Amyloid beta (Abeta) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. The mechanisms underlying such toxicity on synaptic functions are complex and not fully understood. Here, we provide the first evidence that these mechanisms involve protein phosphatase 1 (PP1). Using a novel transgenic mouse model expressing human APP with the Swedish and Arctic mutations that render Abeta more prone to form oligomers (arcAbeta mice), we show that the LTP impairment induced by Abeta oligomers can be fully reversed by PP1 inhibition in vitro. We further demonstrate that the genetic inhibition of endogenous PP1 in vivo confers resistance to Abeta oligomer-mediated toxicity and preserves LTP. Overall, these results reveal that PP1 is a key player in the mechanisms of AD pathology.
Hepatic encephalopathy (HE) is a severe and frequent complication of liver cirrhosis characterized by abnormal cerebral function. Little is known about the underlying neural mechanisms in HE and human data are sparse. Electrophysiological methods such as evoked brain potentials after somatic stimuli can be combined with inverse modeling of the underlying brain activity. Thereby, information on neuronal dynamics and brain activity can be studied in vivo. The aim of this study was to investigate the sensory brain processing in patients with HE.
Twelve patients with minimal or overt HE and 26 healthy volunteers were included in the study. Cerebral sensory processing was investigated as (i) an auditory reaction time task; (ii) visual and somatosensory evoked brain potentials, and (iii) reconstruction of the underlying brain activity.
Somatosensory evoked potentials were reproducible (all P>0.05), whereas flash evoked potentials were not reproducible (all P
OBJECTIVE: To determine whether the somatosensory pathways are involved or not in konzo. METHODS: In 1998, 21 konzo subjects (15 females and 6 males; mean age 21 years) underwent a SEP study with a two-channel-equipment (Medtronic Keypoint, Denmark) whereas in 2000, 15 subjects (7 females and 8 males; mean age 21 years) participated in a study with a 4-channel-equipment. RESULTS: Most subjects (19/21 in 1998 and 12/15 in 2000) showed normal median SEPs. The remainders had no median cortical responses. All 21 subjects in 1998 and 9 out of 15 in 2000 showed abnormalities of tibial SEPs mainly consisting of absence of cortical responses, prolonged cortical latencies, and central sensory delay to the lumbar spine. Most subjects showed normal absolute latencies both at peripheral and spinal levels. The SEP findings did not correlate with the severity, neither the duration of konzo, nor the experience or not of sensory symptoms at the onset of the disease. CONCLUSION: Our findings are not specific of konzo. However, they suggest involvement of intracranial somatosensory pathways and point to similarities with other motor neuron diseases.
This study analyzes accidental fatalities caused by electricity--at work and during leisure time--to evaluate risk factors, the role of alcohol, and to identify possible preventive strategies. In Sweden, data on fatalities by electrocution from 1975 through 2000 were collected from the National Cause-of-Death Register. Additional cases were found in the archives of The Swedish National Electrical Safety Board. Suicides and deaths by lightning were excluded. Two hundred and eighty-five deaths were found, including occupational (n=132), leisure time (n=151), and unknown (n=2). Most deaths were caused by aerial power lines, and the most common place for an electrical injury was a railway area or residential property. Postmortem blood from 20% (n=47) of the tested cases was found positive for alcohol, and these persons were killed mainly during leisure time. During the study period, the overall incidence of electricity-related fatalities has decreased, in spite of increased use of electricity. This indicates that safety improvements have been successful.
Quantitative magnetic resonance (QMR) has previously been shown to both overestimate and underestimate average fat mass (FM) in humans. Eight-electrode bioelectrical impedance analysis (BIA) has previously been found biased as well as successfully validated. We report cross-sectional accuracy of QMR and eight-electrode BIA evaluated with air displacement plethysmography (ADP) as reference method.
Fat mass and fat free mass (FFM) by QMR and eight-electrode BIA were evaluated against ADP as reference in 38 normal weight and 30 obese women. Total body water estimates by QMR and eight-electrode BIA were compared.
Long-term results of electroimpulse treatment for cardiac fibrillation in 1292 patients performed in cardiological clinics of Moscow and Kaunas have been compared. It is shown that more strict selection, longer preparation for the impulse exposure may secure a significant decrease in the number of the fibrillation recurrences both 1 and 6 months after recovery of the normal rhythm.