Effect of dietary supplementation on the prognostic value of urinary and serum 8-isoprostaglandin F2α in chemically-induced mammary carcinogenesis in the rat

<p>Abstract</p> <p>Backround</p> <p>The aim of the present study was to assess the effects of zinc or copper and polyphenolic compounds on the 8-isoprostaglandin F_2αconcentration in the serum and urine of rats with mammary cancer (<it>adenocarcinoma</it>) induced with 7,12-dimethylbenz[a]antracene. The research focused on the kinetics of alterations in urinary 8-isoPGF_2αat the early stage of carcinogenesis as well as the influence of dietary factors on the process. The impact of selected compounds on the intensity of DMBA - induced carcinogenesis was also assessed.</p> <p>Result and conclusions</p> <p>Administration of DMBA, a compound that inducers mammary tumors in experimental animals, increased the serum and urinary 8-isoPGF_2αlevels in study rats. In the rat model, diet supplementation with zinc, combined with selected polyphenolic compounds (resveratrol or genistein) yielded a statistically significant decrease in the rat serum and urinary biomarker concentration with a simultaneously significant stimulation of carcinogenesis.</p> <p>The results indicate that there is an inverse correlation between the intensity of DMBA-induced carcinogenicity and the level of 8-isoPGF_2αin urine and serum of rats.</p

The impact of antiandrogen 2-hydroxyflutamide on the expression of steroidogenic enzymes in cultured porcine ovarian follicles

We used our model system for agonism and antagonism of the androgen receptor (AR), in which the porcine ovarian follicles were exposed on the excessive concentration of an AR agonist- testosterone (T) or an AR antagonist- 2-hydroxyflutamide (2-Hf) to: (1) analyze the spatiotemporal expression of ovarian 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), cytochrome P450 17 alpha-hydroxylase/c17,20-lyase (P450c17) and cytochrome P450 aromatase (P450arom); (2) to determine the contribution of AR-mediated action during steroidogenesis and (3) to establish some correlations between the onset and expression pattern of the investigated proteins. Whole follicles (6-8 mm in diameter) isolated from mature porcine ovaries have been incubated (for 24 h) in an organ culture system in the presence of T (10(-7) M), 2-Hf (1.7 x 10(-4) M) or both T and 2-hydroxyflutamide (T+2-Hf, at the same concentrations as when added separately). Thereafter, sections obtained from cultured follicles were processed for main steroidogenic enzymes detection by immunohistochemistry. Moreover, expression of their mRNA and protein was determined by real-time PCR and Western blot analysis. Progesterone, androgens and estradiol concentrations in the culture media were measured by radioimmunoassays (RIA). Our results demonstrated that 2-Hf can influence the steroidogenic activity of porcine follicles in vitro through the blockade of AR. It was shown that follicular 2-Hf treatment brought about dramatic decline in the production of the investigated steroids. What is more the addition of 2-Hf separately caused a negative effect on 3 beta-HSD and P450c17 mRNA and protein expression by ovarian follicles, while it was without effect on P450arom mRNA level. Quite opposite effect was observed in case of the simultaneous addition of 2-Hf and T. It caused high increase, in both P450arom mRNA and its protein. What was interesting, addition T+2-Hf evoked 3 beta-HSD and P450c17 increase on mRNA level, but decreased their protein expression. This was against our expectations but the reason for that finding remains undiscovered, intriguing and worth reporting. These results suggest that alike, steroidogenic enzymes activity and their expression is associated with the presence of androgens and AR in the porcine ovary

Review of anti-adhesion prophylaxis methods – the past and the present

Abstract Formation of postoperative adhesions presents a serious and complex problem in clinical practice. Apart from standard surgical procedures, a variety of different sub-stances to prevent adhesions is available, but no universal method has been devel-oped so far. Clinical trials and animal studies on preventing the formation of postop-erative adhesions and substances that can have potential anti-adhesive properties have been carried out for over one hundred years. Considerable discrepancies and ambiguities regarding research results, as well as a great number of anti-adhesive substances to be tested, demonstrate the scope and the nature of the problem. Re-cently, new anti-adhesive fluids and pharmacological agents have been developed, which in preliminary observations seem to be almost perfect. The following paper reviews available literature on anti-adhesive methods and the authors’ limited experienc

Ogniska zakażeń szpitalnych w województwie małopolskim w latach 2011-2013

Despite the continuous advances of medicine and higher safety standards for patients, nosocomial infections are a major problem accompanying of treatment process. Infected patients are exposed to prolonged hospital stay, require additional medical procedures, theresofore their treatment and care are associated with additional costs for health facility. In the present study the number of outbreaks of nosocomial infections, which occurred in hospitals in the Malopolska province and in Poland, as well as etiological factors of the infections in the years 2011–2013 were analyzed. In the analyzed period we observed increase in the number of outbreaks of infections in Poland and in Malopolska (from 339 to 394 and from 19 to 26 in Poland and Malopolska respectively). The most frequently identified factor is C. difficile and Rotavirus, followed by K. pneumoniae ESBL, and Norovirus. There was a decrease in the number of outbreaks of unknown etiology, both in Poland and in Malopolska. The analysis identified an increase in the number of outbreaks caused by C. difficile, Noroviruses and Rotaviruses, as the main problem in the recent years. This trend occurs in the Malopolska region and in the country. However, the analysis of the reports shows improved reportability of outbreaks in Malopolska and in Poland which will allow for better control of nosocomial infections

Starość zależna: opieka i pomoc społeczna: perspektywa gerontologii społecznej

Praca recenzowana / peer-reviewed pape

Renalase is associated with adverse left atrial remodelling and disease burden in patients with atrial fibrillation undergoing pulmonary vein isolation

Background: Renalase is a catecholamine-metabolising enzyme, but its possible association with atrial fibrillation (AF) remains unknown. Aim: We sought to evaluate plasma renalase concentration in patients with AF undergoing pulmonary vein isolation (PVI) with respect to AF clinical characteristics, left atrial (LA) remodelling, and PVI efficacy. Methods: This case-control study included 69 patients (median age 58 years) with either paroxysmal (89%) or persistent (11%) AF, referred for PVI, and a control group consisting of 15 patients without AF, matched for age, sex, and comorbidi­ties. An evaluation of transthoracic echocardiography with LA speckle tracking and plasma renalase concentration using an enzyme-linked immunosorbent assay was performed. AF recurrence was defined as any AF episode on seven-day electro­cardiographic monitoring at six-month follow-up. Results: Renalase level was higher in the study group than in the control group (mean 27.99 vs. 21.48 μg/mL, p = 0.004), but it was lower in patients with persistent AF (19.05 vs. 28.77 μg/mL; p = 0.023) and among patients with AF episodes di­rectly preceding PVI (24.50 vs. 29.66 μg/mL; p = 0.04). Renalase concentration within the first quartile was associated with higher mean heart rate (70 vs. 61 bpm, p = 0.029), greater AF burden (36.9% vs. 9.3%, p = 0.027), greater LA diameter (41.1 vs. 37.9 mm, p = 0.011), and a trend towards less negative global LA strain (–9.4 vs. –13.5, p = 0.082). Logistic regres­sion revealed that global four-chamber LA strain was the only independent predictor of renalase variability (p = 0.0045). Renalase concentration did not predict AF recurrence at six-month follow-up (area under curve [AUC] = 0.614, p = 0.216). Conclusions: Low renalase level may be associated with impaired rate control, higher AF burden, and advanced LA remodel­ling in AF patients undergoing PVI, but it does not predict sinus rhythm maintenance

Marketing

Praca recenzowana / peer-reviewed pape

Influence of antiandrogen vinclozolin on porcine ovary function : an in vitro study

Androgeny to kluczowe związki biorące udział w regulacji procesów rozrodczych u samicy, działające głównie przez receptor androgenowy (AR), należący do nadrodziny receptorów jądrowych. Androgeny są jednymi z ważniejszych związków wpływających na proces folikulogenezy. Z jednej strony modulują funkcje pęcherzyka poprzez interakcje z różnymi czynnikami i wspierają różnicowanie komórek ziarnistych. Z drugiej strony, mogą hamować rozwój pęcherzyka poprzez indukcję procesu apoptozy komórek ziarnistych, co w konsekwencji może prowadzić do atrezji pęcherzyka jajnikowego. W jajnikach ssaków większość pęcherzyków ulega atrezji przed owulacją. Coraz częściej mówi się, że substancje występujące w środowisku, mogą w sposób zasadniczy wpływać na procesy życiowe wielu organizmów, w tym na różnicowanie płci u ssaków. Związki te, to Endocrine Disrupting Chemicals (EDCs), czyli m. in. związki powstające w wyniku działalności człowieka, przedostające się do środowiska i w efekcie zaburzające regulację hormonalną poprzez interakcje z receptorami hormonów steroidowych. Taki mechanizm działania negatywnie wpływa na szereg procesów zachodzących w układzie rozrodczym samicy. Celem prezentowanej pracy było określenie wpływu androgenów, testosteronu (T) i dihydrotestoseronu (DHT) oraz fungicydu o właściwościach antyandrogennych, winklozoliny (Vnz) na ekspresję AR na poziomie mRNA i białka, aktywność steroidogenną i mechanizm apoptozy zarówno w komórkach ziarnistych jak całych pęcherzykach jajnikowych świni (Ø 4-6mm). Komórki ziarniste izolowane z pęcherzyków jajnikowych hodowano przez 24 godziny i następnie dodawano: T (10-7M), DHT (10-7M) i Vnz (1,4×10-5M) osobno lub w kombinacji: T i Vnz lub DHT i Vnz na kolejne 24 godziny. Całe pęcherzyki jajnikowe hodowano narządowo przez 24 godziny, stosując warianty hodowli takie jak w przypadku hodowli pierwotnych. Androgeny (T, DHT) i antyandrogen środowiskowy winkolzolina (Vnz) wpływają na ekspresję AR na poziomie mRNA i białka w komórkach ziarnistych pęcherzyków jajnikowych świni. Wykazano lokalizację cytoplazmatyczną i około jądrową AR w komórkach ziarnistych traktowanych Vnz. Stwierdzono wzrost ekspresji AR na poziomie mRNA i białka w komórkach ziarnistych pod wpływem Vnz oraz kombinacji T+Vnz lub DHT+Vnz. W przypadku pęcherzyków jajnikowych hodowanych w obecności androgenów i antyandrogenu jednocześnie (T+Vnz i DHT+Vnz) obserwowano wzrost ekspresji mRNA AR z jednoczesnym spadkiem ekspresji na poziomie białka. W komórkach ziarnistych i pęcherzykach jajnikowych świni androgeny (T i DHT) oraz antyandrogen (Vnz) wpływają na aktywność steroidogenną. Zmiany poziomu hormonów steroidowych, tak w medium hodowlanym jak w płynie pęcherzykowym, świadczą o zaburzonym przebiegu steroidogenezy w komórkach ziarnistych i całych pęcherzykach jajnikowych świni. Androgeny (T, DHT) i antyandrogen środowiskowy winkolzolina (Vnz) wpływają w sposób znaczący na mechanizm apoptozy. Obserwowano zmiany morfologii komórek ziarnistych i całych pęcherzyków jajnikowych świni, co świadczy o destrukcyjnym wpływie tych związków na prawidłową strukturę komórki i pęcherzyka. Vnz powoduje nekrozę hodowanych komórek ziarnistych oraz indukuje apoptozę komórek ziarnistych w całych pęcherzykach jajnikowych. Wykazano, że dodanie T, DHT lub Vnz do medium hodowlanego komórek ziarnistych lub pęcherzyków powoduje uruchomienie procesu programowanej śmierci komórki, ponieważ obserwowano wzrost ekspresji i aktywności kaspazy-3. Vnz zakłóca klasyczny receptorowy oraz mitochondrialny szlak apoptozy. Ponadto wykazano, że traktowanie komórek ziarnistych Vnz powoduje spadek ekspresji białek antyapoptotycznych, z jednoczesnym brakiem wzrostu ekspresji białek proapoptotycznych. Prawdopodobnie stosowanie Vnz wpływa na prawidłowe podziały komórki (zatrzymuje cykl komórkowy), gdyż obserwowano spadek ekspresji białka p53 i surwiwiny. Co więcej, dodanie Vnz do medium hodowlanego komórek ziarnistych skutkuje wzrostem fosforylacji kinazy ERK1/2 i Akt. Sugeruje to pozagenomowy mechanizm działania Vnz. Co ważniejsze, prezentowane badania wykazały zdecydowanie antyapoptotyczne działanie wysokiego stężenia androgenów stosowanych jednocześnie z Vnz, o czym m. in. świadczy spadek ilości komórek apoptotycznych i aktywności kaspazy-3. Podsumowując uzyskane wyniki, można stwierdzić, że winklozolina może zaburzać prawidłowe funkcje jajnika, ponieważ działając za pośrednictwem AR uruchamia niegenomowe szlaki przekazywania sygnału i zakłóca fizjologiczne procesy programowanej śmierci komórkowej. W konsekwencji może to prowadzić do obniżenia potencjału rozrodczego samicy.Androgens are the key regulators in female reproductive physiology. They act primarily via the androgen receptor (AR), a member of the nuclear receptor superfamily, which operates as ligand-regulated transcription factor. Androgens are one of the most important agents influencing folliculogenesis. They can modulate follicular function by interactions with various factors and promote granulosa cells differentiation. On the other hand, androgens can antagonize follicular development by inducing apoptosis in granulosa cells and in this way they can promote follicular atresia. In mammalian ovaries the majority of follicles are lost at various stages before ovulation by atresia. Recently, there has been an increasing concern about potential for Environmental Endocrine Disrupting Chemicals (EDCs) to alter sexual differentiation in mammals. They originate as a result of human industrial activities, enter the natural environment and then disturb hormonal regulation by interaction with steroid hormone receptors. Such a mechanism of action negatively influences on many process taking place in the reproductive tract of a female. The aim of this study was to investigate whether the androgens testosterone (T) and dihydrotestosterone (DHT) and the antiandrogenic fungicide vinclozolin (Vnz) influence AR expression on mRNA and protein level, steroidogenic activity, and mechanism of apoptosis both in granulosa cells and in whole porcine ovarian follicles (Ø 4-6mm). Granulosa cells isolated from pig follicles were cultured for 24 hours, and then were exposed to T (10-7M), DHT (10-7M), Vnz (1,4×10-5M) or the equivalent concentrations of T and Vnz or DHT and Vnz for further 24 hours. Whole porcine follicles were also exposed to the same compounds and combinations of compounds for 24 hours. Androgens (T and DHT) and an antiandrogen (Vnz) influence on AR mRNA and protein expression in porcine ovarian granulosa cells and whole follicles. The immunostaining for AR was detected mainly in the cytoplasm and assembled in the perinuclear region after exposure to Vnz. Treatment with Vnz and combinations of T+Vnz and DHT+Vnz, granulosa cells resulted in an increase in the expression of AR on both mRNA and protein levels. In the whole follicles treatment with T+Vnz and DHT+Vnz resulted in an increased expression of mRNA for AR with simultaneous decrease of AR protein. In porcine granulosa cells and whole ovarian follicles androgens (T and DHT) and an antiandrogen (Vnz) affected their steroidogenic activity. Incorrect or disturbed process of steroidogenesis was observed in all experimental groups of cells and follicles. Besides all compounds tested caused the disturbance of hormonal balance in the follicular fluid. Androgens (T and DHT) and an antiandrogen (Vnz) in a significant manner influenced on the mechanism of apoptosis. Morphological changes in granulosa cells and ovarian follicles indicated destructive effects of this agents. Vnz caused massive necrosis of granulosa cells and induced apoptosis of granulosa cells in whole follicles. Androgens induced apoptosis in granulosa cells of ovarian follicles . It was found out that the addition of T, DHT or Vnz to the culture media of granulosa cells or follicles caused the induction of the process of programmed cell death, because an increased caspase-3 expression and activity have been observed. It seems that Vnz disrupted classical receptor and mitochondrial signaling pathways of apoptosis. Also, it was shown that Vnz treatment caused a decrease in the expression of antiapoptotic proteins, but without an increase in that of proapoptotic ones. Probably supplementation with Vnz altered normal cell division (cell-cycle arrest), because a decrease in p53 and survivin proteins expression has been observed. Moreover, the addition of Vnz to the culture media of granulosa cells increased phosphorylation of ERK1/2 and Akt kinases. It is suggested that Vnz may interfere with the nongenomic pathway of androgens signaling. What is more important, the presented data clearly showed that Vnz applied together with high concentration of androgens (T and DHT) exerted an antiapoptotic effect, as evidenced by the decreased number of apoptotic cells and caspase-3 activity. In conclusion, these results suggest that normal function of the ovary may be destroyed by the environmental antiandrogenic fungicide vinclozolin. It can activate the nongenomic signaling pathway used by androgens or act through the AR. This mechanism of action disturbs the physiological process of programmed cell death. It seems that selective destruction of porcine follicles is a serious consequence of their exposure to vinclozolin leading to premature ovarian failure in the affected organism