) and extent of platelets adhered to fibrin pentamer was nearly the same at both shear rates. Starting with surface-bound fibrinogen and alternating addition of thrombin and fibrinogen fibrin pentamer was prepared using the stepwise synthesis. This methodology is based on the observation that at low concentration immobilized fibrin monomer binds fibrinogen in 1:1 molar ratio. The gradually formed fibrin of a defined size and composition can be a useful tool in the further understanding of the role of fibrin architecture in the pathophysiology of thrombosis.