Annals of the New York Academy of Sciences
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Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time-dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time-dependent inflammatory reaction with effects opposite those of cortisol. ⋯ Accordingly, the intensity of the arthritic pain varies consistently as a function of the hour of the day: pain is greater after waking up in the morning than in the afternoon or evening. The reduced cortisol and adrenal androgen secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with glucocoticoids, should be clearly considered as a "relative adrenal insufficiency" in the presence of a sustained inflammatory process, and allows Th1 type cytokines to be produced in higher amounts during the late night. In conclusion, the right timing (early morning) for the glucocorticoid therapy in arthritis is fundamental and well justified by the circadian rhythms of the inflammatory mechanisms.
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Ann. N. Y. Acad. Sci. · Dec 2005
ReviewAmyotrophic lateral sclerosis and primary lateral sclerosis: The role of diffusion tensor imaging and other advanced MR-based techniques as objective upper motor neuron markers.
Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, is a motor neuron disease characterized by progressive degeneration of upper motor neuron (UMN) and lower motor neuron (LMN), while primary lateral sclerosis (PLS) is defined by pure UMN involvement. A reliable objective marker of UMN involvement is critical for the early diagnosis and monitoring of disease progression in patients with ALS and PLS. Diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and magnetic resonance spectroscopy (MRS), which provide insight into the pathophysiological process of ALS and PLS, show great promise in this regard. Further investigation is needed to determine and to compare the utility of various neuroimaging markers.
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Coxiella burnetii is an obligate intracellular bacterium that causes a worldwide zoonosis, Q fever, and can be misused as a biological warfare agent. Infection in animals (coxiellosis) is mostly persistent. Infection in humans is often asymptomatic, but it can manifest as an acute disease (usually a self-limited flu-like illness, pneumonia, or hepatitis) or as a chronic form (mainly endocarditis, but also hepatitis and chronic fatigue syndrome). ⋯ Its intracellular large cell variant, adapted to survive under harsh conditions of phagolysosomes, enables long-term survival and persistence of C. burnetii, namely in monocytes/macrophages. Host factors such as underlying disease and cell-mediated immunity play a decisive role in the clinical expression of C. burnetii infection. Complete genome analysis of C. burnetii will certainly contribute to better understanding of the pathogenesis of C. burnetii infection and will improve Q fever diagnosis and immunoprophylaxis.
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Ann. N. Y. Acad. Sci. · Aug 2005
ReviewPotentially neuroprotective and therapeutic properties of nitrous oxide and xenon.
Despite the beneficial effects of prototypical glutamatergic receptor antagonists in animal models, the pharmacological attempts by the use of such agents have met with very limited clinical success because these compounds produce adverse side effects and possess an intrinsic neurotoxicity at neuroprotective and therapeutic concentrations. Interestingly, nitrous oxide and xenon, which are anesthetic gases with a remarkably safe clinical profile, have been shown to be effective inhibitors of the NMDA receptor. We briefly review accumulating evidence that nitrous oxide and xenon at subanesthetic concentrations may have potentially neuroprotective and therapeutic properties, with a particular focus on their beneficial effects on ischemia-induced neuronal death and amphetamine-induced sensitization. ⋯ However, at a higher concentration of 75-vol%, xenon shows potentially neurotoxic properties and adverse side effects. Because both agents are rapidly eliminated from the body, it is plausible that their administration at appropriate subanesthetic neuroprotective and therapeutic concentrations may not be associated, in contrast with prototypical NMDA receptor antagonists, with adverse side effects and potentially neurotoxicity. Finally, the possible therapeutic implications in humans are discussed.
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Human umbilical cord blood (HUCB) is now considered a valuable source for stem cell-based therapies. HUCB cells are enriched for stem cells that have the potential to initiate and maintain tissue repair. This potential is especially attractive in neural diseases for which no current cure is available. ⋯ Alternatively, various cell types within the graft may promote neural repair by delivering neural protection and secretion of neurotrophic factors. In this review, we evaluate the preclinical studies in which HUCB was applied for treatment of neurodegenerative diseases and for traumatic and ischemic brain damage. We discuss how transplantation of HUCB cells affects these disorders and we present recent clinical studies with promising outcome.