Study of cardiac autonomic function in drug-naive, newly diagnosed epilepsy patients

Background: Epilepsy is associated with ictal autonomic dysfunction which may extend into the inter-ictal period. Antiepileptic drugs have often been blamed for cardiac autonomic dysfunction in epilepsy patients. In this study we have investigated cardiac autonomic parameters in order to evaluate autonomic functions of drug-naive epilepsy patients. METHOD: Twenty drug-naive patients (15 males and 5 females) with epilepsy, and an equal number of age and gender matched controls, were evaluated for short-term resting heart rate variability and conventional cardiovascular autonomic measurements. Results: The mean age of patients was 29.30 +/- 9.80 yrs (17-55 yrs), mean age at seizure onset was 19.70 +/- 9.15 yrs (3-40 yrs) and mean length of time since last seizure was 5.60 +/- 7.00 days (1-30 days). While there was no difference in the resting heart rate or conventional autonomic test parameters, time domain heart rate variability measurements showed a decreased percentage of R-R intervals of less than 50 ms and root mean square of R-R intervals in patients, when compared to controls. Frequency domain parameters showed a decreased total power (patients: 1,796.58 +/- 1,052.45 ms2; controls: 2,934.23 +/- 1,767.06 ms2, p = 0.008). Parameters indicative of decreased vagal tone, i.e. decreased high frequency power and increased low to high frequency ratio (patients: 1.69 +/- 0.94; controls: 1.14 +/- 0.64, p = 0.045), were observed among patients compared to controls. CONCLUSION: Subtle but definite cardiac autonomic dysfunction, especially in vagal tone, was identified in drug-naive, new-onset epilepsy patients. Seizures can cause long-term and often progressive cardiac autonomic dysfunction which may be independent of concomitant antiepileptic drugs

Enhanced dehydroepiandrosterone levels are positively correlated with N3 sleep stage in long-term mindfulness meditation practitioners

Objectives: Meditation practices positively influence the neural, hormonal and autonomic systems. We have demonstrated that long-term practice of mindfulness meditation increases N3 and rapid eye movement (REM) sleep stages and bring efficient autonomic modulation during sleep. In the present study, the probable humoral correlation that could bring about these changes is evaluated. Material and Methods: Long-term Vipassana meditators (n=41) and controls (n=24) (males, 30-60 years of age) underwent a two-day consecutive whole night polysomnography recording. During the second day, with exposure to 100Lux brightness, blood was sampled from the antecubital vein between 8-9 PM and in subsequent early morning. Sleep stage was scored as per American Society of Sleep Medicine (ASSM) guidelines for the second-day recording. Sleep-related hormones were estimated - melatonin by radioimmunoassay; dehydroepiandrosterone (DHEA), cortisol, growth hormone (GH) and prolactin with enzyme-linked immunosorbent assay (ELISA); DHEA/cortisol ratio was calculated. Percentage of sleep stages and hormonal levels were compared between both groups using independent ‘t’ test and Pearson’s correlation was estimated between sleep stages and hormonal levels. Results: Meditators showed increased N3, REM sleep stages. Though evening cortisol was comparable between the two groups; early morning cortisol, diurnal DHEA and melatonin were significantly higher in meditators. Diurnal DHEA correlated significantly with the N3 sleep stage in meditators. Discussion: Higher diurnal DHEA despite variations in corresponding cortisol in meditators demonstrates that long-term Vipassana meditation practice modulates the hypothalamicpituitary-adrenal (HPA) axis and thereby influences sleep. Thus, the study provides evidence to explore the mechanism most likely involved with mindfulness meditation intervention in insomnia

A dual-time-window protocol to reduce acquisition time of dynamic tau PET imaging using [F-18]MK-6240

Background [F-18]MK-6240 is a PET tracer with sub-nanomolar affinity for neurofibrillary tangles. Therefore, tau quantification is possible with [F-18]MK-6240 PET/CT scans, and it can be used for assessment of Alzheimer's disease. However, long acquisition scans are required to provide fully quantitative estimates of pharmacokinetic parameters. Therefore, on the present study, dual-time-window (DTW) acquisitions was simulated to reduce PET/CT acquisition time, while taking into consideration perfusion changes and possible scanning protocol non-compliance. To that end, time activity curves (TACs) representing a 120-min acquisition (TAC(120)) were simulated using a two-tissue compartment model with metabolite corrected arterial input function from 90-min dynamic [F-18]MK-6240 PET scans of three healthy control subjects and five subjects with mild cognitive impairment or Alzheimer's disease. Therefore, TACs corresponding to different levels of specific binding were generated and then various perfusion changes were simulated. Next, DTW acquisitions were simulated consisting of an acquisition starting at tracer injection, a break and a second acquisition starting at 90 min post-injection. Finally, non-compliance with the PET/CT scanning protocol were simulated to assess its impact on quantification. All TACs were quantified using reference Logan's distribution volume ratio (DVR) and standardized uptake value ratio (SUVR90) using the cerebellar cortex as reference region. Results It was found that DVR from a DTW protocol with a 60-min break between two 30-min dynamic scans closely approximates the DVR from the uninterrupted TAC(120), with a regional bias smaller than 2.5%. Moreover, SUVR90 estimates were more susceptible (regional bias</p

Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro

Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM) derived from human embryonic kidney (HEK) cells in a kainic acid (KA) induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM) for 24 hrs (lesion group) whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM). We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF) and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host’s endogenous cell survival mechanisms

Physiotherapy versus placebo or no intervention in Parkinson's disease

Background: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. Physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety, and well-being, thereby enhancing quality of life.  Objectives: To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD.  Search methods: We identified relevant trials by conducting electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and by handsearching major journals, abstract books, conference proceedings, and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012.  Selection criteria: Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD.  Data collection and analysis: Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions.  Main results: We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI -1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician-rated disability using the Unified Parkinson’s Disease Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001; activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: -5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed.  Authors' conclusions: Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two- or six-minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited.  This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well-designed randomised controlled trials undertaken to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD

Evaluation of New Adenoviral Mediated In Vivo FES-Herl PET Tracer-Reporter Gene System for Gene Therapy Monitoring.

The Fifth Annual Meeting The Society for Molecular Imagin

In vivo Evaluation of Adenoviral Mediated FES-hERL PET Tracer-Reporter Gene System for Gene Therapy Monitoring

A key step in advancing gene therapy protocols is to establish an efficient monitoring system following target gene delivery. Earlier, we reported our new adenoviral mediated PET reporter gene system utilizing [18F]16alpha-fluoroestradiol (FES) as PET probe and human estrogen receptor alpha ligand binding domain (hERL) as PET reporter gene and evaluated basic cell culture and initial in vivo autoradiographic studies in mice [1]. Now, we report further cell model studies and in vivo PET imaging in rats.An in vitro FES binding study was performed on MRC-5 (human lung fibroblasts) and Cos-7 (African green monkey kidney) cells infected with varying titers of test and control viruses or transfected with varying amounts of test plasmid. After 10 min uptake and 30 min intermittent wash, the FES accumulation was higher in both the cell lines infected with test virus than those transfected by test plasmid. The uptake also increased with rise in viral titer in contrast to decreasing uptake with increased plasmid amounts. The co-expression of hERL and a model therapeutic gene by the correspondingly infected cells confirmed the results of binding study.The rats were injected with test and control adenoviruses into opposite hind limb adductor muscles. In vivo PET imaging in 6-days post-infected rat yielded positive accumulation of FES on the side injected with test virus. Furthermore, the correspondingly resected muscle samples were subjected to immunohistochemical staining and the expression of reporter and therapeutic genes were confirmed. Thus, we could successfully image the expression of our reporter gene hERL in vivo in a localized area of muscle tissue in rats. We hope confirmation of reporter gene expression following infection in other target areas will enable our system to be a significant addition to the existing repertoires of reporter gene system.Joint Molecular Imaging Conferenc