Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study

In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a ^99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed.     

番茄红素与成骨细胞、破骨细胞及骨质疏松症

学术背景:骨质疏松症是较易发生的疾病,研究骨质疏松的发病机制寻找治疗骨质疏松的药物是预防老年性骨质疏松症的理想选择。目的:综述近几年来国内外关于氧化应激及番茄红素在骨质疏松发病中的作用的相关研究,为开发预防和治疗骨质骨质疏松的药物提供理论依据。检索策略:应用计算机检索Medline和Science Direct Online数据库1989-01/2007-04期间的相关文章,检索词为"oxidative stress,osteoclast,osteoblast,lycopene,osteoporosis",限定文章语言种类为English。同时计算机检索中国期刊全文数据库2000-01/2007-04期间的相关文章,检索词为"氧化应激,骨质疏松,成骨细胞,破骨细胞,番茄红素",限定文章语言种类为中文。对资料进行初审,选择有关人体内氧化应激形成机制、氧化应激与成骨细胞、氧化应激与破骨细胞、氧化应激与抗氧化剂、番茄红素与成骨细胞及破骨细胞和番茄红素与骨质疏松症关系的最新进展文献,共收集到121篇,排除综述类及重复研究。文献评价:符合纳入标准的31篇文献中,5篇涉及骨质疏松症的概述,20篇涉及氧化应激和抗氧化剂在骨质疏松症发病中作用的相关研究,6篇涉及番茄红素与氧化应激、成骨细胞、破骨细胞及绝经后骨质疏松关系的相关研究。资料综合:氧化应激是骨质疏松发病的一个危险因素。氧化应激不但作用于成骨细胞还作用于破骨细胞。国内外学者对于番茄红素的抗氧化性能研究取得了很大进展,已通过细胞培养观察到其对成骨细胞和破骨细胞均有作用,通过临床研究发现,番茄红素通过其抗氧化功能而影响成骨细胞和破骨细胞的功能,从而能够对骨质疏松症发生发展的病理过程进行有效干预,最终阻止和减缓骨质疏松症的发生。结论:番茄红素具有的抗氧化功能使其在骨质疏松的预防及治疗方面起着重要的作用。     

Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy

Pyridoxine (vitamin B6) intoxicated rodents develop a peripheral neuropathy characterized by sensory nerve conduction deficits associated with disturbances of nerve fiber geometry and axonal atrophy. To investigate the possibility that glucagon-like peptide-1 (7-36)-amide (GLP-1) receptor agonism may influence axonal structure and function through neuroprotection neurotrophic support, effects of GLP-1 and its long acting analog, Exendin-4 (Ex4) treatment on pyridoxine-induced peripheral neuropathy were examined in rats using behavioral and morphometric techniques. GLP-1 is an endogenous insulinotropic peptide secreted from the gut in response to the presence of food. GLP-1 receptors (GLP-1R) are coupled to the cAMP second messenger pathway, and are expressed widely throughout neural tissues of humans and rodents. Recent studies have established that GLP-1 and Ex4, have multiple synergistic effects on glucose-dependent insulin secretion pathways of pancreatic beta-cells and on neural plasticity. Data reported here suggest that clinically relevant doses of GLP-1 and Ex4 may offer some protection against the sensory peripheral neuropathy induced by pyridoxine. Our findings suggest a potential role for these peptides in the treatment of neuropathies, including that associated with type II diabetes mellitus.     

Ionic permeabilities of the frog perineurium

Ionic permeation was investigated across the perineurium of the frog sciatic nerve, under normal conditions and following treatment by hypertonic Ringer, ouabain or amiloride. A cylindrical segment of perineurium removed from the nerve and mounted in vitro on two cannulae was continuously perfused. Permeation rates of²²Na and⁴²K across the perineurium were the same in either direction and were unaffected by the drugs. The mean²²Na permeability coefficient at the perineurium equaled1.68 ± 0.08 (S.E.M.) × 10⁻⁶cm/sec. Simultaneous measurement of transperineurial fluxes of²²Na,⁴²K and³⁶Cl indicated that the K/Na permeability ratio exceeded the ratio of limiting conductances of these ions in free solution, but that the Cl/K permeability ratio did not differ from the respective limiting conductance ratio. Immersion of the perineurial cylinder in Ringer, made hypertonic by addition of NaCl, increased the absolute permeability coefficients of the three ionic tracers but did not affect their permeability ratios. The flux ratio of²²Na/[¹⁴C] sucrose, however, was decreased by hypertonic treatment.It is concluded that there is no evidence of active Na or K transport across the perineurium and that the paracellular path in the perineurium exhibits size-dependent permselectivity properties. In addition, the low rates of transperineurial permeation of ions and water-soluble non-electrolytes (e.g. sucrose) are comparable to those in epithelia with tight junctions. These permeability coefficients provide quantitative estimates of the diffusion barrier properties of the perineurium.