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https://www.readbyqxmd.com/read/27877030/application-of-a-diagnostic-algorithm-for-the-rare-deficient-variant-mmalton-of-alpha-1-antitrypsin-deficiency-a-new-approach
#1
Irene Belmonte, Miriam Barrecheguren, Rosa M López-Martínez, Cristina Esquinas, Esther Rodríguez, Marc Miravitlles, Francisco Rodríguez-Frías
BACKGROUND AND OBJECTIVES: Alpha-1-antitrypsin deficiency (AATD) is associated with a high risk for the development of early-onset emphysema and liver disease. A large majority of subjects with severe AATD carry the ZZ genotype, which can be easily detected. Another rare pathologic variant, the Mmalton allele, causes a deficiency similar to that of the Z variant, but it is not easily recognizable and its detection seems to be underestimated. Therefore, we have included a rapid allele-specific genotyping assay for the detection of the Mmalton variant in the diagnostic algorithm of AATD used in our laboratory...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27871846/the-oxidant-antioxidant-equilibrium-activities-of-selected-lysosomal-enzymes-and-activity-of-acute-phase-protein-in-peripheral-blood-of-18-year-old-football-players-after-aerobic-cycle-ergometer-test-combined-with-ice-water-immersion-or-recovery-at-room-temperature
#2
Paweł Sutkowy, Alina Woźniak, Tomasz Boraczyński, Michał Boraczyński, Celestyna Mila-Kierzenkowska
The goal of the study was to evaluate the effect of an aerobic exercise bout followed by ice-water immersion or recovery at room temperature on the redox state, activities of selected lysosomal enzymes and activity of α1-antitrypsin (AAT) in the blood of healthy sportsmen. Eleven amateur football players aged 18 were randomly assigned to two similar 30-min aerobic cycle ergometer tests followed by a recovery at room temperature (20 °C; Experiment 1) or ice-water immersion (3 °C, 5 min; Experiment 2). Peripheral blood was collected three times during both study experiments: before (baseline), as well as 20 and 40 min after the recovery or immersion...
November 18, 2016: Cryobiology
https://www.readbyqxmd.com/read/27857848/the-effect-of-%C3%AE-1-antitrypsin-deficiency-combined-with-increased-bacterial-loads-on-chronic-obstructive-pulmonary-disease-pharmacotherapy-a-prospective-parallel-controlled-pilot-study
#3
Marwa G Hennawy, Noha M Elhosseiny, Hussein Sultan, Wael Abdelfattah, Yousry Akl, Nirmeen A Sabry, Ahmed S Attia
Chronic obstructive pulmonary disease (COPD) is caused by α1-antitrypsin deficiency (AATD) genetic susceptibility and exacerbated by infection. The current pilot study aimed at studying the combined effect of AATD and bacterial loads on the efficacy of COPD conventional pharmacotherapy. Fifty-nine subjects (29 controls and 30 COPD patients) were tested for genetic AATD and respiratory function. The bacterial loads were determined to the patients' group who were then given a long acting beta-agonist and corticosteroid inhaler for 6 months...
November 2016: Journal of Advanced Research
https://www.readbyqxmd.com/read/27855487/transfer-of-therapeutic-genes-into-fetal-rhesus-monkeys-using-recombinant-adeno-associated-type-i-viral-vectors
#4
Thomas J Conlon, Cathryn S Mah, Christina A R Pacak, Mary B Rucker Henninger, Kirsten E Erger, Marda L Jorgensen, Charles C Lee, Alice F Tarantal, Barry J Byrne
Neuromuscular disorders such as Pompe disease (glycogen storage disease, type II), result in early and potentially irreversible cellular damage with a very limited opportunity for intervention in the newborn period. Pompe disease is due to deficiency in acid α-glucosidase (GAA) leading to lysosomal accumulation of glycogen in all cell types, abnormal myofibrillogenesis, respiratory insufficiency, neurological deficits, and reduced contractile function in striated muscle. Previous studies have shown that fetal delivery of recombinant adeno-associated virus (rAAV) encoding GAA to the peritoneal cavity of Gaa-/- mice resulted in high-level transduction of the diaphragm...
November 17, 2016: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/27827549/advances-in-identifying-urine-serum-biomarkers-in-alpha-1-antitrypsin-deficiency-for-more-personalized-future-treatment-strategies
#5
Ilaria Ferrarotti, Angelo Guido Corsico, Jan Stolk, Stefania Ottaviani, Marco Fumagalli, Sabina Janciauskiene, Paolo Iadarola
Alpha1-antitrypsin deficiency (AATD) is a genetic disorder characterized by reduced serum levels of alpha1-antitrypsin (AAT) and increased risk for developing both early-onset lung emphysema and chronic liver disease. Laboratory diagnosis of AATD is not just a matter of degree, although the AAT serum level is the most important determinant for risk of lung damage. While being a single-gene disease, the clinical phenotype of AATD is heterogeneous. The current standard of care for patients affected by AATD-associated pulmonary emphysema is replacement therapy with weekly i...
November 9, 2016: COPD
https://www.readbyqxmd.com/read/27824883/biomarkers-of-environmental-enteropathy-are-positively-associated-with-immune-responses-to-an-oral-cholera-vaccine-in-bangladeshi-children
#6
Muhammad Ikhtear Uddin, Shahidul Islam, Naoshin S Nishat, Motaher Hossain, Tanzeem Ahmed Rafique, Rasheduzzaman Rashu, Mohammad Rubel Hoq, Yue Zhang, Amit Saha, Jason B Harris, Stephen B Calderwood, Taufiqur Rahman Bhuiyan, Edward T Ryan, Daniel T Leung, Firdausi Qadri
Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27821710/exploration-of-%C3%AE-1-antitrypsin-treatment-protocol-for-islet-transplantation-dosing-plan-and-route-of-administration
#7
Boris M Baranovski, Eyal Ozeri, Galit Shahaf, David E Ochayon, Ronen Schuster, Nofar Bahar, Noa Kalay, Pablo Cal, Mark I Mizrahi, Omer Nisim, Pnina Strauss, Eran Schenker, Eli C Lewis
Life-long weekly infusions of human α1-antitrypsin (hAAT) are currently administered as augmentation therapy for patients with genetic AAT deficiency (AATD). Several recent clinical trials attempt to extend hAAT therapy to conditions outside AATD, including type 1 diabetes. Since the endpoint for AATD is primarily the reduction of risk for pulmonary emphysema, the present study explores hAAT dose protocols and routes of administration in attempt to optimize hAAT therapy for islet-related injury. Islet-grafted mice were treated with hAAT (Glassia™; i...
November 7, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27818805/hepatocellular-carcinoma-with-prominent-intracytoplasmic-inclusions-a-report-of-two-cases
#8
Adeline R Chelliah, Jasim M Radhi
Hepatocellular carcinoma (HCC) is the commonest primary malignant neoplasm of the liver in most countries with a notoriously poor prognosis. Variation in global incidence is well-recognized and the occurrence of HCC is linked to several established environmental, dietary, and lifestyle factors. HCC demonstrates morphological heterogeneity both within the same tumor and from patient to patient. Differing architectural patterns and cytological variants may be seen. Inclusion bodies are believed to represent organized structures of proteins which contribute to their pathogenesis and share several constituents like chaperones, p62, ubiquitin, and Valosin containing protein...
2016: Case Reports in Hepatology
https://www.readbyqxmd.com/read/27816594/electrochemical-sandwich-type-biosensors-for-%C3%AE-1-antitrypsin-with-carbon-nanotubes-and-alkaline-phosphatase-labeled-antibody-silver-nanoparticles
#9
Gangbing Zhu, Hye Jin Lee
A novel sandwich-type biosensor was developed for the electrochemical detection of α-1 antitrypsin (AAT, a recognized biomarker for Alzheimer's disease). The biosensor was composed of 3, 4, 9, 10-perylene tetracarboxylic acid/carbon nanotubes (PTCA-CNTs) as a sensing platform and alkaline phosphatase-labeled AAT antibody functionalized silver nanoparticles (ALP-AAT Ab-Ag NPs) as a signal enhancer. CNTs offer high surface area and good electrical conductivity. Importantly, Ag NPs could increase the amount of ALP on the sensing surface and the ALP could dephosphorylate 4-amino phenyl phosphate (APP) enzymatically to produce electroactive species 4-aminophenol (AP)...
September 25, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27812629/prevalence-of-alpha-1-antitrypsin-deficiency-and-allele-frequency-in-patients-with-copd-in-brazil
#10
Rodrigo Russo, Laura Russo Zillmer, Oliver Augusto Nascimento, Beatriz Manzano, Ivan Teruaki Ivanaga, Leandro Fritscher, Fernando Lundgren, Marc Miravitlles, Heicilainy Del Carlos Gondim, Gildo Santos, Marcela Amorim Alves, Maria Vera Oliveira, Altay Alves Lino de Souza, Maria Penha Uchoa Sales, José Roberto Jardim
Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping...
September 2016: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
https://www.readbyqxmd.com/read/27802778/transplantation-of-adipose-tissue-derived-mesenchymal-stem-cell-atmsc-expressing-alpha-1-antitrypsin-reduces-bone-loss-in-ovariectomized-osteoporosis-mice
#11
Mohammad Ahsanul Akbar, Yuanqing Lu, Ahmed S Elshikha, Mong-Jen Chen, Yuan Ye, Elizabeth M Whitley, Lexie Shannon Holliday, Chang Lung-Ji, Sihong Song
Osteoporosis is a common health problem severely affecting the life quality of many people, especially women. Current treatment options for osteoporosis are limited due to their association with several side-effects and moderate efficacy. Therefore, novel therapies for osteoporosis are needed. In this study, we tested the feasibility of adipose tissue-derived mesenchymal stem cell (ATMSC) based human AAT (hAAT) gene therapy for the prevention of bone loss in an ovariectomized (OVX) mouse model. Eight-week-old female C57BL6 mice underwent ovariectomy and treated with hAAT (protein therapy), ATMSC (stem cell therapy), ATMSC+hAAT (combination of ATMSC and hAAT therapy), ATMSCs infected with lentiviral vectors expressing hAAT (ATMSC based hAAT gene therapy)...
November 1, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27800527/improving-antimicrobial-stewardship-by-antibiotic-allergy-delabeling-evaluation-of-knowledge-attitude-and-practices-throughout-the-emerging-infections-network
#12
Jason A Trubiano, Susan E Beekmann, Leon J Worth, Philip M Polgreen, Karin A Thursky, Monica A Slavin, M Lindsay Grayson, Elizabeth J Phillips
Antibiotic allergy testing (AAT) practices of Emerging Infections Network infectious disease physicians were surveyed. Although AAT was perceived to be necessary for removal of inappropriate or unnecessary allergy labels, there was limited access to any form of testing. In this study, we discuss current antibiotic allergy knowledge gaps and the development of AAT practices within antimicrobial stewardship programs, which will potentially improve antimicrobial prescribing.
September 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27792648/sulfur-dioxide-protects-against-collagen-accumulation-in-pulmonary-artery-in-association-with-downregulation-of-the-transforming-growth-factor-%C3%AE-1-smad-pathway-in-pulmonary-hypertensive-rats
#13
Wen Yu, Die Liu, Chen Liang, Todd Ochs, Stella Chen, Selena Chen, Shuxu Du, Chaoshu Tang, Yaqian Huang, Junbao Du, Hongfang Jin
BACKGROUND: We aimed to explore the role of endogenous sulfur dioxide (SO2) in pulmonary vascular collagen remodeling induced by monocrotaline and its mechanisms. METHODS AND RESULTS: A rat model of monocrotaline-induced pulmonary vascular collagen remodeling was developed and administered with l-aspartate-β-hydroxamate or SO2 donor. The morphology of small pulmonary arteries and collagen metabolism were examined. Cultured pulmonary arterial fibroblasts stimulated by transforming growth factor β1 (TGF-β1) were used to explore the mechanism...
October 17, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27770734/downregulated-endogenous-sulfur-dioxide-aspartate-aminotransferase-pathway-is-involved-in-angiotensin-ii-stimulated-cardiomyocyte-autophagy-and-myocardial-hypertrophy-in-mice
#14
Qinghua Chen, Lulu Zhang, Siyao Chen, Yaqian Huang, Kun Li, Xiaoqi Yu, Huijuan Wu, Xiaoyu Tian, Chunyu Zhang, Chaoshu Tang, Junbao Du, Hongfang Jin
BACKGROUND: The study was designed to investigate if endogenous sulfur dioxide (SO2) was involved in cardiomyocyte autophagy and myocardial hypertrophy stimulated by angiotensin II (Ang II). METHODS: Thirty-two C57 mice were randomly divided into control, SO2, Ang II and Ang II+SO2 groups. Human myocardial cell line H9c2 was divided into four groups including control, SO2, Ang II and Ang II+SO2 groups. Blood pressure and myocardial hypertrophy of the mice were measured two weeks after Ang II administration...
September 30, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27754421/assessment-of-amino-acid-drug-transporters-for-renal-transport-of-18-f-fluciclovine-anti-18-f-facbc-in-vitro
#15
Masahiro Ono, Atsumi Baden, Hiroyuki Okudaira, Masato Kobayashi, Keiichi Kawai, Shuntaro Oka, Hirokatsu Yoshimura
[(18)F]Fluciclovine (trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid; anti-[(18)F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97-230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [(18)F]fluciclovine reuptake. [(14)C]Fluciclovine (trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid) was used because of its long half-life...
October 14, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27739542/quantitative-analysis-of-protease-recognition-by-inhibitors-in-plasma-using-microscale-thermophoresis
#16
T Dau, E V Edeleva, S A I Seidel, R A Stockley, D Braun, D E Jenne
High abundance proteins like protease inhibitors of plasma display a multitude of interactions in natural environments. Quantitative analysis of such interactions in vivo is essential to study diseases, but have not been forthcoming, as most methods cannot be directly applied in a complex biological environment. Here, we report a quantitative microscale thermophoresis assay capable of deciphering functional deviations from in vitro inhibition data by combining concentration and affinity measurements. We obtained stable measurement signals for the substrate-like interaction of the disease relevant inhibitor α-1-antitrypsin (AAT) Z-variant with catalytically inactive elastase...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721913/role-of-endogenous-sulfur-dioxide-in-regulating-vascular-structural-remodeling-in-hypertension
#17
Jia Liu, Yaqian Huang, Selena Chen, Chaoshu Tang, Hongfang Jin, Junbao Du
Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27720264/aats-2016-ethics-forum-working-virtues-in-surgical-practice
#18
Larry R Churchill
Moral virtues are the complement to ethical principles. They constitute the elements of character that drive habits and daily routines. Certain virtues are especially important in surgery, shaping surgical practice even when no big decisions are at hand. Eight virtues are described and the work they do is explored: trustworthiness, equanimity, empathy, advocacy, compassion, courage, humility, and hope.
September 17, 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27701692/-alpha-1-antitrypsin-deficiency-an-update
#19
Nikolas Bernhard, Robert Bals, Sebastian Fähndrich
Alpha-1-antitrypsin deficiency is a genetic risk factor for the development of chronic obstructive airway disease (COPD) and liver cirrhosis. The disease is widely underdiagnosed. The hallmarks of therapy are smoking cessation, prevention from environmental dust exposure and augmentation therapy. Findings from the recently published prospective, placebo-controlled and randomized RAPID trial proved effectiveness of AAT augmentation therapy for slowing progression of emphysema, measured by CT lung density. CT lung density may be more sensitive than forced exspiratory volume in one second (FEV1) or monoxid diffusion capacity (DLCO)...
September 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27698942/optimization-of-early-response-monitoring-and-prediction-of-cancer-antiangiogenesis-therapy-via-noninvasive-pet-molecular-imaging-strategies-of-multifactorial-bioparameters
#20
Xiao Bao, Ming-Wei Wang, Jian-Min Luo, Si-Yang Wang, Yong-Ping Zhang, Ying-Jian Zhang
Objective: Antiangiogenesis therapy (AAT) has provided substantial benefits regarding improved outcomes and survival for suitable patients in clinical settings. Therefore, the early definition of therapeutic effects is urgently needed to guide cancer AAT. We aimed to optimize the early response monitoring and prediction of AAT efficacy, as indicated by the multi-targeted anti-angiogenic drug sunitinib in U87MG tumors, using noninvasive positron emission computed tomography (PET) molecular imaging strategies of multifactorial bioparameters...
2016: Theranostics
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