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Drug therapy

Oriane Blanquie, Frank Bradke
Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone...
March 12, 2018: Current Opinion in Neurobiology
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Grace Juyun Kim, Kye Hwa Lee, Ju Han Kim
BACKGROUND: The Beers Criteria released by the American Geriatrics Society includes a list of drugs to avoid in the geriatric population and is frequently used as a safety resource in geriatric pharmacotherapy. OBJECTIVE: To evaluate the exposure of South Korean geriatrics to potentially inappropriate medications according to the Beers Criteria and the risk of adverse events from these medications. METHODS: This study included medications recommended to be avoided in patients 65 years or older regardless of concomitant drug therapy or disease...
2018: PloS One
Muyang Yang, Lixia Yu, Ruiwei Guo, Anjie Dong, Cunguo Lin, Jianhua Zhang
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell...
March 15, 2018: Nanomaterials
Vanessa Lin Lin Lee, Brandon Kar Meng Choo, Yin-Sir Chung, Uday P Kundap, Yatinesh Kumari, Mohd Farooq Shaikh
Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect...
March 15, 2018: International Journal of Molecular Sciences
David Vrana, Viktor Hlavac, Veronika Brynychova, Radka Vaclavikova, Cestmir Neoral, Jiri Vrba, Rene Aujesky, Marcel Matzenauer, Bohuslav Melichar, Pavel Soucek
The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful...
March 15, 2018: International Journal of Molecular Sciences
Leslee Sprague, Joel M Lee, Brian J Hutzen, Pin-Yi Wang, Chun-Yu Chen, Joe Conner, Lynne Braidwood, Kevin A Cassady, Timothy P Cripe
High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro...
March 15, 2018: Viruses
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Gabriel Carvajal, Denis Dupoiron, Valerie Seegers, Nathalie Lebrec, François Boré, Pierre-Yves Dubois, Damien Leblanc, Thierry Delorme, Sabrina Jubier-Hamon
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France...
March 14, 2018: Anesthesia and Analgesia
Mohammed Saji Salahudeen, Prasad S Nishtala
OBJECTIVE: To summarize studies that used the international Resident Assessment home care instrument (interRAI HC) to examine study outcomes for older people. METHODS: A comprehensive systematic search was performed to identify relevant studies, using five databases from 1990 until October 2016. The Cochrane Risk-Bias assessment tool and Newcastle-Ottawa Scale was used to assess the quality of RCTs and non-RCTs, respectively. RESULTS: Based on the full-text analysis, 40 studies met the inclusion criteria out of 506 total records...
March 2, 2018: Clinical Gerontologist
Norelle Sherry, Benjamin Howden
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the "re-discovery" of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas Covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam...
March 15, 2018: Expert Review of Anti-infective Therapy
Kuikun Yang, Yijing Liu, Yi Liu, Qian Zhang, Chuncai Kong, Chenglin Yi, Zijian Zhou, Zhantong Wang, Guofeng Zhang, Yang Zhang, Niveen M Khashab, Xiaoyuan Chen, Zhihong Nie
This article describes the fabrication of nanosized magneto-vesicles (MVs) comprising tunable layers of densely-packed superparamagnetic iron oxide nanoparticles (SPIONs) in membranes via cooperative assembly of polymer-tethered SPIONs and free poly(styrene)-b-poly(acrylic acid) (PS-b-PAA). The membrane thickness of MVs could be well controlled from 9.8 to 93.2 nm by varying the weight ratio of PS-b-PAA to SPIONs. The increase in membrane thickness was accompanied with the transition from monolayer MVs, to double-layered MVs and to multilayered MVs (MuMVs)...
March 15, 2018: Journal of the American Chemical Society
Bo Zhang, Shuyuan Wang, Jie Qian, Wenjia Yang, Fangfei Qian, Jun Lu, Yanwei Zhang, Rong Qiao, Baohui Han
BACKGROUND: Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown. METHODS: From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed...
March 15, 2018: Cancer
M A Akulov, O R Orlova, T V Tabashnikova, V V Karnaukhov, A S Orlova
Surgical treatment of posterior cranial fossa and cerebellopontine angle tumors is associated with a risk of facial nerve dysfunction. The causes for facial muscle paresis include nerve compression by the tumor, destruction of the nerve structure by the tumor growing from nerve fibers, nerve injury during surgical removal of the tumor, etc. The first 3 months after facial nerve injury are a potential therapeutic window for the use of botulinum toxin type A (BTA). During this period, the drug is introduced both in the healthy side to improve the facial symmetry at rest and during mimetic movements and in the affected side to induce drug-induced ptosis...
2018: Zhurnal Voprosy Neĭrokhirurgii Imeni N. N. Burdenko
A Zh Fursova, N V Chubar, M S Tarasov, M A Vasilyeva, G G Pustovaya, I F Saifullina
The apparent success of antiangiogenic therapy in patients with neovascular age-related macular degeneration (nAMD) shows the significance of effect prognosis and continuous observation. PURPOSE: to study the influence of prognostic factors on the dynamics of functional and morphological response during anti-VEGF therapy in patients with nAMD. MATERIAL AND METHODS: Retrospective analysis of anti-angiogenic therapy results was performed on the data of 1020 patients with nAMD...
2018: Vestnik Oftalmologii
A V Dolzhich, S E Avetisov
PURPOSE: to assess the neurophysiological effect and clinical effectiveness of transcranial direct current stimulation in combination with drug therapy in amblyopic children. MATERIAL AND METHODS: The study involved 32 healthy children in the age of 5-12 years and 97 patients of the same age with refractive strabismic amblyopia. All study subjects underwent standard examination including ophthalmological (visometry, refractometry in normal conditions and in cycloplegia, biomicroscopy, ophthalmoscopy, type of vision), neurophysiological methods (determination of retinal electric sensitivity threshold, electric lability of optic nerve, amplitude and latency period of visual evoked potentials, electroencephalogram wave amplitudes, localization of peak electrical activity area of the cerebral cortex), assessment of neuropsychic development and estimation of mental development coefficient with age tests...
2018: Vestnik Oftalmologii
Arezoo Mohammadi Gazestani, Samideh Khoei, Sepideh Khoee, Soraya Emamgholizadeh Minaei, Manijeh Motevalian
Magnetite nanographene oxide has exhibited great potential in drug delivery and photothermal therapy (PTT) for cancer treatment. Here we developed 5-fluorouracil-loaded poly (lactic-co-glycolic acid)-coated magnetite nanographene oxide (NGO-SPION-PLGA-5-Fu) to simplify combined PTT and chemotherapy in one complex. The nanocarrier was synthesized using a modified O1 /W1 /O2 /W2 multiple emulsion solvent evaporation method and was characterized for size, zeta potential, drug loading, in vitro and in vivo release...
March 15, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Stephan R Bohl, Lars Bullinger, Frank G Rücker
The majority of patients with acute myeloid leukemia (AML) are older and exhibit a poor prognosis even after intensive therapy. Inducing differentiation and apoptosis of leukemic blasts by DNA-hypomethylating agents, like e.g. azacytidine (AZA) and decitabine (DAC), represent well-tolerated alternative treatment approaches. Both agents show convincing response as single agents in AML. However, there is a lack of knowledge regarding molecular mechanisms and predictive biomarkers for these agents. Areas covered: This review will (i) provide an overview of the current knowledge of molecular mechanisms underlying the action of these drugs, (ii) report promising predictive biomarkers, (iii) elude on new combined treatment options, and (iv) discuss novel approaches to improve outcomes...
March 15, 2018: Expert Review of Hematology
Juan Li, Yang Du, Zhenqi Jiang, Yuchen Tian, Nianxiang Qiu, Yinjie Wang, Muhammad Zubair Lqbal, Menying Hu, Ruifen Zou, Lijia Luo, Shiyu Du, Jie Tian, Aiguo Wu
Due to the molecular and cellular heterogeneity of glioma, discovery of novel targeted sites and ligands for glioma imaging and therapy remains challenging. Neuropeptide Y (NPY) Y1 receptors (Y1 Rs) are highly over expressed in various brain tumors including glioma, and can serve as potential targeting sites for glioma imaging and therapy. Here, we show by in vivo fluorescent imaging that a highly selective Y1 R ligand, [Asn6 , Pro34 ] NPY (AP-NPY), facilitated circumvention of the blood brain barrier (BBB) by nanomicelles specifically targeting glioma...
March 15, 2018: Nanoscale
Wei Sun, Ju-Dong Luo, Hua Jiang, Dayue Darrel Duan
Tumor cells produce and secrete more nucleic acids, proteins and lipids than normal cells. These molecules are transported in the blood or around the cells in membrane-encapsulated exosomes. Tumor-derived or tumor-associated exosomes (usually 30-100 nm in diameter) contain abundant biological contents resembling those of the parent cells along with signaling messengers for intercellular communication involved in the pathogenesis, development, progression, and metastasis of cancer. As these exosomes can be detected and isolated from various body fluids, they have become attractive new biomarkers for the diagnosis and prognosis of cancer...
March 15, 2018: Acta Pharmacologica Sinica
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