Subthalamic nucleus deep brain stimulation on motor-symptoms of Parkinson's disease: Focus on neurochemistry.

Deep brain stimulation (DBS) has become a standard therapy for Parkinson's disease (PD) and it is also currently under investigation for other neurological and psychiatric disorders. Although many scientific, clinical and ethical issues are still unresolved, DBS delivered into the subthalamic nucleus (STN) has improved the quality of life of several thousands of patients. The mechanisms underlying STN-DBS have been debated extensively in several reviews; less investigated are the biochemical consequences, which are still under scrutiny. Crucial and only partially understood, for instance, are the complex interplays occurring between STN-DBS and levodopa (LD)-centred therapy in the post-surgery follow-up. The main goal of this review is to address the question of whether an improved motor control, based on STN-DBS therapy, is also achieved through the additional modulation of other neurotransmitters, such as noradrenaline (NA) and serotonin (5-HT). A critical issue is to understand not only acute DBS-mediated effects, but also chronic changes, such as those involving cyclic nucleotides, capable of modulating circuit plasticity. The present article will discuss the neurochemical changes promoted by STN-DBS and will document the main results obtained in microdialysis studies. Furthermore, we will also examine the preliminary achievements of voltammetry applied to humans, and discuss new hypothetical investigational routes, taking into account novel players such as glia, or subcortical regions such as the pedunculopontine (PPN) area. Our further understanding of specific changes in brain chemistry promoted by STN-DBS would further disseminate its utilisation, at any stage of disease, avoiding an irreversible lesioning approach.

[Comparison and relevance of rheumatoid factors, antikeratin antibodies and anti-cyclic citrullinated peptides antibodies in rheumatoid arthritis]. / Comparaison et intérêt des dosages des facteurs rhumatoïdes, des anticorps anti-filaggrine (anti-kératine) et des anticorps anti-peptides cycliques citrullinés dans la polyarthrite rhumatoïde.

OBJECTIVES: to evaluate specificity and sensibility of the rheumatoid factors (RF), the anti-cyclic citrullinated peptide antibodies (CCP) and the anti-keratin antibodies (AKA) according to the rheumatoid arthritis (RA) diagnosis; pathology other than RA with at least one of these marker positive; the significance of the flocculent fluorescence of the antibodies AKA by indirect immunofluorescence (IIF). METHOD: two hundred forty height patients were studied: 121 RA, 89 inflammatory rheumatisms, 23 non inflammatory rheumatisms, and 15 non rheumatic affections. The RF was investigated by nephelometry, the anti-CCP by immunofluorometry and the AKA by IIF on rat oesophagus. RESULTS: specificity and sensibility were respectively in a retrospective manner: 68% and 83% for the RF, 95% and 76% for the anti- CCP, 83% and 40% for the AKA during RA with evolution of less than one year. The rates of agreements were: RF versus CCP: 81%, RF versus AKA: 57%, CCP versus AKA: 73%. Twelve patients with pathologies different from RA have positive anti-CCP or AKA. Thirty three of the patients with anti-CCP level superior to 130 U/mL have flocculent AKA versus only 5% when the anti-CCP are lower than 130 U/mL. CONCLUSION: the RF and the anti-CCP are complementary in RA. Autoimmune and neoplasic pathologies are sometimes responsible for the positivity of the anti-CCP and the AKA. The flocculent aspect of AKA in IIF may be associated with raised concentrations of anti-CCP.

c-Kit-positive mast cells in portal tracts cannot be used to distinguish acute cellular rejection from recurrent hepatitis C infection in liver allografts.

Cirrhosis secondary to chronic hepatitis C virus (HCV) is the most common indication for liver transplantation. Recurrence of HCV infection in the liver allograft occurs at a high rate. The differentiation of recurrent HCV infection from acute cellular rejection (ACR) represents a difficult challenge in transplantation pathology. The c-Kit receptor is a tyrosine kinase membrane protein encoded by the c-Kit proto-oncogene, which is expressed on mast cells and on hematopoietic stem and progenitor cells. Mast cells are important effector cells of a broad range of immune responses. Recently, c-Kit+ mast cells were shown to form part of the inflammatory infiltrate in acute liver allograft rejection. A strong relationship was found between c-Kit+ cell densities and increasingly severe rejection. The present study sought to determine whether the presence of c-Kit+ cells could be used to distinguish between ACR and recurrent HCV in liver allografts. Immunohistochemical staining for c-Kit was performed on 20 transplant biopsy specimens from 10 patients with mild to moderate ACR and 10 other patients with recurrent hepatitis C. The number of c-Kit+ cells per portal tract varied with the density of the overall inflammatory infiltrate. There was no significant difference between the number of c-Kit+ cells in the biopsy specimens that carried a diagnosis of ACR and those from patients who had been diagnosed as having recurrent HCV. It was concluded that immunohistochemical staining for the presence of c-Kit+ mast cells cannot be used to differentiate between ACR and recurrent HCV infection in liver allograft biopsy specimens.

Deep brain stimulation in Parkinson's disease patients: biochemical evidence.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients augments STN-driven excitation of the internal globus pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we report the biochemical effects of STN-DBS in two basal ganglia stations (putamen--PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA). In six advanced PD patients undergoing surgery, microdialysis samples were collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP was measured in the GPi and PUT as an index of glutamatergic transmission, whereas GABA was measured in the VA. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in the VA (-25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area: it activates the STN-GPi pathway while inhibiting the GPi-VA one. These findings support a thalamic dis-inhibition, as the main responsible for the clinical effect of STN-DBS. This, in turn, re-establishes a more physiological level of PUT activity.

Kinetics of IL-10 production after segmental antigen challenge of atopic asthmatic subjects.

BACKGROUND: IL-10 is an anti-inflammatory cytokine made by lymphocytes, monocytes-macrophages, and eosinophils, and it may have an important role in regulating the asthmatic inflammatory response. IL-10 levels have been reported to be reduced in asthmatic airways, potentially contributing to more intense inflammation. OBJECTIVE: We sought to determine whether IL-10 levels were deficient in patients with mild asthma compared with controls and to determine whether IL-10 levels were associated with the resolution of eosinophilic inflammation. METHODS: We quantified IL-10 levels in the bronchoalveolar lavage (BAL) fluid (ELISA), BAL cells (quantitative immunocytochemistry), purified alveolar macrophages-monocytes studied ex vivo (ELISA), before (day 1) and after (24 hours [day 2], 1 week [day 9], and 2 weeks [day 16]) segmental antigen challenge (SAC), and investigated the effect of glucocorticoid treatment on ex vivo macrophage-monocyte IL-10 production. RESULTS: IL-10 levels were significantly higher in the BAL fluid of mild asthmatic subjects who demonstrated a dual reaction (both early and late) after whole lung ragweed inhalation challenge compared with nonallergic, nonasthmatic control subjects before and 24 hours and 1 week after SAC. Macro-phages-monocytes obtained before and after SAC from asthmatic patients also secreted increased amounts of IL-10 ex vivo than those from controls. Dexamethasone did not significantly change spontaneous IL-10 secretion from macrophages-monocytes in vitro. Quantitative immunocytochemical analysis of BAL cells demonstrated increased IL-10 in macrophages 24 hours after SAC and a similar trend in eosinophils. CONCLUSION: IL-10 is not deficient in mild asthma. Furthermore, BAL IL-10 levels are significantly higher in asthmatic subjects with a dual response than in control subjects before and after SAC. The increase in IL-10 was coincident with the initial increase in BAL eosinophils, although BAL eosinophilia persisted after IL-10 levels had returned to baseline, suggesting that the increased IL-10 levels could not promptly terminate this localized eosinophilic response.