Intrathecal bradykinin administration: opposite effects on nociceptive transmission

Injected intrathecally, bradykinin (BK) produced either hyperalgesia (0.15 microg) or antinociception (6.0 microg) in rats when thermal noxious stimuli were used. Similarly, des-Arg(9)-BK at the lower dose (0.15 microg) decreased, whereas at the higher dose (6.0 microg) it increased the threshold to thermal noxious stimuli; however, these effects were less pronounced than those of BK. The antinociception induced by BK was abolished by HOE 140, a B(2) receptor antagonist, injected intrathecally at a dose of 1.3 ng and was markedly attenuated by des-Arg(10)-HOE 140, a B(1) receptor antagonist (1.15 ng i.t.). The results obtained in this study showed that--depending on the dose used--BK and des-Arg(9)-BK could produce pro- as well as antinociceptive actions. Both B(2) and B(1) receptors are involved in the action of intrathecally applied BK.     

NoiseChem: An European Commission research project on the effects of exposure to noise and industrial chemicals on hearing and balance

Exposure to multiple physical and chemical agents is common in occupational environments but workplace hazards and occupational safety criteria for combined exposures is lacking. NoiseChem is an European Commission research project examining the effects of exposure to noise and chemicals on hearing and balance. Partners in Sweden, Finland, France, Denmark, UK and Poland with expert guidance from partners in USA will examine workers and study the mechanisms of action in animals to determine the levels of risk associated with joint exposure to noise and solvents. This paper briefly outlines the project details.     

Neuronal basis of neuroleptic-induced extrapyramidal side effects

The article reviews presently commonly accepted concepts of neuronal basis of neuroleptic-induced extrapyramidal side effects. The data obtained both, in humans and laboratory animals, point to the blockade of a large number of the striatal dopamine D2 receptors by neuroleptics as a primary cause of these disturbances. This phenomenon leads to the appearance of parkinsonian symptoms shortly after therapy commencement. On the other hand, chronic administration of neuroleptics evokes supersensitivity to dopamine connected with the increased number of D2 receptors and supersensitivity of D1 receptors, which can be significant for the development of tardive dyskinesia. Primary and secondary changes in the function of dopamine receptors lead to partially opposite, pathological changes in the activity of neuronal pathways connecting the basal ganglia. Besides functional changes, neuroleptic-induced lesions of the striatal neurons and genetic predispositions can also play a role in tardive dyskinesia.     

The assessment of development of binding antibodies to interferon beta during interferon beta 1a treatment of multiple sclerosis

The importance of binding antibodies (BAb) that develop during the treatment of multiple sclerosis with interferon beta has not been fully explained yet. However, they are generally regarded as one of factors that may diminish treatment efficacy. The aim of the study was to evaluate firstly, BAb occurrence in interferon beta 1-a (IFN beta 1-a)-treated MS patients and secondly, BAb impact on clinical efficacy of this medication. In the 36-month study participants were 21 patients with relapsing-remitting multiple sclerosis, RR-MS, (14 women, 7 men, aged 29.6 +/- 8.5). All the patients were receiving intramuscular IFN beta-1a (Avonex) for 24 months, in the dose of 30 micrograms per week. Clinical parameters and serum BAb levels (the EIA method) were estimated every 3 months. Two control groups, examined only once, included 20 RR-MS patients without IFN-beta therapy and 20 healthy volunteers. While before treatment a high BAb level was found in 2 patients (9.5%), at 6 months of treatment it was found in 8 patients (38.1%). A similar number of patients with high BAb levels was seen throughout the study during the IFN-beta treatment. On therapy completion serum BAb levels decreased very rapidly. After 2 years of treatment, disability as measured by the EDSS scale was more pronounced in patients with serum BAb, but the differences were statistically not significant. No statistically significant relationship was found either between elevated BAb levels and the number of relapses during the IFN-beta treatment (including relapses that required steroid therapy).     

Relationship between oxidative stress and extrinsic coagulation pathway in haemodialyzed patients

Enhanced oxidative stress (SOX), endothelial dysfunction and haemostatic abnormalities are common in end-stage renal failure patients undergoing maintenance haemodialysis (HD). We studied associations among circulating immunoreactive total lipid peroxides as a marker of short-time SOX, autoantibodies against oxidized LDL as a surrogate of prolonged SOX, copper/zinc superoxide dismutase (Cu/Zn SOD) as a major antioxidant enzyme, tissue factor (TF) as a principal initiator of extrinsic coagulation pathway counteracted by its inhibitor (TFPI), and prothrombin fragment 1+2 (F 1+2) as a surrogate of activated haemostasis.

Pre-dialysis blood levels of all the markers studied were higher in 24 clinically stable HD patients compared to 11 healthy controls. Spearman's correlations among the three SOX markers were positive but nonsignificant in both HD patients and controls. In HD subjects, increased Cu/Zn SOD levels directly correlated with those of TF (rho=0.551, p=0.005) and TFPI (rho=0.501, p=0.001); the coagulation markers were also positively associated with each other (rho=0.663, p=0.0004). In healthy subjects, the relations between Cu/Zn SOD, TF and TFPI levels were inverse but not significant, and the direct association between TF and TFPI was nonsignificant either.

In conclusion, increased plasma levels of Cu/Zn SOD, the antioxidant enzyme with emerging endothelial cell-protective and antithrombotic properties, may be a novel part of the system counteracting activated extrinsic coagulation system in maintenance HD patients.     

Interaction between cerebellar neurons

Cross-correlation methods were applied to examine interaction between the cerebellar cortex and the interaction between Purkinje neurons and neurons of the deep cerebellar nuclei. Patterns of interaction between different cerebellar cortical neurons are described.     

An examination of cancer risk beliefs among adults from Toronto's Somali, Chinese, Russian and Spanish-speaking communities

BACKGROUND: Canada's growing ethnocultural diversity challenges health professionals to develop culturally sensitive cancer prevention strategies. Little is known about the ethnocultural specificity of cancer risk beliefs. This qualitative pilot study examined cancer risk beliefs, focusing on diet, among adults from Toronto's Somali, Chinese, Russian, and Spanish-speaking communities. METHOD: Group interviews (n = 4) were conducted with convenience samples of adults (total n = 45) from four ethnocultural communities (total 45 participants). RESULTS: The constant comparison method of data analysis identified three common themes: knowledge of cancer risk factors, concern about the food supply, and the roles of spiritual and emotional well-being. Two areas of contrasting belief concerning specific mediators of cancer risk were identified. INTERPRETATION: Findings support the investigation of cultural-specific health promotion strategies emphasizing both the maintenance of traditional cancer protective eating practices and the adoption of additional healthy eating practices among new Canadians. More research is needed to enhance our understanding of ethnoculturally specific cancer risk beliefs and practices to ensure the cultural relevance of programming.     

Evaluation of blood flow velocity and cerebrovascular reactivity in patient with posterior circulation stroke

The aim of our study was to determine the type of blood flow disturbances and cerebrovascular reactivity of major anterior and posterior circulation cerebral vessels in patients with posterior stroke (POCI). The examined group consisted of 17 patients, mean age 57 +/- 12 yr, with posterior circulation infarct. Neurological examination, brain CT and Doppler examination including evaluation of BFV and CVR of MCA, PCA and VA was performed in each patient. Doppler examination was done using Pioneer TC 2020 and capnograph Tidal Wave sp Novametrix. RESULTS: BFV of ICA's, MCA's, ACA's and PCA's were diminished while BFV of VA's were significantly diminished in the examined patients compared to healthy controls. CVR of MCA in posterior circulation stroke patients was significantly lower compared to controls. CVR of PCA and VA was significantly lower compared to CVR of MCA in patients with posterior circulation stroke. CONCLUSION: Impairment of CVR, especially in posterior circulation, plays an important role in posterior circulation stroke pathogenesis.