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Any collection of non-blocking four-dimensional cubes, whose total volume does not exceed 17/81, can be packed into the unit four-dimensional cube. This bound is tight for the parallel packing. [ABSTRACT FROM AUTHOR]

Aims: The current review aims to outline and summarize the latest research on aflatoxin, with research studies describing natural, herbal and chemical compound applications in animal (pig) models and in vitro cellular studies. Aflatoxin, a carcinogenic toxin metabolite, is produced by Aspergillus flavus in humid environments, posing a threat to human health and crop production. The current treatment involves the prevention of exposure to aflatoxin and counteracting its harmful toxic effects, enabling survival and research studies on an antidote for aflatoxin. Objectives: To summarize current research prospects and to outline the influence of aflatoxin on animal forage in farm production, food and crop processing. The research application of remedies to treat aflatoxin is undergoing development to pinpoint biochemical pathways responsible for aflatoxin effects transmission and actions of treatment. Significance: To underline the environmental stress of aflatoxin on meat and dairy products; to describe clinical syndromes associated with aflatoxicosis on human health that are counteracted with proposed treatment and preventive interventions. To understand how to improve the health of farm animals with feed conditions. [ABSTRACT FROM AUTHOR]

The aim: In this study was to determine if sigmoid colorectal cancer (SCC) and colorectal cancer (CRC) in women (W) and men (M) is accompanied by zearalenone (ZEN) mycotoxicosis and changes in selected steroid levels. Materials and Methods: This cohort study was conducted on female and male patients selected from a population based on the presence of SCC or CRC, which was accompanied by the presence or absence (control group) of ZEN in their blood. The control group consisted of 17 patients with symptoms of SCC and CRC, where ZEN and its metabolites were not detected in the peripheral blood. The experimental groups comprised a total of 16 patients with SCC and CRC, where ZEN, but not its metabolites, was detected in their peripheral blood samples. Results: In groups SCC and CRC, the ZEN levels were very high, in the range from 214 to 289 ng/mL of blood. Considerable variations were observed in the concentrations of steroid hormones. Estradiol (E2) levels ranged from 166.25 (group C) to 325 pg/mL (group CRC) in women and from 98 (group C) to 95.5 pg/mL (group CRC) in men. Progesterone (P4) levels ranged from 12.09 (group C) to 13.64 ng/mL (group SCC) in women and from 6.98 (group CRC) to 12.01 ng/mL (group C) in men. Conclusions: These results indicate that post-menopausal women and similarly aged elderly men have a high and individualized demand for estrogen that is relatively effectively met by ZEN, which triggers qualitative changes in estrogen receptors. The shortage of ZEN metabolites (values under the sensitivity of the method) confirmed the high estrogen demand in the studied subjects. The presence or absence of ZEN could have influenced the therapeutic outcomes in the analyzed patients. [ABSTRACT FROM AUTHOR]

This study was conducted to determine if a low monotonic dose of zearalenone (ZEN) affects the immunohistochemical expression (IE) of oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) in the intestines of sexually immature gilts. Group C (control group; n = 18) gilts were given a placebo. Group E (experimental group; n = 18) gilts were dosed orally with 40 μg ZEN /kg body weight (BW), each day before morning feeding. Samples of intestinal tissue were collected post-mortem six times. The samples were stained to analyse the IE of ERα and Erβ in the scanned slides. The strongest response was observed in ERα in the duodenum (90.387—average % of cells with ERα expression) and in ERβ in the descending colon (84.329—average % of cells with ERβ expression); the opposite response was recorded in the caecum (2.484—average % of cells with ERα expression) and the ascending colon (2.448—average % of cells with ERα expression); on the first two dates of exposure, the digestive tract had to adapt to ZEN in feed. The results of this study, supported by a mechanistic interpretation of previous research findings, suggest that ZEN performs numerous functions in the digestive tract. [ABSTRACT FROM AUTHOR]

Simple Summary: African catfish is one of the most perspective fish species in modern aquaculture. However, the main cost involved in its production is focused chiefly on the cost of feeds. The main reason for this is the behavior of this species (predatory fish) and the high rate of cannibalism in intensive culture. That is why it is essential to assess functional bioactive additives to be used in commercial feed with a positive effect on the growth and survival rates of this commercially valued fish species. In the present study, African catfish juveniles were fed diets enriched with honeybee pollen (BP) and were tested for growth, survival, intestinal microbiota, and tissue histomorphology. It has been shown that BP addition positively affected all the analyzed parameters. This research study spotlights the benefits of BP as a prebiotic supplement for improving the functionality of feeds prepared for African catfish. This study aimed to determine the dietary effects of honeybee pollen (BP) on growth parameters, intestinal microbiota, hepatic histoarchitecture, and intestinal histomorphometry of African catfish Clarias gariepinus juveniles. The feeding experiment was carried out in a recirculating aquaculture system under controlled conditions for 21 days to achieve more than a 10-fold increase in weight in fish from the control group. Fish were fed well-balanced commercial feed without any supplements and served as a reference group (group C) and other diets enriched with varying BP levels as 1% (BP1), 2% (BP2), and 3% (BP3). Results showed a significant (p < 0.05) effect of the dietary BP not only on the growth parameters (such as final body weight: 5.0 g to 6.6–7.5 g, weight gain: 0.23 g/d to 0.31–0.35 g/d, body length: 84.7 mm to 93.8–95.9 mm, and specific growth rate: 11.7%/d to 13.1–13.7%/d, group C vs. experimental groups, respectively) but also on the development of beneficially important gut microbiota, such as lactic acid-producing bacteria. In BP-enriched groups, an average of 45% higher body weight gain was observed compared to those reared in the control group. The histological analysis showed that dietary BP may have a positive effect on the development of the intestinal tract and may enhance the absorption of nutrients with the potential ability to maintain a normal hepatic histoarchitecture of the treated African catfish. The results obtained suggest the optimum level of BP additive to feed for African catfish should be 1%. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether low doses of zearalenone (ZEN) affect the carry-over of ZEN and its metabolites to intestinal tissues and the expression of CYP1A1 and GSTπ1 in the large intestine. Prepubertal gilts (with a BW of up to 14.5 kg) were exposed in group ZEN to daily ZEN5 doses of 5 μg/kg BW (n = 15); in group ZEN10, 10 μg/kg BW (n = 15); in group ZEN15, 15 μg/kg BW (n = 15); or were administered a placebo (group C, n = 15) throughout the experiment. After euthanasia, tissues were sampled on exposure days 7, 21, and 42 (D1, D2, and D3, respectively). The results confirmed that the administered ZEN doses (LOAEL, NOAEL, and MABEL) were appropriate to reliably assess the carry-over of ZEN. Based on the observations made during 42 days of exposure to pure ZEN, it can be hypothesized that all mycotoxins (ZEN, α-zearalenol, and β-zearalenol) contribute to a balance between intestinal cells and the expression of selected genes encoding enzymes that participate in biotransformation processes in the large intestine; modulate feminization processes in prepubertal gilts; and elicit flexible, adaptive responses of the macroorganism to mycotoxin exposure at the analyzed doses. [ABSTRACT FROM AUTHOR]

Gastrointestinal neuropathy in diabetes is one of numerous diseases resulting in abnormal functioning of the gastrointestinal tract (GIT), and it may affect any section of the GIT, including the descending colon. In the gastrointestinal system, the neurons are arranged in an interconnecting network defined as the enteric nervous system (ENS) which includes the myenteric plexus and the submucosal plexuses: inner and outer. Regular functioning of the ENS is determined by normal synthesis of the neurotransmitters and neuromodulators. This paper demonstrates the effect of hyperglycaemia on the number of enteric neurons which are immunoreactive to: neural isoform of nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), galanin (GAL), calcitonin generelated peptide (CGRP) and cocaine amphetamine-regulated transcript (CART) in the porcine descending colon. It was demonstrated that there was a statistically significant increase in the number of neurons within the myenteric plexus immunoreactive to all investigated substances. In the outer submucosal plexus, the CART-positive neurons were the only ones not to change, whereas no changes were recorded for nNOS or CART in the inner submucosal plexus. This study is the first study to discuss quantitative changes in the neurons immunoreactive to nNOS, VIP, GAL, CGRP and CART in the descending colon in diabetic pigs. [ABSTRACT FROM AUTHOR]

Any sequence of 4-dimensional cubes of total volume not greater than 1/8 can be online packed into the unit cube. [ABSTRACT FROM AUTHOR]

One of the most frequently reported disorders associated with diabetes is gastrointestinal (GI) disturbance. Although pathogenesis of these complications is multifactorial, the complicity of the enteric nervous system (ENS) in this respect has significant importance. Therefore, this paper analysed changes in substance P- (SP-), calcitonin gene-related peptide- (CGRP-), and leu5-enkephalin- (L-ENK-) like immunoreactivity (LI) in enteric stomach neurons caused by chemically induced diabetes in a porcine model. Using double immunofluorescent labelling, it was found that acute hyperglycaemia led to significant changes in the chemical coding of stomach enteric neurons. Generally, the response to artificially inducted diabetes depended on the “kind” of enteric plexus as well as the stomach region studied. A clear increase in the percentage of neurons immunoreactive to SP and CGRP was visible in the myenteric plexus (MP) in the antrum, corpus, and pylorus as well as in the submucosal plexus (SmP) in the corpus. For L-ENK, an increase in the number of L-ENK-LI neurons was observed in the MP of the antrum and SmP in the corpus, while in the MP of the corpus and pylorus, a decrease in the percentage of L-ENK-LI neurons was noted. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in Europe. Pigs are an animal species that is most susceptible to this mycotoxin. Deoxynivalenol causes significant losses in pig production by lowering feed intake, decreasing daily weight gains, disrupting immune responses, and increasing susceptibility to diseases. The aim of this experiment was to determine the influence of feed contaminated with DON at concentrations insignificantly higher than recommended by the European Commission (900 μg/kg). The experimental feed contained 1008 μg DON/kg. The experiment was performed on eight weaners from the same litter. The animals were randomly divided into two groups: an experimental group (M, n = 4) fed contaminated feed and a control group (C, n = 4) administered feed free of mycotoxins. The experiment lasted for six weeks, and peripheral blood samples were collected from the animals for analyses of selected morphological parameters and changes in the percentages of CD4+8-, CD4-8+, and CD4+8+ lymphocytes and antigen-presenting cells (APC) with CD14+172+ (monocytes), CD172ahigh4-14- (conventional dendritic cells, cDC), and CD172adim4+14- (plasmacytoid dendritic cells, pDC) phenotypes. The morphological parameters of porcine blood samples were determined by flow cytometry with non-fluorescent particle-size calibration standards, and no differences were observed between groups M and C. An immunophenotyping analysis of lymphocytes and dendritic cells (DC) revealed an increase in the percentage of CD4+8-, CD172ahigh4-14-, and CD172adim4+14- cells, and a decrease in the number of CD4-8+ cells in group M. The results of this experiment suggest that prolonged exposure to low doses of DON can change the proportions of immunocompetent cells (a shift towards humoral immunity), without affecting their overall counts. [ABSTRACT FROM AUTHOR]

This study demonstrates that low doses (somewhat above the No Observed Adverse Effect Level, NOAEL) of the mycoestrogen zearalenone (ZEN) and its metabolites display multispecificity towards various biological targets in gilts. The observed responses in gilts were surprising. The presence of ZEN and zearalenols (ZELs) did not evoke a response in the porcine gastrointestinal tract, which was attributed to dietary tolerance. Lymphocyte proliferation was intensified in jejunal mesenteric lymph nodes, and lymphocyte counts increased in the jejunal epithelium with time of exposure. In the distal digestive tract, fecal bacterial counts decreased, the activity of fecal bacterial enzymes and lactic acid bacteria increased, and cecal water was characterized by higher genotoxicity. The accompanying hyperestrogenism led to changes in mRNA activity of selected enzymes (cytochrome P450, hydroxysteroid dehydrogenases, nitric oxide synthases) and receptors (estrogen and progesterone receptors), and it stimulated post-translational modifications which play an important role in non-genomic mechanisms of signal transmission. Hyperestrogenism influences the regulation of the host's steroid hormones (estron, estradiol and progesteron), it affects the virulence of bacterial genes encoding bacterial hydroxysteroid dehydrogenases (HSDs), and it participates in detoxification processes by slowing down intestinal activity, provoking energy deficits and promoting antiporter activity at the level of enterocytes. In most cases, hyperestrogenism fulfils all of the above roles. The results of this study indicate that low doses of ZEN alleviate inflammatory processes in the digestive system, in particular in the proximal and distal intestinal tract, and increase body weight gains in gilts. [ABSTRACT FROM AUTHOR]

A 3.8165-competitive 2-space bounded 2-dimensional bin packing algorithm is described. Moreover, a 3.6-competitive online square packing algorithm with two active bins is presented. [ABSTRACT FROM AUTHOR]

Zearalenone and deoxynivalenol are secondary metabolites of fungi of the genus Fusarium. The presence of mycotoxins in cereals and the resulting contamination of feeds and foods pose health risks for animals and humans. The dangers associated with high doses of mycotoxins have been extensively researched but very little is known about NOAEL (No Observed Adverse Effect Level) doses or exposure to a combination of mycotoxins (mixed mycotoxicoses). The aim of this study was to determine the effects of six-week exposure to NOAEL doses of individual and combined mycotoxins on the subpopulations of CD4+8-, CD4-8+ and CD4+8+ lymphocytes in the peripheral blood of pigs. The experiment was performed on 72 gilts with average body weight of 25 kg, divided into three experimental groups (E1, E2 and E3, administered zearalenone (ZEN), deoxynivalenol (DON) and ZEN + DON, respectively, on a daily basis) and a control group (C) receiving placebo. Changes in lymphocyte subpopulations were evaluated by flow cytometry at weekly intervals (experimental days 7, 14, 21, 28, 35 and 42). A linear increase in the percentage of CD4+8+ lymphocytes was highly correlated with time (r = 0.682) in group C. The correlations and linear increase in the above subpopulation were disrupted in the remaining groups. In group E3, a statistically significant (p < 0.05) decrease in CD4+8+ counts was observed in week 5, which could point to a transient depletion of regulatory mechanisms of immune responses. The noted results also suggest that in mixed mycotoxicosis, ZEN and DON exerted stronger immunomodulatory effects. [ABSTRACT FROM AUTHOR]

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers' interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm. [ABSTRACT FROM AUTHOR]

Immature gilts were administered per os with zearalenone (ZEN) at 40 μg/kg BW (group Z, n = 9), deoxynivalenol (DON) at 12 μg/kg BW (group D, n = 9), a mixture of ZEN and DON (group M, n = 9) or a placebo (group C, n = 9) over a period of six weeks. The pigs were sacrificed after one, three, or six weeks of the treatment (12 pigs per each time-point). Histological investigations revealed an increase in the mucosal thickness and the crypt depth as well as a decrease in the ratio of the villus height to the crypt depth in groups D and M after six weeks of exposure to the mycotoxins. The number of goblet cells in the villus epithelium was elevated in groups Z and M after one week and in group D after three weeks. The administration of ZEN increased the lymphocyte number in the villus epithelium after 1 week and the plasma cell quantity in the lamina propria after one, three, and six weeks of the experiment. DON treatment resulted in an increase in the lymphocyte number in the villus epithelium and the lamina propria after six weeks, and in the plasma cell quantity in the lamina propria after one, three, and six weeks of exposure. In group M, lymphocyte counts in the epithelium and the lamina propria increased significantly after six weeks. Neither mycotoxin induced significant adverse changes in the ultrastructure of the mucosal epithelium and the lamina propria or in the intestinal barrier permeability. Our results indicate that immune cells are the principal target of low doses of ZEN and DON. [ABSTRACT FROM AUTHOR]

Zearalenone and its metabolites, α-zearalenol and β-zearalenol, demonstrate estradiol-like activity and disrupt physiological functions in animals. This article evaluates the carryover of zearalenone and its selected metabolites from the digesta to intestinal walls (along the entire intestines) in pre-pubertal gilts exposed to low doses of zearalenone over long periods of time. The term "carryover" describes the transfer of mycotoxins from feed to edible tissues, and it was used to assess the risk of mycotoxin exposure for consumers. The experimental gilts with body weight of up to 25 kg were per os administered zearalenone at a daily dose of 40 µg/kg BW (Group E, n = 18) or placebo (Group C, n = 21) over a period of 42 days. In the first weeks of exposure, the highest values of the carryover factor were noted in the duodenum and the jejunum. In animals receiving pure zearalenone, the presence of metabolites was not determined in intestinal tissues. In the last three weeks of the experiment, very high values of the carryover factor were observed in the duodenum and the descending colon. The results of the study indicate that in animals exposed to subclinical doses of zearalenone, the carryover factor could be determined by the distribution and expression of estrogen receptor beta. [ABSTRACT FROM AUTHOR]

The study evaluated the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars exposed to deoxynivalenol and zearalenone in naturally contaminated feed. The evaluation was performed with the use of the MTT assay and 2 mitogens: lipopolysaccharide (LPS) and concanavalin A. Intensified proliferative processes in T and B lymphocytes were revealed. The mitogenic activity of LPS was more expressed in the lymphocytes of both iliac and jejunal lymph nodes in comparison with the control group. Proliferative activity was higher in iliac lymph nodes than in jejunal lymph nodes. A reverse trend was observed in the percentage of live cells, which was higher in jejunal lymph nodes during the evaluation of lymphocyte proliferation. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the effect of exposure of pigs to the Fusarium mycotoxins zearalenone (ZEN) and deoxynivalenol (DON), administered together and separately, on the colon microbiota. An experiment was conducted for 42 days on gilts, randomly assigned to four groups and administered either ZEN, DON, ZEN+DON, or a placebo. The number of aerobic mesophilic bacteria, yeasts, molds, anaerobic Clostridium perfringens, fecal streptococci, Enterobacteriaceae, Escherichia coli, and lactic acid bacteria (LAB) were determined in the contents of the ascending colon. The influence of mycotoxins on the functional diversity of the colonic microbiota was assessed using EcoPlate tests (Biolog). Analysis revealed the predominance of LAB in all groups of pigs. Zearalenone, administered separately and together with DON, was found to have an adverse effect on mesophilic aerobic bacteria, but only after long exposure to this mycotoxin. During the six weeks of the experiment, the concentration of C. perfringens, E. coli, and other bacteria in the family Enterobacteriaceae was most considerably reduced in the experimental groups exposed to zearalenone, both separately and together with DON. Mycotoxins also affected the functional biodiversity of microorganisms. Both Shannon's diversity index and the number of catabolized substrates in Biolog plate (the R index) were much higher in the group subjected to mixed mycotoxicosis. [ABSTRACT FROM AUTHOR]

Deoxynivalenol is also known as vomitoxin due to its impact on livestock through interference with animal growth and acceptance of feed. At the molecular level, deoxynivalenol disrupts normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation and apoptosis. Because of concerns related to deoxynivalenol, the United States FDA has instituted advisory levels of 5 μg/g for grain products for most animal feeds and 10 μg/g for grain products for cattle feed. The aim of the study was to determine the effect of low doses of deoxynivalenol applied per os on the presence of this mycotoxin in selected tissues of the alimentary canal of gilts. The study was performed on 39 animals divided into two groups (control, C; n = 21 and experimental, E; n = 18), of 20 kg body weight at the beginning of the experiment. Gilts received the toxin in doses of 12 μg/kg b.w./day (experimental group) or placebo (control group) over a period of 42 days. Three animals from two experimental groups were sacrificed on days 1, 7, 14, 21, 28, 35 and 42, excluding day 1 when only three control group animals were scarified. Tissues samples were prepared for high performance liquid chromatography (HPLC) analyses with the application of solid phase extraction (SPE). The results show that deoxynivalenol doses used in our study, even when applied for a short period, resulted in its presence in gastrointestinal tissues. The highest concentrations of deoxynivalenol reported in small intestine samples ranged from 7.2 (in the duodenum) to 18.6 ng/g (in the ileum) and in large intestine samples from 1.8 (in transverse the colon) to 23.0 ng/g (in the caecum). In liver tissues, the deoxynivalenol contents ranged from 6.7 to 8.8 ng/g. [ABSTRACT FROM AUTHOR]

The aim of the study was to verify the hypothesis that intoxication with low doses of mycotoxins leads to changes in the mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes in tissues of the gastrointestinal tract and the liver. The experiment involved four groups of immature gilts (with body weight of up to 25 kg) which were orally administered zearalenone in a daily dose of 40 μg/kg BW (group Z, n = 18), deoxynivalenol at 12 μg/kg BW (group D, n = 18), zearalenone and deoxynivalenol (group M, n = 18) or placebo (group C, n = 21) over a period of 42 days. The lowest mRNA expression levels of nitric oxide synthase-1 and nitric oxide synthase-2 genes were noted in the sixth week of the study, in particular in group M. Our results suggest that the presence of low mycotoxin doses in feed slows down the mRNA expression of both nitric oxide synthase isomers, which probably lowers the concentrations of nitric oxide, a common precursor of inflammation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether low doses of zearalenone (ZEN) influence the carry-over of ZEN and its metabolites to the bone marrow microenvironment and, consequently, haematological parameters. Pre-pubertal gilts (with a body weight of up to 14.5 kg) were exposed to daily ZEN doses of 5 μg/kg BW (group ZEN5, n = 15), 10 μg/kg BW (group ZEN10, n = 15), 15 μg/kg BW (group ZEN15, n = 15), or were administered a placebo (group C, n = 15) throughout the entire experiment. Bone marrow was sampled on three dates (exposure dates 7, 21, and 42—after slaughter) and blood for haematological analyses was sampled on 10 dates. Significant differences in the analysed haematological parameters (WBC White Blood Cells, MONO—Monocytes, NEUT—Neutrophils, LYMPH—Lymphocytes, LUC—Large Unstained Cells, RBC—Red Blood Cells, HGB—Haemoglobin, HCT—Haematocrit, MCH—Mean Corpuscular Volume, MCHC—Mean Corpuscular Haemoglobin Concentrations, PLT—Platelet Count and MPV—Mean Platelet Volume) were observed between groups. The results of the experiment suggest that exposure to low ZEN doses triggered compensatory and adaptive mechanisms, stimulated the local immune system, promoted eryptosis, intensified mycotoxin biotransformation processes in the liver, and produced negative correlations between mycotoxin concentrations and selected haematological parameters. [ABSTRACT FROM AUTHOR]

This study applied multi-mycotoxin liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methods to determine the biomarkers of exposure in urine and serum samples from a dose-response study with pigs. The 24 studied pigs were divided into three groups: a control and two experimental ones (with different levels of feed contamination). They were exposed to feed prepared from cereals contaminated with deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA) and citrinin (CIT) for 14 days. After that, both experimental groups received the same feed as the control group for the next 14 days to determine the kinetics of the disappearance of mycotoxin biomarkers. Urine samples were collected daily in the morning and blood samples—eight-times during the experiment. The study reported herein was the first prolonged exposure experiment for multiple mycotoxins like OTA and CIT in pigs. The urinary and serum levels of all biomarkers correlated well with the respective toxin intake; thereby demonstrating that they are suitable biomarkers of exposure in pigs. Urine is a good candidate to monitor DON, ZEN, OTA, CIT exposure while serum may be used to monitor DON, OTA and CIT. Additionally, OTA has even been quantified in both matrices in the experimental groups two weeks after changing the contaminated feed back to the control, this result differed from those produced by the other mycotoxins which were only quantified during the first two weeks. Therefore both matrices are suitable candidates to monitor prolonged OTA exposure in pigs. [ABSTRACT FROM AUTHOR]

Vascular toxicity induced by xenobiotics is associated with dysfunctions or damage to endothelial cells, changes in vascular permeability or dysregulation of the vascular redox state. The aim of this study was to determine whether per os administration of zearalenone (ZEN) influences selected hemostatic parameters in prepubertal gilts. This study was performed on female gilts divided into a control group which received placebo and an experimental group which received ZEN at a dose of 5.0 µg·kg−1 b.w. × day−1. On days 14, 28 and 42, blood samples were collected from the animals for analyses of hematological, coagulation and fibrinolysis parameters, nitric oxide, von Willebrand factor antigen content and catalase activity. The results demonstrated that the treatment of gilts with ZEN at a dose below no observable adverse effect level did not affect the primary hemostasis and the blood coagulation cascade. However, ZEN could have temporarily affected the selected indicators of endothelial cell function (increase of von Willebrand factor, decrease of nitric oxide levels) and the oxidative status plasma (decrease of catalase activity) of the exposed gilts. In summary, these results suggest that the adaptive response to ZEN-exposure can induce a transient imbalance in the vascular system by acting on vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEN) and its metabolites, alpha-zearalenol (α-ZEL) and beta-zearalenol (β-ZEL), are ubiquitous in plant materials used as feed components in dairy cattle diets. The aim of this study was to confirm the occurrence of ZEN and its selected metabolites in blood samples collected from different sites in the hepatic portal system (posthepatic–external jugular vein EJV; prehepatic–abdominal subcutaneous vein ASV and median caudal vein MCV) of dairy cows diagnosed with mastitis, ovarian cysts and pyometra. The presence of mycotoxins in the blood plasma was determined with the use of combined separation methods involving immunoaffinity columns, a liquid chromatography system and a mass spectrometry system. The parent compound was detected in all samples collected from diseased cows, whereas α-ZEL and β-ZEL were not identified in any samples, or their concentrations were below the limit of detection (LOD). Zearalenone levels were highest in cows with pyometra, where the percentage share of average ZEN concentrations reached 44%. Blood sampling sites were arranged in the following ascending order based on ZEN concentrations: EJV (10.53 pg/mL, 44.07% of the samples collected from this site), ASV (14.20 pg/mL, 49.59% of the samples) and MCV (26.67 pg/mL, 67.35% of the samples). The results of the study indicate that blood samples for toxicological analyses should be collected from the MCV (prehepatic vessel) of clinically healthy cows and/or cows with subclinical ZEN mycotoxicosis. This sampling site increases the probability of correct diagnosis of subclinical ZEN mycotoxicosis. [ABSTRACT FROM AUTHOR]

The carry-over of zearalenone (ZEN) to the myocardium and its effects on coronary vascular reactivity in vivo have not been addressed in the literature to date. Therefore, the objective of this study was to verify the hypothesis that low ZEN doses (MABEL, NOAEL and LOAEL) administered per os to prepubertal gilts for 21 days affect the accumulation of ZEN, α-ZEL and β-ZEL in the myocardium and the reactivity of the porcine coronary arteries to vasoconstrictors: acetylcholine, potassium chloride and vasodilator sodium nitroprusside. The contractile response to acetylcholine in the presence of a cyclooxygenase (COX) inhibitor, indomethacin and / or an endothelial nitric oxide synthase (e-NOS) inhibitor, L-NAME was also studied. The results of this study indicate that the carry-over of ZEN and its metabolites to the myocardium is a highly individualized process that occurs even at very low mycotoxin concentrations. The concentrations of the accumulated ZEN metabolites are inversely proportional to each other due to biotransformation processes. The levels of vasoconstrictors, acetylcholine and potassium chloride, were examined in the left anterior descending branch of the porcine coronary artery after oral administration of ZEN. The LOAEL dose clearly decreased vasoconstriction in response to both potassium chloride and acetylcholine (P < 0.05 for all values) and increased vasodilation in the presence of sodium nitroprusside (P = 0.021). The NOAEL dose significantly increased vasoconstriction caused by acetylcholine (P < 0.04), whereas the MABEL dose did not cause significant changes in the vascular response. Unlike higher doses of ZEN, 5 μg/kg had no negative influence on the vascular system. [ABSTRACT FROM AUTHOR]

Plant materials can be contaminated with Fusarium mycotoxins and their derivatives, whose toxic effects on humans and animals may remain subclinical. Zearalenone (ZEN), a low-molecular-weight compound, is produced by molds in crop plants as a secondary metabolite. The objective of this study will be to analyze the in vivo correlations between very low monotonic doses of ZEN (5, 10, and 15 μg ZEN/kg body weight—BW for 42 days) and the carryover of this mycotoxin and its selected metabolites from the intestinal contents to the intestinal walls, the mRNA expression of estrogen receptor alfa (ERα) and estrogen receptor beta (ERβ) genes, and the mRNA expression of genes modulating selected colon enzymes (CYP1A1 and GSTP1) in the intestinal mucosa of pre-pubertal gilts. An in vivo experiment will be performed on 60 clinically healthy animals with initial BW of 14.5 ± 2 kg. The gilts will be randomly divided into a control group (group C, n = 15) and three experimental groups (group ZEN5, group ZEN10, and group ZEN15; n = 15). Group ZEN5 will be administered per os 5 μg ZEN/kg BW (MABEL), group ZEN10—10 μg ZEN/kg BW (NOAEL), and group ZEN15—15 µg ZEN/kg BW (low LOAEL). In each group, five animals will be euthanized on analytical dates 1 (exposure day 7), 2 (exposure day 21), and 3 (exposure day 42). Samples for in vitro analyses will be collected from an intestinal segment resected from the following regions: the third (horizontal) part of the duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, and descending colon. The experimental material will be collected under special conditions, and it will be transported to specialist laboratories where samples will be obtained for further analyses. [ABSTRACT FROM AUTHOR]