Effects of prenatal maternal ethanol on male offspring progressive-ratio performance and response to amphetamine

This study was designed to further explore the nature of our previously reported reduction in the efficacy of food reinforcers for prenatal ethanol-exposed mice. We determined the effect of prenatal ethanol exposure on responding for food delivered on a progressive-ratio (PR) reinforcement schedule, which has been shown to be sensitive to changes in motivation and/or value of reinforcers, and we assessed the effects of amphetamine on responding maintained by the PR schedule. Subjects were adult (12 months old) male offspring of C57BL/6J mice fed liquid diets containing either ethanol (25% ethanol-derived calories, N = 12) or sucrose (25% sucrose-derived calories, N = 9) during gestation days 5–17. Prenatal ethanol-exposed mice differed from controls by having lower response rates and a greater disruption of responding following amphetamine injections. The reduced responding for food reward on the PR schedule supports our previously advanced hypothesis that prenatal ethanol reduces the efficacy of food reinforcers. The enhanced effects of amphetamine found in these adult mice is in agreement with previous reports on young rats. Although either of the effects of prenatal ethanol exposure observed in the present study are suggestive of altered DA systems, current neurochemical studies on either rats or mice provide no support for the hypothesis.     

Novel markers of the human follicle-associated epithelium identified by genomic profiling and microdissection

BACKGROUND & AIMS: Regulation of gene expression in the follicle-associated epithelium (FAE) over Peyer's patches is largely unknown. CCL20, a chemokine that recruits immature dendritic cells, is one of the few FAE-specific markers described so far. Lymphotoxin beta (LTalpha1beta2) expressed on the membrane of immune cells triggers CCL20 expression in enterocytes. In this study, we measured expression profiles of LTalpha1beta2-treated intestinal epithelial cells and selected CCL20 -coregulated genes to identify new FAE markers. METHODS: Genomic profiles of T84 and Caco-2 cell lines treated with either LTalpha1beta2, flagellin, or tumor necrosis factor alpha were measured using the Affymetrix GeneChip U133A. Clustering analysis was used to select CCL20 -coregulated genes, and laser dissection microscopy and real-time polymerase chain reaction on human biopsy specimens was used to assess the expression of the selected markers. RESULTS: Applying a 2-way analysis of variance, we identified regulated genes upon the different treatments. A subset of genes involved in inflammation and related to the nuclear factor kappaB pathway was coregulated with CCL20 . Among these genes, the antiapoptotic factor TNFAIP3 was highly expressed in the FAE. CCL23 , which was not coregulated in vitro with CCL20 , was also specifically expressed in the FAE. CONCLUSIONS: We have identified 2 novel human FAE specifically expressed genes. Most of the CCL20 -coregulated genes did not show FAE-specific expression, suggesting that other signaling pathways are critical to modulate FAE-specific gene expression.     

Murine M cells express annexin V specifically

The specialized epithelium covering the lymphoid follicles of Peyer's patches in the gut mediates transcytosis of antigens to the underlying immune cells, mainly through the membranous, or M, cells. At present, the molecular processes involved in the mucosal immune response, and in antigen transport across the follicle-associated epithelium (FAE) and M cells, are poorly understood. To characterize FAE and M cells, we compared the gene expression profiles of small intestine FAE and villus epithelium (VE) in BALB/c mice by microarray analysis; 91 genes were found to be up-regulated and four down-regulated at least two-fold (p<0.01) in the FAE. The differential expression of a subset of these genes was shown to be confirmed by quantitative RT-PCR. Using immunohistochemistry on BALB/c Peyer's patches, cathepsin H and clusterin expression was increased in the FAE compared to the VE. Moreover, we demonstrated M cell-specific expression of annexin V, which has recently been reported to be important in endocytic transport and membrane scaffolding, suggesting that annexin V has a function in M cell-mediated transcytosis.     

Diagnostic perspective of fetal alcohol and tobacco syndromes

ABSTRACT  Maldevelopment of the brain in offspring whose mothers drank and/or smoked during pregnancy was evaluated using Japanese data. The diagnostic criteria for fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) revealed that FAS infants exhibited a severer degree of CNS involvement than FAE infants. In addition to the criteria for fetal tobacco syndrome (FTS), we proposed the term "fetal tobacco effects (FTE)" for when the gestational age is less than 37 weeks. Maldevelopment of the brain was not severer in FTS than FTE, to which factors other than smoking causing a reduction in the gestational period, and ones during pregnancy and delivery may contribute. The effects on the CNS of alcohol were more frequent and severer than those of tobacco. CNS involvement was shown to increase with increasing consumption of alcohol or tobacco.     

Fetal alcohol syndrome: diagnosis, epidemiology, and developmental outcomes

In Australia the issue of fetal alcohol syndrome (FAS) has not been the subject of policy development or of extensive research. There is a lack of knowledge, both in the general community and by health professionals, of the nature of the risks associated with heavy alcohol consumption during pregnancy and the factors that increase this risk. This paper reviews the literature surrounding FAS with the aim of providing the reader an understanding of the diagnostic features and epidemiology of FAS and of the developmental sequelae associated with this syndrome.     

Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin

In this study, a polymeric lipid nanoparticle (NP) (simplified as Lipid NP) was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide) (PLGA) core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA) was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC) and entrapment efficiency (EE) for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI) environment for a long time. In addition, a human microfold cell (M-cell) transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.     

Defining the anatomical localisation of subsets of the murine mononuclear phagocyte system using integrin alpha X (Itgax, CD11c) and colony stimulating factor 1 receptor (Csf1r, CD115) expression fails to discriminate dendritic cells from macrophages

The murine mononuclear phagocyte (MNP) system comprises a diverse population of cells, including monocytes, dendritic cells (DC) and macrophages. Derived from the myeloid haematopoietic lineage, this group of cells express a variety of well characterized surface markers. Expression of the integrin alpha X (Itgax, CD11c) is commonly used to identify classical DC, and similarly expression of colony stimulating factor 1 receptor (Csf1r, CD115) to identify macrophages. We have characterized the expression of these markers using a variety of transgenic mouse models. We confirmed previous observations of Itgax expression in anatomically defined subsets of MNPs in secondary lymphoid organs, including all MNPs identified within the germinal centres. The majority of MNPs in the intestinal lamina propria and lung express Itgax. All mucosal Itgax expressing cells also express Csf1r suggesting Csf1-dependent haematopoietic derivation. This double-positive population included germinal centre MNPs. These data reveal that Itgax expression alone does not specifically define classical DC. These results suggest more cautious interpretation of Itgax-dependent experimentation and direct equation with uniquely DC-mediated activities, particularly in the functioning of non-lymphoid MNPs within the intestinal lamina propria.     

Oat-based breakfast cereals are a rich source of polyphenols and high in antioxidant potential

Oats are a rich source of β-glucans and bioactive phytochemicals. The established health-beneficial properties of oats have led to an increase in the consumption of oats and oat-based food products in recent years. The objective of the present study was to analyse and compare the polyphenol content and total antioxidant capacity (via FRAP (ferric ion reducing antioxidant power) and DPPH (2,2-diphenyl-1-picrylhydrazyl) inhibition) of 30 commercially available oat-based breakfast cereals. All of the breakfast cereals analysed were a significant source of polyphenols (1506–1853 μg gallic acid equivalents (GAE)/g) and antioxidants (1682–3542 μmol/l FRAP; 30–201% inhibition of DPPH compared to gallic acid standard). There was little difference between premium and budget brand varieties of the breakfast cereals. The polyphenol levels in an average serving (40 g) of an oat-based breakfast cereal are comparable to those found in fruits and vegetables. Overall, our findings suggest that consumption of oat-based breakfast cereals could be a significant contributor to the total polyphenol content and antioxidant potential of the diet.     

The mucosal immune system for vaccine development

Mucosal surfaces are continuously exposed to the external environment and therefore represent the largest lymphoid organ of the body. In the mucosal immune system, gut-associated lymphoid tissues (GALTs), including Peyer's patches and isolated lymphoid follicles, play an important role in the induction of antigen-specific immune responses in the gut. GALTs have unique organogenesis characteristics and interact with the network of dendritic cells and T cells for the simultaneous induction and regulation of IgA responses and oral tolerance. In these lymphoid tissues, antigens are up taken by M cells in the epithelial layer, and antigen-specific immune responses are subsequently initiated by GALT cells. Nasopharynx- and tear-duct-associated lymphoid tissues (NALTs and TALTs) are key organized lymphoid structures in the respiratory tract and ocular cavities, respectively, and have been shown to interact with each other. Mucosal surfaces are also characterized by host-microbe interactions that affect the genesis and maturation of mucosa-associated lymphoid tissues and the induction and regulation of innate and acquired mucosal immune responses. Because most harmful pathogens enter the body through mucosal surfaces by ingestion, inhalation, or sexual contact, the mucosa is a candidate site for vaccination. Mucosal vaccination has some physiological and practical advantages, such as decreased costs and reduced risk of needle-stick injuries and transmission of bloodborne diseases, and it is painless. Recently, the application of modern bioengineering and biochemical engineering technologies, including gene transformation and manipulation systems, resulted in the development of systems to express vaccine antigens in transgenic plants and nanogels, which will usher in a new era of delivery systems for mucosal vaccine antigens. In this review, based on some of our research group's thirty seven years of progress and effort, we highlight the unique features of mucosal immune systems and the application of mucosal immunity to the development of a new generation of vaccines.