318 research outputs found

    ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation

    Get PDF
    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1G93A ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1G93A mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1G93A mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.link_to_OA_fulltex

    A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign prostatic hyperplasia

    Get PDF
    BACKGROUND: Prostate cancer and benign prostatic hyperplasia are very common diseases in older American men, thus having a reliable treatment modality for both diseases is of great importance. The currently used treating options, mainly surgical ones, have numerous complications, which include the many side effects that accompany such procedures, besides the invasive nature of such techniques. Focused ultrasound is a relatively new treating modality that is showing promising results in treating prostate cancer and benign prostatic hyperplasia. Thus this technique is gaining more attention in the past decade as a non-invasive method to treat both diseases. METHODS: In this paper, the design, construction and evaluation of a 1.75 dimensional ultrasound phased array to be used for treating prostate cancer and benign prostatic hyperplasia is presented. With this array, the position of the focus can be controlled by changing the electrical power and phase to the individual elements for electronically focusing and steering in a three dimensional volume. The array was designed with a maximum steering angle of ± 13.5° in the transverse direction and a maximum depth of penetration of 11 cm, which allows the treatment of large prostates. The transducer piezoelectric ceramic, matching layers and cable impedance have been designed for maximum power transfer to tissue. RESULTS: To verify the capability of the transducer for focusing and steering, exposimetry was performed and the results correlated well with the calculated field. Ex vivo experiments using bovine tissue were performed with various lesion sizes and indicated the capability of the transducer to ablate tissue using short sonications. CONCLUSION: A 1.75 dimensional array, that overcame the drawbacks associated with one-dimensional arrays, has been designed, built and successfully tested. Design issues, such as cable and ceramic capacitances, were taken into account when designing this array. The final prototype overcame also the problem of generating grating lobes at unwanted locations by tapering the array elements

    Noninvasive, Transient and Selective Blood-Brain Barrier Opening in Non-Human Primates In Vivo

    Get PDF
    The blood-brain barrier (BBB) is a specialized vascular system that impedes entry of all large and the vast majority of small molecules including the most potent central nervous system (CNS) disease therapeutic agents from entering from the lumen into the brain parenchyma. Microbubble-enhanced, focused ultrasound (ME-FUS) has been previously shown to disrupt noninvasively, selectively, and transiently the BBB in small animals in vivo. For the first time, the feasibility of transcranial ME-FUS BBB opening in non-human primates is demonstrated with subsequent BBB recovery. Sonications were combined with two different types of microbubbles (customized 4–5 ”m and DefinityÂź). 3T MRI was used to confirm the BBB disruption and to assess brain damage

    A family based tailored counselling to increase non-exercise physical activity in adults with a sedentary job and physical activity in their young children: design and methods of a year-long randomized controlled trial

    Get PDF
    Background. Epidemiological evidence suggests that decrease in sedentary behaviour is beneficial for health. This family based randomized controlled trial examines whether face-to-face delivered counselling is effective in reducing sedentary time and improving health in adults and increasing moderate-to-vigorous activities in children. Methods. The families are randomized after balancing socioeconomic and environmental factors in the JyvÀskylÀ region, Finland. Inclusion criteria are: healthy men and women with children 3-8 years old, and having an occupation where they self-reportedly sit more than 50% of their work time and children in all-day day-care in kindergarten or in the first grade in primary school. Exclusion criteria are: body mass index > 35 kg/m2, self-reported chronic, long-term diseases, families with pregnant mother at baseline and children with disorders delaying motor development. From both adults and children accelerometer data is collected five times a year in one week periods. In addition, fasting blood samples for whole blood count and serum metabonomics, and diurnal heart rate variability for 3 days are assessed at baseline, 3, 6, 9, and 12 months follow-up from adults. Quadriceps and hamstring muscle activities providing detailed information on muscle inactivity will be used to realize the maximum potential effect of the intervention. Fundamental motor skills from children and body composition from adults will be measured at baseline, and at 6 and 12 months follow-up. Questionnaires of family-influence-model, health and physical activity, and dietary records are assessed. After the baseline measurements the intervention group will receive tailored counselling targeted to decrease sitting time by focusing on commute and work time. The counselling regarding leisure time is especially targeted to encourage toward family physical activities such as visiting playgrounds and non-built environments, where children can get diversified stimulation for play and practice fundamental of motor skills. The counselling will be reinforced during the first 6 months followed by a 6-month maintenance period. Discussion. If shown to be effective, this unique family based intervention to improve lifestyle behaviours in both adults and children can provide translational model for community use. This study can also provide knowledge whether the lifestyle changes are transformed into relevant biomarkers and self-reported health. Trial registration number. ISRCTN: ISRCTN28668090peerReviewe

    Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

    Get PDF
    Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10 +/- 1 x 10(3) to 17 +/- 2 x 10(3) mu m(2); 6 weeks: 13 +/- 2 x 10(3) to 24 +/- 3 x 10(3) mu m(2)). After 3, but not 6, weeks of hypertension, the arterial diameter was increased (empty set: 385 +/- 13 to 463 +/- 14 mu m). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 x 10(3) +/- 1 x 10(3) mu m(2)). The diameter of the HF arteries of normotensive rats increased (empty set: 463 +/- 22 mu m) but no expansion occurred in the HF arteries of hypertensive rats (empty set: 471 +/- 16 mu m). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (empty set: 419 +/- 13 to 475 +/- 16 mu m). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean empty set between 235 and 290 mu m), and infiltration of monocyte/ macrophages. SOL1 treatment did not affect the arterial diameter of LF arteries but reduced the infiltration of monocyte/ macrophages. We show for the first time that flow-induced remodeling is impaired during the development of DOCA-salt hypertension and that this can be prevented by chronic NEP/ECE inhibition. Hypertension Research (2012) 35, 1093-1101; doi:10.1038/hr.2012.94; published online 12 July 201
    • 

    corecore