Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.     

Deletion of glutamate receptor-A (GluR-A) AMPA receptor subunits impairs one-trial spatial memory.

Genetically modified mice lacking the glutamate receptor A (GluR-A) subunit of the AMPA receptor (GluR-A-/- mice) display normal spatial reference memory but impaired spatial working memory (SWM). This study tested whether the SWM impairment in these mice could be explained by a greater sensitivity to within-session proactive interference. The SWM performance of GluR-A-/- and wild-type mice was assessed during nonmatching-to-place testing under conditions in which potential proactive interference from previous trials was reduced or eliminated. SWM was impaired in GluR-A-/- mice, both during testing with pseudotrial-unique arm presentations on the radial maze and when conducting each trial on a different 3-arm maze, each in a novel testing room. Experimentally naive GluR-A-/- mice also exhibited chance performance during a single trial of spontaneous alternation. This 1-trial spatial memory deficit was present irrespective of the delay between the sample information and the response choice (0 or 45 min) and the length of the sample phase (0.5 or 5 min). These results imply that the SWM deficit in GluR-A-/- mice is not due to increased susceptibility to proactive interference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Comparison of GluR-A-Deficient and Wild-Type Mice on a Test Battery Assessing Sensorimotor, Affective, and Cognitive Behaviors.

Previous studies have demonstrated a spatial working memory deficit in glutamate receptor (GluR)-A (GluR1) AMPA receptor subunit knockout mice. The present study evaluated male and female wild-type and GluR-A/ mice on a test battery that assessed sensorimotor, affective, and cognitive behaviors. Results revealed a behavioral phenotype more extensive than previously described. GluR-A/ mice were hyperactive, displayed a subtle lack of motor coordination, and were generally more anxious than wild-type controls. In addition, they showed a deficit in spontaneous alternation, consistent with previous reports of a role for GluR-A-dependent plasticity in hippocampus-dependent, spatial working memory. Although changes in motor coordination or anxiety cannot explain the dissociations already reported within the spatial memory domain, it is clear that they could significantly affect interpretation of results obtained in other kinds of behavioral tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial Septal Lesions Mimic Effects of Both Selective Dorsal and Ventral Hippocampal Lesions.

Electrolytic medial septal (MS) lesions, which depleted acetylcholinesterase staining in both dorsal and ventral hippocampus, produced a constellation of behaviors, combining aspects of both selective dorsal and ventral hippocampal lesion effects. MS lesions impaired spatial working memory on the T maze, thus resembling the effects of dorsal hippocampal lesions. In addition, MS lesions reduced anxiety during successive alleys (a modified form of the elevated plus-maze), social interaction, and hyponeophagia tests. MS lesions also reduced postshock freezing. These effects more closely resemble those of ventral hippocampal lesions. Therefore, the effects of electrolytic MS lesions derive from the resulting combined deafferentation of dorsal and ventral hippocampal regions, suggesting that previously reported effects of cytotoxic dorsal hippocampal lesions are unlikely to be due to a demyelination of fibers of passage coursing through the septal pole. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular epidemiology and cluster analysis of human listeriosis cases in three U.S. states

To better understand the transmission and epidemiology of human listeriosis, 647 Listeria monocytogenes isolates obtained from human listeriosis cases in four U.S. locations (Michigan, Ohio, New York State, and New York City) over 61 months (1998 to 2003) were characterized by automated EcoRI ribotyping. A total of 65 ribotypes were differentiated among the characterized isolates; 393, 227, and 24 isolates were classified into lineages I, II, and III, respectively, and 3 isolates were not classified to lineage. The three most common ribotypes (responsible for 39% of all cases) represented L. monocytogenes epidemic clones, each of which had previously been linked to at least two human listeriosis outbreaks. Categorical analyses revealed that ribotypes and lineages were nonrandomly distributed among the four locations. Temporal cluster analysis of cases identified 13 statistically significant temporal subtype clusters, which represented 26% of all cases. Three of these clusters matched previously described human listeriosis outbreaks. Isolates involved in clusters belonged to nine ribotypes. Four, eight, and one cluster were caused by lineages I, II, and III, respectively. The two largest clusters were both caused by the epidemic clone representing ribotype DUP-1044A. Categorical analyses revealed no significant associations between lineage or ribotype and clinical manifestation (central nervous system infection, septicemia, fetal infection, or other infection) or disease outcome (fatal or not fatal). Although human listeriosis cases are caused by isolates belonging to a diversity of EcoRI ribotypes, specific lineage I epidemic clones cause a large number of human listeriosis cases. Many human listeriosis cases can be grouped into statistically significant temporal clusters, including widely distributed and region-specific clusters associated with isolates of various ribotypes. L. monocytogenes lineages and EcoRI ribotypes do not appear to differ in their likelihood of causing different clinical manifestations or mortality.     

Differential effects of ibotenic acid lesions of the hippocampus and blockade of N-methyl-D-aspartate receptor-dependent long-term potentiation on contextual processing in rats

The contextual specificity of appetitive conditioned responding was examined in rats undergoing chronic intracerebroventricular infusion of 15 or 30 mM D-2-amino-5-phosphonopentanoic acid (D-AP5) or with excitotoxic hippocampal lesions. The magnitude of conditioned responding by control rats and rats infused with D-AP5 to a conditioned stimulus (CS) trained in Context A was attenuated when the same stimulus was presented in Context B. By contrast, hippocampal-lesioned rats displayed comparable levels of responding to the CS when presented in either Context A or B. Subsequent in vivo electrophysiological investigations showed that the D-AP5 concentrations were effective in blocking long-term potentiation (LTP) in the dentate gyrus. Results indicate that rats are capable of processing contextual information in the absence of N-methyl-D-aspartate (NMDA) receptor-dependent LTP and demonstrate an important dissociation between the effects of hippocampal lesions and the blockade of NMDA receptors in the hippocampus.     

Investigating the antecedents of perceived social support: Parents' views of and behavior toward their children.

College students' perceptions of generalized social support were investigated from a developmental perspective. 262 undergraduates completed questionnaires concerning general and relationship-specific social support. Questionnaires were mailed to students' parents and a sibling. Student reports of past and present parental relationships predicted parents' questionnaire return. Parents' views of students' personal characteristics predicted students' general perceptions of social support. Relationship-specific social support perceived from father but not mother was predicted by that parent's view of the student. Students' self-views and feelings of parental acceptance, variables theoretically associated with general social support, were also predicted by parents' views. Parental views of siblings did not in general predict student variables. Results are discussed in terms of relationship-based family antecedents of social support. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A multistate outbreak of Salmonella enterica serotype typhimurium infection linked to raw milk consumption--Ohio, 2003

In December 2002, the Ohio Department of Health was notified of two children with Salmonella infection. Both had a history of drinking raw milk from a combination dairy-restaurant-petting zoo (dairy). The dairy was the only establishment in Ohio licensed to sell raw milk and reported 1.35 million visitors annually. We investigated to determine the extent of the outbreak and identify illness risk factors. A case patient was any person with pulsed-field gel electrophoresis-matched Salmonella enterica serotype Typhimurium from 30 November 2002 to 18 February 2003. Sixty-two met the confirmed case definition. Forty dairy case patient patrons were included in a case-control study; 56 controls were their well meal companions. Consumption of raw milk was found to be associated with illness (odds ratio, 45.1; 95% confidence interval, 8.8 to 311.9). The dairy discontinued selling raw milk. Because 27 other states still allow the sale of raw milk, awareness of the hazards of its consumption should be raised and relevant regulations carefully reviewed.     

Investigation into the risk of exposure to antibiotic residues contaminating meat and egg in Ghana

In Ghana and many developing countries, little is known about food safety in relation to antibiotic residues. The objectives of the study were to (i) determine the prevalence of antibiotic residues in animal source food and estimate the risk to consumers (ii) identify factors predisposing animal source food to contamination with antibiotic drug residues. A total of 634 samples of various animal source foods, including beef, chevon, mutton, pork and egg were screened for drug residues. Additionally, epidemiological data related to antibiotic usage on animals and consumption patterns of animal source food was collected from animal farmers and consumers of animal source food respectively. Overall, the prevalence of drug residues in animal source food was 21.1%, which translates to an average risk of exposure every fifth time animal source food is consumed. The prevalence rates of drug residues in the various animal source foods were; 30.8% (beef); 29.3% (chevon); 28.6% (pork); 24% (mutton); and 6.8% (egg). The trends of consumption of the animal source foods were similar, and majority of the consumers consumed the food every week. Considering the relatively high contamination rates of animal source food as well as their high rates of consumption, it is likely that consumers experience a high risk of exposure to drug residues, especially through beef. Specific causal factors associated with non-adherence of withdrawal requirements of drugs, and therefore contaminations of food were mainly knowledge related factors. This underscores the importance of health education of farmers in dealing with the problem of drug residues contaminating animal source food.