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.
In a previous randomised controlled trial we showed that acupuncture with a combination of manual- and electrical stimulation (EA) did not affect the level of pain, as compared with acupuncture with manual stimulation (MA) and standard care (SC), but reduced the need for other forms of pain relief, including epidural analgesia. To dismiss an under-treatment of pain in the trial, we did a long-term follow up on the recollection of labour pain and the birth experience comparing acupuncture with manual stimulation, acupuncture with combined electrical and manual stimulation with standard care. Our hypothesis was that despite the lower frequency of use of other pain relief, women who had received EA would make similar retrospective assessments of labour pain and the birth experience 2 months after birth as women who received standard care (SC) or acupuncture with manual stimulation (MA).
Secondary analyses of data collected for a randomised controlled trial conducted at two delivery wards in Sweden. A total of 303 nulliparous women with normal pregnancies were randomised to: 40 min of MA or EA, or SC without acupuncture. Questionnaires were administered the day after partus and 2 months later.
Two months postpartum, the mean recalled pain on the visual analogue scale (SC: 70.1, MA: 69.3 and EA: 68.7) did not differ between the groups (SC vs MA: adjusted mean difference 0.8, 95% confidence interval [CI] -6.3 to 7.9 and SC vs EA: mean difference 1.3 CI 95% -5.5 to 8.1). Positive birth experience (SC: 54.3%, MA: 64.6% and EA: 61.0%) did not differ between the groups (SC vs MA: adjusted Odds Ratio [OR] 1.8, CI 95% 0.9 to 3.7 and SC vs EA: OR 1.4 CI 95% 0.7 to 2.6).
Despite the lower use of other pain relief, women who received acupuncture with the combination of manual and electrical stimulation during labour made the same retrospective assessments of labour pain and birth experience 2 months postpartum as those who received acupuncture with manual stimulation or standard care.
Cites: BJOG. 2002 Jun;109(6):637-4412118641
Cites: Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S160-7212011880
Polycystic ovary syndrome (PCOS) affects 5-10 percent of all fertile women and is associated with anovulation/oligoovulation, hyperandrogenism, and polycystic ovaries. Pharmacological treatment is often effective but associated with unwanted side effects. Acupuncture treatments have been shown to improve menstrual bleeding patterns and ovulation as well as hyperandrogenism, without side effects. The purpose of the present study was to describe the experience of acupuncture for women diagnosed with PCOS.
Eight women with PCOS living in western Sweden, were interviewed following repeated acupuncture treatments. Data was analyzed using systematic text condensation as described by Malterud.
The experience of acupuncture for women diagnosed with PCOS can be described in five categories; the experience of hope, getting results, feelings of responsibility, skepticism and proof of effect, and feeling normal.
Since acupuncture is a promising treatment for the symptoms of the common syndrome PCOS, the present study adds to the knowledge base by providing the important experiences of patients receiving the treatment. Acupuncture provides a possibility for patients to gain hope as the treatment shows results. The results show that acupuncture empowers the patients to take responsibility for their future well-being, although they may have been initially skeptical to the treatment. Because the syndrome had affected them for some time, even small changes offered a chance for them to feel that their bodies were capable of normal function.
Skeletal muscle performance declines with advancing age, and the underlying mechanism is not completely understood. A large body of convincing evidence has demonstrated a crucial role for interstitial K+ concentration ([K+]o) in modulating contractile function of skeletal muscle. The present study tested the hypothesis that during muscle contraction there is a greater accumulation of [K+]o in aged compared with adult skeletal muscle. Twitch muscle contraction was induced by electrical stimulation of the sciatic nerves of 8- and 32-mo-old Fischer 344 x Brown Norway rats. Levels of [K+]o were measured continuously by a microdialysis technique with the probes inserted into the gastrocnemius muscle. Stimulation at 1, 3, and 5 Hz elevated muscle [K+]o by 52, 64, and 88% in adult rats, and by 78, 98, and 104% in aged rats, respectively, and the increase was significantly higher in aged than in adult rats. Recovery for [K+]o, as measured by the time for [K+]o to recover by 20 and 50% from peak response after stimulation, was slower in aged rats. Ouabain (5 mM), a specific inhibitor of the Na+-K+ pump, was added in the perfusate to inhibit the reuptake of K+ into the cells to assess the role of the pump in the overall K+ balance. Ouabain elevated muscle [K+]o at rest, and the effect was significantly attenuated in aged animals. The present data demonstrated an augmented [K+]o in aged skeletal muscle compared with adult skeletal muscle, and the data suggested that an alteration in the function of the Na+-K+ pump may contribute, in part, to the deficiency in K+ balance in skeletal muscle of aged rats.
Vagus nerve stimulation (VNS) therapy is an established method for treating patients with refractory seizures. Although the initial cost of the device is about 10,000 US dollars, the battery life of the model 100 implanted in the patients in this analysis can exceed 5 years at standard settings. It is important to understand what type of cost-benefit can be expected after implantation. Our aim was to assess unplanned hospital costs 18 months before and 18 months after VNS implantation in 43 patients. The VNS therapy system was implanted according to standard procedures and stimulation of 0.75 to 2.0 mA was delivered either as 30 seconds on and 5 minutes off or 7 seconds on and 14 seconds off. Seizure frequency was calculated before and after 18 months of treatment. During this time no changes were made with other therapies for epilepsy. Hospitalization for emergency room (ER) visits, ward stays, and intensive care days were calculated according to the costs at Sahlgrenska University Hospital in Sweden. Therapy response was defined as 25% or greater reduction in seizure frequency. For all patients, intensive care unit (ICU) costs were reduced from 46,875 to 0 US dollars, ER visits from 13,000 to 9,000 US dollars, and ward stays from 151,125 to 21,375 US dollars. Total hospital costs for the 43 patients studied before VNS therapy were 211,000 US dollars and after 18 months of treatment were reduced to 30,375 US dollars, an average annual cost savings of approximately 3,000 US dollars per patient. The cost savings applied to all patients, irrespective of whether they responded to VNS therapy. VNS therapy resulted in annual reductions of approximately 3000 US dollars in unplanned hospital costs per study patient. Such direct savings sustained over the battery life of the VNS therapy system can equal or exceed the purchase price of the device.
In a group of 100 patients admitted to the Department of Psychiatry in Umeå between January 1973 and July 1974 with depressive syndromes, pain measures - PM - and visual averaged evoked responses - V.AER - have been investigated and the patients have been rated by the doctor by means of the Cronholm-Ottosson depression rating scale. According to the results of V. AER patients have been grouped as augmenters or reducers, depending upon the tendency to augment or to reduce the intensity of incoming signals with increasing stimulus intensity. V. AER are found to vary with age but not with sex. Differences are found between patients with and those without a psychotic dimension of their depressive syndromes. Patients with depressive syndromes of psychotic dimension tend more often to be reducers. When patients are divided according to diagnostic groups no differences are found. PM are found to vary with sex and detection threshold - DT - are found to vary with age while pain threshold - PT - tolerance level - TL - and pain endurance - PE - do not vary with age. Patients with depressive syndromes of a psychotic dimension are found to have higher PM while there is no consistent picture when patients are divided according to diagnostic groups. Possible explanations for contradictory results found by other authors are discussed.
Serum levels of cholesterol, HDL-cholesterol, triglycerides, lipoprotein Lp(a), and the fibrinolysis factors tPA (tissue plasminogen activator) and PAI-1 activity (plasminogen activator inhibitor) were compared with sensory thresholds for vibration, electrical current perception, and pain in a population-based study comprising 239 patients with diabetes mellitus Type 1, aged 15-50 years. Univariate regression analyses (n = 180) showed significant correlations between elevated sensory thresholds and age, duration of diabetes, serum cholesterol and triglycerides, and HbA1c. In multivariate regression analysis, age, duration of diabetes, height, and serum triglycerides showed significant independent associations with five or six of the six measured sensory threshold variables. In addition there was a significant association between increased thresholds for vibration and Lp(a) levels. Thus, increased sensory thresholds for vibration, current perception, and pain in patients with Type 1 diabetes are associated with increased serum triglyceride levels, and Lp(a) levels are associated with increased threshold for vibration. Fibrinolytic activity is unrelated to these measures of nerve function in Type 1 diabetic patients.