Effects of gestational and lactational exposure to PCB126 and methylmercury on circulating steroid hormone levels at weaning and puberty in the rat

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A statement on the developmental immunotoxicity of bisphenol A (BPA) : answer to the question from the Dutch Ministry of Health, Welfare and Sport

The Panel wishes to thank EFSA staff member Cristina Croera for the support provided to this scientific opinion.Publisher PD

Advancing human health risk assessment

Acknowledgements: The European Food Safety Authority (EFSA) and authors wish to thank the participants of the break‐out session ‘Advancing risk assessment science – Human health’ at EFSA's third Scientific Conference ‘Science, Food and Society’ (Parma, Italy, 18–21 September 2018) for their active and valuable contributions to the discussion. We also thank Hans Verhagen for carefully proofreading it.Peer reviewedPublisher PD

Classification of current anticancer immunotherapies

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches

Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis

Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation

Effects of inorganic and organic mercury on intracellular calcium levels in rat t lymphocytes

The importance of cytosolic free calcium level (fCa2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury com-pounds, which have been shown to have immunomodulatory and immunotoxic properties. Using fura-2 as fluorescent Ca2+ indicator, we found that both methyl- mercury (MeHg; 0.02-2 nM) and inorganic mercury (HgCI2; 0.01-1 pM) increased [Ca2+]i in lymphocytes from rat spleen in a concentration-dependent manner. The effect of MeHg was rapid and the increase of Ca2+ level was sustained in time, while HgCI2 caused a slow rise in [Ca2+]i. The effects of mercury compounds did not appear to be associated with alterations of membrane integrity, since there was no significant difference in the extent of MnCI2 quench between control and mercury-treated cells. However, HgCI2 (1 jtM) and MeHg (2 nM) appeared to cause membrane damage at longer incubation times (15 min). When cells were incubated in Ca2+-free medium (in the presence of 1 mM EDTA) MeHg still increased [Ca2+]i, though to a lesser extent, while HgCI2 had no effect. Heparin, an inhibitor of inositol 1, 4, 5,-trisphosphate-induced Ca2+ mobilization partially blocked this rise of [Ca2+]i, white carbonyl cyanide m-chlorophenylhydraxone (CCCP),. © 1988 by Hemisphere Publishing Corporation

DEPRESSED NEUTROPHIL-MEDIATED TUMOR CELL CYTOTOXICITY IN SUBJECTS AFFECTED BY HEREDITARY MYELOPEROXIDASE DEFICIENCY AND SECONDARY NEOPLASIA

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Interaction of mercury compounds with muscarinic receptor subtypes in the rat brain

The in vitro effects of mercuric chloride (HgCl2) and methylmercury (CH3HgOH) on the M1 and M2 muscarinic receptor subtypes were investigated in rat brain cortical membranes. HgCl2 and CH3HgOH were almost equipotent in inhibiting the binding of [3H]telenzepine to M1 receptors (IC50s = 2.2 and 3.4 microM, respectively). Conversely, HgCl2 was a thirty-fold more potent inhibitor of [3H]AF-DX 384 binding to M2 sites than CH3HgOH (lC50s = 5 and 149 microM, respectively). In all cases HgCl2 showed steep and monophasic inhibition curves, whereas those of CH3HgOH were biphasic (M1) or shallow (M2). CH3HgOH-induced inhibition of both [3H]telenzepine and [3H]AF-DX 384 binding was of the competitive type, while HgCl2 caused a pronounced reduction of the Bmax value associated with a small change in affinity. CH3HgOH also decreased the affinity of the agonist carbachol for M1 and M2 receptors, while inorganic mercury had minimal effects on the carbachol dose-response curves. These results indicate that inorganic and organic mercury differ in their interaction with muscarinic receptor subtypes and that M1 receptors may represent a preferential target for their effects