Subchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health

Cadmium (Cd) was recently identified as a risk factor for osteoporosis. Skeletal damage may be the critical effect of low-level long-term exposure to Cd in the general population exposed via food, but the mechanisms behind this are not clearly understood.We investigated the effects of dietary Cd exposure on metals involved in bone turnover. Female rats received a Cd-supplemented diet (0, 10, 50, or 200 CdCl2 mg/kg diet) for 13 weeks. Cd and essential metals stored in the liver were measured by ICP-MS multianalysis. Mineral content of the livers was modified according to Cd level : iron, magnesium and selenium decreased while copper, zinc and manganese increased with increasing Cd levels. Iron was the most strikingly affected metal, falling to one-fifth of control values at high dietary Cd exposure. In this dosage group, selenium decreased to 36% of mean control concentrations while zinc increased to 168%. This mineral imbalance, especially depleted iron stores, can contribute, at least in part, to the Cd-associated risk of osteoporosis. The association between iron metabolism and Cd exposure should be investigated in humans, as Cd and low iron stores could act synergistically as risk factors for osteoporosis

HPLC assay of zearalenone and reduced metabolites in S9 fractions of duck liver

HPLC analysis of zearalenone (ZEA), zearalenols (-ZOL and ß-ZOL) and zearalanols (-ZAL and ß-ZAL) was developed, in order to obtain a sensitive and reproducible method to quantify ZEA and its reduced metabolites in subcellular fractions of animal livers (S9 samples). Optimal in vitro metabolism was observed by incubating 5 mg S9 proteins with 0.016 μmol. ZEA. Acetonitrile and diethylether/chloroform mixture were compared for extraction, as well as different mobile phases and two detection modes in HPLC analysis. Extracted samples were eluted with water/acetonitrile (55:45, v/v) at a flow-rate of 1.0 ml/min-1, resulting in well separated peaks between ZEA and the metabolites. The limits of detection ranged from 0.5 to 2 ng/mg S9 proteins using UV, and from 0.04 to 4 ng/mg S9 proteins, using fluorescence detection. Fluorescence showed a ten-fold higher sensitivity than UV detection for ZEA and -ZOL. Repeatability (10 assays) was 2.7% to 6.99% for zearalenols. Day-by-day coefficients of variation for zearalenone and zeranols with UV detection were 3.3 to 8.5 %, and 2.5 to 4.3 %, respectively. This analysis applied to S9 samples from ducks after 30 min of ZEA incubation allowed to demonstrate that -ZOL is the main reduced metabolite in the duck. The present method is particularly adapted for studying in vitro metabolism of ZEA and inter-species variations

Variations in zearalenone activation in avian food species

Zearalenone (ZEA), a widely distributed oestrogenic fusariotoxin, constitutes a potential risk for human and animal health. ZEA is metabolised to the main metabolites identified in vitro and in vivo: alpha-zearalenol (α-ZOL) and beta-zearalenol (β-ZOL). The efficiency to produce alpha-reduced metabolites appears of particular interest in risk assessment as alpha-reduced metabolites constitute activated forms whereas beta-reduced metabolites are less oestrogenic than ZEA. In this study ZEA activation was compared in avian food species. ZEA and its reduced metabolites were quantified in subcellular fractions of six avian species and rat livers. The α-ZOL/β-ZOL ratio in rats was 19. The various avian food species cannot be considered to be equivalent in terms of ZEA reduction (P<0.001). Quails represented high “beta reducers”, with α-ZOL/β-ZOL ratio less than two. Weak “beta reducers” included on one part ducks and chickens showing α-ZOL/β-ZOL ratio greater than 3 and up to 5.6 and on a second part geese, showing a lower production of α-ZOL than other poultry. Comparisons of enzyme kinetics in ducks and in quails show that these variations can be explained by the action of various isoforms of dehydrogenases. These results are relevant to food safety, in the context of frequently inevitable contamination of animal feed

Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions

Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches. Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147220/1/pmr2414.pd

Central pain mechanisms in the rheumatic diseases: Future directions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96384/1/37739_ftp.pd

Newer treatments for fibromyalgia syndrome

Fibromyalgia syndrome is a common chronic pain disorder of unknown etiology. The lack of understanding of the pathophysiology of fibromyalgia has made this condition frustrating for patients and clinicians alike. The most common symptoms of this disorder are chronic widespread pain, fatigue, sleep disturbances, difficulty with memory, and morning stiffness. Emerging evidence points towards augmented pain processing within the central nervous system (CNS) as having a primary role in the pathophysiology of this disorder. Currently the two drugs that are approved by the United States Food and Drug Administration (FDA) for the management of fibromyalgia are pregabalin and duloxetine. Newer data suggests that milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, may be promising for the treatment of fibromyalgia. A double-blind, placebo-controlled trial of milnacipran in 125 fibromyalgia patients showed significant improvements relative to placebo. Milnacipran given either once or twice daily at doses up to 200 mg/day was generally well tolerated and yielded significant improvements relative to placebo on measures of pain, patient’s global impression of change in their disease state, physical function, and fatigue. Future studies are needed to validate the efficacy of milnacipran in fibromyalgia

Development of a pig jejunal explant culture for studying the gastrointestinal toxicity of the mycotoxin deoxynivalenol: histopathological analysis

The digestive tract is a target for the mycotoxin deoxynivalenol (DON), a major cereals grain contaminant of public health concern in Europe and North America. Pig, the most sensitive species to DON toxicity, can be regarded as the most relevant animal model for studying the intestinal effects of DON. A pig jejunal explants culture was developed to assess short-term effects of DON. In a first step, jejunal explants from 9-13 week-old and from 4-5 week-old pigs were cultured in vitro for up to 8 hours. Explants from younger animals were better preserved after 8 hours, as assessed by morphological scores and by villi lengths. In a second step, dose-related alterations of the jejunal tissue were observed, including shortened and coalescent villi, lysis of enterocytes, oedema. After 4h of DON exposure of explants from 4-5 week-old pigs, a no-effect concentration level of 1 µM was estimated (corresponding to diet contaminated with 0.3 mg DON/kg) based on morphological scores, and of 0.2 µM based on villi lengths. In conclusion, our data indicate that pig intestinal explants represent a relevant and sensitive model to investigate the effects of food contaminants

Higher-order mutual information reveals synergistic sub-networks for multi-neuron importance

Quantifying which neurons are important with respect to the classification decision of a trained neural network is essential for understanding their inner workings. Previous work primarily attributed importance to individual neurons. In this work, we study which groups of neurons contain synergistic or redundant information using a multivariate mutual information method called the O-information. We observe the first layer is dominated by redundancy suggesting general shared features (i.e. detecting edges) while the last layer is dominated by synergy indicating local class-specific features (i.e. concepts). Finally, we show the O-information can be used for multi-neuron importance. This can be demonstrated by re-training a synergistic sub-network, which results in a minimal change in performance. These results suggest our method can be used for pruning and unsupervised representation learning.Comment: Paper presented at InfoCog @ NeurIPS 202