Opioids trigger alpha 5 beta 1 integrin-mediated monocyte adhesion

Inflammatory reactions involve a network of chemical and molecular signals that initiate and maintain host response. In inflamed tissue, immune system cells generate opioid peptides that contribute to potent analgesia by acting on specific peripheral sensory neurons. In this study, we show that opioids also modulate immune cell function in vitro and in vivo. By binding to its specific receptor, the opioid receptor-specific ligand DPDPE triggers monocyte adhesion. Integrins have a key role in this process, as adhesion is abrogated in cells treated with specific neutralizing anti-alpha5beta1 integrin mAb. We found that DPDPE-triggered monocyte adhesion requires PI3Kgamma activation and involves Src kinases, the guanine nucleotide exchange factor Vav-1, and the small GTPase Rac1. DPDPE also induces adhesion of pertussis toxin-treated cells, indicating involvement of G proteins other than Gi. These data show that opioids have important implications in regulating leukocyte trafficking, adding a new function to their known effects as immune response modulators.

Canine microglial cells: stereotypy in immunophenotype and specificity in function?

Microglial cells represent the endogenous immune system of the central nervous system (CNS). Upon pathological insults they reveal their immunological potential aimed at regaining homeostasis. These reactions have long been believed to follow a uniform and unspecific pattern which is irrespective to the underlying disease entity. Evidence is growing that this view seriously underrates microglial competence as the defenders of the CNS. In the present study, microglial cells of 47 dogs were examined ex vivo by means of flow cytometry. Ex vivo examination included immunophenotypic characterization using eight different surface markers and functional studies such as phagocytosis assay and the reactive oxygen species (ROS) generation test. The dogs were classified according to their histopathological diagnoses in disease categories (controls, canine distemper virus (CDV) induced demyelination, other diseases of the CNS) and results of microglial reaction profiles were compared. Immunophenotypic characterization generally revealed relative high conformity in the microglial disease response among the different groups, however the functional response was shown to be more specific. Dogs with intracranial inflammation and dogs with demyelination showed an enhanced phagocytosis, whereas a significant up-regulation of ROS generation was found in dogs with demyelination due to CDV infection. This strongly suggests a specific response of microglia to infection with CDV in the settings of our study and underlines the pivotal role of microglial ROS generation in the pathogenesis of demyelinating diseases, such as canine distemper.

Hypertonic NaCl infusions affect milk composition in goats

The capability of goats to maintain milk production during water deprivation is remarkable and not yet fully understood. The aim of the present study was to investigate whether intravenous infusions of hypertonic NaCl cause release of both vasopressin and oxytocin and whether the peptides, in combination with the hyperosmolality, affect milk flow and milk composition. Six Swedish domestic landrace goats in their first to third lactation were milked every 30 min during experiments. Hypertonic NaCl (HNaCl) or isotonic NaCl (IsoNaCl) were infused for 90 min. Goats were not allowed to drink during infusions. Plasma vasopressin concentration increased during HNaCl infusions, and did not change in response to IsoNaCl infusions. Plasma oxytocin concentration did not change during either infusion. Milk flow was maintained during the infusions. Milk fat concentration decreased in the three samples taken before onset of the infusions, but then increased gradually during HNaCl infusions, while it continued to fall during the IsoNaCl infusions. Milk osmolality followed the rise in plasma osmolality during the HNaCl infusions and did not change in IsoNaCl experiments. Milk lactose concentration increased throughout both series of experiments, the concentration being higher during HNaCl infusions. Milk protein concentration did not change during HNaCl infusions, but fell in the IsoNaCl experiments. It is concluded that the hyperosmolality in combination with elevated plasma vasopressin levels did not disturb the secretory activity of the mammary cells, but rather facilitated emptying of the alveolar milk. Such a mechanism may help to explain the sustained milk production in water deprived goats.

Plasticity in the adult language system: a longitudinal electrophysiological study on second language learning

Event-related potentials (ERPs) were used to trace changes in brain activity related to progress in second language learning. Twelve English-speaking exchange students learning German in Switzerland were recruited. ERPs to visually presented single words from the subjects' native language (English), second language (German) and an unknown language (Romansh) were measured before (day 1) and after (day 2) 5 months of intense German language learning. When comparing ERPs to German words from day 1 and day 2, we found topographic differences between 396 and 540 ms. These differences could be interpreted as a latency shift indicating faster processing of German words on day 2. Source analysis indicated that the topographic differences were accounted for by shorter activation of left inferior frontal gyrus (IFG) on day 2. In ERPs to English words, we found Global Field Power differences between 472 and 644 ms. This may due to memory traces related to English words being less easily activated on day 2. Alternatively, it might reflect the fact that--with German words becoming familiar on day 2--English words loose their oddball character and thus produce a weaker P300-like effect on day 2. In ERPs to Romansh words, no differences were observed. Our results reflect plasticity in the neuronal networks underlying second language acquisition. They indicate that with a higher level of second language proficiency, second language word processing is faster and requires shorter frontal activation. Thus, our results suggest that the reduced IFG activation found in previous fMRI studies might not reflect a generally lower activation but rather a shorter duration of activity.

Sex Differences in Semantic Processing: Event-Related Brain Potentials Distinguish between Lower and Higher Order Semantic Analysis during Word Reading

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processing.

Memory of childbirth in the second year: the long-term effect of a negative birth experience and its modulation by the perceived intranatal relationship with caregivers

OBJECTIVE: To assess the memory of various subdimensions of the birth experience in the second year postpartum, and to identify women in the first weeks postpartum at risk of developing a long-term negative memory. DESIGN, METHOD, OUTCOME MEASURES: New mothers' birth experience (BE) was assessed 48-96 hours postpartum (T1) by means of the SIL-Ger and the BBCI (perception of intranatal relationships); early postnatal adjustment (week 3 pp: T1(bis)) was also assessed. Then, four subgroups of women were defined by means of a cluster-analysis, integrating the T1/T1(bis) variables. To evaluate the memory of the BE, the SIL-Ger was again applied in the second year after childbirth (T2). First, the ratings of the SIL-Ger dimensions of T1 were compared to those at T2 in the whole sample. Then, the four subgroups were compared with respect to their ratings of the birth experience at T2 (correlations, ANOVAs and t-tests). RESULTS: In general, fulfillment, emotional adaptation, physical discomfort, and anxiety improve spontaneously over the first year postpartum, whereas in negative emotional experience, control, and time-going-slowly no shift over time is observed. However, women with a negative overall birth experience and a low level of perceived intranatal relationship at T1 run a high risk of retaining a negative memory in all of the seven subdimensions of the birth experience. CONCLUSIONS: Women at risk of developing a negative long-term memory of the BE can be identified at the time of early postpartum, when the overall birth experience and the perceived intranatal relationship are taken into account.

Differential expression of CD45 on canine microglial cells

CD45, also called leucocyte common antigen is a transmembrane protein tyrosine phosphatase on the surface of nearly all white blood cells and has a functional role in signal transduction. In the brain, the expression of CD45 can be used to distinguish microglial cells with a characteristic phenotype of CD11b/c+ and CD45(low) from other central nervous system (CNS) macrophages which show an expression of CD11b/c+ and CD45(high). In the course of pathological changes in the CNS, microglia in rodents is known to readily upregulate expression of various surface molecules, such as CD45. Understanding the mechanisms that regulate expression of surface molecules is essential to study the pathogenesis of CNS diseases. In the present study, the expression of CD45 on microglia of 42 dogs was examined ex vivo by means of flow cytometry. The dogs were classified in two groups according to the histopathological diagnosis in the CNS. All dogs without changes in the CNS (group I; n = 22) only showed low percentages of CD45+ microglial cells. In group II consisting of 20 dogs with different intracranial diseases varying results were obtained. Thirteen dogs showed a low percentage of CD45+ microglial cells whereas seven dogs exhibited high percentages of microglial cells expressing CD45. Evaluation of expression intensity in these seven dogs revealed two subpopulations of CD45+ microglial cells: a large subpopulation with CD45(low) and a small subpopulation with CD45(high). The expression intensity of CD45(high) was comparable with that of canine monocytes. It was attempted to correlate these findings to age of the animals, underlying disease, duration of clinical signs, medical treatment, occurrence of seizure activity and the expression of other surface molecules. It appeared that dogs with high percentages of CD45+ suffered from long-lasting CNS disease with seizures. In future studies, the reason and consequences for upregulated CD45 in long-lasting CNS diseases has to be further evaluated.

Treatment of tibial fractures with plates using minimally invasive percutaneous osteosynthesis in dogs and cats

OBJECTIVES: The aim of the here described case series was to develop and evaluate the minimally invasive percutaneous osteosynthesis for the plate fixation of tibial fractures in dogs and cats. METHODS: Six dogs and four cats with shaft fractures of the tibia were treated using minimally invasive percutaneous osteosynthesis. Follow-up radiographs four to six weeks after fracture fixation were evaluated for fracture healing. For the long-term follow-up (minimum 2.4 years), owners were contacted by phone to complete a questionnaire. RESULTS: All fractures healed without the need for a second procedure. Follow-up radiographs obtained after four to six weeks in seven cases showed advanced bony healing with callus formation and filling of the fracture gaps with calcified tissue in all seven. All the patients had a good to excellent long-term result with full limb function. The time needed for regaining full limb use was two to three months. CLINICAL SIGNIFICANCE: Minimally invasive percutaneous osteosynthesis seems to be a useful technique for the treatment of tibial shaft fractures in dogs and cats.

De novo ceramide biosynthesis is associated with resveratrol-induced inhibition of ornithine decarboxylase activity

Previous studies could demonstrate, that the naturally occuring polyphenol resveratrol inhibits cell growth of colon carcinoma cells at least in part by inhibition of protooncogene ornithine decarboxylase (ODC). The objective of this study was to provide several lines of evidence suggesting that the induction of ceramide synthesis is involved in this regulatory mechanisms. Cell growth was determined by BrdU incorporation and crystal violet staining. Ceramide concentrations were detected by HPLC-coupled mass-spectrometry. Protein levels were examined by Western blot analysis. ODC activity was assayed radiometrically measuring [(14)CO(2)]-liberation. A dominant-negative PPARgamma mutant was transfected in Caco-2 cells to suppress PPARgamma-mediated functions. Antiproliferative effects of resveratrol closely correlate with a dose-dependent increase of endogenous ceramides (p<0.001). Compared to controls the cell-permeable ceramide analogues C2- and C6-ceramide significantly inhibit ODC-activity (p<0.001) in colorectal cancer cells. C6-ceramide further diminished protein levels of protooncogenes c-myc (p<0.05) and ODC (p<0.01), which is strictly related to the ability of ceramides to inhibit cell growth in a time- and dose-dependent manner. These results were further confirmed using inhibitors of sphingolipid metabolism, where only co-incubation with a serine palmitoyltransferase (SPT) inhibitor could significantly counteract resveratrol-mediated actions. These data suggest that the induction of ceramide de novo biosynthesis but not hydrolysis of sphingomyelin is involved in resveratrol-mediated inhibition of ODC. In contrast to the regulation of catabolic spermidine/spermine acetyltransferase by resveratrol, inhibitory effects on ODC occur PPARgamma-independently, indicating independent pathways of resveratrol-action. Due to our findings resveratrol could show great chemopreventive and therapeutic potential in the treatment of colorectal cancers.