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ALS Therapy

Paulo José Lorenzoni, Renata Dal-Prá Ducci, Giuliano Ohde Dalledone, Claudia Suemi Kamoi Kay, Sérgio Monteiro de Almeida, Lineu Cesar Werneck, Rosana Hermínia Scola
HIV-associated motor neuron disease (MND), or amyotrophic lateral sclerosis (ALS)-like syndrome associated with HIV infection, is a rare manifestation of HIV infection. HIV-associated MND has only been identified in few cases to date. We analysed two Brazilian patients with HIV infection who developed MND. The diagnosis of HIV infection was concomitant with diagnosis of MND in one patient and it occurred eight years before the MND symptoms in another patient. The manifestation of MND in our patients with HIV infection was similar to classic ALS...
June 10, 2018: Clinical Neurology and Neurosurgery
Erhan Saracoglu, Salih Kılıç, Ertan Vuruşkan, Irfan Düzen, Yusuf Çekici, Zülfiye Kuzu, Arafat Yıldırım, Mehmet Küçükosmanoğlu, Mustafa Çetin
BACKGROUND AND AIMS: Few studies have shown the direct effect of familial hypercholesterolemia (FH) on myocardial systolic function. Studies focused on heterozygote FH patients but not homozygote ones, and they did not perform genetic analyses. We aimed to evaluate all types of patients with FH using the potentially more sensitive speckle tracking echocardiography (STE) technique to identify early left ventricular (LV) dysfunction. METHODS: Genetic analyses of patients with FH were conducted for LDL-receptor, PCSK9, and ApoB100...
June 5, 2018: Echocardiography
Jinxuan Li, Jing-Yi Chen, Ya-Lin Deng, Qian Zhou, Yinuo Wu, Deyan Wu, Hai-Bin Luo
Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized...
2018: Frontiers in Chemistry
Shir Galin, Irit Heruti, Noa Barak, Marc Gotkine
The psychological phenotype in amyotrophic lateral sclerosis (ALS) is less negative than in other neurodegenerative diseases, manifested by a lower prevalence of psychopathology, such as anxiety and major depression, and a higher perceived quality of life by patients, irrespective of physical impairment. We hypothesized that positive psychological factors such as hope, optimism, and self-efficacy in people with ALS (PALS) were key determinants of satisfaction with life (SWL), despite physical impairment, and were protective against psychopathology...
May 31, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Tianhang Wang, Jiling Cheng, Shuyu Wang, Xudong Wang, Hongquan Jiang, Yueqing Yang, Ying Wang, Chunting Zhang, Weiwei Liang, Honglin Feng
Amyotrophic lateral sclerosis (ALS) is a degenerative disease with a progressive loss of motor neurons in the central nervous system (CNS). However, there are unsolved problems with the therapies for this disease. α-Lipoic acid (LA) is a natural, universal antioxidant capable of scavenging hydroxyl radicals as well as regenerating a series of antioxidant enzymes that has been widely used in clinical settings. This study aimed to evaluate the antioxidant and neuroprotective effects of LA in ALS cell and Drosophila models with mutant G85R and G93A hSOD1 genes...
May 26, 2018: Brain Research Bulletin
Fuling Zhou, Hui Dong, Yaling Liu, Lina Yan, Can Sun, Pengli Hao, Yuanyuan Liu, Jingxu Zhai, Yakun Liu
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease, and at present, therapies for ALS are limited. Estrogen is a potential therapeutic agent for ALS but has undesirable effects that might increase the risk of breast and uterine cancers or stroke. Raloxifene (Ral) has estrogenic properties but does not exhibit these adverse effects. However, the mechanism of Ral in ALS has not been studied. We thus investigated the effects of Ral in an NSC34 model of ALS that stably expresses the 25-kDa C-terminal fragment of TDP-43 (i...
May 25, 2018: Brain Research Bulletin
Patrizia Bossolasco, Francesca Sassone, Valentina Gumina, Silvia Peverelli, Maria Garzo, Vincenzo Silani
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease, mainly affecting the motor neurons (MNs) and without effective therapy. Drug screening is hampered by the lack of satisfactory experimental and pre-clinical models. Induced pluripotent stem cells (iPSCs) could help to define disease mechanisms and therapeutic strategies as they could be differentiated into MNs, otherwise inaccessible from living humans. In this study, given the seminal role of TDP-43 in ALS pathophysiology, MNs were obtained from peripheral blood mononuclear cells-derived iPSCs of an ALS patient carrying a p...
May 17, 2018: Stem Cell Research
Peter J Trainer, John Newell-Price, John Ayuk, Simon Aylwin, D Aled Rees, Wm Drake, Philippe Chanson, Thierry Brue, Susan M Webb, Carmen Fajardo Montañana, Javier Aller, Ann I McCormack, David J Torpy, George Tachas, Lynne Atley, David Ryder, Martin Bidlingmaier
OBJECTIVE: ATL1103 is a second-generation antisense oligomer targeting the human GH receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. DESIGN: 26 patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200 mg either once- or twice-weekly for 13 weeks, and monitored for a further 8-week washout period. METHODS: The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts...
May 22, 2018: European Journal of Endocrinology
Agustín A Silberberg, Josefina Robetto, Mora Achával
Decision making in advanced Amyotrophic Lateral Sclerosis (ALS) patients keeps on being a controversial issue. The aim of this work is to discuss ethical implications of withdrawing respiratory support treatment in patients with ALS. Through a bibliographic search on Pubmed database (2010-2016) we investigated whether or not the use of Non-Invasive Ventilation (NIV) and Mechanical Ventilation (MV) would increase survival and quality of life. We included 38 review articles. From these papers, results and ethical implications of initiating and mainly withdrawing respiratory support were analyzed...
May 2018: Cuadernos de Bioética: Revista Oficial de la Asociación Española de Bioética y Ética Médica
Neda Soveyd, Mina Abdolahi, Sama Bitarafan, Abbas Tafakhori, Payam Sarraf, Mansoureh Togha, Ali Asghar Okhovat, Mahsa Hatami, Mohsen Sedighiyan, Mahmoud Djalali, Niyaz Mohammadzadeh Honarvar
Migraine is a common chronic inflammatory neurological disease with the progressive and episodic course. Much evidence have shown a role of inflammation in the pathogenesis of migraine. Omega-3 fatty acids are an important components of cell membranes phospholipids. The intake of these fatty acids is related to decrease concentration of C-reactive protein (CRP), proinflammatory eicosanoids, cytokines, chemokines and other inflammation biomarkers. Many of clinical trials have shown the beneficial effect of dietary supplementation with omega-3 fatty acids in inflammatory and autoimmune diseases in human, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS) and migraine headaches...
October 7, 2017: Iranian Journal of Neurology
Selina Winter, Mirja Christine Nolff, Sven Reese, Andrea Meyer-Lindenberg
ZIEL: der Studie war, die Keimbelastung sowie die klinische Effizienz von Polyhexanid, Argon-Kaltplasma und Kochsalzlösung zur Reduktion der Bioburden bei Hundebissverletzungen zu überprüfen. MATERIAL UND METHODEN: In die Studie eingeschlossen wurden Hunde mit Bissverletzungen, die durch ein chirurgisches Debridement mit anschließender Wundbehandlung durch Lavage mit Polyhexanid-Biguanid (A), Therapie mit kaltem Argonplasma (B) oder Lavage mit physiologischer Kochsalzlösung (C) versorgt wurden...
April 2018: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
Michael Christopher Kurz, Robert H Schmicker, Brian Leroux, Graham Nichol, Tom P Aufderheide, Sheldon Cheskes, Brian Grunau, Jamie Jasti, Peter Kudenchuk, Gary M Vilke, Jason Buick, Lynn Wittwer, Ritu Sahni, Ronald Straight, Henry E Wang
BACKGROUND: Prior observational studies suggest no additional benefit from advanced life support (ALS) when compared with providing basic life support (BLS) for patients with out-of-hospital cardiac arrest (OHCA). We compared the association of ALS care with OHCA outcomes using prospective clinical data from the Resuscitation Outcomes Consortium (ROC). METHODS: Included were consecutive adults OHCA treated by participating emergency medical services (EMS) agencies between June 1, 2011, and June 30, 2015...
April 30, 2018: Resuscitation
Jessica de Wit, Anita Beelen, Constance H C Drossaert, Ruud Kolijn, Leonard H van den Berg, Johanna M A Visser-Meily, Carin D Schröder
BACKGROUND: Informal caregivers of patients with Amyotrophic Lateral Sclerosis (ALS) or Progressive Muscular Atrophy (PMA) face stressful demands due to severe impairments and prospect of early death of the patients they care for. Caregivers often experience feelings of psychological distress and caregiver burden, but supportive interventions are lacking. The objective of this study is to investigate the effectiveness of a psychosocial support program aimed at enhancing feelings of control over caregiving tasks and reducing psychological distress...
May 2, 2018: BMC Psychology
Tianzhi Yang, Laine Ferrill, Leanne Gallant, Sarah McGillicuddy, Tatiana Fernandes, Nicole Schields, Shuhua Bai
Riluzole is currently one of two approved medications for the treatment of amyotrophic lateral sclerosis (ALS). However, brain disposition of riluzole, as a substrate of P-glycoprotein (P-gp), is limited by the efflux transporters at the blood-brain barrier (BBB). We propose to develop a liposomal co-delivery system that could effectively transport riluzole to brain cells by reducing efflux pumps with a P-gp inhibitor, verapamil. Riluzole and verapamil cocktail liposomes were prepared by lipid film hydration...
April 25, 2018: European Journal of Pharmaceutical Sciences
Sabreena J Slavin, Heidi Sucharew, Kathleen Alwell, Charles J Moomaw, Daniel Woo, Opeolu Adeoye, Matthew L Flaherty, Simona Ferioli, Jason McMullan, Jason Mackey, Felipe De Los Rios La Rosa, Sharyl Martini, Brett M Kissela, Dawn O Kleindorfer
BACKGROUND AND PURPOSE: Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND). METHODS: Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND...
April 27, 2018: Emergency Medicine Journal: EMJ
N Kvirkvelia, R Shakarishvili, T Kanashvili
The authors present a case of 75-year-old male patient with typical clinical and electroneuromyographic signs of Amyotrophic Lateral Sclerosis (ALS), manifested in 4 years after a diagnosis of generalized Myasthenia Gravis (MG) had been made. The aim of the article is to assess the possibility of pathogenetic integrated comorbidity of MG and ALS, which may have resulted from a common aberrant immune process and to emphasize the importance of detailed clinical analysis and adequate diagnostic methods essential for correct diagnosis and treatment...
March 2018: Georgian Medical News
Benjamin Rix Brooks, James A Jorgenson, Barbara J Newhouse, Jeremy M Shefner, Wendy Agnese
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease affecting approximately 5 out of every 100,000 individuals living in the United States. ALS is associated with 50% mortality within 30 months of initial symptom onset. The rarity of the disease, along with the significant inter- and intra-patient variability in clinical course and a lack of reliable biomarkers, have rendered the development of effective agents to treat ALS a challenge. Because oxidative stress is considered a contributing factor to ALS onset and progression, drugs that eliminate free radicals may protect motor neurons from damage potentially caused by free-radical and oxidative stress...
April 2018: American Journal of Managed Care
Ágatha Oliveira-Giacomelli, Yahaira Naaldijk, Laura Sardá-Arroyo, Maria C B Gonçalves, Juliana Corrêa-Velloso, Micheli M Pillat, Héllio D N de Souza, Henning Ulrich
Since proving adenosine triphosphate (ATP) functions as a neurotransmitter in neuron/glia interactions, the purinergic system has been more intensely studied within the scope of the central nervous system. In neurological disorders with associated motor symptoms, including Parkinson's disease (PD), motor neuron diseases (MND), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's Disease (HD), restless leg syndrome (RLS), and ataxias, alterations in purinergic receptor expression and activity have been noted, indicating a potential role for this system in disease etiology and progression...
2018: Frontiers in Pharmacology
Ranjeet Prasad Dash, R Jayachandra Babu, Nuggehally R Srinivas
The recent approval of edaravone has provided an intravenous option to treat amyotrophic lateral sclerosis (ALS) in addition to the existing oral agent, riluzole. The present work was primarily undertaken to provide a comprehensive clinical pharmacokinetic summary of the two approved ALS therapeutics. The key objectives of the review were to (i) tabulate the clinical pharmacokinetics of riluzole and edaravone with emphasis on absorption, distribution, metabolism and excretion (ADME) properties; (ii) provide a comparative scenario of the pharmacokinetics of the two drugs wherever possible; and (iii) provide perspectives and introspection on the gathered clinical pharmacokinetic data of the two drugs with appropriate conjectures to quench scientific curiosity...
April 23, 2018: Clinical Pharmacokinetics
Tiina M Andersen, Astrid Sandnes, Ove Fondenes, Roy M Nilsen, Ole-Bjørn Tysnes, John-Helge Heimdal, Hege H Clemm, Thomas Halvorsen, Maria Vollsæter, Ola D Røksund
BACKGROUND: Respiratory complications represent the major cause of death in amyotrophic lateral sclerosis (ALS). Noninvasive respiratory support is the mainstay therapy, but treatment becomes challenging as the disease progresses, possibly due to a malfunctioning larynx, which is the entrance to the airways. We studied laryngeal response patterns to mechanically assisted cough (mechanical insufflation-exsufflation) as ALS progresses. METHODS: This prospective longitudinal study of 13 consecutively included subjects with ALS were followed up during 2011-2016 with repeated tests of lung function, neurological status, and laryngeal responses to mechanical insufflation-exsufflation using video-recorded flexible transnasal fiberoptic laryngoscopy...
May 2018: Respiratory Care
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