A history of opioid exposure in females increases the risk of metabolic disorders in their future male offspring

© 2019 Society for the Study of Addiction Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation. Thus, we examined diet-induced modifications in F1 male progeny of morphine-exposed female rats (MORF1). When fed a high fat-sugar diet (FSD) for 6 weeks, MORF1 males display features of emerging metabolic syndrome; they consume more food, gain more weight, and develop fasting-induced hyperglycemia and hyperinsulinemia. In the hypothalamus, proteins involved in energy homeostasis are modified and RNA sequencing revealed down-regulation of genes associated with neuronal plasticity, coupled with up-regulation of genes associated with immune, inflammatory, and metabolic processes that are specific to FSD-maintained MORF1 males. Thus, limited preconception morphine exposure in female rats increases the risk of metabolic syndrome/type 2 diabetes in the next generation

Processing and characterization of chitosan microspheres to be used as templates for layer-by-layer assembly

Chitosan (Ch) microspheres have been developed by precipitation method, cross-linked with glutaraldehyde and used as a template for layer-by-layer (LBL) deposition of two natural polyelectrolytes. Using a LBL methodology, Ch microspheres were alternately coated with hyaluronic acid (HA) and Ch under mild conditions. The roughness of the Ch-based crosslinked microspheres was characterized by atomic force microscopy (AFM). Morphological characterization was performed by environmental scanning electron microscopy (ESEM), scanning electron microscopy (SEM) and stereolight microscopy. The swelling behaviour of the microspheres demonstrated that the ones with more bilayers presented the highest water uptake and the uncoated cross-linked Ch microspheres showed the lowest uptake capability. Microspheres presented spherical shape with sizes ranging from 510 to 840 lm. ESEM demonstrated that a rougher surface with voids is formed in multilayered microspheres caused by the irregular stacking of the layers. A short term mechanical stability assay was also performed, showing that the LBL procedure with more than five bilayers of HA/Ch over Ch cross-linked microspheres provide higher mechanical stability

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity

Aims/hypothesis. Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. Methods. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. Results. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy −/− mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo–pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. Conclusions/interpretation. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding

Commentary: mechanistic considerations for associations between formaldehyde exposure and nasopharyngeal carcinoma

Occupational exposure to formaldehyde has been linked to nasopharyngeal carcinoma. To date, mechanistic explanations for this association have primarily focused on formaldehyde-induced cytotoxicity, regenerative hyperplasia and DNA damage. However, recent studies broaden the potential mechanisms as it is now well established that formaldehyde dehydrogenase, identical to S-nitrosoglutathione reductase, is an important mediator of cGMP-independent nitric oxide signaling pathways. We have previously described mechanisms by which formaldehyde can influence nitrosothiol homeostasis thereby leading to changes in pulmonary physiology. Considering evidences that nitrosothiols govern the Epstein-Barr virus infection cycle, and that the virus is strongly implicated in the etiology of nasopharyngeal carcinoma, studies are needed to examine the potential for formaldehyde to reactivate the Epstein-Barr virus as well as additively or synergistically interact with the virus to potentiate epithelial cell transformation

Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium

Tuft cells represent a fourth type of intestinal secretory cell that constitutes the primary source of endogenous intestinal opioids and are the only epithelial cell that constitutively express cyclooxygenases

Spectral deconvolution in electrophoretic NMR to investigate the migration of neutral molecules in electrolytes

Electrophoretic nuclear magnetic resonance (eNMR) is a powerful tool in studies of nonaqueous electrolytes, such as ionic liquids. It delivers electrophoretic mobilities of the ionic constituents and thus sheds light on ion correlations. In applications of liquid electrolytes, uncharged additives are often employed, detectable via 1H NMR. Characterizing their mobility and coordination to charged entities is desirable; however, it is often hampered by small intensities and 1H signals overlapping with major constituents of the electrolyte. In this work, we evaluate methods of phase analysis of overlapping resonances to yield electrophoretic mobilities even for minor constituents. We use phase-sensitive spectral deconvolution via a set of Lorentz distributions for the investigation of the migration behavior of additives in two different ionic liquid-based lithium salt electrolytes. For vinylene carbonate as an additive, no field-induced drift is observed; thus, its coordination to the Li+ ion does not induce a correlated drift with Li+. On the other hand, in a solvate ionic liquid with tetraglyme (G4) as an additive, a correlated migration of tetraglyme with lithium as a complex solvate cation is directly proven by eNMR. The phase evaluation procedure of superimposed resonances thus broadens the applicability of eNMR to application-relevant complex electrolyte mixtures containing neutral additives with superimposed resonances

The Ras-ERK pathway is required for the induction of neuronal nitric oxide synthase in differentiating PC12 cells

We have studied the role of MAP kinase pathways in neuronal nitric oxide synthase (nNOS) induction during the differentiation of PC12 cells. In nerve growth factor (NGF)-treated PC12 cells, we find nNOS induced at RNA and protein levels, resulting in increased NOS activity. We note that neither nNOS mRNA, nNOS protein nor NOS activity is induced by NGF treatment in cells that have been infected with a dominant negative Ras adenovirus. We have also used drugs that block MAP kinase pathways and assessed their ability to inhibit nNOS induction. Even though U0126 and PD98059 are both MEK inhibitors, we find that U0126, but not PD98059, blocks induction of nNOS protein and NOS activity in NGF-treated PC12 cells. Also, the p38 kinase inhibitor, SB203580, does not block nNOS induction in our clone of PC12 cells. Since the JNK pathway is not activated in NGF-treated PC12 cells, we conclude that the Ras-ERK pathway and not the p38 or JNK pathway is required for nNOS induction in NGF-treated PC12 cells. We find that U0126 is much more effective than PD98059 in blocking the Ras-ERK pathway, thereby explaining the discrepancy in nNOS inhibition. We conclude that the Ras-ERK pathway is required for nNOS induction