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Disease modifying drugs

Md Junaid, Nazrul Islam, Md Kamal Hossain, M Obayed Ullah, Mohammad A Halim
Among neurodegenerative disorders, Alzheimer's disease (AD) is one of the most common disorders showing slow progressive cognitive decline. Targeting acetylcholinesterase (AChE) is one of the major strategies for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are compromised. Herein, we report the design of some copper and other metal based donepezil derivatives, employing density functional theory (DFT). All designed compounds are optimized at the B3LYP/SDD level of theory...
2019: PloS One
David Baker, Gareth Pryce, Samuel S Herrod, Klaus Schmierer
Oral cladribine is a novel treatment for relapsing multiple sclerosis (MS). This appears to be a semi-selective immune-reconstitution therapy that induces long-term therapy from short treatment cycles. It has a relatively good safety profile that currently does not require extensive monitoring associated with some continuous immunosuppressive and relatively non-selective immune reconstitution therapies. The efficacy and safety of cladribine relates to its particular physicochemical properties, the function of the lymphocyte subsets that are selectively targeted by the drug and the repopulation kinetics of these subsets...
February 14, 2019: Multiple Sclerosis and related Disorders
Katja Dankhoff, Aamir Ahmad, Birgit Weber, Bernhard Biersack, Rainer Schobert
In order to identify new active drug candidates against cancer diseases we investigated the tumor cell growth inhibition, formation of reactive oxygen species, mitochondrial membrane damage, cell cycle arrest and DNA binding activity of a new bis(triethylammonium) tris[1,1-bis(indol-3-yl)-1-(3,4-catecholate)methane]vanadate(IV) complex. It exhibited significant antiproliferative activity against various cancer cell lines, showed a stronger DNA binding than cisplatin and led to mitochondrial damage, a formation of reactive oxygen species, and a cell cycle arrest in the G2/M phase of cancer cells...
February 13, 2019: Journal of Inorganic Biochemistry
Shazli Azmi, Maryam Ferdousi, Alise Kalteniece, Hamad Al-Muhannadi, Abdulrahman Al-Mohamedi, Nebras H Hadid, Salah Mahmoud, Harun A Bhat, Hoda Y A Gad, Adnan Khan, Georgios Ponirakis, Ioannis N Petropoulos, Uazman Alam, Rayaz A Malik
The diagnosis and management of diabetic neuropathy can be a major challenge. Late diagnosis contributes to significant morbidity in the form of painful diabetic neuropathy, foot ulceration, amputation, and increased mortality. Both hyperglycaemia and cardiovascular risk factors are implicated in the development of somatic and autonomic neuropathy and an improvement in these risk factors can reduce their rate of development and progression. There are currently no US Food and Drug Administration (FDA)-approved disease-modifying treatments for either somatic or autonomic neuropathy, as a consequence of multiple failed phase III clinical trials...
2019: Therapeutic Advances in Endocrinology and Metabolism
Qingmei Sun, Fufeng Liu, Jingcheng Sang, Miaoman Lin, Jiale Ma, Xiao Xiao, Sicheng Yan, C Benjamin Naman, Ning Wang, Shan He, Xiaojun Yan, Wei Cui, Hongze Liang
β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer's disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aβ fibrillization in vitro . Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aβ fibril formation than fascaplysin...
February 18, 2019: Marine Drugs
Yanfei Wang, Chi-Hsiu Liu, Tianjiao Ji, Manisha Mehta, Weiping Wang, Elizabeth Marino, Jing Chen, Daniel S Kohane
Choroidal neovascularization (CNV) is the major cause of vision loss in wet age-related macular degeneration (AMD). Current therapies require repeated intravitreal injections, which are painful and can cause infection, bleeding, and retinal detachment. Here we develop nanoparticles (NP-[CPP]) that can be administered intravenously and allow local drug delivery to the diseased choroid via light-triggered targeting. NP-[CPP] is formed by PEG-PLA chains modified with a cell penetrating peptide (CPP). Attachment of a DEACM photocleavable group to the CPP inhibits cellular uptake of NP-[CPP]...
February 18, 2019: Nature Communications
Hideaki Nakajima, Kenzo Uchida, Toshihiko Taguchi, Toshihiko Yamashita, Toshikatsu Tominaga, Masato Tanaka, Masatsune Yamagata, Takashi Kaito, Takahiro Ushida
BACKGROUND: We termed chronic neuropathic pain (NeP) in patients with diseases associated with spinal cord damage as "spinal cord-related pain syndrome". We conducted a survey of patients with the syndrome to assess the type and severity of NeP and its effect on QOL, and treatment modalities. METHODS: This cross-sectional study was conducted in 185 patients recruited from 15 medical institutions. We analyzed the questionnaires sent to clinicians (basic information, magnetic resonance imaging (MRI) findings, type and effectiveness of medications) and patients [modified Neuropathic Pain Symptom Inventory (NPSI) and short form (SF)-36 healthy survey]...
February 15, 2019: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
Daniel R Wynn
Multiple sclerosis (MS) is a chronic progressive neurodegenerative demyelinating disease affecting the central nervous system. Glatiramer acetate (GA; Copaxone®) was the first disease-modifying treatment (DMT) for MS successfully tested in humans (1977) and was approved by the US Food and Drug Administration in December 1996. Since then, there have been numerous developments in the MS field: advances in neuroimaging allowing more rapid and accurate diagnosis; the availability of a range of DMTs including immunosuppressant monoclonal antibodies and oral agents; a more holistic approach to treatment by multidisciplinary teams; and an improved awareness of the need to consider a patient's preferences and patient-reported outcomes such as quality of life...
2019: Multiple Sclerosis International
Rutviz Rajendra Mistry, Pallavi Patro, Vikas Agarwal, Durga Prasanna Misra
In this narrative review, we overview the recent literature on enthesitis-related arthritis (ERA). For the purpose of our review, we searched Scopus for recent articles on this subject from 2013 onward, including some classic older articles for perspective. ERA is a juvenile idiopathic arthritis (JIA) subtype more common in males, associated in a majority with human leucocyte antigen B27. Such children generally present with asymmetric oligoarthritis or polyarthritis, predominantly of lower limb joints, associated with enthesitis or sacroiliitis...
2019: Open Access Rheumatology: Research and Reviews
Ewelina Bąk, Czesław Marcisz, Adriana Borodzicz, Danuta Sternal, Sylwia Krzemińska
Purpose: The main purpose of this study was to compare the level of health-related quality of life (HRQoL) using Nottingham Health Profile (NHP) in Polish patients with rheumatoid arthritis (RA) during therapy applying disease-modifying antirheumatic drugs (DMARDs) with conventional synthetics (csDMARDs) or with csDMARDs in combination with biological drugs (bDMARDs). The second purpose was to analyze the correlation between the domain values of NHP and the demographic and clinical parameters, functional efficiency, and mood...
2019: Patient Preference and Adherence
Chen-Shan Chen Woodcock, Stephen Y Chan
Pulmonary hypertension (PH) and its severe subtype pulmonary arterial hypertension (PAH) encompass a set of multifactorial diseases defined by sustained elevation of pulmonary arterial pressure and pulmonary vascular resistance leading to right ventricular failure and subsequent death. Pulmonary hypertension is characterized by vascular remodeling in association with smooth muscle cell proliferation of the arterioles, medial thickening, and plexiform lesion formation. Despite our recent advances in understanding its pathogenesis and related therapeutic discoveries, PH still remains a progressive disease without a cure...
February 17, 2019: Journal of Cardiovascular Pharmacology and Therapeutics
Edit Kun, Lóránt Dienes, Gábor Simonyi, Ervin Finta
The control and planning of the treatment of hypertensive patients need specific attention. As regards concomitant diseases and treatments, glaucoma and the use of eye drops should be taken into consideration. The ingredients of the administered eye drops get through the nasolacrimal canal and can be absorbed by the nasal mucosa. Because of the lack of enterohepatic 'first pass' effect, they can act systemically - like after intravenous administration. This way they can cause systemic side effects. The authors present a case of a patient, too, who was examined and medically checked regularly for years with negative results because of repeated syncope...
February 2019: Orvosi Hetilap
François Montastruc, Christel Renoux, Marie Hudson, Sophie Dell'Aniello, Teresa A Simon, Samy Suissa
OBJECTIVE: To assess whether abatacept as initial biologic disease-modifying antirheumatic drug (DMARD) in the treatment of rheumatoid arthritis is associated with an increased risk of serious infections, including bone and joint, gastrointestinal, respiratory tract, skin and soft tissue, and urinary tract, when compared with other biologic DMARDs. METHODS: We performed a population-based cohort study among patients newly-treated with biologic DMARDs within the US-based Truven MarketScan® population and Supplemental US Medicare from 2007 to 2014...
January 25, 2019: Seminars in Arthritis and Rheumatism
Zhenhua Li, Yuping Liu, Xuejin Huang, Changming Hu, Hongwei Wang, Lin Yuan, John L Brash, Hong Chen
Gene transfection, as an effective treatment for inherited and acquired life threatening diseases caused by genetic deficiencies and abnormalities, has evolved as a promising therapeutic strategy for cancer and other intractable diseases. Non-target-specific vectors will affect normal cells as well as pathogenic cells, resulting in a relative decrease in transfection efficiency and unnecessary cytotoxicity. In the present work, gold nanoparticles (AuNPs) functionalized with folate (FA)-modified polyethylenimine (PEI-FA) were prepared by a single step method (without additional reducing agent) for targeted gene transfection in tumor cells...
February 6, 2019: Colloids and Surfaces. B, Biointerfaces
Ricardo Alonso, Edgar Carnero Contentti, Gaston Imhoff, Pablo A Lopez, Adrian Rubstein, Santiago Tizio
Current multiple sclerosis (MS) therapeutic options have significantly increased treatment algorithm complexity. This urges physicians to take into account multiple factors in the decision-making process and make an even more thorough analysis of the risk-benefit balance. We carried out a descriptive review aiming to assess some factors that endanger the proper MS treatment fulfillment, focusing mainly on Latin American countries. Firstly, it is paramount to warrant the correct, fair and timely treatment access...
February 7, 2019: Multiple Sclerosis and related Disorders
Hugh Kearney, Tucker Price, Jane Cryan, Alan Beausang, Seamus Looby, Francesca M Brett, Michael Farrell
BACKGROUND: Knowledge of the clinical outcome in tumefactive demyelination remains limited. AIMS: This study aims to characterise the natural history of biopsy-proven, pathogen-free, cerebral demyelination in an adult Irish population. METHODS: We identified all patients with biopsy-proven demyelination in a single neuropathology centre between 1999 and 2017. A baseline, and at least one follow-up MRI scan was available in each instance (mean of 3 scans per patient), together with both the presenting and most recent clinical details including disability level and disease-modifying drugs...
February 15, 2019: Irish Journal of Medical Science
F Mahfoud, M Böhm, C M Bongarth, R Bosch, R E Schmieder, H Schunkert, C Stellbrink, P Trenkwalder, O Vonend, J Weil, R Kreutz
Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League...
February 15, 2019: Der Internist
Kari Hansen Berg, Gudrun Rohde, Anne Prøven, Esben Esther Pirelli Benestad, Monika Østensen, Glenn Haugeberg
OBJECTIVE: To explore the relationship between demographic, disease related variables, treatment and sexual quality of life (SQOL) in men and women with Axial Spondyloarthritis (ax-SpA). METHODS: Ax-SpA patients were consecutively recruited from two rheumatology outpatient clinics in Sothern Norway. A broad specter of demographic, disease, treatment and quality of life data were systematically collected. SQOL was assessed using the SQOL-F questionnaire (score range 18-108)...
February 15, 2019: Journal of Rheumatology
Nara Lins Meira Quintão, Maria Verônica Dávila Pastor, Carla de Souza Antonialli, Gislaine Francieli da Silva, Lilian Wünsch Rocha, Talita Elisa Berté, Márcia Maria de Souza, Christiane Meyre-Silva, Ruth Meri Lucinda-Silva, Tania Mari Belle Bresolin, Valdir Cechinel Filho
ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general, and the nut oil had been topically applied to treat arthritis and other joint pain, however the seeds are classified as toxic for oral use. AIM: Faced with the need for new alternative to treat the symptoms and modify rheumatoid arthritis (RA) the aim of this work was to evaluate the effects of A...
February 12, 2019: Journal of Ethnopharmacology
Oh Chan Kwon, Ji Seon Oh, Seokchan Hong, Chang-Keun Lee, Bin Yoo, Yong-Gil Kim
OBJECTIVES: To investigate the effect of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis. METHODS: Patients with RA who were newly diagnosed with osteoporosis (T-score ≤ -2.5) between 2010 and 2017 were included. All patients received background bisphosphonate for treatment of osteoporosis. BMD was measured at baseline and after one year. To identify csDMARDs or other factors associated with significant increase in BMD (≥3%) at lumbar spine and femoral neck at one year, we performed logistic regression analysis...
February 11, 2019: Clinical and Experimental Rheumatology
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