Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Apr 2010
ReviewProthymosin alpha as robustness molecule against ischemic stress to brain and retina.
Following stroke or traumatic damage, neuronal death via both necrosis and apoptosis causes loss of functions, including memory, sensory perception, and motor skills. As necrosis has the nature to expand, while apoptosis stops the cell death cascade in the brain, necrosis is considered to be a promising target for rapid treatment for stroke. We identified the nuclear protein, prothymosin alpha (ProTalpha) from the conditioned medium of serum-free culture of cortical neurons as a key protein-inhibiting necrosis. ⋯ In the ischemic brain or retina, ProTalpha showed a potent inhibition of both necrosis and apoptosis. By use of anti-brain-derived neurotrophic factor or anti-erythropoietin IgG, we found that ProTalpha inhibits necrosis, but causes apoptosis, which is in turn inhibited by ProTalpha-induced neurotrophins under the condition of ischemia. From the experiment using anti-ProTalpha IgG or antisense oligonucleotide for ProTalpha, it was revealed that ProTalpha has a pathophysiological role in protecting neurons in stroke.
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Ann. N. Y. Acad. Sci. · Apr 2010
ReviewPsoriatic arthritis: clinical improvement and correlation with hormone axes in etanercept-treated patients.
In a chronic inflammatory disease, such as rheumatoid arthritis (RA), the hypothalamic-pituitary-adrenal axis is altered in three ways: (1) the inflammation-related spontaneous and stimulated secretion of cortisol is inadequate; (2) the inflammation-related secretion of adrenocorticotropic hormone (ACTH) is low; and (3) the levels of adrenal androgens decrease. In patients with RA, long-term therapy with anti-TNF therapy sensitizes the pituitary gland and improves adrenal androgen secretion. We have recently found that the mean serum levels of ACTH, cortisol, 17-hydroxyprogesterone (17OHP), and androstenedione (ASD) in 11 prednisolone-naïve patients with psoriatic arthritis did not markedly change during 12 weeks of etanercept treatment, nor did the serum cortisol/ACTH ratio. However, the greater increase in serum cortisol in comparison with serum 17OHP or ASD was related to clinical improvement, which indicates that the improvement was more related to the higher cortisol levels.
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Ann. N. Y. Acad. Sci. · Mar 2010
Historical ArticleThe early days at the National Institutes of Health.
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Dolichoectasia (dilatative arteriopathy) describes marked elongation, widening, and tortuosity of arteries. The intracranial vertebral and basilar arteries are preferentially involved. ⋯ Flow in dilated arteries can become bidirectional, resulting in reduced antegrade flow and thrombus formation. Elongation and angulation of arteries can stretch and distort the orifices of arterial branches, leading to decreased blood flow, especially in penetrating branches.
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Ann. N. Y. Acad. Sci. · Jan 2010
ReviewFamilial pain syndromes from mutations of the NaV1.7 sodium channel.
The literature currently suggests that voltage-gated sodium channels play a major role in the pathogenesis of neuropathic pain. Alterations in the expression and targeting of specific sodium channels within injured dorsal root ganglia neurons appear to predispose the neurons to abnormal firing properties, allowing for the development of neuropathic pain. Mutations of one particular sodium channel (Na(v)1.7) have been shown to cause inherited neuropathic pain in humans, specifically in erythromelalgia and paroxysmal extreme pain disorder. ⋯ Conversely, a loss-of-function of the Na(v)1.7 channel can produce channelopathy-associated insensitivity to pain. Therefore, the Na(v)1.7 channel may provide a unique target for the pharmacotherapy of pain in humans. In this review article we summarize current knowledge regarding several different disease manifestations arising from changes within the Na(v)1.7 channel.