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https://www.readbyqxmd.com/read/28438674/current-state-and-challenges-in-developing-oral-vaccines
#1
REVIEW
Julia E Vela Ramirez, Lindsey A Sharpe, Nicholas A Peppas
While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection...
April 21, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28435447/a-unique-recombinant-fluoroprobe-targeting-activated-platelets-allows-in-vivo-detection-of-arterial-thrombosis-and-pulmonary-embolism-using-a-novel-three-dimensional-fluorescence-emission-computed-tomography-flect-technology
#2
Bock Lim, Yu Yao, Alex Lin-I Huang, May Lin Yap, Ulrike Flierl, Jathushan Palasubramaniam, Maria T K Zaldivia, Xiaowei Wang, Karlheinz Peter
Progress in pharmaceutical development is highly-dependent on preclinical in vivo animal studies. Small animal imaging is invaluable for the identification of new disease markers and the evaluation of drug efficacy. Here, we report for the first time the use of a three-dimensional fluorescence bioimager called FLuorescence Emission Computed Tomography (FLECT) for the detection of a novel recombinant fluoroprobe that is safe, easily prepared on a large scale and stably stored prior to scan. This novel fluoroprobe (Targ-Cy7) comprises a single-chain antibody-fragment (scFvTarg), which binds exclusively to activated-platelets, conjugated to a near-infrared (NIR) dye, Cy7, for detection...
2017: Theranostics
https://www.readbyqxmd.com/read/28429751/preclinical-study-of-raav2-strail-pharmaceutical-efficacy-biodistribution-and-safety-in-animals
#3
Q Ru, W Li, X Wang, S Zhang, L Chen, Y Zhang, Y Ge, Y Zu, Y Liu, D Zheng
The recombinant sTRAIL has been in clinical trial for various human malignancies. However, the half-life time of sTRAIL is very short, which might be an important factor influencing its clinical efficacy for cancer therapy. We previously reported the recombinant adeno-associated virus (AAV)-encoding sTRAIL95-281-mediated sTRAIL expression in vivo up to 8 months and suppressed tumor growth markedly in mouse xenografts. In the present study, we further evaluated the clinical potency for cancer gene therapy and the safety in mouse and non-human primates...
April 21, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28420742/synergistic-internal-ribosome-entry-site-microrna-based-approach-for-flavivirus-attenuation-and-live-vaccine-development
#4
Konstantin A Tsetsarkin, Guangping Liu, Evgeniya Volkova, Alexander G Pletnev
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and expressed under translational control from an IRES...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28412223/bioengineered-robust-hybrid-hydrogels-enrich-the-stability-and-efficacy-of-biological-drugs
#5
Moon Soo Gil, Jinhwan Cho, Thavasyappan Thambi, V H Giang Phan, Inchan Kwon, Doo Sung Lee
Biological drugs are exquisitely tailored components offering the advantages of high specificity and efficacy that are considered safe for treating diseases. Nevertheless, the effectiveness of biological drugs is limited by their inherent short biological half-life and poor stability in vivo. Herein, we engineered a novel delivery platform based on hybrid injectable hydrogels, in which pH- and temperature-responsive biodegradable copolymers were site-specifically coupled to the sulfhydryl group of human serum albumin, which effectively enhances the stability and circulation half-life of the biological drug, recombinant uricase enzyme (Uox)...
April 12, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28407278/prevention-and-treatment-of-complications-of-selective-internal-radiation-therapy-expert-guidance-and-systematic-review
#6
REVIEW
Bruno Sangro, Diego Martínez-Urbistondo, Lourens Bester, Jose I Bilbao, Douglas M Coldwell, Patrick Flamen, Andrew Kennedy, Jens Ricke, Ricky A Sharma
Selective internal radiation therapy (SIRT or radioembolisation) by intraarterial injection of radioactive yttrium-90 ((90) Y)-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source so that its effects are limited to the site of delivery. However the off-target diversion of (90) Y microspheres to tissues other than the tumor may lead to complications. The most prominent ones include: radiation gastritis and gastrointestinal (GI) ulcers, cholecystitis, radiation pneumonitis, and radioembolisation-induced liver disease (REILD)...
April 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28404856/a-dose-dependent-plasma-signature-of-the-safety-and-immunogenicity-of-the-rvsv-ebola-vaccine-in-europe-and-africa
#7
Angela Huttner, Christophe Combescure, Stéphane Grillet, Mariëlle C Haks, Edwin Quinten, Christine Modoux, Selidji Todagbe Agnandji, Jessica Brosnahan, Julie-Anne Dayer, Ali M Harandi, Laurent Kaiser, Donata Medaglini, Tom Monath, Pascale Roux-Lombard, Peter G Kremsner, Tom H M Ottenhoff, Claire-Anne Siegrist
The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28400164/intranasal-and-sublingual-delivery-of-inactivated-polio-vaccine
#8
Heleen Kraan, Peter Soema, Jean-Pierre Amorij, Gideon Kersten
Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains...
May 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28399893/ultrasound-guided-steroid-tendon-sheath-injections-in-juvenile-idiopathic-arthritis-a-10-year-single-center-retrospective-study
#9
Shannon E Peters, Ronald M Laxer, Bairbre L Connolly, Dimitri A Parra
BACKGROUND: The aims of this study were to: (a) Identify tendon sheaths most commonly treated with steroid injections in a pediatric patient population with Juvenile Idiopathic Arthritis (JIA); (b) Describe technical aspects of the procedure; (c) Characterize sonographic appearance of tenosynovitis in JIA; (d) Assess agreement between clinical request and sites injected. METHODS: This was a 10 year single-center retrospective study (May 2006-April 2016) of patients with JIA referred by Rheumatology for ultrasound-guided tendon sheath injections...
April 11, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28379417/subcutaneous-injection-of-testosterone-is-an-effective-and-preferred-alternative-to-intramuscular-injection-demonstration-in-female-to-male-transgender-patients
#10
Daniel I Spratt, India Stewart, Clara Savage, Wendy Craig, Norman P Spack, Donald Walt Chandler, Lindsey V Spratt, Toni Eimicke, Jerrold S Olshan
Context: Testosterone is commonly administered intramuscularly (IM) to treat hypogonadal males and female-to-male transgender (FTM) patients. However, these injections can involve significant discomfort and may require arrangements for administration by others. Objective: We assessed whether T could be administered effectively and safely by the subcutaneously (SC) as an alternative to IM injections. Design: Retrospective cohort study. Setting: Outpatient Reproductive Endocrinology Clinic at an academic medical center...
April 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28378280/efficacy-of-phenyl-quinoline-phenol-derivatives-as-cox-2-inhibitors-an-approach-to-emergent-the-small-molecules-as-the-anti-inflammatory-and-analgesic-therapeutics
#11
A Manikandan, S Ravichandran, K I Sathiyanarayanan, A Sivakumar
2-(4-phenylquinoline-2-yl)phenol derivatives (4a-l) with COX-2 enzyme inhibition, analgesic, anti-inflammatory and antipyretic potentials were executed and reported. From the in vitro COX-2 enzyme inhibition assay, compounds 4 h (IC50 0.026 µM) and 4j (IC50 0.102 µM) were found as most potent COX-2 inhibitors. Consequently, to get more insight into the binding mode with COX-2, compounds 4a-l were docked into the COX-2 (PDB ID: 1CX2) active site. In the Human Red Blood Cells (HRBC) membrane stabilization assay (in vitro anti-inflammatory), compounds 4f (IC50 0...
April 4, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28376315/safety-and-efficacy-of-a-novel-drug-elores-ceftriaxone-sulbactam-disodium-edetate-in-the-management-of-multi-drug-resistant-bacterial-infections-in-tertiary-care-centers-a-post-marketing-surveillance-study
#12
Manu Chaudhary, Mohd Amin Mir, Shiekh Gazalla Ayub
OBJECTIVE: In India, elores (CSE-1034: ceftriaxone+sulbactam+disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of ESBL/MBL infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with ESBL/MBL infections and identify the incidence of adverse events in real clinical settings. METHODS: This PMS study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with CSE-1034...
April 1, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28365225/safety-and-immunogenicity-of-one-versus-two-doses-of-takeda-s-tetravalent-dengue-vaccine-in-children-in-asia-and-latin-america-interim-results-from-a-phase-2-randomised-placebo-controlled-study
#13
Xavier Sáez-Llorens, Vianney Tricou, Delia Yu, Luis Rivera, Suely Tuboi, Pedro Garbes, Astrid Borkowski, Derek Wallace
BACKGROUND: Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4)...
March 29, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28340549/long-term-in-vivo-monitoring-of-adult-derived-human-liver-stem-progenitor-cells-by-bioluminescence-imaging-pet-and-contrast-enhanced-ct
#14
Mei-Ju Hsu, Julie Prigent, Pierre-Edouard Dollet, Joachim Ravau, Lionel Larbanoix, Gaetan Van Simaeys, Anne Bol, Vincent Grégoire, Serge Goldman, Gisèle Deblandre, Mustapha Najimi, Etienne Sokal, Catherine Lombard
Adult-derived human liver stem/progenitor cells (ADHLSCs) have the potential to alleviate liver injury. However, the optimal delivery route and long-term biodistribution of ADHLSCs remains unclear. In this paper, we used a triple fusion reporter system to determine the kinetic differences in the biodistribution of ADHLSCs following intrasplenic (IS) and intrahepatic (IH) administration in SCID-beige mice. ADHLSCs were transduced with a lentiviral vector expressing a triple-fusion reporter comprising renilla luciferase, monomeric red fluorescent protein and truncated HSV-1 thymidine kinase...
March 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28339449/reversal-of-progressive-conscious-disturbance-with-epidural-blood-patch-for-cerebrospinal-fluid-leakage-at-c2-level
#15
Yi-Chen Lai, Yuan-Yi Chia, Wei-Hung Lien
Intracranial hypotension syndrome (IHS) is generally caused by cerebrospinal fluid (CSF) leakage. Complications include bilateral subdural hygroma or haematoma and herniation of the cerebellar tonsils. Epidural blood patch (EBP) therapy is indicated if conservative treatment is ineffective. We reported the case of a 46-year-old man with a history of postural headache and dizziness. The patient was treated with bed rest and daily hydration with 2000 mL of fluid for 2 weeks. However, dizziness and headache did not resolve, and he became drowsy and disoriented with incomprehensible speech...
March 2017: Pain Physician
https://www.readbyqxmd.com/read/28338414/targeted-therapy-of-octreotide-modified-oleanolic-acid-liposomes-to-somatostatin-receptor-overexpressing-tumor-cells
#16
Qianqian Wang, Ruiyan Zhu, Meili Wang, Shanshan Xing, Lei Li, Yuchu He, Weiwei Cao, Dawei Gao
AIM: To prepare and validate the efficacy of a novel targeted drug delivery system - octreotide (Oct)-modified oleanolic acid (OA) liposomes. MATERIALS & METHODS: OA liposomes (OA-L) were prepared by an ethanol injection method. The Oct-modified OA liposomes (O-OA-L) were synthesized and their properties were evaluated. Cellular uptake and competition inhibition studies were performed. RESULTS: The OA vesicles presented satisfactory particles size (100-200 nm), stability and drug release characteristics; their ζ potential was -1...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28331145/modified-marionette-technique-for-laparoscopic-colorectal-surgery
#17
Seiichi Shinji, Hayato Kan, Takeshi Yamada, Michihiro Koizumi, Aya Yamagishi, Yasuyuki Yokoyama, Goro Takahashi, Takuma Iwai, Keisuke Hara, Kohki Takeda, Keiichiro Ohta, Eiji Uchida
INTRODUCTION: Single-port laparoscopic surgery has some technical limitations with respect to control of the forceps inserted through the single-access site, which results in increased internal collisions due to coaxial alignment of the instruments, as well as and decreased range of motion and visualization. To overcome these limitations, we employ a "modified marionette technique" as a way to carry out laparoscopic colorectal surgery. Materials and Surgical Technique: The procedures for the modified marionette technique are performed as follows: An Internal Organ Retractor (IOR)™ and an atraumatic clip designed to firmly grasp tissue, with 1-0 nylon thread, are inserted through a 12-mm trocar and secured in place where adequate visualization and traction for cutting with a radio knife is required...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/28326559/a-phase-1-study-to-evaluate-the-safety-and-ldl-cholesterol-lowering-effects-of-rg7652-a-fully-human-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9
#18
Amos Baruch, Diana Luca, Robert S Kahn, Kyra J Cowan, Maya Leabman, Nageshwar R Budha, Cecilia P C Chiu, Yan Wu, Daniel Kirchhofer, Andrew Peterson, John C Davis, Whittemore G Tingley
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates low-density lipoprotein (LDL) receptors, thereby leading to a rise in circulating LDL cholesterol (LDL-C). RG7652 is a fully human monoclonal antibody against PCSK9. This placebo-controlled, phase 1 ascending-dose study in healthy subjects evaluated the safety of RG7652 and its efficacy as a potential LDL-C-lowering drug. HYPOTHESIS: Anti-PCSK9 antibody therapy safely and effectively reduces LDL-C...
March 22, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28321422/autologous-tenocyte-injection-for-the-treatment-of-chronic-recalcitrant-gluteal-tendinopathy-a-prospective-pilot-study
#19
Thomas A Bucher, Jay R Ebert, Anne Smith, William Breidahl, Michael Fallon, Tao Wang, Ming-Hao Zheng, Gregory C Janes
BACKGROUND: Gluteal tendinopathy is a common cause of lateral hip pain, and existing conservative treatment modalities demonstrate high symptom recurrence rates. Autologous tenocyte injection (ATI) is a promising cell therapy that may be useful for the treatment of gluteal tendinopathy. PURPOSE: To investigate the safety and effectiveness of ATI, specifically in patients with chronic recalcitrant gluteal tendinopathy. STUDY DESIGN: Case series; Level of evidence, 4...
February 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28316066/long-term-results-and-tolerability-of-tandem-peptide-receptor-radionuclide-therapy-with-90-y-177-lu-dotatate-in-neuroendocrine-tumors-with-respect-to-the-primary-location-a-10-year-study
#20
Jolanta Kunikowska, Dariusz Pawlak, Marianna I Bąk, Beata Kos-Kudła, Renata Mikołajczak, Leszek Królicki
INTRODUCTION: The peptide receptor radionuclide therapy (PRRT) with (90)Y and (177)Lu is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET). AIM: The aim of the study was to evaluate clinical results and long-term side effects of tandem (90)Y /(177)Lu-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site. MATERIALS AND METHODS: 59 patients with disseminated NET were included in the study prospectively...
March 18, 2017: Annals of Nuclear Medicine
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