Postsynaptic nigrostriatal dopamine receptors and their role in movement regulation

The article presents the hypothesis that nigrostriatal dopamine may regulate movement by modulation of tone and contraction in skeletal muscles through a concentration-dependent influence on the postsynaptic D1 and D2 receptors on the follow manner: nigrostriatal axons innervate both receptor types within the striatal locus somatotopically responsible for motor control in agonist/antagonist muscle pair around a given joint. D1 receptors interact with lower and D2 receptors with higher dopamine concentrations. Synaptic dopamine concentration increases immediately before movement starts. We hypothesize that increasing dopamine concentrations stimulate first the D1 receptors and reduce muscle tone in the antagonist muscle and than stimulate D2 receptors and induce contraction in the agonist muscle. The preceded muscle tone reduction in the antagonist muscle eases the efficient contraction of the agonist. Our hypothesis is applicable for an explanation of physiological movement regulation, different forms of movement pathology and therapeutic drug effects. Further, this hypothesis provides a theoretical basis for experimental investigation of dopaminergic motor control and development of new strategies for treatment of movement disorders

Biochemistry and physiology of gastrointestinal somatostatin

Somatostatin, a tetradecapeptide initially isolated from the ovine hypothalamus, is widely distributed throughout the gastrointestinal tract where it may act as a hormone, local chemical messenger, or neurotransmitter to elicit many physiological actions. Release of somatostatin from D cells in the gut is regulated by mechanisms that are both dependent on and independent of cAMP. In most cases somatostatin acts to inhibit the function of its target cells. It performs this action in part via pertussis-toxin-sensitive inhibitory guanine nucleotide-binding proteins that regulate adenylate cyclase activity. Other mechanisms may involve sites of action distal to intracellular second messenger systems .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44411/1/10620_2005_Article_BF01536041.pd

Personal non-commercial use only

ABSTRACT. Objective. The aim of our study was to evaluate the safety and the efficacy of tocilizumab (TCZ) for refractory Takayasu arteritis (TA). Methods. We retrospectively assessed the outcome of blocking interleukin (IL)-6 with TCZ in 7 consecutive patients with refractory TA using a combination of clinical and imaging assessment. Results. During a median followup visit at 14 months, 4 patients taking TCZ [including 2 nonresponders to tumor necrosis factor (TNF) inhibitors] achieved clinical response, suggesting a nonredundant role for IL-6 in TA. Inflammatory markers normalized in all patients treated with TCZ. However, vascular progression occurred in 4 patients, suggesting the involvement of other inflammatory pathways and confirming the limitations of erythrocyte sedimentation rate and C-reactive protein for disease activity assessment while taking TCZ. Three patients experienced adverse events and 2 suspended TCZ. Conclusion. TCZ may be effective in a subset of patients with refractory TA, even in cases of unresponsiveness to TNF inhibitors. Inflammatory markers are not valid markers of TA activity on TCZ. Further studies are needed to confirm these preliminary observations. (J Rheumatol Firs

Personal non-commercial use only

ABSTRACT. Objective. The aim of our study was to evaluate the safety and the efficacy of tocilizumab (TCZ) for refractory Takayasu arteritis (TA). Methods. We retrospectively assessed the outcome of blocking interleukin (IL)-6 with TCZ in 7 consecutive patients with refractory TA using a combination of clinical and imaging assessment. Results. During a median followup visit at 14 months, 4 patients taking TCZ [including 2 nonresponders to tumor necrosis factor (TNF) inhibitors] achieved clinical response, suggesting a nonredundant role for IL-6 in TA. Inflammatory markers normalized in all patients treated with TCZ. However, vascular progression occurred in 4 patients, suggesting the involvement of other inflammatory pathways and confirming the limitations of erythrocyte sedimentation rate and C-reactive protein for disease activity assessment while taking TCZ. Three patients experienced adverse events and 2 suspended TCZ. Conclusion. TCZ may be effective in a subset of patients with refractory TA, even in cases of unresponsiveness to TNF inhibitors. Inflammatory markers are not valid markers of TA activity on TCZ. Further studies are needed to confirm these preliminary observations. (First Release Nov

Quantification of the Trömner signs: a sensitive marker for cervical spondylotic myelopathy

The Trömner sign is commonly used as a clinical neurological examination for upper motor neuron lesions above the fifth or sixth cervical segments of the spinal cord. This study aims to assess and quantify the Trömner signs utilizing electrophysiological test, and correlate to the severity of cord compression in cervical spondylotic myelopathy (CSM). We enlisted 46 CSM patients, and 30 healthy persons as controls. Manual Trömner and Hoffmann signs were tested in all subjects. By using a self-designed instrument, we performed electrophysiological assessments for the Trömner signs in patients and controls. Parameters of conduction latencies and amplitude of muscle action potentials were measured and compared with the cord compression ratios in CSM patients. The results showed a greater diagnostic sensitivity for the quantified Trömner signs in comparison to those of manual Trömner signs and Hoffmann signs. We found a positive correlation between the amplitude of muscle action potentials obtained in the Trömner signs and the cord compression ratios in the patients with CSM. In conclusion, the Trömner signs can be measured by electrophysiological assessments. We demonstrate a new quantification method for an established neurological sign. Not only is Trömner sign a highly sensitive test in clinical neurological examination, the electrophysiological assessment of this sign can also serve as an objective marker for evaluation of the severity of cervical cord compression