The Impact of Diet and Physical Activity on Psoriasis: A Narrative Review of the Current Evidence.

Psoriasis is an inflammatory disease with strong genetic links and numerous features of autoimmunity that are also influenced by environment and lifestyle, including nutritional factors and physical activity (PA), with regards to the condition of patients. Recent reports in the field of nutrigenomics indicate a significant impact of nutrients in modulating microRNAs. However, few studies have evaluated the effect of nutritional systems and PA on treating psoriasis. This narrative review updates information regarding the current dietary recommendations for individuals with psoriasis and discusses the role of diet and PA in psoriasis prevention and treatment. Application of nutrigenetics in psoriasis therapy is also discussed. The PubMed and Google Scholar databases were searched using the MeSH terms for "nutrigenomics", "dietetics", "diet therapy", "diet", "physical activity", and "exercise" in conjunction with the MeSH terms for "psoriasis" and "dermatology". Evidence has shown that patients with psoriasis should have a personalized anti-inflammatory diet. Psoriasis patients are less physically active; most performed exercises of low-to-moderate intensity and were less likely to undertake regular exercise. Identifying nutrigenomic discoveries and the current lifestyle interventions associated with psoriasis can help physicians and physical therapists develop educational programs to manage and protect against the disease.

Serum Iron Level and 10-Year Survival after Melanoma.

The malignant melanoma of the skin is a very aggressive tumor. The determination of prognostic biomarkers is important for the early detection of recurrence, and for the enrollment of the patients into different treatment regimens. An evaluation of a cohort of 375 Polish MM cases revealed that a low serum iron concentration (i.e., below 893.05 µg/L) was associated with increased mortality. The study group was followed up from the date of melanoma diagnosis until death or 2020. Patients were assigned to one of four categories in accordance with increasing iron level (I-IV quarters). Patients with a low iron level of below 893.05 µg/L (I quarter) had a significantly lower survival rate when compared to the subgroup with the highest iron level, above 1348.63 µg/L (IV quarter; HR = 4.12; p = 0.028 and HR = 4.66; p = 0.019 for uni- and multivariable models, respectively). Multivariable analysis took into account the following factors: iron levels, Clark, sex, and age. Future studies based upon the examination of a larger number of cases should be conducted to confirm our findings.

Antioxidative properties of phenolic compounds and their effect on oxidative stress induced by severe physical exercise.

Extensive research has found strongly increased generation of reactive oxygen species, free radicals, and reactive nitrogen species during acute physical exercise that can lead to oxidative stress (OS) and impair muscle function. Polyphenols (PCs), the most abundant antioxidants in the human diet, are of increasing interest to athletes as antioxidants. Current literature suggests that antioxidants supplementation can effectively modulate these processes. This overview summarizes the actual knowledge of chemical and biomechanical properties of PCs and their impact as supplements on acute exercise-induced OS, inflammation control, and exercise performance. Evidence maintains that PC supplements have high potency to positively impact redox homeostasis and improve skeletal muscle's physiological and physical functions. However, many studies have failed to present improvement in physical performance. Eleven of 15 representative experimental studies reported a reduction of severe exercise-induced OS and inflammation markers or enhancement of total antioxidant capacity; four of eight studies found improvement in exercise performance outcomes. Further studies should be continued to address a safe, optimal PC dosage, supplementation timing during a severe training program in different sports disciplines, and effects on performance response and adaptations of skeletal muscle to exercise.

Morphology and serum and bone tissue calcium and magnesium concentrations in the bones of male rats chronically treated with letrozole, a nonsteroidal cytochrome P450 aromatase inhibitor.

Purpose/Aim of the study: The role of estrogen (E) in the regulation of bone turnover in women is well established, though the contributions of E versus testosterone (T) in the control of bone turnover in men are poorly understood. The aim of this study was to examine the association between chronic treatment with letrozole, a nonsteroidal inhibitor blocking the aromatase activity and thus the conversion of androgens into estrogens, and cortical bone morphology in the femur and humerus of male adult rats.Materials and Methods: Adult male rats were treated with letrozole for 6 months and the body and femur weight, morphology, collagen structure, blood serum, and bone tissue concentrations of calcium and magnesium were examined.Results: Long-term aromatase inhibition resulted in a decrease in femur mass, a wavelike arrangement of bone and lamellae with an altered organization of collagen in compact bone, a increased concentration of calcium in blood serum, and no change in calcium bone tissue concentration, magnesium serum, or bone tissue concentration. MicroCT study of the humerus revealed significant decreases of whole bone tissue volume, cortical bone thickness, cortical bone volume, and external cortical bone thickness with letrozole treatment.Conclusion: Chronic treatment with letrozole affected cortical bone structure and produced histomorphological changes in male rat bone similar to that observed in the aging processes.

Assessment of morphological changes and steroid receptors in the uteri of postmenopausal women.

INTRODUCTION: The morphology of the endometrium constantly changes in the reproductive period, depending on the levels of ovarian steroid hormones, and undergoes atrophic changes during menopause as a result of their insufficiency. The purpose of this study was to analyze morphological and morphometric changes in the mucous and muscle layers of the uterine wall in postmenopausal women, and to assess localization and number of cells showing the expression of steroid hormone receptors, namely estrogen receptor α (ER-α), progesterone receptor (PR), and androgen receptor (AR) in glandular epithelial cells and smooth muscle cells in particular groups of women. MATERIAL AND METHODS: The study material consisted of uterine specimens sectioned across the full thickness of the uterine wall, and embedded in 164 paraffin blocks. The specimens came from women without menopausal hormone therapy (MHT) operated due to reproductive organ prolapse or uterine myomas. The material was divided into four groups depending on the time interval from menopause to surgery: group I - from 1 to 5 years after menopause, group II - from 6 to 10 years after menopause, group III - more than 11 years after menopause, and group IV - women over 70 years of age. The sections were stained by standard HE, Masson's trichrome, and immunohistochemical methods (ERα, PR, AR). Quantitative assessment of the results was based on computer image analysis. RESULTS: Analysis of morphological changes in the endometrium and myometrium revealed the presence of increasing regressive changes, such as various types of atrophy, fibrosis, and calcification, augmented over time from the last menstruation. Furthermore, endometrial polyps, foci of endometriosis, and leiomyomas were observed. Based on the results of morphometric measurements, a constant decrease in the endometrial and myometrial thickness was noticed in the studied groups (I-IV). Significant differences between the groups were observed in the number of ER-α positive cells in the myometrium, but not in the endometrial glandular epithelium. Statistically significant differences in the number of AR positive cells were detected in the endometrial epithelium and in the uterine muscle. The analysis the number of PR positive cells demonstrated differences between the groups in the endometrial stroma and the myometrium. CONCLUSION: The uterus of postmenopausal woman undergo major morphological changes (mainly atrophic lesions in the endometrium and myometrium), leading to a decline in their morphometric parameters over time from the last menstruation. Localization and number of cells showing the expression of steroid receptors: ER-α, PR, and AR in the uterus of postmenopausal women, depending on the time interval from the last menstruation.

Biocompatibility of synthetic ultraviolet radiation cross-linked polymers - Subcutaneous implantation study.

Photo-cross-linked polymers have attracted a lot of attention in the biomedical field. The main benefits of these materials are related to the fact that they are most of the time viscous liquids or pastes that adapt a custom and fixed shape on demand of the user. Present study deals specifically with the biological response upon subcutaneous implantation of four different materials in rabbits. In the study 20 rabbits were divided into four groups (each five rabbits): Groups 1-3 were implanted with tested new obtained by us macromonomers (P1838-DMA; P1838-UR; PDEGA-UR - respectively), while group 4 (control) was implanted with the mesh (PLA) routinely used for surgical treatment of a hernia. The new compounds were polarized earlier using ultraviolet radiation to obtain cross-linked networks. The polymers in the form of discs were then implanted subcutaneously in dorsal region of rabbits. After 28 days polymers were explanted and examined. Microscopic observation evaluated: thickness of the connective tissue capsule around the discs, cells of inflammatory response, disc surface erosion, spectroscopic analysis. The examined materials cause no chronic inflammation, abscesses or tissue necrosis, and the biological response is similar to observed in control group. Therefore, new synthetic materials could be considered as biocompatible and safe. Materials undergo slow degradation of ester bonds and surface erosion and degradation products could be eliminated probably by phagocytosis. On the basis on the afore mentioned knowledge, we formulated hypothesis, that the new polymers are well tolerated by the adjacent tissues. The aim of the following study was to examine reaction of the tissue on new types of prepolymerized material implanted subcutaneously. The obtained results suggest, that the new UV cross-linked polymers do not affect negatively on the connective tissue that is in the contact with the implants. Furthermore, the used materials are in the liquid form, thus they could be easily performed in in minimally invasive laparoscopic treatment of abdominal hernias. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1889-1897, 2019.

Reactivity of pyruvic acid and its derivatives towards reactive oxygen species.

Pyruvic acid and its derivatives occurring in most biological systems are known to exhibit several pharmacological properties, such as anti-inflammatory, neuroprotective or anticancer, many of which are suggested to originate from their antioxidant and free radical scavenger activity. The therapeutic potential of these compounds is a matter of particular interest, due to their mechanisms of action, particularly their possible antioxidant behaviour. Here, we report the results of a study of the effect of pyruvic acid (PA), ethyl pyruvate (EP) and sodium pyruvate (SP) on reactions generating reactive oxygen species (ROS), such as superoxide anion radicals, hydroxyl radicals and singlet oxygen, and their total antioxidant capacity. Chemiluminescence (CL) and spectrophotometry techniques were employed. The pyruvate analogues studied were found to inhibit the CL signal arising from superoxide anion radicals in a dose-dependent manner with IC50 = 0.0197 ± 0.002 mM for EP and IC50 = 69.2 ± 5.2 mM for PA. These compounds exhibited a dose-dependent decrease in the CL signal of the luminol + H2O2 system over the range 0.5-10 mM with IC50 values of 1.71 ± 0.12 mM for PA, 3.85 ± 0.21 mM for EP and 22.91 ± 1.21 mM for SP. Furthermore, these compounds also inhibited hydroxyl radical-dependent deoxyribose degradation in a dose-dependent manner over the range 0.5-200 mM, with IC50 values of 33.2 ± 0.3 mM for SP, 116.1 ± 6.2 mM for EP and 168.2 ± 6.2 mM for PA. All the examined compounds also showed antioxidant capacity when estimated using the ferric-ferrozine assay. The results suggest that the antioxidant activities of pyruvate derivatives may reflect a direct effect on scavenging ROS and, in part, be responsible for their pharmacological actions.

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor.

The function of testis is under hormonal control and any disturbance of hormonal homeostasis can lead to morphological and physiological changes. Therefore the aim of the study was to investigate the expression of androgen and estrogen receptors (AR, ERs), vanilloid receptor (TRPV1), cytochrome P450 aromatase (P450arom), as well as apoptosis of cells in testis of adult rats chronically treated with letrozole (LT), a non-steroidal aromatase inhibitor, for 6 months. The testicular tissues were fixed in Bouin's fixative and embedded in paraffin. Immunohistochemistry with monoclonal antibodies (abs) against AR, ERa, P450arom, and polyclonalabs against ERß, TRPV1, caspase-3 was applied. Long-lasting estradiol deficiency, as an effect of LT treatment, produced changes in the morphology of testis and altered the expression of the studied receptors in cells of the seminiferous tubules and rate of cell apoptosis. The immunostaining for AR was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle. The intensity of staining for P450arom was lower in the testis of LT-treated rats as compared to control animals. The immunofluorescence of ERα and ERß was observed exclusively in the nuclei of Leydig cells of LT-treated rats. There were no changes in localization of TRPV1, however, the intensity of reaction was stronger in germ cells of the seminiferous epithelium after LT treatment. The apoptosis in both groups of animals was observed within the population of spermatocytes and spermatids in II and III stages of the seminiferous epithelium cycle. In testis of LT-treated rats the immunoexpression of caspase-3 was additionally found in the germ cells in I and IV stages, and Sertoli, myoid and Leydig cells. In conclusion, our results underline the important role of letrozole treatment in the proper function of male reproductive system, and additionally demonstrate that hormonal imbalance can produce the morphological abnormalities in testis.

Expression of the c-Kit receptor in germ cells of the seminiferous epithelium in rats with hormonal imbalance.

The aim of the study was to investigate the effects of pharmacologically induced hormonal imbalance in adult male rats treated with letrozole and rats exposed to soya isoflavones on the testicular morphology and c-Kit receptor (c-Kit-R) expression in germ cells. The study was conducted during all developmental periods: prenatal period, lactation, youth, and sexual maturity. Morphological and morphometrical analyses were performed on testicular section, and c-Kit-R was identified using immunohistochemistry. In addition, concentration of circulating steroids was measured in mature rats exposed to soya isoflavones. A significant reduction in testosterone level in rats exposed to soya isoflavones, and the sloughing of the premature germ cells into the lumen of the seminiferous tubules in the testes of both groups of rats were observed. Immunohistochemistry showed a decrease in c-Kit-R expression in germ cells of both experimental groups. Morphometric analysis indicated a decreased thickness of the layers occupied by c-Kit-R-positive spermatogonia, and a decreased diameter of the seminiferous tubules in the testes of both experimental groups of animals. In conclusion, the pharmacologically induced reduction of the estradiol level in adult rats and the diminished level of testosterone in rats exposed to soya isoflavones during the prenatal period, lactation and up to maturity caused similar morphological and functional changes associated with the decreased c-Kit-R expression in germ cells in the seminiferous epithelium. These findings demonstrate the importance of the estrogen/androgen balance for normal testicular morphology and spermatogenesis.

Dietary fat and physical activity in relation to breast cancer among Polish women.

BACKGROUND: Dietary fat has been inconsistently associated with the risk of breast cancer. The purpose of this study was to examine the relationship between meat and animal and plant fat intake and breast cancer risk in subgroups by total lifetime physical activity, using data from a case-control study conducted in the Region of Western Pomerania, Poland. MATERIALS AND METHODS: The study included 858 women with histological confirmed breast cancer and 1,085 controls, free of any cancer diagnosis. The study was based on a self-administered questionnaire including questions about socio-demographic characteristics, current weight and height, reproductive factors, family history of breast cancer and lifestyle habits. Unconditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: High animal fat intake significantly increased OR from 1.7 times (OR=1.66, 95%CI=1.07-3.59) to 2.9 times (OR=2.9, 95%CI=1.37- 6.14) independent of physical activity level, comparing the third versus the lowest quartile. Women with a high intake of red meat or processed meat and low physical activity showed increased risk of breast cancer: OR=2.70, 95%CI=1.21-6.03 and 1.78, 95%CI=1.04-3.59, respectively. The plant fat dietary pattern was negatively associated with breast cancer in sedentary women (OR=0.57, 95%CI=0.32-0.99). CONCLUSIONS: These results indicated that a diet characterized by a high consumption of animal fat is associated with a higher breast cancer risk in sedentary women, while consumption of plant fat products may reduce risk in the same group.

Disrupted pro- and antioxidative balance as a mechanism of neurotoxicity induced by perinatal exposure to lead.

The aim of this paper was to examine if pre- and neonatal exposure that results in lead (Pb) concentration below 'safe level' (10 µg/dL) in offspring blood may cause disruption of the pro/antioxidant balance in the developing rat brain. We studied oxidative stress intensity (malondialdehyde (MDA) concentration) as well as mRNA, protein expression and the activity of copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (GPx4), catalase (CAT), glutathione reductase (GSR). We also measured glutathione (GSH) concentrations in selected structures of the rat brain (forebrain cortex, FC, cerebellum, C, and hippocampus, H) and showed cellular localization of GPx4, SOD1 and SOD2 expressions in the hippocampus by immunohistochemical examinations. Despite low Pb level in blood we observed decrease of the activity of some antioxidant enzymes as well as mRNA and protein expression downregulation associated with an increase of MDA level and CAT expression upregulation, especially in the hippocampus region. At the subcellular level, downregulation of SOD2 expression and decreased enzyme activity as well as mitochondrial pool of GSH suggest also that mitochondrial mechanisms might account for Pb neurotoxicity mechanism. For some enzymes, we found differences in the effects of Pb on the level of expression and activity. The activity of CAT decreased despite an increase in mRNA and protein expression; and likewise the activities SOD1, GPx1 GPx4 decreased, despite substantially unchanged level of expression. These effects may be the result of impairment of catalytic function of the enzyme protein caused by Pb interaction or of reduction in the availability of cofactors. We conclude that antioxidant system of the hippocampus of immature rat brain is highly vulnerable to perinatal Pb exposure. Therefore, oxidative stress may be one of the possible mechanisms disturbing cellular metabolism in this structure. Disruption of pro- and antioxidant balance should be considered as a potential mechanism of the observed Pb adverse effects, leading to the impaired learning ability caused by Pb exposure in children.

Changes in male reproductive system and mineral metabolism induced by soy isoflavones administered to rats from prenatal life until sexual maturity.

OBJECTIVE: This study aimed to determine the influence of high-dose soy isoflavones (daidzein and genistein) administered from prenatal life to sexual maturity on testosterone and estradiol levels, testicular and epididymal morphology, the number of epididymal spermatozoa, and mineral metabolism in rats. METHODS: Pregnant Wistar rats received orally soy isoflavones, daidzein, and genistein at a dose of 200 mg/kg of body weight per day. After separating sucklings from their mothers, male rats received the same dose of isoflavones until reaching the age of sexual maturity, i.e., for 3 mo. RESULTS: In the isoflavone-treated group, statistically significant decreased concentrations of zinc (determined using atomic absorption spectrophotometry) in blood serum and increased concentrations in bone were observed. The isoflavones induced changes in the morphology of the seminiferous epithelium of rat testes. However, there were no significant changes in the number of spermatozoa in the epididymis. The levels of estradiol in serum and cauda epididymis homogenates of rats receiving phytoestrogens were significantly higher than in the control group. No differences were observed in testosterone concentrations in the serum of treated and control rats. The testosterone levels in the homogenates of the treated rat testes were significantly lower than in the control group. CONCLUSION: The relatively mild effects of phytoestrogen administration on the morphology of testes and epididymides and the number of epididymal spermatozoa were observed despite the high dose used. The exposure of rats to genistein and daidzein during intrauterine life until sexual maturity influenced the mineral metabolism of the organism by significant decreases of Zn concentration in serum and increased Zn concentration in bones.

Hymenolepis diminuta: the effects of infection on transepithelial ion transport and tight junctions in rat intestines.

In this study, we examine the effect of Hymenolepis diminuta on ion transport in the ileum and on tight junctions in the ileum and colon of rats. We also evaluate the effect of H. diminuta on C-fiber endings in the ileum, the direct habitat of H. diminuta, before and after mechanical stimulation and pharmacological modification by capsaicin (C-fiber irritant). Wistar rats were orally infected with five cysticercoids of H. diminuta. Using a modified Ussing chamber, electrophysiological parameters of the ileum were measured (transepithelial electrical potential difference and transepithelial electrical resistance) as well as the deposition of occludin (a tight junction protein) in the ileum and colon of the rats 8, 16, 25, 35, 40 and 60 days post infection. We observed a significant reduction in transepithelial electrical potential difference in the ileum of rats infected with H. diminuta. In both the ileum and colon of rats infected with H. diminuta we also observed a decrease in occludin deposition, which indicates leakage of tight junctions, correlating with the decrease in transepithelial electrical resistance of these tissues. The application of capsaicin confirmed the hypothesis that H. diminuta in rats affects the C-fiber sensory receptors, causing changes in ion transport in the ileum. The results of the performed electrophysiological and immunohistochemical examinations indicate hymenolepidosis-related changes in the active transport of ions and the passive movement of ions.

Changes in the concentration of microelements in the teeth of rats in the final stage of type 1 diabetes, with an absolute lack of insulin.

The mineral content of tooth hard tissue may influence the rate of decay change. Considering this fact, we aimed at examining if type 1 diabetes might be a contributing factor to the appearance of tooth decay. The experiment was conducted on female Wistar rats. To induce diabetes, rats were intravenously injected with 1 mL streptozocine 0.01 M citrate buffer. The control group of rats was injected with 1 mL 0.01 M citrate buffer only. After 10 days, teeth and blood serum samples were obtained. Fluoride concentration was determined by potentiometer method, and calcium and magnesium, by AAS. Serum concentrations of glucose and estradiol in the diabetic rats were significantly higher compared to the control group. In the experimental group, a statistically significant decrease of fluorine concentration in both teeth and serum were observed. Calcium and magnesium concentrations in blood serum and dental magnesium concentration were significantly higher in rats with type 1 diabetes compared with the control. A downward trend in the content of dental calcium in streptozotocin-induced diabetic rats was observed. The results obtained indicate that caries initiation and progression could be promoted by metabolic changes associated with diabetes affecting the mineral composition of tooth hard tissue.

Conjugated linoleic acids regulate triacylglycerol and cholesterol concentrations in macrophages/foam cells by the modulation of CD36 expression.

Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in food, e.g. linoleic acid and n-3 unsaturated fatty acids can modulate expression of CD36 on the macrophage surface. Conjugated linoleic acid isomers (CLA) that originate from the human diet, have demonstrated antiatherogenic properties in several experiments. Animal study evidenced that CLA could induce resolution of plaque by activation of peroxisome proliferator activated receptors and down-regulation of pro-inflammatory genes. Less unequivocal results were obtained in human studies (on the CLA effects on the inflammatory process). Therefore in this study we investigated the influence of CLA on CD36 expression and lipid accumulation in human macrophages. Macrophages were incubated with 30 µM cis-9,trans-11 CLA, trans-10,cis-12 CLA or linoleic acid for 48 h. After that, expression of CD36 as well as accumulation of lipids were measured by flow cytometry, microscopy and a spectroscopic method. We demonstrate that both cis-9,trans-11 C 18 : 2 CLA and linoleic acid slightly elevated expression of CD36, whereas second isomer ­ trans-10,cis-12 CLA ­ did not. Nevertheless, only trans-10,cis-12 CLA triggered delipidation of macrophages, that is decreased triacylglycerols concentration. Also in human adipocytes, trans-10,cis-12 CLA causes cell delipidation by reduction of PPAR receptor expression. We propose a similar mechanism for human macrophages/foam cells.

The immunoexpression of FSH-R in the ductuli efferentes and the epididymis of men and rat: effect of FSH on the morphology and steroidogenic activity of rat epididymal epithelial cells in vitro.

The Sertoli cells were regarded as the only target for FSH in male reproductive system. The expression of FSH receptor (FSH-R) was detected also in epithelial cells of the caput epididymis of rat and monkey. We showed in the immunohistochemistry study the expression of FSH-R in rat and human ductuli efferentes and the caput, corpus, and cauda epididymis, moreover, by Western blot analysis in the caput and cauda epididymis of rat. Additionally, we presented that the morphology of rat epididymal epithelial cells in vitro was affected by FSH, and FSH stimulation resulted in the increase of 17beta-estradiol synthesis by rat caput epididymal cells in dose-depended manner. In conclusion, the identification of FSH receptors in human and rat epididymides supports our results that the epididymis is a target organ not only for LH but additionally for FSH. On the basis of the results we showed for the first time that morphology of epididymal epithelial cells and epididymal steroidogenesis can be regulated by FSH.

Conjugated linoleic acid increases intracellular ROS synthesis and oxygenation of arachidonic acid in macrophages.

OBJECTIVE: Conjugated linoleic acids (CLAs) have potential antiatherosclerotic properties: they may inhibit atherosclerotic processes by reducing the intensity of inflammatory processes. However, in vivo studies have shown that the application of trans-10, cis-12 CLA in obese men increased their oxidative stress. The objective of this study was to determine whether CLA can lead to an increase in oxidative stress and to isoprostane synthesis in macrophages. METHODS: Monocytes from peripheral blood and human monocytic leukemia cells were used in this study. Monocytes were differentiated to macrophages, and were incubated with 30 microM cis-9, trans-11 CLA and trans-10, cis-12 CLA or linoleic acid for 2 days. In some experiments the inhibitors of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) or respiratory chain were added. After incubation, synthesis of reactive oxygen species (ROS), total cellular concentration of adenosine triphosphate, concentration of 8-epi-prostaglandin F2 alpha, activity of cytoplasolic phospholipase A2 (cPLA2), activity of mitochondria, and expression of mRNA of PPAR-alpha were measured. RESULTS: In cells cultured with CLAs intercellular ROS synthesis increased. In this condition the mitochondrial energy potential was high, and the inhibitors of the respiratory chain and PPAR-alpha reduced ROS concentration. At the same time, the cPLA2 activity was abolished. In contrast, 8-iPF2 alpha III synthesis increased in CLA cells. CONCLUSION: Cultivation of cells with CLA leads to an increased ROS synthesis, partly by PPAR-alpha mechanism. An increase in ROS concentration and inhibition of cPLA2 activity can stimulate oxygenation of arachidonic acid and contribute to an increase in 8-epi-PF2 alpha III level and in the apoptosis process in macrophages.

Morphology of the bone marrow, spleen and liver during hematopoietic cell mobilization with cyclophosphamide in mice.

Cyclophosphamide (CY), the agent with cytoreductive activity, is widely exploited in cancer chemotherapy, and can be used alone or in combination with various cytokines and growth factors to stimulate the egress of hematopoietic stem/progenitor cells (HSPC) from the BM compartment. The aim of the present study was to exam the morphology and ultrastructure of the bone marrow, spleen and liver of mice injected intraperitoneally with a single dose of cyclophosphamide (200 mg/kg bw) and the localization of cells expressing markers of early hematopoietic cells in studied organs and the peripheral blood. We observed that the CY-induced morphological changes in the BM and spleen were reconstructed on day 4. of experiment, and the spleen was repopulated by HSPC on the 6th day. In this time, the highest number of c-Kit-R-positive cells was determined by flow cytometry in the peripheral blood. The results confirmed, that the egress of HSPC from the bone marrow into the peripheral blood was delayed compared to mice treated with G-CSF or GCS-F plus CY.

Rat epididymal epithelial cells and 17beta-estradiol synthesis under hCG stimulation in vitro.

Epithelial cells of human and animal epididymis display features of steroidogenic cells. Rat epididymal epithelial cells in vitro produce androgens which are converted to 17beta-estradiol, and released into the medium. The regulation of the epididymal steroidogenesis is not fully understood but it could be expected that it remains under LH influence. In previous study we observed that the morphology of rat epididymal epithelial cells in vitro was affected by hCG and the increase of amount of lipid droplets, glycogen and PAS-positive substances was observed. The present studies show the organelles which take part in synthesis of steroids in rat epididymal epithelial cells in vitro and the effect of hCG on E2 synthesis. The cells were cultured in the medium with/without DHT and without DHT in supplementation with hCG. After hCG stimulation the amount of an active mitochondria were increased when compared to the amount of mitochondria in the epididymal epithelial cells cultured without DHT. Ultrastructure of the cells was similar to the cells cultured with DHT, while the cytoplasm of the cells cultured without DHT was disorganized. The synthesis of 17beta-estradiol was stimulated by hCG, that exerted its effect through LH/hCG receptors, localized in the epididymal epithelial cells.

Hormonal status of male reproductive system: androgens and estrogens in the testis and epididymis. In vivo and in vitro approaches.

The purpose of this article was to summarize our results on the role of androgens and estrogens in human, rodent and equine testes and epididymides, in both, physiological and patological conditions, obtained in the space of the Solicited Project (084/PO6/2002) financially supported by the State Committee for Scientific Research during the last three years. Testosterone produced by Leydig cells of the testes is clearly the major androgen in the circulation of men and adult males of most mammalian species. However, androgen metabolites make up a significant fraction of total circulating steroids. Moreover, androgen metabolism may proceed to amplify the action of testosterone through its conversion to dihydrotestosterone (DHT) or its aromatization to estradiol. The distribution of androgen and estrogen receptors (ARs and ERs) within male reproductive tissues is important because of their crucial role in mediating androgen and/or estrogen action. Attempts were undertaken to discuss not only the role of aromatase and ERs in mediating the action of estrogens in the male, but also the importance of DHT in hormonal regulation of the epididymis. In the latter, alterations caused by finasteride treatment and lead-induced oxidative stress are described. Male reproductive function of the testis and epididymis reflected by the alterations in enzymatic activity, distribution of steroid hormone receptors, differences in steroid hormone levels and altered gene expression of antioxidant enzymes are also discussed.