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Trichothecenes are toxic metabolites produced by fungi that constitute a worldwide hazard for agricultural production and both animal and human health. More than 40 countries have introduced regulations or guidelines for food and feed contamination levels of the most prevalent trichothecene, deoxynivalenol (DON), on the basis of its ability to cause growth suppression. With the development of analytical tools, evaluation of food contamination and exposure revealed that a significant proportion of the human population is chronically exposed to DON doses exceeding the provisional maximum tolerable daily dose. Accordingly, a better understanding of trichothecene impact on health is needed. Upon exposure to low or moderate doses, DON and other trichothecenes induce anorexia, vomiting and reduced weight gain. Several recent studies have addressed the mechanisms by which trichothecenes induce these symptoms and revealed a multifaceted action targeting gut, liver and brain and causing dysregulation in neuroendocrine signaling, immune responses, growth hormone axis, and central neurocircuitries involved in energy homeostasis. Newly identified trichothecene toxicosis biomarkers are just beginning to be exploited and already open up new questions on the potential harmful effects of chronic exposure to DON at apparently asymptomatic very low levels. This review summarizes our current understanding of the effects of DON and other trichothecenes on food intake and weight growth. [ABSTRACT FROM AUTHOR]

Abstract: Neurotrophins, and in particular BDNF, play important roles in proliferation, differentiation and survival of neurons during development, as well as in the synaptic activity and plasticity in many groups of mature neurons. Several lines of evidence suggest that BDNF and its high affinity receptor TrkB contribute to food intake and body weight control. In rodents, pharmacological treatments with BDNF induce reduction in food intake, whereas genetic models with an altered BDNF/TrkB signalling display hyperphagia and obesity. Genetic studies in humans have shown that mutations in the BDNF or TrkB genes may account for certain types of obesity or other forms of eating disorders. Since circulating levels of BDNF correlate with eating disorders in humans and peripheral BDNF treatments reduce hyperphagia and hyperglycaemia in obese diabetic rodents, an endocrine role of BDNF appears plausible and requires further investigation. A central anorectic action of BDNF has also been documented, with a primary focus on the hypothalamus and a more recent highlight on the brainstem integrator of energy homeostasis, the dorsal vagal complex. In this review, we will briefly present neurotrophins and their receptors and focus on experimental evidence which point out BDNF as a signalling component of food intake regulation, with a particular emphasis on the localization of the central anorectic action of BDNF. [Copyright &y& Elsevier]

Reports that three novel toxins belonging to the scorpion K+ channel-inhibitor family were purified to homogeneity from the venom of the Chinese scorpion Buthus martensi. Process of purification of the toxins; Physicochemical characterization of the toxins; Effects of Bm toxins on voltage-gated K+ channels; Effects of Bm toxins on BKCa channels.

Investigates the mechanism of action of 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of 2,5-dialkylpyrrolidines, in vitro on preparations of the ventral nerve cord of the crayfish Procambarus clarkii. Study methodology; Results of study; Indication that Pyr9 blocks spike conduction without affecting the resting potential; Discussion of the results.

Abstract: T-2 toxin is one of the most toxic Fusarium-derived trichothecenes found on cereals and constitutes a widespread contaminant of agricultural commodities as well as commercial foods. Low doses toxicity is characterized by reduced weight gain. To date, the mechanisms by which this mycotoxin profoundly modifies feeding behavior remain poorly understood and more broadly the effects of T-2 toxin on the central nervous system (CNS) have received limited attention. Through an extensive characterization of sickness-like behavior induced by T-2 toxin, we showed that its per os (p.o.) administration affects not only feeding behavior but also energy expenditure, glycaemia, body temperature and locomotor activity. Using c-Fos expression mapping, we identified the neuronal structures activated in response to T-2 toxin and observed that the pattern of neuronal populations activated by this toxin resembled that induced by inflammatory signals. Interestingly, part of neuronal pathways activated by the toxin were NUCB-2/nesfatin-1 expressing neurons. Unexpectedly, while T-2 toxin induced a strong peripheral inflammation, the brain exhibited limited inflammatory response at a time point when anorexia was ongoing. Unilateral vagotomy partly reduced T-2 toxin-induced brainstem neuronal activation. On the other hand, intracerebroventricular (icv) T-2 toxin injection resulted in a rapid (<1h) reduction in food intake. Thus, we hypothesized that T-2 toxin could signal to the brain through neuronal and/or humoral pathways. The present work provides the first demonstration that T-2 toxin modifies feeding behavior by interfering with central neuronal networks devoted to central energy balance. Our results, with a particular attention to peripheral inflammation, strongly suggest that inflammatory mediators partake in the T-2 toxin-induced anorexia and other symptoms. In view of the broad human and breeding animal exposure to T-2 toxin, this new mechanism may lead to reconsider the impact of the consumption of this toxin on human health. [Copyright &y& Elsevier]

Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals, has been implicated in mycotoxicoses in both humans and farm animals. Low-dose toxicity is characterized by reduced weight gain, diminished nutritional efficiency, and immunologic effects. The levels and patterns of human food commodity contamination justify that DON consumption constitutes a public health issue. DON stability during processing and cooking explains its large presence in human food. We characterized here DON intoxication by showing that the toxin concomitantly affects feeding behavior, body temperature, and locomotor activity after both per os and central administration. Using c-Fos expression mapping, we identified the neuronal structures activated in response to DON and observed that the pattern of neuronal populations activated by the toxin resembled those induced by inflammatory signals. By real-time PCR, we report the first evidences for a DON-induced central inflammation, attested by the strong upregulation of interleukin-1β, interleukin-6, tumor necrosis factor-α, cyclooxygenase-2, and microsomal prostaglandin synthase-1 (mPGES-1) messenger RNA. However, silencing prostaglandins E2 signaling pathways using mPGES-1 knockout mice, which are resistant to cytokine-induced sickness behavior, did not modify the responses to the toxin. These results reveal that, despite strong similarities, behavioral changes observed after DON intoxication differ from classical sickness behavior evoked by inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Physiological regulations of energy balance and body weight imply highly adaptive mechanisms which match caloric intake to caloric expenditure. In the central nervous system, the regulation of appetite relies on complex neurocircuitry which disturbance may alter energy balance and result in anorexia or obesity. Deoxynivalenol (DON), a trichothecene, is one of the most abundant mycotoxins found on contaminated cereals and its stability during processing and cooking explains its widespread presence in human food. DON has been implicated in acute and chronic illnesses in both humans and farm animals including weight loss. Here, we provide the first demonstration that DON reduced feeding behavior and modified satiation and satiety by interfering with central neuronal networks dedicated to food intake regulation. Moreover, our results strongly suggest that during intoxication, DON reaches the brain where it modifies anorexigenic balance. In view of the widespread human exposure to DON, the present results may lead to reconsider the potential consequences of chronic DON consumption on human eating disorders. [ABSTRACT FROM AUTHOR]

The article presents several cases related to anti-trust laws in several countries. Information on a case is presented in which the Argentine Supreme Court of Justice (CSJN) reversed the judgment of the Argentine Court of Appeals in Civil and Commercial Matters, in which it had held that the Argentine Antitrust Commission (AAC) should investigate and decide its cases independently of the Secretary of Domestic Trade of Argentina, with reference to the mergers of several companies.

Abstract: Numerous studies, focused on the hypothalamus, have recently implicated endocannabinoids (EC) as orexigenic factors in the central control of food intake. However, the EC system is also highly expressed in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). Previous studies have shown that exogenous cannabinoids, by acting on cannabinoid 1 receptor (CB1R), suppress GABAergic and glutamatergic neuronal transmission in adult rat dorsal motor nucleus of the vagus nerve (DMNV), the principal efferent compartment of the DVC. However, no endogenous release of EC has been demonstrated in DVC to date. Using patch-clamp techniques on mouse coronal brainstem slices, we confirmed that both inhibitory and excitatory neurotransmission were depressed by WIN 55,212-2, a CB1R agonist. We demonstrated that DMNV neurons exhibited a rapid and reversible depolarization-induced suppression of electrically evoked GABAergic IPSCs (eIPSCs), classically known as DSI (depolarization-induced suppression of inhibition), while spontaneous or miniature IPSCs activity remained unaltered. Further, no depolarization-induced suppression of glutamatergic eEPSCs (DSE) occurred. Our results indicate that DSI was blocked by SR141716A (Rimonabant), a selective CB1R antagonist, and was dependent on calcium elevation in DMNV neurons, suggesting a release of EC in the DVC. Moreover, the analysis of the paired-pulse ratio, of the coefficient of variation and of the failure rate of eIPSCs support the fact that EC-mediated suppression of GABAergic inhibition takes place at the presynaptic level. These results show for the first time that DMNV neurons release EC in an activity-dependent manner, which in turn differentially regulates their inhibitory and excitatory synaptic inputs. [Copyright &y& Elsevier]

The avoidance of being overweight or obese is a daily challenge for a growing number of people. The growing proportion of people suffering from a nutritional imbalance in many parts of the world exemplifies this challenge and emphasizes the need for a better understanding of the mechanisms that regulate nutritional balance. Until recently, research on the central regulation of food intake primarily focused on neuronal signaling, with little attention paid to the role of glial cells. Over the last few decades, our understanding of glial cells has changed dramatically. These cells are increasingly regarded as important neuronal partners, contributing not just to cerebral homeostasis, but also to cerebral signaling. Our understanding of the central regulation of energy balance is part of this (r)evolution. Evidence is accumulating that glial cells play a dynamic role in the modulation of energy balance. In the present review, we summarize recent data indicating that the multifaceted glial compartment of the brainstem dorsal vagal complex (DVC) should be considered in research aimed at identifying feeding-related processes operating at this level. [ABSTRACT FROM AUTHOR]

Four peptidyl inhibitors of the small-conductance Ca2+-activated K+ channels (SKca) have been isolated from the venom of the Chinese scorpion Buthus martensi. These peptides were identified by screening C18 HPLC fractions of the crude venom by means of mass analysis by matrix-assisted-laser-desorption/ionization time-of-flight mass spectrometry, and toxicological tests in mice. Edman degradation analysis of the purified peptides showed sequences of 28–31 amino acids including 6 cysteine residues. Three of the sequences were similar to the P01 peptides from Androctonus scorpions, showing 76% sequence similarity for the most closely related, named BmP01. and 46% for the other two, named BmP02 and BmP03. Like the P01 peptides, these molecules showed a low toxic activity in mice after intracerebro-ventricular injection, and competed (K0.5 > 1 μM) with iodinated apamin for binding to its receptor site from rat brain, which has been proved to be the SKca channels. The fourth toxin was structurally related to the P05/leiurotixin I toxin family, with 90% similarity, and was named BmP05. This toxin exhibited a high toxic activity with lethal effects in mice. Due to its small representation in the venom [less than 0.01% (by mass)], its biological properties have been assessed on the synthetic analogue of BmP05. which was assembled on a solid phase by means of Fmoc methodology. The synthetic peptide was physicochemically identical to the natural peptide, as shown by comparison of their molecular masses and amino acid compositions, and by their coelution after coinjection on capillary electrophoresis. These results confirmed the primary structure of BmP05 including an amidated C-terminus. Similarly to natural BmP05, synthetic BmP05 produced toxic and lethal effects after intracerebroventricular injection in mice (LD50 = 37 rig). and was able to compete with iodinated apamin for binding to its receptor in rat brain (K0.5 = 20 pM). [ABSTRACT FROM AUTHOR]

The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located in the hypothalamus and the dorsal vagal complex (DVC), which integrate nutritional, humoral and nervous information from the periphery. The glial cells' contribution to these processes emerged few year ago. However, its underlying mechanism remains unclear. Glial connexin 43 hemichannels (Cx43 HCs) enable direct exchange with the extracellular space and can regulate neuronal network activity. In the present study, we sought to determine the possible involvement of glial Cx43 HCs in energy balance regulation. We here show that Cx43 is strongly expressed in the hypothalamus and DVC and is associated with glial cells. Remarkably, we observed a close apposition of Cx43 with synaptic elements in both the hypothalamus and DVC. Moreover, the expression of hypothalamic Cx43 mRNA and protein is modulated in response to fasting and diet-induced obesity. Functionally, we found that Cx43 HCs are largely open in the arcuate nucleus (ARC) from acute mice hypothalamic slices under basal condition, and significantly inhibited by TAT-GAP19, a mimetic peptide that specifically blocks Cx43 HCs activity. Moreover, intracerebroventricular (i.c.v.) TAT-GAP19 injection strongly decreased food intake, without further alteration of glycaemia, energy expenditures or locomotor activity. Using the immediate early gene c-Fos expression, we found that i.c.v. TAT-GAP19 injection induced neuronal activation in hypothalamic and brainstem nuclei dedicated to food intake regulation. Altogether, these results suggest a tonic delivery of orexigenic molecules associated with glial Cx43 HCs activity and a possible modulation of this tonus during fasting and obesity. [ABSTRACT FROM AUTHOR]