Long-term effects of galantamine treatment on brain functional activities as measured by PET in Alzheimer's disease patients

The effects of galantamine (16 to 24 mg/day) treatment on brain functional activities (blood flow and glucose metabolism) were examined in 18 patients with mild Alzheimer's disease (AD) in relation to brain acetylcholinesterase (AChE) activity and nicotinic receptors and cognitive function. The study consisted of an initial double-blind phase of three months (short-term) followed by an open-label phase until twelve months after the beginning of the study (long-term). The AD patients underwent positron emission tomography (PET) studies with the tracers [15O]-H2O for measurement of regional cerebral blood flow (rCBF) at baseline, 3 weeks, 3 and 12 months treatment, and [18F]-fluoro-deoxyglucose (FDG) for measurement of regional cerebral metabolic rate for glucose (rCMRglc) at baseline and 12 months. A battery of neuropsychological assessments was performed on each patient in order to follow changes in cognition during the treatment period. Throughout the study, different cortical areas showed significant increases in rCBF after galantamine treatment. rCBF positively correlated with AChE activity, nicotinic receptors and cognition. In addition to these positive changes, an increase in rCMRglc in the frontal brain region and stabilization in other cortical areas was observed after 12 months galantamine treatment. This stabilization in rCMRglc was also correlated with a stabilization of cognition. Our results ultimately suggest that treatment with galantamine has a long-term positive effect on brain perfusion and rCMRglc and stabilizes cognition.     

Mandibular stability and condylar changes following orthognathic surgery in mandibular hypoplasia patients associated with preoperative condylar resorption

Clinical Oral Investigations - To evaluate postoperative mandibular stability and condylar changes in patients with mandibular hypoplasia and preoperative condylar resorption (CR) undergoing...     

Tacrine restores cholinergic nicotinic receptors and glucose metabolism in alzheimer patients as visualized by positron emission tomography

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [¹⁸F]-fluoro-deoxy-glucose (¹⁸F-FDG) (tracer for glucose metabolism); ¹¹C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-¹¹C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of ¹¹C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)¹¹C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)¹¹C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.     

金属硫蛋白对大鼠肝脏线粒体氧自由基损伤的保护作用

目的：研究金属硫蛋白（ＭＴ）对氧自由基损伤线粒体的保护作用以探讨其细胞保护机制。方法：采用ＦｅＳＯ４／抗坏血酸自由基发生系统直接损伤线粒体，测定Ｃａ（２＋）－Ｍｇ（２＋）－ＡＴＰａｓｅ活性和Ｃａ（２＋）摄入的变化。结果：ＭＴ能够直接拮抗氧自由基对线粒体Ｃａ（２＋）－Ｍｇ（２＋）－ＡＴＰａｓｅ活性和Ｃａ（２＋）摄入的抑制作用（Ｐ＜０．０１）。结论：ＭＴ对氧自由基损伤线粒体有明显保护作用，ＭＴ对细胞器线粒体的保护作用可能是细胞保护机制之一。