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https://www.readbyqxmd.com/read/29778822/formulation-techniques-for-high-dose-dry-powders
#1
Ashlee D Brunaugh, Hugh D C Smyth
Delivery of drugs to the lungs via dry powder inhaler (DPI) is a promising approach for the treatment of both local pulmonary conditions and systemic diseases. Though DPIs are widely used for the pulmonary deposition of potent bronchodilators, anticholinergics, and corticosteroids, there is growing interest in the utilization of this delivery system for the administration of high drug doses to the lungs, as made evident by recent regulatory approvals for anti-microbial, anti-viral and osmotic agents. However, the formulation of high dose DPIs carries several challenges from both a physiological and physicochemical standpoint...
May 17, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29778602/structure-guided-combinatorial-engineering-facilitates-affinity-and-specificity-optimization-of-anti-cd81-antibodies
#2
Bryce Nelson, Jarrett Adams, Andreas Kuglstatter, Zhijian Li, Seth F Harris, Yang Liu, Sandya Bohini, Han Ma, Klaus Klumpp, Junjun Gao, Sachdev S Sidhu
Hepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block Hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop (LEL) in order to guide affinity maturation of two distinct antibodies by phage display...
May 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29778179/recombinant-adenovirus-delivered-soluble-cd163-and-sialoadhesin-receptors-protected-pigs-from-porcine-reproductive-and-respiratory-syndrome-virus-infection
#3
Wenlong Xia, Zhi Wu, Changming Guo, Shanyuan Zhu, Xinyu Zhang, Xiaoli Xia, Huaichang Sun
Porcine reproductive and respiratory syndrome (PRRS) is one of the most important swine diseases affecting pig industry worldwide. Sialoadehesin (Sn) and CD163 are the two specific receptors for PRRSV infection of porcine alveolar macrophages. Our previous study showed that the soluble Sn receptor Sn4D-Fc and soluble CD163 receptor SRCR59-Fc expressed by the two recombinant adenoviral (rAd) vectors have an additive anti-PRRSV effect in vitro. In the present study, rAd-Sn4D-Fc and rAd-SRCR59-Fc were inoculated into pigs, and the efficient expression of Sn4D-Fc and SRCR59-Fc proteins was detected by ELISA...
June 2018: Veterinary Microbiology
https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#4
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29777445/a-reverse-genetics-system-for-enterovirus-d68-using-human-rna-polymerase-i
#5
Minglei Pan, Shuai Gao, Zhenwei Zhou, Keke Zhang, Sihua Liu, Zhiyun Wang, Tao Wang
Human enterovirus D68 (EV-D68) is a highly contagious virus, which causes respiratory tract infections. However, no effective vaccines are currently available for controlling EV-D68 infection. Here, we developed a reverse genetics system to recover EV-D68 minireplicons and infectious EV-D68 from transfected plasmids using the RNA polymerase I (Pol I) promoter. The EV-D68 minireplicons contained the luciferase reporter gene, which flanked by the non-coding regions of the EV-D68 RNA. The luciferase signals could be detected in cells after transfection and Pol I promoter-mediated luciferase signal was significantly stronger than that mediated by the T7 promoter...
May 17, 2018: Virus Genes
https://www.readbyqxmd.com/read/29775725/anti-hepatitis-c-virus-activity-and-synergistic-effect-of-nymphaea-alba-extracts-and-bioactive-constituents-in-liver-infected-cells
#6
Sidra Rehman, Usman Ali Ashfaq, Bushra Ijaz, Sheikh Riazuddin
BACKGROUND: Without an effective vaccine, hepatitis C virus (HCV) remains a global threat, inflicting 170-300 million carriers worldwide at risk of cirrhosis and hepatocellular carcinoma (HCC). Though various direct acting antivirals have been redeemed the hepatitis C treatment, a few restraints persist including possible side effects, viral resistance emergence, excessive cost which restricts its availability to a common person. HYPOTHESIS: There is no preventive HCV vaccine available today so the discovery of potent antiviral natural flora and their bioactive constituents may help to develop preventive cures against HCV infection...
May 15, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29774454/analysis-of-three-ultrasound-elastography-techniques-for-grading-liver-fibrosis-in-patients-with-chronic-hepatitis-b
#7
Xinping Ren, Shujun Xia, Zhongxin Ni, Weiwei Zhan, Jianqiao Zhou
BACKGROUND: Evaluation of liver fibrosis is important to assess prognosis and guide the treatment for chronic hepatitis B. OBJECTIVE: To analyze and compare transient, point, and two-dimensional (2D) shear wave elastography techniques in grading the liver fibrosis. METHODS: Based on the severity of liver inflammation and fibrosis (Scheuer criteria), 158 patients with chronic hepatitis B were assigned into group 1 (either G or S classification < 2) or group 2 (either G or S classification ≥ 2)...
May 17, 2018: La Radiologia Medica
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#8
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29773661/phase-i-study-of-oncolytic-vaccinia-virus-gl-onc1-in-patients-with-peritoneal-carcinomatosis
#9
Ulrich M Lauer, Martina Schell, Julia Beil, Susanne Berchtold, Ursula Koppenhöfer, Jörg Glatzle, Alfred Königsrainer, Robert Möhle, Dominik Nann, Falko Fend, Christina Pfannenberg, Michael Bitzer, Nisar P Malek
OBJECTIVE: Peritoneal carcinomatosis (PC) is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Since current therapies are mostly ineffective, new thera-peutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and anti-tumor activity of intra-peri-toneal (i.p.) administration of oncolytic vaccinia virus GL-ONC1 in advanced stage PC patients. DESIGN: GL-ONC1 was administered i...
May 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29773094/replication-and-pathology-of-duck-influenza-virus-subtype-h9n2-in-chukar
#10
Yin Chuan Zhu, Bin Zhang, Zeng Hui Sun, Xi Jing Wang, Xiao Hui Fan, Ling Xi Gao, Ying Liang, Xiao Yan Chen, Zeng Feng Zhang
To investigate the susceptibility of Chukars to duck avian influenza virus H9N2 and explore their role in interspecies transmission of influenza viruses. Chukars were inoculated with duck avian influenza viruses H9N2. The present study demonstrated that inflammatory lesions and virus antigen were present in the trachea, bronchus, and parabronchus, and the viruses could be isolated from throat swabs and lung tissue homogenate supernatants. At 14 d post virus inoculation, anti-H9 influenza virus antibody in the serum was detected...
April 2018: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29772748/drug-delivery-strategies-for-antivirals-against-hepatitis-b-virus
#11
REVIEW
Latavia Singh, Sunaina Indermun, Mershen Govender, Pradeep Kumar, Lisa C du Toit, Yahya E Choonara, Viness Pillay
Chronic hepatitis B virus (HBV) infection poses a significant health challenge due to associated morbidity and mortality from cirrhosis and hepatocellular cancer that eventually results in the breakdown of liver functionality. Nanotechnology has the potential to play a pivotal role in reducing viral load levels and drug-resistant HBV through drug targeting, thus reducing the rate of evolution of the disease. Apart from tissue targeting, intracellular delivery of a wide range of drugs is necessary to exert a therapeutic action in the affected organelles...
May 17, 2018: Viruses
https://www.readbyqxmd.com/read/29772664/the-cholinergic-anti-inflammatory-response-and-the-role-of-macrophages-in-hiv-induced-inflammation
#12
REVIEW
Manuel Delgado-Vélez, José A Lasalde-Dominicci
Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) in macrophages led to the establishment of the cholinergic anti-inflammatory response (CAR) in which the activation of this receptor inactivates macrophage production of proinflammatory cytokines...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29770055/hepatitis-a-virus-infection-associated-with-cannabis-use
#13
C Sikora, G Tipples, X-L Pang, A Andonov
We identified a case of acute Hepatitis A virus (HAV) infection linked to cannabis use. The local Public Health department received report of a man in his mid-20s with a classic presentation of hepatitis - jaundice, abdominal pain, vomiting, general malaise, and dark urine - as well as elevated serum aminotransferase levels and a positive anti-HAV IgM. Upon questioning, he reported no contact with ill individuals, or travel outside his metropolitan area. His exclusive source of water was the local municipal supply...
November 2, 2017: Canada Communicable Disease Report, Relevé des Maladies Transmissibles Au Canada
https://www.readbyqxmd.com/read/29769725/mxra8-is-a-receptor-for-multiple-arthritogenic-alphaviruses
#14
Rong Zhang, Arthur S Kim, Julie M Fox, Sharmila Nair, Katherine Basore, William B Klimstra, Rebecca Rimkunas, Rachel H Fong, Hueylie Lin, Subhajit Poddar, James E Crowe, Benjamin J Doranz, Daved H Fremont, Michael S Diamond
Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769339/differential-responses-by-human-respiratory-epithelial-cell-lines-to-respiratory-syncytial-virus-reflect-distinct-patterns-of-infection-control
#15
Philippa Hillyer, Rachel Shepard, Megan Uehling, Mina Krenz, Faruk Sheikh, Kalyn R Thayer, Lei Huang, Lihan Yan, Debasis Panda, Cindy Luongo, Ursula J Buchholz, Peter L Collins, Raymond P Donnelly, Ronald L Rabin
RSV infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of types I and III interferons (IFNs) and pro-inflammatory cytokines, the balance of which may restrict viral replication and affect disease severity. We explored this balance by infecting two respiratory epithelial cell lines with low doses of recombinant RSV expressing green fluorescent protein (rgRSV). A549 cells were highly permissive whereas BEAS-2B cells restricted infection to individual cells or small foci...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769087/replacement-of-feline-foamy-virus-bet-by-feline-immunodeficiency-virus-vif-yields-replicative-virus-with-novel-vaccine-candidate-potential
#16
Carmen Ledesma-Feliciano, Sarah Hagen, Ryan Troyer, Xin Zheng, Esther Musselman, Dragana Slavkovic Lukic, Ann-Mareen Franke, Daniel Maeda, Jörg Zielonka, Carsten Münk, Guochao Wei, Sue VandeWoude, Martin Löchelt
BACKGROUND: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29769036/estimates-of-state-level-chronic-hepatitis-c-virus-infection-stratified-by-race-and-sex-united-states-2010
#17
Eric W Hall, Eli S Rosenberg, Patrick S Sullivan
BACKGROUND: Hepatitis C virus (HCV) is the most common blood-borne viral infection in the United States. Previously, we used data from the National Health and Nutrition Examination Survey (NHANES) and mortality data from the National Vital Statistics System (NVSS) to estimate the prevalence of HCV antibodies (anti-HCV) and HCV RNA among all U.S. states. However, demographic differences in HCV burden at the state-level have not been systematically described. This analysis quantified the HCV burden stratified by sex and race (and associated disparities) for each U...
May 16, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29768944/zataria-multiflora-essential-oil-reduces-replication-rate-of-avian-influenza-virus-h9n2-subtype-in-challenged-broiler-chicks
#18
Arzhang Shayeganmehr, Mehdi Vasfi Marandi, Vahid Karimi, Abbas Barin, Arash Ghalyanchi-Langeroudi
The effect of Zataria multiflora essential oil on replication rate of the H9N2 virus in target organs was determined by real-time PCR. One-day-old broiler chicks were randomly divided into six groups and were challenged with H9N2 influenza. Two groups received either 20 or 40 µl/kg body weight/day Zataria multiflora essential oils (ZM) seven days before the challenge while two other groups received the essential oil at the same dosage but after H9N2 challenge. One group received 4 mg/kg body weight/day of the anti-viral compound amantadine after challenge and the last group received no treatment and served as the control...
May 17, 2018: British Poultry Science
https://www.readbyqxmd.com/read/29768691/detection-of-hepatitis-b-virus-dna-among-chronic-and-potential-occult-hbv-patients-in-resource-limited-settings-by-loop-mediated-isothermal-amplification-assay
#19
Arifa Akram, S M Rashedul Islam, Saif Ullah Munshi, Shahina Tabassum
Transmission of Hepatitis B Virus (HBV) usually occurs due to the transfusion of blood or blood products from chronic HBV (CHB) or occult HBV infected (OBI) patients. Besides serological tests e.g. HBsAg and anti-HBc (total), detection of HBV-DNA is necessary for the diagnosis of OBI patients. Different nucleic acid tests (NATs) including real-time-Polymerase Chain Reaction (qPCR) are used for the detect HBV-DNA. The NATs are expensive and require technical expertise which are barriers to introducing them in resource-limited settings...
May 16, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29768180/dietary-fiber-confers-protection-against-flu-by-shaping-ly6c-patrolling-monocyte-hematopoiesis-and-cd8-t-cell-metabolism
#20
Aurélien Trompette, Eva S Gollwitzer, Céline Pattaroni, Isabel C Lopez-Mejia, Erika Riva, Julie Pernot, Niki Ubags, Lluis Fajas, Laurent P Nicod, Benjamin J Marsland
Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c- patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways...
May 15, 2018: Immunity
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