Impact of Perinatal Bisphenol A and High Fat Diets on Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease among youth in the United States. This recent rise of NAFLD may be partially due to perinatal programming, where in utero exposures alter the lifelong health trajectory of offspring. Maternal pregnancy diet and endocrine disrupting chemical exposure have been identified as drivers of perinatal programming. However, the potential for maternal diet to modify the impact of perinatal chemical exposure is not well understood. This dissertation examined whether perinatal exposure to two common environmental toxicants, bisphenol A (BPA) and high fat diets (HFDs), would affect NAFLD incidence in offspring. A longitudinal mouse exposure study and a human birth cohort were used to investigate this hypothesis and to evaluate the translation of findings across species. Oral exposure to one of six diets: Control, Western HFD, Mediterranean HFD or each diet with 50ug BPA/kg added, occurred pre-gestation through lactation. All mice were weaned onto the Control diet, thus isolating exposure to the perinatal period. Offspring NAFLD was assessed via hepatic steatosis and hepatic oxidative response at postnatal day 10 (PND10) and 10-months. Hepatic triglyceride (TG) levels were altered by perinatal HFD in dams, but in offspring perinatal exposures affected metabolic outcomes not hepatic TGs. Hepatic histology from 10-month offspring highly correlated with hepatic TG levels, validating the TG findings. Hepatic 8-isoprostane (8-iso) levels differed by perinatal exposure in PND10 and 10-month offspring, but alterations were age and sex-specific. Perinatal HFD and BPA minimally impacted offspring redox parameters (EhGSH, EhCys, S-glut), suggestive of greater homeostatic control of these parameters compared to lipid oxidation. Dam metabolic phenotype significantly altered offspring hepatic steatosis and oxidative response, even when perinatal HFD and BPA did not, emphasizing the critical role of the maternal environment on offspring health. The impact of maternal BPA exposure and gestational Mediterranean diet adherence (MDS) on the metabolic health of peripubertal youth was examined in a well-established human birth cohort. Youth metabolic and oxidative health was assessed via metabolic risk score (MRS) and serum 8-iso. Maternal pregnancy average and Trimester 2 BPA were associated with a suggestive decrease in youth MRS driven by boys, but a suggestive increase in 8-iso levels driven by girls. Maternal MDS did not affect youth MRS, but altered youth serum 8-iso in opposite directions based on sex. Additional youth characteristics (peripubertal BPA, MDS, vigorous activity, and pubertal status) contributed to predictive models of MRS and 8-iso, underscoring the impact healthy lifestyle behaviors may have, potentially even modifying perinatal programming. The unexpected lack of protection exerted by the Mediterranean diet in both mouse and human studies, suggests the beneficial effect observed in adults may not apply to perinatal exposure. Greater impact of HFDs in mice but BPA in humans highlights the need to carefully scrutinize findings before translating across species. Despite this difference, sex-specific effects occurred in both species, emphasizing the importance of investigating perinatal programming in all offspring. This research suggests that perinatal BPA and HFD exposure may be insufficient to induce perinatal programming of NAFLD. The significant impact of dam metabolic phenotype in mice and peripubertal behaviors in humans on metabolic and oxidative outcomes suggest NAFLD risk can be altered and potentially prevented at multiple life stages.PHDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/145959/1/marcheh_1.pd

Dynamics of ibuprofen biodegradation by Bacillus sp. B1(2015b)

High intake of over-the-counter, non-steroidal anti-inflammatory drugs, such as ibuprofen, has resulted in their presence in wastewaters and surface waters. The potentially harmful effect of ibuprofen present in the waters has led to a search for new methods of drugs' removal from the environment. One of the most important technological and economical solutions comprises microbiological degradation of these resistant pollutants. Searching for new strains able to degrade ibuprofen could be one of the answers for increasing the detection of pharmaceuticals in the waters. In this study, the ability of bacterial strain Bacillus thuringiensis B1(2015b) to remove ibuprofen is described. Bacteria were cultured in both monosubstrate and cometabolic systems with 1, 3, 5, 7 and 9 mg L-1 ibuprofen and 1 g L-1 glucose as a carbon source. Bacillus thuringiensis B1(2015b) removed ibuprofen up to 9 mg L-1 in 232 hours in the monosubstrate culture, whereas in the cometabolic culture the removal of the drug was over 6 times faster. That is why the examined strain could be used to enhance the bioremediation of ibuprofen

Polish Eastern Borderlands in prince Adam Jerzy Czartoryski’s political program in exile : an iconographic contribution

The article is a contribution to the reflection on the place of the Eastern Borderlands of the Polish-Lithuanian Commonwealth in the political program of Prince Adam Jerzy Czartoryski and his followers after 1831. This program was expressed and implemented in various ways, and its addressees were both the Poles and the public opinion of Western Europe. Without trying to present the whole issue, three iconographic representations that contained elements of this program were analyzed here. What they had in common was that all of them were to honor the closest British ally of Prince Adam – Lord Dudley Coutts Stuart (1803–1854). In 1846 he received a decorative tapestry from Polish emigrants, in 1847 a golden watch, and after his death a medal made by J.F.A. Bovy was minted in his honor. The heraldic and cartographic motifs adorning theses items indicate that Prince Adam and his associates saw the future of the Eastern Borderlands in connection with the rebirth of Poland. These representations were a persuasive message addressed to Polish and foreign audiences, the purpose of which was to convince them of the importance of this issue in Czartoryski’s plan for the restitution of the Polish state

Over-the-counter monocyclic non-steroidal anti-inflammatory drugs in environment-sources, risks, biodegradation

Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic nonsteroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may be caused by fungal or bacterial microorganisms. Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases. The key intermediate of the paracetamol degradation pathways is hydroquinone. Sometimes, after hydrolysis of this drug, 4- aminophenol is formed, which is a dead-end metabolite. Ibuprofen is metabolized by hydroxylation or activation with CoA, resulting in the formation of isobutylocatechol. The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of over-the-counter antiinflammatory drugs, their sources and the biotransformation and/or biodegradation pathways of these drugs

Bacillus thuringiensis B1(2015b) is a gram-positive bacteria able to degrade naproxen and ibuprofen

A Gram-positive bacterium, designated as strain B1(2015b), was isolated from the soil of the chemical factory BOrganika-Azot^ in Jaworzno, Poland. On the basis of 16S rRNA gene sequence analysis, the isolated strain was classified as a Bacillus thuringiensis species. Strain B1(2015b) is able to degrade ibuprofen and naproxen, however, these compounds are not sufficient carbon sources for this strain. In the presence of glucose, Bacillus thuringiensis B1(2015b) degrades ibuprofen and naproxen with higher efficiency. Twenty milligrams per liter of ibuprofen was degraded within 6 days and 6 mg l−1 of naproxen was removed within 35 days. Simultaneously, the growth of the bacterial culture was observed. The obtained results suggest that Bacillus thuringiensis B1(2015b) appears to be a powerful and useful tool in the bioremediation of nonsteroidal anti-inflammatory drugs-contaminated environment

Bone marrow morphology during haematopoietic stem cell mobilisation with cyclophosphamide in mice

The aim of the study was to examine the morphology of the bone marrow of mice after stimulation with cyclophosphamide (Cy). The experimental mice were given a single intraperitoneal injection with 250 mg/kg bw cyclophosphamide. After 2, 4 and 6 days of experiment the femurs were obtained for morphological study. On the 2nd day after the mobilisation of the mice with Cy destruction of the bone marrow was observed with a decrease in the haematopoietic compartment and an increase in the area occupied by sinusoids filled with erythrocytes. Erythrocytes were located among the haematopoietic cells, which indicated that the endothelial barrier had been disrupted. On the 4th day after treating the mice with Cy, repair processes in the bone marrow were conducted, including macrophages. The cells filled with haemosiderin migrated from the extravascular compartment of the bone marrow into the lumen of the sinusoids. There were proliferating cells among the haematopoietic cells. On the 6th day the morphology of the bone marrow was similar to the morphology of that in the control mice. However, more haematopoietic cells were visible compared to the control bone marrow. The presence of an increased number of leucocytes in the sinusoid lumen in comparison with the control suggested that at that time the migration of haematopoietic cells from the bone marrow had been initiated

DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions

In rats with a DHT deficiency induced by finasteride, morphological changes in the seminiferous epithelium were observed. The structural alterations were manifested by the premature germ cells sloughing into the lumen of seminiferous tubules. The etiology of this disorder could be connected with intercellular junctions disintegration. We showed in the immunohistochemical study the changes in expression of some proteins building tight and adherens junctions. The depression of N-cadherin, β-catenin and occludin immunoexpressions could be the reason for the release of immature germ cells from the seminiferous epithelium. However, the observed increase of the immunohistochemical reaction intensity of vinculin, one of the cadherin/catenin complex regulators, could be insufficient to maintain the proper function of adherens junctions. The hormonal imbalance appears to influence the pattern of expression of junctional proteins in the seminiferous epithelium. It could lead to untimely germ cells sloughing, and ultimately could impair fertility. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 1, 62–71

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\u27s 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

Possible involvement of microtubules and microfilaments of the epididymal epithelial cells in 17beta-estradiol synthesis.

The rat epididymal epithelial cells revealed features of steroidogenic cells and released 17beta-estradiol (E2) into the culture medium. In steroidogenic cells, elements of the cytoskeleton due to their influence on organelle distribution are implicated in the regulation of steroidogenesis. In the present study, the morphology of cultured epididymal epithelial cells in light, scanning and transmission electron microscopes was evaluated. The organization of microtubules and microfilaments revealed by fluorescence microscopy, and the concentration of E2 in cultured medium were also studied. The epididymal epithelial cells were cultured in different conditions: in the medium with or without exogenous testosterone (T) and in the co-culture with Leydig cells as a source of androgens. The cells in co-culture located close to Leydig cells were rich in glycogen, PAS-positive substances and lipid droplets, in higher amount than the cells cultured with addition of exogenous testosterone. Stress fibers and microtubules of epididymal epithelial cells cultured with exogenous T and in co-culture with Leydig cells presented typical structure, and numerous granular protrusions appeared on the surface of the cells. Disorganization of microtubules and shortening of stress fibers as well as the smooth cell surface deprived of granular protrusions were observed in the epididymal epithelial cells cultured without T. Change of the cytoskeleton organization caused by the absence of androgen in culture medium resulted in an increased E2 secretion

Bone marrow morphology during haematopoietic stem cell mobilization with G-CSF in mice

The aim of the work was to examine the morphology of the bone marrow of mice during stimulation with G-CSF. Experimental Balb C mice were daily injected subcutaneously with 250 μg/kg b.w. G-CSF (Neupogen). After 2, 4 and 6 days of the experiment femurs were obtained for morphological study. On day 2 of the mobilization the amount of haematopoietic cells in the bone marrow increased and dilatation of the sinusoids was observed. Only single leukocytes were observed in the lumen of the vessels. There were numerous leukocytes in the lumen of the sinusoids on day 4 of the mobilization. The morphology of the bone marrow on day 6 was similar to that of the control. Mobilization of mice with G-CSF resulted in migration of haematopoietic cells from the bone marrow and the process is most pronounced on day 4