The environmental neurotoxin trimethyltin (TMT) destroys parts of the hippocampal formation as well as the entorhinal cortex but leaves the septal cholinergic projection to the hippocampus and dentate gyrus intact. In this study we measured choline acetyltransferase (ChAT) activity in micropunch samples of the dentate gyrus, the CA1 region of Ammon's horn, and the caudate-putamen as a measure of density of cholinergic innervation in control rats and rats exposed to 7 mg/kg TMT by means of gastric intubation. Three months after the rats were exposed to a single dose of TMT both the dentate gyrus and CA1 demonstrated significantly higher ChAT activity in TMT-exposed rats than in control rats. No differences were found between groups for the caudate-putamen samples. These results support the hypothesis that exposure to TMT causes reactive synaptogenesis in the cholinergic septohippocampal system.

Background: Elevation of C-reactive protein (CRP) levels in blood was recognized as one of the cardiac disease risk factors. Consumption of wine is shown to reduce the risk from heart disease and improve longevity. Objectives: In the present study, we evaluated the effect of various wine polyphenolic compounds and several active synthetic derivatives of resveratrol on the inflammatory cytokines (IL-1β+IL-6)-induced CRP expression in Hep3B cells. Results: Among the wine phenolics tested, quercetin and resveratrol, in a dose-dependent manner, suppressed cytokine-induced CRP expression. Two of the synthetic derivatives of resveratrol, R3 and 7b, elicited a fiftyfold higher suppressive effect compared with resveratrol. The inhibitory effects of resveratrol and its derivatives on CRP expression were at the level of mRNA production. Investigation of signaling pathways showed that the cytokines induced the phosphorylation of p38 and p44/42 MAP kinases. Inhibitors of p38 and p44/42 mitogen-activated protein kinase (MAPK) activation inhibited CRP expression, implicating the involvement of both pathways in cytokine-induced CRP expression. These data revealed a previously unrecognized role of the p44/42 MAPK signaling pathway in CRP expression. Wine polyphenolics or the synthetic compounds of resveratrol did not affect cytokine-activated phosphorylation of these MAPKs. Conclusions: Wine phenolics inhibit CRP expression; however, to do so, they do not utilize the MAPK pathways.

C-reactive protein (CRP) is made in liver and its serum concentration increases in inflammation. Measurement of serum CRP is recommended for use as an indicator of inflammation and predictor of atherosclerosis. Cholesterol-lowering drugs statins also lower CRP. To evaluate statin-mediated CRP reduction and to reassess clinical usefulness of CRP, we investigated regulation of CRP gene expression. Here, we show that pravastatin and simvastatin prevent the induction of CRP expression in human hepatoma Hep3B cells exposed to proinflammatory cytokines IL-6 and IL-1β. The nitric oxide (NO) donor, sodium nitroprusside, also prevented the induction of CRP expression while the CRP inducers IL-6 and IL-1β were present with the cells. The effect of NO on CRP expression was at the level of transcription. These findings suggest that the decrease in CRP level in vivo after statin-treatment does not necessarily reflect absence of inflammation, and that NO-releasing drugs have the potential to reduce serum CRP levels. Thus, the measurement of serum CRP levels alone in individuals on statin/NO-therapy is not as useful as was imagined.

C-reactive protein (CRP) that has been conserved throughout evolution is a host-defense molecule. Its attraction towards phosphocholine-ligands, such as modified low-density lipoprotein, and apoptotic cells leads to the "masking" of these substances that have the capabilities to otherwise engage in deleterious activities. Complement activation by CRP complexes and the modulation by CRP of complement activation by its ligands add up to its beneficial effects. In the presence of CRP, production of membrane-damaging last product of the complement pathway is arrested. CRP is currently serving as an indicator of cardiovascular diseases, but to pinpoint the role of CRP in atherosclerosis, a drug that can lower cholesterol levels, but not the CRP levels, is needed for experimentation.

Summary. Despite its being the most efficacious drug for symptom reversal in Parkinson's disease (PD), there is concern that chronic levodopa (L-DOPA) treatment may be detrimental. In this paper we review the potential for L-DOPA to 1) autoxidize from a catechol to a quinone, and 2) generate other reactive oxygen species (ROS). Overt toxicity and neuroprotective effects of L-DOPA, both in vivo and in vitro, are described in the context of whether L-DOPA may accelerate or delay progression of human Parkinson's disease.

Acute phase proteins (APP) are ideal biomarkers for inflammation due to their stability, relative ease of assay and apparent relation between their concentration and the extent of the insult to tissue. C-reactive protein (CRP) is a positive major APP in dogs and can be used as a predictive marker for risk of disease and to monitor the response to treatment. Increased concentrations in certain diseases are associated with poor outcome. This cross-sectional, observational study of 75 dogs naturally infected with Babesia rossi, a cause of virulent canine babesiosis, was designed to examine the association of CRP concentration at admission and the magnitude of CRP change 24 hours after admission with outcome. Dogs were excluded if there was evidence of concurrent inflammatory diseases at the time of admission, infection with subtypes other than B. rossi, concurrent Ehrlichia canis infections or euthanasia for reasons other than poor prognosis. Diagnosis was confirmed by polymerase chain reaction and reverse line blot. CRP concentrations were determined by an automated human CRP Turbidometric Immunoassay (TIA), previously validated for use in dogs (Bayer CRP TIA, Newbury, UK), on serum samples collected by jugular venipuncture on admission, prior to any therapy, and thereafter daily until discharge or death. There was no significant difference in admission CRP concentration between survivors (n = 57; median = 97.4 mg/l; mean ± SD = 107.5 ± 49.5), and non-survivors (n = 11; median = 101.4 mg/l; mean ± SD = 122.1 ± 64.6) (p = 0.39). After elimination of non-significant predictors, a multiple exact logistic regression model for predicting mortality contained glucose and CRP. Mortality was associated with decreased glucose levels (p = 0.0002) and increased CRP levels (p = 0.045) on admission. Multiple regression analysis failed to show a significant relationship between admission CRP concentration and number of days of hospitalization in the survivors, adjusting for age and sex (p = 0.65). No significance was found in the relationship between the magnitude of change in CRP concentration 24 hours after admission, and the number of days of hospitalization in survivors, (p = 0.34). Using an admission CRP concentration cut-off of 60 mg/l, survival proportions between the two groups were no different (p = 0.34) and when applied to the group of dogs that survived, it was not associated with length of hospitalization (p = 0.25). In corroboration with previous reports glucose was identified as a major prognostic marker for mortality, but additionally the pro-inflammatory marker CRP was identified as a significant co-prognosticator. Copyright / Dissertation (MMedVet)--University of Pretoria, 2009. / Companion Animal Clinical Studies / unrestricted

Reactive attachment disorder (RAD), a disorder marked by a severe disruption in developmental attachment, is most often diagnosed in youth who have received substandard or negligent care from their primary caregiver. Such youth have increased risk of behavioral and emotional issues as well as future relationship problems; they generally do not respond to traditional evidence-based practices of therapy. The present study examined the use of the biofield energy practice of Healing Touch (HT) as a viable therapeutic option for improved quality of life for youth diagnosed with RAD. A quantitative, quasi-experimental research study using secondary data was conducted. Eligible participants were 40 children between the ages of 6and 21 residing at a residential facility and having the diagnosis of RAD. Half of the participants received HT therapy while the other half did not. Dependent variables of frequencies of seclusion, aggression, self-injury/self-harm, property damage in excess of $50, and running away from the facility were assessed at set intervals before and after implementation of HT therapy. Findings from a 2 x 2 mixed factorial design using mixed ANOVAs lacked statistical significance; therefore, the alternative hypotheses were not supported. However, the potential remains for positive social change. Clinical importance was evidenced in several variables demonstrating improvement in behaviors for many participants. In addition, while statistical significance was not obtained, the study contributes to the knowledge base regarding the use of HT therapy for future studies.

This study assesses the effectiveness of an innovative shoulder training and rehabilitation device, the Rotr 1. The device uses mechanically created motion to disturb the balance of muscular forces around the shoulder, thereby facilitating dynamic training of the muscles. The hypothesis is that random disturbances provided by the device would potentially in-crease shoulder muscle activation as users try to resist the device’s motion. To test the efficacy of the device, shoulder muscle activation from two groups (ten non-athletes and seven athletes), was assessed in three different shoulder positions and four different exercise conditions (aka configurations). Muscle activation of seven different shoulder muscles was recorded using electromyography (EMG). 3D motion capture was used to ensure repeatability of the positions during testing. ANOVA was done to assess the differences in muscle activation across groups, positions and exercise conditions. This device has the potential to improve performance and rehabilitation of overhead athletes, by increasing the body’s ability to effectively react and protect the shoulder.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12816号 / 論医博第2078号 / 新制||医||1004(附属図書館) / 31303 / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩井 一宏, 教授 長田 重一, 教授 川口 義弥 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18851号 / 医博第3962号 / 新制||医||1007(附属図書館) / 31802 / 京都大学大学院医学研究科医学専攻 / (主査)教授 別所 和久, 教授 鈴木 茂彦, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM