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https://www.readbyqxmd.com/read/28430000/neuroprotective-and-regenerative-roles-of-intranasal-wnt-3a-administration-after-focal-ischemic-stroke-in-mice
#1
Zheng Zachory Wei, James Ya Zhang, Tammi M Taylor, Xiaohuan Gu, Yingying Zhao, Ling Wei
Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28416501/protocol-for-a-placebo-controlled-within-participants-crossover-trial-evaluating-the-efficacy-of-intranasal-oxytocin-to-improve-pain-and-function-among-women-with-chronic-pelvic-musculoskeletal-pain
#2
Joshua A Rash, Kirsti Toivonen, Magali Robert, Maryam Nasr-Esfahani, John F Jarrell, Tavis S Campbell
INTRODUCTION: This protocol presents the rationale and design for a trial evaluating the efficacy of intranasal oxytocin in improving pain and function among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide traditionally recognised for involvement in labour, delivery and lactation. Novel evidence suggests that oxytocin decreases pain sensitivity in humans. While oxytocin administration has been reported to lower pain sensitivity among patients experiencing chronic back pain, headache, constipation and colon pain, no research has evaluated the association between intranasal oxytocin and chronic pelvic musculoskeletal pain...
April 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/28400164/intranasal-and-sublingual-delivery-of-inactivated-polio-vaccine
#3
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...
April 8, 2017: Vaccine
https://www.readbyqxmd.com/read/28386312/alleviation-of-oxidative-damage-and-involvement-of-nrf2-are-pathway-in-mesodopaminergic-system-and-hippocampus-of-status-epilepticus-rats-pretreated-by-intranasal-pentoxifylline
#4
Yunxiao Kang, Wensheng Yan, Hui Fang, Guoliang Zhang, Yakun Du, Lei Wang, Huixian Cui, Geming Shi
The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28382978/long-term-treatment-with-intranasal-insulin-ameliorates-cognitive-impairment-tau-hyperphosphorylation-and-microglial-activation-in-a-streptozotocin-induced-alzheimer-s-rat-model
#5
Zhangyu Guo, Yanxing Chen, Yan-Fang Mao, Tingting Zheng, Yasi Jiang, Yaping Yan, Xinzhen Yin, Baorong Zhang
Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer's disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381402/transcutaneous-immunization-with-a-bandaid-prevents-experimental-otitis-media-in-a-polymicrobial-model
#6
Laura A Novotny, John D Clements, Steven D Goodman, Lauren O Bakaletz
Otitis media (OM) is a common pediatric disease and nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic OM, recurrent OM and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an upper respiratory tract viral infection predisposes to ascension of NTHI from the nasopharynx, the site of colonization, to the normally sterile middle ear, resulting in disease. Using a clinically relevant viral-bacterial co-infection model of NTHI-induced OM, we performed transcutaneous immunization (TCI) via a bandaid delivery system to administer each of three promising NTHI vaccine candidates derived from bacterial adhesive proteins and biofilm mediators: rsPilA, chimV4 and integration host factor...
April 5, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28372335/effects-of-regular-and-long-acting-insulin-on-cognition-and-alzheimer-s-disease-biomarkers-a-pilot-clinical-trial
#7
Suzanne Craft, Amy Claxton, Laura D Baker, Angela J Hanson, Brenna Cholerton, Emily H Trittschuh, Deborah Dahl, Erin Caulder, Bryan Neth, Thomas J Montine, Youngkyoo Jung, Joseph Maldjian, Christopher Whitlow, Seth Friedman
BACKGROUND: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. OBJECTIVE: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD...
March 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28364244/intranasal-delivery-of-peptide-morpholinos-to-knockdown-influenza-host-factors-in-mice
#8
Ricardo Rajsbaum
Influenza viruses replicate primarily in the lung tissue of different host species. For efficient replication the virus utilizes host factors that are expressed in target cells. Cell-penetrating peptide-conjugated Morpholino oligomers (PPMOs) designed to target viral proteins have shown promising results as potential antiviral drugs in tissue culture and animal models. However, since viruses tend to have high rates of mutations, targeting viral proteins may result in viral escape mutants. An alternative approach to inhibit virus replication with PPMOs is to target host factors that are required for virus replication...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28363190/nose-to-brain-delivery-in-rats-effect-of-surface-charge-of-rhodamine-b-labeled-nanocarriers-on-brain-subregion-localization
#9
A Bonaccorso, T Musumeci, M F Serapide, R Pellitteri, I F Uchegbu, G Puglisi
Nose to brain delivery and nanotechnology are the combination of innovative strategies for molecules to reach the brain and to bypass blood brain barriers. In this work we investigated the fate of two rhodamine B labeled polymeric nanoparticles (Z-ave <250nm) of opposite surface charge in different areas of the brain after intranasal administration in rats. A preliminary screening was carried out to select the suitable positive (chitosan/poly-l-lactide-co-glycolide) nanocarrier through photon correlation spectroscopy and turbiscan...
March 18, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28356312/an-intranasally-delivered-peptide-drug-ameliorates-cognitive-decline-in-alzheimer-transgenic-mice
#10
Yu-Sung Cheng, Zih-Ten Chen, Tai-Yan Liao, Chen Lin, Howard C-H Shen, Ya-Han Wang, Chi-Wei Chang, Ren-Shyan Liu, Rita P-Y Chen, Pang-Hsien Tu
Alzheimer's disease (AD) is the most common neurodegenerative disease. Imbalance between the production and clearance of amyloid β (Aβ) peptides is considered to be the primary mechanism of AD pathogenesis. This amyloid hypothesis is supported by the recent success of the human anti-amyloid antibody aducanumab, in clearing plaque and slowing clinical impairment in prodromal or mild patients in a phase Ib trial. Here, a peptide combining polyarginines (polyR) (for charge repulsion) and a segment derived from the core region of Aβ amyloid (for sequence recognition) was designed...
March 29, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28346434/optimization-of-adeno-associated-virus-vector-mediated-gene-transfer-to-the-respiratory-tract
#11
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
#12
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
#13
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
#14
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
#15
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 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
#16
Shakeeb Ahmed, Azka Gull, Tahir Khuroo, Mohd Aqil, Yasmin Sultana
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
#17
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
#18
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
#19
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
#20
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
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