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Alvaro Sanchez-Martinez, Michelle Beavan, Matthew E Gegg, Kai-Yin Chau, Alexander J Whitworth, Anthony H V Schapira
GBA gene mutations are the greatest cause of Parkinson disease (PD). GBA encodes the lysosomal enzyme glucocerebrosidase (GCase) but the mechanisms by which loss of GCase contributes to PD remain unclear. Inhibition of autophagy and the generation of endoplasmic reticulum (ER) stress are both implicated. Mutant GCase can unfold in the ER and be degraded via the unfolded protein response, activating ER stress and reducing lysosomal GCase. Small molecule chaperones that cross the blood brain barrier help mutant GCase refold and traffic correctly to lysosomes are putative treatments for PD...
2016: Scientific Reports
Lizbeth Carrillo, Héctor Sumano, Luis Medina-Torres, Graciela Tapia, Lilia Gutiérrez
The rheological properties of pooled tracheobronchial secretions (TBS) of chicken, including mucus, have not been characterized. Yet mucolytic drugs are frequently used in poultry medicine. To define such properties, TBS from healthy untreated and from chickens treated with various mucolytic drugs was studied. Three hundred, three-week-old Rhode Island Red chickens were divided into five groups, with three repetitions each (n = 20) as follows: ambroxol (GAmb), ethylene diamine dihydro-iodide (GEddi), carbocysteine (GCs), bromhexine (GBr), and an untreated control group (CG)...
July 14, 2016: Poultry Science
Katsuyuki Takeda, Nobuaki Miyahara, Shigeki Matsubara, Christian Taube, Kenichi Kitamura, Astushi Hirano, Mitsune Tanimoto, Erwin W Gelfand
Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge...
June 2016: Immune Network
C de Mey, S Koelsch, E Richter, T Pohlmann, R Sousa
A pooled analysis is presented of 7 placebo-controlled RCT that investigated lozenges containing ambroxol for pain relief in acute sore throat.2 242 patients were treated with different ambroxol doses or control treatments, 2 183 were evaluable for efficacy. The present analysis is focused on the recommended dose of 20 mg (AXL20): 856 patients were treated with AXL20, 847 with matched placebo lozenges (PL).The average reduction in pain intensity over the first 3 h after the first AXL20 ranged from 38% to 52% of the maximum achievable effect (MAE)...
July 2016: Drug Research
Gali Maor, Or Cabasso, Olga Krivoruk, Joe Rodriguez, Hermann Steller, Daniel Segal, Mia Horowitz
Gaucher disease (GD) results from mutations in the acid β-glucocerebrosidase (GCase) encoding gene, GBA, which leads to accumulation of glucosylceramides. GD patients and carriers of GD mutations have a significantly higher propensity to develop Parkinson disease (PD) in comparison to the non-GD population.In the present study we used the fruit fly Drosophila melanogaster to show that development of PD in carriers of GD mutations results from the presence of mutant GBA alleles. Drosophila has two GBA orthologs (CG31148 and CG31414), each of which has a minos insertion, which creates C-terminal deletion in the encoded GCase...
May 9, 2016: Human Molecular Genetics
Zhening Guo, Yangsheng Chen, Xiaoliang Ding, Chenrong Huang, Liyan Miao
A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). Sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters ACQUITY UPLC BEH C18 column using gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring (MRM) mode by monitoring the ion transitions form m/z 378...
April 30, 2016: Biomedical Chromatography: BMC
Wenlei Wang, Jialin Yu, Yu He, Zhengli Wang, Fang Li
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause severe infections in immunocompromised individuals. Because it forms biofilms, which protect against host immune attack and increase resistance to conventional antibiotics, mucoid P. aeruginosa is nearly impossible to eradicate. Moreover, mucoid conversion of P. aeruginosa in cystic fibrosis (CF) patients leads to poor outcomes. This conversion is mainly due to mucA gene mutation, which is thought to be induced by polymorphonuclear leukocytes (PMNs) and the reactive oxygen species they release...
July 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Laura Isabell Immohr, Claas Hedfeld, Artur Lang, Miriam Pein-Hackelbusch
Manipulation of liquid oral drugs by mixing them into foodstuff is a common procedure for taste-masking of OTC pharmaceuticals when administered to children. However, the taste-masking capability of such application media is not systematically evaluated, and recommendations for suitable media are hardly published. In this study, a sensor array of commercially available and self-developed electronic tongue sensors was employed to assess the taste-masking efficiency of eight different beverages (tap water, apple juice, carrot juice, fennel tea, fruit tea, milk, cocoa, and Alete meal to drink) on the OTC pharmaceuticals Ambroxol-ratiopharm®, Cetirizin AL, and Laxoberal® by multivariate data analysis...
April 13, 2016: AAPS PharmSciTech
Aya Narita, Kentarou Shirai, Shinji Itamura, Atsue Matsuda, Akiko Ishihara, Kumi Matsushita, Chisako Fukuda, Norika Kubota, Rumiko Takayama, Hideo Shigematsu, Anri Hayashi, Tomohiro Kumada, Kotaro Yuge, Yoriko Watanabe, Saori Kosugi, Hiroshi Nishida, Yukiko Kimura, Yusuke Endo, Katsumi Higaki, Eiji Nanba, Yoko Nishimura, Akiko Tamasaki, Masami Togawa, Yoshiaki Saito, Yoshihiro Maegaki, Kousaku Ohno, Yoshiyuki Suzuki
OBJECTIVE: Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone...
March 2016: Annals of Clinical and Translational Neurology
Yaojun Ni, Lili Hou, Liang Chen, Jiang Fan
OBJECTIVE: In this study, a modified LC-MS/MS method was used to determine plasma ambroxol concentration and thereby examine the bioequivalence of two ambroxol medications among healthy Chinese male volunteers. METHODS: The study used a single-dose, randomized, open-label design principle and calculated pharmacokinetic parameters for the comparison of the two formulations. RESULTS: Administration of a single oral dose of either the test drug or reference drug was found to be safe in healthy subjects...
May 2016: International Journal of Clinical Pharmacology and Therapeutics
Choya Yoon, Roman J Giger
In this issue, Chandran et al. (2016) pursue a multi-level bioinformatics approach combined with wet bench validation to identify gene networks associated with the regenerative state of injured adult sensory neurons. A small molecular compound, ambroxol, mimics aspects of the identified gene expression patterns and promotes axon regeneration in the injured adult mouse CNS, demonstrating feasibility of in silico-based methods to identify compounds that promote neuronal growth following CNS injury.
March 2, 2016: Neuron
Ling-tian Ge, Ya-nan Liu, Xi-xi Lin, Hui-juan Shen, Yong-liang Jia, Xin-wei Dong, Yun Sun, Qiang-min Xie
Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4 days. Inhaled solution of ambroxol was aerosolized 20 min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5 AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE)...
April 2016: International Immunopharmacology
Shui-juan Zhang, Juan-xia Jiang, Qian-qian Ren, Yong-liang Jia, Jian Shen, Hui-juan Shen, Xi-xi Lin, Hong Lu, Qiang-min Xie
Ambroxol, a metabolite of bromhexine, is shown to exert several pharmacological activities, including secretolytic, anti-inflammatory and antioxidant actions. Oral and intravenous administration of ambroxol is useful for the airway inflammatory diseases. However, little is known about its potential in inhalation therapy for lipopolysaccharide (LPS)-induced mucous hypersecretion and inflammatory response. In the present study, we compared the pharmacological effects of ambroxol by inhalation with intravenous administration and preliminarily explored its mechanism of action...
March 15, 2016: European Journal of Pharmacology
Ludger Klimek, Annette Sperl
Sore throat should be treated symptomatically in self-medication. Due to the mainly viral origin of the disease and the lack of efficiency data, local antibiotics or antiseptics should not be recommended. systemic analgesics as acetylsalicylic acid, acetaminophen, flurbiprofen, or ibuprofen are valid treatment options. Clinical trials suggest that ibuprofen shows the best benefit-risk profile. Flurbiprofen could show efficiency in current trials but head-to-head data with other analgesics (e.g. ibuprofen) are missing...
December 2015: Medizinische Monatsschrift Für Pharmazeuten
C D Navo, F Corzana, E M Sánchez-Fernández, J H Busto, A Avenoza, M M Zurbano, E Nanba, K Higaki, C Ortiz Mellet, J M García Fernández, J M Peregrina
A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver β-glucosidase/β-galactosidase and specific inhibition of human β-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location...
January 28, 2016: Organic & Biomolecular Chemistry
Víctor García, Maribel Lara-Chica, Irene Cantarero, Olov Sterner, Marco A Calzado, Eduardo Muñoz
Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX...
January 26, 2016: Oncotarget
Xinyang Su, Zefu Li, Meilin Wang, Zhenzhu Li, Qingbo Wang, Wenxian Lu, Xiaoli Li, Youfei Zhou, Hongmei Xu
The purpose of this study was to establish a rat model of a brain injury with tracheotomy and compared the wetting effects of different airway humidification liquids, afterward, the best airway humidification liquid was selected for the clinical trial, thus providing a theoretical basis for selecting a proper airway humidification liquid in a clinical setting. Rats were divided into a sham group, group A (0.9% NaCl), group B (0.45% NaCl), group C (0.9% NaCl+ambroxol) and group D (0.9% NaCl+Pulmicort). An established rat model of traumatic brain injury with tracheotomy was used...
February 10, 2016: Gene
K-U Kern, T Weiser
BACKGROUND: Neuropathic pain is difficult to treat and available options are frequently not sufficient. The expectorant ambroxol also works as a strong local anesthetic and blocks sodium channels about 40 times more potently than lidocaine. Ambroxol preferentially inhibits the channel subtype Nav 1.8, which is expressed particularly in nociceptive C fibers. Due to the low toxicity, topical ambroxol seemed to represent a reasonable therapeutic attempt for treatment of neuropathic pain resistant to other standard options...
December 2015: Der Schmerz
Giorgio Fois, Nina Hobi, Edward Felder, Andreas Ziegler, Pika Miklavc, Paul Walther, Peter Radermacher, Thomas Haller, Paul Dietl
Ambroxol (Ax) is a frequently prescribed drug used to facilitate mucociliary clearance, but its mode of action is yet poorly understood. Here we show by X-ray spectroscopy that Ax accumulates in lamellar bodies (LBs), the surfactant storing, secretory lysosomes of type II pneumocytes. Using lyso- and acidotropic substances in combination with fluorescence imaging we confirm that these vesicles belong to the class of acidic Ca(2+) stores. Ax lead to a significant neutralization of LB pH, followed by intracellular Ca(2+) release, and to a dose-dependent surfactant exocytosis...
December 2015: Cell Calcium
Moreno Lelli, Sachin R Chaudhari, David Gajan, Gilles Casano, Aaron J Rossini, Olivier Ouari, Paul Tordo, Anne Lesage, Lyndon Emsley
Efficient dynamic nuclear polarization (DNP) in solids, which enables very high sensitivity NMR experiments, is currently limited to temperatures of around 100 K and below. Here we show how by choosing an adequate solvent, (1)H cross effect DNP enhancements of over 80 can be obtained at 240 K. To achieve this we use the biradical TEKPol dissolved in a glassy phase of ortho-terphenyl (OTP). We study the solvent DNP enhancement of both TEKPol and BDPA in OTP in the range from 100 to 300 K at 9.4 and 18.8 T. Surprisingly, we find that the DNP enhancement decreases only relatively slowly for temperatures below the glass transition of OTP (Tg = 243 K), and (1)H enhancements around 15-20 at ambient temperature can be observed...
November 25, 2015: Journal of the American Chemical Society
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