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https://www.readbyqxmd.com/read/28346434/optimization-of-adeno-associated-virus-vector-mediated-gene-transfer-to-the-respiratory-tract
#1
F Kurosaki, R Uchibori, N Mato, Y Sehara, Y Saga, M Urabe, H Mizukami, Y Sugiyama, A Kume
An efficient adeno-associated virus (AAV) vector was constructed for the treatment of respiratory diseases. AAV serotypes, promoters, and routes of administration potentially influencing the efficiency of gene transfer to airway cells were examined in the present study. Among the nine AAV serotypes (AAV1-9) screened in vitro and four serotypes (AAV1, 2, 6, 9) evaluated in vivo, AAV6 showed the strongest transgene expression. As for promoters, the cytomegalovirus (CMV) early enhancer/chicken β-actin (CAG) promoter resulted in more robust transduction than the CMV promoter...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28345745/in-vitro-and-in-vivo-assessment-of-the-abuse-potential-of-pf614-a-novel-bio-md%C3%A2-prodrug-of-oxycodone
#2
D Lynn Kirkpatrick, William K Schmidt, Ricardo Morales, John Cremin, Julie Seroogy, Craig Husfeld, Thomas Jenkins
OBJECTIVE: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28344402/preparation-of-mucosal-nanoparticles-and-polymer-based-inactivated-vaccine-for-newcastle-disease-and-h9n2-ai-viruses
#3
Heba M El Naggar, Mohamed Sayed Madkour, Hussein Ali Hussein
AIM: To develop a mucosal inactivated vaccines for Newcastle disease (ND) and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. MATERIALS AND METHODS: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2) based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens...
February 2017: Veterinary World
https://www.readbyqxmd.com/read/28344017/intranasal-delivery-of-n-terminal-modified-leptin-pluronic-conjugate-for-treatment-of-obesity
#4
Dongfen Yuan, Xiang Yi, Yuling Zhao, Chi-Duen Poon, Kristin M Bullock, Kim M Hansen, Therese S Salameh, Susan A Farr, William A Banks, Alexander V Kabanov
Leptin is an adipocyte-secreted hormone that is delivered via a specific transport system across the blood-brain barrier (BBB) to the brain where it acts on the hypothalamus receptors to control appetite and thermogenesis. Peripheral resistance to leptin due to its impaired brain delivery prevents therapeutic use of leptin in overweight and moderately obese patients. To address this problem, we modified the N-terminal amine of leptin with Pluronic P85 (LepNP85) and administered this conjugate intranasally using the nose-to-brain (INB) route to bypass the BBB...
March 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28333957/immune-response-of-rats-vaccinated-orally-with-various-plant-expressed-recombinant-cysteine-proteinase-constructs-when-challenged-with-fasciola-hepatica-metacercariae
#5
Malgorzata Kesik-Brodacka, Agnieszka Lipiec, Monika Kozak Ljunggren, Luiza Jedlina, Katarzyna Miedzinska, Magdalena Mikolajczak, Andrzej Plucienniczak, Andrzej B Legocki, Halina Wedrychowicz
BACKGROUND: Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica (CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli...
March 23, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28302022/glial-cell-a-potential-target-for-cellular-and-drug-based-therapy-in-various-cns-diseases
#6
Shakeeb Ahmed, Yasmin Sultana, Azka Gull, Tahir Khuroo, Mohd Aqil
Glial cells are integrated part of neurovascular unit of blood brain barrier (BBB). They undergo mitosis and mainly classified as astrocytes, oligodendrocytes, microglia, ependymal cells and nerve glial antigen 2 cells. Being a most versatile glial cell, astrocytes provide structural support to neurons, maintain brain homeostasis, take part in neuronal communication, and perform some housekeeping functions. Oligodendrocytes myelinate the neuronal axons for proper transmission of nerve impulse and microglia are brain immune cells...
March 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28290002/plasma-and-cerebrospinal-fluid-pharmacokinetics-of-select-chemotherapeutic-agents-following-intranasal-delivery-in-a-non-human-primate-model
#7
James C League-Pascual, Cynthia M Lester-McCully, Shaefali Shandilya, Lukas Ronner, Louis Rodgers, Rafael Cruz, Cody J Peer, William D Figg, Katherine E Warren
The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure...
March 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28289281/oxytocin-by-intranasal-and-intravenous-routes-reaches-the-cerebrospinal-fluid-in-rhesus-macaques-determination-using-a-novel-oxytocin-assay
#8
M R Lee, K B Scheidweiler, X X Diao, F Akhlaghi, A Cummins, M A Huestis, L Leggio, B B Averbeck
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28259944/ursolic-acid-nanoparticles-inhibit-cervical-cancer-growth-in-vitro-and-in-vivo-via-apoptosis-induction
#9
Shaoguang Wang, Xiaomei Meng, Yaozhong Dong
Cervical cancer is a cause of cancer death, making it one of the most common causes of death among women globally. Previously, a variety of studies have revealed the molecular mechanisms by which cervical cancer develops. However, there are still limitations in treatment for cervical cancer. Ursolic acid is a naturally derived pentacyclic triterpene acid, exhibiting broad anticancer effects. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions...
February 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28259806/awake-long-term-intranasal-insulin-treatment-does-not-affect-object-memory-odor-discrimination-or-reversal-learning-in-mice
#10
Genevieve A Bell, Debra Ann Fadool
Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm...
March 2, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28259526/review-of-intranasally-administered-medications-for-use-in-the-emergency-department
#11
Abby M Bailey, Regan A Baum, Karolyn Horn, Tameka Lewis, Kate Morizio, Amy Schultz, Kyle Weant, Stephanie N Justice
BACKGROUND: Intranasal (IN) medication delivery is a viable alternative to other routes of administration, including intravenous (IV) and intramuscular (IM) administration. The IN route bypasses the risk of needle-stick injuries and alleviates the emotional trauma that may arise from the insertion of an IV catheter. OBJECTIVE: This review aims to evaluate published literature on medications administered via the IN route that are applicable to practice in emergency medicine...
March 1, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28253982/clinical-aspects-of-glucose-metabolism-and-chronic-disease
#12
J W Culberson
The burden of chronic disease is an emerging world health problem. Advances made in the treatment of individual disease states often fail to consider multimorbidity patterns in clinical research models. Adjusting for age as a confounder ignores its contribution as a powerful risk factor for most chronic diseases. Sarcopenia is an age-related loss of skeletal muscle mass, which is accelerated by chronic inflammation and its resulting cascade of cytokines. Skeletal muscle loss results in insulin resistance, hyperglycemia, and altered mitochondrial glucose signaling pathways...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28248603/cochrane-corner-extracts-from-the-cochrane-library
#13
Richard Orlandi, Clair Hopkins, Carl Philpott, Richard M Rosenfeld
The Cochrane Corner is a section in the journal that highlights systematic reviews relevant to otolaryngology-head and neck surgery, with invited commentary to aid clinical decision making. This installment features a pair of related Cochrane Reviews on intranasal steroids for chronic rhinosinusitis, which identify low- to moderate-quality evidence for a beneficial effect on overall symptoms, nasal congestion, and rhinorrhea. There is no evidence, however, to suggest superiority of any particular steroid preparation or drug delivery system...
March 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28242958/intranasal-delivery-of-mir-146a-mimics-delayed-seizure-onset-in-the-lithium-pilocarpine-mouse-model
#14
Hua Tao, Jianghao Zhao, Tingting Liu, Yujie Cai, Xu Zhou, Huaijie Xing, Yan Wang, Mingkang Yin, Wangtao Zhong, Zhou Liu, Keshen Li, Bin Zhao, Haihong Zhou, Lili Cui
Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28238945/nose-to-brain-transport-of-imatinib-mesylate-a-pharmacokinetic-evaluation
#15
Nobuko Hada, William Joseph Netzer, Fanny Belhassan, Lawrence Paul Wennogle, Sveinbjörn Gizurarson
The delivery of drugs to the brain is a constant challenge due to limitations imposed by the blood-brain barrier (BBB). Various methods of bypassing the BBB are under investigation. One approach is intranasal administration, where the olfactory region of the nasal cavity extends up to the cranial cavity and provides direct access to the brain. The pharmacokinetics of this transport and factors that determine transport rates and capacity is of vital importance for evaluating the clinical value of this route...
February 24, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28228715/central-nervous-insulin-administration-before-nocturnal-sleep-decreases-breakfast-intake-in-healthy-young-and-elderly-subjects
#16
João C P Santiago, Manfred Hallschmid
Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28224119/vesicular-stomatitis-virus-vectored-multi-antigen-tuberculosis-vaccine-limits-bacterial-proliferation-in-mice-following-a-single-intranasal-dose
#17
Ming Zhang, Chunsheng Dong, Sidong Xiong
Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28222522/intranasal-insulin-transport-is-preserved-in%C3%A2-aged-samp8-mice-and-is-altered-by-albumin-and-insulin-receptor-inhibition
#18
Elizabeth M Rhea, Samantha R Humann, Surabhi Nirkhe, Susan A Farr, John E Morley, William A Banks
Insulin delivered to the level of the cribriform plate (intranasal insulin) is being investigated for its ability to enhance memory in people with Alzheimer's disease (AD). Recent work has shown intranasal insulin can be detected in young CD-1 mice within 5 min and is still present 60 min after injection. The current study determined whether intranasal insulin transport and the subsequent brain distribution of insulin varies in young, healthy mice (CD-1) compared to those with an AD-like phenotype (aged SAMP8) or those pre-disposed to develop such a phenotype (young SAMP8)...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28214044/enhancement-of-antigen-specific-cd4-and-cd8-t-cell-responses-using-a-self-assembled-biologic-nanolipoprotein-particle-vaccine
#19
Dina Weilhammer, Alexis D Dunkle, Craig D Blanchette, Nicholas O Fischer, Michele Corzett, Doerte Lehmann, Tyler Boone, Paul Hoeprich, Adam Driks, Amy Rasley
To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. We utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4(+) and CD8(+) T cells in vitro compared to co-administration of free OVA and MPLA...
February 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28174292/hypothalamic-and-striatal-insulin-action-suppresses-endogenous-glucose-production-and-may-stimulate-glucose-uptake-during-hyperinsulinemia-in-lean-but-not-in-overweight-men
#20
Martin Heni, Robert Wagner, Stephanie Kullmann, Sofiya Gancheva, Michael Roden, Andreas Peter, Norbert Stefan, Hubert Preissl, Hans Ulrich Häring, Andreas Fritsche
Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive.Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with D-[6,6-(2)H2]-glucose infusion to measure endogenous glucose production and glucose disappearance. On two days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an iv insulin bolus on placebo day...
February 7, 2017: Diabetes
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