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Fernando J Martinez, Klaus F Rabe, Gary T Ferguson, Leonardo M Fabbri, Stephen Rennard, Gregory J Feldman, Sanjay Sethi, Selwyn Spangenthal, Gregory M Gottschlich, Roberto Rodriguez-Roisin, Samir Arora, Thomas M Siler, Shahid Siddiqui, Patrick Darken, Tracy Fischer, Andrea Maes, Michael Golden, Chad Orevillo, Colin Reisner
BACKGROUND: Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combinations are a treatment option for patients with chronic obstructive pulmonary disease (COPD) who continue to have symptoms despite treatment with a LAMA or LABA alone. OBJECTIVES: The PINNACLE-1 (NCT01854645) and -2 (NCT01854658) trials investigated the efficacy and safety of a novel GFF MDI (glycopyrrolate [GP]/formoterol [FF] 18/9.6 μg metered dose inhaler [MDI]) formulated using Co-Suspension™ Delivery Technology, in patients with moderate-to-very severe COPD...
December 1, 2016: Chest
Stephen W Stein, Charles G Thiel
In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems...
October 17, 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
A Brad Hall, April Novotny, Donna M Bhisitkul, James Melton, Tim Regan, Maureen Leckie
Introduction While pediatric asthma continues to be a highly studied disease, data to suggest clear strategies to decrease asthma related revisits or readmissions is lacking. The purpose of our study was to assess the effect of emergency department (ED) direct dispensing of beta-agonist metered dose inhalers on pediatric asthma ED revisit and readmission rates. Methods We conducted a retrospective cohort study of pediatric patients discharged from the pediatric ED with a diagnosis of asthma. Our primary outcome measured the rate of asthma revisits to the ED or admissions to the hospital within 28 days...
October 7, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Nobutaka Suzuki, Tatsuo Ito, Hisanori Matsui, Masayuki Takizawa
TAK-475 (lapaquistat acetate) and its active metabolite-I (TAK-475 M-I) inhibit squalene synthase, which catalyzes the conversion of farnesyl diphosphate (FPP) to squalene. FPP is a substrate for synthesis of other mevalonate-derived isoprenoids (MDIs) such as farnesol (FOH), geranlygeranyl diphosphate (GGPP), and geranylgeraniol. In patients with MKD, a rare autosomal recessive disorder, defective activity of mevalonate kinase leads to a shortage of MDIs. MDIs especially GGPP are required for prenylation of proteins, which is a posttranslation modification necessary for proper functioning of proteins like small guanosine triphosphatases...
2016: SpringerPlus
Kostas Zygogiannis, Daniel Wismeijer, Azin Parsa
PURPOSE: The aim of this study was to investigate the effect of immediately loaded mini dental implants (MDIs) used to support mandibular overdentures on the peri-implant bone level as well as patients' related levels of satisfaction and quality of life. MATERIALS AND METHODS: Four MDIs were placed in the interforaminal region of 10 completely edentulous patients, and the implants were loaded immediately (same day) with an overdenture. Radiographic assessment of the bone loss during a period of 18 months was performed by measuring the bone level changes at the mesial and distal aspects of each implant on panoramic radiographs...
September 2016: International Journal of Oral & Maxillofacial Implants
Brian Kilgore, Khalid Al Katranji, Meredith Woodall, Meagan Shepherd, Susan L Flesher
Studies show the delivery of inhaled medications is maximized when a metered-dose inhaler (MDI) with a spacer is utilized. Our residents expressed concern with their knowledge of MDIs and spacers. This study was designed to address those concerns. Residents were given a 12-question pre-intervention, self-assessment questionnaire that explored their overall knowledge and comfort in utilizing MDI with spacers. Participants then received educational intervention via multimedia videos and a demonstration of proper use of MDI with spacer...
October 2016: Clinical Pediatrics
David B Price, Anna Rigazio, Mary Buatti Small, Thomas J Ferro
BACKGROUND: Using a metered-dose inhaler (MDI) beyond the labeled number of actuations may result in inadequate dosing of medication, which can lead to poor clinical outcomes. This study compared respiratory-related emergency department (ED) visit rates in patients with asthma, chronic obstructive pulmonary disease, or both when they used albuterol MDIs with versus without dose counters. METHODS: This retrospective study used US claims data to identify patients (ages 4-64 years) with asthma, chronic obstructive pulmonary disease, or both, using albuterol MDIs with or without an integrated dose counter...
2016: Journal of Asthma and Allergy
R S Pirie, B C McGorum, C Owen, O Carr, H Oakley, G McLachlan
Despite frequent use of metered dose inhalers (MDIs) and spacers in equine practice, limited information exists on the efficiency of aerosol delivery using such devices. We determined the particle size distribution within an MDI-generated salbutamol aerosol delivered via an equine spacer using 'best practice' delivery technique and assessed the effect of variations in MDI use technique (shaking prior to each actuation, rapid repetitive actuations, and MDI angulation) on aerosol delivery efficiency. Under optimal conditions, only 53(±18) μg salbutamol per 100 μg actuation was delivered beyond the spacer...
September 4, 2016: Journal of Veterinary Pharmacology and Therapeutics
Katalin Módis, YoungJun Ju, Akbar Ahmad, Ashley A Untereiner, Zaid Altaany, Lingyun Wu, Csaba Szabo, Rui Wang
Mammalian cells can utilize hydrogen sulfide (H2S) to support mitochondrial respiration. The aim of our study was to explore the potential role of S-sulfhydration (a H2S-induced posttranslational modification, also known as S-persulfidation) of the mitochondrial inner membrane protein ATP synthase (F1F0 ATP synthase/Complex V) in the regulation of mitochondrial bioenergetics. Using a biotin switch assay, we have detected S-sulfhydration of the α subunit (ATP5A1) of ATP synthase in response to exposure to H2S in vitro...
November 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Richard Goodwin, Tiranvir Chander, Neha Shah, Steve Tomlin
AIM: To evaluate whether healthcare professionals within the local community are able to counsel paediatric patients on the essential steps required for drug delivery with multi-dose inhalers (MDI), MDIs with a spacer and turbohalers. METHOD: An expert panel produced and piloted checklists for essential and good practice counselling steps. Eligible participants included healthcare professionals regularly counselling children on inhaler devices, including doctors, nurses and pharmacy team members...
September 2016: Archives of Disease in Childhood
Gréta Varkoly, János Bencze, László Módis, Tibor Hortobágyi
The human cornea is rich in extracellular matrix. The stroma constitutes the main thickness of the cornea, which consists of collagens and proteoglycans mainly. The epithelial-stromal and stromal dystrophies of the cornea are either autosomal dominant or recessive inherited disorders, which are unrelated to inflammation or trauma. The diseases can manifest in each layer of the cornea, but in most cases the corneal stroma is affected. Generally, they develop in childhood or young adulthood but the diagnosis is only possible when clinical signs (epithelial erosions, decreased visual acuity, photophobia) develop...
August 2016: Orvosi Hetilap
Nadiya Druzhyna, Bartosz Szczesny, Gabor Olah, Katalin Módis, Antonia Asimakopoulou, Athanasia Pavlidou, Petra Szoleczky, Domokos Gerö, Kazunori Yanagi, Gabor Törö, Isabel López-García, Vassilios Myrianthopoulos, Emmanuel Mikros, John R Zatarain, Celia Chao, Andreas Papapetropoulos, Mark R Hellmich, Csaba Szabo
Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the 'Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4-methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H2S) production...
November 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Manabu Kanazawa, Jocelyne Feine, Shahrokh Esfandiari
This article describes the flapless placement of mini-dental implants (MDI) to retain mandibular overdentures. Clinical inclusion/exclusion criteria and clinical protocols for the flapless placement of MDIs and for retrofitting the overdenture are presented. A minimum bone height of 13 mm and a minimal flap are recommended. After drilling, the 4 implants are placed with a self-tapping process. A minimum of 15 Ncm of resistance upon final insertion indicates that immediate loading can be performed. The metal housings with O-rings are incorporated into the prosthesis using autopolymerizing resin...
August 1, 2016: Journal of Prosthetic Dentistry
Jan Šoupal, Lenka Petruželková, Milan Flekač, Tomáš Pelcl, Martin Matoulek, Martina Daňková, Jan Škrha, Štěpán Svačina, Martin Prázný
OBJECTIVE: To compare different treatment modalities for patients with type 1 diabetes (T1D) based on real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG) combined with multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: Sixty-five T1D patients were followed up for a year. Of these, 27 started RT-CGM as part of a sensor-augmented insulin regimen (SAIR); within this SAIR group, 15 subjects started sensor-augmented pump (SAP) therapy and the remaining 12 continued with MDIs (MDIs + RT-CGM)...
September 2016: Diabetes Technology & Therapeutics
Sepideh Momeni, Ali Nokhodchi, Saeed Ghanbarzadeh, Hamed Hamishehkar
PURPOSE: Respiratory drug delivery has been attracted great interest for the past decades, because of the high incidence of pulmonary diseases. However, despite its invaluable benefits, there are some major drawbacks in respiratory drug delivery, mainly due to the relatively high drug deposition in undesirable regions. One way to improve the efficiency of respiratory drug delivery through metered-dose inhalers (MDI) is placing a respiratory spacer between the inhaler exit and the mouth...
June 2016: Advanced Pharmaceutical Bulletin
Haruhiko Machida, Isao Tanaka, Rika Fukui, Yun Shen, Takuya Ishikawa, Etsuko Tate, Eiko Ueno
Single-source dual-energy (DE) computed tomography (CT) with fast switching of tube voltage allows projection-based image reconstruction, substantial reduction of beam-hardening effects, reconstruction of accurate monochromatic images and material decomposition images (MDIs), and detailing of material composition by using x-ray spectral information. In vascular applications, DE CT is expected to overcome limitations of standard single-energy CT angiography, including patient exposure to nephrotoxic contrast medium and carcinogenic radiation, insufficient contrast vascular enhancement, interference from metallic and beam-hardening artifacts and severe vessel calcification, and limited tissue characterization and perfusion assessment...
July 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Ashley A Untereiner, Ming Fu, Katalin Módis, Rui Wang, YoungJun Ju, Lingyun Wu
We previously showed that hydrogen sulfide (H2S) upregulates peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α in primary hepatocytes. PGC-1α is a crucial regulator of mitochondrial biogenesis, a process required to maintain cellular energy homeostasis. We investigated the regulation of hepatic mitochondrial biogenesis by cystathionine γ-lyase (CSE)-generated H2S under physiological conditions. Primary hepatocytes isolated from CSE knockout (KO) and wild-type (WT) mice were used in all experiments...
August 31, 2016: Nitric Oxide: Biology and Chemistry
Gréta Varkoly, János Bencze, Tibor Hortobágyi, László Módis
The cornea is the first refractive element of the eye. The transparency of the cornea results from the regularly arranged collagen fibrils, forming lamellar structure and the leucin rich proteoglycans, which make interactions between the fibrils. The adult cornea consists mainly of fibril-forming collagens. The cornea has less amount of fibril associated and non-fibrillar collagens. The main proteoglycans of the cornea are keratan-sulfate proteoglycans and it also contains dermatan-sulfate proteoglycans. Disorders of the proteoglycan synthesis lead to the disruption of the unique pattern and result in thicker collagen fibrils...
June 19, 2016: Orvosi Hetilap
Celia Chao, John R Zatarain, Ye Ding, Ciro Coletta, Amy A Mrazek, Nadiya Druzhyna, Paul Johnson, Haiying Chen, Judy L Hellmich, Antonia Asimakopoulou, Kazunori Yanagi, Gabor Olah, Petra Szoleczky, Gabor Törö, Fredrick J Bohanon, Minal Cheema, Rachel Lewis, David Eckelbarger, Akbar Ahmad, Katalin Módis, Ashley Untereiner, Bartosz Szczesny, Andreas Papapetropoulos, Jia Zhou, Mark R Hellmich, Csaba Szabo
Colon cancer cells contain high levels of cystathionine-beta-synthase (CBS). Its product, hydrogen sulfide (H2S) promotes the growth and proliferation of colorectal tumor cells. In order to improve the antitumor efficacy of the prototypical CBS inhibitor aminooxyacetic acid (AOAA), we designed and synthesized YD0171, a methyl ester derivative of AOAA. The antiproliferative effect of YD0171 exceeded the antiproliferative potency of AOAA in HCT116 human colon cancer cells. The esterase inhibitor paraoxon prevented the cellular inhibition of CBS activity by YD0171...
May 16, 2016: Molecular Medicine
D A Lewis, H O'shea, T K Church, G Brambilla, Daniela Traini, Paul M Young
Pharmacopoeial methods for measurement of the aerodynamic particle size distribution (APSD) of metered dose inhalers (MDIs) by cascade impaction specify a sampling flow rate of 28.3L/min. However, there is little data within the literature to rationalize this figure, or to support its clinical relevance. In addition, the standard United States Pharmacopoeia Induction Port (USP IP) used for testing is known to inaccurately reflect deposition behavior in the upper airway, further compromising the relevance of testing, for product development...
May 19, 2016: International Journal of Pharmaceutics
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