Antiplatelet effects of R,S-(meso)-alpha, alpha'-bis[3-(N,N-diethylcarbamoyl) piperidino]-p-xylene ex vivo in the dog and in vivo in the mouse

1. The nipecotamide alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene (A-1) is a platelet aggregation inhibitor. The meso diastereomer A-1c is superior in potency and duration to the synthetic diastereomeric mixture consisting of the R,R-, S,S-, and R,S- (meso) isomers in inhibiting collagen-induced platelet aggregation ex vivo in the dog. 2. A-1c also is more potent and longer acting than A-1 in protecting mice from collagen+epinephrine-induced thromboembolic death. 3. The mechanism of antiplatelet action of this compound appears to be related to its ability to prevent agonist-induced inhibition of platelet cyclic adenosine monophosphate (cAMP) levels.     

Comparison of Holstein and Jersey innate immune responses to Escherichia coli intramammary infection

Mastitis is one of the most prevalent diseases in cattle and remains among the most costly diseases to the dairy industry. Various surveys have indicated a greater prevalence of and risk for mastitis in Holstein cows than in Jersey cows. The innate immune system comprises the immediate host defense mechanisms that respond to infection, and differences in the magnitude and rapidity of this response are known to influence susceptibility to and clearance of infectious pathogens. The reported differences in the prevalence of mastitis between Holstein and Jersey cows may suggest the occurrence of breed-dependent differences in the innate immune response to intramammary infection. The objective of the current study was to compare the acute phase and cytokine responses of Holstein and Jersey cows following intramammary infection by the bacterial pathogen Escherichia coli, a leading cause of clinical mastitis. All cows in the study were in similar stages of lactation, of the same parity, subjected to the same housing and management conditions, and experimentally infected on the same day with the same inoculum preparation. Before and after infection, the following innate immune parameters were monitored: bacterial clearance; febrile response; induction of the acute phase proteins serum amyloid A and lipopolysaccharide-binding protein; alterations in total and differential white blood cell counts; changes in milk somatic cell counts and mammary vascular permeability; and induction of the cytokines IFN-γ, IL-1β, IL-8, IL-12, and tumor necrosis factor-α. Overall innate immune responses were similar between the 2 breeds; however, temporal differences in the onset, cessation, and duration of several responses were detected. Despite these differences, intramammary clearance of E. coli was comparable between the breeds. Together, these data demonstrate a highly conserved innate immune response of Holstein and Jersey cows to E. coli intramammary infection.     

Proteomic analysis of differentially expressed proteins in bovine milk during experimentally induced Escherichia coli mastitis

The objectives of the current study were to profile changes in protein composition using 2-dimensional gel electrophoresis on whey samples from a group of 8 cows before and 18 h after infection with Escherichia coli and to identify differentially expressed milk proteins by peptide sequencing using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry post source decay. Only proteins present in whey fractions of all 8 cows were sequenced to avoid reporting a protein response unique to only a subset of infected cows. Despite the overwhelming presence of casein and β-lactoglobulin, the low abundance proteins transthyretin, lactadherin, β-2-microglobulin precursor, α-1-acid glycoprotein, and complement C3 precursor could be identified in whey samples from healthy cows. Whey samples at 18 h postinfection were characterized by an abundance of serum albumin, in spots of varying mass and isoelectric point, as well as increased transthyretin and complement C3 precursor levels. Also detected at 18 h postinoculation were the antimicrobial peptides cathelicidin, indolicidin, and bactenecin 5 and 7, and the proteins β-fibrinogen, α-2-HS-glycoprotein, S100-A12, and α-1-antiproteinase. Most notable was the detection of the acute phase protein α-1-acid glycoprotein in mastitic whey samples, a result not previously reported. In contrast to methods used in previous proteomic analyses of bovine milk, the methods used in the current study enabled the rapid identification of milk proteins with minimal sample preparation. Use of a larger sample size than previous analyses also allowed for more robust protein identification. Results indicate that examination of the protein profile of whey samples from cows after inoculation with E. coli could provide a rapid survey of milk protein modulation during coliform mastitis and aid in the identification of biomarkers of this disease.     

Targeted deletion of the GluR-1 AMPA receptor in mice dissociates general and outcome-specific influences of appetitive rewards on learning.

The authors assessed the hypothesis that deletion of the GluR-1 subtype of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor in mice disrupts the associative activation of a sensory-specific representation of an appetitive reward. In Experiment 1, mice received training on a Pavlovian-instrumental transfer task. In the test stage, conditioned stimulus (CS) presentations enhanced instrumental actions in both groups. However, this effect was specific to the action that shared the same outcome as the CS in wild-type (WT), but not GluR-1-/-, mice. In Experiment 2, the mice were trained on a heterogeneous instrumental chain in which rewards were obtained for emitting 1 response (R1, that was distal to reward delivery), followed by a 2nd response (R2, that was proximal to reward delivery). A change in general motivational state (from hungry to sated) reduced the number of R2 responses in both groups. In contrast, an outcome-specific satiety treatment produced a selective decline in R1 responding only in WT mice. The results support the hypothesis that GluR-1 deletion impairs the associative activation of a representation of the sensory-specific incentive motivational properties of an appetitive reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the entorhinal cortex in a process of attentional modulation: Evidence from a novel variant of an IDS/EDS procedure.

Novel behavioral assays were used to assess the role of the entorhinal cortex in modulating attention to components of stimulus compounds. In Stage 1, rats received discrimination training with compounds constructed from 3 dimensions (auditory, visual, and tactile); in each compound the combination of components from 2 dimensions (e.g., auditory and visual) were relevant to the solution of the discrimination, and the remaining dimension (e.g., tactile) was irrelevant. In Stage 2, rats received a different discrimination in which the relevant dimensions were either congruent (auditory and visual) or incongruent (auditory and tactile) with those that were relevant in Stage 1. Sham-operated rats acquired the congruent discrimination more rapidly than the incongruent discrimination—a finding indicative of a process of attentional modulation—whereas rats with excitotoxic lesions of the entorhinal cortex acquired both discriminations equally readily. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Mesocortical Dopamine Projection to Anterior Cingulate Cortex Plays No Role in Guiding Effort-Related Decisions.

Both mesolimbic dopamine (DA) and the anterior cingulate cortex (ACC) have been implicated in enabling animals to expend effort to obtain greater reward. To investigate the role of the DA pathway to ACC in working for reward, the authors tested rats on a cost-benefit T-maze paradigm in which they could either climb a barrier to obtain large reward in 1 arm (high reward [HR]) or select the low-effort alternative containing less reward (low reward [LR]). Surprisingly, ACC DA depletions had no effect on choice performance. Manipulations of barrier and reward sizes demonstrated that lesioned rats were as sensitive to the costs and benefits of the alternatives as controls. These results imply that the DA projection to ACC is not involved in guiding effort-related decisions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze": Correction to Oswald et al. (2003).

Reports an error in "Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze" by C. J. P. Oswald, D. M. Bannerman, B. K. Yee, J. N. P. Rawlins, R. C. Honey and M. Good (Behavioral Neuroscience, 2003[Jun], Vol 117[3], 588-595). The definitions "Present = intramaze landmark present during Stage 2" and "Absent = intramaze landmark absent during Stage 2" appear incorrectly in the caption to Figure 3. These terms and definitions should appear in the caption to Figure 4. (The following abstract of the original article appeared in record 2003-05069-018.) This study with rats examined the effects of excitotoxic lesions to the entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a disruption to the use of extramaze cues, but not intramaze cues, whereas EC lesions had no effect on the use of these cues when they were encountered for the fast time. However, prior navigation training in which 1 type of cue was relevant disrupted navigation with the other type in rats with EC lesions. Results show that the EC contributes to the processing of spatial information, but that this contribution is most apparent when there is a conflict between 2 sources of navigational cues in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of function within the hippocampus: A comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions.

Rats with complete cytotoxic hippocampal lesions exhibited spatial memory impairments in both the water maze and elevated T maze. They were hyperactive in photocell cages; swam faster in the water maze; and were less efficient on a nonspatial, differential reinforcement of low rates (DRL) task. Performance on both spatial tasks was also impaired by selective dorsal but not ventral lesions; swim speed was increased by ventral but not dorsal lesions. Both partial lesions caused a comparable reduction in DRL efficiency, although these effects were smaller than those of complete lesions. Neither partial lesion induced hyperactivity when rats were tested in photocell cages, although both complete and ventral lesion groups showed increased activity after footshock in other studies (Richmond et al., see record 1999-01985-006). These results demonstrate possible functional dissociations along the septotemporal axis of the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats with hippocampal lesions learn about allocentric place cues in a non-navigational task.

Hippocampal-lesioned rats (HPC) and sham controls (SH) learned constant-negative visual discriminations among scenes in a Y-maze. Any arm could be start arm for a trial. Two choice scenes ("constant" and "variable") were shown in the other arms. In Experiment 1, each problem had 2 constants. One or the other constant appeared on every trial, and the variable changed every trial; choosing the variable was rewarded. There were 4 problem types. Each constant might be always in a given direction from the start arm (added egocentric [Ego] cue), always in a given maze arm (added allocentric [Allo] cue), both, or neither. SH rats' visual learning was enhanced by Ego and by Allo cues. HPC rats' visual learning was enhanced by Ego cues, and by Allo cues, but only if there was no Ego cue. Experiment 2 confirmed that Allo cues helped HPC rats as much as SH, in the absence of Ego cues. Rats with HPC lesions can learn about allocentric place cues when navigation and idiothetic cue control are not required. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation of function within the hippocampus: Spatial memory and hyponeophagia.

Complete and dorsal hippocampal lesions impaired spatial performance on 2 working memory tasks: rewarded alternation on the T maze and matching to position in the water maze. In contrast, ventral hippocampal lesions had no effect on these tasks, even when task difficulty was increased by the introduction of delays. Ventral lesions did resemble complete lesions in reducing anxiety in 3 commonly used tests of anxiety (social interaction, plus-maze, and hyponeophagia). Dorsal lesions also appeared to be anxiolytic in the social interaction and plus-maze tests, but they did not affect hyponeophagia. Complete- and dorsal-lesioned rats displayed hyperactivity, whereas ventral-lesioned rats did not. These results show a double dissociation between dorsal and ventral hippocampal lesions (hyponeophagia vs. spatial memory), suggesting differentiation of function along the septotemporal axis of this structure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)