Sample records for intranasal nanoparticle transit

  1. [Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

    PubMed

    Lu, Jin; Guo, Li-Wei; Fu, Ting-Ming; Zhu, Guo-Long; Dai, Zhen-Nan; Zhan, Guan-Jun; Chen, Li-Li

    2017-06-01

    PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration. Copyright© by the Chinese Pharmaceutical Association.

  2. Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan nanoparticles for pain relief.

    PubMed

    Patel, Deepa; Naik, Sachin; Chuttani, Krishna; Mathur, Rashi; Mishra, Anil K; Misra, Ambikanandan

    2013-09-01

    The purpose of present investigation was to formulate and characterize the cyclobenzaprine HCl (CBZ)-loaded thiolated chitosan nanoparticles and assessment of in-vitro cell viability, trans-mucosal permeability on RPMI2650 cell monolayer, in-vivo pharmacokinetic and pharmacodynamic study of thiolated chitosan nanoparticles on Swiss albino mice after intranasal administration. A significant high permeation of drug was observed from thiolated chitosan nanoparticles with less toxicity on nasal epithelial cells. Brain uptake of the drug after (99m)Tc labeling was significantly enhanced after thiolation of chitosan. CBZ-loaded thiolated chitosan NPs significantly reverse the N-Methyl-.-Aspartate (NMDA)-induced hyperalgesia by intranasal administration than the CBZ solution. The studies of present investigation revealed that thiolation of chitosan significantly reduce trans-mucosal toxicity with enhanced trans-mucosal permeability via paracellular pathway and brain uptake of a hydrophilic drug (normally impermeable across blood brain barrier) and pain alleviation activity via intranasal route.

  3. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    NASA Astrophysics Data System (ADS)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  4. Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

    PubMed

    Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

    2008-07-04

    In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, p<0.05). In addition, the average percentage of aortic lesions in the entire aorta area in the rabbits intranasally vaccinated with nanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, p<0.01) and was similar to those intramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

  5. Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

    PubMed

    Zhang, Shu; Huang, Shengshi; Lu, Lu; Song, Xinlei; Li, Pingli; Wang, Fengshan

    2018-01-01

    The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration. By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)- O -(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride ( O -HTCC) nanoparticles were prepared by interacting CS with O -HTCC, and the adjuvancy of the nanoparticles was investigated. The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/ O -HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/ O -HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/ O -HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/ O -HTCC evoked a significantly higher level of Ova-specific antibodies. Therefore, these results suggest that CS/ O -HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

  6. Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

    PubMed Central

    Pan, Li; Zhang, Zhongwang; Lv, Jianliang; Zhou, Peng; Hu, Wenfa; Fang, Yuzhen; Chen, Haotai; Liu, Xinsheng; Shao, Junjun; Zhao, Furong; Ding, Yaozhong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Zhang, Yongguang; Wang, Yonglu

    2014-01-01

    The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD). In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1) chitosan-coated poly(lactic-co-glycolic acid) (PLGA) loaded with plasmid DNA (Chi-PLGA-DNA) and (2) chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV) (Chi-Tre-Inactivated). Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (Ig)A (sIgA) antibodies in nasal washes were initially detected at 4 days postvaccination (dpv) with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles (P<0.05). FMDV-specific IgA antibodies in serum showed a similar pattern. All animals immunized by intranasal route developed low levels of detectable IgG in serum at 10 dpv. Following stimulation with FMDV, the highest levels of proliferation were observed in splenocytes harvested from Chi-PLGA-DNA-immunized animals, followed by proliferation of cells harvested from Chi-Tre-Inactivated nanoparticle-immunized animals (P<0.05). Higher protection rates were associated with the highest sIgA antibody responses induced in

  7. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

    PubMed Central

    Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

    2006-01-01

    Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced

  8. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

    PubMed

    Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

    2006-08-24

    Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery

  9. Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

    PubMed

    Zhao, Ying-Zheng; Jin, Rong-Rong; Yang, Wei; Xiang, Qi; Yu, Wen-Ze; Lin, Qian; Tian, Fu-Rong; Mao, Kai-Li; Lv, Chuan-Zhu; Wáng, Yi-Xiáng J; Lu, Cui-Tao

    2016-01-01

    Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats. The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats. PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration. With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

  10. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

    PubMed

    Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

    2016-09-20

    Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (<200nm) as determined by dynamic light scattering technique and transmission electron microscopy, assured transcellular transport across olfactory axons whose diameter was ≈200nm and then paving a direct path to brain. TFB-NPs and TFB-SLNs resulted in 64.11±2.21% and 57.81±5.32% entrapment efficiencies respectively which again asserted protection of drug from chemical and biological degradation in nasal cavity. In vitro release studies proved the sustained release of TFB from TFB-NPs and TFB-SLNs in comparison with pure drug, indicating prolonged residence times of drug at targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics

    PubMed Central

    Fatouh, Ahmed M; Elshafeey, Ahmed H; Abdelbary, Ahmed

    2017-01-01

    Purpose Agomelatine is a novel antidepressant drug suffering from an extensive first-pass metabolism leading to a diminished absolute bioavailability. The aim of the study is: first to enhance its absolute bioavailability, and second to increase its brain delivery. Methods To achieve these aims, the nasal route was adopted to exploit first its avoidance of the hepatic first-pass metabolism to increase the absolute bioavailability, and second the direct nose-to-brain pathway to enhance the brain drug delivery. Solid lipid nanoparticles were selected as a drug delivery system to enhance agomelatine permeability across the blood–brain barrier and therefore its brain delivery. Results The optimum solid lipid nanoparticles have a particle size of 167.70 nm ±0.42, zeta potential of −17.90 mV ±2.70, polydispersity index of 0.12±0.10, entrapment efficiency % of 91.25%±1.70%, the percentage released after 1 h of 35.40%±1.13% and the percentage released after 8 h of 80.87%±5.16%. The pharmacokinetic study of the optimized solid lipid nanoparticles revealed a significant increase in each of the plasma peak concentration, the AUC(0–360 min) and the absolute bioavailability compared to that of the oral suspension of Valdoxan® with the values of 759.00 ng/mL, 7,805.69 ng⋅min/mL and 44.44%, respectively. The optimized solid lipid nanoparticles gave a drug-targeting efficiency of 190.02, which revealed more successful brain targeting by the intranasal route compared with the intravenous route. The optimized solid lipid nanoparticles had a direct transport percentage of 47.37, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. Conclusion The intranasal administration of agomelatine solid lipid nanoparticles has effectively enhanced both the absolute bioavailability and the brain delivery of agomelatine. PMID:28684900

  12. Intranasal gene delivery for treating Parkinson's disease: overcoming the blood-brain barrier.

    PubMed

    Aly, Amirah E-E; Waszczak, Barbara L

    2015-01-01

    Developing a disease-modifying gene therapy for Parkinson's disease (PD) has been a high priority for over a decade. However, due to the inability of large biomolecules to cross the blood-brain barrier (BBB), the only means of delivery to the brain has been intracerebral infusion. Intranasal administration offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors, and the genes encoding them, directly to the brain. This review summarizes: i) evidence demonstrating intranasal delivery to the brain of a number of biomolecules having therapeutic potential for various CNS disorders; and ii) evidence demonstrating neuroprotective efficacy of a subset of biomolecules specifically for PD. The intersection of these two spheres represents the area of opportunity for development of new intranasal gene therapies for PD. To that end, our laboratory showed that intranasal administration of glial cell line-derived neurotrophic factor (GDNF), or plasmid DNA nanoparticles encoding GDNF, provides neuroprotection in a rat model of PD, and that the cells transfected by the nanoparticle vector are likely to be pericytes. A number of genes encoding neurotrophic factors have therapeutic potential for PD, but few have been tested by the intranasal route and shown to be neuroprotective in a model of PD. Intranasal delivery provides a largely unexplored, promising approach for development of a non-invasive gene therapy for PD.

  13. Survival of Verwey transition in gadolinium-doped ultrasmall magnetite nanoparticles.

    PubMed

    Yeo, Sunmog; Choi, Hyunkyung; Kim, Chul Sung; Lee, Gyeong Tae; Seo, Jeong Hyun; Cha, Hyung Joon; Park, Jeong Chan

    2017-09-28

    We have demonstrated that the Verwey transition, which is highly sensitive to impurities, survives in anisotropic Gd-doped magnetite nanoparticles. Transmission electron microscopy analysis shows that the nanoparticles are uniformly distributed. X-ray photoelectron spectroscopy and EDS mapping analysis confirm Gd-doping on the nanoparticles. The Verwey transition of the Gd-doped magnetite nanoparticles is robust and the temperature dependence of the magnetic moment (zero field cooling and field cooling) shows the same behaviour as that of the Verwey transition in bulk magnetite, at a lower transition temperature (∼110 K). In addition, irregularly shaped nanoparticles do not show the Verwey transition whereas square-shaped nanoparticles show the transition. Mössbauer spectral analysis shows that the slope of the magnetic hyperfine field and the electric quadrupole splitting change at the same temperature, meaning that the Verwey transition occurs at ∼110 K. These results would provide new insights into understanding the Verwey transition in nano-sized materials.

  14. Calcitonin intranasal--unigene: Salcatonin intranasal--unigene.

    PubMed

    2004-01-01

    An intranasal spray formulation of recombinant salmon calcitonin [salcatonin] is in development with Unigene Laboratories as therapy for postmenopausal osteoporosis. Calcitonin is an endogenous polypeptide hormone that regulates calcium and bone metabolism. It is produced by the parafollicular cells of the thyroid gland in humans and other species. Calcitonin inhibits bone loss through the suppression of osteoclast activity. Salmon calcitonin is approximately 40-50 times more potent than natural human calcitonin at inhibiting osteoclast function. It can be obtained naturally from salmon or can be synthesised with the same chemical structure. Calcitonin was originally available only as an injectable formulation, but in recent years more convenient formulations have become available. Unigene is actively seeking to license its intranasal calcitonin product in Europe and other territories outside the US. nigene licensed its intranasal calcitonin product to Upsher-Smith Laboratories in December 2002, under a $US10 million exclusive US licensing agreement. Under the terms of the agreement, Unigene received an upfront payment of $US3 million from Upsher-Smith and will be eligible to receive milestone payments and royalty payments on product sales. Unigene will be responsible for manufacturing the product at its Boonton facility in New Jersey, USA, and will sell finished calcitonin product to Upsher-Smith. Upsher-Smith will package, market and distribute the product nationwide. Unigene granted an exclusive license to Faran Laboratories in September 2003 for its intranasal calcitonin osteoporosis product in Greece. Unigene will sell the finished product to Faran, who will promote and market it throughout the country after Unigene obtains European regulatory approval and local pricing approval. Unigene will receive an upfront payment and is eligible to receive milestone payments prior to product launch. Faran will pay Unigene a fixed price for each unit of product received

  15. "Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route* ".

    PubMed

    Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

    2016-08-01

    The objective of the present investigation was to optimize and develop quetiapine fumarate (QF) loaded chitosan nanoparticles (QF-NP) by ionic gelation method using Box-Behnken design. Three independent variables viz., X1-Concentration of chitosan, X2-Concentration of sodium tripolyphosphate and X3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y1-Size, Y2-PDI and Y3-%EE). Optimized formula of QF-NP was selected from the design space which was further evaluated for physicochemical, morphological, solid state characterization, nasal diffusion and in-vivo distribution for brain targeting following non-invasive intranasal administration. The average particle size, PDI, %EE and nasal diffusion were found to be 131.08±7.45nm, 0.252±0.064, 89.93±3.85% and 65.24±5.26% respectively. Neither toxicity nor structural damage on nasal mucosa was observed upon histopathological examination. Significantly higher brain/blood ratio and 2 folds higher nasal bioavailability in brain with QF-NP in comparison to drug solution following intranasal administration revealed preferential nose to brain transport bypassing blood-brain barrier and prolonged retention of QF at site of action suggesting superiority of chitosan as permeability enhancer. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

    PubMed

    Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

    2015-01-01

    Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully

  17. Gelatin nanoparticle-mediated intranasal delivery of substance P protects against 6-hydroxydopamine-induced apoptosis: an in vitro and in vivo study.

    PubMed

    Lu, Cui-Tao; Jin, Rong-Rong; Jiang, Yi-Na; Lin, Qian; Yu, Wen-Ze; Mao, Kai-Li; Tian, Fu-Rong; Zhao, Ya-Ping; Zhao, Ying-Zheng

    2015-01-01

    The aim of this study was to investigate the protective role of intranasally administered substance P-loaded gelatin nanoparticles (SP-GNPs) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in vitro and in vivo, and to provide a new strategy for treating brain pathology, such as Parkinson's disease. SP-GNPs were prepared by a water-in-water emulsion method, and their stability, encapsulating efficiency, and loading capacity were evaluated. PC-12 cells were used to examine the enhancement of growth and inhibition of apoptosis by SP-GNPs in vitro using MTT assays. In the in vivo study, hemiparkinsonian rats were created by intracerebroventricular injection of 6-OHDA. The rats then received intranasal SP-GNPs daily for 2 weeks. Functional improvement was assessed by quantifying rotational behavior, and the degree of apoptosis was assessed by immunohistochemical staining for caspase-3 in the substantia nigra region. PC-12 cells with 6-OHDA-induced disease treated with SP-GNPs showed higher cell viability than their untreated counterparts, and cell viability increased as the concentration of substance P (SP) increased, indicating that SP could enhance cell growth and inhibit the cell apoptosis induced by 6-OHDA. Rats with 6-OHDA-induced hemiparkinsonism treated with SP-GNPs made fewer rotations and showed less staining for caspase-3 than their counterparts not treated with SP, indicating that SP protects rats with 6-OHDA-induced hemiparkinsonism from apoptosis and therefore demonstrates their functional improvement. Intranasal delivery of SP-GNPs protects against 6-OHDA-induced apoptosis both in vitro and in vivo.

  18. Polymeric nanoparticles - Influence of the glass transition temperature on drug release.

    PubMed

    Lappe, Svenja; Mulac, Dennis; Langer, Klaus

    2017-01-30

    The physico-chemical characterisation of nanoparticles is often lacking the determination of the glass transition temperature, a well-known parameter for the pure polymer carrier. In the present study the influence of water on the glass transition temperature of poly (DL-lactic-co-glycolic acid) nanoparticles was assessed. In addition, flurbiprofen and mTHPP as model drugs were incorporated in poly (DL-lactic-co-glycolic acid), poly (DL-lactic acid), and poly (L-lactic acid) nanoparticles. For flurbiprofen-loaded nanoparticles a decrease in the glass transition temperature was observed while mTHPP exerted no influence on this parameter. Based on this observation, the release behaviour of the drug-loaded nanoparticles was investigated at different temperatures. For all preparations an initial burst release was measured that could be attributed to the drug adsorbed to the large nanoparticle surface. At temperatures above the glass transition temperature an instant drug release of the nanoparticles was observed, while at lower temperatures less drug was released. It could be shown that the glass transition temperature of drug loaded nanoparticles in suspension more than the corresponding temperature of the pure polymer is the pivotal parameter when characterising a nanostructured drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Transition metal-substituted cobalt ferrite nanoparticles for biomedical applications.

    PubMed

    Sanpo, Noppakun; Berndt, Christopher C; Wen, Cuie; Wang, James

    2013-03-01

    Transition metals of copper, zinc, chromium and nickel were substituted into cobalt ferrite nanoparticles via a sol-gel route using citric acid as a chelating agent. The microstructure and elemental composition were characterized using scanning electron microscopy combined with energy-dispersive X-ray spectroscopy. Phase analysis of transition metal-substituted cobalt ferrite nanoparticles was performed via X-ray diffraction. Surface wettability was measured using the water contact angle technique. The surface roughness of all nanoparticles was measured using profilometry. Moreover, thermogravimetric analysis and differential scanning calorimetry were performed to determine the temperature at which the decomposition and oxidation of the chelating agents took place. Results indicated that the substitution of transition metals influences strongly the microstructure, crystal structure and antibacterial property of the cobalt ferrite nanoparticles. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson's disease treatment.

    PubMed

    Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

    Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.

  1. Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy.

    PubMed

    Yenigun, Alper; Yilmaz, Sinan; Dogan, Remzi; Goktas, Seda Sezen; Calim, Muhittin; Ozturan, Orhan

    2018-01-01

    Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p < 0.05). Sedative effects were observed in three patients in the intranasal ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p < 0.05). Cognitive impairment, constipation, nausea, vomiting and bleeding were not observed in any of the groups. This study showed that either intranasal ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain

  2. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

    PubMed Central

    Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

    2016-01-01

    Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. PMID:27994458

  3. Intranasal instillation of iron oxide nanoparticles induces inflammation and perturbation of trace elements and neurotransmitters, but not behavioral impairment in rats.

    PubMed

    Askri, Dalel; Ouni, Souhir; Galai, Said; Arnaud, Josiane; Chovelon, Benoit; Lehmann, Sylvia G; Sturm, Nathalie; Sakly, Mohsen; Sève, Michel; Amara, Salem

    2018-06-01

    Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis. Rats were treated during seven consecutive days by intranasal instillations at a dose of 10 mg/kg body weight. The mean body weight increased significantly in IONP-exposed rats. Moreover, several hematological parameters were normal in treated rats except the platelet count which was increased. The biochemical study revealed that phosphatase alkaline level decreased in IONP-exposed rats, but no changes were observed for the other hepatic enzymes (ALT and AST) levels. The trace element homeostasis was slightly modulated by IONP exposure. Sub-acute intranasal exposure to IONPs increased dopamine and norepinephrine levels in rat brain; however, it did not affect the emotional behavior, the anxiety index, and the learning/memory capacities of rats.

  4. History of intranasal splints.

    PubMed

    Lau, J; Elhassan, H A; Singh, N

    2018-03-01

    Intranasal splints have long been utilised as a post-operative adjunct in septoplasty, intended to reduce the risk of adhesions and haematoma formation, and to maintain alignment during healing. A Medline literature review of the history and evolution of intranasal splint materials and designs was performed. Advantages and disadvantages of various splints are discussed. Intranasal splints fashioned from X-ray film were first reported in 1955. Since then, a variety of materials have been utilised, including polyethylene coffee cup lids, samarium cobalt magnets and dental utility wax. Most contemporary splints are produced from silicon rubber or polytetrafluoroethylene (Teflon). Designs have varied in thickness, flexibility, shape, absorption and the inclusion of built-in airway tubes. Future directions in splint materials and designs are discussed. Intranasal splints have steadily evolved since 1955, with numerous novel innovations. Despite their simplicity, they play an important role in nasal surgery and will continue to evolve over time.

  5. Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer's disease.

    PubMed

    Meng, Qingqing; Wang, Aiping; Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang

    2018-01-01

    Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer's disease (AD). To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. HupA Lf-TMC NPs were prepared using the emulsion-solvent evaporation method and optimized using the Box-Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography-tandem mass spectrometry. Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus

  6. A surface phase transition of supported gold nanoparticles.

    PubMed

    Plech, Anton; Cerna, Roland; Kotaidis, Vassilios; Hudert, Florian; Bartels, Albrecht; Dekorsy, Thomas

    2007-04-01

    A thermal phase transition has been resolved in gold nanoparticles supported on a surface. By use of asynchronous optical sampling with coupled femtosecond oscillators, the Lamb vibrational modes could be resolved as a function of annealing temperature. At a temperature of 104 degrees C the damping rate and phase changes abruptly, indicating a structural transition in the particle, which is explained as the onset of surface melting.

  7. Plasmonics and SERS activity of post-transition metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Bezerra, A. G.; Machado, T. N.; Woiski, T. D.; Turchetti, D. A.; Lenz, J. A.; Akcelrud, L.; Schreiner, W. H.

    2018-05-01

    Nanoparticles of the post-transition metals, In, Sn, Pb, and Bi, and of the metalloid Sb were produced by laser ablation synthesis in solution (LASiS) and tested for localized surface plasmon resonances (LSPR) and surface-enhanced Raman scattering (SERS). The nanoparticles were characterized by UV-Vis optical absorption, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Several organic and biological molecules were tested, and SERS activity was demonstrated for all tested nanoparticles and molecules. The Raman enhancement factor for each nanoparticle class and molecule was experimentally determined. The search for new plasmonic nanostructures is important mainly for life sciences-related applications and this study expands the range of SERS active systems.

  8. Intranasal Oxytocin: Myths and Delusions.

    PubMed

    Leng, Gareth; Ludwig, Mike

    2016-02-01

    Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

    PubMed Central

    Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei

    2018-01-01

    Background Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD). Purpose To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods HupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry. Results Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse

  10. Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

    PubMed

    Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

    2012-04-02

    This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

  11. 21 CFR 874.4780 - Intranasal splint.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4780 Intranasal splint. (a) Identification... septum and the nasal cavity. It is placed in the nasal cavity after surgery or trauma. The intranasal splint is constructed from plastic, silicone, or absorbent material. (b) Classification. Class I (general...

  12. 21 CFR 874.4780 - Intranasal splint.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4780 Intranasal splint. (a) Identification... septum and the nasal cavity. It is placed in the nasal cavity after surgery or trauma. The intranasal splint is constructed from plastic, silicone, or absorbent material. (b) Classification. Class I (general...

  13. 21 CFR 874.4780 - Intranasal splint.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4780 Intranasal splint. (a) Identification... septum and the nasal cavity. It is placed in the nasal cavity after surgery or trauma. The intranasal splint is constructed from plastic, silicone, or absorbent material. (b) Classification. Class I (general...

  14. 21 CFR 874.4780 - Intranasal splint.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4780 Intranasal splint. (a) Identification... septum and the nasal cavity. It is placed in the nasal cavity after surgery or trauma. The intranasal splint is constructed from plastic, silicone, or absorbent material. (b) Classification. Class I (general...

  15. 21 CFR 874.4780 - Intranasal splint.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DEVICES EAR, NOSE, AND THROAT DEVICES Surgical Devices § 874.4780 Intranasal splint. (a) Identification... septum and the nasal cavity. It is placed in the nasal cavity after surgery or trauma. The intranasal splint is constructed from plastic, silicone, or absorbent material. (b) Classification. Class I (general...

  16. Synthesis of TiO2 Nanoparticle and its phase Transition

    NASA Astrophysics Data System (ADS)

    Mangrola, M. H.; Joshi, V. G.; Parmar, B. H.

    2011-12-01

    Here we report the synthesis of titanium dioxide (TiO2) nanoparticles and study of its phase transition from anataze to rutile. Titanium dioxide (TiO2) nanoparticles have been prepared by hydrolysis of Titanium isopropoxide an aqueous solution with constant value of pH 2 and peptizing the resultant suspension gel(white-Blue) and calcinate gel at different temperature. Structures of synthetic samples of TiO2 have been examined by X-ray diffraction (XRD) and scanning electron microscope (SEM). The anatase-rutile transition has been a popular topic due to its interest to scientific and engineering fields. . Here we have seen that the 100 °C calcinate powder consist of anatase fine crystalline phase with a particle size 14 to 15 nm. The prepared TiO2 nanoparticles have uniform size and morphology, and the phase transformation kinetics of obtained material was studied by interpretation of the X-ray diffraction patterns peaks. The phase transform occurred from anatase to rutile at calcinate temperature up to 600 °C. A very fine network texture made from uniform nanoparticles was revealed by scanning electron microscopy (SEM) analyses.

  17. Absorption of clonazepam after intranasal and buccal administration.

    PubMed Central

    Schols-Hendriks, M W; Lohman, J J; Janknegt, R; Korten, J J; Merkus, F W; Hooymans, P M

    1995-01-01

    Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection. PMID:7640154

  18. Intranasal melatonin nanoniosomes: pharmacokinetic, pharmacodynamics and toxicity studies.

    PubMed

    Priprem, Aroonsri; Johns, Jeffrey R; Limsitthichaikoon, Sucharat; Limphirat, Wanwisa; Mahakunakorn, Pramote; Johns, Nutjaree Prateepawanit

    2017-06-01

    Intranasal melatonin encapsulated in nanosized niosomes was preclinically evaluated. A formula of melatonin niosomes (MN) was selected through physicochemical and cytotoxic data for pharmacokinetic, pharmacodynamics and toxicity studies in male Wistar rats. Intranasal MN was bioequivalent to intravenous injection of melatonin, providing therapeutic level doses. Acute and subchronic toxicity screening showed no abnormal signs, symptoms or hematological effects in any animals. Transient nasal irritations with no inflammation were observed with intranasal MN, leading it to be categorized as relatively harmless. The intranasal MN could deliver melatonin to the brain to induce sleep and provide delayed systemic circulation, relative to intravenous injection and also distribute to peripheral tissue.

  19. Synthesis, structural and optical properties of PVP coated transition metal doped ZnS nanoparticles

    NASA Astrophysics Data System (ADS)

    Desai, N. V.; Shaikh, I. A.; Rawal, K. G.; Shah, D. V.

    2018-05-01

    The room temperature photoluminescence (PL) of transition metal doped ZnS nanoparticles is investigated in the present study. The PVP coated ZnS nanoparticles doped with transition metals are synthesized by facile wet chemical co-precipitation method with the concentration of impurity 1%. The UV-Vis absorbance spectra have a peak at 324nm which shifts slightly to 321nm upon introduction of the impurity. The incorporation of the transition metal as dopant is confirmed by X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS). The particle size and the morphology are characterized by scanning electron microscopy (SEM), XRD and UV-Vis spectroscopy. The average size of synthesized nanoparticles is about 2.6nm. The room temperature photoluminescence (PL) of undoped and doped ZnS nanoparticles show a strong and sharp peak at 782nm and 781.6nm respectively. The intensity of the PL changes with the type of doping having maximum for manganese (Mn).

  20. Intranasal scopolamine preparation and method

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi (Inventor); Cintron, Nitza M. (Inventor)

    1991-01-01

    A new method and preparation for intranasal delivery of scopolamine provides a safe and effective treatment for motion sickness and other conditions requiring anticholinergic therapy. The preparation can be in the form of aqueous nasal drops, mist spray, gel or oinment. Intranasal delivery of scopolamine has similar bioavailability and effect of intravenous delivery and is far superior to oral dosage. Scopolamine is prepared in a buffered saline solution at the desired dosage rate for effective anticholinergic response.

  1. Intranasal medications in pediatric emergency medicine.

    PubMed

    Del Pizzo, Jeannine; Callahan, James M

    2014-07-01

    Intranasal medication administration in the emergency care of children has been reported for at least 20 years and is gaining popularity because of ease of administration, rapid onset of action, and relatively little pain to the patient. The ability to avoid a needle stick is often attractive to practitioners, in addition to children and their parents. In time-critical situations for which emergent administration of medication is needed, the intranasal route may be associated with more rapid medication administration. This article reviews the use of intranasal medications in the emergency care of children. Particular attention will be paid to anatomy and its impact on drug delivery, pharmacodynamics, medications currently administered by this route, delivery devices available, tips for use, and future directions.

  2. Dual structural transition in small nanoparticles of Cu-Au alloy

    NASA Astrophysics Data System (ADS)

    Gafner, Yuri; Gafner, Svetlana; Redel, Larisa; Zamulin, Ivan

    2018-02-01

    Cu-Au alloy nanoparticles are known to be widely used in the catalysis of various chemical reactions as it was experimentally defined that in many cases the partial substitution of copper with gold increases catalytic activity. However, providing the reaction capacity of alloy nanoparticles the surface electronic structure strongly depends on their atomic ordering. Therefore, to theoretically determine catalytic properties, one needs to use a most real structural model complying with Cu-Au nanoparticles under various external influences. So, thermal stability limits were studied for the initial L12 phase in Cu3Au nanoalloy clusters up to 8.0 nm and Cu-Au clusters up to 3.0 nm at various degrees of Au atom concentration, with molecular dynamics method using a modified tight-binding TB-SMA potential. Dual structural transition L12 → FCC and further FCC → Ih is shown to be possible under the thermal factor in Cu3Au and Cu-Au clusters with the diameter up to 3.0 nm. The temperature of the structural transition FCC → Ih is established to decrease for small particles of Cu-Au alloy under the increase of Au atom concentration. For clusters with this structural transition, the melting point is found to be a linear increasing function of concentration, and for clusters without FCC → Ih structural transition, the melting point is a linear decreasing function of Au content. Thus, the article shows that doping Cu nanoclusters with Au atoms allows to control the forming structure as well as the melting point.

  3. Preparation of transition metal nanoparticles and surfaces modified with (CO)polymers synthesized by RAFT

    DOEpatents

    McCormick, III., Charles L.; Lowe, Andrew B.; Sumerlin, Brent S.

    2006-11-21

    A new, facile, general one-phase method of generating thio-functionalized transition metal nanoparticles and surfaces modified by (co)polymers synthesized by the RAFT method is described. The method includes the stops of forming a (co)polymer in aqueous solution using the RAFT methodology, forming a colloidal transition metal precursor solution from an appropriate transition metal; adding the metal precursor solution or surface to the (co)polymer solution, adding a reducing agent into the solution to reduce the metal colloid in situ to produce the stabilized nanoparticles or surface, and isolating the stabilized nanoparticles or surface in a manner such that aggregation is minimized. The functionalized surfaces generated using these methods can further undergo planar surface modifications, such as functionalization with a variety of different chemical groups, expanding their utility and application.

  4. Preparation of transition metal nanoparticles and surfaces modified with (co)polymers synthesized by RAFT

    DOEpatents

    McCormick, III, Charles L.; Lowe, Andrew B [Hattiesburg, MS; Sumerlin, Brent S [Pittsburgh, PA

    2011-12-27

    A new, facile, general one-phase method of generating thiol-functionalized transition metal nanoparticles and surfaces modified by (co)polymers synthesized by the RAFT method is described. The method includes the steps of forming a (co)polymer in aqueous solution using the RAFT methodology, forming a colloidal transition metal precursor solution from an appropriate transition metal; adding the metal precursor solution or surface to the (co)polymer solution, adding a reducing agent into the solution to reduce the metal colloid in situ to produce the stabilized nanoparticles or surface, and isolating the stabilized nanoparticles or surface in a manner such that aggregation is minimized. The functionalized surfaces generated using these methods can further undergo planar surface modifications, such as functionalization with a variety of different chemical groups, expanding their utility and application.

  5. Intranasal insulin improves memory in humans.

    PubMed

    Benedict, Christian; Hallschmid, Manfred; Hatke, Astrid; Schultes, Bernd; Fehm, Horst L; Born, Jan; Kern, Werner

    2004-11-01

    Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function. Also, improvements in mood were expected. We investigated the effects of 8 weeks of intranasal administration of insulin (human regular insulin 4 x 40 IU/d) on declarative memory (immediate and delayed recall of word lists), attention (Stroop test), and mood in 38 healthy subjects (24 males) in a double blind, between-subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions. Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration (words recalled, Placebo 2.92 +/- 1.00, Insulin 6.20 +/- 1.03, p < 0.05). Moreover, subjects after insulin reported signs of enhanced mood, such as reduced anger (p < 0.02) and enhanced self-confidence (p < 0.03). Results indicate a direct action of prolonged intranasal administration of insulin on brain functions, improving memory and mood in the absence of systemic side effects. These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer's disease.

  6. Intranasal sedatives in pediatric dentistry

    PubMed Central

    AlSarheed, Maha A.

    2016-01-01

    Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry. Results: Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its’ onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Conclusion: Intranasal midazolam, ketamine and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine and sufentanil have proven to be effective premedications. PMID:27570849

  7. Intranasal sedatives in pediatric dentistry.

    PubMed

    AlSarheed, Maha A

    2016-09-01

    To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol, and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry.  Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its' onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Intranasal midazolam, ketamine, and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine, and sufentanil have proven to be effective premedications.

  8. Intranasal volume increases with age: Computed tomography volumetric analysis in adults.

    PubMed

    Loftus, Patricia A; Wise, Sarah K; Nieto, Daniel; Panella, Nicholas; Aiken, Ashley; DelGaudio, John M

    2016-10-01

    It is theorized that intranasal cavity volumes change throughout the aging process, possibly secondary to hormonal changes and atrophy of the sinonasal mucosa. Our objective is to compare intranasal volumes from different age groups to test the hypothesis that intranasal cavity volume increases with age. Case series. An analysis of computed tomography (CT) scans performed for reasons other than sinonasal complaints. Intranasal volumes of three groups (age 20-30 years, 40-50 years, and 70 years and above) were calculated using Vitrea software. The total intranasal volume was measured from the nasal vestibule anteriorly, the nasopharynx posteriorly, the olfactory cleft superiorly, and the nasal floor inferiorly. The total volume included the sum of the right and left sides. Sixty-two CT scans were analyzed. There was a progressive, relatively linear, increase in intranasal volume with increasing age: 20 to 30 years = 15.73 mL, 40 to 50 years = 17.30 mL, and 70 years and above = 18.38 mL. Mean intranasal volume for males was 19.07 mL, and for females was 15.23 mL. Analysis of variance demonstrated significant group differences in mean intranasal volume for age (P = .003) and gender (P < .001), with moderate-to-large effect size of 0.206 and 0.289 (partial η(2) ), respectively. Post hoc testing revealed a significant difference between the 20 to 30-year and >70-year age groups (P = .006). There was no significant difference in intranasal volume dependent upon body mass index. Intranasal volume increases with age and is larger in males. Specific etiologies responsible for increased intranasal cavity volume with age are actively being evaluated. 4 Laryngoscope, 126:2212-2215, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Non-Clinical Safety Evaluation of Intranasal Iota-Carrageenan

    PubMed Central

    Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

    2015-01-01

    Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug’s action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application. PMID:25875737

  10. Non-clinical safety evaluation of intranasal iota-carrageenan.

    PubMed

    Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

    2015-01-01

    Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  11. Effects of interband transitions on Faraday rotation in metallic nanoparticles.

    PubMed

    Wysin, G M; Chikan, Viktor; Young, Nathan; Dani, Raj Kumar

    2013-08-14

    The Faraday rotation in metallic nanoparticles is considered based on a quantum model for the dielectric function ϵ(ω) in the presence of a DC magnetic field B. We focus on effects in ϵ(ω) due to interband transitions (IBTs), which are important in the blue and ultraviolet for noble metals used in plasmonics. The dielectric function is found using the perturbation of the electron density matrix due to the optical field of the incident electromagnetic radiation. The calculation is applied to transitions between two bands (d and p, for example) separated by a gap, as one finds in gold at the L-point of the Fermi surface. The result of the DC magnetic field is a shift in the effective optical frequency causing IBTs by ±μBB/ħ, where opposite signs are associated with left/right circular polarizations. The Faraday rotation for a dilute solution of 17 nm diameter gold nanoparticles is measured and compared with both the IBT theory and a simpler Drude model for the bound electron response. Effects of the plasmon resonance mode on Faraday rotation in nanoparticles are also discussed.

  12. Behavioral responses to two intranasal vaccine applicators in horses and ponies.

    PubMed

    Grogan, Elkanah H; McDonnell, Sue M

    2005-05-15

    To evaluate behavioral compliance of horses and ponies with simulated intranasal vaccination and assess development of generalized aversion to veterinary manipulations. Clinical trial. 28 light horse mares, 3 pony geldings, 2 light horse stallions, and 3 pony stallions that had a history of compliance with veterinary procedures. Behavioral compliance with 2 intranasal vaccine applicators was assessed. Compliance with standard physical examination procedures was assessed before and after a single experience with either of the applicators or a control manipulation to evaluate development of generalized aversion to veterinary manipulation. In all 30 horses, simulated intranasal vaccination or the control manipulation could be performed without problematic avoidance behavior, and simulated intranasal vaccination did not have any significant effect on duration of or compliance with a standardized physical examination that included manipulation of the ears, nose, and mouth. Results were similar for the 2 intranasal vaccine applicators, and no difference in compliance was seen between horses in which warm versus cold applicators were used. For 3 of the 6 ponies, substantial avoidance behavior was observed in association with simulated intranasal vaccination, and compliance with physical examination procedures decreased after simulated intranasal vaccination. Although some compliance problems were seen with ponies, neither problems with compliance with simulated intranasal vaccination nor adverse effects on subsequent physical examination were identified in any of the horses. Further study is needed to understand factors involved in practitioner reports of aversion developing in association with intranasal vaccination.

  13. Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

    PubMed

    Spalink, Christy L; Barnes, Erin; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2017-08-01

    To report the use of intranasal dexmedetomidine, an α 2 -adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. Case series. Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

  14. Integrated analytical techniques with high sensitivity for studying brain translocation and potential impairment induced by intranasally instilled copper nanoparticles.

    PubMed

    Bai, Ru; Zhang, Lili; Liu, Ying; Li, Bai; Wang, Liming; Wang, Peng; Autrup, Herman; Beer, Christiane; Chen, Chunying

    2014-04-07

    Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p<0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements was observed by synchrotron radiation X-ray fluorescence (SRXRF). H&E staining and immunohistochemical analysis showed that CuNPs produced damages to nerve cells and astrocyte might be the one of the potential targets of CuNPs. The changes of neurotransmitter levels in different brain regions demonstrate that the dysfunction occurred in exposed groups. These data indicated that CuNPs could enter the brain after nasal inhalation and induced damages to the central nervous system (CNS). Integration of effective analytical techniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Size-dependent structural transformations of hematite nanoparticles. 1. Phase transition.

    PubMed

    Chernyshova, I V; Hochella, M F; Madden, A S

    2007-04-14

    Using Fourier Transform InfraRed (FTIR) spectroscopy, Raman spectroscopy, X-ray diffraction (XRD), and Transmission Electron Microscopy (TEM), we characterize the structure and/or morphology of hematite (alpha-Fe(2)O(3)) particles with sizes of 7, 18, 39 and 120 nm. It is found that these nanoparticles possess maghemite (gamma-Fe(2)O(3))-like defects in the near surface regions, to which a vibrational mode at 690 cm(-1), active both in FTIR and Raman spectra, is assigned. The fraction of the maghemite-like defects and the net lattice disorder are inversely related to the particle size. However, the effect is opposite for nanoparticles grown by sintering of smaller hematite precursors under conditions when the formation of a uniform hematite-like structure throughout the aggregate is restricted by kinetic issues. This means that not only particle size but also the growth kinetics determines the structure of the nanoparticles. The observed structural changes are interpreted as size-induced alpha-Fe(2)O(3)<-->gamma-Fe(2)O(3) phase transitions. We develop a general model that considers spinel defects and absorbed/adsorbed species (in our case, hydroxyls) as dominant controls on structural changes with particle size in hematite nanoparticles, including solid-state phase transitions. These changes are represented by trajectories in a phase diagram built in three phase coordinates-concentrations of spinel defects, absorbed impurities, and adsorbed species. The critical size for the onset of the alpha-->gamma phase transition depends on the particle environment, and for the dry particles used in this study is about 40 nm. The model supports the existence of intermediate phases (protohematite and hydrohematite) during dehydration of goethite. We also demonstrate that the hematite structure is significantly less defective when the nanoparticles are immersed in water or KBr matrix, which is explained by the effects of the electrochemical double layer and increased rigidity of

  16. Intranasal drug delivery in neuropsychiatry: focus on intranasal ketamine for refractory depression.

    PubMed

    Andrade, Chittaranjan

    2015-05-01

    Intranasal drug delivery (INDD) systems offer a route to the brain that bypasses problems related to gastrointestinal absorption, first-pass metabolism, and the blood-brain barrier; onset of therapeutic action is rapid, and the inconvenience and discomfort of parenteral administration are avoided. INDD has found several applications in neuropsychiatry, such as to treat migraine, acute and chronic pain, Parkinson disease, disorders of cognition, autism, schizophrenia, social phobia, and depression. INDD has also been used to test experimental drugs, such as peptides, for neuropsychiatric indications; these drugs cannot easily be administered by other routes. This article examines the advantages and applications of INDD in neuropsychiatry; provides examples of test, experimental, and approved INDD treatments; and focuses especially on the potential of intranasal ketamine for the acute and maintenance therapy of refractory depression. © Copyright 2015 Physicians Postgraduate Press, Inc.

  17. Intranasal oxytocin, but not vasopressin, augments neural responses to toddlers in human fathers.

    PubMed

    Li, Ting; Chen, Xu; Mascaro, Jennifer; Haroon, Ebrahim; Rilling, James K

    2017-07-01

    This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1-2year old children to receive either 24IU intranasal OT before one scan and placebo before the other scan (n=15) or 20IU intranasal AVP before one scan and placebo before the other scan (n=15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Preparation of surface multiple-coated polylactide acid drug-loaded nanoparticles for intranasal delivery and evaluation on its brain-targeting efficiency.

    PubMed

    Bian, Junjie; Yuan, Zhixiang; Chen, Xiaoliang; Gao, Yuan; Xu, Chaoqun; Shi, Jianyou

    2016-01-01

    To prepare a mixture of multiple-coated aniracetam nasal polylactic-acid nanoparticles (M-C-PLA-NP) and evaluate its stability preliminarily in vitro and its brain-targeting efficiency in vivo. The solvent diffusion-evaporation combined with magnetic stirring method has been chosen for the entrapment of aniracetam. The M-C-PLA-NP was characterized with respect to its morphology, particle size, size distribution and aniracetam entrapment efficiency. The in vivo distribution was studied in male SD rats after an intranasal administration. In vitro release of M-C-PLA-NP showed two components with an initial rapid release due to the surface-associated drug and followed by a slower exponential release of aniracetam, which was dissolved in the core. The AUC0 → 30 min of M-C-PLA-NP in brain tissues resulted in a 5.19-fold increase compared with aniracetam solution. The ratios of AUC in brain to that in other tissues obtained after nasal application of M-C-PLA-NP were significantly higher than those of aniracetam solution. Therefore, it can be concluded that M-C-PLA-NP demonstrated its potential on increasing the brain-targeting efficiency of drugs and will be used as novel brain-targeting agent for nasal drug delivery.

  19. Self-assembly of noble metal monolayers on transition metal carbide nanoparticle catalysts

    DOE PAGES

    Hunt, Sean T.; Milina, Maria; Alba-Rubio, Ana C.; ...

    2016-05-20

    Here, we demonstrated the self-assembly of transition metal carbide nanoparticles coated with atomically thin noble metal monolayers by carburizing mixtures of noble metal salts and transition metal oxides encapsulated in removable silica templates. This approach allows for control of the final core-shell architecture, including particle size, monolayer coverage, and heterometallic composition. Carbon-supported Ti 0.1W 0.9C nanoparticles coated with Pt or bimetallic PtRu monolayers exhibited enhanced resistance to sintering and CO poisoning, achieving an order of magnitude increase in specific activity over commercial catalysts for methanol electrooxidation after 10,000 cycles. These core-shell materials provide a new direction to reduce the loading,more » enhance the activity, and increase the stability of noble metal catalysts.« less

  20. Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates

    PubMed Central

    Galbusera, Alberto; De Felice, Alessia; Girardi, Stefano; Bassetto, Giacomo; Maschietto, Marta; Nishimori, Katsuhiko; Chini, Bice; Papaleo, Francesco; Vassanelli, Stefano; Gozzi, Alessandro

    2017-01-01

    The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse, we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions and a sustained activation of hippocampal and forebrain areas characterized by high oxytocin receptor density. By contrast, intranasal administration of AVP produced a robust and sustained deactivation in cortico-parietal, thalamic and mesolimbic regions. Importantly, intravenous administration of OXT and AVP did not recapitulate the patterns of modulation produced by intranasal dosing, supporting a central origin of the observed functional changes. In keeping with this notion, hippocampal local field potential recordings revealed multi-band power increases upon intranasal OXT administration. We also show that the selective OXT-derivative TGOT reproduced the pattern of activation elicited by OXT and that the deletion of OXT receptors does not affect AVP-mediated deactivation. Collectively, our data document divergent modulation of brainwide neural systems by intranasal administration of OXT and AVP, an effect that involves key substrates of social and emotional behavior. The observed divergence calls for a deeper investigation of the systems-level mechanisms by which exogenous OXT and AVP modulate brain function and exert their putative therapeutic effects. PMID:27995932

  1. Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates.

    PubMed

    Galbusera, Alberto; De Felice, Alessia; Girardi, Stefano; Bassetto, Giacomo; Maschietto, Marta; Nishimori, Katsuhiko; Chini, Bice; Papaleo, Francesco; Vassanelli, Stefano; Gozzi, Alessandro

    2017-06-01

    The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse, we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions and a sustained activation of hippocampal and forebrain areas characterized by high oxytocin receptor density. By contrast, intranasal administration of AVP produced a robust and sustained deactivation in cortico-parietal, thalamic and mesolimbic regions. Importantly, intravenous administration of OXT and AVP did not recapitulate the patterns of modulation produced by intranasal dosing, supporting a central origin of the observed functional changes. In keeping with this notion, hippocampal local field potential recordings revealed multi-band power increases upon intranasal OXT administration. We also show that the selective OXT-derivative TGOT reproduced the pattern of activation elicited by OXT and that the deletion of OXT receptors does not affect AVP-mediated deactivation. Collectively, our data document divergent modulation of brainwide neural systems by intranasal administration of OXT and AVP, an effect that involves key substrates of social and emotional behavior. The observed divergence calls for a deeper investigation of the systems-level mechanisms by which exogenous OXT and AVP modulate brain function and exert their putative therapeutic effects.

  2. Adhesion and Wetting of Soft Nanoparticles on Textured Surfaces: Transition between Wenzel and Cassie-Baxter States

    DOE PAGES

    Cao, Zhen; Stevens, Mark J.; Carrillo, Jan-Michael Y.; ...

    2015-01-16

    We use a combination of the molecular dynamics simulations and scaling analysis to study interactions between gel-like nanoparticles and substrates covered with rectangular shape posts. Our simulations have shown that nanoparticle in contact with substrate undergo first order transition between Wenzel and Cassie-Baxter state which location depends on nanoparticle shear modulus, the strength of nanoparticle-substrate interactions, height of the substrate posts and nanoparticle size, R p. There is a range of system parameters where these two states coexist such that the average indentation δ produced by substrate posts changes monotonically with nanoparticle shear modulus, G p. We have developed amore » scaling model that describes deformation of nanoparticle in contact with patterned substrate. In the framework of this model the effect of the patterned substrate can be taken into account by introducing an effective work of adhesion, W eff, which describes the first order transition between Wenzel and Cassie-Baxter states. There are two different shape deformation regimes for nanoparticles with shear modulus G p and surface tension γ p. Shape of small nanoparticles with size R p < γ p 3/2G p -1 W eff -1/2 is controlled by capillary forces while deformation of large nanoparticles, R p > γ p 3/2G p -1 W eff -1/2« less

  3. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    PubMed

    Mann, Alex J; Noulin, Nicolas; Catchpole, Andrew; Stittelaar, Koert J; de Waal, Leon; Veldhuis Kroeze, Edwin J B; Hinchcliffe, Michael; Smith, Alan; Montomoli, Emanuele; Piccirella, Simona; Osterhaus, Albert D M E; Knight, Alastair; Oxford, John S; Lapini, Giulia; Cox, Rebecca; Lambkin-Williams, Rob

    2014-01-01

    We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and

  4. Semiconductor-metal transition of Se in Ru-Se Catalyst Nanoparticles

    NASA Astrophysics Data System (ADS)

    Babu, P. K.; Lewera, Adam; Oldfield, Eric; Wieckowski, Andrzej

    2009-03-01

    Ru-Se composite nanoparticles are promising catalysts for the oxygen reduction reaction (ORR) in fuel cells. Though the role of Se in enhancing the chemical stability of Ru nanoparticles is well established, the microscopic nature of Ru-Se interaction was not clearly understood. We carried out a combined investigation of ^77Se NMR and XPS on Ru-Se nanoparticles and our results indicate that Se, a semiconductor in elemental form, becomes metallic when interacting with Ru. ^77Se spin-lattice relaxation rates are found to be proportional to T, the well-known Korringa behavior characteristic of metals. The NMR results are supported by the XPS binding energy shifts which suggest that a possible Ru->Se charge transfer could be responsible for the semiconductor->metal transition of Se which also makes Ru less susceptible to oxidation during ORR.

  5. Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures.

    PubMed

    Reynolds, Stacy L; Bryant, Kathleen K; Studnek, Jonathan R; Hogg, Melanie; Dunn, Connell; Templin, Megan A; Moore, Charity G; Young, James R; Walker, Katherine Rivera; Runyon, Michael S

    2017-12-01

    We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine. This randomized controlled trial compared 1 mg/kg intranasal ketamine to 1.5 μg/kg intranasal fentanyl in children 4 to 17 years old with acute pain from suspected isolated extremity fractures presenting to an urban Level II pediatric trauma center from December 2015 to November 2016. Patients, parents, treating physicians, and outcome assessors were blinded to group allocation. The primary outcome, a tolerability measure, was the frequency of cumulative side effects and adverse events within 60 minutes of drug administration. The secondary outcomes included the difference in mean pain score reduction at 20 minutes, the proportion of patients achieving a clinically significant reduction in pain in 20 minutes, total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the emergency department (ED) stay, and the feasibility of enrolling children presenting to the ED in acute pain into a randomized trial conducted under U.S. regulations. All patients were monitored until 6 hours after their last dose of study drug or until admission to the hospital ward or operating room. Of 629 patients screened, 87 received the study drug and 82 had complete data for the primary outcome (41 patients in each group). The median (interquartile range) age was 8 (6-11) years and 62% were male. Baseline pain scores were similar among patients randomized to receive ketamine (73 ± 26) and fentanyl (69 ± 26; mean difference [95% CI] = 4 [-7 to 15]). The cumulative number of side effects was 2.2 times higher in the ketamine group, but there were no serious adverse events and no patients in either group required intervention. The most

  6. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    NASA Astrophysics Data System (ADS)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

  7. Use of intranasal corticosteroids in adenotonsillar hypertrophy.

    PubMed

    Sakarya, E U; Bayar Muluk, N; Sakalar, E G; Senturk, M; Aricigil, M; Bafaqeeh, S A; Cingi, C

    2017-05-01

    This review examined the efficacy of intranasal corticosteroids for improving adenotonsillar hypertrophy. The related literature was searched using PubMed and Proquest Central databases. Adenotonsillar hypertrophy causes mouth breathing, nasal congestion, hyponasal speech, snoring, obstructive sleep apnoea, chronic sinusitis and recurrent otitis media. Adenoidal hypertrophy results in the obstruction of nasal passages and Eustachian tubes, and blocks the clearance of nasal mucus. Adenotonsillar hypertrophy and obstructive sleep apnoea are associated with increased expression of various mediators of inflammatory responses in the tonsils, and respond to anti-inflammatory agents such as corticosteroids. Topical nasal steroids most likely affect the anatomical component by decreasing inspiratory upper airway resistance at the nasal, adenoidal or tonsillar levels. Corticosteroids, by their lympholytic or anti-inflammatory effects, might reduce adenotonsillar hypertrophy. Intranasal corticosteroids reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil and adenoid mixed-cell culture system. Intranasal corticosteroids have been used in adenoidal hypertrophy and adenotonsillar hypertrophy patients, decreasing rates of surgery for adenotonsillar hypertrophy.

  8. Statistical and methodological considerations for the interpretation of intranasal oxytocin studies

    PubMed Central

    Walum, Hasse; Waldman, Irwin D.; Young, Larry J.

    2015-01-01

    Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this paper we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, pre-study odds and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future. PMID:26210057

  9. Solid-liquid and liquid-solid transitions in metal nanoparticles.

    PubMed

    Hou, M

    2017-02-22

    The melting and solidification temperatures of nanosystems may differ by several hundred Kelvin. To understand the origin of this difference, transitions in small metallic nanoparticles on the atomic scale were analyzed using molecular dynamics (MD). Palladium was used as a case study, which was then extended to a range of other elemental metals. It was argued that in realistic environments, such as gases at low pressure (of the order of 1 mbar), heat transfers allow the microcanonical thermal equilibrium evolution of the nanoparticles between successive collisions with gas atoms. This is shown to have no significant influence on the mechanism of melting, whereas in an isolated nanoparticle, solidification triggers a huge and rapid increase in temperature. A simple relationship between the melting and solidification temperatures was found, indicating that the magnitude of the latent heat of melting governs undercooling. Whereas melting occurs via heterogeneous nucleation, solidification displays characteristics of spinodal decomposition. Consistently, the melting temperature scales with the surface-to-volume ratio, whereas the solidification temperature displays no significant dependence on the particle size.

  10. Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

    DTIC Science & Technology

    2017-10-01

    Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive Function in Multiple Sclerosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...going to evaluate if intranasal insulin improves cognition in people with MS, as assessed by standardized cognitive assessment tests . 2. KEYWORDS...Multiple Sclerosis, Cognitive Impairment, Neurodegenerative diseases, Intranasal Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive

  11. Intranasal Delivery of Topically-Acting Levofloxacin to Rats: a Proof-of-Concept Pharmacokinetic Study.

    PubMed

    Sousa, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

    2017-11-01

    To evaluate the potential of levofloxacin intranasal administration as a promising alternative approach to treat local infections such as chronic rhinosinusitis, by delivering drug concentrations directly to the site of infection. Drug concentrations were measured in plasma, olfactory bulb and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24 mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic parameters were compared between routes. For intranasal administration a thermoreversible in-situ gel was used. Plasma and olfactory bulb exposure to levofloxacin was minimal following intranasal dose, preventing systemic and central nervous system adverse effects. Levofloxacin concentration-time profile in ANM revealed higher concentrations during the first 60 min of the study following intranasal administration than the corresponding ones obtained after intravenous administration. A rapid and continuous decay of levofloxacin concentration in this nasal region was observed after intranasal delivery, resulting in much lower values at the last sampling time-points. The higher dose-normalized concentrations and pharmacokinetic exposure parameters of levofloxacin in ANM after intranasal administration, demonstrates that intranasal delivery of the formulated gel is, by itself, advantageous for delivering levofloxacin to biophase and thus an attractive approach in management of chronic rhinosinusitis.

  12. Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration.

    PubMed

    Wei, Yan; Ying, Mingzhen; Xu, Shuai; Wang, Feng; Zou, Aifeng; Cao, Shilei; Jiang, Xinguo; Wang, Yajie

    2016-01-01

    The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From the in vivo results, scopolamine intranasal administration can avoid hepatic first-pass effect. Tmax plasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8-70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery.

  13. Magnetic circular dichroism of thiolate-protected plasmonic gold nanoparticles: separating the effects of interband transitions and surface magnetoplasmon resonance

    NASA Astrophysics Data System (ADS)

    Shiratsu, Taisuke; Yao, Hiroshi

    2016-10-01

    Magneto-optical activity is demonstrated in thiolate-protected Au nanoparticles with magnetic circular dichroism (MCD) spectroscopy. The samples examined are decanethiolate-protected Au nanoparticles with the mean diameters ranging from 2.0 to 4.7 nm. The nanoparticles larger than 2.4 nm in diameter exhibit a derivative-like MCD signal, indicating the presence of two circular modes of surface magnetoplasmon, but the spectral shape is so asymmetric that its identification is rather difficult. This is due to the contribution of interband transitions occurring at around the localized surface plasmon resonance (LSPR) frequency. We then develop an efficient method to phenomenologically separate the effects of magnetoplasmonic intraband (= Drude) and interband transitions in the measured MCD spectra using an approximation that the optical response of the Au nanoparticle with a critical size (˜2.0 nm) for the disappearance of LSPR, which is also experimentally obtainable, is substantially dominated by the interband transitions. The consistency of the method is ensured for tiopronin-protected Au nanoparticles, and a very small bisignate magnetoplasmonic response hidden in the total MCD spectrum can be extracted. The practical advantage of the proposed method is that we can intuitively and effectively evaluate the characteristic features of the surface magnetoplasmon of thiolate-protected Au nanoparticles without performing complicated Mie or quasielectrostatic calculations.

  14. Chronic and acute intranasal oxytocin produce divergent social effects in mice.

    PubMed

    Huang, Huiping; Michetti, Caterina; Busnelli, Marta; Managò, Francesca; Sannino, Sara; Scheggia, Diego; Giancardo, Luca; Sona, Diego; Murino, Vittorio; Chini, Bice; Scattoni, Maria Luisa; Papaleo, Francesco

    2014-04-01

    Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors.

  15. Metal-Insulator Transition in Nanoparticle Solids: Insights from Kinetic Monte Carlo Simulations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qu, Luman; Vörös, Márton; Zimanyi, Gergely T.

    Progress has been rapid in increasing the efficiency of energy conversion in nanoparticles. However, extraction of the photo-generated charge carriers remains challenging. Encouragingly, the charge mobility has been improved recently by driving nanoparticle (NP) films across the metal-insulator transition (MIT). To simulate MIT in NP films, we developed a hierarchical Kinetic Monte Carlo transport model. Electrons transfer between neighboring NPs via activated hopping when the NP energies differ by more than an overlap energy, but transfer by a non-activated quantum delocalization, if the NP energies are closer than the overlap energy. As the overlap energy increases, emerging percolating clusters supportmore » a metallic transport across the entire film. We simulated the evolution of the temperature-dependent electron mobility. We analyzed our data in terms of two candidate models of the MIT: (a) as a Quantum Critical Transition, signaled by an effective gap going to zero; and (b) as a Quantum Percolation Transition, where a sample-spanning metallic percolation path is formed as the fraction of the hopping bonds in the transport paths is going to zero. We found that the Quantum Percolation Transition theory provides a better description of the MIT. We also observed an anomalously low gap region next to the MIT. We discuss the relevance of our results in the light of recent experimental measurements.« less

  16. Metal-Insulator Transition in Nanoparticle Solids: Insights from Kinetic Monte Carlo Simulations

    DOE PAGES

    Qu, Luman; Vörös, Márton; Zimanyi, Gergely T.

    2017-08-01

    Progress has been rapid in increasing the efficiency of energy conversion in nanoparticles. However, extraction of the photo-generated charge carriers remains challenging. Encouragingly, the charge mobility has been improved recently by driving nanoparticle (NP) films across the metal-insulator transition (MIT). To simulate MIT in NP films, we developed a hierarchical Kinetic Monte Carlo transport model. Electrons transfer between neighboring NPs via activated hopping when the NP energies differ by more than an overlap energy, but transfer by a non-activated quantum delocalization, if the NP energies are closer than the overlap energy. As the overlap energy increases, emerging percolating clusters supportmore » a metallic transport across the entire film. We simulated the evolution of the temperature-dependent electron mobility. We analyzed our data in terms of two candidate models of the MIT: (a) as a Quantum Critical Transition, signaled by an effective gap going to zero; and (b) as a Quantum Percolation Transition, where a sample-spanning metallic percolation path is formed as the fraction of the hopping bonds in the transport paths is going to zero. We found that the Quantum Percolation Transition theory provides a better description of the MIT. We also observed an anomalously low gap region next to the MIT. We discuss the relevance of our results in the light of recent experimental measurements.« less

  17. Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

    PubMed

    Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

    2014-08-01

    This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs. © 2014 British Small Animal Veterinary Association.

  18. The radiative decays of excited states of transition elements located inside and near core-shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Pukhov, Konstantin K.

    2017-12-01

    Here we discuss the radiative decays of excited states of transition elements located inside and outside of the subwavelength core-shell nanoparticles embedded in dielectric medium. Based on the quantum mechanics and quantum electrodynamics, the general analytical expressions are derived for the probability of the spontaneous transitions in the luminescent centers (emitter) inside and outside the subwavelength core-shell nanoparticle. Obtained expressions holds for arbitrary orientation of the dipole moment and the principal axes of the quadrupole moment of the emitter with respect to the radius-vector r connecting the center of the emitter with the center of the nanoparticle. They have simple form and show how the spontaneous emission in core-shell NPs can be controlled and engineered due to the dependence of the emission rates on core-shell sizes, radius-vector r and permittivities of the surrounding medium, shell, and core.

  19. The effect of size and composition on structural transitions in monometallic nanoparticles

    NASA Astrophysics Data System (ADS)

    Rossi, Kevin; Pavan, Luca; Soon, YeeYeen; Baletto, Francesca

    2018-02-01

    Predicting the morphological stability of nanoparticles is an essential step towards the accurate modelling of their chemophysical properties. Here we investigate solid-solid transitions in monometallic clusters of 0.5-2.0 nm diameter at finite temperatures and we report the complex dependence of the rearrangement mechanism on the nanoparticle's composition and size. The concerted Lipscomb's Diamond-Square-Diamond mechanisms which connects the decahedral or the cuboctahedral to the icosahedral basins, take place only below a material dependent critical size above which surface diffusion prevails and leads to low-symmetry and defected shapes still belonging to the initial basin.

  20. Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.

    PubMed

    Vyas, Tushar K; Babbar, A K; Sharma, R K; Singh, Shashi; Misra, Ambikanandan

    2006-03-01

    The aim of this investigation was to prepare clonazepam microemulsions (CME) for rapid drug delivery to the brain to treat acute status epileptic patients and to characterize and evaluate the performance of CME in vitro and in vivo in rats. The CME were prepared by the titration method and were characterized for globule size and size distribution, zeta potential, and drug content. CME was radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain was studied in Swiss albino rats after intranasal and intravenous administrations. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. Pre and postCME formulation treated human nasal mucosa was subjected to transmission electron microscopy to investigate the mechanism of drug uptake across the nasal mucosa. CME were transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. Transmission electron microscopy revealed significant accretion of CMME within interstitial spaces and paracellular mode of transport due to stretching of the tight junctions present in the nasal mucosa. This investigation demonstrates a more

  1. Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons.

    PubMed

    Salehi, Mohammad Saied; Khazali, Homayoun; Mahmoudi, Fariba; Janahmadi, Mahyar

    2017-08-01

    The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

  2. Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

    PubMed

    Dellweg, Dominic; Wenze, Markus; Hoehn, Ekkehard; Bourgund, Olaf; Haidl, Peter

    2013-08-01

    Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P < .001). In our subjects intranasal humidity dropped significantly, from 40.3 ± 8.7% to 35.3 ± 5.8%, 32 ± 5.6%, and 29.0 ± 6.8% at flows of 1, 2, and 3 L, respectively, when oxygen was given intra-nasally without humidification (P = .001, P < .001, and P < .001, respectively). We observed no significant change in airway humidity when oxygen was given pre-nasally without humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

  3. Iatrogenic Cushing's syndrome caused by intranasal steroid use.

    PubMed

    Dursun, Fatma; Kirmizibekmez, Heves

    2017-01-01

    Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

  4. Experimental transmission of enzootic intranasal tumors of goats.

    PubMed

    De las Heras, M; García de Jalón, J A; Minguijón, E; Gray, E W; Dewar, P; Sharp, J M

    1995-01-01

    The successful experimental transmission of enzootic intranasal tumor (EIT) from goat to goat is described. Ten kids, less than 48 hours old, from a flock free of the disease and seronegative for ruminant lentiviruses were inoculated intranasally or intrasinusally with either nasal fluid from goats with naturally occurring EIT or EIT retrovirus concentrated from such fluids. EIT was induced in three kids after 12-24 months. The EIT retrovirus was demonstrated in tumor material from each of the three kids by western blotting and electron microscopy. All kids were seronegative for ruminant lentiviruses.

  5. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    PubMed

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  6. Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

    PubMed

    Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

    2018-03-14

    The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

  7. Smart Nanoparticles Undergo Phase Transition for Enhanced Cellular Uptake and Subsequent Intracellular Drug Release in a Tumor Microenvironment.

    PubMed

    Ye, Guihua; Jiang, Yajun; Yang, Xiaoying; Hu, Hongxiang; Wang, Beibei; Sun, Lu; Yang, Victor C; Sun, Duxin; Gao, Wei

    2018-01-10

    Inefficient cellular uptake and intracellular drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticle that undergoes phase transition in a tumor microenvironment (TME). The smart nanoparticle is generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH-sensitive hydrophobic poly-l-histidine core and is loaded with the antitumor drug doxorubicin (DOX). The smart nanoparticle undergoes a two-step phase transition at two different pH values in the TME: (i) At the TME (pH e : 7.0-6.5), the smart nanoparticle swells, and its surface potential turns from negative to neutral, facilitating the cellular uptake; (ii) After internalization, at the acid endolysosome (pH endo : 6.5-4.5), the smart nanoparticle dissociates and induces endolysosome escape to release DOX into the cytoplasm. In addition, a tumor-penetrating peptide iNRG was modified on the surface of the smart nanoparticle as a tumor target moiety. The in vitro studies demonstrated that the iNGR-modified smart nanoparticles promoted cellular uptake in the acidic environment (pH 6.8). The in vivo studies showed that the iNGR-modified smart nanoparticles exerted more potent antitumor efficacy against late-stage aggressive breast carcinoma than free DOX. These data suggest that the smart nanoparticles may serve as a promising delivery system for sequential uptake and intracellular drug release of antitumor agents. The easy preparation of these smart nanoparticles may also have advantages in the future manufacture for clinical trials and clinical use.

  8. A Randomized Controlled Trial Comparing Intranasal Midazolam and Chloral Hydrate for Procedural Sedation in Children.

    PubMed

    Stephen, Marie Christy Sharafine; Mathew, John; Varghese, Ajoy Mathew; Kurien, Mary; Mathew, George Ani

    2015-12-01

    To evaluate the efficacy and safety of intranasal midazolam and chloral hydrate syrup for procedural sedation in children. Prospective randomized placebo-controlled trial (double blind, double dummy). Tertiary care hospital over 18 months. Eighty-two children, 1 to 6 years old, undergoing auditory brainstem response testing were randomized to receive either intranasal midazolam with oral placebo or chloral hydrate syrup with placebo nasal spray. Intranasal midazolam was delivered at 0.5 mg/kg (100 mcg per spray) and oral syrup at 50 mg/kg. Children not sedated at 30 minutes had a second dose at half the initial dose. The primary outcomes measured were safety and efficacy. Secondary outcomes were time to onset of sedation, parental separation, nature of parental separation, parental satisfaction, audiologist's satisfaction, time to recovery, and number of attempts. Forty-one children were in each group, and no major adverse events were noted. The chloral hydrate group showed earlier onset of sedation (66%) compared with the intranasal midazolam group (33%). Significant difference in time to recovery was noted in the chloral hydrate group (78 minutes) versus the intranasal midazolam group (108 minutes). The parents' and audiologist's satisfaction was higher for chloral hydrate (95% and 75%) than for intranasal midazolam (49% and 29%, respectively). Overall, sedation was 95% with chloral hydrate versus 51% with intranasal midazolam. Both drugs maintained sedation. Intranasal midazolam and chloral hydrate are both safe and efficacious for pediatric procedural sedation. Chloral hydrate was superior to intranasal midazolam, with an earlier time to onset of sedation, a faster recovery, better satisfaction among parents and the audiologist, and successful sedation. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  9. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

    PubMed

    Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J

    2018-01-01

    Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p  < 0.05) reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared to

  10. Comparison of incidence of hyponatremia between intranasal and oral desmopressin in patients with central diabetes insipidus.

    PubMed

    Kataoka, Yuko; Nishida, Sachi; Hirakawa, Akihiro; Oiso, Yutaka; Arima, Hiroshi

    2015-01-01

    Central diabetes insipidus (CDI), which is characterized by polyuria and polydipsia, is caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP, the intranasal formulation is inconvenient and CDI patients reportedly prefer the oral formulation to the intranasal one. In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when the desmopressin orally disintegrating tablet (ODT) was approved for treatment. In this study we analyzed 26 patients with CDI in whom intranasal desmopressin was switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was 10 ± 8 μg/day, and that of desmopressin ODT was 142 ± 59 μg/day. The mean serum sodium levels were 140 ± 5 mmol/L and 140 ± 3 mmol/L with intranasal desmopressin and desmopressin ODT, respectively, and there were no significant differences between these values. The frequency of hyponatremia (<135 mmol/L) with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%, while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed that incidence of hyponatremia was significantly decreased after the switch to desmopressin ODT. Thus, it is suggested that water balance is better controlled with desmopressin ODT than with intranasal desmopressin in patients with CDI.

  11. Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?

    PubMed Central

    van Woensel, Matthias; Wauthoz, Nathalie; Rosière, Rémi; Amighi, Karim; Mathieu, Véronique; Lefranc, Florence; van Gool, Stefaan W.; de Vleeschouwer, Steven

    2013-01-01

    Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma. PMID:24202332

  12. Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

    PubMed

    Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

    2017-12-01

    Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

  13. Deposition of intranasal glucocorticoids--preliminary study.

    PubMed

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  14. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

    PubMed

    Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

    2017-09-01

    Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

  15. Size-controlled synthesis of transition metal nanoparticles through chemical and photo-chemical routes

    NASA Astrophysics Data System (ADS)

    Tangeysh, Behzad

    The central objective of this work is developing convenient general procedures for controlling the formation and stabilization of nanoscale transition metal particles. Contemporary interest in developing alternative synthetic approaches for producing nanoparticles arises in large part from expanding applications of the nanomaterials in areas such as catalysis, electronics and medicine. This research focuses on advancing the existing nanoparticle synthetic routes by using a new class of polymer colloid materials as a chemical approach, and the laser irradiation of metal salt solution as a photo-chemical method to attain size and shape selectivity. Controlled synthesis of small metal nanoparticles with sizes ranging from 1 to 5nm is still a continuing challenge in nanomaterial synthesis. This research utilizes a new class of polymer colloid materials as nano-reactors and protective agents for controlling the formation of small transition metal nanoparticles. The polymer colloid particles were formed from cross-linking of dinegatively charged metal precursors with partially protonated poly dimethylaminoethylmethacrylate (PDMAEMA). Incorporation of [PtCl6]2- species into the colloidal particles prior to the chemical reduction was effectively employed as a new strategy for synthesis of unusually small platinum nanoparticles with narrow size distributions (1.12 +/-0.25nm). To explore the generality of this approach, in a series of proof-of-concept studies, this method was successfully employed for the synthesis of small palladium (1.4 +/-0.2nm) and copper nanoparticles (1.5 +/-0.6nm). The polymer colloid materials developed in this research are pH responsive, and are designed to self-assemble and/or disassemble by varying the levels of protonation of the polymer chains. This unique feature was used to tune the size of palladium nanoparticles in a small range from 1nm to 5nm. The procedure presented in this work is a new convenient room temperature route for synthesis of

  16. Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters.

    PubMed

    Shah, Brijesh; Khunt, Dignesh; Bhatt, Himanshu; Misra, Manju; Padh, Harish

    2015-10-12

    In the present investigation, Quality by Design (QbD) approach was applied on the development and optimization of solid lipid nanoparticle (SLN) formulation of hydrophilic drug rivastigmine (RHT). RHT SLN were formulated by homogenization and ultrasonication method using Compritol 888 ATO, tween-80 and poloxamer-188 as lipid, surfactant and stabilizer respectively. The effect of independent variables (X1 - drug: lipid ratio, X2 - surfactant concentration and X3 - homogenization time) on quality attributes of SLN i.e. dependent variables (Y1 - size, Y2 - PDI and Y3 - %entrapment efficiency (%EE)) were investigated using 3(3) factorial design. Multiple linear regression analysis and ANOVA were employed to indentify and estimate the main effect, 2FI, quadratic and cubic effect. Optimized RHT SLN formula was derived from an overlay plot on which further effect of probe sonication was evaluated. Final RHT SLN showed narrow size distribution (PDI- 0.132±0.016) with particle size of 82.5±4.07 nm and %EE of 66.84±2.49. DSC and XRD study showed incorporation of RHT into imperfect crystal lattice of Compritol 888 ATO. In comparison to RHT solution, RHT SLN showed higher in-vitro and ex-vivo diffusion. The diffusion followed Higuchi model indicating drug diffusion from the lipid matrix due to erosion. Histopathology study showed intact nasal mucosa with RHT SLN indicating safety of RHT SLN for intranasal administration. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Emission quenching of magnetic dipole transitions near an absorbing nanoparticle (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chigrin, Dmitry N.; Kumar, Deepu; von Plessen, Gero

    2016-09-01

    Emission quenching is analysed at nanometer distances from the surface of an absorbing nanoparticle. It is demonstrated that emission quenching at small distances to the surface is much weaker for magnetic-dipole (MD) than for electric-dipole (ED) transitions. This difference is explained by the fact that the electric field induced by a magnetic dipole has a weaker distance dependence than the electric field of an electric dipole. It is also demonstrated that in the extreme near-field regime the non-locality of the optical response of the metal results in additional emission quenching for both ED and MD transitions.

  18. Brain temperature in volunteers subjected to intranasal cooling.

    PubMed

    Covaciu, L; Weis, J; Bengtsson, C; Allers, M; Lunderquist, A; Ahlström, H; Rubertsson, S

    2011-08-01

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20°C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20°C in awake, unsedated volunteers.

  19. Phase transitions and kinetic properties of gold nanoparticles confined between two-layer graphene nanosheets

    NASA Astrophysics Data System (ADS)

    Wang, Gang; Wu, Nanhua; Chen, Jionghua; Wang, Jinjian; Shao, Jingling; Zhu, Xiaolei; Lu, Xiaohua; Guo, Lucun

    2016-11-01

    The thermodynamic and kinetic behaviors of gold nanoparticles confined between two-layer graphene nanosheets (two-layer-GNSs) are examined and investigated during heating and cooling processes via molecular dynamics (MD) simulation technique. An EAM potential is applied to represent the gold-gold interactions while a Lennard-Jones (L-J) potential is used to describe the gold-GNS interactions. The MD melting temperature of 1345 K for bulk gold is close to the experimental value (1337 K), confirming that the EAM potential used to describe gold-gold interactions is reliable. On the other hand, the melting temperatures of gold clusters supported on graphite bilayer are corrected to the corresponding experimental values by adjusting the εAu-C value. Therefore, the subsequent results from current work are reliable. The gold nanoparticles confined within two-layer GNSs exhibit face center cubic structures, which is similar to those of free gold clusters and bulk gold. The melting points, heats of fusion, and heat capacities of the confined gold nanoparticles are predicted based on the plots of total energies against temperature. The density distribution perpendicular to GNS suggests that the freezing of confined gold nanoparticles starts from outermost layers. The confined gold clusters exhibit layering phenomenon even in liquid state. The transition of order-disorder in each layer is an essential characteristic in structure for the freezing phase transition of the confined gold clusters. Additionally, some vital kinetic data are obtained in terms of classical nucleation theory.

  20. [Efficacy of intranasal antihistamine in the treatment of allergic rhinitis: a meta-analysis].

    PubMed

    Feng, Shaoyan; Deng, Chuntao; Li, Lei; Liao, Wei; Fan, Yunping; Xu, Geng; Li, Huabin

    2014-10-01

    To systematically evaluate the efficacy of intranasal antihistamine in the treatment of allergic rhinitis. The randomized controlled trials (RCT) about intranasal antihistamines for the treatment of allergic rhinitis between January 1985 and January 2014 were searched in OVID, PubMed, EMBASE, CNKI, WanFang Data and Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality, then meta-analysis was performed by using RevMan 5.1 software. A total of thirteen RCTs were included. The results of meta-analysis showed that the efficacy of intranasal antihistamine group was superior to the placebo group in total nasal symptom scores (TNSS), the difference was significant[WMD = -1.96, 95%CI (-2.06;-1.85), P < 0.01], and individual nasal symptom scores (blocked nose, rhinorrhea, and sneezing) [WMD = -0.18, 95%CI (-0.28;-0.08); WMD = -0.45, 95%CI (-0.52;-0.38); WMD = -0.41, 95%CI (-0.58;-0.24), all P < 0.01], with significant differences. There was no significant difference between the intranasal antihistamine group and the corticosteroid group in TNSS [WMD = -1.51, 95%CI (-3.51;0.49), P = 0.14], but the intranasal antihistamines group was superior to the corticosteroid group in individual nasal symptom scores (blocked nose, rhinorrhea, and sneezing) [WMD = -0.23, 95%CI (-0.40;-0.06); WMD = -0.35, 95%CI (-0.65;-0.05); WMD = -0.25, 95%CI (-0.42;-0.08), all P < 0.05], with significant differences. The intranasal antihistamine group was superior to the oral antihistamines group in TNSS [WMD = -0.88, 95%CI (-1.51;-0.25), P < 0.01]. Intranasal antihistamine is effective in the control of nasal symptoms in AR patients.

  1. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans.

    PubMed

    Gancheva, Sofiya; Koliaki, Chrysi; Bierwagen, Alessandra; Nowotny, Peter; Heni, Martin; Fritsche, Andreas; Häring, Hans-Ulrich; Szendroedi, Julia; Roden, Michael

    2015-06-01

    Studies in rodents suggest that insulin controls hepatic glucose metabolism through brain-liver crosstalk, but human studies using intranasal insulin to mimic central insulin delivery have provided conflicting results. In this randomized controlled crossover trial, we investigated the effects of intranasal insulin on hepatic insulin sensitivity (HIS) and energy metabolism in 10 patients with type 2 diabetes and 10 lean healthy participants (CON). Endogenous glucose production was monitored with [6,6-(2)H2]glucose, hepatocellular lipids (HCLs), ATP, and inorganic phosphate concentrations with (1)H/(31)P magnetic resonance spectroscopy. Intranasal insulin transiently increased serum insulin levels followed by a gradual lowering of blood glucose in CON only. Fasting HIS index was not affected by intranasal insulin in CON and patients. HCLs decreased by 35% in CON only, whereas absolute hepatic ATP concentration increased by 18% after 3 h. A subgroup of CON received intravenous insulin to mimic the changes in serum insulin and blood glucose levels observed after intranasal insulin. This resulted in a 34% increase in HCLs without altering hepatic ATP concentrations. In conclusion, intranasal insulin does not affect HIS but rapidly improves hepatic energy metabolism in healthy humans, which is independent of peripheral insulinemia. These effects are blunted in patients with type 2 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Intranasal hydroxypropyl-β-cyclodextrin-adjuvanted influenza vaccine protects against sub-heterologous virus infection.

    PubMed

    Kusakabe, Takato; Ozasa, Koji; Kobari, Shingo; Momota, Masatoshi; Kishishita, Natsuko; Kobiyama, Kouji; Kuroda, Etsushi; Ishii, Ken J

    2016-06-08

    Intranasal vaccination with inactivated influenza viral antigens is an attractive and valid alternative to currently available influenza (flu) vaccines; many of which seem to need efficient and safe adjuvant, however. In this study, we examined whether hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used pharmaceutical excipient to improve solubility and drug delivery, can act as a mucosal adjuvant for intranasal flu vaccines. We found that intranasal immunization of mice with hemagglutinin split- as well as inactivated whole-virion influenza vaccine with HP-β-CD resulted in secretion of antigen-specific IgA and IgGs in the airway mucosa and the serum as well. As a result, both HP-β-CD adjuvanted-flu intranasal vaccine protected mice against lethal challenge with influenza virus, equivalent to those induced by experimental cholera toxin-adjuvanted ones. Of note, intranasal use of HP-β-CD as an adjuvant induced significantly lower antigen-specific IgE responses than that induced by aluminum salt adjuvant. These results suggest that HP-β-CD may be a potent mucosal adjuvant for seasonal and pandemic influenza vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia.

    PubMed

    Drees, R; Forrest, L J; Chappell, R

    2009-07-01

    Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity.

  4. Determining the Catalytic Activity of Transition Metal-Doped TiO2 Nanoparticles Using Surface Spectroscopic Analysis

    NASA Astrophysics Data System (ADS)

    Yang, Sena; Lee, Hangil

    2017-11-01

    The modified TiO2 nanoparticles (NPs) to enhance their catalytic activities by doping them with the five transition metals (Cr, Mn, Fe, Co, and Ni) have been investigated using various surface analysis techniques such as scanning electron microscopy (SEM), Raman spectroscopy, scanning transmission X-ray microscopy (STXM), and high-resolution photoemission spectroscopy (HRPES). To compare catalytic activities of these transition metal-doped TiO2 nanoparticles (TM-TiO2) with those of TiO2 NPs, we monitored their performances in the catalytic oxidation of 2-aminothiophenol (2-ATP) by using HRPES and on the oxidation of 2-ATP in aqueous solution by taking electrochemistry (EC) measurements. As a result, we clearly investigate that the increased defect structures induced by the doped transition metal are closely correlated with the enhancement of catalytic activities of TiO2 NPs and confirm that Fe- and Co-doped TiO2 NPs can act as efficient catalysts.

  5. Ameliorating Impact of Prophylactic Intranasal Oxytocin on Signs of Fear in a Rat Model of Traumatic Stress

    PubMed Central

    Renicker, Micah D.; Cysewski, Nicholas; Palmer, Samuel; Nakonechnyy, Dmytro; Keef, Andrew; Thomas, Morgan; Magori, Krisztian; Daberkow, David P.

    2018-01-01

    Oxytocin treatment reduces signs of long-term emotional stress after exposure to trauma; however, little is known about the potential protective effects of oxytocin treatment on behavioral and physiological changes associated with extreme stress exposure. The objective of this study was to investigate oxytocin treatment as a prophylactic measure against rat signs of fear. Two separate experiments were conducted in which the time of intranasal oxytocin administration differed. Intranasal oxytocin (1.0 μg/kg) was administered 5 min after daily exposure to foot shock in Experiment #1 and 1 h before foot shock in Experiment #2. In Experiment #1, possible massage-evoked oxytocin release (5 min after foot shock) was also investigated. In both experiments, a contextual fear conditioning procedure was employed in which stress was induced via inescapable foot shock (3 days, 40 shocks/day, 8 mA/shock) in a fear conditioning chamber. Male Sprague-Dawley rats (n = 24) were divided into four groups (n = 6, per group) for each experiment. Experiment #1 groups: Control Exp#1 (intranasal saline and no foot shock); Stress Exp#1 (intranasal saline 5 min after foot shock); Massage+Stress Exp#1 (massage-like stroking and intranasal saline 5 min after foot shock); Oxytocin+Stress Exp#1 (intranasal oxytocin 5 min after foot shock). Experiment #2 groups: Control Exp#2 (intranasal saline and no foot shock); Stress Exp#2 (intranasal saline 1 h before foot shock); Oxytocin Exp#2 (intranasal oxytocin and no foot shock); Oxytocin+Stress Exp#2 (intranasal oxytocin 1 h before foot shock). One week after fear conditioning (and other treatments), rats were independently evaluated for behavioral signs of fear. Two weeks after conditioning, physiological signs of fear were also assessed (Experiment #1). Relative to controls, rats treated with intranasal oxytocin 5 min after daily foot shock sessions exhibited significantly less immobility upon re-exposure to the shock chamber and attenuated

  6. Intranasal delivery of ciprofloxacin to rats: A topical approach using a thermoreversible in situ gel.

    PubMed

    Sousa, Joana; Alves, Gilberto; Oliveira, Paula; Fortuna, Ana; Falcão, Amílcar

    2017-01-15

    Intranasal administration of antibiotics is an alternative and attractive delivery approach in the treatment of local infections such as chronic rhinosinusitis. This topical route has the advantage of delivering high drug concentrations directly to the site of infection when trying to eradicate the highly resistant bacterial biofilms. The purpose of this study was to assess and compare the pharmacokinetic parameters of ciprofloxacin following intranasal and intravenous administrations to rats in plasma, olfactory bulb and nasal mucosa of two different nasal regions. For intranasal administration a thermoreversible in situ gel was used to increase drug residence time in nasal cavity. Ciprofloxacin concentration time-profile in nasal mucosa of the studied anterior region (at naso- and maxilloturbinates level) was markedly higher after intranasal administration (0.24mg/kg) than that following intravenous administration (10mg/kg), while in nasal mucosa of the more posterior region (at ethmoidal turbinates level) ciprofloxacin concentrations were found to be higher after intranasal administration when the different dose administered by both routes is taken into account. A plateau in ciprofloxacin concentration was observed in nasal mucosa of both studied regions after intranasal administration, suggesting a slow delivery of the drug over a period of time using the nasal gel formulation. In plasma and olfactory bulb, concentration of ciprofloxacin was residual after intranasal administration, which demonstrates this is a safe administration route by preventing systemic and particularly central nervous system adverse effects. Dose-normalized pharmacokinetic parameters of ciprofloxacin exposure to nasal mucosa revealed higher values after intranasal delivery not only in the anterior region but also in the posterior nasal region. In conclusion, topical intranasal administration appears to be advantageous for delivering ciprofloxacin to the biophase, with negligible systemic

  7. Design and Efficacy of Nanogels Formulations for Intranasal Administration.

    PubMed

    Aderibigbe, Blessing A; Naki, Tobeka

    2018-05-23

    Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration.

  8. A Novel Approach to Brachycephalic Syndrome. 1. Evaluation of Anatomical Intranasal Airway Obstruction.

    PubMed

    Oechtering, Gerhard U; Pohl, Sabine; Schlueter, Claudia; Lippert, Johanna P; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Schuenemann, Riccarda

    2016-02-01

    To evaluate airway obstruction due to abnormal intranasal anatomy in 3 brachycephalic dog breeds using computed tomography and rhinoscopy. Prospective clinical study. A total of 132 brachycephalic dogs (66 Pugs, 55 French Bulldogs, and 11 English Bulldogs) with severe respiratory distress due to brachycephalic syndrome. Computed tomography and anterior and posterior rhinoscopy were performed to evaluate endonasal obstruction. All dogs had abnormal conchal growth that obstructed the intranasal airways. Rostral aberrant turbinates (RAT) were common in Pugs (90.9%) but less frequent in French (56.4%) and English (36.4%) Bulldogs. Caudal aberrant turbinates (CAT) obstructing the nasopharyngeal meatus were commonly found in all breeds (66.7%). Deviation of the nasal septum was an almost consistent finding in Pugs (98.5%) but was less common in bulldogs. Obstructing turbinates had multiple points of mucosal contact responsible for obstruction of the intranasal airway. Interconchal and intraconchal mucosal contacts were evident in 91.7% of dogs. Selective breeding for short head conformation reduces the size of the nasal cavities to such an extent that intranasal structures grow aberrantly and malformed, leading to obstructed air conducting spaces. Intranasal airway obstruction of brachycephalic dogs may contribute to their exercise and heat intolerance because of impaired pulmonary ventilation and compromised thermoregulatory functions of the canine nose. Failure to address intranasal obstruction might be an explanation for lack of therapeutic success after conventional surgery for brachycephalic syndrome. Future consideration should be given to the diagnosis, management, and treatment of this newly described aspect of airway obstruction. © Copyright 2016 by The American College of Veterinary Surgeons.

  9. Intranasal mast cell tumor in the dog: A case series

    PubMed Central

    Khoo, Alison; Lane, Amy; Wyatt, Ken

    2017-01-01

    The medical records of 4 dogs with histologically confirmed intranasal mast cell tumors (MCTs) were retrospectively evaluated to determine their biological behavior. Information on signalment, presenting clinical signs, tumor grade, treatment administered, and survival times was obtained from the medical record. All 4 patients had high grade tumors and received chemotherapy. Survival times ranged from 27 to 134 days. All 4 dogs showed signs of local or distant disease progression, suggestive of an aggressive behavior of intranasal MCTs. PMID:28761193

  10. A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs.

    PubMed

    Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

    2009-08-01

    To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.

  11. Relative Bioavailability, Intranasal Abuse Potential, and Safety of Benzhydrocodone/Acetaminophen Compared with Hydrocodone Bitartrate/Acetaminophen in Recreational Drug Abusers.

    PubMed

    Guenther, Sven M; Mickle, Travis C; Barrett, Andrew C; Roupe, Kathryn Ann; Zhou, Jing; Lam, Vincent

    2018-05-01

    Benzhydrocodone is a hydrocodone prodrug that has been combined with acetaminophen (APAP) in a novel immediate-release analgesic. This study evaluated the relative bioavailability, intranasal abuse potential, and safety of benzhydrocodone/APAP compared with commercially available hydrocodone bitartrate (HB)/APAP. Single-center, randomized, double-blind, double-dummy, two-part study comprising a Dose Selection (Part A) phase and a Main Study (Part B) phase. Clinical research site. Healthy adult, nondependent, recreational opioid users with a history of intranasal abuse. Subjects (N = 42) in Part B received five in-clinic treatments consisting of intranasal and oral benzhydrocodone/APAP (13.34/650 mg), intranasal and oral hydrocodone/APAP (15/650 mg), and placebo, with four or more days of washout between treatments. Pharmacodynamic assessments included subjective effects of Drug Liking, Overall Drug Liking, and Take Drug Again (assessed on visual analog scale [VAS]), as well as nasal irritation. Pharmacokinetics and safety were also assessed. Hydrocodone Cmax was 11% lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P = 0.0027). Early cumulative hydrocodone exposures for intranasal benzhydrocodone/APAP through 0.5, 1, and 2 hours were reduced by approximately 50%, 29%, and 15%, respectively (P ≤ 0.0024). Correspondingly, Drug Liking VAS values up to two hours postdose were significantly lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P ≤ 0.0079), although peak Drug Liking VAS (Emax) scores were not different (P = 0.2814). Adverse nasal effects were more frequent for intranasal benzhydrocodone/APAP vs intranasal HB/APAP. Reduced hydrocodone exposure and drug liking at early time intervals, coupled with adverse nasal effects, can be expected to provide a level of deterrence to the intranasal route of abuse for benzhydrocodone/APAP.

  12. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    PubMed

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  13. Comparison of computed tomography and magnetic resonance imaging for the evaluation of canine intranasal neoplasia

    PubMed Central

    Drees, R.; Forrest, L. J.; Chappell, R.

    2009-01-01

    Objectives Canine intranasal neoplasia is commonly evaluated using computed tomography to indicate the diagnosis, to determine disease extent, to guide histological sampling location and to plan treatment. With the expanding use of magnetic resonance imaging in veterinary medicine, this modality has been recently applied for the same purpose. The aim of this study was to compare the features of canine intranasal neoplasia using computed tomography and magnetic resonance imaging. Methods Twenty-one dogs with confirmed intranasal neoplasia underwent both computed tomography and magnetic resonance imaging. The images were reviewed retrospectively for the bony and soft tissue features of intranasal neoplasia. Results Overall computed tomography and magnetic resonance imaging performed very similarly. However, lysis of bones bordering the nasal cavity and mucosal thickening was found on computed tomography images more often than on magnetic resonance images. Small amounts of fluid in the nasal cavity were more often seen on magnetic resonance images. However, fluid in the frontal sinuses was seen equally well with both modalities. Clinical Significance We conclude that computed tomography is satisfactory for evaluation of canine intranasal neoplasia, and no clinically relevant benefit is gained using magnetic resonance imaging for intranasal neoplasia without extent into the cranial cavity. PMID:19508490

  14. Police officer attitudes towards intranasal naloxone training.

    PubMed

    Ray, Bradley; O'Donnell, Daniel; Kahre, Kailyn

    2015-01-01

    One approach to reduce fatal opioid overdose is by distributing naloxone to law enforcement officers. While several cities have implemented these naloxone programs, little research has investigated officer attitudes about their training. The present research attempts to fill this gap by analyzing survey data from police officers following intranasal naloxone training. All of the police officers within the same district in Indianapolis, Indiana, underwent training to recognize opioid overdose and to administer intranasal naloxone (N=117). Following training, officers completed a survey that measured prior experience with opioid overdose, perceived importance of training, and items from the Opioid Overdose Attitudes Scale (OOAS) to measure attitudes following training. The officers had overwhelmingly positive feelings about the training, that it was not difficult, and that other officers should be trained to use naloxone. The OOAS items suggest that officers know the appropriate actions to take in the event of an overdose and feel that administering intranasal naloxone will not be difficult. Finally, we found that officers who had more experience with opioid overdose had more positive attitudes about the training. Distributing naloxone to police officers is likely a trend that will continue so it is important to understand how police officers respond to training to assure that future trainings are as effective as possible. Further research is needed to investigate the impact that these programs have on the community. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

    PubMed

    Dal Monte, Olga; Noble, Pamela L; Turchi, Janita; Cummins, Alex; Averbeck, Bruno B

    2014-01-01

    Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

  16. The Association of Industry Payments to Physicians with Prescription of Brand-Name Intranasal Corticosteroids.

    PubMed

    Morse, Elliot; Fujiwara, Rance J T; Mehra, Saral

    2018-06-01

    Objectives To examine the association of industry payments for brand-name intranasal corticosteroids with prescribing patterns. Study Design Cross-sectional retrospective analysis. Setting Nationwide. Subjects and Methods We identified physicians prescribing intranasal corticosteroids to Medicare beneficiaries 2014-2015 and physicians receiving payment for the brand-name intranasal corticosteroids Dymista and Nasonex. Prescription and payment data were linked by physician, and we compared the proportion of prescriptions written for brand-name intranasal corticosteroids in industry-compensated vs non-industry-compensated physicians. We associated the number and dollar amount of industry payments with the relative frequency of brand-name prescriptions. Results In total, 164,587 physicians prescribing intranasal corticosteroids were identified, including 7937 (5%) otolaryngologists; 10,800 and 3886 physicians received industry compensation for Dymista and Nasonex, respectively. Physicians receiving industry payment for Dymista prescribed more Dymista as a proportion of total intranasal corticosteroid prescriptions than noncompensated physicians (3.1% [SD = 9.6%] vs 0.2% [SD = 2.5%], respectively, P < .001). Similar trends were seen for Nasonex (12.0% [SD = 16.8%] vs 4.8% [SD = 13.6%], P < .001). The number and dollar amount of payment were significantly correlated to the relative frequency of Dymista (ρ = 0.26, P < .001 and ρ = 0.20, P < .001, respectively) and Nasonex prescriptions (ρ = 0.09, P < .001 and ρ = 0.15, P < .001, respectively). For Dymista, this association was stronger in otolaryngologists than general practitioners ( P < .001). There was a stronger correlation between the percentage of prescriptions and the number and dollar amount of payments for Dymista than for Nasonex ( P = .014 and P < .001). Conclusions Industry compensation for brand-name intranasal corticosteroids is significantly associated with prescribing patterns. The magnitude of

  17. Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice

    PubMed Central

    Kageyama, Haruaki; Shiba, Kanako; Hirako, Satoshi; Wada, Nobuhiro; Yamanaka, Satoru; Nogi, Yukinori; Takenoya, Fumiko; Nonaka, Naoko; Hirano, Tsutomu; Inoue, Shuji; Shioda, Seiji

    2016-01-01

    Galanin-like peptide (GALP) has an anti-obesity effect in rats and mice. It has been reported that the uptake of GALP by the brain is higher after intranasal administration than with intravenous injection. This study therefore aimed to clarify the effect of intranasal administration of GALP on the feeding behavior of lean and obese mice. Autoradiography revealed the presence of 125I-GALP in the olfactory bulb and the brain microcirculation. The body weights of ob/ob mice gradually increased during vehicle treatment, but remained unchanged in response to repeated intranasal administration of GALP, with both ob/ob and diet-induced obese mice displaying significantly decreased food intake, water intake and locomotor activity when treated with GALP. These results suggest that intranasal administration is an effective route whereby GALP can exert its effect as an anti-obesity drug. PMID:27323911

  18. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    PubMed

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice

    PubMed Central

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Martinez, Ana; Faghihi, Mohammad A.; Jope, Richard S.; Beurel, Eleonore

    2017-01-01

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA– or HDAC4 siRNA–induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1–/– mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets. PMID:28352664

  20. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

    PubMed

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Eldar-Finkelman, Hagit; Martinez, Ana; Faghihi, Mohammad A; Jope, Richard S; Beurel, Eleonore

    2017-03-23

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1 -/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

  1. Intranasal nerve growth factor attenuating the seizure onset via p75R/Caspase pathway in the experimental epilepsy.

    PubMed

    Lei, Jing'an; Feng, Fang; Duan, Yuanyuan; Xu, Feng; Liu, Zhiguang; Lian, Lifei; Liang, Qiming; Zhang, Na; Wang, Furong

    2017-09-01

    Nerve growth factor (NGF) shows neuroprotection while it is hard to cross the blood-brain barrier due to its large molecular weight. Our study used intranasal delivery of NGF to treat the experimental epilepsy. The seizure was induced by injection of pentylenetetrazol (40mg/kg) into the rat. Based on the behavior performance, the successful models were randomized into control and NGF groups, given medium or NGF intranasally, respectively. The onset and duration of seizure were recorded. The neuron loss was assessed by immunohistochemistry and TUNEL staining. The expressions of Caspase-3, p75R and TrkA were measured by western blotting. Intranasal NGF significantly reduced the seizure onset and shortened the seizure duration. Intranasal NGF alleviated the neuron loss in the epileptic brain. The number of TUNEL-positive cells in the NGF group was less than that in the control group (P<0.05). Overexpression of Caspase-3 and activation of p75R induced by seizure were inhibited by intranasal NGF. Intranasal NGF protected neurons in the epileptic brain by inactivation of p75R/Caspase pathway. Intranasal NGF may be a novel therapeutic strategy for epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Intranasal bacille Calmette–Guérin (BCG) vaccine dosage needs balancing between protection and lung pathology

    PubMed Central

    TREE, J A; WILLIAMS, A; CLARK, S; HALL, G; MARSH, P D; IVANYI, J

    2004-01-01

    Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette–Guérin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs. PMID:15544615

  3. Growth-dissolution-regrowth transitions of Fe3O4 nanoparticles as building blocks for 3D magnetic nanoparticle clusters under hydrothermal conditions.

    PubMed

    Lin, Mouhong; Huang, Haoliang; Liu, Zuotao; Liu, Yingju; Ge, Junbin; Fang, Yueping

    2013-12-10

    Magnetic nanoparticle clusters (MNCs) are a class of secondary structural materials that comprise chemically defined nanoparticles assembled into clusters of defined size. Herein, MNCs are fabricated through a one-pot solvothermal reaction featuring self-limiting assembly of building blocks and the controlled reorganization process. Such growth-dissolution-regrowth fabrication mechanism overcomes some limitations of conventional solvothermal fabrication methods with regard to restricted available feature size and structural complexity, which can be extended to other oxides (as long as one can be chelated by EDTA-2Na). Based on this method, the nanoparticle size of MNCs is tuned between 6.8 and 31.2 nm at a fixed cluster diameter of 120 nm, wherein the critical size for superparamagnetic-ferromagnetic transition is estimated from 13.5 to 15.7 nm. Control over the nature and secondary structure of MNCs gives an excellent model system to understand the nanoparticle size-dependent magnetic properties of MNCs. MNCs have potential applications in many different areas, while this work evaluates their cytotoxicity and Pb(2+) adsorption capacity as initial application study.

  4. Understanding the Enhanced Catalytic Performance of Ultrafine Transition Metal Nanoparticles-Graphene Composites

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Meng, Changgong; Han, Yu

    2015-09-01

    Catalysis, as the key to minimize the energy requirement and environmental impact of today's chemical industry, plays a vital role in many fields directly related to our daily life and economy, including energy generation, environment control, manufacture of chemicals, medicine synthesis, etc. Rational design and fabrication of highly efficient catalysts have become the ultimate goal of today's catalysis research. For the purpose of handling and product separation, heterogeneous catalysts are highly preferred for industrial applications and a large part of which are the composites of transition metal nanoparticles (TMNPs). With the fast development of nanoscience and nanotechnology and assisted with theoretical investigations, basic understanding on tailoring the electronic structure of these nanocomposites has been gained, mainly by precise control of the composition, morphology, interfacial structure and electronic states. With the rise of graphene, chemical routes to prepare graphene were developed and various graphene-based composites were fabricated. Transition metal nanoparticles-reduced graphene oxide (TMNPs-rGO) composites have attracted considerable attention, because of their intriguing catalytic performance which have been extensively explored for energy- and environment-related applications to date. This review summarizes our recent experimental and theoretical efforts on understanding the superior catalytic performance of subnanosized TMNPs-rGO composites.

  5. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

    PubMed

    Galinkin, J L; Fazi, L M; Cuy, R M; Chiavacci, R M; Kurth, C D; Shah, U K; Jacobs, I N; Watcha, M F

    2000-12-01

    Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during

  6. The effects of adjunctive intranasal oxytocin in patients with schizophrenia.

    PubMed

    Ota, Miho; Yoshida, Sumiko; Nakata, Masanori; Yada, Toshihiko; Kunugi, Hiroshi

    2018-01-01

    Both human and animal studies have suggested that oxytocin may have therapeutic potential in the treatment of schizophrenia. We evaluated the effects of intranasal oxytocin on cognition and its predictive factors in Japanese patients with schizophrenia. Subjects were 16 chronic schizophrenia patients who underwent intranasal oxytocin treatment for 3 months and were assessed for changes in severity of clinical symptoms and cognitions. Fifteen of the 16 subjects underwent 3-Tesla magnetic resonance imaging. Oxytocin significantly reduced scores on the positive and negative syndrome scale, especially on the negative symptoms. As for cognition, there was an improvement of the verbal fluency. Furthermore, the change of the negative score in positive and negative syndrome scale showed a negative correlation with the gray matter volumes of the right insula and left cingulate cortex. Our results indicate that daily administration of intranasal oxytocin may be effective for ameliorating clinical symptoms and cognitive functions in chronic schizophrenia patients, and this improvement may be related to the gray matter volume of the right insula and left cingulate cortex.

  7. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration.

    PubMed

    Lochhead, Jeffrey J; Wolak, Daniel J; Pizzo, Michelle E; Thorne, Robert G

    2015-03-01

    The intranasal administration route is increasingly being used as a noninvasive method to bypass the blood-brain barrier because evidence suggests small fractions of nasally applied macromolecules may reach the brain directly via olfactory and trigeminal nerve components present in the nasal mucosa. Upon reaching the olfactory bulb (olfactory pathway) or brainstem (trigeminal pathway), intranasally delivered macromolecules appear to rapidly distribute within the brains of rodents and primates. The mechanisms responsible for this distribution have yet to be fully characterized. Here, we have used ex vivo fluorescence imaging to show that bulk flow within the perivascular space (PVS) of cerebral blood vessels contributes to the rapid central distribution of fluorescently labeled 3 and 10 kDa dextran tracers after intranasal administration in anesthetized adult rats. Comparison of tracer plasma levels and fluorescent signal distribution associated with the PVS of surface arteries and internal cerebral vessels showed that the intranasal route results in unique central access to the PVS not observed after matched intravascular dosing in separate animals. Intranasal targeting to the PVS was tracer size dependent and could be regulated by modifying nasal epithelial permeability. These results suggest cerebral perivascular convection likely has a key role in intranasal drug delivery to the brain.

  8. Intranasal and sublingual delivery of inactivated polio vaccine.

    PubMed

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    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. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  9. Enhancement of immunogenic response and protection in model rats by CSTM nanoparticles anticaries DNA vaccine.

    PubMed

    Li, Hongjiao; Lu, Yiming; Xiang, Jingjie; Jiang, Hailong; Zhong, Yanqiang; Lu, Ying

    2016-06-01

    To construct anticaries DNA vaccine and evaluate its ability to elicit mucosal and systemic immune responses in rats. wapA fragment was cloned into pVAX1 plasmid to generate pVAX1-wapA. The pVAX1-wapA/trimethyl chitosan nanoparticles were prepared by complex coacervation method. Significantly higher specific IgG antibody titers were observed in rats immunized with nanoparticles compared with rats immunized with naked pVAX1-wapA. Anti-WapA IgA and IgG antibody levels after intranasal immunization were significantly higher than those following intramuscular delivery of nanoparticles or naked pVAX1-wapA. Furthermore, fewer enamel, slight dentin and dentin moderate lesions were observed in rats immunized with nanoparticles. The results implicate WapA as an excellent candidate for anticaries vaccine development and nanoparticles as an effective delivery system.

  10. Determination of phenolic compounds using spectral and color transitions of rhodium nanoparticles.

    PubMed

    Gatselou, Vasiliki; Christodouleas, Dionysios C; Kouloumpis, Antonios; Gournis, Dimitrios; Giokas, Dimosthenis L

    2016-08-17

    This work reports a new approach for the determination of phenolic compounds based on their interaction with citrate-capped rhodium nanoparticles. Phenolic compounds (i.e., catechins, gallates, cinnamates, and dihydroxybenzoic acids) were found to cause changes in the size and localized surface plasmon resonance of rhodium nanoparticles, and therefore, give rise to analyte-specific spectral and color transitions in the rhodium nanoparticle suspensions. Upon reaction with phenolic compounds (mainly dithydroxybenzoate derivatives, and trihydroxybenzoate derivatives), new absorbance peaks at 350 nm and 450 nm were observed. Upon reaction with trihydroxybenzoate derivatives, however, an additional absorbance peak at 580 nm was observed facilitating the speciation of phenolic compounds in the sample. Both absorbance peaks at 450 nm and 580 nm increased with increasing concentration of phenolic compounds over a linear range of 0-500 μM. Detection limits at the mid-micromolar levels were achieved, depending on the phenolic compound involved, and with satisfactory reproducibility (<7.3%). On the basis of these findings, two rhodium nanoparticles-based assays for the determination of the total phenolic content and total catechin content were developed and applied in tea samples. The obtained results correlated favorably with commonly used methods (i.e., Folin-Ciocalteu and aluminum complexation assay). Not the least, the finding that rhodium nanoparticles can react with analytes and exhibit unique localized surface plasmon resonance bands in the visible region, can open new opportunities for developing new optical and sensing analytical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  12. Realization of atomistic transitions with colloidal nanoparticles using an ultrafast laser

    NASA Astrophysics Data System (ADS)

    Akguc, Gursoy; Ilday, Serim; Ilday, Omer; Gulseren, Oguz; Makey, Ghaith; Yavuz, Koray

    We report on realization of rapid atomistic transitions with colloidal nanoparticles in a setting that constitutes a dissipative far-from-equilibrium system subject to stochastic forces. Large colloidal crystals (comprising hundreds of particles) can be formed and transitions between solid-liquid-gas phases can be observed effortlessly and within seconds. Furthermore, this system allows us to form and dynamically arrest metastable phases such as glassy structures and to controllably transform a crystal pattern from square to hexagonal lattices and vice versa as well as to observe formation and propagation of crystal defects (i.e. line defects, point defects, planar defects). The mechanism largely relies on an interplay between convective forces induced by femtosecond pulses and strong Brownian motion; the former drags the colloids to form and reinforce the crystal and the latter is analogous to lattice vibrations, which makes it possible to observe phase transitions, defect formation and propagation and lattice transformation. This unique system can help us get insight into the mechanisms underlying various solid state phenomena that were previously studied under slowly evolving (within hours/days), near-equilibrium colloidal systems.

  13. Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine.

    PubMed

    Weerts, Aurélie P; Pattyn, Nathalie; Putcha, Lakshmi; Hoag, Stephen W; Van Ombergen, Angelique; Hallgren, Emma; Van de Heyning, Paul H; Wuyts, Floris L

    2015-12-01

    Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. This double-blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. © The Author(s) 2015.

  14. Intranasal pirodavir (R77,975) treatment of rhinovirus colds.

    PubMed Central

    Hayden, F G; Hipskind, G J; Woerner, D H; Eisen, G F; Janssens, M; Janssen, P A; Andries, K

    1995-01-01

    A randomized, double-blind, placebo-controlled trial assessed the therapeutic efficacy of intranasal pirodavir in naturally occurring rhinovirus colds. Adults with symptoms of < or = 2 days' duration were randomly assigned to intranasal sprays of pirodavir (2 mg per treatment) or placebo six times daily for 5 days. In people with laboratory-documented rhinovirus colds (53 in the pirodavir group, 55 in the placebo group), no significant differences in the resolution of respiratory symptoms were apparent between the groups. The median duration of illness was 7 days in each group. Similarly, scores for individual symptoms found no differences in favor of pirodavir during or after treatment. In contrast, reduced frequencies of rhinovirus shedding were observed in the pirodavir group on day 3 (70 versus 23%; P < 0.001) and day 5 (38 versus 12%; P = 0.002) but not after the cessation of treatment, on day 7 (19 versus 21%). No pirodavir-resistant viruses were recovered from treated individuals. The pirodavir group had higher rates of nasal dryness, blood in mucus, or unpleasant taste on several study days. In summary, intranasal sprays of pirodavir were associated with significant antiviral effects but no clinical benefit in treating naturally occurring rhinovirus colds. PMID:7726484

  15. Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

    PubMed

    Wu, Lei; Boyd, Jason L; Daniels, Vernie; Wang, Zuwei; Chow, Diana S-L; Putcha, Lakshmi

    2015-02-01

    Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness. © 2014, The American College of Clinical Pharmacology.

  16. Abnormal cubic-tetragonal phase transition of barium strontium titanate nanoparticles studied by in situ Raman spectroscopy and transmission electron microscopy heating experiments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Yin; Chen, Chen; Gao, Ran

    2015-11-02

    Phase stability of the ferroelectric materials at high temperature is extremely important to their device performance. Ba{sub x}Sr{sub 1−x}TiO{sub 3} (BST) nanoparticles with different Sr contents (x = 1, 0.91, 0.65, 0.4, and 0) are prepared by a facile hydrothermal method. Using Raman spectroscopy and transmission electron microscopy (TEM) analyses under in situ heating conditions (up to 300 °C), the phase transitions of BST nanoparticles between 25 °C and 280 °C are comprehensively investigated. The original Curie temperature of BST nanoparticles decreases abruptly with the increase in Sr content, which is more obvious than in the bulk or film material. Besides, an abnormal phase transitionmore » from cubic to tetragonal structure is observed from BST nanoparticles and the transition temperature rises along with the increase in Sr content. Direct TEM evidences including a slight lattice distortion have been provided. Differently, BaTiO{sub 3} nanoparticles remained in the tetragonal phase during the above temperature ranges.« less

  17. Kinetic Transition of Crystal Morphology from Nanoparticles to Dendrites during Electron Beam Induced Deposition of Gold

    NASA Astrophysics Data System (ADS)

    Park, Jeung Hun; Schneider, Nicholas; Bau, Haim; Kodambaka, Suneel; Ross, Frances

    2015-03-01

    We studied the kinetic transition from compact nanoparticle to dendritic morphology during electron beam-induced Au deposition using in situ liquid cell-based transmission electron microcopy. Radiolysis of water by electrons generates radicals and molecular species. Hydrated electrons and hydrogen and hydroxide radicals can act as reducing agents and initiate the reduction of the water-soluble precursor, HAuCl4, resulting in the precipitation of Au as nanostructures. We tracked nucleation, growth, and morphological transition of Au from movies recorded in situ, as a function of irradiated dose and liquid thickness. We identified several distinct regimes that depend on the irradiation time: (1) nucleation; (2) linear volumetric growth; (3) formation of dendritic structures; (4) coalescence and dissolution. A diffusion and reaction model for the radiolytic species and metal ions in the confined geometry of the irradiated volume is used to understand the nucleation sites and morphological transitions. We finally describe how nanoparticles can be made to grow in a stepwise manner by switching the supply of Au ions on and off electrochemically, and discuss possibilities for creating more complex nanostructures. This research was partially funded by the National Science Foundation (DMR-1310639, CMMI-1129722, and CBET-1066573).

  18. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    PubMed

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

    PubMed

    Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

    2016-01-01

    Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

  20. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women.

    PubMed

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-04-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value.

  1. Long-term exposure to intranasal oxytocin in a mouse autism model

    PubMed Central

    Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P

    2014-01-01

    Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT. PMID:25386957

  2. Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

    PubMed

    Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

    2015-01-01

    Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

  3. Noble-transition metal nanoparticle breathing in a reactive gas atmosphere.

    PubMed

    Petkov, Valeri; Shan, Shiyao; Chupas, Peter; Yin, Jun; Yang, Lefu; Luo, Jin; Zhong, Chuan-Jian

    2013-08-21

    In situ high-energy X-ray diffraction coupled to atomic pair distribution function analysis is used to obtain fundamental insight into the effect of the reactive gas environment on the atomic-scale structure of metallic particles less than 10 nm in size. To substantiate our recent discovery we investigate a wide range of noble-transition metal nanoparticles and confirm that they expand and contract radially when treated in oxidizing (O2) and reducing (H2) atmospheres, respectively. The results are confirmed by supplementary XAFS experiments. Using computer simulations guided by the experimental diffraction data we quantify the effect in terms of both relative lattice strain and absolute atomic displacements. In particular, we show that the effect leads to a small percent of extra surface strain corresponding to several tenths of Ångström displacements of the atoms at the outmost layer of the particles. The effect then gradually decays to zero within 4 atomic layers inside the particles. We also show that, reminiscent of a breathing type structural transformation, the effect is reproducible and reversible. We argue that because of its significance and widespread occurrence the effect should be taken into account in nanoparticle research.

  4. Effect of particle size on phase transition among metastable alumina nanoparticles: A view from high resolution 2D solid-state 27Al NMR study

    NASA Astrophysics Data System (ADS)

    Kim, H.; Lee, S.

    2012-12-01

    The detailed knowledge of atomic structures of diverse metastable/stable polymorphs in alumina nanoparticles is essential to understand their macroscopic properties. Alumina undergoes successive phase transitions from metastable γ-, δ-, and θ-alumina to stable α-alumina depending on types of precursors, annealing duration, and temperature. As large surface area of nanoparticles plays an important role in controlling their phase transitions, it is also necessary to explore the effect of particle size on nature of phase transition. Solid-state ^{27}Al NMR allows us to determine the atomic structure of Al sites in diverse amorphous/disordered silicates including alumina. However, generally, the crystallographically distinct Al sites among alumina polymorphs were not fully resolved in ^{27}Al magic angle spinning (MAS) NMR spectrum without performing a simulation of overlapped peaks for Al sites of metastable alumina in the spectra. Unfortunately, the simulation of 27Al MAS NMR spectra for alumina nanoparticles cannot be achieved well due to unconfirmed NMR parameters for Al sites of γ- and δ-alumina. The recent progress in triple-quantum (3Q) MAS can provide the much higher resolution for crystallographically distinct Al sites in amorphous alumina (Lee et al., 2009, Phys. Rev. Lett., 103, 095501; Lee et al., 2010, J. Phys. Chem. C, 114, 13890-13894) and aluminosilicate glasses (Lee, 2011, Proc. Natl. Acad. Sci., 108, 6847-6852) as well as crystalline layer silicates (Lee and Weiss, 2008, Am. Mineral. 93, 1066-1071). In this study, we report the ^{27}Al 2D 3QMAS and 1D MAS NMR spectra for alumina nanoparticles with varying particle size (e.g., 15, 19, and 27 nm) and temperature with an aim to explore the atomic structure of alumina polymorphs and nature of their phase transition sequence. The ^{27}Al 2D 3QMAS spectra show the resolved crystallographically distinct ^{[6]}Al and ^{[4]}Al sites in (γ, δ)-, θ-, and α-alumina in nanoparticles consisting of random

  5. Using Dynamic Covalent Chemistry To Drive Morphological Transitions: Controlled Release of Encapsulated Nanoparticles from Block Copolymer Vesicles

    PubMed Central

    2017-01-01

    Dynamic covalent chemistry is exploited to drive morphological order–order transitions to achieve the controlled release of a model payload (e.g., silica nanoparticles) encapsulated within block copolymer vesicles. More specifically, poly(glycerol monomethacrylate)–poly(2-hydroxypropyl methacrylate) (PGMA–PHPMA) diblock copolymer vesicles were prepared via aqueous polymerization-induced self-assembly in either the presence or absence of silica nanoparticles. Addition of 3-aminophenylboronic acid (APBA) to such vesicles results in specific binding of this reagent to some of the pendent cis-diol groups on the hydrophilic PGMA chains to form phenylboronate ester bonds in mildly alkaline aqueous solution (pH ∼ 10). This leads to a subtle increase in the effective volume fraction of this stabilizer block, which in turn causes a reduction in the packing parameter and hence induces a vesicle-to-worm (or vesicle-to-sphere) morphological transition. The evolution in copolymer morphology (and the associated sol–gel transitions) was monitored using dynamic light scattering, transmission electron microscopy, oscillatory rheology, and small-angle X-ray scattering. In contrast to the literature, in situ release of encapsulated silica nanoparticles is achieved via vesicle dissociation at room temperature; moreover, the rate of release can be fine-tuned by varying the solution pH and/or the APBA concentration. Furthermore, this strategy also works (i) for relatively thick-walled vesicles that do not normally exhibit stimulus-responsive behavior and (ii) in the presence of added salt. This novel molecular recognition strategy to trigger morphological transitions via dynamic covalent chemistry offers considerable scope for the design of new stimulus-responsive copolymer vesicles (and hydrogels) for targeted delivery and controlled release of cargoes. In particular, the conditions used in this new approach are relevant to liquid laundry formulations, whereby enzymes require

  6. Intranasal Mesenchymal Stem Cell Treatment for Neonatal Brain Damage: Long-Term Cognitive and Sensorimotor Improvement

    PubMed Central

    Donega, Vanessa; van Bel, Frank; Kas, Martien J. H.; Kavelaars, Annemieke; Heijnen, Cobi J.

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI). Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5×106 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy. PMID:23300948

  7. A randomized controlled trial of intranasal ketamine in migraine with prolonged aura.

    PubMed

    Afridi, Shazia K; Giffin, Nicola J; Kaube, Holger; Goadsby, Peter J

    2013-02-12

    The aim of our study was to test the hypothesis that ketamine would affect aura in a randomized controlled double-blind trial, and thus to provide direct evidence for the role of glutamatergic transmission in human aura. We performed a double-blinded, randomized parallel-group controlled study investigating the effect of 25 mg intranasal ketamine on migraine with prolonged aura in 30 migraineurs using 2 mg intranasal midazolam as an active control. Each subject recorded data from 3 episodes of migraine. Eighteen subjects completed the study. Ketamine reduced the severity (p = 0.032) but not duration of aura in this group, whereas midazolam had no effect. These data provide translational evidence for the potential importance of glutamatergic mechanisms in migraine aura and offer a pharmacologic parallel between animal experimental work on cortical spreading depression and the clinical problem. This study provides class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.

  8. Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs

    PubMed Central

    Ellis, John A.; Gow, Sheryl P.; Lee, Lindsey B.; Lacoste, Stacey; Ball, Eileen C.

    2017-01-01

    In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs. PMID:28761185

  9. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    PubMed Central

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  10. Edge states and topological phase transitions in chains of dielectric nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kruk, Sergey; Slobozhanyuk, Alexey; Denkova, Denitza

    Recently introduced field of topological photonics aims to explore the concepts of topological insulators for novel phenomena in optics. Here polymeric chains of subwavelength silicon nanodisks are studied and it is demonstrated that these chains can support two types of topological edge modes based on magnetic and electric Mie resonances, and their topological properties are fully dictated by the spatial arrangement of the nanoparticles in the chain. Here, it is observed experimentally and described how theoretically topological phase transitions at the nanoscale define a change from trivial to nontrivial topological states when the edge mode is excited.

  11. Edge states and topological phase transitions in chains of dielectric nanoparticles

    DOE PAGES

    Kruk, Sergey; Slobozhanyuk, Alexey; Denkova, Denitza; ...

    2017-01-12

    Recently introduced field of topological photonics aims to explore the concepts of topological insulators for novel phenomena in optics. Here polymeric chains of subwavelength silicon nanodisks are studied and it is demonstrated that these chains can support two types of topological edge modes based on magnetic and electric Mie resonances, and their topological properties are fully dictated by the spatial arrangement of the nanoparticles in the chain. Here, it is observed experimentally and described how theoretically topological phase transitions at the nanoscale define a change from trivial to nontrivial topological states when the edge mode is excited.

  12. Transferrin receptor antibody-modified α-cobrotoxin-loaded nanoparticles enable drug delivery across the blood-brain barrier by intranasal administration

    NASA Astrophysics Data System (ADS)

    Liu, Lin; Zhang, Xiangyi; Li, Wuchao; Sun, Haozhen; Lou, Yan; Zhang, Xingguo; Li, Fanzhu

    2013-11-01

    A novel drug carrier for brain delivery, maleimide-poly(ethyleneglycol)-poly(lactide) (maleimide-PEG-PLA) nanoparticles (NPs) conjugated with mouse-anti-rat monoclonal antibody OX26 (OX26-NPs), was developed and its brain delivery property was evaluated. The diblock copolymers of maleimide-PEG-PLA were synthesized and applied to α-cobrotoxin (αCT)-loaded NPs which were characterized by transmission electron micrograph imaging, Fourier-transform IR, and X-ray diffraction. The NPs encapsulating αCT had a round and vesicle-like shape with a mean diameter around 100 nm, and the OX26 had covalently conjugated to the surface of NPs. MTT studies in brain microvascular endothelial cells (BMEC) revealed a moderate decrease in the cell viability of αCT, when incorporated in OX26-NPs compared to free αCT in solution. A higher affinity of the OX26-αCT-NPs to the BMEC was shown in comparison to αCT-NPs. Then, OX26-αCT-NPs were intranasally (i.n.) administered to rats, and αCT in the periaqueductal gray was monitored for up to 480 min using microdialysis technique in free-moving rats, with i.n. αCT-NPs, i.n. OX26-αCT-NPs, intramuscular injection (i.m.) αCT-NPs, and i.m. OX26-αCT-NPs. The brain transport results showed that the corresponding absolute bioavailability ( F abs) of i.n. OX26-αCT-NPs were about 125 and 155 % with i.n. αCT-NPs and i.m. OX26-αCT-NPs, respectively, and it was found that both the C max and AUC of the four groups were as follows: i.n. OX26-αCT-NPs > i.n. αCT-NPs > i.m. OX26-αCT-NPs > i.m. αCT-NPs, while αCT solution, as control groups, could hardly enter the brain. These results indicated that OX26-NPs are promising carriers for peptide brain delivery.

  13. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

    PubMed Central

    Arias, Mauricio A.; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

    2011-01-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. PMID:21145913

  14. Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

    PubMed

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

    2018-05-16

    Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Chronic Intranasal Oxytocin Causes Long-term Impairments in Partner Preference Formation in Male Prairie Voles

    PubMed Central

    Bales, Karen L.; Perkeybile, Allison M.; Conley, Olivia G.; Lee, Meredith H.; Guoynes, Caleigh D.; Downing, Griffin M.; Yun, Catherine R.; Solomon, Marjorie; Jacob, Suma; Mendoza, Sally P.

    2012-01-01

    Background Oxytocin (OT) is a hormone shown to be involved in social bonding in animal models. Intranasal OT is currently in clinical trials for use in disorders such as autism and schizophrenia. We examined long-term effects of intranasal OT given developmentally in the prairie vole (Microtus ochrogaster), a socially monogamous rodent, often used as an animal model to screen drugs that have therapeutic potential for social disorders. Methods We treated voles with one of three dosages of intranasal OT, or saline, from day 21 (weaning) through day 42 (sexual maturity). We examined both social behavior immediately following administration, as well as long-term changes in social and anxiety behavior after treatment ceased. Group sizes varied from 8 to 15 voles (n = 89 voles total). Results Treatment with OT resulted in acute increases in social behavior in males with familiar partners, as seen in humans. However, long-term developmental treatment with low doses of intranasal OT resulted in a deficit in partner preference behavior (a reduction of contact with a familiar opposite-sex partner, used to index pair-bond formation) by males. Conclusions Long-term developmental treatment with OT may show results different to those predicted by short-term studies, as well as significant sex differences and dosage effects. Further animal study is crucial to determining safe and effective strategies for use of chronic intranasal OT, especially during development. PMID:23079235

  16. Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.

    PubMed

    Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2017-05-09

    Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

  17. The effects of oral d-amphetamine on impulsivity in smoked and intranasal cocaine users.

    PubMed

    Reed, Stephanie Collins; Evans, Suzette M

    2016-06-01

    Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. The Effects of Oral d-Amphetamine on Impulsivity in Smoked and Intranasal Cocaine Users

    PubMed Central

    Reed, Stephanie Collins; Evans, Suzette M.

    2016-01-01

    BACKGROUND Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. METHODS The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. RESULTS Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). CONCLUSIONS Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. PMID:27114203

  19. Survival times for canine intranasal sarcomas treated with radiation therapy: 86 cases (1996-2011).

    PubMed

    Sones, Evan; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Taylor, Kathryn; Haney, Siobhan; Wypij, Jackie; Keyerleber, Michele; Arthur, Jennifer; Hamilton, Terrance; Lawrence, Jessica; Gieger, Tracy; Sellon, Rance; Wright, Zack

    2013-01-01

    Sarcomas comprise approximately one-third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily-fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily-fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily-fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits. © 2012 Veterinary Radiology & Ultrasound.

  20. Predicted trends of core-shell preferences for 132 late transition-metal binary-alloy nanoparticles.

    PubMed

    Wang, Lin-Lin; Johnson, Duane D

    2009-10-07

    Transition-metal alloyed nanoparticles with core-shell features (shell enrichment by one of the metals) are becoming ubiquitous, from (electro-)catalysis to biomedical applications, due to their size control, performance, biocompatibility, and cost. We investigate 132 binary-alloyed nanoparticle systems (groups 8 to 11 in the Periodic Table) using density functional theory (DFT) and systematically explore their segregation energies to determine core-shell preferences. We find that core-shell preferences are generally described by two independent factors: (1) cohesive energy (related to vapor pressure) and (2) atomic size (quantified by the Wigner-Seitz radius), and the interplay between them. These independent factors are shown to provide general trends for the surface segregation preference for atoms in nanoparticles, as well as semi-infinite surfaces, and give a simple correlation (a "design map") for the alloying and catalytic behavior. Finally, we provide a universal description of core-shell preference via tight-binding theory (band-energy differences) that (i) quantitatively reproduces the DFT segregation energies and (ii) confirms the electronic origins and correlations for core-shell behavior.

  1. Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.

    PubMed

    Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Servadio, Michela; Melancia, Francesca; Ratano, Patrizia; Campolongo, Patrizia; Trezza, Viviana; Cortesi, Rita; Nastruzzi, Claudio

    2017-09-01

    This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.

  2. Effect of administration method, animal weight and age on the intranasal delivery of drugs to the brain.

    PubMed

    Krishnan, Jishnu K S; Arun, Peethambaran; Chembukave, Bhadra; Appu, Abhilash P; Vijayakumar, Nivetha; Moffett, John R; Puthillathu, Narayanan; Namboodiri, Aryan M A

    2017-07-15

    The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ( 3 H-2-PAM) to the brain of rats. We found that using upright vs. supine posture did not significantly affect 3 H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

    PubMed

    Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

    2006-02-01

    Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

  4. A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

    PubMed Central

    Lapidus, Kyle A.B.; Levitch, Cara F.; Perez, Andrew M.; Brallier, Jess W.; Parides, Michael K.; Soleimani, Laili; Feder, Adriana; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.

    2014-01-01

    Background The N-methyl-d-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods Twenty patients with major depression were randomized and 18 completed two treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized, double-blind, crossover study. The primary efficacy outcome measure was change in depression severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results Patients showed significant improvement in depressive symptoms at 24 hours following ketamine compared to placebo [t=4.39, p<0.001; estimated mean MADRS score difference of 7.6 ± 3.7 (95% CI: 3.9 – 11.3)]. Eight of 18 patients (44%) met response criteria 24 hours following ketamine administration, compared to 1 of 18 (6%) following placebo (p=0.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. Trial Registration clinicaltrials.gov identifier NCT01304147 PMID:24821196

  5. Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

    NASA Technical Reports Server (NTRS)

    Tietze, Karen J.

    1990-01-01

    Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

  6. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study

    PubMed Central

    Lahat, Eli; Goldman, Michael; Barr, Joseph; Bistritzer, Tzvi; Berkovitch, Matithyahu

    2000-01-01

    Objective To compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures. Design Prospective randomised study. Setting Paediatric emergency department in a general hospital. Subjects 47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period. Interventions Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg). Main outcome measures Time from arrival at hospital to starting treatment and cessation of seizures. Results Intranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7.9 to 8.3). No significant side effects were observed in either group. Conclusion Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home. PMID:10884257

  7. Hydrophobic nanoparticles promote lamellar to inverted hexagonal transition in phospholipid mesophases.

    PubMed

    Bulpett, Jennifer M; Snow, Tim; Quignon, Benoit; Beddoes, Charlotte M; Tang, T-Y D; Mann, Stephen; Shebanova, Olga; Pizzey, Claire L; Terrill, Nicholas J; Davis, Sean A; Briscoe, Wuge H

    2015-12-07

    This study focuses on how the mesophase transition behaviour of the phospholipid dioleoyl phosphatidylethanolamine (DOPE) is altered by the presence of 10 nm hydrophobic and 14 nm hydrophilic silica nanoparticles (NPs) at different concentrations. The lamellar to inverted hexagonal phase transition (Lα-HII) of phospholipids is energetically analogous to the membrane fusion process, therefore understanding the Lα-HII transition with nanoparticulate additives is relevant to how membrane fusion may be affected by these additives, in this case the silica NPs. The overriding observation is that the HII/Lα boundaries in the DOPE p-T phase diagram were shifted by the presence of NPs: the hydrophobic NPs enlarged the HII phase region and thus encouraged the inverted hexagonal (HII) phase to occur at lower temperatures, whilst hydrophilic NPs appeared to stabilise the Lα phase region. This effect was also NP-concentration dependent, with a more pronounced effect for higher concentration of the hydrophobic NPs, but the trend was less clear cut for the hydrophilic NPs. There was no evidence that the NPs were intercalated into the mesophases, and as such it was likely that they might have undergone microphase separation and resided at the mesophase domain boundaries. Whilst the loci and exact roles of the NPs invite further investigation, we tentatively discuss these results in terms of both the surface chemistry of the NPs and the effect of their curvature on the elastic bending energy considerations during the mesophase transition.

  8. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

    PubMed

    Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

    2011-02-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. A comparative study of the magnetization in transition metal ion doped CeO2, TiO2 and SnO2 nanoparticles

    NASA Astrophysics Data System (ADS)

    Apostolov, A. T.; Apostolova, I. N.; Wesselinowa, J. M.

    2018-05-01

    Using the microscopic s-d model taking into account anharmonic spin-phonon interactions we have studied the magnetic properties of Co and Cu ion doped CeO2 and TiO2 nanoparticles and compared them with those of SnO2. By Co-doping there is a maximum in the magnetization M(x) curve for all nanoparticles observed in the most transition metal doped ones. The s-d interaction plays an important role by the decrease of M at higher dopant concentration. We have discussed the magnetization in dependence of different model parameters. By small Cu-ion doping there are some differences. In CeO2M decreases with the Cu-concentration, whereas in TiO2 and SnO2M increases. For higher Cu dopant concentrations M(X) decreases in TiO2 nanoparticles. We obtain room temperature ferromagnetism also in Zn doped CeO2, TiO2 and SnO2 nanoparticles, i.e. in non-transition metal ion doped ones. The different behavior of M in Co and Cu doped nanoparticles is due to a combination effect of multivalent metal ions, oxygen vacancies, different radius of cation dopants, connection between lattice and magnetism, as well as competition between the s-d and d-d ferromagnetic or antiferromagnetic interactions.

  10. RGC Neuroprotection Following Optic Nerve Trauma Mediated By Intranasal Delivery of Amnion Cell Secretome

    PubMed Central

    Grinblat, Gabriela A.; Khan, Reas S.; Dine, Kimberly; Wessel, Howard; Brown, Larry; Shindler, Kenneth S.

    2018-01-01

    Purpose Intranasally delivered ST266, the biological, proteinaceous secretome of amnion-derived multipotent progenitor cells, reduces retinal ganglion cell (RGC) loss, optic nerve inflammation, and demyelination in experimental optic neuritis. This unique therapy and novel administration route delivers numerous cytokines and growth factors to the eye and optic nerve, suggesting a potential to also treat other optic neuropathies. Thus, ST266-mediated neuroprotection was examined following traumatic optic nerve injury. Methods Optic nerve crush injury was surgically induced in C57BL/6J mice. Mice were treated daily with intranasal PBS or ST266. RGC function was assessed by optokinetic responses (OKRs), RGCs were counted, and optic nerve sections were stained with luxol fast blue and anti-neurofilament antibodies to assess myelin and RGC axon damage. Results Intranasal ST266 administered daily for 5 days, beginning at the time that a 1-second optic nerve crush was performed, significantly attenuated OKR decreases. Furthermore, ST266 treatment reduced damage to RGC axons and myelin within optic nerves, and blocked RGC loss. Following a 4-second optic nerve crush, intranasal ST266 increased RGC survival and showed a trend toward reduced RGC axon and myelin damage. Ten days following optic nerve crush, ST266 prevented myelin damage, while also inducing a trend toward increased RGC survival and visual function. Conclusions ST266 significantly attenuates traumatic optic neuropathy. Neuroprotective effects of this unique combination of biologic molecules observed here and previously in optic neuritis suggest potential broad application for preventing neuronal damage in multiple optic nerve disorders. Furthermore, results support intranasal delivery as a novel, noninvasive therapeutic modality for eyes and optic nerves. PMID:29847652

  11. Intranasal Dexmedetomidine for Procedural Sedation in Children, a Suitable Alternative to Chloral Hydrate.

    PubMed

    Cozzi, Giorgio; Norbedo, Stefania; Barbi, Egidio

    2017-04-01

    Sedation is often required for children undergoing diagnostic procedures. Chloral hydrate has been one of the sedative drugs most used in children over the last 3 decades, with supporting evidence for its efficacy and safety. Recently, chloral hydrate was banned in Italy and France, in consideration of evidence of its carcinogenicity and genotoxicity. Dexmedetomidine is a sedative with unique properties that has been increasingly used for procedural sedation in children. Several studies demonstrated its efficacy and safety for sedation in non-painful diagnostic procedures. Dexmedetomidine's impact on respiratory drive and airway patency and tone is much less when compared to the majority of other sedative agents. Administration via the intranasal route allows satisfactory procedural success rates. Studies that specifically compared intranasal dexmedetomidine and chloral hydrate for children undergoing non-painful procedures showed that dexmedetomidine was as effective as and safer than chloral hydrate. For these reasons, we suggest that intranasal dexmedetomidine could be a suitable alternative to chloral hydrate.

  12. Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review.

    PubMed

    Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M

    2017-12-27

    Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

    PubMed

    Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

    2017-12-06

    Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  14. Photochemical Fabrication of Transition Metal Nanoparticles Using CdS Template and Their Co-Catalysis Effects for TiO2 Photocatalysis

    NASA Astrophysics Data System (ADS)

    Badhwar, Nidhi; Gupta, Nidhi; Pal, Bonamali

    2013-09-01

    Transition metal nanoparticles were prepared by chemical dissolution of CdS template from metal photodeposited CdS nanorod (length = 70-85 nm and width = 5-6 nm) heterocomposites. Size (9-10 nm) of metal nanoparticles obtained after CdS removal was larger than the size (4-6 nm) of metal nanodeposits over CdS template. The obtained Au nanoparticles displayed a broad red shifted absorption band at 660 nm, whereas Pt, Pd and Rh nanoparticles exhibit featureless absorption spectra. Elemental analysis confirms the complete removal of CdS template from Au-CdS (Au — 2.65 at.%) and Ag-CdS (Ag — 2.06 at.%) composites showing no Cd peak. These metal nanoparticles imparted dissimilar co-catalytic activity of TiO2 for photocatalytic degradation of salicylic acid in the order Au > Pt > Pd > Ag > Rh as a function of their nature, electronegativity, redox potential and work function.

  15. Brain delivery of buspirone hydrochloride chitosan nanoparticles for the treatment of general anxiety disorder.

    PubMed

    Bari, Naimat Kalim; Fazil, Mohammad; Hassan, Md Quamrul; Haider, Md Rafi; Gaba, Bharti; Narang, Jasjeet K; Baboota, Sanjula; Ali, Javed

    2015-11-01

    The present work discusses the preparation, characterization and in vivo evaluation of thiolated chitosan nanoparticles (TCS-NPs) of buspirone hydrochloride (BUH) for brain delivery through intranasal route. TCS NPs were prepared by ionic gelation method and characterized for various parameters. The NPs formed were having particle size of 226.7±2.52nm with PDI 0.483±0.031. Drug entrapment efficiency (EE) and loading capacity (LC) were found to be 81.13±2.8 and 49.67±5.5%. The cumulative percentage drug permeation through nasal mucosa was 76.21%. Bioadhesion study carried out on porcine mucin and showed a bioadhesion efficiency of 90.218±0.134%. Nose-to-brain delivery of placebo NPs was investigated by confocal laser scanning microscopy (CLSM) technique using rhodamine-123 as a marker. The brain concentration achieved after intranasal administration of TCS-NPs was 797.46±35.76ng/ml with tmax 120min which was significantly higher than achieved after intravenous administration on BUH solution 384.15±13.42ng/ml and tmax of 120min and intranasal administration of BUH solution 417.77±19.24ng/ml and tmax 60min. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. CXCR6 is a marker for protective antigen-specific cells in the lungs after intranasal immunization against Mycobacterium tuberculosis.

    PubMed

    Lee, Lian Ni; Ronan, Edward O; de Lara, Catherine; Franken, Kees L M C; Ottenhoff, Tom H M; Tchilian, Elma Z; Beverley, Peter C L

    2011-08-01

    Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium tuberculosis antigen 85A (adenovirus-85A) induces protective lower respiratory tract immunity against pulmonary challenge with Mycobacterium tuberculosis, while intradermal immunization with adenovirus-85A does not. Here we report that intranasal immunization with adenovirus-85A induces expression of the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive antigen-specific T cell numbers are increased among bronchoalveolar lavage-recoverable cells. Similarly, intranasal immunization with recombinant antigen 85A with adjuvant induces CXCR6 expression on lung CD4 cells in BALB/c and C57BL/6 mice, while a synthetic ESAT6(1-20) peptide with adjuvant induces CXCR6 expression in C57BL/6 mice. Parenteral immunization fails to do so. Upregulation of CXCR6 is accompanied by a transient elevation of serum CXCL16 after intranasal immunization, and lung cells cultured ex vivo from mice immunized intranasally show increased production of CXCL16. Administration of CXCL16 and cognate antigen intranasally to mice previously immunized parenterally increases the number of antigen-specific T lymphocytes in the bronchoalveolar lavage-recoverable population, which mediates inhibition of the early growth of Mycobacterium tuberculosis after challenge. We conclude that expression of CXCR6 on lung T lymphocytes is a correlate of local protective immunity against Mycobacterium tuberculosis after intranasal immunization and that CXCR6 and CXCL16 play an important role in the localization of T cells within lung tissue and the bronchoalveolar lavage-recoverable compartment.

  17. CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis▿

    PubMed Central

    Lee, Lian Ni; Ronan, Edward O.; de Lara, Catherine; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.; Tchilian, Elma Z.; Beverley, Peter C. L.

    2011-01-01

    Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium tuberculosis antigen 85A (adenovirus-85A) induces protective lower respiratory tract immunity against pulmonary challenge with Mycobacterium tuberculosis, while intradermal immunization with adenovirus-85A does not. Here we report that intranasal immunization with adenovirus-85A induces expression of the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive antigen-specific T cell numbers are increased among bronchoalveolar lavage-recoverable cells. Similarly, intranasal immunization with recombinant antigen 85A with adjuvant induces CXCR6 expression on lung CD4 cells in BALB/c and C57BL/6 mice, while a synthetic ESAT61–20 peptide with adjuvant induces CXCR6 expression in C57BL/6 mice. Parenteral immunization fails to do so. Upregulation of CXCR6 is accompanied by a transient elevation of serum CXCL16 after intranasal immunization, and lung cells cultured ex vivo from mice immunized intranasally show increased production of CXCL16. Administration of CXCL16 and cognate antigen intranasally to mice previously immunized parenterally increases the number of antigen-specific T lymphocytes in the bronchoalveolar lavage-recoverable population, which mediates inhibition of the early growth of Mycobacterium tuberculosis after challenge. We conclude that expression of CXCR6 on lung T lymphocytes is a correlate of local protective immunity against Mycobacterium tuberculosis after intranasal immunization and that CXCR6 and CXCL16 play an important role in the localization of T cells within lung tissue and the bronchoalveolar lavage-recoverable compartment. PMID:21628524

  18. Anti-ferromagnetic/ferromagnetic transition in half-metallic Co9Se8 nanoparticles

    NASA Astrophysics Data System (ADS)

    Singh, Jai; Kumar, Pushpendra

    2015-09-01

    The size, shape and defects of the half-metallic Co9Se8 nanoparticles (NPs) play a crucial role in the magnetic transition at the local magnetic regime at low temperatures. A general, non-injection, one-pot reaction route without toxic reagents, such as TOPO/TOPSe, surfactant and/or chelating agent, were used to synthesize gram scale of well-dispersed, high-quality Co9Se8 NPs. The calculated mean crystallite size of the NPs was ∼10 nm, which is consistent with the transmission electron microscope data. This study reveals an unusual anti-ferromagnetic/ferromagnetic transition with some super-paramagnetic character in the low temperature region of Co9Se8 NPs. These investigations are expected not only to help the observed phenomenon, but also help in identifying new half-metallic magnetic NPs for spintronics devices. The outcome provides better understanding of the occurrence of superparamagnetism at low temperatures in the nano-regime, for half-metallic systems.

  19. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    PubMed

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  20. CNA-loaded PLGA nanoparticles improve humoral response againstS. aureus-mediated infections in a mouse model: subcutaneous vs. nasal administration strategy.

    PubMed

    Genta, Ida; Colonna, Claudia; Conti, Bice; Caliceti, Paolo; Salmaso, Stefano; Speziale, Pietro; Pietrocola, Giampiero; Chiesa, Enrica; Modena, Tiziana; Dorati, Rossella

    2016-12-01

    The aim of this work was the assessment of the "in vivo" immune response of a poly(lactide-co-glycolide)-based nanoparticulate adjuvant for a sub-unit vaccine, namely, a purified recombinant collagen-binding bacterial adhesion fragment (CNA19), against Staphylococcus aureus-mediated infections. "In vivo" immunogenicity studies were performed on mice: immunisation protocols encompassed subcutaneous and intranasal administration of CNA19 formulated as nanoparticles (NPs) and furthermore, CNA19-loaded NPs formulated in a set-up thermosetting chitosan-β-glycerolphosphate (chitosan-β-GP) solution for intranasal route in order to extend antigen exposure to nasal mucosa. CNA19 loaded NPs (mean size of about 195 nm, 9.04 ± 0.37μg/mg as CNA19 loading capacity) confirmed as suitable vaccine for subcutaneous administration with a more pronounced adjuvant effect (about 3-fold higher) with respect to aluminium, recognised as "reference" adjuvant. CNA19 loaded NPs formulated in an optimised thermogelling chitosan-β-GP solution showed promising results for eliciting an effective humoral response and a good chance as intranasal boosting dose.

  1. OUTCOME OF DOGS WITH INTRANASAL LYMPHOMA TREATED WITH VARIOUS RADIATION AND CHEMOTHERAPY PROTOCOLS: 24 CASES.

    PubMed

    George, Rebecca; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Kent, Michael; Wypij, Jackie; Borrego, Juan; Moore, Antony; Keyerleber, Michele; Kraiza, Sarah

    2016-05-01

    Tumors of the nasal cavity comprise approximately 1% of all neoplasms in dogs. Canine intranasal lymphoma is rare and reports evaluating the outcome of treatment are lacking. The goal of this observational, descriptive, multi-institutional study was to evaluate the overall median survival times (MSTs) in a group of dogs with intranasal lymphoma that were treated with irradiation and/or chemotherapy. Dogs meeting these inclusion criteria were retrospectively recruited from medical archives at multiple institutions. Eighteen cases of intermediate to high grade intranasal lymphoma and six cases of low-grade intranasal lymphoma were identified. The date of diagnosis, method of diagnosis, treatment received (radiation and/or chemotherapy protocols), and date of death were recorded. Kaplan-Meier survival analysis was performed on the intermediate to high grade group to calculate overall MST. Log-rank tests were performed to compare effects of treatment with radiation therapy ± chemotherapy and chemotherapy alone. Kaplan-Meier survival analysis was performed separately on the low-grade group. The overall MST was 375 days for the intermediate to high grade group. Cases treated with radiation ± chemotherapy had an MST of 455 days (n = 12) and those treated with chemotherapy alone (n = 6) had an MST of 157 days in the intermediate to high grade group. The MST was 823 days for the low-grade group. Results support the use of radiation therapy for treatment of canine intranasal lymphoma, however a randomized, controlled, clinical trial would be needed for more definitive recommendations. The role of adjunctive chemotherapy also may require further investigation. © 2016 American College of Veterinary Radiology.

  2. Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects

    PubMed Central

    Pantaleon, Carmela; Iverson, Matthew; Smith, Michael D.; Kinzler, Eric R.; Aigner, Stefan

    2018-01-01

    Objective To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.

  3. Visualizing the Cu/Cu2(O) Interface Transition in Nanoparticles with Environmental Scanning Transmission Electron Microscopy.

    PubMed

    LaGrow, Alec P; Ward, Michael R; Lloyd, David C; Gai, Pratibha L; Boyes, Edward D

    2017-01-11

    Understanding the oxidation and reduction mechanisms of catalytically active transition metal nanoparticles is important to improve their application in a variety of chemical processes. In nanocatalysis the nanoparticles can undergo oxidation or reduction in situ, and thus the redox species are not what are observed before and after reactions. We have used the novel environmental scanning transmission electron microscope (ESTEM) with 0.1 nm resolution in systematic studies of complex dynamic oxidation and reduction mechanisms of copper nanoparticles. The oxidation of copper has previously been reported to be dependent on its crystallography and its interaction with the substrate. By following the dynamic oxidation process in situ in real time with high-angle annular dark-field imaging in the ESTEM, we use conditions ideal to track the oxidation front as it progresses across a copper nanoparticle by following the changes in the atomic number (Z) contrast with time. The oxidation occurs via the nucleation of the oxide phase (Cu 2 O) from one area of the nanoparticle which then progresses unidirectionally across the particle, with the Cu-to-Cu 2 O interface having a relationship of Cu{111}//Cu 2 O{111}. The oxidation kinetics are related to the temperature and oxygen pressure. When the process is reversed in hydrogen, the reduction process is observed to be similar to the oxidation, with the same crystallographic relationship between the two phases. The dynamic observations provide unique insights into redox mechanisms which are important to understanding and controlling the oxidation and reduction of copper-based nanoparticles.

  4. Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

    PubMed Central

    Lile, Joshua A.; Stoops, William W.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

    2015-01-01

    Background Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABAA activity following chronic stimulant use, and that positive modulation of GABAA receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABAA modulators could be useful as pharmacotherapies for stimulant-use disorders. Methods This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1 mg/day). Results Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment. Conclusions The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABAA positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABAA positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment. PMID:21737214

  5. The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users

    PubMed Central

    Jones, Jermaine D.; Madera, Gabriela; Comer, Sandra D.

    2014-01-01

    Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphine (N=12). Participants were maintained on 2 mg sublingual (SL) BUP and tested with each intranasal or intravenous buprenorphine test dose (0 mg, 2 mg, 4 mg, 8 mg, and 16 mg). During morning laboratory sessions, participants received money (US $20) and sample doses of IN or IV BUP, and then completed subjective effects questionnaires. Later that day, they completed a self-administration task to receive 10% portions of the drug and/or money they previously sampled. In general, positive subjective ratings for both IV and IN BUP were significantly greater than placebo, with IV BUP having a greater effect than IN BUP. All active BUP doses (IV and IN) maintained significantly higher progressive ratio breakpoint values than placebo, but breakpoint values for IV BUP were greater than for IN BUP. Buprenorphine is an effective maintenance treatment for opioid dependence, valued for its ability to reduce the positive subjective effects of other opioids. Nevertheless, the present data demonstrate that in participants maintained on a low dose of SL BUP, the medication itself has abuse liability when used intravenously or intranasally. PMID:24793093

  6. Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users

    PubMed Central

    Harris, Stephen C; Perrino, Peter J; Smith, Ira; Shram, Megan J; Colucci, Salvatore V; Bartlett, Cynthia; Sellers, Edward M

    2014-01-01

    The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1–2 hours) versus OC and Oxy API (0.5–1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion. PMID:24243216

  7. Intranasal hemangiosarcoma in a dog.

    PubMed

    Fujita, Michio; Takaishi, Yumi; Yasuda, Daiji; Hasegawa, Daisuke; Taniguchi, Akiko; Takahashi, Kimimasa; Orima, Hiromitsu

    2008-05-01

    Magnetic resonance (MR) was conducted for an 8-year-old, intact male Spitz with sneezing, serous discharge and epistaxis from the left nasal cavity. MR imaging showed a nasal cavity-occupied mass of iso-intensity on T1WI , high-intensity on T2WI and markedly enhanced on contrast-enhanced T1WI at parts of rostal to medial ocular angle in the left cavity. After Surgery and intraoperative radiation, the mass was diagnosed intranasal hemangiosarcoma by histopathology. Although the dog showed the finding, which suggested recurrence after the treatment ending, about 30 months later, it maintained good conditions without evidence of metastasis.

  8. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    PubMed

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  9. Taking the alternative route: Women's experience of intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia.

    PubMed

    Fleet, Julie-Anne; Jones, Meril; Belan, Ingrid

    2017-10-01

    To compare women's experience of receiving either intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia. A content analysis was undertaken as part of the third phase of a larger randomised controlled trial, using the per-protocol dataset to examine women's experiences of treatment received. Healthy women birthing at term, who received intranasal fentanyl (n=41), subcutaneous fentanyl (n=37) and/or intramuscular pethidine (n=38) for labour analgesia, were contacted at 6 weeks postpartum to complete a phone questionnaire. A tertiary and regional maternity unit in South Australia. Over 80% of women who received intranasal or subcutaneous fentanyl reported that they would use the treatment again compared to 44.8% of women who had received pethidine (self-administered intranasal fentanyl provided more expressive responses emphasising the route provided a strong sense of control and enablement. Route of administration influenced the women's experience, more women who self-administered intranasal fentanyl reported positive emotional responses, with women reporting increased autonomy and satisfaction. Whereas, women who relied on the midwife to administer subcutaneous fentanyl or intramuscular pethidine, were more often focused on the physical effect of the drug. Pethidine was the least preferred option due to adverse effects. For women requesting parenteral analgesia, fentanyl administered by less invasive routes offers women additional options that may better meet their emotional, cognitive and physical needs than the current practice of administering intramuscular pethidine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.

    PubMed

    Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

    2018-01-02

    Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing. To overcome these problems of RHT, microemulsion (ME) and mucoadhesive microemulsion (MME) of RHT were formulated for brain targeting via intranasal delivery route and compared on the basis of in vivo pharmacokinetics. ME and MME formulations containing RHT were developed by water titration method. Characterization of ME and MME was done for various physicochemical parameters, nasal spray pattern, and in vivo pharmacokinetics quantitatively and qualitatively (gamma scintigraphy studies). The developed ME and MME were transparent having globule size approximately in the range of 53-55 nm. Pharmacokinetic studies showed higher values for C max and DTP for intranasal RHT: CH-ME over RHT-ME, thus indicating the effect of chitosan in modulating tight junctions, thereby enhanced paracellular transport of RHT. Gamma scintigraphy and in vivo pharmacokinetic study suggested enhanced RHT concentration, upon intranasal administration of RHT:CH-ME, compare with other groups administered formulations intranasally. These findings suggested the potential of non-invasive intranasal route for brain delivery, especially for therapeutics, facing challenges in oral administration.

  11. A model of chronic diabetic polyneuropathy: benefits from intranasal insulin are modified by sex and RAGE deletion

    PubMed Central

    de la Hoz, Cristiane L.; Cheng, Chu; Fernyhough, Paul

    2017-01-01

    Human diabetic polyneuropathy (DPN) is a progressive complication of chronic diabetes mellitus. Preliminary evidence has suggested that intranasal insulin, in doses insufficient to alter hyperglycemia, suppresses the development of DPN. In this work we confirm this finding, but demonstrate that its impact is modified by sex and deletion of RAGE, the receptor for advanced glycosylation end products. We serially evaluated experimental DPN in male and female wild-type mice and male RAGE null (RN) mice, each with nondiabetic controls, during 16 wk of diabetes, the final 8 wk including groups given intranasal insulin. Age-matched nondiabetic female mice had higher motor and sensory conduction velocities than their male counterparts and had lesser conduction slowing from chronic diabetes. Intranasal insulin improved slowing in both sexes. In male RN mice, there was less conduction slowing with chronic diabetes, and intranasal insulin provided limited benefits. Rotarod testing and hindpaw grip power offered less consistent impacts. Mechanical sensitivity and thermal sensitivity were respectively but disparately changed and improved with insulin in wild-type female and male mice but not RN male mice. These studies confirm that intranasal insulin improves indexes of experimental DPN but indicates that females with DPN may differ in their underlying phenotype. RN mice had partial but incomplete protection from underlying DPN and lesser impacts from insulin. We also identify an important role for sex in the development of DPN and report evidence that insulin and AGE-RAGE pathways in its pathogenesis may overlap. PMID:28223295

  12. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    PubMed

    Chen, Honglei; Wu, Shaoping; Lu, Rong; Zhang, Yong-guo; Zheng, Yuanyuan; Sun, Jun

    2014-01-01

    Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally. For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model. In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  13. Wetting-Dewetting and Dispersion-Aggregation Transitions Are Distinct for Polymer Grafted Nanoparticles in Chemically Dissimilar Polymer Matrix.

    PubMed

    Martin, Tyler B; Mongcopa, Katrina Irene S; Ashkar, Rana; Butler, Paul; Krishnamoorti, Ramanan; Jayaraman, Arthi

    2015-08-26

    Simulations and experiments are conducted on mixtures containing polymer grafted nanoparticles in a chemically distinct polymer matrix, where the graft and matrix polymers exhibit attractive enthalpic interactions at low temperatures that become progressively repulsive as temperature is increased. Both coarse-grained molecular dynamics simulations, and X-ray scattering and neutron scattering experiments with deuterated polystyrene (dPS) grafted silica and poly(vinyl methyl ether) PVME matrix show that the sharp phase transition from (mixed) dispersed to (demixed) aggregated morphologies due to the increasingly repulsive effective interactions between the blend components is distinct from the continuous wetting-dewetting transition. Strikingly, this is unlike the extensively studied chemically identical graft-matrix composites, where the two transitions have been considered to be synonymous, and is also unlike the free (ungrafted) blends of the same graft and matrix homopolymers, where the wetting-dewetting is a sharp transition coinciding with the macrophase separation.

  14. Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

    PubMed

    El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

    2016-09-20

    Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Sumatriptan (intranasal route of administration) for acute migraine attacks in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Intranasal administration may be preferable to oral for individuals experiencing nausea and/or vomiting, although it is primarily absorbed in the gut, not the nasal mucosa. Objectives To determine the efficacy and tolerability of intranasal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using intranasal sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Twelve studies (4755 participants) compared intranasal sumatriptan with placebo or an active comparator. Most of the data were for the 10 mg and 20 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 10 mg versus placebo the NNTs were 7.3, 7.4, and 5.5 for pain-free at two hours, and headache relief at one and two hours, respectively. For sumatriptan 20 mg versus placebo the NNTs were 4.7, 4.9, and 3.5, respectively, for the same outcomes. The 20 mg dose was significantly better than the 10 mg dose for each of these three primary efficacy outcomes. Relief of headache-associated symptoms, including nausea, photophobia, and

  16. Pitfalls of Intranasal Naloxone

    PubMed Central

    Zuckerman, Matthew; Weisberg, Stacy N.; Boyer, Edward W.

    2016-01-01

    We present a case of failed prehospital treatment of fentanyl induced apnea with intranasal (IN) naloxone. While IN administration of naloxone is becoming more common in both lay and pre-hospital settings, older EMS protocols utilized intravenous (IV) administration. Longer-acting, higher potency opioids, such as fentanyl, may not be as easily reversed as heroin, and studies evaluating IN administration in this population are lacking. In order to contribute to our understanding of the strengths and limitations of IN administration of naloxone, we present a case where it failed to restore ventilation. We also describe peer reviewed literature that supports the use of IV naloxone following heroin overdose and explore possible limitations of generalizing this literature to opioids other than heroin and to IN routes of administration. PMID:24830404

  17. Structure, bonding, and catalytic activity of monodisperse, transition-metal-substituted CeO2 nanoparticles.

    PubMed

    Elias, Joseph S; Risch, Marcel; Giordano, Livia; Mansour, Azzam N; Shao-Horn, Yang

    2014-12-10

    We present a simple and generalizable synthetic route toward phase-pure, monodisperse transition-metal-substituted ceria nanoparticles (M0.1Ce0.9O2-x, M = Mn, Fe, Co, Ni, Cu). The solution-based pyrolysis of a series of heterobimetallic Schiff base complexes ensures a rigorous control of the size, morphology and composition of 3 nm M0.1Ce0.9O2-x crystallites for CO oxidation catalysis and other applications. X-ray absorption spectroscopy confirms the dispersion of aliovalent (M(3+) and M(2+)) transition metal ions into the ceria matrix without the formation of any bulk transition metal oxide phases, while steady-state CO oxidation catalysis reveals an order of magnitude increase in catalytic activity with copper substitution. Density functional calculations of model slabs of these compounds confirm the stabilization of M(3+) and M(2+) in the lattice of CeO2. These results highlight the role of the host CeO2 lattice in stabilizing high oxidation states of aliovalent transition metal dopants that ordinarily would be intractable, such as Cu(3+), as well as demonstrating a rational approach to catalyst design. The current work demonstrates, for the first time, a generalizable approach for the preparation of transition-metal-substituted CeO2 for a broad range of transition metals with unparalleled synthetic control and illustrates that Cu(3+) is implicated in the mechanism for CO oxidation on CuO-CeO2 catalysts.

  18. Promotion of allergic immune responses by intranasally-administrated nanosilica particles in mice

    NASA Astrophysics Data System (ADS)

    Yoshida, Tokuyuki; Yoshioka, Yasuo; Fujimura, Maho; Yamashita, Kohei; Higashisaka, Kazuma; Morishita, Yuki; Kayamuro, Hiroyuki; Nabeshi, Hiromi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

    2011-12-01

    With the increase in use of nanomaterials, there is growing concern regarding their potential health risks. However, few studies have assessed the role of the different physical characteristics of nanomaterials in allergic responses. Here, we examined whether intranasally administered silica particles of various sizes have the capacity to promote allergic immune responses in mice. We used nanosilica particles with diameters of 30 or 70 nm (nSP30 or nSP70, respectively), and conventional micro-sized silica particles with diameters of 300 or 1000 nm (nSP300 or mSP1000, respectively). Mice were intranasally exposed to ovalbumin (OVA) plus each silica particle, and the levels of OVA-specific antibodies (Abs) in the plasma were determined. Intranasal exposure to OVA plus smaller nanosilica particles tended to induce a higher level of OVA-specific immunoglobulin (Ig) E, IgG and IgG1 Abs than did exposure to OVA plus larger silica particles. Splenocytes from mice exposed to OVA plus nSP30 secreted higher levels of Th2-type cytokines than mice exposed to OVA alone. Taken together, these results indicate that nanosilica particles can induce allergen-specific Th2-type allergic immune responses in vivo. This study provides the foundations for the establishment of safe and effective forms of nanosilica particles.

  19. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

    PubMed

    Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

    2014-02-01

    Evidence suggests that intranasal oxytocin enhances the perception of emotion in facial expressions during standard emotion identification tasks. However, it is not clear whether this effect is desirable in people who do not show deficits in emotion perception. That is, a heightened perception of emotion in faces could lead to "oversensitivity" to the emotions of others in nonclinical participants. The goal of this study was to assess the effects of intranasal oxytocin on emotion perception using ecologically valid social and nonsocial visual tasks. Eighty-two participants (42 women) self-administered a 24 IU dose of intranasal oxytocin or a placebo in a double-blind, randomized experiment and then completed the perceiving and understanding emotion components of the Mayer-Salovey-Caruso Emotional Intelligence Test. In this test, emotion identification accuracy is based on agreement with a normative sample. As expected, participants administered intranasal oxytocin rated emotion in facial stimuli as expressing greater emotional intensity than those given a placebo. Consequently, accurate identification of emotion in faces, based on agreement with a normative sample, was impaired in the oxytocin group relative to placebo. No such effect was observed for tests using nonsocial stimuli. The results are consistent with the hypothesis that intranasal oxytocin enhances the salience of social stimuli in the environment, but not nonsocial stimuli. The present findings support a growing literature showing that the effects of intranasal oxytocin on social cognition can be negative under certain circumstances, in this case promoting "oversensitivity" to emotion in faces in healthy people. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  20. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Mans, Christoph; Guzman, David Sanchez-Migallon; Lahner, Lesanna L; Paul-Murphy, Joanne; Sladky, Kurt K

    2012-09-01

    Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and effects on cloacal temperature, respiratory rate, and heart rate in manually restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9) were administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint in a complete crossover study. Respiratory rate and sedation scores were recorded before and during capture and during and after 15 minutes of manual restraint. Heart rate and cloacal temperature were recorded during manual restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and the recovery time was recorded. In those birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight, and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects to intranasal midazolam and flumazenil administration were observed. Further studies on the safety of intranasal midazolam and flumazenil in this species are warranted.

  1. Effects of Intranasal Oxytocin on the Interpretation and Expression of Emotions in Anorexia Nervosa.

    PubMed

    Leppanen, J; Cardi, V; Ng, K W; Paloyelis, Y; Stein, D; Tchanturia, K; Treasure, J

    2017-03-01

    Altered social-emotional functioning is considered to play an important role in the development and maintenance of anorexia nervosa (AN). Recently, there has been increasing interest in investigating the role of intranasal oxytocin in social-emotional processing. The present study aimed to investigate the effects of intranasal oxytocin on the interpretation and expression of emotions among people with AN. Thirty women with AN and 29 age-matched healthy women took part in the present study, which used a double-blind, placebo-controlled, cross-over design. The participants received a single dose of 40 IU of intranasal oxytocin in one session and a placebo spray in the other. Fifteen minutes after administration, the participants completed the Reading the Mind in the Eyes Test to assess the interpretation of complex emotions and mental states followed by a video task, which assessed expressions of facial affect when they were viewing humorous and sad film clips. The intranasal oxytocin did not significantly influence the expression or interpretation of emotions in the AN or healthy comparison groups. The AN group expressed significantly less positive emotion, spent more time looking away and reported experiencing a significantly more negative affect in response to the film clips. The finding that intranasal oxytocin had little to no effect on the interpretation or expression of emotions in either group supports the notion that the effects of oxytocin on social-emotional processing are not straightforward and may depend on individual and environmental differences, as well as the emotion being processed. Replication of these findings is necessary to explore the effect of timing on the effects of oxytocin before firm conclusions can be drawn. Nonetheless, these findings add to the steady accumulation of evidence that people with AN have reduced emotional expression and avoidance of emotionally provoking stimuli. © 2017 The Authors. Journal of Neuroendocrinology

  2. Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

    PubMed

    Skoner, D P; Doyle, W J; Boehm, S; Fireman, P

    1991-12-01

    Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

  3. A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

    DTIC Science & Technology

    2013-10-01

    Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder PRINCIPAL INVESTIGATOR: John Gabrieli...SUBTITLE A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder 5a. CONTRACT NUMBER...dysfunctions and (2) oxytocin (OT) administration prior to CBT sessions will each enhance social function in young adults with autism spectrum disorders

  4. Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance.

    PubMed

    Lile, Joshua A; Stoops, William W; Glaser, Paul E A; Hays, Lon R; Rush, Craig R

    2011-12-15

    Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABA(A) activity following chronic stimulant use, and that positive modulation of GABA(A) receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABA(A) modulators could be useful as pharmacotherapies for stimulant-use disorders. This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1mg/day). Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment. The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABA(A) positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABA(A) positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment. Copyright © 2011. Published by Elsevier Ireland Ltd.

  5. Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.

    PubMed

    Leppanen, Jenni; Ng, Kah Wee; Tchanturia, Kate; Treasure, Janet

    2017-07-01

    Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations. Copyright © 2017. Published by Elsevier Ltd.

  6. Effect of Intranasal Oxytocin Administration on Psychiatric Symptoms: A Meta-Analysis of Placebo-Controlled Studies

    PubMed Central

    Hofmann, Stefan G.; Fang, Angela; Brager, Daniel N.

    2015-01-01

    Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1,828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges’ g = 0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. PMID:26094200

  7. Transition-metal-ion-mediated polymerization of dopamine: mussel-inspired approach for the facile synthesis of robust transition-metal nanoparticle-graphene hybrids.

    PubMed

    Yang, Liping; Kong, Junhua; Zhou, Dan; Ang, Jia Ming; Phua, Si Lei; Yee, Wu Aik; Liu, Hai; Huang, Yizhong; Lu, Xuehong

    2014-06-16

    Inspired by the high transition-metal-ion content in mussel glues, and the cross-linking and mechanical reinforcement effects of some transition-metal ions in mussel threads, high concentrations of nickel(II), cobalt(II), and manganese(II) ions have been purposely introduced into the reaction system for dopamine polymerization. Kinetics studies were conducted for the Ni(2+)-dopamine system to investigate the polymerization mechanism. The results show that the Ni(2+) ions could accelerate the assembly of dopamine oligomers in the polymerization process. Spectroscopic and electron microscopic studies reveal that the Ni(2+) ions are chelated with polydopamine (PDA) units, forming homogeneous Ni(2+)-PDA complexes. This facile one-pot approach is utilized to construct transition-metal-ion-PDA complex thin coatings on graphene oxide, which can be carbonized to produce robust hybrid nanosheets with well-dispersed metallic nickel/metallic cobalt/manganese(II) oxide nanoparticles embedded in PDA-derived thin graphitic carbon layers. The nickel-graphene hybrid prepared by using this approach shows good catalytic properties and recyclability for the reduction of p-nitrophenol. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Intranasal immunization with a non-adjuvanted adhesive protein descended from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection in mice.

    PubMed

    Sasaki, Hiraku; Ishikawa, Hiroki; Kojima, Ken; Itoh, Masahiro; Matsumoto, Tetsuya; Itoh, Takumi; Hosomi, Osamu; Kawamoto, Eiichi

    2013-11-19

    Intranasal vaccination is one of the most effective means of protecting against invading and colonizing pathogens because the vaccine elicits a mucosal immune response. The exploitation of vaccine adjuvants and delivery systems for intranasal vaccines is an important way to evoke antigen immunogenicity and elicit a better immune response at the mucosal sites. In the present study, we assessed the potential of intranasal immunization using a non-adjuvanted bacterial adhesive protein toward the host organs. We evaluated intranasal immunization with modified recombinant PnxIIIA (MP3) from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection caused by P. pneumotropica, without using any adjuvants or delivery systems. The 100-kDa MP3 was confirmed to retain its immunogenicity and binding activity to collagen type I similar to the parent PnxIIIA. When MP3 was fused to green-fluorescent protein and inoculated into C57BL/6J mice intranasally, fluorescence intensity in the intranasal airway could be observed until 3 h after inoculation. Mice were intranasally immunized with MP3 at a maximum of 4 doses, with 7-day intervals. The antibody titer of serum IgG and IgA specific for MP3, as well as that of bronchoalveolar lavage fluid IgA, showed more than 9 (log₂) after 3 or 4 rounds of immunization. Experimentally infecting immunized mice with P. pneumotropica resulted in the inability to isolate the bacterium from the nasal cavity, trachea, conjunctiva, or cecum with more than 3 doses in the immunized mice. Although the detection in each organ seldom changed with less than 2 rounds of immunization, unlike that observed in the non-immunized mice, the detection remarkably decreased with 3 or more rounds of immunization. These results suggest that intranasal immunization with a non-adjuvanted adhesive protein could have preventive effects against opportunistic infection by P. pneumotropica. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

    PubMed Central

    Perez, Ana Paula; Mundiña-Weilenmann, Cecilia; Romero, Eder Lilia; Morilla, Maria Jose

    2012-01-01

    Background Molecules taken up by olfactory and trigeminal nerve neurons directly access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase the residence time of intranasal material, favoring the nose-to-brain delivery. In this first approach, brain radioactivity after intranasal administration of 32P-small interference RNA (siRNA) complexed with poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-forming mucoadhesive gels, was determined. Materials 32P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesive gels prepared by blending thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan (1% w/w, PxChi) or carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel release profile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation was intranasally administered to rats, and blood absorption and brain distribution of radioactivity were measured. Results The gelation temperature of both formulations was 23°C. The PxChi liquid showed non-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and the gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonian behavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscosity similar to that of the mucus but higher than that of aqueous solution. The gel released 35% of radiolabel and the released material showed silencing activity in vitro. Three intranasal doses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of 32P-siRNA complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel, and administration of two intranasal doses was necessary to achieve higher brain radioactivity than that achieved by intravenous dendriplexes or intranasal naked siRNA. Conclusion The increased radioactivity within the olfactory bulb suggested that the combination above mentioned favored the

  10. Metal Nanoparticles as Targeted Carriers Circumventing the Blood-Brain Barrier.

    PubMed

    Sintov, A C; Velasco-Aguirre, C; Gallardo-Toledo, E; Araya, E; Kogan, M J

    2016-01-01

    Metal nanoparticles have been proposed as a carrier and a therapeutic agent in biomedical field because of their unique physiochemical properties. Due to these physicochemical properties, they can be used in different fields of biomedicine. In relation to this, plasmonic nanoparticles can be used for detection and photothermal destruction of tumor cells or toxic protein aggregates, and magnetic iron nanoparticles can be used for imaging and for hyperthermia of tumor cells. In addition, both therapy and imaging can be combined in one nanoparticle system, in a process called theranostics. Metal nanoparticles can be synthesized to modulate their size and shape, and conjugated with different ligands, which allow their application in drug delivery, diagnostics, and treatment of central nervous system diseases. This review is focused on the potential applications of metal nanoparticles and their capability to circumvent the blood-brain barrier (BBB). Although many articles have demonstrated delivery of metal nanoparticles to the brain by crossing the BBB after systemic administration, the percentage of the injected dose that reaches this organ is low in comparison to others, especially the liver and spleen. In connection with this drawback, we elaborate the architecture of the BBB and review possible mechanisms to cross this barrier by engineered nanoparticles. The potential uses of metal nanoparticles for treatment of disorders as well as related neurotoxicological considerations are also discussed. Finally, we bring up for discussion a direct and relatively simpler solution to the problem. We discuss this in detail after having proposed the use of the intranasal administration route as a way to circumvent the BBB. This route has not been extensively studied yet for metal nanoparticles, although it could be used as a research tool for mechanistic understanding and toxicity as well as an added value for medical practice. © 2016 Elsevier Inc. All rights reserved.

  11. Comparison of Two Different Intranasal Doses of Dexmedetomidine in Children for Magnetic Resonance Imaging Sedation.

    PubMed

    Tug, Aslihan; Hanci, Ayse; Turk, Hacer Sebnem; Aybey, Ferda; Isil, Canan Tulay; Sayin, Pinar; Oba, Sibel

    2015-12-01

    Anaesthetic agents used for magnetic resonance imaging (MRI) in paediatric patients should cause few adverse effects and allow fast anaesthetic induction and recovery. The administration route is also important and should be minimally invasive. In this study, we aimed to compare two different doses of intranasal dexmedetomidine applied to children for MRI sedation. Sixty patients between 1 and 10 years of age with American Society of Anesthesiologists Physical Status classification I or II who were scheduled for MRI were recruited into this prospective, randomized, double-blind study. Intranasal dexmedetomidine was administered at doses of 3 µg kg(-1) (Group 1) and 4 µg kg(-1) (Group 2) before imaging. Heart rate (HR), peripheral oxygen saturation, respiratory rate and Ramsay Sedation Scale (RSS) scores were recorded before the anaesthetic induction of sedation and every 10 min until discharge. If intranasal sedation failed, an intravenous cannula was placed and propofol was applied as a rescue anaesthetic. Bispectral Index (BIS) scores were also recorded before and after MRI. We recorded onset time of sedation, mood at separation from parents (defined as parental separation score), imaging quality, MRI duration, rescue anaesthetic requirement, total duration of sedation, recovery duration, parents' satisfaction and adverse effects. The results related to age, weight and adverse effects were not statistically different between the groups. The parental separation score was significantly higher in Group 2 (P = 0.003). Rescue anaesthetic requirement was significantly higher in Group 1 (P = 0.002). The results related to recovery duration, MRI duration, parents' satisfaction, onset time of sedation and total duration of sedation were not statistically different. HR was significantly lower in all time intervals compared with basal values in both groups. In Group 2, RSS scores were significantly higher in the 30th, 40th and 50th min. The BIS scores in Group 2 were

  12. Computed Intranasal Spray Penetration: Comparisons Before and After Nasal Surgery

    PubMed Central

    Frank, Dennis O.; Kimbell, Julia S.; Cannon, Daniel; Rhee, John S.

    2012-01-01

    Background Quantitative methods for comparing intranasal drug delivery efficiencies pre- and postoperatively have not been fully utilized. The objective of this study is to use computational fluid dynamics techniques to evaluate aqueous nasal spray penetration efficiencies before and after surgical correction of intranasal anatomic deformities. Methods Ten three-dimensional models of the nasal cavities were created from pre- and postoperative computed tomography scans in five subjects. Spray simulations were conducted using a particle size distribution ranging from 10–110μm, a spray speed of 3m/s, plume angle of 68°, and with steady state, resting inspiratory airflow present. Two different nozzle positions were compared. Statistical analysis was conducted using Student T-test for matched pairs. Results On the obstructed side, posterior particle deposition after surgery increased by 118% and was statistically significant (p-value=0.036), while anterior particle deposition decreased by 13% and was also statistically significant (p-value=0.020). The fraction of particles that by-passed the airways either pre- or post-operatively was less than 5%. Posterior particle deposition differences between obstructed and contralateral sides of the airways were 113% and 30% for pre- and post-surgery, respectively. Results showed that nozzle positions can influence spray delivery. Conclusions Simulations predicted that surgical correction of nasal anatomic deformities can improve spray penetration to areas where medications can have greater effect. Particle deposition patterns between both sides of the airways are more evenly distributed after surgery. These findings suggest that correcting anatomic deformities may improve intranasal medication delivery. For enhanced particle penetration, patients with nasal deformities may explore different nozzle positions. PMID:22927179

  13. Therapeutic effect of intranasal evaporative cooling in patients with migraine: a pilot study.

    PubMed

    Vanderpol, Jitka; Bishop, Barbara; Matharu, Manjit; Glencorse, Mark

    2015-01-26

    Cryotherapy is the most common non-pharmacological pain-relieving method. The aim of this pilot study was to ascertain whether intranasal evaporative cooling may be an effective intervention in an acute migraine attack. Studies have previously demonstrated effectiveness of a variety of cryotherapy approaches. Intranasal evaporative cooling due to vascular anatomy, allows the transfer of venous blood from nasal and paranasal mucous membranes to the dura mater, thereby providing an excellent anatomical basis for the cooling processes. We conducted a prospective, open-label, observational, pilot study. Twenty-eight patients who satisfied the International Classification of Headache Disorders (ICHD 2) diagnostic criteria for migraine were recruited. A total of 20 treatments were administered in 15 patients. All patients provided pain severity scores and migraine-associated symptoms severity scores (based on a 0-10 visual analogue scale, [VAS]). Out of the 20 treatments, intranasal evaporative cooling rendered patients' pain and symptoms free immediately after treatment, in 8 of the treatments (40%), a further 10 treatments (50%) resulted in partial pain relief (headache reduced from severe or moderate to mild) and partial symptoms relief. At 2 hours, 9 treatments (45%) provided full pain and symptoms relief, with a further 9 treatments (45%) resulting in partial pain and symptoms relief. At 24 hours, 10 treatments (50%) resulted in patients reporting pain and symptom freedom and 3 (15%) provided partial pain relief. In summary 13 patients (87%) had benefit from the treatment within 2 hours that was sustained at 24 hours. Intranasal evaporative cooling gave considerable benefit to patients with migraine, improving headache severity and migraine-associated symptoms. A further randomised, placebo controlled, double blinded, parallel clinical trial is required to further investigate the potential of this application. Clinicaltrials.gov registered trial, Clinical

  14. Intranasal administration of testosterone increased immobile-sniffing, exploratory behavior, motor behavior and grooming behavior in rats.

    PubMed

    Zhang, Guoliang; Shi, Geming; Tan, Huibing; Kang, Yunxiao; Cui, Huixian

    2011-04-01

    Currently, testosterone (T) replacement therapy is typically provided by oral medication, injectable T esters, surgically implanted T pellets, transdermal patches and gels. However, most of these methods of administration are still not ideal for targeting the central nervous system. Recently, therapeutic intranasal T administration (InT) has been considered as another option for delivering T to the brain. In the present study, the effects of 21-day InT treatment were assessed on open field behavior in gonadectomized (GDX) rats and intact rats. Subcutaneous injections of T at same dose were also tested in GDX rats. A total of 12 behavioral events were examined in GDX groups with or without T and in intact groups with or without InT. Significant decreases in open field activity were observed in rats after GDX without InT compared to sham-operated rats. The open field activity scores for most tests significantly increased with InT treatment in GDX rats and in intact rats compared with the corresponding GDX rats and intact rats. Intranasal administration of T improved the reduced behaviors resulted from T deficiency better than subcutaneous injection of T, demonstrating that T can be delivered to the brain by intranasal administration. Our results suggest that intranasal T delivery is an effective option for targeting the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Intranasal post-cardiac arrest treatment with orexin-A facilitates arousal from coma and ameliorates neuroinflammation.

    PubMed

    Modi, Hiren R; Wang, Qihong; Gd, Sahithi; Sherman, David; Greenwald, Elliot; Savonenko, Alena V; Geocadin, Romergryko G; Thakor, Nitish V

    2017-01-01

    Cardiac arrest (CA) entails significant risks of coma resulting in poor neurological and behavioral outcomes after resuscitation. Significant subsequent morbidity and mortality in post-CA patients are largely due to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia post-CA syndrome (PCAS). PCAS results in strong inflammatory responses including neuroinflammation response leading to poor outcome. Currently, there are no proven neuroprotective therapies to improve post-CA outcomes apart from therapeutic hypothermia. Furthermore, there are no acceptable approaches to promote cortical or cognitive arousal following successful return of spontaneous circulation (ROSC). Hypothalamic orexinergic pathway is responsible for arousal and it is negatively affected by neuroinflammation. However, whether activation of the orexinergic pathway can curtail neuroinflammation is unknown. We hypothesize that targeting the orexinergic pathway via intranasal orexin-A (ORXA) treatment will enhance arousal from coma and decrease the production of proinflammatory cytokines resulting in improved functional outcome after resuscitation. We used a highly validated CA rat model to determine the effects of intranasal ORXA treatment 30-minute post resuscitation. At 4hrs post-CA, the mRNA levels of proinflammatory markers (IL1β, iNOS, TNF-α, GFAP, CD11b) and orexin receptors (ORX1R and ORX2R) were examined in different brain regions. CA dramatically increased proinflammatory markers in all brain regions particularly in the prefrontal cortex, hippocampus and hypothalamus. Post-CA intranasal ORXA treatment significantly ameliorated the CA-induced neuroinflammatory markers in the hypothalamus. ORXA administration increased production of orexin receptors (ORX1R and ORX2R) particularly in hypothalamus. In addition, ORXA also resulted in early arousal as measured by quantitative electroencephalogram (EEG) markers, and recovery of the associated behavioral neurologic

  16. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder

    PubMed Central

    van Zuiden, Mirjam; Koch, Saskia B.J.; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

    2017-01-01

    Abstract Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. PMID:27614769

  17. Intranasal budesonide treatment for children with mild obstructive sleep apnea syndrome.

    PubMed

    Kheirandish-Gozal, Leila; Gozal, David

    2008-07-01

    Intranasal corticosteroids have been advanced as a nonsurgical therapeutic alternative for pediatric obstructive sleep apnea syndrome, particularly for patients with mild disease, and aims at reducing the size of hypertrophic adenotonsillar tissue. Of 71 possible candidates, 62 children with polysomnographically diagnosed mild obstructive sleep apnea syndrome were recruited onto a double-blind, randomized, crossover trial of intranasal budesonide (32 microg per nostril at bedtime) or placebo for 6 weeks followed by an additional 6-week treatment in the alternative treatment arm after allowing for a 2-week washout period. Polysomnographic assessment and radiographs for assessment of adenoid size were performed after completion of each phase. There were significant improvements in both polysomnographic measures (sleep latency, slow-wave sleep, and rapid-eye-movement sleep), in the magnitude of respiratory disturbance (apnea/hypopnea index, nadir pulse oxygen saturation), and in adenoid size among the 48 children who completed the treatment phase compared with 32 children who received placebo in their initial arm, with normalization of sleep measures in 54.1% of the treated children. Furthermore, discontinuation of treatment for 8 weeks for 25 children revealed a sustained duration of the initial treatment effect. A 6-week treatment with intranasal budesonide effectively reduced the severity of mild obstructive sleep apnea syndrome and the magnitude of the underlying adenoidal hypertrophy, and this effect persisted for at least 8 weeks after cessation of therapy. These findings justify the use of topical steroids as the initial therapeutic option in otherwise healthy children with mild obstructive sleep apnea.

  18. Intranasal naltrexone and atipamezole for reversal of white-tailed deer immobilized with carfentanil and medetomidine

    PubMed Central

    Shury, Todd K.; Caulkett, Nigel A.; Woodbury, Murray R.

    2010-01-01

    Carfentanil and medetomidine were used to immobilize 8 captive female white-tailed deer (Odocoileus virginianus) using mean dosages [± standard deviation (s)] of 14.2 ± 1.11 μg/kg carfentanil and 17.8 ± 2.03 μg/kg of medetomidine. Deer were reversed by intranasally or intramuscularly administered naltrexone and atipamezole. Dosages of carfentanil and medetomidine proved reliable for immobilization of most, but not all deer, with a mean induction time of 13.3 ± 3.13 min. Effective and reliable immobilization will require higher dosages of carfentanil and possibly medetomidine than were used in this study. No significant differences in recovery times were observed for deer given reversal agents intranasally (9.45 ± 5.37 min) versus intramuscularly (7.60 ± 4.42 min). Naltrexone and atipamezole can be administered intranasally at 1.5 mg/kg and 0.1 mg/kg, respectively to safely and quickly reverse the effects of carfentanil and medetomidine in immobilized white-tailed deer. This route could potentially be useful for other reversal agents. PMID:20676292

  19. Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets.

    PubMed

    Vesal, Nasser; Eskandari, Mohammad H

    2006-02-01

    To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. Prospective study. 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.

  20. Intranasal dexmedetomidine for sedation for pediatric computed tomography imaging.

    PubMed

    Mekitarian Filho, Eduardo; Robinson, Fay; de Carvalho, Werther Brunow; Gilio, Alfredo Elias; Mason, Keira P

    2015-05-01

    This prospective observational pilot study evaluated the aerosolized intranasal route for dexmedetomidine as a safe, effective, and efficient option for infant and pediatric sedation for computed tomography imaging. The mean time to sedation was 13.4 minutes, with excellent image quality, no failed sedations, or significant adverse events. Registered with ClinicalTrials.gov: NCT01900405. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The effects of intranasal oxytocin on smoothie intake, cortisol and attentional bias in anorexia nervosa.

    PubMed

    Leppanen, Jenni; Cardi, Valentina; Ng, Kah Wee; Paloyelis, Yannis; Stein, Daniel; Tchanturia, Kate; Treasure, Janet

    2017-05-01

    Anorexia nervosa (AN) is characterised by severe malnutrition as well as intense fear and anxiety around food and eating with associated anomalies in information processing. Previous studies have found that the neuropeptide, oxytocin, can influence eating behaviour, lower the neurobiological stress response and anxiety among clinical populations, and alter attentional processing of food and eating related images in AN. Thirty adult women with AN and twenty-nine healthy comparison (HC) women took part in the current study. The study used double blind, placebo controlled, crossover design to investigate the effects of a single dose of intranasal oxytocin (40 IU) on a standard laboratory smoothie challenge, and on salivary cortisol, anxiety, and attentional bias towards food images before and after the smoothie challenge in AN and HC participants. Attentional bias was assessed using a visual probe task. Relative to placebo intranasal oxytocin reduced salivary cortisol and altered anomalies in attentional bias towards food images in the AN group only. The oxytocin-induced reduction in attentional avoidance of food images correlated with oxytocin induced reduction in salivary cortisol in the AN group before the smoothie challenge. Intranasal oxytocin did not significantly alter subjective feelings of anxiety or intake during the smoothie challenge in the AN or HC groups. Intranasal oxytocin may moderate the automated information processing biases in AN and reduce neurobiological stress. Further investigation of the effects of repeated administration of oxytocin on these processes as well as on eating behaviour and subjective anxiety would be of interest. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    ERIC Educational Resources Information Center

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  3. Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

    PubMed

    Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

    2002-11-01

    Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

  4. Influence of acute bupropion pre-treatment on the effects of intranasal cocaine.

    PubMed

    Stoops, William W; Lile, Joshua A; Glaser, Paul E A; Hays, Lon R; Rush, Craig R

    2012-06-01

    The aim of this experiment was to determine the influence of acute bupropion pre-treatment on subject-rated effects and choice of intranasal cocaine versus money. A randomized, within-subject, placebo-controlled, double-blind experiment. An out-patient research unit. Eight cocaine-using adults. Subjects completed nine experimental sessions in which they were pre-treated with 0, 100 or 200 mg oral immediate release bupropion. Ninety minutes later they sampled an intranasal cocaine dose [4 (placebo), 15 or 45 mg] and made six choices between that dose and an alternative reinforcer (US$0.25), available on independent, concurrent progressive ratio schedules. Subjects also completed a battery of subject-rated, performance and physiological measures following the sample doses of cocaine. After 0 mg bupropion, the high dose of cocaine (45 mg) was chosen five of six times on average compared to 2.25 of six choices for placebo cocaine (4 mg) (P < 0.05). Active bupropion reduced choice of 45 mg cocaine to 3.13 (100 mg) or 4.00 (200 mg) out of six drug choices on average. Bupropion also consistently enhanced positive subject-rated effects of cocaine (e.g. good effects; willing to take again) while having no effects of its own. The atypical antidepressant, bupropion, acutely appears to reduce preference for intranasal cocaine versus a small amount of money but to increase reported positive experiences of the drug. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  5. Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

    PubMed

    Barik, Sailen

    2009-01-01

    Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

  6. Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

    PubMed Central

    Sable, Suraj B.; Cheruvu, Mani; Nandakumar, Subhadra; Sharma, Sunita; Bandyopadhyay, Kakali; Kellar, Kathryn L.; Posey, James E.; Plikaytis, Bonnie B.; Amara, Rama Rao; Shinnick, Thomas M.

    2011-01-01

    Background The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. Methods and Principal Findings In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. Conclusion and Significance Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis. PMID:21799939

  7. Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route.

    PubMed

    Mittal, Deepti; Md, Shadab; Hasan, Quamrul; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Ali, Javed

    2016-01-01

    The aim of the present study was to prepare and evaluate a rasagiline-loaded chitosan glutamate nanoparticles (RAS-CG-NPs) by ionic gelation of CG with tripolyphosphate anions (TPP). RAS-loaded CG-NPs were characterized for particle size, size distribution, encapsulation efficiency and in vitro drug release. The mean particles size, polydispersity index (PDI) and encapsulation efficiency was found to be 151.1 ± 10.31, 0.380 ± 0.01 and 96.43 ± 4.23, respectively. Biodistribution of RAS formulations in the brain and blood of mice following intranasal (i.n.) and intravenous (i.v.) administration was performed using HPLC analytical method. The drug concentrations in brain following the i.n. of CG-NPs were found to be significantly higher at all the time points compared to both drug (i.n.) and drug CG-NPs (i.v.). The Cmax (999.25 ng/ml) and AUC (2086.60 ng h/ml) of formulation CG-NPs (i.n) were found to be significantly higher than CG-NPs (i.v.) and RAS solution (i.n.). The direct transport percentage (DTP%) values of RAS-loaded CG-NPs (i.n.) as compared to drug solution (i.n.) increased from 66.27 ± 1.8 to 69.27 ± 2.1%. The results showed significant enhancement of bioavailability in brain, after administration of the RAS-loaded CG-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson's disease therapy.

  8. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence.

    PubMed

    Freiherr, Jessica; Hallschmid, Manfred; Frey, William H; Brünner, Yvonne F; Chapman, Colin D; Hölscher, Christian; Craft, Suzanne; De Felice, Fernanda G; Benedict, Christian

    2013-07-01

    Research in animals and humans has associated Alzheimer's disease (AD) with decreased cerebrospinal fluid levels of insulin in combination with decreased insulin sensitivity (insulin resistance) in the brain. This phenomenon is accompanied by attenuated receptor expression of insulin and insulin-like growth factor, enhanced serine phosphorylation of insulin receptor substrate-1, and impaired transport of insulin across the blood-brain barrier. Moreover, clinical trials have demonstrated that intranasal insulin improves both memory performance and metabolic integrity of the brain in patients suffering from AD or its prodrome, mild cognitive impairment. These results, in conjunction with the finding that insulin mitigates hippocampal synapse vulnerability to beta amyloid, a peptide thought to be causative in the development of AD, provide a strong rationale for hypothesizing that pharmacological strategies bolstering brain insulin signaling, such as intranasal administration of insulin, could have significant potential in the treatment and prevention of AD. With this view in mind, the review at hand will present molecular mechanisms potentially underlying the memory-enhancing and neuroprotective effects of intranasal insulin. Then, we will discuss the results of intranasal insulin studies that have demonstrated that enhancing brain insulin signaling improves memory and learning processes in both cognitively healthy and impaired humans. Finally, we will provide an overview of neuroimaging studies indicating that disturbances in insulin metabolism--such as insulin resistance in obesity, type 2 diabetes and AD--and altered brain responses to insulin are linked to decreased cerebral volume and especially to hippocampal atrophy.

  9. Recent Advances in Inorganic Nanoparticle-Based NIR Luminescence Imaging: Semiconductor Nanoparticles and Lanthanide Nanoparticles.

    PubMed

    Kim, Dokyoon; Lee, Nohyun; Park, Yong Il; Hyeon, Taeghwan

    2017-01-18

    Several types of nanoparticle-based imaging probes have been developed to replace conventional luminescent probes. For luminescence imaging, near-infrared (NIR) probes are useful in that they allow deep tissue penetration and high spatial resolution as a result of reduced light absorption/scattering and negligible autofluorescence in biological media. They rely on either an anti-Stokes or a Stokes shift process to generate luminescence. For example, transition metal-doped semiconductor nanoparticles and lanthanide-doped inorganic nanoparticles have been demonstrated as anti-Stokes shift-based agents that absorb NIR light through two- or three-photon absorption process and upconversion process, respectively. On the other hand, quantum dots (QDs) and lanthanide-doped nanoparticles that emit in NIR-II range (∼1000 to ∼1350 nm) were suggested as promising Stokes shift-based imaging agents. In this topical review, we summarize and discuss the recent progress in the development of inorganic nanoparticle-based luminescence imaging probes working in NIR range.

  10. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    PubMed

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  11. The neuronal correlates of intranasal trigeminal function – An ALE meta-analysis of human functional brain imaging data

    PubMed Central

    Albrecht, Jessica; Kopietz, Rainer; Frasnelli, Johannes; Wiesmann, Martin; Hummel, Thomas; Lundström, Johan N.

    2009-01-01

    Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO2), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices – a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO2 stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing. PMID:19913573

  12. Cobalt-rhodium heterobimetallic nanoparticle-catalyzed reactions.

    PubMed

    Park, Ji Hoon; Chung, Young Keun

    2008-05-14

    Transition metal nanoparticles have attracted a great deal of attention. This review discusses the synthesis of heterobimetallic cobalt-rhodium nanoparticles and their use as catalysts in organic transformations. Co-Rh nanoparticles (Co2Rh2) with a fixed stoichiometry (2 : 2) were easily obtained from Co2Rh2(CO)12. These nanoparticles were quite effective catalysts for carbonylation reactions. Particularly, special focus is paid to the Pauson-Khand-type reaction.

  13. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    PubMed

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  14. Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

    PubMed

    Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

    2006-08-01

    Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

  15. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

    PubMed

    Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

    2016-09-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

    PubMed

    Mizera, L; Gossrau, G; Hummel, T; Haehner, A

    2017-01-01

    There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without

  17. Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

    PubMed

    Kruger, Tillmann H C; Deiter, Frank; Zhang, Yuanyuan; Jung, Stefanie; Schippert, Cordula; Kahl, Kai G; Heinrichs, Markus; Schedlowski, Manfred; Hartmann, Uwe

    2018-06-01

    The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

  18. Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

    PubMed

    Skulberg, Arne Kristian; Tylleskar, Ida; Nilsen, Turid; Skarra, Sissel; Salvesen, Øyvind; Sand, Trond; Loftsson, Thorsteinn; Dale, Ola

    2018-03-22

    This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. clinicaltrials.gov : NCT02307721.

  19. Labeling and tracking exosomes within the brain using gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Betzer, Oshra; Perets, Nisim; Barnoy, Eran; Offen, Daniel; Popovtzer, Rachela

    2018-02-01

    Cell-to-cell communication system involves Exosomes, small, membrane-enveloped nanovesicles. Exosomes are evolving as effective therapeutic tools for different pathologies. These extracellular vesicles can bypass biological barriers such as the blood-brain barrier, and can function as powerful nanocarriers for drugs, proteins and gene therapeutics. However, to promote exosomes' therapy development, especially for brain pathologies, a better understanding of their mechanism of action, trafficking, pharmacokinetics and bio-distribution is needed. In this research, we established a new method for non-invasive in-vivo neuroimaging of mesenchymal stem cell (MSC)-derived exosomes, based on computed tomography (CT) imaging with glucose-coated gold nanoparticle (GNP) labeling. We demonstrated that the exosomes were efficiently and directly labeled with GNPs, via an energy-dependent mechanism. Additionally, we found the optimal parameters for exosome labeling and neuroimaging, wherein 5 nm GNPs enhanced labeling, and intranasal administration produced superior brain accumulation. We applied our technique in a mouse model of focal ischemia. Imaging and tracking of intranasally-administered GNP-labeled exosomes revealed specific accumulation and prolonged presence at the lesion area, up to 24 hrs. We propose that this novel exosome labeling and in-vivo neuroimaging technique can serve as a general platform for brain theranostics.

  20. Optical diffraction in ordered VO2 nanoparticle arrays

    NASA Astrophysics Data System (ADS)

    Lopez, Rene; Feldman, Leonard; Haglund, Richard

    2006-03-01

    The potential of oxide electronic materials as multifunctional building blocks is one of the driving concepts of the field. In this presentation, we show how nanostructured particle arrays with long-range order can be used to modulate an optical response through exploiting the metal-insulator transition of vanadium dioxide. Arrays of VO2 nanoparticles with long-range order were fabricated by pulsed laser deposition in an arbitrary pattern defined by focused ion-beam lithography. The interaction of light with the nanoparticles is controlled by the nanoparticle size, spacing and geometrical arrangement and by switching between the metallic and semiconducting phases of VO2. In addition to the near-infrared surface plasmon response observed in previous VO2 studies, the VO2 nanoparticle arrays exhibit size-dependent optical resonances in the visible region that likewise show an enhanced optical contrast between the semiconducting and metallic phases. The collective optical response as a function of temperature gives rise to an enhanced scattering state during the evolving phase transition, while the incoherent coupling between the nanoparticles produces an order-disorder-order transition.

  1. Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

    PubMed

    Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

    2017-02-15

    Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [Studies on formulations of Panax notoginsenosides for intranasal administration].

    PubMed

    Xu, Qing-fang; Fang, Xiao-ling; Chen, Dao-feng; Li, Jun-chan

    2003-11-01

    To develop high bioavailability preparations without irritation for Panax notoginsenosides. The effects of some additives such as microcrystalline cellulose, beta-cyclodextrin and hydroxypropyl cellulose on drug in the preparations were examined. Saponins of Panax notoginseng (PNS) was absorbed in rabbits more when administered intranasally than through other routines, and the formulations including MCC both gave high bioavailability and low irritation. Bioavailability of Panax notoginsenosides can be increased through changing routine of administration and formulations.

  3. Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice.

    PubMed

    Pratti, Juliana Elena Silveira; Ramos, Tadeu Diniz; Pereira, Joyce Carvalho; da Fonseca-Martins, Alessandra Marcia; Maciel-Oliveira, Diogo; Oliveira-Silva, Gabriel; de Mello, Mirian França; Chaves, Suzana Passos; Gomes, Daniel Claudio Oliveira; Diaz, Bruno Lourenço; Rossi-Bergmann, Bartira; de Matos Guedes, Herbert Leonel

    2016-10-06

    We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis. C57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads. C57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider's media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy. This study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host.

  4. Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts

    NASA Astrophysics Data System (ADS)

    Tonga, Gulen Yesilbag; Jeong, Youngdo; Duncan, Bradley; Mizuhara, Tsukasa; Mout, Rubul; Das, Riddha; Kim, Sung Tae; Yeh, Yi-Cheun; Yan, Bo; Hou, Singyuk; Rotello, Vincent M.

    2015-07-01

    Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril ‘gate-keeper’ onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.

  5. Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses.

    PubMed

    Harata, G; He, F; Hiruta, N; Kawase, M; Kubota, A; Hiramatsu, M; Yausi, H

    2010-06-01

    To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model. After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0.05). The YAC-1 cell-killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0.01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)-1 beta, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)-1 (P < 0.01). These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell-mediated immune responses following up-regulation of lung natural killer (NK) cell activation. We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract.

  6. Vanadium Dioxide Nanoparticle-based Thermochromic Smart Coating: High Luminous Transmittance, Excellent Solar Regulation Efficiency, and Near Room Temperature Phase Transition.

    PubMed

    Zhu, Jingting; Zhou, Yijie; Wang, Bingbing; Zheng, Jianyun; Ji, Shidong; Yao, Heliang; Luo, Hongjie; Jin, Ping

    2015-12-23

    An annealing-assisted preparation method of well-crystallized VxW1-xO2(M)@SiO2 core-shell nanoparticles for VO2-based thermochromic smart coatings (VTSC) is presented. The additional annealing process reduces the defect density of the initial hydrothermally prepared VxW1-xO2(M) nanoparticles and enhances their crystallinity so that the thermochromic film based on VxW1-xO2(M)@SiO2 nanoparticles can exhibit outstanding thermochromic performance with balanced solar regulation efficiency (ΔTsol) of 17.3%, luminous transmittance (Tlum) up to 52.2%, and critical phase transition temperature (Tc) around 40.4 °C, which is very promising for practical application. Furthermore, it makes great progress in reducing Tc of VTSC to near room temperature (25.2 °C) and simutaneously maintaining excellent optical properties (ΔTsol = 14.7% and Tlum = 50.6%). Such thermochromic performance is good enough to make VTSC applicable to practical architecture.

  7. Nanocomposites for neurodegenerative diseases: hydrogel-nanoparticle combinations for a challenging drug delivery.

    PubMed

    Giordano, Carmen; Albani, Diego; Gloria, Antonio; Tunesi, Marta; Rodilossi, Serena; Russo, Teresa; Forloni, Gianluigi; Ambrosio, Luigi; Cigada, Alberto

    2011-12-01

    Neurodegenerative disorders are expected to strike social and health care systems of developed countries heavily in the coming decades. Alzheimer's and Parkinson's diseases (AD/PD) are the most prevalent neurodegenerative pathologies, and currently their available therapy is only symptomatic. However, innovative potential drugs are actively under development, though their efficacy is sometimes limited by poor brain bioavailability and/or sustained peripheral degradation. To partly overcome these constraints, the development of drug delivery devices made by biocompatible and easily administrable materials might be a great adjuvant. In particular, materials science can provide a powerful tool to design hydrogels and nanoparticles as basic components of more complex nanocomposites that might ameliorate drug or cell delivery in AD/PD. This kind of approach is particularly promising for intranasal delivery, which might increase brain targeting of neuroprotective molecules or proteins. Here we review these issues, with a focus on nanoparticles as nanocomponents able to carry and tune drug release in the central nervous system, without ignoring warnings concerning their potential toxicity.

  8. Intranasal approach for manipulating the depressor septi nasi.

    PubMed

    Oh, Sang-Ha; Choi, Sangmun; Kim, Dong Woon; Jeong, Jae Yong

    2012-03-01

    A hyperactivated depressor septi nasi is an important factor contributing to nasal tip drooping. Although many studies have examined this, its treatment remains controversial. This study presents a surgical intervention based on an anatomic study.Ten fresh cadavers with large noses were used for the anatomic study. Between April 2008 and September 2010, 20 patients underwent surgical intervention for hyperactivated depressor septi nasi.In all of the cadaver dissections, the depressor septi nasi was present, although it was difficult to identify the muscle clearly in 6 of the cadavers. We found that the depressor septi nasi in the other 4 cadavers consisted of 3 fascicles. The medial fascicles were divided into superficial and deep fibers. Both the deep and superficial fibers were inserted into the dermocartilaginous ligament in the nearby nasal tip. After the superficial fibers were interdigitated with the orbicularis oris, they originated from the alveolar bone. The deep fibers originated at the anterior nasal spine. The intermediate fascicles inserted to the footplates of the medial crus and caudal septum. After interdigitating with the medial fascicles and orbicularis oris, they also originated from the alveolar bone. The drooping nasal tips were improved in all cases using an intranasal approach to manipulate the depressor septi nasi. No specific complication was seen. Surgical intervention of a hyperactivated depressor septi nasi using an intranasal approach was a useful method for correcting a drooping nasal tip.

  9. Antiviral Activity of Intranasally Applied Human Leukocyte Interferon

    PubMed Central

    Greenberg, Stephen B.; Harmon, Maurice W.; Johnson, Paul E.; Couch, Robert B.

    1978-01-01

    Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm2) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application. PMID:214028

  10. Bioavailability of intranasal promethazine dosage forms in dogs

    NASA Technical Reports Server (NTRS)

    Ramanathan, R.; Geary, R. S.; Bourne, D. W.; Putcha, L.

    1998-01-01

    Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

  11. AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

    PubMed Central

    Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.

    2014-01-01

    This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  12. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial.

    PubMed

    Schmidt, H; Kern, W; Giese, R; Hallschmid, M; Enders, A

    2009-04-01

    The 22q13 deletion syndrome (Phelan-McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 deletion syndrome. We performed exploratory clinical trials in six children with 22q13 deletion syndrome who received intranasal insulin over a period of 1 year. Short-term (during the first 6 weeks) and long-term effects (after 12 months of treatment) on motor skills, cognitive functions, or autonomous functions, speech and communication, emotional state, social behaviour, behavioural disorders, independence in daily living and education were assessed. The children showed marked short-term improvements in gross and fine motor activities, cognitive functions and educational level. Positive long-term effects were found for fine and gross motor activities, nonverbal communication, cognitive functions and autonomy. Possible side effects were found in one patient who displayed changes in balance, extreme sensitivity to touch and general loss of interest. One patient complained of intermittent nose bleeding. We conclude that long-term administration of intranasal insulin may benefit motor development, cognitive functions and spontaneous activity in children with 22q13 deletion syndrome.

  13. Chronic orbital inflammatory disease and optic neuropathy associated with long-term intranasal cocaine abuse: 2 cases and literature review.

    PubMed

    Siemerink, Martin J; Freling, Nicole J M; Saeed, Peerooz

    2017-10-01

    Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemia.

  14. Quetiapine Nanoemulsion for Intranasal Drug Delivery: Evaluation of Brain-Targeting Efficiency.

    PubMed

    Boche, Mithila; Pokharkar, Varsha

    2017-04-01

    To evaluate the possibility of improved drug delivery of quetiapine fumarate (QTP), a nanoemulsion system was developed for intranasal delivery. Effects of different HLBs of Emalex LWIS 10, PEG 400 and Transcutol P, as co-surfactants, were studied on isotropic region of pseudoternary-phase diagrams of nanoemulsion system composed of capmul MCM (CPM) as oil phase, Tween 80 as surfactant and water. Phase behaviour, globule size, transmission electron microscope (TEM) photographs and brain-targeting efficiency of quetiapine nanoemulsion were investigated. In vitro dissolution study of optimised nanoemulsion formulation, with mean diameter 144 ± 0.5 nm, showed more than twofold increase in drug release as compared with pure drug. According to results of in vivo tissue distribution study in Wistar rats, intranasal administration of QTP-loaded nanoemulsion had shorter T max compared with that of intravenous administration. Higher drug transport efficiency (DTE%) and direct nose-to-brain drug transport (DTP%) was achieved by nanoemulsion. The nanoemulsion system may be a promising strategy for brain-targeted delivery of QTP.

  15. Optical properties of medium size noble and transition metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Idrobo, Juan C.; Pantelides, Sokrates T.

    2009-03-01

    Using first-principles methods within time dependent density functional theory and the local density approximation (TDLDA) the absorption spectra of medium size (˜20-80 atoms) silver, gold and copper nanoparticles have been calculated. The nanoparticles are fcc fragments with different aspect ratios. We find that in the case of Ag nanoparticles is well reproduced by classical electrodynamics theory based in Mie's formalism, using the dielectric function of bulk Ag and taking into account the nanoparticle shape. For the case of Cu and Au, there is a similarity in the overall features of the quantum mechanical and classical spectra, but no detailed agreement. We will discuss the role that the d-electrons among all the different elements and the surface states play in controlling the optical properties of the nanoparticles. This work was supported by GOALI NSF grant (DMR-0513048), DOE, the Office of Basic Energy Sciences, Division of Materials Sciences and Engineering, and Alcoa Inc.

  16. Use of Intranasal Naloxone by Basic Life Support Providers.

    PubMed

    Weiner, Scott G; Mitchell, Patricia M; Temin, Elizabeth S; Langlois, Breanne K; Dyer, K Sophia

    2017-01-01

    Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu Qingfeng; Shao Xiayan; Chen Jie

    Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain weremore » measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-{alpha} level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.« less

  18. Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

    DOE PAGES

    Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.; ...

    2018-01-11

    Gadolinium silicide (Gd 5Si 4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd 5Si 4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd 5Si 4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd 5Si 3 impurity. Here as the particle sizes decrease, the volumemore » fraction of Gd 5Si 3 phase increases at the expense of the Gd 5Si 4 phase, and the ferromagnetic transition temperature of Gd 5Si 4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.« less

  19. Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.; Gupta, Shalabh; Pecharsky, Vitalij K.; Hadimani, Ravi L.

    2018-05-01

    Gadolinium silicide (Gd5Si4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd5Si4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd5Si4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd5Si3 impurity. As the particle sizes decrease, the volume fraction of Gd5Si3 phase increases at the expense of the Gd5Si4 phase, and the ferromagnetic transition temperature of Gd5Si4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.

  20. Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.

    Gadolinium silicide (Gd 5Si 4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd 5Si 4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd 5Si 4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd 5Si 3 impurity. Here as the particle sizes decrease, the volumemore » fraction of Gd 5Si 3 phase increases at the expense of the Gd 5Si 4 phase, and the ferromagnetic transition temperature of Gd 5Si 4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.« less

  1. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

    PubMed Central

    Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

    2014-01-01

    Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. PMID:25014738

  2. Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium.

    PubMed

    Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

    2016-01-01

    The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a . Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a , whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b . Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b . Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose

  3. Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium

    PubMed Central

    Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

    2016-01-01

    The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and

  4. Intranasal immunization with novel EspA-Tir-M fusion protein induces protective immunity against enterohemorrhagic Escherichia coli O157:H7 challenge in mice.

    PubMed

    Lin, Ruqin; Zhu, Bo; Zhang, Yiduo; Bai, Yang; Zhi, Fachao; Long, Beiguo; Li, Yawen; Wu, Yuhua; Wu, Xianbo; Fan, Hongying

    2017-04-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome in humans. Due to the risks associated with antibiotic treatment against EHEC O157:H7 infection, vaccines represent a promising method for prevention of EHEC O157:H7 infection. Therefore, we constructed the novel bivalent antigen EspA-Tir-M as a candidate EHEC O157:H7 subunit vaccine. We then evaluated the immunogenicity of this novel EHEC O157:H7 subunit vaccine. Immune responses to the fusion protein administered by intranasal and subcutaneous routes were compared in mice. Results showed higher levels of specific mucosal and systemic antibody responses induced by intranasal as compared to subcutaneous immunization. Intranasal immunization enhanced the concentration of interleukin-4, interleukin-10, and interferon-γ, while subcutaneous immunization enhanced only the latter two. In addition, intranasal immunization protected against EHEC O157:H7 colonization and infection in mice at a rate of 90%.Histopathological analysis revealed that vaccination reduced colon damage, especially when administered intranasally. In contrast, subcutaneous immunization elicited a weak immune response and exhibited a low protection rate. These findings demonstrate that intranasal immunization with the fusion protein induces both humoral and cellular immune (Th1/Th2) responses in mice. The novel EspA-Tir-M novel fusion protein therefore represents a promising subunit vaccine against EHEC O157:H7 infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Intranasal exposure to monoclonal antibody Fab fragments to Japanese cedar pollen Cry j1 suppresses Japanese cedar pollen‐induced allergic rhinitis

    PubMed Central

    Mizutani, N

    2016-01-01

    Background and Purpose Fab fragments (Fabs) of antibodies have the ability to bind to specific allergens but lack the Fc portion that exerts effector functions via binding to receptors including FcεR1 on mast cells. In the present study, we investigated whether intranasal administration of the effector function‐lacking Fabs of a monoclonal antibody IgG1 (mAb, P1‐8) to the major allergen Cry j1 of Japanese cedar pollen (JCP) suppressed JCP‐induced allergic rhinitis in mice. Experimental Approach Balb/c mice sensitized with JCP on days 0 and 14 were challenged intranasally with the pollen on days 28, 29, 30 and 35. Fabs prepared by the digestion of P1‐8 with papain were also administered intranasally 15 min before each JCP challenge. Key Results Intranasal administration of P1‐8 Fabs was followed by marked suppression of sneezing and nasal rubbing in mice with JCP‐induced allergic rhinitis. The suppression of these allergic symptoms by P1‐8 Fabs was associated with decreases in mast cells and eosinophils and decreased hyperplasia of goblet cells in the nasal mucosa. Conclusions and Implications These results demonstrated that intranasal exposure to P1‐8 Fabs was effective in suppressing JCP‐induced allergic rhinitis in mice, suggesting that allergen‐specific mAb Fabs might be used as a tool to regulate allergic pollinosis. PMID:26895546

  6. Causality Assessment of Olfactory and Gustatory Dysfunction Associated with Intranasal Fluticasone Propionate: Application of the Bradford Hill Criteria.

    PubMed

    Muganurmath, Chandrashekhar S; Curry, Amy L; Schindzielorz, Andrew H

    2018-02-01

    Causality assessment is crucial to post-marketing pharmacovigilance and helps optimize safe and appropriate use of medicines by patients in the real world. Self-reported olfactory and gustatory dysfunction are common in the general population as well as in patients with allergic rhinitis and nasal polyposis. Intranasal corticosteroids, including intranasal fluticasone propionate (INFP), are amongst the most effective drugs indicated in the treatment of allergic rhinitis and nasal polyposis. While intranasal corticosteroids are associated with olfactory and gustatory dysfunction and are currently labeled for these adverse events, causality assessment has not been performed to date. Although there is no single widely accepted method to assess causality in pharmacovigilance, the Bradford Hill criteria offer a robust and comprehensive approach because nine distinct aspects of an observed potential drug-event association are assessed. In this literature-based narrative review, Hill's criteria were applied to determine causal inference between INFP and olfactory and gustatory dysfunction.

  7. A randomised controlled trial of oral chloral hydrate vs. intranasal dexmedetomidine before computerised tomography in children.

    PubMed

    Yuen, V M; Li, B L; Cheuk, D K; Leung, M K M; Hui, T W C; Wong, I C; Lam, W W; Choi, S W; Irwin, M G

    2017-10-01

    Chloral hydrate is commonly used to sedate children for painless procedures. Children may recover more quickly after sedation with dexmedetomidine, which has a shorter half-life. We randomly allocated 196 children to chloral hydrate syrup 50 mg.kg -1 and intranasal saline spray, or placebo syrup and intranasal dexmedetomidine spray 3 μg.kg -1 , 30 min before computerised tomography studies. More children resisted or cried after drinking chloral hydrate syrup than placebo syrup, 72 of 107 (67%) vs. 42 of 87 (48%), p = 0.009, but there was no difference after intranasal saline vs. dexmedetomidine, 49 of 107 (46%) vs. 40 of 87 (46%), p = 0.98. Sedation was satisfactory in 81 of 107 (76%) children after chloral hydrate and 64 of 87 (74%) children after dexmedetomidine, p = 0.74. Of the 173 children followed up for at least 4 h after discharge, 38 of 97 (39%) had recovered normal function after chloral hydrate and 32 of 76 (42%) after dexmedetomidine, p = 0.76. Six children vomited after chloral hydrate syrup and placebo spray vs. none after placebo syrup and dexmedetomidine spray, p = 0.03. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  8. Comparison of the Efficacy, Side Effects, and Cost of Modafinil and Intranasal Mometasone Furoate in Obstructive Sleep Apnea-Hypopnea Syndrome: A Preliminary Clinical Study

    PubMed Central

    Zhang, Shujia; Duan, Zhongnin

    2018-01-01

    Background Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated episodes of reduction in airflow due to the collapse of the upper airway during sleep. The aim of this study was to compare clinical outcome, side effects, and cost of treatment between modafinil and intranasal mometasone furoate in patients with OSAHS. Material/Methods Patients with OSAHS (N=250) were divided into two groups: the modafinil group (MG) (N=125) were treated with 100 mg modafinil twice a day; the intranasal mometasone furoate group (IMFG) (N=125) were treated with 100 μg of intranasal mometasone furoate in the evening. Quality of life, grading of OSAHS, plain-film radiography, the adenoidal-nasopharyngeal ratio (AN ratio), side effects, cost of treatment, and beneficial effects after discontinuation of treatment were evaluated for all patients. Results Duration of sleep apnea was significantly reduced in the IMFG compared with the MG (p=0.0145, q=9.262). Modafinil and intranasal mometasone furoate both had moderate effects on improvement of the OSAHS score. The IMFG showed a significantly greater beneficial effect on the AN ratio when compared with the MG (p=0.0001, q=6.584). No adverse events of treatment with modafinil and intranasal mometasone furoate were reported. Cost of treatment and beneficial effect after discontinuation were both significantly greater for the IMFG compared with the MG. Conclusions The findings of this preliminary clinical study were that for patients diagnosed with OSAHS, night-time treatment with intranasal mometasone furoate was more effective than modafinil. PMID:29749371

  9. Magnesium nanoparticles with transition metal decoration for hydrogen storage

    NASA Astrophysics Data System (ADS)

    Pasquini, Luca; Callini, Elsa; Brighi, Matteo; Boscherini, Federico; Montone, Amelia; Jensen, Torben R.; Maurizio, Chiara; Vittori Antisari, Marco; Bonetti, Ennio

    2011-11-01

    We report on the hydrogen storage behaviour of Mg nanoparticles (NPs) (size range 100 nm-1 μm) with metal-oxide core-shell morphology synthesized by inert gas condensation and decorated by transition metal (TM) (Pd or Ti) clusters via in situ vacuum deposition. The structure and morphology of the as-prepared and hydrogenated NPs is studied by electron microscopy, X-ray diffraction including in situ experiments and X-ray absorption spectroscopy, in order to investigate the relationships with the hydrogen storage kinetics measured by the volumetric Sieverts method. With both Pd and Ti, the decoration deeply improves the hydrogen sorption properties: previously inert NPs exhibit complete hydrogenation with fast transformation kinetics, good stability and reversible gravimetric capacity that can attain 6 wt%. In the case of Pd-decoration, the occurrence of Mg-Pd alloying is observed at high temperatures and in dependence of the hydrogen pressure conditions. These structural transformations modify both the kinetics and thermodynamics of hydride formation, while Ti-decoration has an effect only on the kinetics. The experimental results are discussed in relation with key issues such as the amount of decoration, the heat of mixing between TM and Mg and the binding energy between TM and hydrogen.

  10. Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior

    PubMed Central

    Calcutt, Sarah E.; Burke, Kimberly; de Waal, Frans B. M.

    2017-01-01

    Oxytocin has been suggested as a treatment to promote positive social interactions in people with Autism Spectrum Disorders (ASD). However, it is difficult to test this effect outside of the laboratory in realistic social situations. One way to resolve this issue is to study behavioral changes in closely related species with complex social relationships, such as chimpanzees. Here, we use captive, socially housed chimpanzees to evaluate the effects of oxytocin in a socially complex environment. After administering intranasal oxytocin or a placebo to an individual chimpanzee (total n = 8), she was returned to her social group. An experimenter blind to the condition measured the subject's social behavior. We failed to find a behavioral difference between conditions. As one of the goals for oxytocin administration as a treatment for ASD is increasing prosocial behaviors during ‘real world’ encounters, it is problematic that we failed to detect behavioral changes in our closest living relatives. However, our null findings may be related to methodological challenges such as determining an effective dose of oxytocin for chimpanzees and how long oxytocin takes to cross the blood-brain barrier. Thus, more research on intranasal oxytocin dosing and uptake are needed to continue exploring whether oxytocin changes social behavior in naturalistic settings and as a treatment for ASD. PMID:28845444

  11. [Intranasal epitalon infusion modulates neuronal activity in the rat neocortex].

    PubMed

    Sibarov, D A; Vol'nova, A B; Frolov, D S; Nosdrachev, A D

    2006-08-01

    Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.

  12. Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception.

    PubMed

    Saccone, Phillip A; Lindsey, Angela M; Koeppe, Robert A; Zelenock, Kathy A; Shao, Xia; Sherman, Phillip; Quesada, Carole A; Woods, James H; Scott, Peter J H

    2016-11-01

    The goal of this study was to evaluate the effects of intranasally administered opioids in rhesus monkeys using the tail-withdrawal assay, and to correlate these effects with measures of receptor occupancy using positron emission tomography (PET) imaging. Initial experiments characterized the antinociceptive effects of intranasal (IN) fentanyl and buprenorphine relative to intramuscular (IM) injection. Fentanyl (0.010-0.032 mg/kg) and buprenorphine (0.1-1.0 mg/kg) produced dose-dependent increases in tail-withdrawal latency that did not differ between routes of delivery. The second experiment compared the ability of IN and intravenous (IV) naloxone (NLX) to block the antinociceptive effects IV fentanyl, and to measure receptor occupancy at equipotent doses of NLX using PET imaging. IN and IV NLX (0.0032-0.032 mg/kg) produced dose-dependent decreases in fentanyl-induced antinociception. Again, there was no difference observed in overall potency between routes. PET imaging showed that IV and IN NLX produced similar decreases in receptor occupancy as measured by [ 11 C]carfentanil blocking, although there was a trend for IV NLX to produce marginally greater occupancy changes. This study validated the first procedures to evaluate the IN effects of opioids in rhesus monkeys. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Mg-doped VO2 nanoparticles: hydrothermal synthesis, enhanced visible transmittance and decreased metal-insulator transition temperature.

    PubMed

    Zhou, Jiadong; Gao, Yanfeng; Liu, Xinling; Chen, Zhang; Dai, Lei; Cao, Chuanxiang; Luo, Hongjie; Kanahira, Minoru; Sun, Chao; Yan, Liuming

    2013-05-28

    This paper reports the successful preparation of Mg-doped VO2 nanoparticles via hydrothermal synthesis. The metal-insulator transition temperature (T(c)) decreased by approximately 2 K per at% Mg. The Tc decreased to 54 °C with 7.0 at% dopant. The composite foils made from Mg-doped VO2 particles displayed excellent visible transmittance (up to 54.2%) and solar modulation ability (up to 10.6%). In addition, the absorption edge blue-shifted from 490 nm to 440 nm at a Mg content of 3.8 at%, representing a widened optical band gap from 2.0 eV for pure VO2 to 2.4 eV at 3.8 at% doping. As a result, the colour of the Mg-doped films was modified to increase their brightness and lighten the yellow colour over that of the undoped-VO2 film. A first principle calculation was conducted to understand how dopants affect the optical, Mott phase transition and structural properties of VO2.

  14. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988).

    PubMed

    O'Brien, R T; Evans, S M; Wortman, J A; Hendrick, M J

    1996-02-01

    To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Retrospective study. Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia.

  15. Comparison of sedation by intranasal dexmedetomidine and oral chloral hydrate for pediatric ophthalmic examination.

    PubMed

    Cao, Qianzhong; Lin, Yiquan; Xie, Zhubin; Shen, Weihua; Chen, Ying; Gan, Xiaoliang; Liu, Yizhi

    2017-06-01

    Pediatric ophthalmic examinations can be conducted under sedation either by chloral hydrate or by dexmedetomidine. The objective was to compare the success rates and quality of ophthalmic examination of children sedated by intranasal dexmedetomidine vs oral chloral hydrate. One hundred and forty-one children aged from 3 to 36 months (5-15 kg) scheduled to ophthalmic examinations were randomly sedated by either intranasal dexmedetomidine (2 μg·kg -1 , n = 71) or oral chloral hydrate (80 mg·kg -1 , n = 70). The primary endpoint was successful sedation to complete the examinations including slit-lamp photography, tonometry, anterior segment analysis, and refractive error inspection. The secondary endpoints included quality of eye position, intraocular pressure, onset time, duration of examination, recovery time, discharge time, any side effects during examination, and within 48 h after discharge. Sixty-one children were sedated by dexmedetomidine with a success rate of 85.9%, which is significantly higher than that by chloral hydrate (64.3%) [OR 3.39, 95% CI: 1.48-7.76, P = 0.003]. Furthermore, children in the dexmedetomidine group displayed better eye position in anterior segment analysis than in chloral hydrate group median difference. All children displayed stable hemodynamics and none suffered hypoxemia in both groups. Oral chloral hydrate induced higher percentages of vomiting and altered bowel habit after discharge than dexmedetomidine. Intranasal dexmedetomidine provides more successful sedation and better quality of ophthalmic examinations than oral chloral hydrate for small children. © 2017 John Wiley & Sons Ltd.

  16. Oral steroids alone or followed by intranasal steroids versus watchful waiting in the management of otitis media with effusion.

    PubMed

    Hussein, A; Fathy, H; Amin, S M; Elsisy, N

    2017-10-01

    To evaluate the effects of oral steroids alone or followed by intranasal steroids versus watchful waiting on the resolution of otitis media with effusion in children aged 2-11 years. A total of 290 children with bilateral otitis media with effusion were assigned to 3 groups: group A was treated with oral steroids followed by intranasal steroids, group B was treated with oral steroids alone and group C was managed with watchful waiting. Patients were evaluated with audiometry and tympanometry. The complete resolution rates of otitis media with effusion were higher in groups A and B than in group C at six weeks. There were no significant differences in otitis media with effusion resolution rates between the groups at three, six and nine months. Oral steroids lead only to a quick resolution of otitis media with effusion, with no long-term benefits. There was no benefit of using intranasal steroids in the management of otitis media with effusion.

  17. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    NASA Technical Reports Server (NTRS)

    Wu, L.; Tam, V.; Chow, Diana S. L.; Putcha, Lakshmi

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND). The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial with INSCOP.

  18. Adsorbate Diffusion on Transition Metal Nanoparticles

    DTIC Science & Technology

    2015-01-01

    different sizes and shapes using density functional theory calculations. We show that nanoparticles bind adsorbates more strongly than the...structure theoretical methods, a quantitative study with accurate density functional theory (DFT) calculations is still missing. Here, we perform a...functional theory . The projector augmented wave (PAW) potentials29,30 were used for electron- ion interactions and the generalized gradient approximation

  19. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona

    2012-11-15

    The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatialmore » memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.« less

  20. Buccal sulcus versus intranasal approach for postoperative periorbital oedema and ecchymosis in lateral nasal osteotomy.

    PubMed

    Ghazipour, Ali; Alani, Nadereh; Ghavami Lahiji, Shervin; Akbari Dilmaghani, Nader

    2014-10-01

    Lateral osteotomies are used in rhinoplasty to narrow the nasal bones, close the open roof deformity after hump removal, and achieve symmetry of an asymmetrical framework. But this procedure causes periorbital oedema & ecchymosis. Different techniques have been described for lateral osteotomy. To compare the postoperative ecchymosis and oedema after buccal sulcus lateral osteotomy versus intranasal lateral osteotomy. In a prospective experimental study, buccal sulcus approach was performed on the right side and an intranasal approach performed on the left side of patients randomly. Then blind analysis of postoperative photographs was performed to determine the incidence of oedema and ecchymosis on each side. Fifty patients were enrolled in the study after exclusion of unfit patients. On the right side (buccal approach osteotomies), a significantly lower incidence of upper and lower eyelid oedema and upper eyelid ecchymosis was seen on both the 2nd day and after 7th day (P < 0.05). The odds ratio of progression of ecchymosis was 2.66 (OR = 2.66, 95% CI: 1.09-5.52, p = 0.048) in intranasal group compare to buccal sulcus group. No significant complication observed. The buccal sulcus approach is a safe method for lateral osteotomy with a lower rate of postoperative oedema and ecchymosis and no significant complications. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  1. Intranasal delivery of recombinant parvovirus-like particles elicits cytotoxic T-cell and neutralizing antibody responses.

    PubMed

    Sedlik, C; Dridi, A; Deriaud, E; Saron, M F; Rueda, P; Sarraseca, J; Casal, J I; Leclerc, C

    1999-04-01

    We previously demonstrated that chimeric porcine parvovirus-like particles (PPV:VLP) carrying heterologous epitopes, when injected intraperitoneally into mice without adjuvant, activate strong CD4(+) and CD8(+) T-cell responses specific for the foreign epitopes. In the present study, we investigated the immunogenicity of PPV:VLP carrying a CD8(+) T-cell epitope from the lymphocytic choriomeningitis virus (LCMV) administered by mucosal routes. Mice immunized intranasally with recombinant PPV:VLP, in the absence of adjuvant, developed high levels of PPV-specific immunoglobulin G (IgG) and/or IgA in their serum, as well as in mucosal sites such as the bronchoalveolar and intestinal fluids. Antibodies in sera from mice immunized parenterally or intranasally with PPV:VLP were strongly neutralizing in vitro. Intranasal immunization with PPV:VLP carrying the LCMV CD8(+) T-cell epitope also elicited a strong peptide-specific cytotoxic-T-cell (CTL) response. In contrast, mice orally immunized with recombinant PPV:VLP did not develop any antibody or CTL responses. We also showed that mice primed with PPV:VLP are still able to develop strong CTL responses after subsequent immunization with chimeric PPV:VLP carrying a foreign CD8(+) T-cell epitope. These results highlight the attractive potential of PPV:VLP as a safe, nonreplicating antigen carrier to stimulate systemic and mucosal immunity after nasal administration.

  2. Intranasal Delivery of Recombinant Parvovirus-Like Particles Elicits Cytotoxic T-Cell and Neutralizing Antibody Responses

    PubMed Central

    Sedlik, C.; Dridi, A.; Deriaud, E.; Saron, M. F.; Rueda, P.; Sarraseca, J.; Casal, J. I.; Leclerc, C.

    1999-01-01

    We previously demonstrated that chimeric porcine parvovirus-like particles (PPV:VLP) carrying heterologous epitopes, when injected intraperitoneally into mice without adjuvant, activate strong CD4+ and CD8+ T-cell responses specific for the foreign epitopes. In the present study, we investigated the immunogenicity of PPV:VLP carrying a CD8+ T-cell epitope from the lymphocytic choriomeningitis virus (LCMV) administered by mucosal routes. Mice immunized intranasally with recombinant PPV:VLP, in the absence of adjuvant, developed high levels of PPV-specific immunoglobulin G (IgG) and/or IgA in their serum, as well as in mucosal sites such as the bronchoalveolar and intestinal fluids. Antibodies in sera from mice immunized parenterally or intranasally with PPV:VLP were strongly neutralizing in vitro. Intranasal immunization with PPV:VLP carrying the LCMV CD8+ T-cell epitope also elicited a strong peptide-specific cytotoxic-T-cell (CTL) response. In contrast, mice orally immunized with recombinant PPV:VLP did not develop any antibody or CTL responses. We also showed that mice primed with PPV:VLP are still able to develop strong CTL responses after subsequent immunization with chimeric PPV:VLP carrying a foreign CD8+ T-cell epitope. These results highlight the attractive potential of PPV:VLP as a safe, nonreplicating antigen carrier to stimulate systemic and mucosal immunity after nasal administration. PMID:10074120

  3. Nanoparticle engineering of colloidal suspension behavior

    NASA Astrophysics Data System (ADS)

    Chan, Angel Thanda

    We investigate the effects of highly charged nanoparticles on the phase behavior, structure, and assembly of colloidal microsphere suspensions. Specifically, by selectively tuning the electrostatic interactions between silica microspheres and polystyrene nanoparticles, we study the behavior of four key systems: (i) strongly repulsive, (ii) haloing, (iii) weakly attractive, and (iv) strongly attractive systems. In each system, a combination of nanoparticle adsorption, zeta potential, and confocal microscopy measurements are carried out to systematically study the effects of nanoparticle volume fraction, microsphere/nanoparticle size ratios, and interparticle interactions on their behavior. Our observations indicate that minimal adsorption of highly charged nanoparticles occurs on like-charged and negligibly-charged microspheres, whereas their extent of association increases dramatically with increasing microsphere-nanoparticle attraction. A rich phase behavior emerges in these systems based on whether the nanoparticle species serve as depletants, haloing, or bridging species. The phase transitions in the haloing system occur at constant nanoparticle volume fractions, φnano, over a broad range of microsphere volume fractions, φmicro . By contrast, the observed transitions in the weakly and strongly attractive mixtures occur at a constant number ratio of nanoparticles per microsphere, Nnano/Nmicro. Important structural differences emerge, which can be exploited in the assembly of colloidal gels for direct ink writing and colloidal crystals on epitaxially patterned substrates. Finally, for the first time, we explore nanoparticle haloing as a new route for stabilizing hydrophobic colloidal drugs in aqueous suspensions media for preparation of injectable pharmaceuticals. These microsphere suspensions exhibit improved stability relative to their surfactant-stabilized counterparts after autoclaving, a critical processing step for this target applications. This research

  4. No effect of adjunctive, repeated dose intranasal insulin treatment on psychopathology and cognition in patients with schizophrenia

    PubMed Central

    Fan, Xiaoduo; Liu, Emily; Freudenreich, Oliver; Copeland, Paul; Hayden, Douglas; Ghebremichael, Musie; Cohen, Bruce; Ongur, Dost; Goff, Donald C.; Henderson, David C.

    2015-01-01

    Objective This study examined the effect of adjunctive intranasal insulin therapy on psychopathology and cognition in patients with schizophrenia. Methods Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and been on stable antipsychotics for at least one month. In an 8-week randomized, double blind, placebo controlled study, subjects received either intranasal insulin (40 IU 4 times per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery was used to assess cognitive performance. The assessment for psychopathology and cognition was conducted at baseline, week 4 and week 8. Results A total number of 45 subjects were enrolled in the study (21 in the insulin group, 24 in the placebo group). The mixed model analysis showed that there were no significant differences between the two groups at week 8 on various psychopathology and cognitive measures (p’s > 0.1). Conclusion Adjunctive therapy with intranasal insulin did not seem to be beneficial in improving schizophrenia symptoms or cognition in the present study. The implications for future studies were discussed. PMID:23422397

  5. No effect of adjunctive, repeated dose intranasal insulin treatment on body metabolism in patients with schizophrenia

    PubMed Central

    Li, Jie; Li, Xue; Liu, Emily; Copeland, Paul; Freudenreich, Oliver; Goff, Donald C.; Henderson, David C.; Song, Xueqin; Fan, Xiaoduo

    2013-01-01

    Objective This study examined the effect of adjunctive intranasal insulin therapy on body metabolism in patients with schizophrenia. Method Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and had been on stable dose of antipsychotic agent for at least one month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either intranasal insulin (40IU 4 times per day) or placebo. The whole body dual-energy X-ray absorptiometry (DXA) was used to assess body composition. Lipid particles were assessed using nuclear magnetic resonance (NMR) spectroscopy. All assessments were conducted at baseline, and repeated at week 8. Results A total number of 39 subjects completed the study (18 in the insulin group, 21 in the placebo group). There were no significant differences between the two groups in week 8 changes for body weight, body mass index, waist circumference, as well as various measures of lipid particles (p′s > 0.100). The DXA assessment showed no significant differences between the two groups in week 8 changes for fat mass, lean mass or total mass (p's > 0.100). Conclusion In the present study, adjunctive therapy of intranasal insulin did not seem to improve body metabolism in patients with schizophrenia. The implications for future studies were discussed. PMID:23434504

  6. Inorganic Nanoparticle Induced Morphological Transition for Confined Self-Assembly of Block Copolymers within Emulsion Droplets.

    PubMed

    Zhang, Yan; He, Yun; Yan, Nan; Zhu, Yutian; Hu, Yuexin

    2017-09-07

    Recently, it has been reported that the incorporation of functional inorganic nanoparticles (NPs) into the three-dimensional (3D) confined self-assembly of block copolymers (BCPs) creates the unique nanostructured hybrid composites, which can not only introduce new functions to BCPs but also induce some interesting morphological transitions of BCPs. In the current study, we systematically investigate the cooperative self-assembly of a series of size-controlled and surface chemistry-tunable gold nanoparticles (AuNPs) and polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymer within the emulsion droplets. The influences of the size, content, and surface chemistry of the AuNPs on the coassembled nanostructures as well as the spatial distribution of AuNPs in the hybrid particles are examined. It is found that the size and content of the AuNPs are related to the entropic interaction, while the surface chemistry of AuNPs is related to the enthalpic interaction, which can be utilized to tailor the self-assembled morphologies of block copolymer confined in the emulsion droplets. As the content of PS-coated AuNPs increases, the morphology of the resulting AuNPs/PS-b-P2VP hybrid particles changes from the pupa-like particles to the bud-like particles and then to the onion-like particles. However, a unique morphological transition from the pupa-like particles to the mushroom-like particles is observed as the content of P4VP-coated AuNPs increases. More interestingly, it is observed that the large AuNPs are expelled to the surface of the BCP particles to reduce the loss in the conformational entropy of the block segment, which can arrange into the strings of necklaces on the surfaces of the hybrid particles.

  7. Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

    PubMed

    Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

    2015-10-01

    Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

    PubMed

    Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

    2009-04-01

    Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

  9. Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes.

    PubMed

    Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

    2017-01-01

    Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide- co -glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP-mediated PSDT on MH7A synoviocytes. The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP-mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP-mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP-mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N -acetylcysteine. Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP-mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition nanoparticle-mediated PSDT in the future.

  10. Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

    PubMed Central

    Tang, Qin; Cui, Jianyu; Tian, Zhonghua; Sun, Jiangchuan; Wang, Zhigang; Chang, Shufang; Zhu, Shenyin

    2017-01-01

    Background Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide-co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP–mediated PSDT on MH7A synoviocytes. Methods The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP–mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation. Results The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP–mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP–mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N-acetylcysteine. Conclusion Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP–mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition

  11. Synthesis of carbon-encapsulated metal nanoparticles from wood char

    Treesearch

    Yicheng Du; Chuji Wang; Hossein Toghiani; Zhiyong Cai; Xiaojian Liu; Jilei Zhang; Qiangu Yan

    2010-01-01

    Carbon-encapsulated metal nanoparticles were synthesized by thermal treatment of wood char, with or without transition metal ions pre-impregnated, at 900ºC to 1,100ºC. Nanoparticles with concentric multilayer shells were observed. The nanoparticles were analyzed by scanning electron microscopy, transmission electron microscopy (TEM), X-ray diffraction...

  12. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

    PubMed

    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  13. Differential effects of intranasal oxytocin on sexual experiences and partner interactions in couples.

    PubMed

    Behnia, Behnoush; Heinrichs, Markus; Bergmann, Wiebke; Jung, Stefanie; Germann, Janine; Schedlowski, Manfred; Hartmann, Uwe; Kruger, Tillmann H C

    2014-03-01

    Knowledge about the effects of the neuropeptide oxytocin (OXT) on human sexual behaviors and partner interactions remains limited. Based on our previous studies, we hypothesize that OXT should be able to positively influence parameters of sexual function and couple interactions. Employing a naturalistic setting involving 29 healthy heterosexual couples (n=58 participants), we analyzed the acute effects of intranasally administered OXT (24IU) on sexual drive, arousal, orgasm and refractory aspects of sexual behavior together with partner interactions. Data were assessed by psychometric instruments (Acute Sexual Experiences Scale, Arizona Sexual Experience Scale) as well as biomarkers, such as cortisol, α-amylase and heart rate. Intranasal OXT administration did not alter "classical" parameters of sexual function, such as sexual drive, arousal or penile erection and lubrication. However, analysis of variance and a hierarchical linear model (HLM) revealed specific effects related to the orgasmic/post-orgasmic interval as well as parameters of partner interactions. According to HLM analysis, OXT increased the intensity of orgasm, contentment after sexual intercourse and the effect of study participation. According to ANOVA analysis, these effects were more pronounced in men. Men additionally indicated higher levels of sexual satiety after sexual intercourse with OXT administration. Women felt more relaxed and subgroups indicated better abilities to share sexual desires or to empathize with their partners. The effect sizes were small to moderate. Biomarkers indicated moderate psychophysiological activation but were not affected by OXT, gender or method of contraception. Using a naturalistic setting, intranasal OXT administration in couples exerted differential effects on parameters of sexual function and partner interactions. These results warrant further investigations, including subjects with sexual and relationship problems. Copyright © 2014 Elsevier Inc. All

  14. Pediatric emergency department triage-based pain guideline utilizing intranasal fentanyl: Effect of implementation.

    PubMed

    Schoolman-Anderson, Kristin; Lane, Roni D; Schunk, Jeff E; Mecham, Nancy; Thomas, Richard; Adelgais, Kathleen

    2018-01-16

    Pain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction. This was a prospective study of patients 3-17 years with an isolated orthopedic injury presenting to a pediatric ED before and after instituting a triage-based pain guideline allowing for administration of INF by triage nurses. Our primary outcome was median TTA and secondary outcomes included the proportion of patients who received INF for pain, had unnecessary IV placement, and patient and parent satisfaction. We enrolled 132 patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between groups. Median TTA was not different between groups (34.5 min vs. 33 min, p = .7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p = .01) and unnecessary IV placement decreased from 24% to 0% (p = .002). Patients and parents preferred the IN route for analgesia administration. A triage-based pain protocol utilizing INF did not reduce TTA, but did result in increased INF use, decreased unnecessary IV placement, and was preferred by patients and parents to IV medication. INF is a viable analgesia alternative for children with isolated extremity injuries. Copyright © 2018. Published by Elsevier Inc.

  15. Continual model of magnetic dynamics for antiferromagnetic particles in analyzing size effects on Morin transition in hematite nanoparticles

    NASA Astrophysics Data System (ADS)

    Mishchenko, I.; Chuev, M.; Kubrin, S.; Lastovina, T.; Polyakov, V.; Soldatov, A.

    2018-05-01

    Alternative explanation to the effect of disappearance of the Morin transition on hematite nanoparticles with their size decreasing is proposed basing on an idea of the predominant role of the shape anisotropy for nanosize particles. Three types of the magnetic structure of hematite nanoparticles with various sizes are found by Mössbauer spectroscopy: coexistence of the well-pronounced antiferromagnetic and weakly ferromagnetic phases for particles with average diameters of about 55 nm, non-uniform distribution of the magnetization axes which concentrate on the vicinity of the basal plane (111) for prolonged particles with cross sections of about 20 nm, and uniform distribution of the easy axes in regard to the crystalline directions for 3-nm particles. Description of the temperature evolution of experimental data within novel model of the magnetic dynamics for antiferromagnetic particles which accounts the exchange, relativistic, and anisotropy interactions is provided, and the structural as well as energy characteristics of the studied systems are reconstructed.

  16. Intranasal delivery: physicochemical and therapeutic aspects.

    PubMed

    Costantino, Henry R; Illum, Lisbeth; Brandt, Gordon; Johnson, Paul H; Quay, Steven C

    2007-06-07

    Interest in intranasal (IN) administration as a non-invasive route for drug delivery continues to grow rapidly. The nasal mucosa offers numerous benefits as a target issue for drug delivery, such as a large surface area for delivery, rapid drug onset, potential for central nervous system delivery, and no first-pass metabolism. A wide variety of therapeutic compounds can be delivered IN, including relatively large molecules such as peptides and proteins, particularly in the presence of permeation enhancers. The current review provides an in-depth discussion of therapeutic aspects of IN delivery including consideration of the intended indication, regimen, and patient population, as well as physicochemical properties of the drug itself. Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route.

  17. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

    PubMed

    Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W

    2016-03-24

    Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong

  18. Sedation with intranasal midazolam of Angolan children undergoing invasive procedures.

    PubMed

    Kawanda, Lumana; Capobianco, Ivan; Starc, Meta; Felipe, Daniel; Zanon, Davide; Barbi, Egidio; Munkela, Nadine; Rodrigues, Verónica; Malundo, Lúis; Not, Tarcisio

    2012-07-01

    Ambulatory surgery is a daily requirement in poor countries, and limited means and insufficient trained staff lead to the lack of attention to the patient's pain. Midazolam is a rapid-onset, short-acting benzodiazepine which is used safely to reduce pain in children. We evaluated the practicability of intranasal midazolam sedation in a suburban hospital in Luanda (Angola), during the surgical procedures. Intranasal midazolam solution was administered at a dose of 0.5 mg/kg. Using the Ramsay's reactivity score, we gave a score to four different types of children's behaviour: moaning, shouting, crying and struggling, and the surgeon evaluated the ease of completing the surgical procedure using scores from 0 (very easy) to 3 (managing with difficulty). Eighty children (median age, 3 years) were recruited, and 140 surgical procedures were performed. Fifty-two children were treated with midazolam during 85 procedures, and 28 children were not treated during 55 procedures. We found a significant difference between the two groups on the shouting, crying and struggling parameters (p < 0.001). The mean score of the ease of completing the procedures was significantly different among the two groups (p < 0.0001). These results provide a model of procedural sedation in ambulatory surgical procedures in poor countries, thus abolishing pain and making the surgeon's job easier. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  19. Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial.

    PubMed

    Stanca, Carmen M; Montazem, Andre H; Lawal, Adeyemi; Zhang, Jin X; Schiano, Thomas D

    2010-01-01

    Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient). Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

  20. Non-invasive intranasal delivery of quetiapine fumarate loaded microemulsion for brain targeting: Formulation, physicochemical and pharmacokinetic consideration.

    PubMed

    Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

    2016-08-25

    Systemic drug delivery in schizophrenia is a major challenge due to presence of obstacles like, blood-brain barrier and P-glycoprotein, which prohibit entry of drugs into the brain. Quetiapine fumarate (QF), a substrate to P-glycoprotein under goes extensive first pass metabolism leading to limited absorption thus necessitating frequent oral administration. The aim of this study was to develop QF based microemulsion (ME) with and without chitosan (CH) to investigate its potential use in improving the bioavailability and brain targeting efficiency following non-invasive intranasal administration. QF loaded ME and mucoadhesive ME (MME) showed globule size, pH and viscosity in the range of 29-47nm, 5.5-6.5 and 17-40cP respectively. CH-ME with spherical globules having mean size of 35.31±1.71nm, pH value of 5.61±0.16 showed highest ex-vivo nasal diffusion (78.26±3.29%) in 8h with no sign of structural damage upon histopathological examination. Circular plume with an ovality ratio closer to 1.3 for CH-ME depicted ideal spray pattern. Significantly higher brain/blood ratio of CH-ME in comparison to QF-ME and drug solution following intranasal administration revealed prolonged retention of QF at site of action suggesting superiority of CH as permeability enhancer. Following intranasal administration, 2.7 and 3.8 folds higher nasal bioavailability in brain with CH-ME compared to QF-ME and drug solution respectively is indicative of preferential nose to brain transport (80.51±6.46%) bypassing blood-brain barrier. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Rescue Sedation With Intranasal Dexmedetomidine for Pediatric Ophthalmic Examination After Chloral Hydrate Failure: A Randomized, Controlled Trial.

    PubMed

    Gan, Xiaoliang; Lin, Haotian; Chen, Jingjing; Lin, Zhuoling; Lin, Yiquan; Chen, Weirong

    2016-06-01

    It is a challenge to rescue ophthalmology examinations performed in children in the sedation room after initial chloral hydrate failure. Intranasal dexmedetomidine can be used in rescue sedation in children undergoing computed tomography. The present study aimed to assess the efficacy and tolerability of intranasal dexmedetomidine use in children undergoing ophthalmic examination after chloral hydrate failure. Sixty uncooperative pediatric patients with cataract (aged 5-36 months; weight, 7-15 kg) presented for follow-up ophthalmic examination. Patients who experienced chloral hydrate failure were randomized to 1 of 2 groups to receive intranasal dexmedetomidine 1 or 2 μg/kg for rescue sedation. Each group contained 30 patients. The primary outcome was the rate of a successful ophthalmic examination. Secondary outcomes included sedation onset time, recovery time, duration of examination, discharge time, and adverse events, including percentage of heart rate reduction, respiratory depression, vomiting, and postsedative agitation. A successful ophthalmic examination was achieved in 93.3% (28/30) of patients in the 2-μg/kg dose group and in 66.7% (20/30) of patients in the 1-μg/kg dose group (P = 0.021). The onset time, recovery time, and discharge time did not significantly differ between the 2 groups. None of the patients required clinical intervention due to heart rate reduction, and none of the patients in either group experienced vomiting, respiratory depression, or agitation after the administration of dexmedetomidine. In children undergoing ophthalmic examination, intranasal dexmedetomidine can be administered in the sedation room for rescue sedation after chloral hydrate failure, with the 2-μg/kg dose being more efficacious than the 1-μg/kg dose, as measured by success rate. ClinicalTrials.gov identifier: NCT02077712. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  2. Efficacy of Intranasal Scopolamine Gel for Motion Sickness Treatment in Aviation Candidates

    DTIC Science & Technology

    2009-04-13

    Baseline 15 25 80 115 145 190 M ea n B lo o d P re ss u re (m m H g ) 0 20 40 60 80 100 120 140 Systolic BP P Systolic BPIN Diastolic BPP Diastolic...scopolamine when compared to placebo, p < .05. BPP = Blood Pressure, Placebo, BPIN = Blood Pressure, Intranasal Scopolamine 31 Time (min) Baseline 15 25 80

  3. Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant.

    PubMed

    Neto, Lázaro Moreira Marques; Zufelato, Nicholas; de Sousa-Júnior, Ailton Antônio; Trentini, Monalisa Martins; da Costa, Adeliane Castro; Bakuzis, Andris Figueiroa; Kipnis, André; JunqueiraKipnis, Ana Paula

    2018-06-18

    Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe 2 O 4 NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4 + IFN-γ + (Th1) and CD8 + IFN-γ + responses. Intranasal vaccination induced specific Th1, Th17 (CD4 + IL-17 + ) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.

  4. Comparative pathogenesis of H3N2 canine influenza virus in beagle dogs challenged by intranasal and intratracheal inoculation.

    PubMed

    Luo, Jie; Lu, Gang; Ye, Shaotang; Ou, Jiajun; Fu, Cheng; Zhang, Xin; Wang, Xiangbin; Huang, Ji; Wu, Peixin; Xu, Haibin; Wu, Liyan; Li, Shoujun

    2018-05-31

    As important companion animals, dogs may serve as intermediate hosts for transmitting influenza virus to humans. However, knowledge regarding H3N2 canine influenza virus (CIV) pathogenicity is not comprehensive, which directly affects the animal models of pathogenicity in H3N2 CIV vaccine research. Here, to assess H3N2 CIV pathogenicity, we utilized 30 ten-week-old purpose-bred beagles intratracheally or intranasally inoculated with 10 6 50 % egg-infectious dose. Intratracheal inoculation was more virulent to dogs than intranasal inoculation as shown by lung pathology score, histopathological changes, clinical symptoms, and body temperature. More intense virus replication was observed in the upper and lower respiratory tracts by intratracheal than intranasal inoculation according to nasal swabs, various organ virus titers, and antigen expression. These results may enhance the H3N2 CIV infection model, providing a more complete experimental basis for studying intrinsic H3N2 CIV pathogenic mechanism, and also serving a reference role for CIV prevention and treatment. Copyright © 2018. Published by Elsevier B.V.

  5. Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer’s Disease

    PubMed Central

    Claxton, Amy; Baker, Laura D.; Wilkinson, Charles W.; Trittschuh, Emily H.; Chapmana, Darla; Watson, G. Stennis; Cholerton, Brenna; Plymate, Stephen R.; Arbuckle, Matthew; Craft, Suzanne

    2014-01-01

    A previous clinical trial demonstrated that four months of treatment with intranasal insulin improves cognition and function for patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), but prior studies suggest that response to insulin treatment may differ by sex and ApoE ε4 carriage. Thus, responder analyses using repeated measures analysis of covariance were completed on the trial’s 104 participants with MCI or AD who received either placebo or 20 or 40 IU of insulin for 4 months, administered by a nasal delivery device. Results indicate that men and women with memory impairment responded differently to intranasal insulin treatment. On delayed story memory, men and women showed cognitive improvement when taking 20 IU of intranasal insulin, but only men showed cognitive improvement for the 40 IU dose. The sex difference was most apparent for ApoE ε4 negative individuals. For the 40 IU dose, ApoE ε4 negative men improved while ApoE ε4 negative women worsened. Their ApoE ε4 positive counterparts remained cognitively stable. This sex effect was not detected in functional measures. However, functional abilities were relatively preserved for women on either dose of intranasal insulin compared with men. Unlike previous studies with young adults, neither men nor women taking intranasal insulin exhibited a significant change in weight over 4 months of treatment. PMID:23507773

  6. Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

    PubMed

    Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

    2016-02-01

    The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

  7. Data on energy-band-gap characteristics of composite nanoparticles obtained by modification of the amorphous potassium polytitanate in aqueous solutions of transition metal salts

    PubMed Central

    Zimnyakov, D.A.; Sevrugin, A.V.; Yuvchenko, S.A.; Fedorov, F.S.; Tretyachenko, E.V.; Vikulova, M.A.; Kovaleva, D.S.; Krugova, E.Y.; Gorokhovsky, A.V.

    2016-01-01

    Here we present the data on the energy-band-gap characteristics of composite nanoparticles produced by modification of the amorphous potassium polytitanate in aqueous solutions of different transition metal salts. Band gap characteristics are investigated using diffuse reflection spectra of the obtained powders. Calculated logarithmic derivative quantity of the Kubelka–Munk function reveals a presence of local maxima in the regions 0.5–1.5 eV and 1.6–3.0 eV which correspond to band gap values of the investigated materials. The values might be related to the constituents of the composite nanoparticles and intermediate products of their chemical interaction. PMID:27158654

  8. Intranasal scopolamine affects the semicircular canals centrally and peripherally.

    PubMed

    Weerts, Aurélie P; Putcha, Lakshmi; Hoag, Stephen W; Hallgren, Emma; Van Ombergen, Angelique; Van de Heyning, Paul H; Wuyts, Floris L

    2015-08-01

    Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS. Copyright © 2015 the American Physiological Society.

  9. Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction.

    PubMed

    Rilling, James K; Demarco, Ashley C; Hackett, Patrick D; Chen, Xu; Gautam, Pritam; Stair, Sabrina; Haroon, Ebrahim; Thompson, Richmond; Ditzen, Beate; Patel, Rajan; Pagnoni, Giuseppe

    2014-01-01

    Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses

  10. Alkaline Capacitors Based on Nitride Nanoparticles

    NASA Technical Reports Server (NTRS)

    Aldissi, Matt

    2003-01-01

    High-energy-density alkaline electrochemical capacitors based on electrodes made of transition-metal nitride nanoparticles are undergoing development. Transition- metal nitrides (in particular, Fe3N and TiN) offer a desirable combination of high electrical conductivity and electrochemical stability in aqueous alkaline electrolytes like KOH. The high energy densities of these capacitors are attributable mainly to their high capacitance densities, which, in turn, are attributable mainly to the large specific surface areas of the electrode nanoparticles. Capacitors of this type could be useful as energy-storage components in such diverse equipment as digital communication systems, implanted medical devices, computers, portable consumer electronic devices, and electric vehicles.

  11. A field trial, of preshipment vaccination, with intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccines.

    PubMed Central

    Martin, W; Willson, P; Curtis, R; Allen, B; Acres, S

    1983-01-01

    A total of 849 calves, 278 controls, 335 vaccinated intranasally with IBR-PI3/TS and 236 vaccinated intranasally with IBR-PI3/PTC were studied in a field trial of preimmunization. All calves were vaccinated in Saskatchewan at least three weeks prior to shipment to feedlots. Four hundred and twenty six calves were not sold within eight weeks of vaccination; however, seven of these died within four weeks of vaccination. Treatment rates varied from 1.0% to 5.2%. There was no significant effect of vaccination on treatment rates. Similarly, there was no significant effect of vaccination in the 74 calves sold to feedlots in Saskatchewan. Three hundred and forty nine calves were sold to feedlots in Ontario. Two of these died from fibrinous pneumonia. Treatment rates varied from 1.7% to 33.3% in different feedlots, but there was no significant effect of vaccination on treatment rates. Therefore, preimmunization is unlikely to significantly reduce the overall treatment rate in calves entering feedlots. PMID:6315194

  12. Role of SiO2 coating in multiferroic CoCr2O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Kamran, M.; Ullah, Asmat; Mehmood, Y.; Nadeem, K.; Krenn, H.

    2017-02-01

    Effect of silica (SiO2) coating concentration on structural and magnetic properties of multiferroic cobalt chromite (CoCr2O4) nanoparticles have been studied. The nanoparticles with average crystallite size in the range 19 to 28 nm were synthesised by sol-gel method. X-ray diffraction (XRD) analysis has verified the composition of single-phase cubic normal spinel structure of CoCr2O4 nanoparticles. The average crystallite size and cell parameter decreased with increasing SiO2 concentration. TEM image revealed that the shape of nanoparticles was non-spherical. Zero field cooled/field cooled (ZFC/FC) curves revealed that nanoparticles underwent a transition from paramagnetic (PM) state to collinear short-range ferrimagnetic (FiM) state, and this PM-FiM transition temperature decreased from 101 to 95 K with increasing SiO2 concentration or decreasing crystallite size. A conical spin state at Ts = 27 K was also observed for all the samples which decreased with decreasing average crystallite size. Low temperature lock-in transition was also observed in these nanoparticles at 12 K for uncoated nanoparticles which slightly shifted towards low temperature with decreasing average crystallite size. Saturation magnetization (Ms) showed decreasing trend with increasing SiO2 concentration, which was due to decrease in average crystallite size of nanoparticles and enhanced surface disorder in smaller nanoparticles. The temperature dependent AC-susceptibility also showed the decrease in the transition temperature (Tc), broadening of the Tc peak and decrease in magnetization with increasing SiO2 concentration or decreasing average crystallite size. In summary, the concentration of SiO2 has significantly affected the structural and magnetic properties of CoCr2O4 nanoparticles.

  13. Magnetic properties of GdMnO3 nanoparticles embedded in mesoporous silica

    NASA Astrophysics Data System (ADS)

    Tajiri, Takayuki; Mito, Masaki; Deguchi, Hiroyuki; Kohno, Atsushi

    2018-05-01

    Perovskite manganite GdMnO3 nanoparticles were synthesized using mesoporous silica as a template, and their magnetic properties and crystal structure were investigated. Powder X-ray diffraction data indicated successful synthesis of the GdMnO3 nanoparticles, with mean particle sizes of 13.9 and 20.9 nm. The lattice constants for the nanoparticles were slightly different from those for the bulk material and varied with the particle size. The magnetic transition temperatures for the nanoparticles were higher than those of the bulk crystal. The synthesized GdMnO3 nanoparticles exhibited superparamagnetic behaviors: The blocking temperature, coercive field, and transition temperature depended on the particle size. Magnetic measurements and crystal structure analysis suggest that the changes in the magnetic properties for GdMnO3 nanoparticles can be attributed to the modulation of the crystallographic structure.

  14. Formulation of Convenient, Easily Scalable, and Efficient Granisetron HCl Intranasal Droppable Gels.

    PubMed

    Ibrahim, Howida K; Abdel Malak, Nevine S; Abdel Halim, Sally A

    2015-06-01

    Deacetylated gellan gum and two sodium alginate polymer types were used each at three concentrations in the suitable range for their sol-gel transition. The prepared nine droppable gels were evaluated in vitro, ex vivo through sheep nasal mucosa, as well as in vivo in comparison to drug solution given intravenously and orally at the same dose. The prepared formulas gelled instantaneously in simulated nasal fluid and the obtained gels sustained their shear thinning and thixotropic behavior up to 48 h. Polymer type and concentration had significant effects on the apparent viscosities and the in vitro release profile of granisetron from the prepared gels. The drug release data best fitted a modified Higuchi equation with initial burst and followed Fickian diffusion mechanism. A 0.5% gellan-gum-based formula sustained the in vitro drug release up to 3 h and enhanced the drug permeation without need for an enhancer. The histopatholgical study revealed the safety of the tested formula. Intranasal delivery recorded double the drug bioavailabilty in comparison to the oral route. It had an absolute bioavailability of 0.6539 and the maximum plasma drug concentration reached after 1.5 h. The developed formula could be promising for the management of chemotherapy-induced nausea and vomiting regarding its improved bioavailability, patient acceptability, and ease of production.

  15. Origin of the magnetic transition at 100 K in ɛ-Fe2O3 nanoparticles studied by x-ray absorption fine structure spectroscopy

    NASA Astrophysics Data System (ADS)

    López-Sánchez, J.; Muñoz-Noval, A.; Castellano, C.; Serrano, A.; del Campo, A.; Cabero, M.; Varela, M.; Abuín, M.; de la Figuera, J.; Marco, J. F.; Castro, G. R.; Rodríguez de la Fuente, O.; Carmona, N.

    2017-12-01

    The current study unveils the structural origin of the magnetic transition of the ɛ-Fe2O3 polymorph from an incommensurate magnetic order to a collinear ferrimagnetic state at low temperature. The high crystallinity of the samples and the absence of other iron oxide polymorphs have allowed us to carry out temperature-dependent x-ray absorption fine structure spectroscopy experiments out. The deformation of the structure is followed by the Debye-Waller factor for each selected Fe-O and Fe-Fe sub-shell. For nanoparticle sizes between 7 and 15 nm, the structural distortions between the Fete and Fe-D1oc sites are localized in a temperature range before the magnetic transition starts. On the contrary, the inherent interaction between the other sub-shells (named Fe-O1,2 and Fe-Fe1) provokes cooperative magneto-structural changes in the same temperature range. This means that the Fete with Fe-D1oc polyhedron interaction seems to be uncoupled with temperature dealing with these nanoparticle sizes wherein the structural distortions are likely moderate due to surface effects.

  16. Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

    PubMed

    Yao, Wenjun; Peng, Yixing; Du, Mingzhu; Luo, Juan; Zong, Li

    2013-08-05

    Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p < 0.01) and intramuscular administration of a pGRP solution (p < 0.05) to mice. In addition, immunization with MCS/pGRP nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p < 0.01) or that in the pGRP group (1.12 ± 0.37 g) (p < 0.05). Cell binding and cellular uptake results indicated that MCS/pGRP nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

  17. Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia.

    PubMed

    Cheung, C W; Ng, K F J; Liu, J; Yuen, M Y V; Ho, M H A; Irwin, M G

    2011-09-01

    Dexmedetomidine (DEX) is an alpha 2-adrenoreceptor agonist, which induces sedation and analgesia. This study aimed to determine whether intranasal DEX offered perioperative sedation and better postoperative analgesia. Patients having unilateral third molar surgery under local anaesthesia were recruited and allocated to receive either intranasal DEX 1 µg kg(-1) (Group D) or same volume of saline (Group P) 45 min before surgery. Patient-controlled sedation with propofol was offered as a rescue sedative. Perioperative sedation, postoperative pain relief and analgesic consumption, vital signs, adverse events, postoperative recovery, and satisfaction in sedation and analgesia were assessed. Thirty patients from each group were studied. Areas under curve (AUC) of postoperative numerical rating scale (NRS) pain scores 1-12 h at rest and during mouth opening were significantly lower in Group D (P=0.003 and 0.009, respectively). AUC BIS values and OAA/S sedation scores were significantly lower before surgery and at the recovery area (all P<0.01) with significantly less intra-operative propofol used in group D (P<0.01). In group D, heart rate was significantly lower at recovery period (P=0.005) while systolic blood pressure in different periods of the study (all P<0.01), but the decreases did not require treatment. More patients from placebo group experienced dizziness (P=0.026) but no serious adverse event was found. No difference was found in postoperative psychomotor recovery and satisfaction in pain relief and sedation. Patients receiving intranasal DEX for unilateral third molar surgery with local anaesthesia were more sedated perioperatively with better postoperative pain relief. No delay in psychomotor recovery was seen.

  18. Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration.

    PubMed

    Withington, S; Chambers, S T; Beard, M E; Inder, A; Allen, J R; Ikram, R B; Schousboe, M I; Heaton, D C; Spearing, R I; Hart, D N

    1998-01-01

    The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

  19. Pharmacokinetics and Abuse Potential of Benzhydrocodone, a Novel Prodrug of Hydrocodone, After Intranasal Administration in Recreational Drug Users.

    PubMed

    Mickle, Travis C; Guenther, Sven M; Barrett, Andrew C; Roupe, Kathryn Ann; Zhou, Jing; Dickerson, Daniel; Webster, Lynn R

    2017-10-28

    Developing an acetaminophen-free, immediate-release hydrocodone product remains an unmet medical need; however, new opioid analgesics should not introduce new abuse risks. Benzhydrocodone is a prodrug of hydrocodone that must be metabolized into hydrocodone by enzymes in the intestinal tract to optimally deliver its pharmacologic effects. This study evaluated the intranasal pharmacokinetics and abuse potential of benzhydrocodone active pharmaceutical ingredient (API) compared with hydrocodone bitartrate (HB) API. Single-center, randomized, double-blind, crossover study. Clinical research site. Healthy adult, nondependent, recreational opioid users. Subjects (N = 51 Completers) were randomized to receive 13.34 mg of intranasal benzhydrocodone API and 15.0 mg of intranasal HB API (molar-equivalent doses of hydrocodone). Blood samples were taken, and Drug Liking scores (assessed on a bipolar visual analog scale) were obtained throughout each dosing interval. Nasal irritation and safety were assessed. Peak hydrocodone plasma concentration (Cmax) was 36.0% lower, and total hydrocodone exposures (AUClast and AUCinf) were 20.3% and 19.5% lower, respectively, for benzhydrocodone API compared with HB API (P < 0.0001). All partial AUC values were lower for benzhydrocodone API, with a ≥ 75% reduction in hydrocodone exposure at all time intervals up to one hour postdose (P < 0.0001). Median Tmax of hydrocodone following benzhydrocodone API was delayed by more than one hour compared with HB. Drug Liking score, as assessed by maximal liking (Emax), was significantly lower for benzhydrocodone API vs HB API (P = 0.004), with 45% of subjects showing a ≥ 30% reduction in Drug Liking Emax. Reductions in hydrocodone exposure and associated decreases in Drug Liking relative to HB suggest that the prodrug benzhydrocodone may deter intranasal abuse. © 2017 American Academy of Pain Medicine.

  20. Immunogenicity and protective efficacy of an elastase-dependent live attenuated swine influenza virus vaccine administered intranasally in pigs.

    PubMed

    Masic, Aleksandar; Lu, Xinya; Li, Junwei; Mutwiri, George K; Babiuk, Lorne A; Brown, Earl G; Zhou, Yan

    2010-10-08

    Influenza A virus is an important respiratory pathogen of swine that causes significant morbidity and economic impact on the swine industry. Vaccination is the first choice for prevention and control of influenza infections. Live attenuated influenza vaccines (LAIV) are approved for use in humans and horses and their application provides broad protective immunity, however no LAIV against swine influenza virus (SIV) exists in the market. Previously we reported that an elastase-dependent mutant SIV A/Sw/Sk-R345V (R345V) derived from A/Sw/Saskatchewan/18789/02 (H1N1) (SIV/Sk02) is highly attenuated in pigs. Two intratracheal administrations of R345V induced strong cell-mediated and humoral immune responses and provided a high degree of protection to antigenically different SIV infection in pigs. Here we evaluated the immunogenicity and the protective efficacy of R345V against SIV infection by intranasal administration, the more practical route for vaccination of pigs in the field. Our data showed that intranasally administered R345V live vaccine is capable of inducing strong antigen-specific IFN-γ response from local tracheo-bronchial lymphocytes and antibody responses in serum and respiratory mucosa after two applications. Intranasal vaccination of R345V provided pigs with complete protection not only from parental wild type virus infection, but also from homologous antigenic variant A/Sw/Indiana/1726/88 (H1N1) infection. Moreover, intranasal administration of R345V conferred partial protection from heterologous subtypic H3N2 SIV infection in pigs. Thus, R345V elastase-dependent mutant SIV can serve as a live vaccine against antigenically different swine influenza viruses in pigs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Effect of a Combination of Intranasal Ketorolac and Nitrous Oxide on the Success of the Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis: A Prospective, Randomized, Double-blind Study.

    PubMed

    Stentz, Daniel; Drum, Melissa; Reader, Al; Nusstein, John; Fowler, Sara; Beck, Mike

    2018-01-01

    Previous studies in patients with irreversible pulpitis have reported increased success of the inferior alveolar nerve block (IANB) using premedication with ketorolac. Preemptive nitrous oxide administration has also shown an increase in the success of the IANB. Recently, ketorolac has been made available for intranasal delivery. Perhaps combining ketorolac and nitrous oxide would increase success. Therefore, the purpose of this prospective, randomized, double-blind study was to determine the effect of a combination of intranasal ketorolac and nitrous oxide/oxygen on the anesthetic success of the IANB in patients presenting with symptomatic irreversible pulpitis. One hundred two patients experiencing spontaneous moderate to severe pain with symptomatic irreversible pulpitis in a mandibular posterior tooth participated. Patients were randomly divided into 2 groups and received either 31.5 mg intranasal ketorolac or intranasal saline placebo 20 minutes before the administration of nitrous oxide/oxygen. Ten minutes after the administration of nitrous oxide/oxygen, the IANB was given. After profound lip numbness, endodontic treatment was performed. Success was defined as the ability to perform endodontic access and instrumentation with no pain or mild pain. The odds of success for the IANB was 1.631 in the intranasal saline/nitrous oxide group versus the intranasal ketorolac/nitrous oxide group with no significant difference between the groups (P = .2523). Premedication with intranasal ketorolac did not significantly increase the odds of success for the IANB over the use of nitrous oxide/oxygen alone. Supplemental anesthesia will still be needed to achieve adequate anesthesia. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  2. Nanoemulsions for Intranasal Delivery of Riluzole to Improve Brain Bioavailability: Formulation Development and Pharmacokinetic Studies.

    PubMed

    Parikh, Rajesh H; Patel, Ravish J

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS), a motor neuron disease (MND), is a progressive neurodegenerative disorder characterized by the deterioration of both upper and lower motor neurons. Only one drug (riluzole) has been approved for the treatment of ALS. Riluzole is a BCS class II drug having 60% absolute bioavailability. It is a substrate of P-glycoprotein and BBB restricts its entry in brain. This investigation was aimed to develop O/W nanoemulsion system of riluzole to improve its brain bioavailability. Riluzole loaded nanoemulsion was prepared by phase titration method. It was consisting of 3% w/w Sefsol 218, 28.3% w/w Tween 80:Carbitol (1:1) and 68.7% w/w water. It was characterized for drop size, drop size distribution, transmittance, viscosity, pH, zeta potential, conductivity and nasal ciliotoxicity study. Thermodynamic stability and room temperature stability of prepared nanoemulsion formulation were evaluated. Pharmacokinetic and brain uptake study was carried out using albino rats (wistar) post intranasal and oral administration. Riluzole loaded nanoemulsion was having a drop size of 23.92±0.52 nm. It was free from nasal ciliotoxicity and stable for three months. Brain uptake of riluzole post intranasal administration of riluzole loaded nanoemulsion was significantly (P <4.10 × 10-6) higher when it was compared with oral administration of riluzole loaded nanoemulsion. This study indicates that nanoemulsion of riluzole for intranasal administration could be a promising approach for the treatment of ALS to minimize the dose of riluzole in order to avoid dose related adverse events.

  3. Spin canting and magnetic transition in NixZn1-xFe2O4 (x=0.0, 0.5 and 1.0) nanoparticles

    NASA Astrophysics Data System (ADS)

    Rani, Stuti; Raghav, Dharmendra Singh; Yadav, Prashant; Varma, G. D.

    2018-04-01

    Nanoparticles of NixZn1-xFe2O4(x=0.0, 0.5 and 1.0) have been synthesized via co-precipitation method and studied thestructural and magnetic properties. Rietveld refinement of X ray diffraction data of as synthesized samples revealthat the samples have mixed spinel structure with space group Fd-3m. The lattice parameter of the samples decreases as doping concentration of Ni ions increases. Magnetic measurements show paramagnetic to ferrimagnetic transition at room temperature on Ni doping in ZnFe2O4 nanoparticles. The magnetic measurements also show spin canting in samples possibly due to their nanocrystalline nature. The spin canting angles have been calculated with the help of Yafet-Kittel (Y-K) model. Furthermore, the Law of approach (LA) fitting of M-H curves indicates that the samples are highly anisotropicin nature. The Arrot plots of as synthesized samples also indicate the paramagnetic to ferrimagnetic transition. The correlation between the structural and observed magnetic properties of NixZn1-xFe2O4(x=0.0, 0.5 and 1.0) nanocrystals will be described and discussed in this paper.

  4. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory.

    PubMed

    Krug, Rosemarie; Benedict, Christian; Born, Jan; Hallschmid, Manfred

    2010-12-01

    We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women. Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone. In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71±0.6 kg/m2; age, 57.61±1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle. Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured. Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44±0.63 yr), i.e. insulin administration did not affect food intake (P>0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (P<0.05). Low estrogen levels as present in postmenopausal women do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.

  5. Gadolinium nanoparticle based switchable mirrors: quenching of hydrogenation-dehydrogenation hysteresis.

    PubMed

    Aruna, I; Mehta, B R; Malhotra, L K

    2007-06-01

    A continuous and reversible 'structural, optical, and electronic' transition between the reflecting metallic dihydride and transparent semiconducting trihydride states observed in rare earth metals on hydrogenation make these materials and their hydrides suitable for switchable mirror, sensing, and other technological applications. Recently Pd capped Gd nanoparticle based 'new generation' switchable mirrors have been fabricated with extended color neutrality, better optical contrast, and faster kinetics in comparison to the polycrystalline, epitaxial, alloy, and multilayer films. The present report aims at investigating the effect of nanoparticle nature on the hydrogenation-dehydrogenation hysteresis in switchable mirrors by carrying out in situ measurement of optical transmittance and electrode potentials during electrochemical hydrogen loading-deloading of Gd nanoparticle samples. Interestingly, Gd nanoparticle samples were observed to exhibit quenched hysteresis. The quenching of hysteresis in hydrogen-induced properties has been attributed to the absence of structural transition upon hydrogenation, reduction in topographical interlocking of the grains and elimination of lateral clamping of the slack nanoparticle layer to the substrate.

  6. Bioluminescent Study of the Distribution of High-Molecular-Weight Protein Fraction of Cellex Daily Preparation in the Brain after Intranasal Administation.

    PubMed

    Baklaushev, V P; Yusubalieva, G M; Burenkov, M S; Mel'nikov, P A; Bozhko, E A; Mentyukov, G A; Lavrent'eva, L S; Sokolov, M A; Chekhonin, V P

    2017-12-01

    Permeability of the blood-brain barrier for protein fractions 50-100 kDa (PF 50-100 ) of Cellex Daily preparation labeled with fluorescent tracer FITC and non-conjugated FITC were compared after intranasal administration of the preparations to healthy rats. Fluorimetrical analysis of the serum and cerebrospinal fluid samples showed that Cellex Daily PF 50-100 -FITC administered intranasally penetrated into the blood and cerebrospinal fluid with maximum accumulation in 2 h after administration and persists in the circulation for 24 h probably due to binding with plasma proteins. The differences in the kinetic profile of PF 50-100 -FITC and free FITC indirectly suggest that the major part of the preparation is not degraded within 24 h and FITC is probably not cleaved from the protein components of the preparation. In vivo fluorescence analysis showed significant fluorescent signal in the olfactory bulbs in 6 h after intranasal administration; hence, the preparation administered via this route can bypass the blood-brain barrier. Scanning laser confocal microscopy of rat brain sections confirmed penetration of the high-molecular weight protein fraction PF 50-100 -FITC into CNS structures. The most pronounced accumulation of the labeled drug was observed in the olfactory bulb in 6 and 12 h after administration. In contrast to free FITC administered in the control group, significant accumulation of PF 50-100 -FITC in the olfactory cortex and frontal cortex neurons with functionally active nuclei was observed in 6, 12 and 24 h after intranasal administration.

  7. The Pharmacokinetics and Efficacy of a Low-dose, Aqueous, Intranasal Scopolamine Spray

    DTIC Science & Technology

    2017-09-27

    In this study , we found no correlation between plasma levels at any time point and the number of head tilts tolerated. However, there was a positive... study protocol was approved by the Naval Medical Research Unit Dayton Institutional Review Board in compliance with all applicable Federal...The study examined both the pharmacokinetic properties and efficacy of a low-dose, aqueous, intranasal scopolamine spray (INSCOP) as an anti-motion

  8. Metal-semiconductor phase transition of order arrays of VO2 nanocrystals

    NASA Astrophysics Data System (ADS)

    Lopez, Rene; Suh, Jae; Feldman, Leonard; Haglund, Richard

    2004-03-01

    The study of solid-state phase transitions at nanometer length scales provides new insights into the effects of material size on the mechanisms of structural transformations. Such research also opens the door to new applications, either because materials properties are modified as a function of particle size, or because the nanoparticles interact with a surrounding matrix material, or with each other. In this paper, we describe the formation of vanadium dioxide nanoparticles in silicon substrates by pulsed laser deposition of ion beam lithographically selected sites and thermal processing. We observe the collective behavior of 50 nm diameter VO2 oblate nanoparticles, 10 nm high, and ordered in square arrays with arbitrary lattice constant. The metal-semiconductor-transition of the VO2 precipitates shows different features in each lattice spacing substrate. The materials are characterized by electron microscopy, x-ray diffraction, Rutherford backscattering. The features of the phase transition are studied via infrared optical spectroscopy. Of particular interest are the enhanced scattering and the surface plasmon resonance when the particles reach the metallic state. This resonance amplifies the optical contrast in the range of near-infrared optical communication wavelengths and it is altered by the particle-particle coupling as in the case of noble metals. In addition the VO2 nanoparticles exhibit sharp transitions with up to 50 K of hysteresis, one of the largest values ever reported for this transition. The optical properties of the VO2 nanoarrays are correlated with the size of the precipitates and their inter-particle distance. Nonlinear and ultra fast optical measurements have shown that the transition is the fastest known solid-solid transformation. The VO2 nanoparticles show the same bulk property, transforming in times shorter than 150 fs. This makes them remarkable candidates for ultrafast optical and electronic switching applications.

  9. Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

    PubMed

    Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

    2015-09-01

    To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

    PubMed

    Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

    2016-10-01

    This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders.

    PubMed

    Ong, Wei-Yi; Shalini, Suku-Maran; Costantino, Luca

    2014-01-01

    Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems.

  12. M4Ag44(p-MBA)30 Molecular Nanoparticles

    NASA Astrophysics Data System (ADS)

    Conn, Brian E.

    In recent years, molecular nanoparticles have attracted much attention due to their unique physical, optical, and electronic properties. The properties of molecular nanoparticles are shown to deviate from their larger bulk counterparts, due to quantum confinement effects and large surface-to-volume ratios. As the size of the nanoparticle shrinks to a cluster of metal atoms (<3 nm in diameter), there is an emergence of a HOMO-LUMO band gap, which is not present in transitional d-block metals. The HOMO-LUMO band gap gives rise to discrete electronic states, leading to new chemical and physical properties. Molecular nanoparticles have had a substantial impact across a diverse range of fields, including catalysis, sensing, photochemistry, optoelectronic, energy conversion, and medicine. Currently many of the synthetic procedures for molecular nanoparticles require low temperatures, long incubation times, multistep purification and hazardous reagents that produce low yields and polydisperse molecular nanoparticles with poor stability. Although silver has very desirable physical properties, good relative abundance and low cost, gold molecular nanoparticles have been widely favored owing to their proved stability and ease of use. Unlike gold, silver is notorious for its susceptibility to oxidation, i.e., tarnishing, which has limited the development of silver-based nanotechnologies. Despite two decades of synthetic efforts, silver molecular nanoparticles that are inert or have long-term stability have remained unrealized. Herein we report a simple synthetic protocol for producing ultrastable M4Ag44(p-MBA)30 nanoparticles as a single-sized molecular product and in exceptionally large quantities. The stability, purity, and yield are substantially better than other metal nanoparticles, including gold, due to several stabilization mechanisms. Also, reported are the structural and mechanical properties of extended crystalline solids of Na4Ag44(p-MBA)30 from large-scale quantum

  13. Intranasal Insulin Prevents Anesthesia-Induced Cognitive Impairment and Chronic Neurobehavioral Changes.

    PubMed

    Chen, Yanxing; Dai, Chun-Ling; Wu, Zhe; Iqbal, Khalid; Liu, Fei; Zhang, Baorong; Gong, Cheng-Xin

    2017-01-01

    General anesthesia increases the risk for cognitive impairment post operation, especially in the elderly and vulnerable individuals. Recent animal studies on the impact of anesthesia on postoperative cognitive impairment have provided some valuable insights, but much remains to be understood. Here, by using mice of various ages and conditions, we found that anesthesia with propofol and sevoflurane caused significant deficits in spatial learning and memory, as tested using Morris Water Maze (MWM) 2-6 days after anesthesia exposure, in aged (17-18 months old) wild-type (WT) mice and in adult (7-8 months old) 3xTg-AD mice (a triple transgenic mouse model of Alzheimer's disease (AD)), but not in adult WT mice. Anesthesia resulted in long-term neurobehavioral changes in the fear conditioning task carried out 65 days after exposure to anesthesia in 3xTg-AD mice. Importantly, daily intranasal administration of insulin (1.75 U/mouse/day) for only 3 days prior to anesthesia completely prevented the anesthesia-induced deficits in spatial learning and memory and the long-term neurobehavioral changes tested 65 days after exposure to anesthesia in 3xTg-AD mice. These results indicate that aging and AD-like brain pathology increase the vulnerability to cognitive impairment after anesthesia and that intranasal treatment with insulin can prevent anesthesia-induced cognitive impairment.

  14. Solution synthesis of metal silicide nanoparticles.

    PubMed

    McEnaney, Joshua M; Schaak, Raymond E

    2015-02-02

    Transition-metal silicides are part of an important family of intermetallic compounds, but the high-temperature reactions that are generally required to synthesize them preclude the formation of colloidal nanoparticles. Here, we show that palladium, copper, and nickel nanoparticles react with monophenylsilane in trioctylamine and squalane at 375 °C to form colloidal Pd(2)Si, Cu(3)Si, and Ni(2)Si nanoparticles, respectively. These metal silicide nanoparticles were screened as electrocatalysts for the hydrogen evolution reaction, and Pd(2)Si and Ni(2)Si were identified as active catalysts that require overpotentials of -192 and -243 mV, respectively, to produce cathodic current densities of -10 mA cm(-2).

  15. Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery

    PubMed Central

    Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji

    2013-01-01

    Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants. PMID:23818778

  16. Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery.

    PubMed

    Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji

    2013-01-01

    Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants.

  17. Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes

    PubMed Central

    Rosada, Rogério S; Torre, Lucimara Gaziola de la; Frantz, Fabiani G; Trombone, Ana PF; Zárate-Bladés, Carlos R; Fonseca, Denise M; Souza, Patrícia RM; Brandão, Izaíra T; Masson, Ana P; Soares, Édson G; Ramos, Simone G; Faccioli, Lúcia H; Silva, Célio L; Santana, Maria HA; Coelho-Castelo, Arlete AM

    2008-01-01

    Background The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally. Results We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 μg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-γ and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 μg). Conclusion Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease. PMID

  18. A novel intranasal breath-powered delivery system for sumatriptan: a review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine.

    PubMed

    Cady, Roger

    2015-01-01

    AVP-825, formerly 'OptiNose Sumatriptan,' is an investigational Breath-Powered(TM) Bi-Directional(TM) intranasal delivery system containing low-dose sumatriptan (22 mg intranasal powder) that avoids limitations of other types of intranasal administration by taking advantage of unique features of nasal anatomy and physiology. This review summarizes intranasal drug delivery for migraine, how the breath-powered technology works, and AVP-825 pharmacokinetic, efficacy and safety/tolerability findings. To identify AVP-825 clinical studies, a PubMed/MEDLINE database search was conducted with the terms AVP-825, OptiNose, OptiNose Sumatriptan, Breath-Powered Nasal Delivery or sumatriptan powder. Of 20 articles, 5 clinical studies were identified, including the head-to-head comparative COMPASS trial (AVP-825 vs oral sumatriptan) and two placebo-controlled studies. AVP-825 has faster sumatriptan absorption versus oral tablets or traditional liquid nasal spray. In Phase II/III randomized, double-blind, placebo-controlled trials, AVP-825 produced early and sustained efficacy with minimal triptan-related adverse effects. In COMPASS, AVP-825 produced earlier reduction of migraine pain intensity and migraine-associated symptoms than 100 mg oral sumatriptan, and higher early rates of pain relief and pain freedom, similar sustained efficacy, and fewer atypical sensations. AVP-825 has the potential to provide migraine patients with improved intranasal administration of sumatriptan that may enhance efficacy and tolerability.

  19. Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice

    PubMed Central

    Mazzeo, Carla; Gámez, Cristina; Rodriguez Marco, Ainara; de Zulueta, Ana; Sanz, Veronica; Bilbao, Izaskun; Ruiz-Cabello, Jesús; Zubeldia, Jose M.; del Pozo, Victoria

    2014-01-01

    Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma. PMID:24637581

  20. IGF-1 intranasal administration rescues Huntington's disease phenotypes in YAC128 mice.

    PubMed

    Lopes, Carla; Ribeiro, Márcio; Duarte, Ana I; Humbert, Sandrine; Saudou, Frederic; Pereira de Almeida, Luís; Hayden, Michael; Rego, A Cristina

    2014-06-01

    Huntington's disease (HD) is an autosomal dominant disease caused by an expansion of CAG repeats in the gene encoding for huntingtin. Brain metabolic dysfunction and altered Akt signaling pathways have been associated with disease progression. Nevertheless, conflicting results persist regarding the role of insulin-like growth factor-1 (IGF-1)/Akt pathway in HD. While high plasma levels of IGF-1 correlated with cognitive decline in HD patients, other data showed protective effects of IGF-1 in HD striatal neurons and R6/2 mice. Thus, in the present study, we investigated motor phenotype, peripheral and central metabolic profile, and striatal and cortical signaling pathways in YAC128 mice subjected to intranasal administration of recombinant human IGF-1 (rhIGF-1) for 2 weeks, in order to promote IGF-1 delivery to the brain. We show that IGF-1 supplementation enhances IGF-1 cortical levels and improves motor activity and both peripheral and central metabolic abnormalities in YAC128 mice. Moreover, decreased Akt activation in HD mice brain was ameliorated following IGF-1 administration. Upregulation of Akt following rhIGF-1 treatment occurred concomitantly with increased phosphorylation of mutant huntingtin on Ser421. These data suggest that intranasal administration of rhIGF-1 ameliorates HD-associated glucose metabolic brain abnormalities and mice phenotype.

  1. Transition metal-chelating surfactant micelle templates for facile synthesis of mesoporous silica nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Hye Sun; Department of Materials Science and Engineering, Yonsei University, Seoul 120-749; Kim, Won Hee

    2012-01-15

    Highly ordered mesoporous silica nanoparticles with tunable morphology and pore-size are prepared by the use of a transition metal-chelating surfactant micelle complex using Co{sup 2+}, Ni{sup 2+}, Cu{sup 2+}, and Zn{sup 2+} ions. These metal ions formed a metal-P123 micelle complex in an aqueous solution, while the metal ions are chelated to the hydrophilic domain such as the poly(ethylene oxide) group of a P123 surfactant. The different complexation abilities of the utilized transition metal ions play an important role in determining the formation of nano-sized ordered MSNs due to the different stabilization constant of the metal-P123 complex. Consequently, from amore » particle length of 1700 nm in the original mesoporous silica materials, the particle length of ordered MSNs through the metal-chelating P123 micelle templates can be reduced to a range of 180-800 nm. Furthermore, the variation of pore size shows a slight change from 8.8 to 6.6 nm. In particular, the Cu{sup 2+}-chelated MSNs show only decreased particle size to 180 nm. The stability constants for the metal-P123 complex are calculated on the basis of molar conductance measurements in order to elucidate the formation mechanism of MSNs by the metal-chelating P123 complex templates. In addition, solid-state {sup 29}Si, {sup 13}C-NMR and ICP-OES measurements are used for quantitative characterization reveal that the utilized metal ions affect only the formation of a metal-P123 complex in a micelle as a template. - Graphical abstract: Metal-chelating surfactant micelle templates support a simple and facile preparations of size-tunable ordered MSNs. Black-Small-Square Highlights: Black-Right-Pointing-Pointer Facile preparation of mesoporous silica nanoparticles (MSNs) was achieved by metal-chelating surfactant micelle complex using Co{sup 2+}, Ni{sup 2+}, Cu{sup 2+}, and Zn{sup 2+} ions. Black-Right-Pointing-Pointer Different complexation of metal ions plays an important role in determining the

  2. In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice

    PubMed Central

    Kimura, Genki; Nakaoki, Takahiro; Colley, Thomas; Rapeport, Garth; Strong, Pete; Kizawa, Yasuo

    2017-01-01

    ABSTRACT PC945 is a novel triazole optimized for lung delivery, and the objective of this study is to determine the effects of intranasally dosed PC945 on Aspergillus fumigatus infection and associated biomarkers in immunocompromised mice. PC945, posaconazole, or voriconazole was administered intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) postinfection in temporarily neutropenic A/J mice infected intranasally with A. fumigatus, and bronchoalveolar lavage fluid (BALF) and serum were collected on day 3. The effects of extended prophylaxis treatment (daily from days −7 to +3 or days −7 to 0) were also compared with those of the shorter treatment regimens (days −1 to +3 or days −1 and 0). Early and late interventions with PC945 (2.8 to 350 μg/mouse; approximately 0.11 to ∼14 mg/kg of body weight) were found to inhibit lung fungal loads and to decrease the concentrations of galactomannan (GM) in both BALF and serum as well as several biomarkers in BALF (interferon gamma [IFN-γ], interleukin-17 [IL-17], and malondialdehyde) and serum (tumor necrosis factor alpha [TNF-α] and IL-6) in a dose-dependent manner and were >3- and >47-fold more potent than intranasally dosed posaconazole and voriconazole, respectively. Furthermore, extended prophylaxis with low-dose PC945 (0.56 μg/mouse; 0.022 mg/kg) was found to inhibit fungal loads and to decrease the concentrations biomarkers more potently than did the shorter treatment regimens. Thus, PC945 dosed intranasally once daily showed potent antifungal effects, and the effects of PC945 accumulated upon repeat dosing and were persistent. Therefore, PC945 has the potential to be a novel inhaled therapy for the treatment of A. fumigatus infection in humans. PMID:28630185

  3. One should avoid retro-orbital pharmacokinetic sample collections for intranasal dosing in rats: Illustration of spurious pharmacokinetics generated for anti-migraine drugs zolmitriptan and eletriptan.

    PubMed

    Patel, Harilal; Patel, Prakash; Modi, Nirav; Shah, Shaival; Ghoghari, Ashok; Variya, Bhavesh; Laddha, Ritu; Baradia, Dipesh; Dobaria, Nitin; Mehta, Pavak; Srinivas, Nuggehally R

    2017-08-30

    Because of the avoidance of first pass metabolic effects due to direct and rapid absorption with improved permeability, intranasal route represents a good alternative for extravascular drug administration. The aim of the study was to investigate the intranasal pharmacokinetics of two anti-migraine drugs (zolmitriptan and eletriptan), using retro-orbital sinus and jugular vein sites sampling. In a parallel study design, healthy male Sprague-Dawley (SD) rats aged between 8 and 12weeks were divided into groups (n=4 or 5/group). The animals of individual groups were dosed intranasal (~1.0mg/kg) and oral doses of 2.1mg/kg of either zolmitriptan or eletriptan. Serial blood sampling was performed from jugular vein or retro-orbital site and plasma samples were analyzed for drug concentrations using LC-MS/MS assay. Standard pharmacokinetics parameters such as T max , C max , AUC last , AUC 0-inf and T 1/2 were calculated and statistics of derived parameters was performed using unpaired t-test. After intranasal dosing, the mean pharmacokinetic parameters C max and AUC inf of zolmitriptan/eletriptan showed about 17-fold and 3-5-fold higher values for retro-orbital sampling as compared to the jugular vein sampling site. Whereas after oral administration such parameters derived for both drugs were largely comparable between the two sampling sites and statistically non-significant. In conclusion, the assessment of plasma levels after intranasal administration with retro-orbital sampling would result in spurious and misleading pharmacokinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. No relevant modulation of TRPV1-mediated trigeminal pain by intranasal carbon dioxide in healthy humans.

    PubMed

    Jürgens, Tim P; Reetz, Romy; May, Arne

    2013-04-10

    Nasal insufflation of CO2 has been shown to exert antinociceptive respectively antihyperalgesic effects in animal pain models using topical capsaicin with activation of TRPV1-receptor positive nociceptive neurons. Clinical benefit from CO2 inhalation in patients with craniofacial pain caused by a putative activation of TRPV1 receptor positive trigeminal neurons has also been reported. These effects are probably mediated via an activation of TRPV1 receptor - positive neurons in the nasal mucosa with subsequent central inhibitory effects (such as conditioned pain modulation). In this study, we aimed to examine the effects of intranasal CO2 on a human model of craniofacial pain elicited by nasal application of capsaicin. In a first experiment, 48 healthy volunteers without previous craniofacial pain received intranasal capsaicin to provoke trigeminal pain elicited by activation of TRVP1 positive nociceptive neurons. Then, CO2 or air was insufflated alternatingly into the nasal cavity at a flow rate of 1 l/min for 60 sec each. In the subsequent experiment, all participants were randomized into 2 groups of 24 each and received either continuous nasal insufflation of CO2 or placebo for 18:40 min after nociceptive stimulation with intranasal capsaicin. In both experiments, pain was rated on a numerical rating scale every 60 sec. Contrary to previous animal studies, the effects of CO2 on experimental trigeminal pain were only marginal. In the first experiment, CO2 reduced pain ratings only minimally by 5.3% compared to air if given alternatingly with significant results for the main factor GROUP (F1,47=4.438; p=0.041) and the interaction term TIME*GROUP (F2.6,121.2=3.3; p=0.029) in the repeated-measures ANOVA. However, these effects were abrogated after continuous insufflation of CO2 or placebo with no significant changes for the main factors or the interaction term. Although mild modulatory effects of low-flow intranasal CO2 could be seen in this human model of TRPV-1

  5. Intranasal oxytocin does not modulate jumping to conclusions in schizophrenia: Potential interactions with caudate volume and baseline social functioning.

    PubMed

    Caravaggio, Fernando; Gerretsen, Philip; Mar, Wanna; Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Kim, Julia; Iwata, Yusuke; Patel, Raihaan; Chakravarty, M Mallar; Remington, Gary; Graff-Guerrero, Ariel; Menon, Mahesh

    2017-07-01

    Patients with schizophrenia (SCZ) tend to sample less information when making a decision, jumping to conclusions (JTC) without sufficient evidence. This "JTC bias" may be a trait marker of the disease and may not improve with antipsychotic treatment. We conducted a double-blind, placebo-controlled trial to test whether intranasal oxytocin could reduce JTC in stable, medicated patients with SCZ and healthy controls (HCs). We also explored whether striatal volume, clinical symptoms, and baseline social functioning (SF) was related to JTC performance. Forty-three male, medicated SCZ patients (Mean Age: 40.81±11.44) and sixteen HCs (Mean Age: 30.38±9.85) participated in a double-blind, placebo-controlled, cross-over study. Participants completed the Beads Task on two separate visits (minimum 20days apart). Participants were randomized to receive either intranasal oxytocin (50IU in solution) or intranasal placebo (saline). Twenty of the SCZ patients and all sixteen HCs also provided T1 MRIs (3-T). Patients with SCZ took fewer draws to decision (DTD) than HCs (t(57)=2.78, p=0.007). Oxytocin did not significantly change DTD in patients (t(42)=-1.11, p=0.27), nor in HCs (t(15)=-0.62, p=0.55). Exploratory analyses found ventral caudate volumes were negatively correlated with DTD (r(18)=-0.50, p=0.03) in patients. Moreover, oxytocin was more likely to improve JTC in patients with lower baseline SF. However, these exploratory findings did not survive correction for multiple comparisons. We replicate increased JTC in SCZ. However, acute intranasal oxytocin did not modify JTC. Future studies with larger samples should explore how brain morphology and SF are related to JTC performance in patients with SCZ. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Canted spin structure and the first order magnetic transition in CoFe2O4 nanoparticles coated by amorphous silica

    NASA Astrophysics Data System (ADS)

    Lyubutin, I. S.; Starchikov, S. S.; Gervits, N. E.; Korotkov, N. Yu.; Dmitrieva, T. V.; Lin, Chun-Rong; Tseng, Yaw-Teng; Shih, Kun-Yauh; Lee, Jiann-Shing; Wang, Cheng-Chien

    2016-10-01

    The functional polymer (PMA-co-MAA) latex microspheres were used as a core template to prepare magnetic hollow spheres consisting of CoFe2O4/SiO2 composites. The spinel type crystal structure of CoFe2O4 ferrite is formed under annealing, whereas the polymer cores are completely removed after annealing at 450 °C. Magnetic and Mössbauer spectroscopy measurements reveal very interesting magnetic properties of the CoFe2O4/SiO2 hollow spheres strongly dependent on the particle size which can be tuned by the annealing temperature. In the ground state of low temperatures, the CoFe2O4 nanoparticles are in antiferromagnetic state due to the canted magnetic structure. Under heating in the applied field, the magnetic structure gradually transforms from canted to collinear, which increases the magnetization. The Mössbauer data revealed that the small size CoFe2O4/SiO2 particles (2.2-4.3 nm) do not show superparamagnetic behavior but transit from the magnetic to the paramagnetic state by a jump-like magnetic transition of the first order This effect is a specific property of the magnetic nanoparticles isolated by inert material, and can be initiated by internal pressure creating at the particle surface. The suggested method of synthesis can be modified with various bio-ligands on the silane surface, and such materials can find many applications in diagnostics and bio-separation.

  7. Limited susceptibility and lack of systemic infection by an H3N2 swine influenza virus in intranasally inoculated chickens.

    PubMed

    Thomas, Colleen; Manin, Timofey B; Andriyasov, Artem V; Swayne, David E

    2008-09-01

    Chickens were intranasally inoculated with the swine influenza virus (SIV) A/swine/NC/307408/04 (H3N2) (NC/04 SIV) to determine the infectivity of a North American SIV for chickens, as well as the possibility of chicken meat serving as a transmission vehicle for SIV. White leghorn (WL) layer-type chickens were used for initial pathotyping and infectivity tests, and a more comprehensive intranasal pathogenesis study was done with white Plymouth rock (WPR) broiler-type chickens. None of the NC/04 SIV-inoculated WL or WPR chickens displayed clinical signs. Serologic tests showed that the virus was able to infect both intranasally inoculated WL and WPR chickens, but the antibody titers were low, suggesting inefficient replication. Some of the NC/04 SIV-inoculated WL chickens shed low levels of virus, mostly from the alimentary tract, but viral shedding was not detected in NC/04 SIV-inoculated WPR chickens. The comprehensive pathogenesis study demonstrated that the virus did not cause systemic infections in WPR chickens, and feeding breast and thigh meat from the NC/04 SIV-inoculated WPR to WL chickens did not transmit NC/04 SIV.

  8. The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

    PubMed

    Greene, R K; Spanos, M; Alderman, C; Walsh, E; Bizzell, J; Mosner, M G; Kinard, J L; Stuber, G D; Chandrasekhar, T; Politte, L C; Sikich, L; Dichter, G S

    2018-03-27

    Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed

  9. Monte Carlo simulation of dynamic phase transitions and frequency dispersions of hysteresis curves in core/shell ferrimagnetic cubic nanoparticle

    NASA Astrophysics Data System (ADS)

    Vatansever, Erol

    2017-05-01

    By means of Monte Carlo simulation method with Metropolis algorithm, we elucidate the thermal and magnetic phase transition behaviors of a ferrimagnetic core/shell nanocubic system driven by a time dependent magnetic field. The particle core is composed of ferromagnetic spins, and it is surrounded by an antiferromagnetic shell. At the interface of the core/shell particle, we use antiferromagnetic spin-spin coupling. We simulate the nanoparticle using classical Heisenberg spins. After a detailed analysis, our Monte Carlo simulation results suggest that present system exhibits unusual and interesting magnetic behaviors. For example, at the relatively lower temperature regions, an increment in the amplitude of the external field destroys the antiferromagnetism in the shell part of the nanoparticle, leading to a ground state with ferromagnetic character. Moreover, particular attention has been dedicated to the hysteresis behaviors of the system. For the first time, we show that frequency dispersions can be categorized into three groups for a fixed temperature for finite core/shell systems, as in the case of the conventional bulk systems under the influence of an oscillating magnetic field.

  10. Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

    PubMed

    Chiaretti, Antonio; Conti, Giorgio; Falsini, Benedetto; Buonsenso, Danilo; Crasti, Matteo; Manni, Luigi; Soligo, Marzia; Fantacci, Claudia; Genovese, Orazio; Calcagni, Maria Lucia; Di Giuda, Daniela; Mattoli, Maria Vittoria; Cocciolillo, Fabrizio; Ferrara, Pietro; Ruggiero, Antonio; Staccioli, Susanna; Colafati, Giovanna Stefania; Riccardi, Riccardo

    2017-01-01

    Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

  11. Magnetite pollution nanoparticles in the human brain

    NASA Astrophysics Data System (ADS)

    Maher, Barbara A.; Ahmed, Imad A. M.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-09-01

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <˜200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

  12. Magnetite pollution nanoparticles in the human brain.

    PubMed

    Maher, Barbara A; Ahmed, Imad A M; Karloukovski, Vassil; MacLaren, Donald A; Foulds, Penelope G; Allsop, David; Mann, David M A; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-09-27

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

  13. Magnetite pollution nanoparticles in the human brain

    PubMed Central

    Maher, Barbara A.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-01-01

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683–7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health. PMID:27601646

  14. Formulation considerations of intranasal corticosteroids for the treatment of allergic rhinitis.

    PubMed

    Meltzer, Eli O

    2007-01-01

    To examine how various aspects of an intranasal corticosteroid (INS) formulation may influence the efficacy, tolerability, and patient preference and adherence to INS therapy. A PubMed search of the literature was conducted for studies on allergic rhinitis published between January 1977 and January 2006 using the keywords intranasal corticosteroid, preservatives, benzalkonium chloride, and tonicity. Prospective studies, retrospective studies, and case reports were selected for inclusion in this review. Currently available INSs are effective first-line treatments for allergic rhinitis. Differences in patient preference for a particular INS are largely attributable to sensory attributes of the nasal spray, which arise from characteristics of the formulation. Additives and preservatives can cause tolerability issues by irritating the mucosal membranes and causing nasal drying, or they can confer an unpleasant odor or taste to an INS formulation. The relative osmotic pressure, or tonicity, of an INS can modulate nasal absorption and retention, thereby potentially influencing the clinical efficacy. Characteristics such as delivery device and spray volume can affect a patient's perception and experience with a particular INS. Newer INSs, such as ciclesonide, are in development for the treatment of allergic rhinitis, and consideration of the formulation characteristics of these agents is an important part of the development process. INSs are an effective treatment option for patients with allergic rhinitis; however, there is room for formulation improvement. Optimization of formulation may increase the efficacy, tolerability, and patient preference and adherence to INSs.

  15. A modified intranasal endoscopic excision for nasal vestibular cyst in China.

    PubMed

    Huang, Zizhen; Li, Jingjia; Yang, Qintai; Li, Peng; Ye, Jin; Liu, Xian; Zhang, Gehua

    2015-03-01

    This study aimed to improve the surgical removal procedure for nasal vestibular cysts. Twenty-three patients with nasal vestibular cysts underwent surgical removal of the cyst via a transoral sublabial approach and another 30 patients via a modified intranasal endoscopic excision method. The 30 patients were treated with local anesthesia and the roof of the cyst, which was firmly attached to the mucous membrane of the anterior floor of the nasal cavity, was removed transnasally with microdebrider. Bleeding of the opening was stopped by electric coagulation without nasal packing. Among the 30 consecutive patients who underwent the modified surgical procedure, all patients were successfully treated. The mean duration of surgery was 5.7 ± 2.6 min. The mean estimated blood loss was 3.5 ± 2.1 ml. All patients were outpatients. The mean hospital stay was 1 h. The mean total cost was 140. The visual analog scale scores of postoperative pain, pressure and nasal obstruction were 1, 0 and 1, respectively. The incidence rate of postoperative lip swelling or numbness was 0 %. Postoperative endoscopic findings revealed that the cyst was replaced by an air-containing sinus with a persistent opening at the anterolateral nasal floor. There was no recurrence during a mean follow-up of 18 months. The modified intranasal endoscopic excision is a simple, less invasive, low-cost and effective surgical procedure for the treatment of nasal vestibular cysts. It might change the pattern of treatment for nasal vestibular cysts in China.

  16. Effects of surface anchoring on the electric Frederiks transition in ferronematic systems

    NASA Astrophysics Data System (ADS)

    Farrokhbin, Mojtaba; Kadivar, Erfan

    2016-11-01

    The effects of anchoring phenomenon on the electric Frederiks transition threshold field in a nematic liquid crystal doped with ferroelectric nanoparticles are discussed. The polarizability of these nanoparticles in combination with confinement effects cause the drastic effects on the ferronematic systems. This study is based on Frank free energy and Rapini-Papoular surface energy for ferronematic liquid crystal having finite anchoring condition. In the case of different anchoring boundary conditions, the Euler-Lagrange equation of the total free energy is numerically solved by using the finite difference method together with the relaxation method and Maxwell construction to select the physical solutions and therefore investigate the effects of different anchoring strengths on the Frederiks transition threshold field. Maxwell construction method is employed to select three periodic solutions for nematic liquid crystal director at the interfaces of a slab. In the interval from zero to half- π, there is only one solution for the director orientation. In this way, NLC director rotates toward the normal to the surface as the applied electric field increases at the walls. Our numerical results illustrate that above Frederiks transition and in the intermediate anchoring strength, nematic molecules illustrate the different orientation at slab boundaries. We also study the effects of different anchoring strengths, nanoparticle volume fractions and polarizations on the Frederiks transition threshold field. We report that decreasing in the nanoparticle polarization results in the saturation Frederiks threshold. However, this situation does not happen for the nanoparticles volume fraction.

  17. Surface plasmon resonances in liquid metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Ershov, A. E.; Gerasimov, V. S.; Gavrilyuk, A. P.; Karpov, S. V.

    2017-06-01

    We have shown significant suppression of resonant properties of metallic nanoparticles at the surface plasmon frequency during the phase transition "solid-liquid" in the basic materials of nanoplasmonics (Ag, Au). Using experimental values of the optical constants of liquid and solid metals, we have calculated nanoparticle plasmonic absorption spectra. The effect was demonstrated for single particles, dimers and trimers, as well as for the large multiparticle colloidal aggregates. Experimental verification was performed for single Au nanoparticles heated to the melting temperature and above up to full suppression of the surface plasmon resonance. It is emphasized that this effect may underlie the nonlinear optical response of composite materials containing plasmonic nanoparticles and their aggregates.

  18. A reliable absorbable intranasal bolster for proper maintenance of fractured nasal bone position.

    PubMed

    Ducic, Y; Hilger, P A

    1999-06-01

    The maintenance of comminuted or otherwise unstable nasal bones in proper position following adequate operative reduction, may, on occasion, be a frustrating experience for both the patient and the surgeon. Migration of the fragments may compromise the aesthetic and functional results of well executed corrective nasal surgery. In this article, we will outline our successful, inexpensive approach to this occasionally challenging problem utilising an absorbable intranasal customised Surgicel bolster.

  19. Silicone nasal prosthesis retained by an intranasal stent: a clinical report.

    PubMed

    Goveas, Reiyal; Puttipisitchet, Ongart; Shrestha, Binit; Thaworanunta, Sita; Srithavaj, M L Theerathavaj

    2012-08-01

    Nasal defects after tumor excision can leave a patient functionally and esthetically impaired. Loss of nasal septal cartilage support causes the soft tissue to collapse or undergo stenosis, further compounding the problem. Intranasal stents can be used to maintain the patency of such nasal defects. This clinical report describes the use of an acrylic resin nasal stent bonded to a silicone nasal prosthesis to rehabilitate a patient with a nasal defect. Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  20. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    PubMed

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-08

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  1. GM-CSF has disparate roles during intranasal and intradermal Francisella tularensis infection.

    PubMed

    Kurtz, Sherry L; Bosio, Catharine M; De Pascalis, Roberto; Elkins, Karen L

    2016-12-01

    Our laboratory has employed in vitro and in vivo mouse models based on Francisella tularensis Live Vaccine Strain (LVS)-induced protection to elucidate immune correlates for intracellular bacteria. Among the effectors found was GM-CSF, a pleiotropic cytokine that is integral to the development and proliferation of myeloid cells, including alveolar macrophages. GM-CSF has roles in resistance to primary murine infection with several intracellular pathogens, but its role during Francisella infection is unknown. Francisella is an intracellular pathogen that infects lungs after inhalation, primarily invading alveolar macrophages. Here we show that GM-CSF has route-dependent roles during primary infection of mice with LVS. GM-CSF deficient (GM-CSF KO) mice were slightly more susceptible than wild type to intradermal infection, but had increased resistance to intranasal infection. Similarly, these mice had increased resistance to pulmonary infection with virulent F. tularensis (SchuS4). LVS-vaccinated GM-CSF KO mice had normal adaptive immune responses, as measured by T cell activities after LVS intradermal or intranasal vaccination, and survived lethal secondary LVS challenge. GM-CSF KO mice also had robust humoral responses, producing elevated levels of serum antibodies following LVS vaccination compared to wild type mice. Taken together, our data demonstrates that the absence of GM-CSF improves resistance to pulmonary, but not intradermal, infection with Francisella. Published by Elsevier Masson SAS.

  2. A prospective, randomized, double-blind trial of intranasal dexmedetomidine and oral chloral hydrate for sedated auditory brainstem response (ABR) testing.

    PubMed

    Reynolds, Jason; Rogers, Amber; Medellin, Eduardo; Guzman, Jonathan A; Watcha, Mehernoor F

    2016-03-01

    Dexmedetomidine is increasingly used by various routes for pediatric sedation. However, there are few randomized controlled trials comparing the efficacy of dexmedetomidine to other commonly used sedatives. To compare the efficacy of sedation with intranasal dexmedetomidine to oral chloral hydrate for auditory brainstem response (ABR) testing. In this double-blind, double-dummy study, children undergoing ABR testing were randomized to receive intranasal dexmedetomidine 3 mcg · kg(-1) plus oral placebo (Group IN DEX) or oral chloral hydrate 50 mg · kg(-1) plus intranasal saline placebo (Group CH). We recorded demographic data, times from sedative administration to start and completion of testing, quality of sedation, occurrence of predefined adverse events, discharge times, and return to baseline activity on the day of testing. Testing completion rates with a single dose of medication were higher in the IN DEX group (89% vs 66% for CH, odds ratio with 95% confidence intervals 4.04 [1.3-12.6], P = 0.018). The median [95% CI)] time to successful testing start was shorter (25 [20-29] min vs 30 [20-49] min for IN DEX and CH, respectively, log rank test P = 0.02) and the proportion of children whose parents reported a return to baseline activity on the day of testing was greater for the IN DEX than the CH group (89% vs 64%, OR [95% CI] 4.71 [1.34-16.6], P = 0.02). There were no major adverse events in either group and no significant differences in the incidence of minor events. Intranasal dexmedetomidine is an effective alternative to oral chloral hydrate sedation for ABR testing, with the advantages of a higher incidence of testing completion with a single dose, shorter time to desired sedation level, and with significantly more patients reported to return to baseline activity on the same day. © 2016 John Wiley & Sons Ltd.

  3. Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice

    PubMed Central

    Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Wei, Ling

    2015-01-01

    Apelin is a peptide originally isolated from bovine stomach tissue extracts and identified as an endogenous ligand of the APJ receptor; recent work showed that apelin ameliorates the ischemic injury in the heart and the brain. Being an analogue to the angiotensin II receptor, the apelin/APJ signaling may mediate angiogenesis process. We explored the noninvasive intranasal brain delivery method and investigated therapeutic effects of apelin-13 in a focal ischemic stroke model of mice. Intranasal administration of apelin-13 (4 mg/kg) was given 30 min after the onset of stroke and repeated once daily. Three days after stroke, mice received apelin-13 had significantly reduced infarct volume and less neuronal death in the penumbra. Western blot analyses showed upregulated levels of apelin, apelin receptor APLNR, and Bcl-2 and decreased caspase-3 activation in the apelin-13-treated brain. The proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1β, and chemokine monocyte chemoattractant protein-1 mRNA increased in the ischemic brain, which were significantly attenuated by apelin-13. Apelin-13 remarkably reduced microglia recruitment and activation in the penumbra according to morphological features of Iba-1-positive cells 3 days after ischemia. Apelin-13 significantly increased the expression of angiogenic factor vascular endothelial growth factor and matrix metalloproteinase-9 14 days after stroke. Angiogenesis illustrated by collagen IV + /5-bromo-2′-deoxyuridin + colabeled cells was significantly increased by the apelin-13 treatment 21 days after stroke. Finally, apelin-13 promoted the local cerebral blood flow restoration and long-term functional recovery. This study demonstrates a noninvasive intranasal delivery of apelin-13 after stroke, suggesting that the reduced inflammatory activities, decreased cell death, and increased angiogenesis contribute to the therapeutic benefits of apelin-13. PMID:26391329

  4. Irreversible phase transitions due to laser-based T-jump heating of precursor Eu:ZrO{sub 2}/Tb:Y{sub 2}O{sub 3} core/shell nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gunawidjaja, Ray; Diez-y-Riega, Helena; Eilers, Hergen, E-mail: eilers@wsu.edu

    2015-09-15

    Amorphous precursors of Eu-doped-ZrO{sub 2}/Tb-doped-Y{sub 2}O{sub 3} (p-Eu:ZrO{sub 2}/p-Tb:Y{sub 2}O{sub 3}) core/shell nanoparticles are rapidly heated to temperatures between 200 °C and 950 °C for periods between 2 s and 60 s using a CO{sub 2} laser. During this heating process the nanoparticles undergo irreversible phase changes. The fluorescence spectra due to Eu{sup 3+} dopants in the core and Tb{sup 3+} dopants in the shell are used to identify distinct phases within the material and to generate time/temperature phase diagrams. Such phase diagrams can potentially help to determine unknown time/temperature histories in thermosensor applications. - Graphical abstract: A CO{sub 2}more » laser is used for rapid heating of p-Eu:ZrO{sub 2}/p-Tb:Y{sub 2}O{sub 3} core/shell nanoparticles. Optical spectra are used to identify distinct phases and to determine its thermal history. - Highlights: • Synthesized oxide precursors of lanthanide doped core/shell nanoparticles. • Heated core/shell nanoparticles via laser-based T-jump technique. • Observed time- and temperature-dependent irreversible phase transition.« less

  5. Preparation and Efficacy of a Live Newcastle Disease Virus Vaccine Encapsulated in Chitosan Nanoparticles

    PubMed Central

    Gao, Ting-ting; Li, Wei; Zhao, Yan; Zhang, Feng-qiang; Wu, Jin; Cui, Xianlan; Wang, Yun-Feng

    2012-01-01

    Background Newcastle disease (ND) is a highly contagious viral disease of poultry caused by pathogenic strains of the Newcastle disease virus (NDV). Live NDV vaccines are administered by drinking water, eyedrops or coarse aerosol spray. To further enhance mucosal immune responses, chitosan nanoparticles were developed for the mucosal delivery of a live NDV vaccine. Methodology/Principal Findings A lentogenic live-virus vaccine (strain LaSota) against NDV encapsulated in chitosan nanoparticles were developed using an ionic crosslinking method. Chitosan nanoparticles containing the lentogenic live-virus vaccine against NDV (NDV-CS-NPs) were produced with good morphology, high stability, a mean diameter of 371.1 nm, an encapsulation rate of 77% and a zeta potential of +2.84 mV. The Western blotting analysis showed that NDV structural proteins were detected in NDV-CS-NPs. The virus release assay results of NDV-CS-NPs indicated that NDV was released from NDV-CS-NPs. Chickens immunized orally or intranasally with NDV-CS-NPs were fully protected whereas one out of five chickens immunized with the LaSota live NDV vaccine and three out of five chickens immunized with the inactivated NDV vaccine were dead after challenge with the highly virulent NDV strain F48E9. Conclusions/Significance NDV-CS-NPs induced better protection of immunized specific pathogen free chickens compared to the live NDV vaccine strain LaSota and the inactivated NDV vaccine. This study lays a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles. PMID:23285276

  6. Syringe Exchange, Injecting and Intranasal Drug Use

    PubMed Central

    Arasteh, Kamyar; McKnight, Courtney; Ringer, Martin; Friedman, Samuel R.

    2016-01-01

    Objective To assess trends in injecting and non-injecting drug use after implementation of large-scale syringe exchange in New York City. The belief that implementation of syringe exchange will lead to increased drug injecting has been a persistent argument against syringe exchange. Methods Administrative data on route of administration for primary drug of abuse among patients entering the Beth Israel methadone maintenance program from 1995 – 2007. Approximately 2000 patients enter the program each year. Results During and after the period of large scale implementation of syringe exchange, the numbers of methadone program entrants reporting injecting drug use decreased while the numbers of entrants reporting intranasal drug use increased (p < .001). Conclusion While assessing possible effects of syringe exchange on trends in injecting drug use is inherently difficult, this may be the strongest data collected to date showing a lack of increase in drug injecting following implementation of syringe exchange. PMID:19891668

  7. High Content Screening in Zebrafish Speeds up Hazard Ranking of Transition Metal Oxide Nanoparticles

    PubMed Central

    Lin, Sijie; Zhao, Yan; Xia, Tian; Meng, Huan; Zhaoxia, Ji; Liu, Rong; George, Saji; Xiong, Sijing; Wang, Xiang; Zhang, Haiyuan; Pokhrel, Suman; Mädler, Lutz; Damoiseaux, Robert; Lin, Shuo; Nel, Andre E.

    2014-01-01

    Zebrafish is an aquatic organism that can be used for high content safety screening of engineered nanomaterials (ENMs). We demonstrate, for the first time, the use of high content bright-field and fluorescence-based imaging to compare the toxicological effect of transition metal oxide (CuO, ZnO, NiO and Co3O4) nanoparticles in zebrafish embryos and larvae. High content bright-field imaging demonstrated potent and dose-dependant hatching interference in the embryos, with the exception of Co3O4 which was relatively inert. We propose that the hatching interference was due to the shedding of Cu and Ni ions, compromising the activity of the hatching enzyme, ZHE1, similar to what we previously proposed for Zn2+. This hypothesis is based on the presence of metal–sensitive histidines in the catalytic center of this enzyme. Co-introduction of a metal ion chelator, diethylene triamine pentaacetic acid (DTPA), reversed the hatching interference of Cu, Zn and Ni. While neither the embryos nor larvae demonstrated morphological abnormalities, high content fluorescence-based imaging demonstrated that CuO, ZnO and NiO could induce increased expression of the heat shock protein 70:enhanced green fluorescence protein (hsp70:eGFP) in transgenic zebrafish larvae. Induction of this response by CuO required a higher nanoparticle dose than the amount leading to hatching interference. This response was also DTPA sensitive. In conclusion, we demonstrate that high content imaging of embryo development, morphological abnormalities and HSP70 expression can be used for hazard ranking and determining the dose-response relationships leading to ENM effects on the development of the zebrafish embryo. PMID:21851096

  8. Nanoparticle halos: A new colloid stabilization mechanism

    PubMed Central

    Tohver, Valeria; Smay, James E.; Braem, Alan; Braun, Paul V.; Lewis, Jennifer A.

    2001-01-01

    A new mechanism for regulating the stability of colloidal particles has been discovered. Negligibly charged colloidal microspheres, which flocculate when suspended alone in aqueous solution, undergo a remarkable stabilizing transition upon the addition of a critical volume fraction of highly charged nanoparticle species. Zeta potential analysis revealed that these microspheres exhibited an effective charge buildup in the presence of such species. Scanning angle reflectometry measurements indicated, however, that these nanoparticle species did not adsorb on the microspheres under the experimental conditions of interest. It is therefore proposed that highly charged nanoparticles segregate to regions near negligibly charged microspheres because of their repulsive Coulombic interactions in solution. This type of nanoparticle haloing provides a previously unreported method for tailoring the behavior of complex fluids. PMID:11447264

  9. Intranasal administration of oxytocin modulates behavioral and amygdala responses to infant crying in females with insecure attachment representations.

    PubMed

    Riem, Madelon M E; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H

    2016-01-01

    The current study examined the effects of oxytocin administration on the response to infant crying in individuals with secure or insecure attachment representations as assessed with the Adult Attachment Interview. We measured feelings of irritation and the use of excessive force as indicated by grip strength using a handgrip dynamometer during exposure to infant crying in 42 women without children who were administered intranasal oxytocin or a placebo. In addition, amygdala responses to infant crying and control sounds were measured with functional magnetic resonance imaging (fMRI). The effects of oxytocin on reactivity to crying were moderated by attachment security. Oxytocin decreased the use of excessive handgrip force and amygdala reactivity in response to crying in individuals with insecure attachment representations. Our findings indicate that insecure individuals, who show emotional, behavioral, and neural hyperreactivity to crying, benefit the most from intranasal oxytocin.

  10. The effects of the time of intranasal splinting on bacterial colonization, postoperative complications, and patient discomfort after septoplasty operations.

    PubMed

    Karatas, Abdullah; Pehlivanoglu, Filiz; Salviz, Mehti; Kuvat, Nuray; Cebi, Isil Taylan; Dikmen, Burak; Sengoz, Gonul

    The main reason for nasal tampon placement after septoplasty is to prevent postoperative hemorrhage, while the secondary purpose is internal stabilization after operations involving the cartilaginous-bony skeleton of the nose. Silicone intranasal splints are as successful as other materials in controlling postoperative hemorrhages of septal origin. The possibility of leaving the splints intranasally for extended periods helps stabilize the septum in the midline. However, there is nothing in the literature about how long these splints can be retained inside the nasal cavity without increasing the risk of infection, postoperative complications, and patient discomfort. The current study aimed to evaluate the association between the duration of intranasal splinting and bacterial colonization, postoperative complications, and patient discomfort. Patients who had undergone septoplasty were divided into three groups according to the day of removal of the silicone splints. The splints were removed on the fifth, seventh, and tenth postoperative days. The removed splints were microbiologically cultured. Early and late complications were assessed, including local and systemic infections, tissue necrosis, granuloma formation, mucosal crusting, synechia, and septal perforation. Postoperative patient discomfort was evaluated by scoring the levels of pain and nasal obstruction. No significant difference was found in the rate of bacterial colonization among the different groups. Decreased mucosal crusting and synechia were detected with longer usage intervals of intranasal silicone splints. Postoperative pain and nasal obstruction were also diminished by the third postoperative day. Silicone splints were well tolerated by the patients and any negative effects on postoperative patient comfort were limited. In fact, prolonged splint usage intervals reduced late complications. Long-term silicone nasal splint usage is a reliable, effective, and comfortable method in patients with

  11. Coupling of demixing and magnetic ordering phase transitions probed by turbidimetric measurements in a binary mixture doped with magnetic nanoparticles.

    PubMed

    Hernández-Díaz, Lorenzo; Hernández-Reta, Juan Carlos; Encinas, Armando; Nahmad-Molinari, Yuri

    2010-05-19

    We present a novel study on the effect of a magnetic field applied on a binary mixture doped with magnetic nanoparticles close to its demixing transition. Turbidity measurements in the Faraday configuration show that the effect of applying an external field produces changes in the critical opalescence of the mixture that allow us to track an aggregation produced by critical Casimir forces and a reversible aggregation due to the formation of chain-like flocks in response to the external magnetic field. The observation of a crossover of the aggregation curves through optical signals is interpreted as the evolution from low to high power dispersion nuclei due to an increase in the radius of the condensation seed brought about by Casimir or magnetic interactions. Finally, evidence of an enhanced magnetocaloric effect due to the coupling between mixing and ordering phase transitions is presented which opens up a nonsolid state approach of designing refrigerating cycles and devices.

  12. Fast and Universal Approach to Encapsulating Transition Bimetal Oxide Nanoparticles in Amorphous Carbon Nanotubes under an Atmospheric Environment Based on the Marangoni Effect.

    PubMed

    Li, Shuoyu; Liu, Yuyi; Guo, Peisheng; Wang, Chengxin

    2017-09-13

    Transition metal oxide nanoparticles capsuled in amorphous carbon nanotubes (ACNTs) are attractive anode materials of lithium-ion batteries (LIBs). Here, we first designed a fast and universal method with a hydromechanics conception which is called Marangoni flow to fabricate transition bimetal oxides (TBOs) in the ACNT composite with a better electrochemistry performance. Marangoni flows can produce a liquid column with several centimeters of height in a tube with one side immersed in the liquid. The key point to induce a Marangoni flow is to make a gradient of the surface tension between the surface and the inside of the solution. With our research, we control the gradient of the surface tension by controlling the viscosity of a solution. To show how our method could be generally used, we synthesize two anode materials such as (a) CoFe 2 O 4 @ACNTs, and (b) NiFe 2 O 4 @ACNTs. All of these have a similar morphology which is ∼20 μm length with a diameter of 80-100 nm for the ACNTs, and the particles (inside the ACNTs) are smaller than 5 nm. In particular, there are amorphous carbons between the nanoparticles. All of the composite materials showed an outstanding electrochemistry performance which includes a high capacity and cycling stability so that after 600 cycles the capacity changed by less than 3%.

  13. Nanoparticle flotation collectors--the influence of particle softness.

    PubMed

    Yang, Songtao; Razavizadeh, Bi Bi Marzieh; Pelton, Robert; Bruin, Gerard

    2013-06-12

    The ability of polymeric nanoparticles to promote glass bead and pentlandite (Pn, nickel sulfide mineral) attachment to air bubbles in flotation was measured as a function of the nanoparticle glass transition temperature using six types of nanoparticles based on styrene/N-butylacrylate copolymers. Nanoparticle size, surface charge density, and hydrophobicity were approximately constant over the series. The ability of the nanoparticles to promote air bubble attachment and perform as flotation collectors was significantly greater for softer nanoparticles. We propose that softer nanoparticles were more firmly attached to the glass beads or mineral surface because the softer particles had a greater glass/polymer contact areas and thus stronger overall adhesion. The diameters of the contact areas between polymeric nanoparticles and glass surfaces were estimated with the Young-Laplace equation for soft, liquidlike particles, whereas JKR adhesion theory was applied to the harder polystyrene particles. The diameters of the contact areas were estimated to be more than an order of magnitude greater for the soft particles compared to harder polystyrene particles.

  14. A clinical trial of WRL 105 strain live attenuated influenza vaccine comparing four methods of intranasal vaccination.

    PubMed Central

    Freestone, D. S.; Bowker, C. H.; Letley, E.; Ferris, R. D.; White, W. G.; Barnes, G. M.

    1976-01-01

    A single intranasal dose of 10(7-0) EID50 recombinant WRL 105 strain live attenuated influenza vaccine was administered intranasally to 193 volunteers either as nose drops or by one of three spray devices which produced sprays of differing physical characteristics. In volunteers with homologous haemagglutinating inhibiting antibody titres of less than or equal to 20 before vaccination, seroconversion rates varied widely from 80% following the administration of drops to 71%, 57% and 28% with the three spray devices. In the week following vaccination 16 (22%) of 74 volunteers who were found to show a fourfold or greater antibody response to took analgesics to control symptoms in comparison with 4 (7%) of 58 volunteers who exhibited no serological response to vaccination (P less than 0-05). However, neither the occurrence of upper respiratory nor systemic symptoms were significantly different in these two groups and the degree of attenuation of the recombinant WRL 105 strain appears to be acceptable for future use. PMID:1064672

  15. IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles

    PubMed Central

    Zhao, Kai; Rong, Guangyu; Hao, Yan; Yu, Lu; Kang, Hong; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Ren, Zhiyu; Li, Zejun

    2016-01-01

    Newcastle disease caused by ND virus (NDV) is a highly contagious disease of birds. Vaccine for effective protection of poultry animals from NDV infection is urgently needed. Mucosal immunity plays a very important role in the antiviral immune response. In this study, a NDV F gene-containing DNA vaccine encapsulated in Ag@SiO2 hollow nanoparticles (pFDNA-Ag@SiO2-NPs) with an average diameter of 500 nm were prepared to assess the mucosal immune response. These nanoparticles exhibited low cytotoxicity and did not destroy the bioactivity of plasmid DNA, which could be expressed in vitro. The plasmid DNA was sustainably released after an initial burst release. In vivo immunization showed that the intranasal immunization of chickens with pFDNA-Ag@SiO2-NPs induced high titers of serum antibody, significantly promoted lymphocyte proliferation and induced higher expression levels of IL-2 and IFN-γ in a dose-dependent manner. These results indicated that the Ag@SiO2 hollow nanoparticles could serve as an efficient and safe delivery carrier for NDV DNA vaccine to induce mucosal immunity. This study has provided promising results for the further development of mucosal vaccines encapsulated in inorganic nanoparticles. PMID:27170532

  16. IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhao, Kai; Rong, Guangyu; Hao, Yan; Yu, Lu; Kang, Hong; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Ren, Zhiyu; Li, Zejun

    2016-05-01

    Newcastle disease caused by ND virus (NDV) is a highly contagious disease of birds. Vaccine for effective protection of poultry animals from NDV infection is urgently needed. Mucosal immunity plays a very important role in the antiviral immune response. In this study, a NDV F gene-containing DNA vaccine encapsulated in Ag@SiO2 hollow nanoparticles (pFDNA-Ag@SiO2-NPs) with an average diameter of 500 nm were prepared to assess the mucosal immune response. These nanoparticles exhibited low cytotoxicity and did not destroy the bioactivity of plasmid DNA, which could be expressed in vitro. The plasmid DNA was sustainably released after an initial burst release. In vivo immunization showed that the intranasal immunization of chickens with pFDNA-Ag@SiO2-NPs induced high titers of serum antibody, significantly promoted lymphocyte proliferation and induced higher expression levels of IL-2 and IFN-γ in a dose-dependent manner. These results indicated that the Ag@SiO2 hollow nanoparticles could serve as an efficient and safe delivery carrier for NDV DNA vaccine to induce mucosal immunity. This study has provided promising results for the further development of mucosal vaccines encapsulated in inorganic nanoparticles.

  17. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

    PubMed

    Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

    2016-07-01

    It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Protein brownian rotation at the glass transition temperature of a freeze-concentrated buffer probed by superparamagnetic nanoparticles.

    PubMed

    Eloi, J-C; Okuda, M; Jones, S E Ward; Schwarzacher, W

    2013-06-18

    For applications from food science to the freeze-thawing of proteins it is important to understand the often complex freezing behavior of solutions of biomolecules. Here we use a magnetic method to monitor the Brownian rotation of a quasi-spherical cage-shaped protein, apoferritin, approaching the glass transition Tg in a freeze-concentrated buffer (Tris-HCl). The protein incorporates a synthetic magnetic nanoparticle (Co-doped Fe3O4 (magnetite)). We use the magnetic signal from the nanoparticles to monitor the protein orientation. As T decreases toward Tg of the buffer solution the protein's rotational relaxation time increases exponentially, taking values in the range from a few seconds up to thousands of seconds, i.e., orders of magnitude greater than usually accessed, e.g., by NMR. The longest relaxation times measured correspond to estimated viscosities >2 MPa s. As well as being a means to study low-temperature, high-viscosity environments, our method provides evidence that, for the cooling protocol used, the following applies: 1), the concentration of the freeze-concentrated buffer at Tg is independent of its initial concentration; 2), little protein adsorption takes place at the interface between ice and buffer; and 3), the protein is free to rotate even at temperatures as low as 207 K. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. Adjuvant action of melittin following intranasal immunisation with tetanus and diphtheria toxoids.

    PubMed

    Bramwell, V W; Somavarapu, S; Outschoorn, I; Alpar, H O

    2003-01-01

    Melittin, a 26-amino acid peptide and the major active component of the venom of the honey bee--Apis mellifera--has recently been shown to have absorption enhancing properties in Caco-2 cells at levels well below the level required for the generation of cytotoxicity. Given the potential of absorption enhancing agents to act as adjuvants when administered nasally [Alpar, H.O., Eyles, J.E., Williamson, E.D. and Somavarapu, S. (2001) "Intranasal vaccination against plague, tetanus and diphtheria", Adv. Drug Delivery Rev. 51, 173-201] we hypothesized that melittin may have potential as a mucosal adjuvant. Following our initial studies reported here, it was found that the co-administration of 4 microg of melittin in conjunction with tetanus toxoid in BALB/c mice was effective in eliciting markedly enhanced antibody titres in comparison to control groups and groups receiving free antigen administered intranasally. Lower concentrations of melittin were less effective and mice receiving 4 microg of melittin plus antigen exhibited antibody titres significantly higher (i.e. P<0.05) than any of the other groups tested. The observed IgG2a titres were shown to be dependent upon the dose of melittin co-administered with the immunising antigen in a similar fashion to the observed total IgG responses. In summary, melittin has been shown here to have potential as a novel mucosal adjuvant for antigens administered via the nasal route.

  20. [Combined palliative hypofractionated radiation and carboplatin chemotherapy of intranasal tumours in dogs].

    PubMed

    Schwietzer, A; Kessler, M; Kandel-Tschiederer, B

    2012-10-17

    Combination therapy of intranasal tumours in dogs with palliative 60 cobalt radiation and carboplatin chemotherapy. Twenty-five dogs with intranasal tumours were treated in the Hofheim Veterinary Hospital (Germany) from 2004 to 2006 with a total radiation dose of 24Gy (3 fractions of 8 Gy on days 0, 7 and 21) and five doses of Carboplatin (270-300 mg/m² BSA i.v. every 21-28 days). In 88% patients, clinical symptoms subsided partially or completely resulting in improvement in quality of life. Computed tomography revealed partial (5/25) or complete (5/25) tumour remissions. Chemotherapy was well tolerated. Radiation therapy caused no or minimal side effects except for 3 dogs (12%), which experienced serious ocular side effects resulting in loss of vision of the affected eye and one dog with epileptic seizures. Survival times ranged from 10-639 days with a median of 156 days. There was no statistically significant correlation between the parameters breed, age, sex, brain invasion or tumour stage and survival time or progression free interval. Survival time and progression free interval were significantly correlated with the degree of tumour remission. It can be concluded from this study that palliative radiation therapy combined with chemotherapy results in excellent palliation of clinical symptoms and acceptable survival times. There was no advantage of combined therapy (radiation with carboplatin) when compared to literature data on results of radiation therapy alone.

  1. Intranasal delivery of antiviral siRNA.

    PubMed

    Barik, Sailen

    2011-01-01

    Intranasal administration of synthetic siRNA is an effective modality of RNAi delivery for the prevention and therapy of respiratory diseases, including pulmonary infections. Vehicles used for nasal siRNA delivery include established as well as novel reagents, many of which have been recently optimized. In general, they all promote significant uptake of siRNA into the lower respiratory tract, including the lung. When properly designed and optimized, these siRNAs offer significant protection against respiratory viruses such as influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). Nasally administered siRNA remains within the lung and does not access systemic blood flow, as judged by its absence in other major organs such as liver, heart, kidney, and skeletal muscle. Adverse immune reaction is generally not encountered, especially when immunogenic and/or off-target siRNA sequences and toxic vehicles are avoided. In fact, siRNA against RSV has entered Phase II clinical trials in human with promising results. Here, we provide a standardized procedure for using the nose as a specific route for siRNA delivery into the lung of laboratory animals. It should be clear that this simple and efficient system has enormous potential for therapeutics.

  2. Multi-Ferroic Polymer Nanoparticle Composites for Next Generation Metamaterials

    DTIC Science & Technology

    2014-07-28

    particle size of magnetite nanoparticles. The PI will continue to develop composites that could be utilized for developing high- bandwidth radio frequency...to improve the efficiency and decrease the size of the device. High performance stretchable magneto-dielectric materials can be accomplished using...nanoparticles oxidize at dimensions smaller than the critical size for superparamagnetic to ferromagnetic transition, which is essential for minimal

  3. Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients.

    PubMed

    van Zuiden, Mirjam; Frijling, Jessie L; Nawijn, Laura; Koch, Saskia B J; Goslings, J Carel; Luitse, Jan S; Biesheuvel, Tessa H; Honig, Adriaan; Veltman, Dick J; Olff, Miranda

    2017-06-15

    There are currently few preventive interventions available for posttraumatic stress disorder (PTSD). Intranasal oxytocin administration early after trauma may prevent PTSD, because oxytocin administration was previously found to beneficially impact PTSD vulnerability factors, including neural fear responsiveness, peripheral stress reactivity, and socioemotional functioning. Therefore, we investigated the effects of intranasal oxytocin administration early after trauma on subsequent clinician-rated PTSD symptoms. We then assessed whether baseline characteristics moderated the intervention's effects. We performed a multicenter, randomized, double-blind, placebo-controlled clinical trial. Adult emergency department patients with moderate to severe acute distress (n = 120; 85% accident victims) were randomized to intranasal oxytocin (8 days/40 IU twice daily) or placebo (8 days/10 puffs twice daily), initiated within 12 days posttrauma. The Clinician-Administered PTSD Scale (CAPS) was administered at baseline (within 10 days posttrauma) and at 1.5, 3, and 6 months posttrauma. The intention-to-treat sample included 107 participants (oxytocin: n = 53; placebo: n = 54). We did not observe a significant group difference in CAPS total score at 1.5 months posttrauma (primary outcome) or across follow-up (secondary outcome). Secondary analyses showed that participants with high baseline CAPS scores receiving oxytocin had significantly lower CAPS scores across follow-up than participants with high baseline CAPS scores receiving placebo. Oxytocin administration early after trauma did not attenuate clinician-rated PTSD symptoms in all trauma-exposed participants with acute distress. However, participants with high acute clinician-rated PTSD symptom severity did show beneficial effects of oxytocin. Although replication is warranted, these findings suggest that oxytocin administration is a promising preventive intervention for PTSD for individuals with high acute PTSD symptoms

  4. Alkylamine capped metal nanoparticle "inks" for printable SERS substrates, electronics and broadband photodetectors.

    PubMed

    Polavarapu, Lakshminarayana; Manga, Kiran Kumar; Yu, Kuai; Ang, Priscilla Kailian; Cao, Hanh Duyen; Balapanuru, Janardhan; Loh, Kian Ping; Xu, Qing-Hua

    2011-05-01

    We report a facile and general method for the preparation of alkylamine capped metal (Au and Ag) nanoparticle "ink" with high solubility. Using these metal nanoparticle "inks", we have demonstrated their applications for large scale fabrication of highly efficient surface enhanced Raman scattering (SERS) substrates by a facile solution processing method. These SERS substrates can detect analytes down to a few nM. The flexible plastic SERS substrates have also been demonstrated. The annealing temperature dependent conductivity of the nanoparticle films indicated a transition temperature above which high conductivity was achieved. The transition temperature could be tailored to the plastic compatible temperatures by using proper alkylamine as the capping agent. The ultrafast electron relaxation studies of the nanoparticle films demonstrated that faster electron relaxation was observed at higher annealing temperatures due to stronger electronic coupling between the nanoparticles. The applications of these highly concentrated alkylamine capped metal nanoparticle inks for the printable electronics were demonstrated by printing the oleylamine capped gold nanoparticles ink as source and drain for the graphene field effect transistor. Furthermore, the broadband photoresponse properties of the Au and Ag nanoparticle films have been demonstrated by using visible and near-infrared lasers. These investigations demonstrate that these nanoparticle "inks" are promising for applications in printable SERS substrates, electronics, and broadband photoresponse devices. © The Royal Society of Chemistry 2011

  5. Optical and Luminescence Properties of β-NaFeO2 Nanoparticles

    NASA Astrophysics Data System (ADS)

    Singh, Sarbjit; Tangra, Ankush Kumar; Lotey, Gurmeet Singh

    2018-05-01

    β-NaFeO2 nanoparticles have been synthesized by sol-gel method and their morphological, structural and optical properties investigated. Transmission electron microscope study reveals that the size of the synthesis nanoparticles is 37 nm and they are possessing spherical symmetry. X-ray diffraction pattern shows the orthorhombic crystal structure of nanoparticles with space group Pn21 a. UV-visible spectra of β-NaFeO2 divulges that these nanoparticles have direct band gap 2.35 eV. The observed Fourier transform infrared spectroscopy spectra confirms the presence of Fe-Na bonding at 1074 cm-1. The photoluminescence study of these nanoparticles shows that these nanoparticles possesses various transition in the visible spectrum.

  6. Light-responsive expansion-contraction of spherical nanoparticle grafted with azopolymers

    NASA Astrophysics Data System (ADS)

    Fu, Jie; Zhang, Xinghua; Miao, Bing; Yan, Dadong

    2017-04-01

    Due to the very importance for both fundamental research and technological applications, smart materials with stimuli-responsive properties have been studied intensively. Theoretical investigation contributes to this endeavor through constructing and analyzing a model system which captures main features of the corresponding complex material, wherefrom useful insight can be provided to the trial-and-error experiments. We here report a theoretical study on the smart spherical nanoparticle grafted with light-responsive azobenzene-containing polymers. Utilizing the photoisomerization ability of the azobenzene group, nanoparticles can undergo a light-induced expansion-contraction transition. The wormlike chain based single chain in mean field theory, which has been developed by us recently, is used to investigate this transition in detail. Exploring a large parameter space, our results definitely determine the parameters, including the chain length and effective Kuhn length of grafted chain, nanoparticle radius, grafting density, and position of the azobenzene group along the chain contour, to admit optimum light-responsive behavior of the smart nanoparticle, which provides a guide for experimentalists to design this type of material in a rational manner.

  7. Combined immunomodulating effects of BCG and Lentinan after intranasal application in guinea pigs.

    PubMed

    Drandarska, Ivanka; Kussovski, Vesselin; Nikolaeva, Sascha; Markova, Nadya

    2005-04-01

    The ability of a Shiitake (Lentinus edodes) medical mushroom-derived bioactive polymer Lentinan (Ajinomoto, Japan) to modulate the immune response makes it a potential candidate for combination therapy with BCG, or as adjunct for BCG vaccination, especially in high-risk individuals. We studied the combined immune-potential effectiveness of intranasal application of Lentinan (at a dose of 1 mg/kg, three times at 2-day intervals), followed by administration of BCG (strain Sofia SL-222 at a dose of 1 x 10(8) CFU, once) in guinea pigs. Samples of broncho-alveolar lavage fluid, as well as tissue fragments of lungs, spleens and lymph nodes were obtained from four groups (combined treatment with Lentinan and BCG; only with Lentinan; only with BCG; control with saline) of animals at different intervals--1, 14 and 45 days after last treatment and were evaluated by several parameters (establishing the number, H2O2 and nitrite production, and killing ability against Mycobacterium tuberculosis and Staphylococcus aureus of alveolar macrophages; spleen index, BCG CFU in spleens and histomorphological observations). Our attention was focused both on local effects in lungs, and systematical effects in reticuloendothelial system. The results indicate that intranasal application of BCG alone, or in combination with Lentinan induced high level of alveolar macrophage activation. Pre-treatment with Lentinan enhanced the local immunohistological response to BCG in lung and reduced the generalized side effects.

  8. Thermoswitchable Janus Gold Nanoparticles with Stimuli-Responsive Hydrophilic Polymer Brushes.

    PubMed

    Niu, Xiaoqin; Ran, Fen; Chen, Limei; Lu, Gabriella Jia-En; Hu, Peiguang; Deming, Christopher P; Peng, Yi; Rojas-Andrade, Mauricio D; Chen, Shaowei

    2016-05-03

    Well-defined thermoswitchable Janus gold nanoparticles with stimuli-responsive hydrophilic polymer brushes were fabricated by combining ligand exchange reactions and the Langmuir technique. Stimuli-responsive polydi(ethylene glycol) methyl ether methacrylate was prepared by addition-fragmentation chain-transfer polymerization. The polymer brushes were then anchored onto the nanoparticle surface by interfacial ligand exchange reactions with hexanethiolate-protected gold nanoparticles, leading to the formation of a hydrophilic (polymer) hemisphere and a hydrophobic (hexanethiolate) one. The resulting Janus nanoparticles showed temperature-switchable wettability, hydrophobicity at high temperatures, and hydrophilicity at low temperatures, due to thermally induced conformational transition of the polymer ligands. The results further highlight the importance of interfacial engineering in the deliberate functionalization of nanoparticle materials.

  9. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

    PubMed Central

    Naggar, Heba M. El; Madkour, Mohamed Sayed; Hussein, Hussein Ali

    2017-01-01

    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. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles Montanide™ adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2) viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses. PMID:28344402

  10. Transition-Metal Decorated Aluminum Nanocrystals.

    PubMed

    Swearer, Dayne F; Leary, Rowan K; Newell, Ryan; Yazdi, Sadegh; Robatjazi, Hossein; Zhang, Yue; Renard, David; Nordlander, Peter; Midgley, Paul A; Halas, Naomi J; Ringe, Emilie

    2017-10-24

    Recently, aluminum has been established as an earth-abundant alternative to gold and silver for plasmonic applications. Particularly, aluminum nanocrystals have shown to be promising plasmonic photocatalysts, especially when coupled with catalytic metals or oxides into "antenna-reactor" heterostructures. Here, a simple polyol synthesis is presented as a flexible route to produce aluminum nanocrystals decorated with eight varieties of size-tunable transition-metal nanoparticle islands, many of which have precedence as heterogeneous catalysts. High-resolution and three-dimensional structural analysis using scanning transmission electron microscopy and electron tomography shows that abundant nanoparticle island decoration in the catalytically relevant few-nanometer size range can be achieved, with many islands spaced closely to their neighbors. When coupled with the Al nanocrystal plasmonic antenna, these small decorating islands will experience increased light absorption and strong hot-spot generation. This combination makes transition-metal decorated aluminum nanocrystals a promising material platform to develop plasmonic photocatalysis, surface-enhanced spectroscopies, and quantum plasmonics.

  11. Novel Polymeric Nanoparticles for Pulmonary Gene Delivery

    NASA Astrophysics Data System (ADS)

    Fields, Rachel Jennifer

    The lung is an important target for gene and drug therapy of many diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), tubuerculosis (TB) and lung cancer. In fact, the pulmonary route has been employed as a means of delivering drugs for centuries, dating back 4000 years to India where inhaled vapors were used for medicinal purpose. Currently, pulmonary administration of small, hydrophobic drugs leads to rapid local and systemic absorption. However, delivery of large biomacromolecules, such as therapeutic genes, has not yet been accomplished. Here, I test the hypothesis that a rationally engineered nanoparticle (NP) vector can improve delivery of large biomacromolecules. . In this dissertation I tested this hypothesis using a hybrid NP delivery system consisting of a blend of poly(lactic-co-glycolic acid) (PLGA) and a poly(beta-amino ester) (PBAE), a cationic polymer that is particularly useful for delivery of nucleic acids.. PBAE/PLGA nanoparticles (15% PBAE) loaded with plasmid DNA were surface modified with cell-penetrating peptides (CPPs) via a PEGylated phospholipid linker. This optimized NP formulation was able to induce substantial intracellular uptake and transfect lung epithelial cells in vitro while imparting minimal cellular toxicity. In order to determine the most effective method to deliver these NPs to the lung I used fluorescently labeled particles to study the biodistribution of particles after administration to the lung of mice via various administration routes. I determined that the intranasal route was most effective. I further investigated this route and determined that an average of 37.1 +/- 15.1 % of lung cells had NP association after 4hrs. I also investigated the association of particles with different lung cell types like macrophages and alveolar epithelial cells and determined that our best particle formulations associated with approximately 80% of both of these cell types. To demonstrate the ability of the

  12. Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans.

    PubMed

    Leppanen, Jenni; Ng, Kah Wee; Kim, Youl-Ri; Tchanturia, Kate; Treasure, Janet

    2018-01-01

    Heightened threat sensitivity is a transdiagnostic feature in several psychiatric disorders. The neuropeptide oxytocin has been shown to reduce fear related behaviours and facilitated fear extinction in animals. These findings have led to increasing interest to explore the effects of intranasal oxytocin on threat processing in humans. The review included 26 studies (N = 1173), nine of which included clinical populations (N = 234). The clinical groups included were people with borderline personality disorder (BPD), anorexia nervosa, bulimia nervosa, depression, anxiety, and alcohol dependence disorder. We examined the effects of a single dose of intranasal oxytocin on startle response, attentional responses, and behavioural responses to threat. A single dose of intranasal oxytocin significantly increased the physiological startle response to threat in healthy people with a small effect size. However, oxytocin did not have significant effects on attentional bias towards social or disorder-specific threat, fixation towards threatening stimuli among healthy or clinical populations, or on threat related behavioural approach or avoidance responses. No studies investigated the effects of oxytocin on the startle response to threat among clinical populations. Additionally, only one of the reviewed studies had sufficient power to detect at least a moderate effect of oxytocin according to our criterion. The synthesis of literature suggest that oxytocin may influence the salience of threatening stimuli among healthy individuals, increasing the startle response to threat. It would be of interest to investigate the effects of oxytocin on the startle response to threat among clinical populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Tunable-Porosity Membranes From Discrete Nanoparticles

    PubMed Central

    Marchetti, Patrizia; Mechelhoff, Martin; Livingston, Andrew G.

    2015-01-01

    Thin film composite membranes were prepared through a facile single-step wire-wound rod coating procedure in which internally crosslinked poly(styrene-co-butadiene) polymer nanoparticles self-assembled to form a thin film on a hydrophilic ultrafiltration support. This nanoparticle film provided a defect-free separation layer 130–150 nm thick, which was highly permeable and able to withstand aggressive pH conditions beyond the range of available commercial membranes. The nanoparticles were found to coalesce to form a rubbery film when heated above their glass transition temperature (Tg). The retention properties of the novel membrane were strongly affected by charge repulsion, due to the negative charge of the hydroxyl functionalized nanoparticles. Porosity was tuned by annealing the membranes at different temperatures, below and above the nanoparticle Tg. This enabled fabrication of membranes with varying performance. Nanofiltration properties were achieved with a molecular weight cut-off below 500 g mol−1 and a low fouling tendency. Interestingly, after annealing above Tg, memory of the interstitial spaces between the nanoparticles persisted. This memory led to significant water permeance, in marked contrast to the almost impermeable films cast from a solution of the same polymer. PMID:26626565

  14. Effect of superparamagnetic iron oxide nanoparticles on fluidity and phase transition of phosphatidylcholine liposomal membranes

    PubMed Central

    Santhosh, Poornima Budime; Drašler, Barbara; Drobne, Damjana; Kreft, Mateja Erdani; Kralj, Slavko; Makovec, Darko; Ulrih, Nataša Poklar

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) with multifunctional properties have shown great promise in theranostics. The aim of our work was to compare the effects of SPIONs on the fluidity and phase transition of the liposomal membranes prepared with zwitterionic phosphatidylcholine lipids. In order to study if the surface modification of SPIONs has any influence on these membrane properties, we have used four types of differently functionalized SPIONs, such as: plain SPIONs (primary size was shown to bê11 nm), silica-coated SPIONs, SPIONs coated with silica and functionalized with positively charged amino groups or negatively charged carboxyl groups (the primary size of all the surface-modified SPIONs was ~20 nm). Small unilamellar vesicles prepared with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipids and multilamellar vesicles prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine lipids were encapsulated or incubated with the plain and surface-modified SPIONs to determine the fluidity and phase transition temperature of the bilayer lipids, respectively. Fluorescent anisotropy and differential scanning calorimetric measurements of the liposomes that were either encapsulated or incubated with the suspension of SPIONs did not show a significant difference in the lipid ordering and fluidity; though the encapsulated SPIONs showed a slightly increased effect on the fluidity of the model membranes in comparison with the incubated SPIONs. This indicates the low potential of the SPIONs to interact with the nontargeted cell membranes, which is a desirable factor for in vivo applications. PMID:26491286

  15. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

    PubMed

    Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

    2015-07-14

    Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

  16. Safety update regarding intranasal corticosteroids for the treatment of allergic rhinitis.

    PubMed

    Blaiss, Michael S

    2011-01-01

    Intranasal corticosteroids (INSs) are the most efficacious medication for the treatment of allergic rhinitis. In 2006, the Joint Task Force of the American College of Allergy, Asthma, and Immunology, and the American Academy of Allergy, Asthma, and Immunology, published a white paper on the potential over-the-counter switch of INS (Bielory L, Blaiss M, Fineman SM, et al. Concerns about intranasal corticosteroids for over-the-counter use: Position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 96:514-525, 2006). The concern of the paper was the safety of the use of these agents without oversight by a health care professional. The objective of this paper was to review published literature on the safety of INS since the publication of the task force white paper. Recent studies, which evaluated topical and systemic adverse events associated with ciclesonide (CIC), fluticasone furoate (FF), mometasone furoate (MF), triamcinolone acetonide, fluticasone propionate, budesonide, and beclomethasone dipropionate were summarized. In general, no significant topical or systemic complications were observed in these studies, although none were >1 year in duration. The newer formulations of topical corticosteroids for allergic rhinitis, such as CIC, FF, and MF, which have less systemic bioavailability, may be safer for long-term use. New studies continue to add to the reassurance of the safety of INSs in the treatment of allergic rhinitis but still do not answer the question if these agents are appropriate for long-term use without oversight by a health care professional.

  17. Evolution from the plasmon to exciton state in ligand-protected atomically precise gold nanoparticles

    DOE PAGES

    Zhou, Meng; Zeng, Chenjie; Chen, Yuxiang; ...

    2016-10-24

    The evolution from the metallic (or plasmonic) to molecular state in metal nanoparticles constitutes a central question in nanoscience research because of its importance in revealing the origin of metallic bonding and offering fundamental insights into the birth of surface plasmon resonance. Previous research has not been able to probe the transition due to the unavailability of atomically precise nanoparticles in the 1–3 nm size regime. Herein, we investigate the transition by performing ultrafast spectroscopic studies on atomically precise thiolate-protected Au 25, Au 38, Au 144, Au 333, Au ~520 and Au ~940 nanoparticles. Our results clearly map out threemore » distinct states: metallic (size larger than Au333, that is, larger than 2.3 nm), transition regime (between Au 333 and Au 144, that is, 2.3–1.7 nm) and non-metallic or excitonic state (smaller than Au 144, that is, smaller than 1.7 nm). As a result, the transition also impacts the catalytic properties as demonstrated in both carbon monoxide oxidation and electrocatalytic oxidation of alcohol.« less

  18. Nanoparticles Stabilize Thin Polymer Films: A Fundamental Study to Understand the Phenomenon

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Michael E. Mackay

    2009-03-04

    A new understanding of thermodynamics at the nanoscale resulted in a recently discovered first order phase transition that nanoparticles in a polymer film will all segregate to the supporting substrate. This is an unusual phase transition that was predicted using a modeling technique developed at Sandia National Laboratories and required the equivalent of many computational years on one computer. This project is a collaboration between Prof. Michael Mackay's group and Dr. Amalie Frischknecht (Sandia National Laboratories) where experimental observation and theoretical rationalization and prediction are brought together. Other discoveries were that this phase transition could be avoided by changing themore » nanoparticle properties yielding control of the assembly process at the nanoscale. In fact, the nanoparticles could be made to assemble to the supporting substrate, to the air interface or not assemble at all within a thin polymer film of order 100 nm in thickness. However, when the assembly process is present it is so robust that it is possible to make rough liquid films at the nanoscale due to nanoparticles assembling around three-dimensional objects. From this knowledge we are able to design and manufacture new coatings with particular emphasis on polymer-based solar cells. Careful control of the morphology at the nanoscale is expected to provide more efficient devices since the physics of these systems is dictated at this length scale and assembly of nanoparticles to various interfaces is critical to operation.« less

  19. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    ERIC Educational Resources Information Center

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  20. Fabrication of Metallic Hollow Nanoparticles

    NASA Technical Reports Server (NTRS)

    Lillehei, Peter T. (Inventor); Chu, Sang-Hyon (Inventor); Park, Yeonjoon (Inventor); Kim, Jae-Woo (Inventor); Choi, Sr., Sang H. (Inventor); King, Glen C. (Inventor); Elliott, James R. (Inventor)

    2016-01-01

    Metal and semiconductor nanoshells, particularly transition metal nanoshells, are fabricated using dendrimer molecules. Metallic colloids, metallic ions or semiconductors are attached to amine groups on the dendrimer surface in stabilized solution for the surface seeding method and the surface seedless method, respectively. Subsequently, the process is repeated with additional metallic ions or semiconductor, a stabilizer, and NaBH.sub.4 to increase the wall thickness of the metallic or semiconductor lining on the dendrimer surface. Metallic or semiconductor ions are automatically reduced on the metallic or semiconductor nanoparticles causing the formation of hollow metallic or semiconductor nanoparticles. The void size of the formed hollow nanoparticles depends on the dendrimer generation. The thickness of the metallic or semiconductor thin film around the dendrimer depends on the repetition times and the size of initial metallic or semiconductor seeds.

  1. Chiromagnetic nanoparticles and gels

    NASA Astrophysics Data System (ADS)

    Yeom, Jihyeon; Santos, Uallisson S.; Chekini, Mahshid; Cha, Minjeong; de Moura, André F.; Kotov, Nicholas A.

    2018-01-01

    Chiral inorganic nanostructures have high circular dichroism, but real-time control of their optical activity has so far been achieved only by irreversible chemical changes. Field modulation is a far more desirable path to chiroptical devices. We hypothesized that magnetic field modulation can be attained for chiral nanostructures with large contributions of the magnetic transition dipole moments to polarization rotation. We found that dispersions and gels of paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices exhibited chiroptical activity in the visible range that was 10 times as strong as that of nonparamagnetic nanoparticles of comparable size. Transparency of the nanoparticle gels to circularly polarized light beams in the ultraviolet range was reversibly modulated by magnetic fields. These phenomena were also observed for other nanoscale metal oxides with lattice distortions from imprinted amino acids and other chiral ligands. The large family of chiral ceramic nanostructures and gels can be pivotal for new technologies and knowledge at the nexus of chirality and magnetism.

  2. Intranasal fluticasone associated with delayed tympanostomy tube placement in children with eustachian tube dysfunction.

    PubMed

    Crowson, Matthew G; Ryan, Marisa A; Ramprasad, Vaibhav H; Choi, Kevin J; Raynor, Eileen

    2017-03-01

    Pediatric patient caregivers may prefer to avoid a surgical intervention and request a medical management option for eustachian tube dysfunction (ETD). However, there are limited published data evaluating the efficacy of intranasal fluticasone in the medical management of ETD as an alternative to tympanostomy tube placement. The objectives of this study were to: 1) determine if intranasal fluticasone (INF) prevented tympanostomy tube placement in children with ETD, and 2) describe differences in patient response to INF related to cleft lip and/or palate (CLP) and Down syndrome. Case series with planned chart review at a Tertiary academic hospital. We reviewed pediatric patients treated with INF for ETD. Inclusion criteria included ETD, no prior intranasal or oral steroid therapy, and no prior tympanostomy tube placement. Outcomes included time-to- tympanostomy tube placement with or without INF and therapy compliance. Kaplan-Meier survival analyses with log-rank tests and Fisher's exact tests were used to examine outcome variables. 676 fulfilled inclusion criteria. 393 (58.7%) were male, and 355 (52.5%) Caucasian with mean age of 27.1 months old. 92 (13.6%) had CLP and 46 (6.8%) had Down Syndrome. 266 (39.4%) received INF, and 202 (88.2%) were compliant at their next visit. 474 (70.1%) had tympanostomy tubes placed. Children treated with INF were less likely to have tympanostomy tubes placed than children not treated (52.6% vs. 81.5%; p < 0.0001). Using survival analyses, INF use was associated with significantly longer mean time-to-tympanostomy tube than no INF use (199.4 vs. 133.7 days; p < 0.0001). INF did not reduce time-to-tympanostomy tube in patients with CLP (p = 0.05) or Down Syndrome (p = 0.27). INF significantly reduces the number of children requiring tympanostomy tube placement for ETD. The CLP and Down Syndrome anatomical variants may attenuate INF efficacy. Further in vivo characterization of INF action on eustachian tube tissues will help

  3. Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

    PubMed

    Alexander, David; Alexander, Keith; Valentino, Joseph

    2012-11-01

    Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Retrospective chart review. Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  4. Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

    NASA Technical Reports Server (NTRS)

    Lakshmi, Putcha; Singh, R. P.; Crady, V. A.; Derendorf, H.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  5. A novel device for delivery of intranasal particulate medication: a pilot study.

    PubMed

    Khalili, Sammy; Tkachenko, Natalia; Rotenberg, Brian

    2013-11-01

    Intranasal medication delivery for allergic rhinitis (AR) is considered a mainstay of therapy but is hampered by poor compliance. Among reasons given are unpleasant sensations associated with spray penetration into the pharynx. Our objective was to study a novel method of particle delivery to the nose that would abrogate these issues. This was a double-blind, randomized study. Subjects who met study criteria underwent intranasal particle delivery using a novel device (Trivair Nasal Deposition System; Trimel Pharmaceuticals, Toronto, Canada) that delivered anhydrous lactose particles into the nose via a transoral air puff (thus elevating soft palate and blocking the nasopharynx). Subjects had nostrils randomized into 4 groups (particle sizes 5 μm and 50 μm × doses 12.5 mg and 25 mg). Particle deposition was assessed at 1 minute, 10 minutes, and 30 minutes on the inferior turbinate, middle turbinate, and nasopharynx, respectively, using high-definition endoscopic photography. Each image was compared using an expert blinded 2-person panel for percentage particles remaining. Nonparametric data was assessed using the Wilcoxon signed-rank test via Strata software. Twelve nostrils in total met study criteria. The results showed no difference in effectiveness of nasal particle retention between the groups based on particle size or dose. No particles entered the nasopharynx or oropharynx. This study provides proof-of-principle data that the Trivair Nasal Deposition System is effective at retaining medication in the nose without pharyngeal penetration. Larger studies on this device are warranted. © 2013 ARS-AAOA, LLC.

  6. Effect of Cr-N codoping on structural phase transition, Raman modes, and optical properties of TiO2 nanoparticles

    NASA Astrophysics Data System (ADS)

    Hassnain Jaffari, G.; Tahir, Adnan; Ali, Naveed Zafar; Ali, Awais; Qurashi, Umar S.

    2018-04-01

    Noncompensated cation-anion codoping in TiO2 nanoparticles has been achieved by a chemical synthesis route. Significant reduction in the optical bandgap and enhancement in the absorption of visible light have been observed. Structural phase transformation has been tracked in detail as a function of doping and heat treatment temperature. Anatase to rutile phase transition temperature for doped samples was higher in comparison to the pure TiO2 nanoparticles. Nitrogen and chromium addition increases the phase transformation barrier, where the effect of the former dopant is of more significance. The Raman results showed an increase in the oxygen content with higher post annealing temperatures. With Cr incorporation, the peak associated with the Eg mode has been found to shift towards a higher wave number, while with nitrogen incorporation, the shift was towards a lower wave number. A decrease in reflectance with N co-doping for all samples, irrespective of phase and annealing temperatures, has been observed. In compositions with nitrogen of the same content, bandgap reduction was higher in the rutile phase in comparison to the anatase phase. In general, overall results revealed that with a higher loading fraction of ammonia, the N content increases, while Cr addition prevents nitrogen loss even up to high post annealing temperatures, i.e., 850 °C.

  7. Surface and exchange-bias effects in compacted CaMnO3-δ nanoparticles

    NASA Astrophysics Data System (ADS)

    Markovich, V.; Fita, I.; Wisniewski, A.; Puzniak, R.; Mogilyansky, D.; Titelman, L.; Vradman, L.; Herskowitz, M.; Gorodetsky, G.

    2008-02-01

    Magnetic properties of compacted 50nm CaMnO3-δ (CMO) nanoparticles have been investigated. Measurements of ac-susceptibility exhibit upon cooling two magnetic transitions at Ttilde 270K accompanied by a small spontaneous magnetic moment and a para-antiferromagnetic (AFM) transition at TN˜120K , observed previously in bulk CMO. Asymmetric magnetization hysteresis loops observed in applied magnetic fields H≤90kOe are attributed to an exchange coupling between the antiferromagnetic core and the ferromagnetic (FM) shell of the CMO nanoparticles. This work provides the observation of exchange bias effect in manganite nanoparticles with inverted AFM-core-FM-shell structure, as compared to the typical FM-core-AFM-shell. Effects of surface and exchange anisotropy are also discussed.

  8. Comparison of subcutaneous versus intranasal immunization of male koalas (Phascolarctos cinereus) for induction of mucosal and systemic immunity against Chlamydia pecorum.

    PubMed

    Waugh, Courtney A; Timms, Peter; Andrew, Dean; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Beagley, Kenneth W

    2015-02-11

    Chlamydia pecorum infections are debilitating in the koala, contributing significantly to morbidity and mortality, with current antibiotic treatments having minimal success and adversely affecting gut microflora. This, combined with the sometimes-asymptomatic nature of the infection, suggests that an efficacious anti-chlamydial vaccine is required to control chlamydial infections in the koala. To date vaccination studies have focused primarily on female koalas, however, given the physiological differences between male and female reproductive tracts, we tested the efficacy of a vaccine in 12 captive male koalas. We evaluated the potential of both subcutaneous and intranasal vaccine delivery to elicit mucosal immunity in male koalas. Our results showed that both intranasal and subcutaneous delivery of a vaccine consisting of C. pecorum major outer membrane protein (MOMP) and the adjuvant immunostimulating complex (ISC) induced significant immune responses in male koalas. Subcutaneous immunization elicited stronger cell-mediated responses in peripheral blood lymphocytes (PBL), and greater plasma antibody levels whereas the intranasal immunization elicited stronger humoral responses in urogenital tract (UGT) secretions. This is the first time a Chlamydia vaccine has been tested in the male koala and the first assessment of a mucosal vaccination route in this species. Our results suggest that vaccination of male koalas can elicit mucosal immunity and could contribute to the long-term survivability of wild populations of the koala. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Intranasal pericytic tumors (glomus tumor and sinonasal hemangiopericytoma-like tumor): report of two cases with review of the literature.

    PubMed

    Li, Xiao-Qiu; Hisaoka, Masanori; Morio, Takashi; Hashimoto, Hiroshi

    2003-05-01

    An intranasal glomus tumor and a sinonasal hemangiopericytoma-like tumor are reported. Both patients were elderly women suffering from nasal bleeding, and presented with a polypoid mass arising in the nasal septum. Microscopically, the glomus tumor displayed a proliferation of uniform rounded or cuboidal epithelioid cells arranged in sheets and interrupted by a rich vasculature with a characteristic configuration mimicking the normal glomus bodies, while the sinonasal hemangiopericytoma-like tumor featured a perivascular proliferation of spindle- to oval-shaped cells that were arranged in short fascicles. Both tumors shared immunohistochemical features supporting their myoid differentiation by the expression of vimentin, alpha-smooth muscle actin and muscle-specific actin, albeit with no immunoreaction to desmin. Both the intranasal glomus tumor and sinonasal hemangiopericytoma-like tumor are characterized by a perivascular growth pattern and myoid differentiation, having a close relation to the 'perivascular myomas', which was recently designated.

  10. Comparative study on the physical properties of transition metal-doped (Co, Ni, Fe, and Mn) ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Azab, A. A.; Ateia, Ebtesam E.; Esmail, S. A.

    2018-07-01

    Nano-crystalline of TM-doped ZnO with general formula Zn0.97TM0.03O (TM: Mn, Fe, Co, and Ni) was prepared using sol-gel method. The dependence of crystal structure, morphology, and optical and magnetic properties on the type of transition metals was investigated. The XRD investigation of pure and TM-doped ZnO nanoparticles samples confirms the formation of single-phase hexagonal wurtzite structure. The estimated crystallite sizes are found in the range of 17 and 38 nm for the doped and pure samples, respectively. The obtained data suggest that the dopant type plays a vital role in the physical properties of the investigated samples. The optical band-gap energy Eg has been calculated from near infrared (NIR) and visible (VIS) reflectance spectra using the Kubelka-Munk function. Minimum value of 2.398 eV and maximum one of 3.29 eV were obtained for Manganese-doped ZnO and pure ZnO, respectively. The analysis of XRD and VSM of the samples confirms that the observed room-temperature (RT) ferromagnetism can be attributed to an intrinsic property of doped material sample and not due to formation of any secondary phase. The magnetic results show that Mn is the most effective dopant for producing ferromagnetism in nanoparticles of ZnO.

  11. Effects of intranasal administration of epitalon on neuron activity in the rat neocortex.

    PubMed

    Sibarov, D A; Vol'nova, A B; Frolov, D S; Nozdrachev, A D

    2007-11-01

    This report discusses the properties of the synthetic tetrapeptide epitalon (Ala-Glu-Asp-Gly), synthesized on the basis of an epiphyseal peptide extract. Intranasal administration of epitalon was selected as a noninvasive means of applying the agent to the CNS by bypassing the blood-brain barrier. The aim of the present work was to assess the characteristics of the action of epitalon on the frequency of spontaneous neuron activity in the cerebral cortex of white rats. Studies were performed using male Wistar rats anesthetized with urethane (1 g/kg). Extracellular activity of cortical neurons was recorded with a glass microelectrode of resistance 1-2 MOmega. Recording of spontaneous neuron discharges for 10-15 min was followed by intranasal administration of epitalon solution and recording of neuron activity to 30 min after doses of 30 ng per animal. Significant activation of neuron activity was seen several minutes after dosage, with an increase (by factors of 2-2.5) in discharge frequency. In some experiments, the effect of epitalon was multiphasic. The first peak of increased neuron discharge frequency at 5-7 min was followed by peaks at 11-12 and 17-18 min. The increase in discharge frequency occurred because of an increase in the discharge frequency of neurons which were already active and the recruitment of previously silent neurons. At least the first peak of increased neuron activity following exposure to epitalon was found to be associated with the direct action of the peptide on cortical cells.

  12. Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome.

    PubMed

    Hall, Scott S; Lightbody, Amy A; McCarthy, Brigid E; Parker, Karen J; Reiss, Allan L

    2012-04-01

    Fragile X syndrome (FXS) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms. Individuals with FXS, males in particular, often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations. We investigated whether oxytocin (OT), a hormone with prosocial and anxiolytic effects, could alleviate symptoms of social anxiety in this population. A randomized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo, 24 IU OT and 48 IU OT. Measures of eye gaze frequency, heart rate, respiratory sinus arrhythmia (RSA), heart rate variability (HRV) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration. Ten low-functioning males with FXS (aged 13-28 years) traveled to Stanford for the initial visit: 8 completed the study. Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose. There was no effect of OT on heart rate, RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others. These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS. Further double-blind placebo-controlled studies of OT, conducted in combination with behavioral treatment programs, may be warranted. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Nanoparticles in alumina: Microscopy and Theory

    NASA Astrophysics Data System (ADS)

    Idrobo, Juan C.; Halabica, Andrej; Rashkeev, Sergey; Glazoff, Michael V.; Boatner, Lynn A.; Haglund, Richard F.; Pennycook, Stephen. J.; Pantelides, Sokrates T.

    2007-03-01

    Transition-metal nanoparticles formed by ion implantation in alumina can be used to modify the optical properties of naturally oxidized and anodized aluminum. Here, we report atomic-resolution Z-contrast images using a scanning transmission electron microscope (STEM) of CoFe and other metal nanoparticles in alumina. We also report electron energy loss spectra (EELS) and relate them to visual appearance and optical properties. Finally, we report first-principles density- functional calculations of nucleation mechanisms for these nanoparticles. This research was sponsored by the Office of Basic Energy Sciences, Division of Materials Sciences and Engineering, U.S. Department of Energy, under contract DE-AC05- 00OR22725 with Oak Ridge National Laboratory, managed and operated by UT-Battelle, by NSF grant No. DMR-0513048, and by Alcoa Inc.

  14. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment

    PubMed Central

    Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

    2015-01-01

    Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

  15. Nanoparticle formation after nanosecond-laser irradiation of thin gold films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ratautas, Karolis; Gedvilas, Mindaugas; Raciukaitis, Gediminas

    2012-07-01

    Evolution in nanoparticle formation was observed after nanosecond-laser irradiation of thin gold films on a silicon substrate and physical phenomena leading to the formation of nanoparticles were studied. Gold films of different thickness (3, 5, 10, 15, 20, and 25 nm) were evaporated on the silicon (110) substrate and irradiated with the pulsed nanosecond laser using different pulse energies and the number of pulses in a burst. Experimentally morphological changes appeared in the films only when the pulse energy was high enough to initiate the phase transition. The threshold energy density for phase transitions in the films was estimated frommore » the thermal model of the laser beam and sample interaction. With the pulse energy just above the threshold, it was possible to observe evolution of nanoparticle formation from a plane metal film by changing the number of pulses applied, as duration of the pulse burst represented the time how long the liquid phase existed. The final size of nanoparticles was a function of the film thickness and was found to be independent of the pulse energy and the number of pulses.« less

  16. Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice

    PubMed Central

    Bell, Genevieve A.; Fadool, Debra Ann

    2017-01-01

    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. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5 μg/μl of insulin twice daily for 30 and 60 days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice performed no different from controls regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3X increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR Kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors – as reported to

  17. Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.

    PubMed

    Bell, Genevieve A; Fadool, Debra Ann

    2017-05-15

    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. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to

  18. Phase stability and dynamics of entangled polymer-nanoparticle composites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mangal, Rahul; Srivastava, Samanvaya; Archer, Lynden A.

    Nanoparticle–polymer composites, or polymer–nanoparticle composites (PNCs), exhibit unusual mechanical and dynamical features when the particle size approaches the random coil dimensions of the host polymer. Here, we harness favourable enthalpic interactions between particle-tethered and free, host polymer chains to create model PNCs, in which spherical nanoparticles are uniformly dispersed in high molecular weight entangled polymers. Investigation of the mechanical properties of these model PNCs reveals that the nanoparticles have profound effects on the host polymer motions on all timescales. On short timescales, nanoparticles slow-down local dynamics of the host polymer segments and lower the glass transition temperature. On intermediate timescales,more » where polymer chain motion is typically constrained by entanglements with surrounding molecules, nanoparticles provide additional constraints, which lead to an early onset of entangled polymer dynamics. Finally, on long timescales, nanoparticles produce an apparent speeding up of relaxation of their polymer host.« less

  19. Revealing nanoparticle assembly under high pressure.

    NASA Astrophysics Data System (ADS)

    Fan, Hongyou

    Precise control of structural parameters through nanoscale engineering to improve optical and electronic properties of functional nanoparticles continuously remains an outstanding challenge. Previous work on nanoparticle assembly has been conducted largely at ambient pressure. Here I will present a new Stress-Induced Fabrication method in which we applied high pressure or stress to nanoparticle arrays to induce structural phase transition and to consolidate new nanomaterials with precisely controlled structures and tunable properties. By manipulating nanoparticle coupling through external pressure, a reversible change in their assemblies and properties can be achieved and demonstrated. In addition, over a certain threshold, the external pressure will force these nanoparticles into contact, thereby allowing the formation and consolidation of one- to three-dimensional nanostructures. Through stress induced nanoparticle assembly, materials engineering and synthesis become remarkably flexible without relying on traditional crystallization process where atoms/ions are locked in a specific crystal structure. Therefore, morphology or architecture can be readily tuned to produce desirable properties for practical applications. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  20. Simulation study of depositing the carbon film on nanoparticles in the magnetized methane plasma

    NASA Astrophysics Data System (ADS)

    Mohammadzadeh, Hosein; Pourali, Nima; Ebadi, Zahra

    2018-03-01

    Plasma coating of nanoparticles in low-temperature magnetized methane plasma is studied by a simulation approach. To this end, by using the global model, the electron temperature and concentration of different species considered in this plasma are determined in the center of a capacitively coupled discharge. Then, the plasma-wall transition region in the presence of an oblique magnetic field is simulated by the multi-component fluid description. Nanoparticles with different radii are injected into the transition region and surface deposition and heating models, as well as dynamics and charging models, are employed to examine the coating process. The results of the simulation show that the non-spherical growth of nanoparticles is affected by the presence of the magnetic field, as with passing time, an oscillating increase is seen in the thickness of the film deposited on nanoparticles. Also, it is shown that the uniformity of the deposited film is dependent on the rotation velocity of nanoparticles. Generally, the obtained results imply that the sphericity of nanoparticles and uniformity of the film coated on them are controllable by the magnitude and orientation of the magnetic field.

  1. Effects of Intranasal Oxytocin on Long-Term Memory in Healthy Humans: A Systematic Review.

    PubMed

    Brambilla, Michela; Manenti, Rosa; de Girolamo, Giovanni; Adenzato, Mauro; Bocchio-Chiavetto, Luisella; Cotelli, Maria

    2016-12-01

    Preclinical Research The neuropeptide oxytocin (Oxt) is implicated in complex emotional and social behaviors and appears to play an important role in learning and memory. Animal studies have shown that the effects of exogenous Oxt on memory vary according to the timing of administration, context, gender, and dose and may improve the memory of social, but not nonsocial stimuli. Oxt is intimately involved in a broad array of neuropsychiatric functions and may therefore be a pharmacological target for several psychiatric disorders. This review summarizes the potential effects of Oxt on long-term memory processes in healthy humans based on a PubMed search over the period 1980-2016. The effects of intranasal Oxt on human memory are controversial and the studies included in this review have applied a variety of learning paradigms, in turn producing variable outcomes. Specifically, data on the long-term memory of nonemotional stimuli found no effect or even worsening in memory, while studies using emotional stimuli showed an improvement of long-term memory performance. In conclusion, this review identified a link between long-term memory performance and exogenous intranasal Oxt in humans, although these results still warrant further confirmation in large, multicenter randomized controlled trials. Drug Dev Res 77 : 479-488, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

    PubMed

    Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2013-01-01

    There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

  3. Dynamics and yielding of binary self-suspended nanoparticle fluids

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Agrawal, Akanksha; Yu, Hsiu-Yu; Srivastava, Samanvaya

    Yielding and flow transitions in bi-disperse suspensions of particles are studied using a model system comprised of self-suspended spherical nanoparticles. An important feature of the materials is that the nanoparticles are uniformly dispersed in the absence of a solvent. Addition of larger particles to a suspension of smaller ones is found to soften the suspensions, and in the limit of large size disparities, completely fluidizes the material. We show that these behaviors coincide with a speeding-up of de-correlation dynamics of all particles in the suspensions and are accompanied by a reduction in the energy dissipated at the yielding transition. Wemore » discuss our findings in terms of ligand-mediated jamming and un-jamming of hairy particle suspensions.« less

  4. Synthesis of new liquid crystals embedded gold nanoparticles for photoswitching properties.

    PubMed

    Rahman, Md Lutfor; Biswas, Tapan Kumar; Sarkar, Shaheen M; Yusoff, Mashitah Mohd; Yuvaraj, A R; Kumar, Sandeep

    2016-09-15

    A new series of liquid crystals decorated gold nanoparticles is synthesized whose molecular architecture has azobenzenes moieties as the peripheral units connected to gold nanoparticles (Au NPs) via alkyl groups. The morphology and mesomorphic properties were investigated by field emission scanning electron microscope, high-resolution transmission electron microscopy, differential scanning calorimetry and polarizing optical microscopy. The thiolated ligand molecules (3a-c) showed enantiotropic smectic A phase, whereas gold nanoparticles (5a-c) exhibit nematic and smectic A phase with monotropic nature. HR-TEM measurement showed that the functionalized Au NPs are of the average size of 2nm and they are well dispersed without any aggregation. The trans-form of azo compounds showed a strong band in the UV region at ∼378nm for the π-π(∗) transition, and a weak band in the visible region at ∼472nm due to the n-π(∗) transition. These molecules exhibit attractive photoisomerization behaviour in which trans-cis transition takes about 15s whereas the cis-trans transition requires about 45min for compound 5c. The extent of reversible isomerization did not decay after 10 cycles, which proved that the photo-responsive properties of 5c were stable and repeatable. Therefore, these materials may be suitably exploited in the field of molecular switches and the optical storage devices. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Standards and Methodologies for Characterizing Radiobiological Impact of High-Z Nanoparticles

    PubMed Central

    Subiel, Anna; Ashmore, Reece; Schettino, Giuseppe

    2016-01-01

    Research on the application of high-Z nanoparticles (NPs) in cancer treatment and diagnosis has recently been the subject of growing interest, with much promise being shown with regards to a potential transition into clinical practice. In spite of numerous publications related to the development and application of nanoparticles for use with ionizing radiation, the literature is lacking coherent and systematic experimental approaches to fully evaluate the radiobiological effectiveness of NPs, validate mechanistic models and allow direct comparison of the studies undertaken by various research groups. The lack of standards and established methodology is commonly recognised as a major obstacle for the transition of innovative research ideas into clinical practice. This review provides a comprehensive overview of radiobiological techniques and quantification methods used in in vitro studies on high-Z nanoparticles and aims to provide recommendations for future standardization for NP-mediated radiation research. PMID:27446499

  6. Supramolecular domains in mixed peptide self-assembled monolayers on gold nanoparticles.

    PubMed

    Duchesne, Laurence; Wells, Geoff; Fernig, David G; Harris, Sarah A; Lévy, Raphaël

    2008-09-01

    Self-organization in mixed self-assembled monolayers of small molecules provides a route towards nanoparticles with complex molecular structures. Inspired by structural biology, a strategy based on chemical cross-linking is introduced to probe proximity between functional peptides embedded in a mixed self-assembled monolayer at the surface of a nanoparticle. The physical basis of the proximity measurement is a transition from intramolecular to intermolecular cross-linking as the functional peptides get closer. Experimental investigations of a binary peptide self-assembled monolayer show that this transition happens at an extremely low molar ratio of the functional versus matrix peptide. Molecular dynamics simulations of the peptide self-assembled monolayer are used to calculate the volume explored by the reactive groups. Comparison of the experimental results with a probabilistic model demonstrates that the peptides are not randomly distributed at the surface of the nanoparticle, but rather self-organize into supramolecular domains.

  7. Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine.

    PubMed

    Kaube, H; Herzog, J; Käufer, T; Dichgans, M; Diener, H C

    2000-07-12

    Migraine aura is probably caused by cortical-spreading depression. No treatment for acute and severe migraine aura has been described previously. The effect of ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling auras resulting from familial hemiplegic migraine. In five patients ketamine reproducibly reduced the severity and duration of the neurologic deficits, whereas in the remaining six patients no beneficial effect was seen. Ketamine offers, for the first time, a possible treatment option for severe and prolonged aura.

  8. Direct synthesis of ultrafine tetragonal BaTiO3 nanoparticles at room temperature

    PubMed Central

    2011-01-01

    A large quantity of ultrafine tetragonal barium titanate (BaTiO3) nanoparticles is directly synthesized at room temperature. The crystalline form and grain size are checked by both X-ray diffraction and transmission electron microscopy. The results revealed that the perovskite nanoparticles as fine as 7 nm have been synthesized. The phase transition of the as-prepared nanoparticles is investigated by the temperature-dependent Raman spectrum and shows the similar tendency to that of bulk BaTiO3 materials. It is confirmed that the nanoparticles have tetragonal phase at room temperature. PMID:21781339

  9. In-situ high-pressure x-ray diffraction study of zinc ferrite nanoparticles

    DOE PAGES

    Ferrari, S.; Kumar, R. S.; Grinblat, F.; ...

    2016-04-23

    We have studied the high-pressure structural behavior of zinc ferrite (ZnFe 2O 4) nanoparticles by powder X-ray diffraction measurements up to 47 GPa. We found that the cubic spinel structure of ZnFe 2O 4 remains up to 33 GPa and a phase transition is induced beyond this pressure. The high-pressure phase is indexed to an orthorhombic CaMn 2O 4-type structure. Upon decompression the low- and high-pressure phases coexist. The compressibility of both structures was also investigated. We have observed that the lattice parameters of the high-pressure phase behave anisotropically upon compression. Further, we predict possible phase transition around 55 GPa.more » For comparison, we also studied the compression behavior of magnetite (Fe 3O 4) nanoparticles by X-ray diffraction up to 23 GPa. Spinel-type ZnFe 2O 4 and Fe 3O 4 nanoparticles have a bulk modulus of 172 (20) GPa and 152 (9) GPa, respectively. Lastly, this indicates that in both cases the nanoparticles do not undergo a Hall-Petch strengthening.« less

  10. In-situ high-pressure x-ray diffraction study of zinc ferrite nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ferrari, S.; Kumar, R. S.; Grinblat, F.

    We have studied the high-pressure structural behavior of zinc ferrite (ZnFe 2O 4) nanoparticles by powder X-ray diffraction measurements up to 47 GPa. We found that the cubic spinel structure of ZnFe 2O 4 remains up to 33 GPa and a phase transition is induced beyond this pressure. The high-pressure phase is indexed to an orthorhombic CaMn 2O 4-type structure. Upon decompression the low- and high-pressure phases coexist. The compressibility of both structures was also investigated. We have observed that the lattice parameters of the high-pressure phase behave anisotropically upon compression. Further, we predict possible phase transition around 55 GPa.more » For comparison, we also studied the compression behavior of magnetite (Fe 3O 4) nanoparticles by X-ray diffraction up to 23 GPa. Spinel-type ZnFe 2O 4 and Fe 3O 4 nanoparticles have a bulk modulus of 172 (20) GPa and 152 (9) GPa, respectively. Lastly, this indicates that in both cases the nanoparticles do not undergo a Hall-Petch strengthening.« less

  11. Intranasal Introduction of Fc-Fused Interleukin-7 Provides Long-Lasting Prophylaxis against Lethal Influenza Virus Infection.

    PubMed

    Kang, Moon Cheol; Choi, Dong-Hoon; Choi, Young Woo; Park, Seong Jeong; Namkoong, Hong; Park, Ki Seok; Ahn, So-Shin; Surh, Charles D; Yoon, Sun-Woo; Kim, Doo-Jin; Choi, Jung-ah; Park, Yunji; Sung, Young Chul; Lee, Seung-Woo

    2015-12-09

    Influenza A virus (IAV) infection frequently causes hospitalization and mortality due to severe immunopathology. Annual vaccination and antiviral drugs are the current countermeasures against IAV infection, but they have a limited efficacy against new IAV variants. Here, we show that intranasal pretreatment with Fc-fused interleukin-7 (IL-7-mFc) protects mice from lethal IAV infections. The protective activity of IL-7-mFc relies on transcytosis via neonatal Fc receptor (FcRn) in the lung and lasts for several weeks. Introduction of IL-7-mFc alters pulmonary immune environments, leading to recruitment of T cells from circulation and their subsequent residency as tissue-resident memory-like T (TRM-like) cells. IL-7-mFc-primed pulmonary TRM-like cells contribute to protection upon IAV infection by dual modes. First, TRM-like cells, although not antigen specific but polyclonal, attenuate viral replication at the early phase of IAV infection. Second, TRM-like cells augment expansion of IAV-specific cytotoxic T lymphocytes (CTLs), in particular at the late phase of infection, which directly control viruses. Thus, accelerated viral clearance facilitated by pulmonary T cells, which are either antigen specific or not, alleviates immunopathology in the lung and mortality from IAV infection. Depleting a subset of pulmonary T cells indicates that both CD4 and CD8 T cells contribute to protection from IAV, although IL-7-primed CD4 T cells have a more prominent role. Collectively, we propose intranasal IL-7-mFc pretreatment as an effective means for generating protective immunity against IAV infections, which could be applied to a potential prophylaxis for influenza pandemics in the future. The major consequence of a highly pathogenic IAV infection is severe pulmonary inflammation, which can result in organ failure and death at worst. Although vaccines for seasonal IAVs are effective, frequent variation of surface viral proteins hampers development of protective immunity. In

  12. Tunneling mechanism and contact mechanics of colloidal nanoparticle assemblies.

    PubMed

    Biaye, Moussa; Zbydniewska, Ewa; Mélin, Thierry; Deresmes, Dominique; Copie, Guillaume; Cleri, Fabrizio; Sangeetha, Neralagatta; Decorde, Nicolas; Viallet, Benoit; Grisolia, Jérémie; Ressier, Laurence; Diesinger, Heinrich

    2016-11-25

    Nanoparticle assemblies with thiol-terminated alkyl chains are studied by conducting atomic force microscopy (c-AFM) regarding their use as strain gauges for touch-sensitive panels. Current-force spectroscopy is used as a characterization tool complementary to the macroscopic setup since it allows a bias to be applied to a limited number of junctions, overcoming the Coulomb blockade energy and focusing on the contact electromechanics and the transport mechanism across the ligand. First, transition voltage spectroscopy is applied with varying force to target the underlying tunneling mechanism by observing whether the transition between the ohmic and exponential current-voltage behavior is force-dependent. Secondly, current-force spectroscopy in the ohmic range below the transition voltage is performed. The current-force behavior of the AFM probe in contact with a nanoparticle multilayer is associated with the spread of force and current within the nanoparticle lattice and at the level of adjacent particles by detailed contact mechanics treatment. The result is twofold: concerning the architecture of sensors, this work is a sample case of contact electromechanics at scales ranging from the device scale down to the individual ligand molecule. Regarding transport across the molecule, the vacuum tunneling mechanism is favored over the conduction by coherent molecular states, which is a decision-making aid for the choice of ligand in applications.

  13. Stimulus-Responsive Nanoparticles and Associated (Reversible) Polymorphism via Polymerization Induced Self-assembly (PISA).

    PubMed

    Pei, Yiwen; Lowe, Andrew B; Roth, Peter J

    2017-01-01

    Polymerization-induced self-assembly (PISA) is an extremely versatile method for the in situ preparation of soft-matter nanoparticles of defined size and morphologies at high concentrations, suitable for large-scale production. Recently, certain PISA-prepared nanoparticles have been shown to exhibit reversible polymorphism ("shape-shifting"), typically between micellar, worm-like, and vesicular phases (order-order transitions), in response to external stimuli including temperature, pH, electrolytes, and chemical modification. This review summarises the literature to date and describes molecular requirements for the design of stimulus-responsive nano-objects. Reversible pH-responsive behavior is rationalised in terms of increased solvation of reversibly ionized groups. Temperature-triggered order-order transitions, conversely, do not rely on inherently thermo-responsive polymers, but are explained based on interfacial LCST or UCST behavior that affects the volume fractions of the core and stabilizer blocks. Irreversible morphology transitions, on the other hand, can result from chemical post-modification of reactive PISA-made particles. Emerging applications and future research directions of this "smart" nanoparticle behavior are reviewed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Observation of relaxor ferroelectricity and multiferroic behaviour in nanoparticles of the ferromagnetic semiconductor La2NiMnO6

    NASA Astrophysics Data System (ADS)

    Masud, Md G.; Ghosh, Arijit; Sannigrahi, J.; Chaudhuri, B. K.

    2012-07-01

    We report a diffuse phase transition (extending over a finite temperature range of ˜50 K) in sol-gel derived nanoparticles (˜25 nm) of the ferromagnetic double perovskite La2NiMnO6. The macroscopic polarization (P-E hysteresis loop), validity of the Vogel-Fulcher relation and high dielectric permittivity (˜9 × 102) confirm relaxor ferroelectric phenomena in these magnetic nanoparticles. Compared to the corresponding bulk sample, appreciably large enhancement of the magnetocapacitive effect (MC ˜ 30%) is observed even under low magnetic field (0.5 T) around the broad relaxor dielectric peak temperature (˜220 K), which is close to the ferromagnetic transition temperature (θf ˜ 196 K). All of these features establish the multiferroic character of the La2NiMnO6 nanoparticles. The inhomogeneities arising from chemical and valence mixing in the present La2NiMnO6 nanoparticles and the inter-site, Ni/Mn-site disorder along with surface disorder of the individual nanoparticles resulting in local polar regions are attributed to the observed dielectric behaviour of the nanoparticles. The wave vector dependent spin-pair correlation is considered to be the plausible cause of the colossal magnetocapacitive response near the transition temperature. High permittivity and large magnetocapacitive properties make these ferromagnetic La2NiMnO6 nanoparticles technologically important.

  15. Intranasal Hydrocodone-Acetaminophen Abuse Induced Necrosis of the Nasal Cavity and Pharynx

    PubMed Central

    Alexander, David; Alexander, Keith; Valentino, Joseph

    2012-01-01

    Objectives Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid trans mucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Study Design Retrospective chart review. Methods Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. Results The majority of patients will initially deny the behavior frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented with one resulting in death. Conclusions The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue that can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Study Design Chart review, level of evidence: 4 PMID:22965281

  16. Intranasal corticosteroids topical characteristics: side effects, formulation, and volume.

    PubMed

    Petty, David A; Blaiss, Michael S

    2013-01-01

    Guidelines from throughout the world recommend intranasal corticosteroids (INSs) as first-line treatment for most patients with moderate to severe allergic rhinitis. In general, limited comparative studies between different INSs have not indicated that one particular steroid moiety is more effective than another in controlling symptoms of allergic rhinitis. However, there are numerous formulations available with different ingredients that may influence a patient's adherence to treatment. This article looks at topical features with these agents, specifically, formulations, vehicles (aqueous vs aerosol), and side effects such as epistaxis and nasal septal perforation. Topical side effects are minimal with INSs with the exception of epistaxis. There are major differences in formulations, volumes, and vehicles between INSs, which could affect adherence. Physicians need to be aware of the different INS attributes to try to match patients' preferences in order to achieve better adherence and improve outcomes in sufferers of allergic rhinitis.

  17. Size-dependent phase diagrams of metallic alloys: A Monte Carlo simulation study on order–disorder transitions in Pt–Rh nanoparticles

    PubMed Central

    Stahl, Christian; Albe, Karsten

    2012-01-01

    Summary Nanoparticles of Pt–Rh were studied by means of lattice-based Monte Carlo simulations with respect to the stability of ordered D022- and 40-phases as a function of particle size and composition. By thermodynamic integration in the semi-grand canonical ensemble, phase diagrams for particles with a diameter of 7.8 nm, 4.3 nm and 3.1 nm were obtained. Size-dependent trends such as the lowering of the critical ordering temperature, the broadening of the compositional stability range of the ordered phases, and the narrowing of the two-phase regions were observed and discussed in the context of complete size-dependent nanoparticle phase diagrams. In addition, an ordered surface phase emerges at low temperatures and low platinum concentration. A decrease of platinum surface segregation with increasing global platinum concentration was observed, when a second, ordered phase is formed inside the core of the particle. The order–disorder transitions were analyzed in terms of the Warren–Cowley short-range order parameters. Concentration-averaged short-range order parameters were used to remove the surface segregation bias of the conventional short-range order parameters. Using this procedure, it was shown that the short-range order in the particles at high temperatures is bulk-like. PMID:22428091

  18. Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions.

    PubMed

    Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K

    2015-07-01

    Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

  19. Comparison of temperature sensing of the luminescent upconversion and ZnCdS nanoparticles

    NASA Astrophysics Data System (ADS)

    Yanina, I. Yu.; Volkova, E. K.; Sagaidachnaya, E. A.; Konyukhova, J. G.; Kochubey, V. I.; Tuchin, V. V.

    2018-02-01

    The luminescence spectra of upconversion nanoparticles (UCNPs) and ZnCdS nanoparticles (ZnCdSNPs) were measured and analyzed in a wide temperature range: from room to human body and further to a hyperthermic temperature resulting in tissue morphology change. The results show that the luminescence signal of UCNPs and ZnCdSNPs placed within the tissue is reasonably good sensitive to temperature change and accompanied by phase transitions of lipid structures of adipose tissue. The most likely that the multiple phase transitions are associated with the different components of fat cells, such as phospholipids of cell membrane and lipids of fat droplets. In the course of fat cell heating, lipids of fat droplet first transit from a crystalline form to a liquid crystal form and then to a liquid form, which is characterized by much less scattering. The results of phase transitions of lipids were observed as the changes in the slope of the temperature dependence of the intensity of luminescence of the film with nanoparticles embedded into tissue. The obtained results confirm a high sensitivity of the luminescent UCNPs and ZnCdSNPs to the temperature variations within thin tissue samples and show a strong potential for the controllable tissue thermolysis.

  20. Electrochromic device containing metal oxide nanoparticles and ultraviolet blocking material

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Garcia, Guillermo; Koo, Bonil; Gregoratto, Ivano

    An electrochromic device includes a nanostructured transition metal oxide bronze layer that includes one or more transition metal oxide and one or more dopant. The electrochromic device also includes nanoparticles containing one or more transparent conducting oxide (TCO), a solid state electrolyte, a counter electrode, and at least one protective layer to prevent degradation of the one or more nanostructured transition metal oxide bronze. The nanostructured transition metal oxide bronze selectively modulates transmittance of near-infrared (NIR) and visible radiation as a function of an applied voltage to the device.

  1. Intranasal administration of Exendin-4 antagonizes Aβ31-35-induced disruption of circadian rhythm and impairment of learning and memory.

    PubMed

    Wang, Xiaohui; Wang, Li; Xu, Yunyun; Yu, Qianqian; Li, Lin; Guo, Yanlin

    2016-12-01

    The deposition of β-amyloid protein (Aβ) is one of the pathological characteristics of Alzheimer's disease (AD) and can disrupt circadian rhythm and impair learning and memory. Exendin-4, a therapeutic drug for type II diabetes mellitus (T2DM), exerts neuroprotective effects from the toxicity of Aβ. However, it is not clear whether Exendin-4 protects against Aβ-induced disruption of circadian rhythm. The neuroprotective effects of Exendin-4 have been studied using injection of Exendin-4 into the lateral ventricle and abdomen. However, these procedures are not suitable for clinical application. First, male C57BL/6 mice received triple distilled water or Exendin-4 (0.1 nmol, 0.5 nmol) by intranasal administration. Exendin-4 levels were measured in the hippocampal samples using an ELISA Kit. Then, the study examined whether intranasal or hippocampal administration of Exendin-4 antagonized Aβ-induced disruption of circadian rhythm as well as impairment of learning and memory using the wheel-running activity assay and the Morris water maze test. The study showed that intranasally administered Exendin-4 passed through the blood-brain barrier. Aβ31-35 given by intrahippocampal injection disrupted circadian rhythm and impaired learning and memory in C57BL/6 mice, and Exendin-4 given by nasal cavity or hippocampal administration ameliorated Aβ31-35-induced circadian rhythm disturbance of locomotor activity and impairment of learning and memory. These findings provide pivotal experimental support for further study of the neuroprotective effects and clinical application of Exendin-4.

  2. The unusual magnetism of nanoparticle LaCoO3.

    PubMed

    Durand, A M; Belanger, D P; Hamil, T J; Ye, F; Chi, S; Fernandez-Baca, J A; Booth, C H; Abdollahian, Y; Bhat, M

    2015-05-08

    Bulk and nanoparticle powders of LaCoO3 (LCO) were synthesized and their magnetic and structural properties were studied using SQUID magnetometry and neutron diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM) below T ≈ 85 K and a crossover from strong to weak antiferromagnetic (AFM) correlations near a transition expressed in the lattice parameters, To≈40 K. This crossover does not occur in the smallest nanoparticles; instead, the magnetic behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles depends on the amount of Co3O4 impurity phase, which induces tensile strain on the LCO lattice. A core-interface model is introduced, with the core region exhibiting the AFM crossover and with FM in the interface region near surfaces and impurity phases.

  3. The unusual magnetism of nanoparticle LaCoO 3

    DOE PAGES

    Durand, A. M.; Belanger, D. P.; Hamil, T. J.; ...

    2015-04-15

    Bulk and nanoparticle powders of LaCoO 3 (LCO) were synthesized and their magnetic and structural properties were studied using SQUID magnetometry and neutron diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM) below T≈85K and a crossover from strong to weak antiferromagnetic (AFM) correlations near a transition expressed in the lattice parameters, To ≈ 40 K. This crossover does not occur in the smallest nanoparticles; instead, the magnetic behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles depends on the amount of Co 3O 4 impurity phase, which induces tensile strain on the LCO lattice. A core-interfacemore » model is introduced, with the core region exhibiting the AFM crossover and with FM in the interface region near surfaces and impurity phases.« less

  4. The unusual magnetism of nanoparticle LaCoO3

    NASA Astrophysics Data System (ADS)

    Durand, A. M.; Belanger, D. P.; Hamil, T. J.; Ye, F.; Chi, S.; Fernandez-Baca, J. A.; Booth, C. H.; Abdollahian, Y.; Bhat, M.

    2015-05-01

    Bulk and nanoparticle powders of LaCoO3 (LCO) were synthesized and their magnetic and structural properties were studied using SQUID magnetometry and neutron diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM) below T ≈ 85 K and a crossover from strong to weak antiferromagnetic (AFM) correlations near a transition expressed in the lattice parameters, To≈40 K. This crossover does not occur in the smallest nanoparticles; instead, the magnetic behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles depends on the amount of Co3O4 impurity phase, which induces tensile strain on the LCO lattice. A core-interface model is introduced, with the core region exhibiting the AFM crossover and with FM in the interface region near surfaces and impurity phases.

  5. Recovery and redispersion of gold nanoparticles using the self-assembly of a pH sensitive zwitterionic amphiphile.

    PubMed

    Morita-Imura, Clara; Imura, Yoshiro; Kawai, Takeshi; Shindo, Hitoshi

    2014-11-04

    The pH-responsive self-assembly of zwitterionic amphiphile C16CA was expanded to the recovery of gold (Au) nanoparticles for environmentally friendly chemistry applications. Multilayered lamellae at pH ∼ 4 were successfully incorporated into nanoparticles by dispersion. Redispersion of nanoparticles was achieved under basic conditions by the transition of self-assembly.

  6. Intranasal Administration of PACAP: Uptake by Brain and Brain Region Targeting with Cyclodextrins

    PubMed Central

    Nonaka, Naoko; Farr, Susan A.; Nakamachi, Tomoya; Morley, John E.; Nakamura, Masanori; Shioda, Seiji; Banks, William A.

    2012-01-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent neurotrophic and neuroprotectant that is transported across the blood-brain barrier in amounts sufficient to affect brain function. However, its short half-life in blood makes it difficult to administer peripherally. Here, we determined whether the radioactively labeled 38 amino acid form of PACAP can enter the brain after intranasal (i.n.) administration. Occipital cortex and striatum were the regions with the highest uptake, peaking at levels of about 2-4 percent of the injected dose per g of brain region. Inclusion of unlabeled PACAP greatly increased retention of I-PACAP by brain probably because of inhibition of the brain-to-blood efflux transporter for PACAP located at the blood-brain barrier. Sufficient amounts of PACAP could be delivered to the brain to affect function as shown by improvement of memory in aged SAMP8 mice, a model of Alzheimer’s disease. We found that each of three cyclodextrins when included in the i.n. injection produced a unique distribution pattern of I-PACAP among brain regions. As examples, β-cyclodextrin greatly increased uptake by the occipital cortex and hypothalamus, α-cyclodextrin increased uptake by the olfactory bulb and decreased uptake by the occipital cortex and striatum, and (2-hydropropyl)-β-cyclodextrin increased uptake by the thalamus and decreased uptake by the striatum. These results show that therapeutic amounts of PACAP can be delivered to the brain by intranasal administration and that cyclodextrins may be useful in the therapeutic targeting of peptides to specific brain regions. PMID:22687366

  7. Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

    PubMed

    Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu

    2011-12-01

    Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

  8. Polarization-independent refractive index tuning using gold nanoparticle-stabilized blue phase liquid crystals.

    PubMed

    Yabu, Shuhei; Tanaka, Yuma; Tagashira, Kenji; Yoshida, Hiroyuki; Fujii, Akihiko; Kikuchi, Hirotsugu; Ozaki, Masanori

    2011-09-15

    Polarization-independent refractive index (RI) modulation can be achieved in blue phase (BP) liquid crystals (LCs) by applying an electric field parallel to the direction of light transmission. One of the problems limiting the achievable tuning range is the field-induced phase transition to the cholesteric phase, which is birefringent and chiral. Here we report the RI modulation capabilities of gold nanoparticle-doped BPs I and II, and we show that field-induced BP-cholesteric transition is suppressed in nanoparticle-doped BP II. Because the LC remains optically isotropic even at high applied voltages, a larger RI tuning range can be achieved.

  9. Outcome of accelerated radiotherapy alone or accelerated radiotherapy followed by exenteration of the nasal cavity in dogs with intranasal neoplasia: 53 cases (1990-2002).

    PubMed

    Adams, William M; Bjorling, Dale E; McAnulty, Jonathan E; Green, Eric M; Forrest, Lisa J; Vail, David M

    2005-09-15

    To compare long-term results of radiotherapy alone versus radiotherapy followed by exenteration of the nasal cavity in dogs with malignant intranasal neoplasia. Retrospective study. 53 dogs with malignant intranasal neoplasia. All dogs underwent radiotherapy consisting of administration of 10 fractions of 4.2 Gy each on consecutive weekdays. For dogs in the surgery group (n=13), follow-up computed tomography was performed, and dogs were scheduled for surgery if persistent or recurrent tumor was seen. Perioperative complications for dogs that underwent surgery included hemorrhage requiring transfusion (2 dogs) and subcutaneous emphysema (8). Rhinitis and osteomyelitis-osteonecrosis occurred significantly more frequently in dogs in the radiotherapy and surgery group (9 and 4 dogs, respectively) than in dogs in the radiotherapy-only group (4 and 3 dogs, respectively). Two- and 3-year survival rates were 44% and 24%, respectively, for dogs in the radiotherapy group and 69% and 58%, respectively, for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (477 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months). Results suggest that exenteration of the nasal cavity significantly prolongs survival time in dogs with intranasal neoplasia that have undergone radiotherapy. Exenteration after radiotherapy may increase the risk of chronic complications.

  10. Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

    PubMed

    Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki

    2016-01-01

    Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based

  11. Silicon nanoparticle-ZnS nanophosphors for ultraviolet-based white light emitting diode

    NASA Astrophysics Data System (ADS)

    Stupca, Matthew; Nayfeh, Osama M.; Hoang, Tuan; Nayfeh, Munir H.; Alhreish, Bahjat; Boparai, Jack; AlDwayyan, Abdullah; AlSalhi, Mohamad

    2012-10-01

    Present red phosphor converters provide spectra dominated by sharp lines and suffer from availability and stability issues which are not ideal for color mixing in display or solid state lighting applications. We examine the use of mono dispersed 3 nm silicon nanoparticles, with inhomogeneously broadened red luminescence as an effective substitute for red phosphors. We tested a 3-phase hybrid nanophosphor consisting of ZnS:Ag, ZnS:Cu,Au,Al, and nanoparticles. Correlated color temperature is examined under UV and LED pumping in the range 254, 365-400 nm. The temperature is found reasonably flat for the longer wavelengths and drops for the shorter wavelengths while the color rendering index increases. The photo stability of the phosphors relative to the silicon nanoparticles is recorded. The variation in the temperature is analyzed in terms of the strength of inter-band-gap transition and continuum band to band transitions.

  12. Effects of polymer-nanoparticle interactions on the viscosity of unentangled polymers under extreme nanoconfinement during capillary rise infiltration.

    PubMed

    Hor, Jyo Lyn; Wang, Haonan; Fakhraai, Zahra; Lee, Daeyeon

    2018-03-28

    We explore the effect of confinement and polymer-nanoparticle interactions on the viscosity of unentangled polymers undergoing capillary rise infiltration (CaRI) in dense packings of nanoparticles. In CaRI, a polymer is thermally induced to wick into the dense packings of nanoparticles, leading to the formation of polymer-infiltrated nanoparticle films, a new class of thin film nanocomposites with extremely high concentrations of nanoparticles. To understand the effect of this extreme nanoconfinement, as well as polymer-nanoparticle interactions on the polymer viscosity in CaRI films, we use two polymers that are known to have very different interactions with SiO2 nanoparticles. Using in situ spectroscopic ellipsometry, we monitor the polymer infiltration process, from which we infer the polymer viscosity based on the Lucas-Washburn model. Our results suggest that physical confinement increases the viscosity by approximately two orders of magnitude. Furthermore, confinement also increases the glass transition temperature of both polymers. Thus, under extreme nanoconfinement, the physical confinement has a more significant impact than the polymer-nanoparticle interactions on the viscosity of unentangled polymers, measured through infiltration dynamics, as well as the glass transition temperature. These findings will provide fundamental frameworks for designing processes to enable the fabrication of CaRI nanocomposite films with a wide range of nanoparticles and polymers.

  13. Surface patterning of nanoparticles with polymer patches

    NASA Astrophysics Data System (ADS)

    Choueiri, Rachelle M.; Galati, Elizabeth; Thérien-Aubin, Héloïse; Klinkova, Anna; Larin, Egor M.; Querejeta-Fernández, Ana; Han, Lili; Xin, Huolin L.; Gang, Oleg; Zhulina, Ekaterina B.; Rubinstein, Michael; Kumacheva, Eugenia

    2016-10-01

    Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest. Surface-patterned particles act as colloidal analogues of atoms and molecules, serve as model systems in studies of phase transitions in liquid systems, behave as ‘colloidal surfactants’ and function as templates for the synthesis of hybrid particles. The generation of micrometre- and submicrometre-sized patchy colloids is now efficient, but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size- and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties. At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles, and nanoparticles with surface ripples or a ‘raspberry’ surface morphology. Here we demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface-pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. These patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization.

  14. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    NASA Technical Reports Server (NTRS)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  15. Effects of intranasal oxytocin on the attentional bias to emotional stimuli in patients with bulimia nervosa.

    PubMed

    Kim, Youl-Ri; Eom, Jin-Sup; Leppanen, Jenni; Leslie, Monica; Treasure, Janet

    2018-05-01

    Bulimia nervosa (BN) is characterized by binge eating and emotional dysregulation including increased negative affectivity (anger, anxiety). The aim of this study was to examine the effect of oxytocin on attentional processes towards anger in patients with BN. The study design consisted of a double-blind, placebo-controlled within-subject crossover, single dose experiment. Sixty-four women (31 patients with BN and 33 healthy comparisons) completed self-reported measures to evaluate emotional difficulties and were administered a single dose of intranasal oxytocin (40IU) or placebo followed by a visual probe detection task to examine attentional orienting to angry or happy faces. Patients with BN reported higher emotional dysregulation and more difficulties in controlling anger compared to the healthy comparison group. Patients with BN and the healthy women exhibited similar attentional bias to angry faces in the placebo condition. Intranasal oxytocin reduced the attentional bias towards angry faces in both the BN patients and the healthy women. We found that a single dose of oxytocin reduced vigilance towards angry faces in patients with BN as well as healthy women. The results showed that patients with BN are not different from healthy women in terms of vigilance towards threat. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Biophysical characterization of gold nanoparticles-loaded liposomes.

    PubMed

    Mady, Mohsen Mahmoud; Fathy, Mohamed Mahmoud; Youssef, Tareq; Khalil, Wafaa Mohamed

    2012-10-01

    Gold nanoparticles were prepared and loaded into the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Biophysical characterization of gold-loaded liposomes was studied by transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy as well as turbidity and rheological measurements. FTIR measurements showed that gold nanoparticles made significant changes in the frequency of the CH(2) stretching bands, revealing that gold nanoparticles increased the number of gauche conformers and create a conformational change within the acyl chains of phospholipids. The transmission electron micrographs (TEM) revealed that gold nanoparticles were loaded in the liposomal bilayer. The zeta potential of DPPC liposomes had a more negative value after incorporating of Au NPs into liposomal membranes. Turbidity studies revealed that the loading of gold nanoparticles into DPPC liposomes results in shifting the temperature of the main phase transition to a lower value. The membrane fluidity of DPPC bilayer was increased by loading the gold nanoparticles as shown from rheological measurements. Knowledge gained in this study may open the door to pursuing liposomes as a viable strategy for Au NPs delivery in many diagnostic and therapeutic applications. Copyright © 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  17. Ribavirin protects Syrian hamsters against lethal hantavirus pulmonary syndrome--after intranasal exposure to Andes virus.

    PubMed

    Ogg, Monica; Jonsson, Colleen B; Camp, Jeremy V; Hooper, Jay W

    2013-11-08

    Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.

  18. Membrane-bound SIV envelope trimers are immunogenic in ferrets after intranasal vaccination with a replication-competent canine distemper virus vector.

    PubMed

    Zhang, Xinsheng; Wallace, Olivia; Wright, Kevin J; Backer, Martin; Coleman, John W; Koehnke, Rebecca; Frenk, Esther; Domi, Arban; Chiuchiolo, Maria J; DeStefano, Joanne; Narpala, Sandeep; Powell, Rebecca; Morrow, Gavin; Boggiano, Cesar; Zamb, Timothy J; Richter King, C; Parks, Christopher L

    2013-11-01

    We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert designs. Vectors containing a gene inserted between the CDV H and L genes, which encoded Env lacking most of its cytoplasmic tail, propagated efficiently in Vero cells, expressed the immunogen on the cell surface, and incorporated the SIV glycoprotein into progeny virus particles. When ferrets were vaccinated intranasally, there were no signs of distress, vector replication was observed in the gut-associated lymphoid tissues, and the animals produced anti-SIV Env antibodies. These data show that live CDV-SIV Env vectors can safely induce anti-Env immune responses following intranasal vaccination. © 2013 Elsevier Inc. All rights reserved.

  19. Acute myelopathy selectively involving lumbar anterior horns following intranasal insufflation of ecstasy and heroin

    PubMed Central

    Riva, Nilo; Riva, Nilo; Morana, Paolo; Cerri, Federica; Gerevini, Simonetta; Amadio, Stefano; Formaglio, Fabio; Comi, Giancarlo; Comola, Mauro; Del Carro, Ubaldo

    2009-01-01

    We report a patient who developed acute myelopathy after intranasal insufflation of amphetamines and heroin. The functional prognosis was very poor; after 4 months, she remained paraplegic. MRI imaging showed selective T2 hyperintensity and intense enhancement confined to the spinal anterior horns and lumbar nerve roots and plexus. This unique MRI pattern, together with neurophysiological data, suggests that the pathological process at the first primary affected spinal anterior horns (SAH), conditioning motoneuron cell death, and then nerve roots and lumbar plexus as a consequence of wallerian degeneration PMID:21686691

  20. Formation of small gold clusters in solution by laser excitation of interband transition

    NASA Astrophysics Data System (ADS)

    Mafuné, Fumitaka; Kondow, Tamotsu

    2003-04-01

    Gold nanoparticles with ˜10 nm in average diameter were prepared by laser ablation of a gold metal plate in an aqueous solution of sodium dodecyl sulfate (SDS) and were fragmented by excitation of an interband transition of gold nanoparticles under irradiation of an intense 355-nm pulsed laser. Fragmentation dynamics was investigated by comparing the fragmentation by excitation of a surface plasmon band of gold nanoparticles by a 532-nm laser. It is found that gold nanoparticles with 1.5-nm average diameter are produced together with small gold clusters by properly optimizing the surfactant concentration.

  1. Effect of Milling Time on the Blocking Temperature of Nanoparticles of Magnetocaloric Gd5Si4

    NASA Astrophysics Data System (ADS)

    Hadimani, Ravi; Gupta, Shalbh; Harstad, Shane; Pecharsky, Vitalij; Jiles, David; David C Jiles Team; Vitalij Pecharsky Collaboration

    Extensive research has been done on giant magnetocaloric material Gd5(SixGe1-x)4 to improve adiabatic temperature/isothermal entropy change. However, there have been only a few reports on fabrication of nanostructure/nanoparticles that can be used to tune various properties by changing the length scale. Recently we have reported fabrication of room temperature ferromagnetic nanoparticles of Gd5Si4 using high energy ball milling. These nanoparticles have potential applications in biomedical engineering such as better T2 MRI contrast agents and in hypothermia. Here we report the effect of milling time on the blocking temperature, micro-structure, crystal structure, and magnetic properties of these nanoparticles. Magnetization vs. temperature at an applied field of 100 Oe is measured for all the ball milled samples. Bulk Gd5Si4 has a transition temperature of ~340 K. There are two phase transitions observed in the nanoparticles, one near 300 K corresponding to the Gd5Si4 phase and another between 75-150 K corresponding to Gd5Si3. Zero Field Cooling (ZFC) and Field Cooling (FC) were measured. The blocking temperatures for the nanoparticles increase with decrease in milling time.

  2. Observation of relaxor ferroelectricity and multiferroic behaviour in nanoparticles of the ferromagnetic semiconductor La(2)NiMnO(6).

    PubMed

    Masud, Md G; Ghosh, Arijit; Sannigrahi, J; Chaudhuri, B K

    2012-07-25

    We report a diffuse phase transition (extending over a finite temperature range of ∼50 K) in sol-gel derived nanoparticles (∼25 nm) of the ferromagnetic double perovskite La(2)NiMnO(6). The macroscopic polarization (P-E hysteresis loop), validity of the Vogel-Fulcher relation and high dielectric permittivity (∼9 × 10(2)) confirm relaxor ferroelectric phenomena in these magnetic nanoparticles. Compared to the corresponding bulk sample, appreciably large enhancement of the magnetocapacitive effect (MC  ∼ 30%) is observed even under low magnetic field (0.5 T) around the broad relaxor dielectric peak temperature (∼220 K), which is close to the ferromagnetic transition temperature (θ(f) ∼ 196 K). All of these features establish the multiferroic character of the La(2)NiMnO(6) nanoparticles. The inhomogeneities arising from chemical and valence mixing in the present La(2)NiMnO(6) nanoparticles and the inter-site, Ni/Mn-site disorder along with surface disorder of the individual nanoparticles resulting in local polar regions are attributed to the observed dielectric behaviour of the nanoparticles. The wave vector dependent spin-pair correlation is considered to be the plausible cause of the colossal magnetocapacitive response near the transition temperature. High permittivity and large magnetocapacitive properties make these ferromagnetic La(2)NiMnO(6) nanoparticles technologically important.

  3. H9N2 Influenza Whole Inactivated Virus Combined with Polyethyleneimine Strongly Enhances Mucosal and Systemic Immunity after Intranasal Immunization in Mice

    PubMed Central

    Qin, Tao; Yin, Yinyan; Huang, Lulu; Yu, Qinghua

    2015-01-01

    Influenza whole inactivated virus (WIV) is more immunogenic and induces protective antibody responses compared with other formulations, like split virus or subunit vaccines, after intranasal mucosal delivery. Polyethyleneimine (PEI), an organic polycation, is widely used as a reagent for gene transfection and DNA vaccine delivery. Although PEI recently has demonstrated potent mucosal adjuvant activity for viral subunit glycoprotein antigens, its immune activity with H9N2 WIV is not well demonstrated. Here, mice were immunized intranasally with H9N2 WIV combined with PEI, and the levels of local respiratory tract and systemic immune responses were measured. Compared to H9N2 WIV alone, antigen-specific IgA levels in the local nasal cavity, trachea, and lung, as well as levels of IgG and its subtypes (IgG1 and IgG2a) in the serum, were strongly enhanced with the combination. Similarly, the activation and proliferation of splenocytes were markedly increased. In addition, PEI is superior as an H9N2 WIV delivery system due to its ability to greatly increase the viral adhesion to mucosal epithelial cells and to enhance the cellular uptake and endosomal escape of antigens in dendritic cells (DCs) and further significantly activate DCs to mature. Taken together, these results provided more insights that PEI has potential as an adjuvant for H9N2 particle antigen intranasal vaccination. PMID:25673304

  4. In vitro and in vivo mRNA delivery using lipid-enveloped pH-responsive polymer nanoparticles

    PubMed Central

    Su, Xingfang; Fricke, Jennifer; Kavanagh, Daniel; Irvine, Darrell J.

    2012-01-01

    Biodegradable core-shell structured nanoparticles with a poly(β-amino-ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery, with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively-charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells (DCs) led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of ~30%. Particles loaded with mRNA administered intranasally in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a timepoint when naked mRNA given i.n. showed no expression. At later timepoints, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for non-invasive delivery of mRNA-based vaccines. PMID:21417235

  5. Synthetic Fabrication of Nanoscale MoS2-Based Transition Metal Sulfides

    PubMed Central

    Wang, Shutao; An, Changhua; Yuan, Jikang

    2010-01-01

    Transition metal sulfides are scientifically and technologically important materials. This review summarizes recent progress on the synthetic fabrication of transition metal sulfides nanocrystals with controlled shape, size, and surface functionality. Special attention is paid to the case of MoS2 nanoparticles, where organic (surfactant, polymer), inorganic (support, promoter, doping) compounds and intercalation chemistry are applied.

  6. Sedative Effects of Intranasal Midazolam Administration in Wild Caught Blue-fronted Amazon (Amazona aestiva) and Orange-winged Amazon (Amazona amazonica) Parrots.

    PubMed

    Schaffer, Débora P H; de Araújo, Nayone L L C; Raposo, Ana Cláudia S; Filho, Emanoel F Martins; Vieira, João Victor R; Oriá, Arianne P

    2017-09-01

    Safe and effective sedation protocols are important for chemical restraint of birds in clinical and diagnostic procedures, such as clinical evaluations, radiographic positioning, and blood collection. These protocols may reduce stress and ease the management of wild-caught birds, which are susceptible to injury or death when exposed to stressful situations. We compare the sedative effect of intranasal midazolam in wild-caught blue-fronted (Amazona aestiva) and orange-winged (Amazona amazonica) Amazon parrots. Ten adult parrots of each species (n = 20), of unknown sex, weighing 0.337 ± 0.04 (blue-fronted) and 0.390 ± 0.03 kg (orange-winged), kg were used. Midazolam (2 mg/kg) was administered intranasally and the total volume of the drug was divided equally between the 2 nostrils. Onset time and total sedation time were assessed. Satisfactory sedation for clinical evaluation was induced in all birds. Onset time and total sedation times were similar in both species: 5.36 ± 1.16 and 25.40 ± 5.72 minutes, respectively, for blue-fronted Amazons and 5.09 ± 0.89 and 27.10 ± 3.73 minutes, respectively, for orange-winged Amazons. A total of 15 animals showed absence of vocalization, with moderate muscle relaxation and wing movement upon handling, and 2 animals presented with lateral recumbence, with intense muscle relaxation and no wing movement, requiring no restraint. Three blue-fronted Amazons had no effective sedation. Intranasally administered midazolam at a dose of 2 mg/kg effectively promoted sedative effects with a short latency time and fast recovery in wild-caught parrots.

  7. Alteration of brain activation patterns in nonallergic rhinitis patients using functional magnetic resonance imaging before and after treatment with intranasal azelastine.

    PubMed

    Bernstein, Jonathan A; Hastings, Lloyd; Boespflug, Erin L; Allendorfer, Jane B; Lamy, Martine; Eliassen, James C

    2011-06-01

    Although nonallergic rhinitis (NAR) patients tend to be more sensitive to chemical/olfactory stimuli, a suprathreshold olfactory response or the presence of specific olfactory receptor genes do not explain why their symptoms are triggered by such exposures. To investigate differential neurogenic responses to azelastine in NAR patients, using functional magnetic resonance imaging (fMRI) in response to specific olfactory triggers. A longitudinal study design on 12 subjects with a physician diagnosis of NAR previously demonstrated to be clinically responsive to intranasal azelastine (Astelin) was performed. Subjects underwent fMRI during exposure to unpleasant (hickory smoke) and pleasant (vanilla) odorants while off and then on azelastine for 2 weeks. The olfactory fMRI paradigm consisted of a visually triggered sniff every 21 seconds with synchronized delivery of a 4 second pulse of odorant. Each odorant was presented 18 times over 4-6-minute fMRI runs. Continuous fresh air was presented to wash out each odorant after presentation. Nonallergic rhinitis patients exhibited increased blood flow to several regions of the brain in response to both pleasant and unpleasant odorants, specifically in odor-sensitive regions, while off intranasal azelastine. Treatment with intranasal azelastine significantly attenuated blood flow to regions of the brain relevant to either olfactory sensation or sensory processing in response to these odorants compared with fresh air. The general reduction compared with increase in brain activation in NAR patients on versus off azelastine suggests that a possible effect of this medication may be reduction of brain responses to odorants. Copyright © 2011. Published by Elsevier Inc.

  8. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth.

    PubMed

    Anagnostou, Evdokia; Soorya, Latha; Brian, Jessica; Dupuis, Annie; Mankad, Deepali; Smile, Sharon; Jacob, Suma

    2014-09-11

    There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. Fifteen children and adolescents with verbal IQs≥70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. ENERGY CONVERSION FOR THE TRANSITION FROM Al TO γ-Al2O3 NANOPARTICLES

    NASA Astrophysics Data System (ADS)

    Wang, Shulin; Li, Shengjuan; Xu, Bo; Jian, Dunliang; Zhu, Yufang

    2013-07-01

    We have successfully converted large volume Al particles into γ-Al2O3 nanostructures by vibration milling at room temperature and successive treatment. We show that there exist special relationships among stacking fault energy (SFE), strain energy (SRE), and surface energy (SE) of the materials, including interdependence, intercompetition, and interconversion during the phase transition. SFE and SRE perform the same changing tendency, while SE just does the opposite. However, it is not the particle size but the energy state that determines the reactivity of the materials. And it is the SE that can directly determine the physical chemical reaction and the conversion into the end product rather than SFE and SRE. When SE goes up, the material reactivity and the product yield will be enhanced; and when SE goes down, the reaction and the product yield will decay. However, the state of SE depends closely on the change tendency of the SFE and SRE. That is, when SFE and SRE goes up, SE will goes down; if SFE and SRE goes down, SE will goes up. It seems that energy conservation law may be followed in a sense in the particle system if the external input keeps constant. The work may be significant for energy conversion in nano-scale and mechanosynthesis of oxide nanoparticles.

  10. Phase transitions and their energetics in calcite biominerals

    NASA Astrophysics Data System (ADS)

    Gilbert, Pupa

    2013-03-01

    Biominerals include mollusk shells and the skeletons of algae, sponges, corals, sea urchins and most other animals. The function of biominerals are diverse: mechanical support, attack, defense, grinding, biting, and chewing, gravitational and magnetic field sensing, light focusing, and many others. The exquisite nanostructure of biominerals is directly controlled by the organisms, which have evolved to master the chemico-physical aspects of mineralization. By controlling the inorganic precursor nanoparticle size, packing, and phase transitions, organisms efficiently fill space, produce tough and hard structures, with micro- or macroscopic morphology optimized for their functions. Specifically, this talk will address two key questions: Q: How are the beautiful biomineral morphologies achieved? A: Using amorphous precursor phases, with phase transitions kinetically regulated (retarded) by proteins. Q: How do organisms co-orient their single-crystalline biominerals? A: Controlling the propagation of crystallinity one nanoparticle at a time, not atom-by-atom.

  11. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines

    PubMed Central

    Gasper, David J.; Neldner, Brandon; Plisch, Erin H.; Rustom, Hani; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M.

    2016-01-01

    CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the

  12. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

    PubMed

    Gasper, David J; Neldner, Brandon; Plisch, Erin H; Rustom, Hani; Carrow, Emily; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M

    2016-12-01

    CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the

  13. Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model.

    PubMed

    Mandal, Surjyanarayan; Mandal, Snigdha Das; Chuttani, Krishna; Sawant, Krutika K; Subudhi, Bharat Bhushan

    2016-08-01

    The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed. Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p < 0.05) on the responses. Rota-rod and open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups. Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.

  14. Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study.

    PubMed

    Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

    2017-09-01

    Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  15. Immunogenicity of an intranasally administered modified live canine parvovirus type 2b vaccine in pups with maternally derived antibodies.

    PubMed

    Martella, Vito; Cavalli, Alessandra; Decaro, Nicola; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Bozzo, Giancarlo; Tarsitano, Elvira; Buonavoglia, Canio

    2005-10-01

    The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of < or = 80 and in 51.6% of pups with titers between 160 and 320.

  16. Recurrent bacterial meningitis occurring five years after closed head injury and caused by an intranasal post-traumatic meningo-encephalocele.

    PubMed Central

    Giunta, G.; Piazza, I.

    1991-01-01

    A case of atypical presentation of a post-traumatic intranasal meningo-encephalocele is described in a patient with a history of recurrent bacterial meningitis occurring 5 years after closed head injury. The usefulness of the CT and MRI findings in diagnostic evaluation of this lesion is emphasized. Images Figure 1 Figure 2 PMID:2068033

  17. Sharp Transition from Nonmetallic Au246 to Metallic Au279 with Nascent Surface Plasmon Resonance.

    PubMed

    Higaki, Tatsuya; Zhou, Meng; Lambright, Kelly J; Kirschbaum, Kristin; Sfeir, Matthew Y; Jin, Rongchao

    2018-05-02

    The optical properties of metal nanoparticles have attracted wide interest. Recent progress in controlling nanoparticles with atomic precision (often called nanoclusters) provide new opportunities for investigating many fundamental questions, such as the transition from excitonic to plasmonic state, which is a central question in metal nanoparticle research because it provides insights into the origin of surface plasmon resonance (SPR) as well as the formation of metallic bond. However, this question still remains elusive because of the extreme difficulty in preparing atomically precise nanoparticles larger than 2 nm. Here we report the synthesis and optical properties of an atomically precise Au 279 (SR) 84 nanocluster. Femtosecond transient absorption spectroscopic analysis reveals that the Au 279 nanocluster shows a laser power dependence in its excited state lifetime, indicating metallic state of the particle, in contrast with the nonmetallic electronic structure of the Au 246 (SR) 80 nanocluster. Steady-state absorption spectra reveal that the nascent plasmon band of Au 279 at 506 nm shows no peak shift even down to 60 K, consistent with plasmon behavior. The sharp transition from nonmetallic Au 246 to metallic Au 279 is surprising and will stimulate future theoretical work on the transition and many other relevant issues.

  18. Size-driven magnetic transitions in La1/3Ca2/3MnO3 nanoparticles

    NASA Astrophysics Data System (ADS)

    Markovich, V.; Fita, I.; Wisniewski, A.; Mogilyansky, D.; Puzniak, R.; Titelman, L.; Gorodetsky, G.

    2010-09-01

    Magnetic properties of electron-doped La1/3Ca2/3MnO3 manganite nanoparticles with average particle size ranging from 12 to 42 nm, prepared by the glycine-nitrate method, have been investigated in temperature range 5-300 K and in magnetic fields up to 90 kOe. Reduction in the particle size suppresses antiferromagnetism and decreases the Néel temperature. In contrast to bulk crystals, the charge ordering does not occur in all studied nanoparticles, while a weak ferromagnetism appears above 200 K. Low temperature magnetic hysteresis loops indicate upon exchange bias effect displayed by horizontal and vertical shifts in field cooled processes. The spontaneous and remanent magnetization at low temperature shows a relatively complex variation with particle size. The size-induced structural/magnetic disorder drives the La1/3Ca2/3MnO3 nanoparticles to a pronounced glassy behavior for the smallest 12 nm particles, as evidenced by large difference between zero field cooled and field cooled magnetization, frequency dependent ac-susceptibility, as well as characteristic slowing down in the spin dynamics. Time evolution of magnetization recorded in magnetic fields after field cooling to low temperatures exhibits pronounced relaxation and a very noisy behavior that may be caused by formation of some collective states. Magnetic properties of the nanoparticle samples are compared with those of La0.2Ca0.8MnO3 nanoparticles. These results shed some light on the coupling between charges and spin degrees of freedom in antiferromagnetic manganite nanoparticles.

  19. The effect of magnetic nanoparticle concentration on the structure organisation of a microferrogel

    NASA Astrophysics Data System (ADS)

    Ryzhkov, A. V.; Melenev, P. V.; Balasoiu, M.; Raikher, Yu L.

    2018-03-01

    Coarse-grained molecular dynamics simulation is applied to study the structural response of micro-sized magnetopolymer objects – microferrogels (MFG). The results for MFGs with different magnetic properties and concentrations of magnetic filler nanoparticles are analysed to detect the transition between non-aggregated configurations and the states with pronounced chains. The nanoparticles are assumed to be either magnetically isotropic or to possess infinite magnetic anisotropy. It is shown that, depending on the type of the particle anisotropy, an applied field in rather different ways affects the MFG structure and shape. Diagrams describing the degree of aggregation as a function of the parameter of the interparticle magnetodipolar interaction and concentration are presented. In particular, it is found that in the case of infinitely anisotropic nanoparticles the aggregation transitions undergoes via a non-trivial scenario. The effect of the structure transformations on the volume change of the MFG objects is studied as well.

  20. Synthesis, Characterization and Comparative Luminescence Studies of Rare-Earth-Doped Gd2O3 Nanoparticles

    NASA Astrophysics Data System (ADS)

    Pyngrope, D.; Singh, L. R.; Prasad, A. I.; Bora, A.

    2018-04-01

    A facile direct precipitation method was used for the synthesis of luminescence nanomaterial. Gd2O3 doped with rare earth element Eu3+ is synthesized by polyol route. The synthesized nanoparticles show their characteristic red emission. The nanoparticles are characterized by x-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and photoluminescence (PL) study. The synthesized nanoparticles are spherical particles with 30 nm size. The photoluminescence studies show the characteristic Eu3+ red emission. The PL study shows the intensity of the magnetic dipole transition ( 5 D0 \\to 7 F1 ) at 592 nm compared to that of the electronic dipole transition ( 5 D0 \\to 7 F2 ) at 615 nm. The nanomaterials can show significant application in various display devices and biomedical applications for tracking.

  1. Reinforcement of a PMMA resin for interim fixed prostheses with silica nanoparticles.

    PubMed

    Topouzi, Marianthi; Kontonasaki, Eleana; Bikiaris, Dimitrios; Papadopoulou, Lambrini; Paraskevopoulos, Konstantinos M; Koidis, Petros

    2017-05-01

    Fractures in long span provisional/interim restorations are a common complication. Adequate fracture toughness is necessary to resist occlusal forces and crack propagation, so these restorations should be constructed with materials of improved mechanical properties. The aim of this study was to investigate the possible reinforcement of neat silica nanoparticles and trietoxyvinylsilane-modified silica nanoparticles in a PMMA resin for fixed interim restorations. Composite PMMA-Silica nanoparticles powders were mixed with PMMA liquid and compact bar shaped specimens were fabricated according to the British standard BS EN ISO 127337:2005. The single-edge notched method was used to evaluate fracture toughness (three-point bending test), while the dynamic thermomechanical properties (Storage Modulus, Loss Modulus, tanδ) of a series of nanocomposites with different amounts of nanoparticles (0.25%, 0.50%, 0.75%, 1% w.t.) were evaluated. Statistical analysis was performed and the statistically significant level was set to p<0.05. The fracture toughness of all experimental composites was remarkably higher compared to control. There was a tendency to decrease of fracture toughness, by increasing the concentration of the filler. No statistically significant differences were detected among the modified/unmodified silica nanoparticles. Dynamic mechanical properties were also affected. By increasing the silica nanoparticles content an increase in Storage Modulus was recorded, while Glass Transition Temperature was shifted at higher temperatures. Under the limitations of this in-vitro study, it can be suggested that both neat silica nanoparticles and trietoxyvinylsilane-modified silica nanoparticles, especially at low concentrations, may enhance the overall performance of fixed interim prostheses, as can effectively increase the fracture toughness, the elastic modulus and the Glass Transition Temperature of PMMA resins used in fixed provisional restorations. Copyright © 2017

  2. A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

    DTIC Science & Technology

    2015-10-01

    Fellowship of the Alexander von Humboldt Foundation , MIT Name: Dina Hirshfeld- Becker , PhD Project Role: Independent Evaluator Researcher Identifier...e.g. ORCID ID): Nearest person month worked: 3 Contribution to Project: Dr. Hirshfeld- Becker has been an independent evaluator and has evaluated ...either intranasal oxytocin or placebo. Participants and evaluators will be blind to treatment condition. In year 1 of the study, we set up the study

  3. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment

    PubMed Central

    Craft, Suzanne; Baker, Laura D.; Montine, Thomas J.; Minoshima, Satoshi; Watson, G. Stennis; Claxton, Amy; Arbuckle, Matthew; Callaghan, Maureen; Tsai, Elaine; Plymate, Stephen R.; Green, Pattie S.; Leverenz, James; Cross, Donna; Gerton, Brooke

    2011-01-01

    Objective To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD). Design Randomized, double-blind, placebo-controlled trial. Setting Clinical research unit of a Veterans Affairs medical center. Participants The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n = 64) or mild to moderate AD (n = 40). Intervention Participants received placebo (n = 30), 20 IU of insulin (n = 36), or 40 IU of insulin (n = 38) for 4 months, administered with a nasal drug delivery device (Kurve Technology, Bothell, Washington). Main Outcome Measures Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included the Alzheimer Disease’s Assessment Scale–cognitive subscale (ADAS-cog) score and the Alzheimer’s Disease Cooperative Study–activities of daily living (ADCS-ADL) scale. A subset of participants underwent lumbar puncture (n = 23) and positron emission tomography with fludeoxyglucose F 18 (n = 40) before and after treatment. Results Outcome measures were analyzed using repeated-measures analysis of covariance. Treatment with 20 IU of insulin improved delayed memory (P < .05), and both doses of insulin (20 and 40 IU) preserved caregiver-rated functional ability (P < .01). Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD (P < .05). Cerebrospinal fluid biomarkers did not change for insulin-treated participants as a group, but, in exploratory analyses, changes in memory and function were associated with changes in the Aβ42 level and in the tau protein–to–Aβ42 ratio in cerebrospinal fluid. Placebo-assigned participants showed decreased fludeoxyglucose F 18

  4. Interaction of Colloidal Gold Nanoparticles with Model Serum Proteins: The Nanoparticle-Protein 'Corona' from a PhysicoChemical Viewpoint

    NASA Astrophysics Data System (ADS)

    Dominguez Medina, Sergio

    When nanoparticles come in contact with biological fluids they become coated with a mixture of proteins present in the media, forming what is known as the nanoparticle-protein 'corona'. This corona changes the nanoparticles' original surface properties and plays a central role in how these get screened by cellular receptors. In the context of biomedical research, this presents a bottleneck for the transition of nanoparticles from research laboratories to clinical settings. It is therefore fundamental to probe these nanoparticle-protein interactions in order to understand the different physico-chemical mechanisms involved. This thesis is aimed to investigate the exposure of colloidal gold nanoparticles to model serum proteins, particularly serum albumin, the main transporter of molecular compounds in the bloodstream of mammals. A set of experimental tools based on optical microscopy and spectroscopy were developed in order to probe these interactions in situ. First, the intrinsic photoluminescence and elastic scattering of individual gold nanoparticles were investigated in order to understand its physical origin. These optical signals were then used to measure the size of the nanoparticles while in Brownian diffusion using fluctuation correlation spectroscopy. This spectroscopic tool was then applied to detect the binding of serum albumin onto the nanoparticle surface, increasing its hydrodynamic size. By performing a binding isotherm as a function of protein concentration, it was determined that serum albumin follows an anti-cooperative binding mechanism on negatively charged gold nanoparticles. This protein monolayer substantially enhanced the stability of the colloid, preventing their aggregation in saline solutions with ionic strength higher than biological media. Cationic gold nanoparticles in contrast, aggregated when serum albumin was present at a low protein-to-nanoparticle ratio, but prevented aggregation if exposed in excess. Single-molecule fluorescence

  5. Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

    NASA Technical Reports Server (NTRS)

    Singh, Rajendra P.; Daniels, Vernie R.; Crady, Camille J.; Derendorf, H.; Putcha, L.

    2011-01-01

    Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  6. The magnetic and adsorption properties of ZnO1-xSx nanoparticles.

    PubMed

    Zhang, Huiyun; Liu, Guixian; Cao, Yanqiang; Chen, Jing; Shen, Kai; Kumar, Ashwini; Xu, Mingxiang; Li, Qi; Xu, Qingyu

    2017-10-11

    Sulfur is easy to be incorporated into ZnO nanoparticles by the solution-combustion method. Herein, the magnetic and adsorption properties of a series of ZnO 1-x S x (x = 0, 0.05, 0.1, 0.15, and 0.2) nanoparticles were systematically investigated. The X-ray diffraction patterns show that the as-prepared ZnO 1-x S x nanoparticles have the hexagonal wurtzite structure of ZnO with a low sulfur content that gradually transforms into the zinc blende structure of ZnS when the x value is greater than 0.1. PL spectra show several bands due to different transitions, which have been explained by the recombination of free excitons or defect-induced transitions. The introduction of sulfur not only modifies the bandgap of ZnO, but also impacts the concentration of Zn vacancies. The as-prepared ZnO shows weak room-temperature ferromagnetism, and the incorporation of sulfur improves the ferromagnetism owing to the increased concentration of Zn vacancies, which may be stabilized by the doped sulfur ions. The adsorption capability of ZnO 1-x S x nanoparticles has been significantly improved, and the process can be well described by the pseudo-first-order kinetic model and the Freundlich isotherm model. The mechanism has been confirmed to be due to the active sulfate groups existing in zinc oxysulfide nanoparticles.

  7. Surface patterning of nanoparticles with polymer patches

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Choueiri, Rachelle M.; Galati, Elizabeth; Thérien-Aubin, Héloïse

    Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest. Surface-patterned particles act as colloidal analogues of atoms and molecules serve as model systems in studies of phase transitions in liquid systems, behave as ‘colloidal surfactants’ and function as templates for the synthesis of hybrid particles. The generation of micrometre- and submicrometre-sized patchy colloids is now efficient but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size- and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties.more » At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles and nanoparticles with surface ripples or a ‘raspberry’ surface morphology. We demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface-pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. Furthermore, these patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization.« less

  8. Surface patterning of nanoparticles with polymer patches

    DOE PAGES

    Choueiri, Rachelle M.; Galati, Elizabeth; Thérien-Aubin, Héloïse; ...

    2016-08-24

    Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest. Surface-patterned particles act as colloidal analogues of atoms and molecules serve as model systems in studies of phase transitions in liquid systems, behave as ‘colloidal surfactants’ and function as templates for the synthesis of hybrid particles. The generation of micrometre- and submicrometre-sized patchy colloids is now efficient but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size- and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties.more » At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles and nanoparticles with surface ripples or a ‘raspberry’ surface morphology. We demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface-pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. Furthermore, these patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization.« less

  9. Immunogenicity of an Intranasally Administered Modified Live Canine Parvovirus Type 2b Vaccine in Pups with Maternally Derived Antibodies

    PubMed Central

    Martella, Vito; Cavalli, Alessandra; Decaro, Nicola; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Bozzo, Giancarlo; Tarsitano, Elvira; Buonavoglia, Canio

    2005-01-01

    The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of ≤80 and in 51.6% of pups with titers between 160 and 320. PMID:16210491

  10. Effect of nanoparticles dispersion on viscoelastic properties of epoxy–zirconia polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Singh, Sushil Kumar; Kumar, Abhishek; Jain, Anuj

    2018-03-01

    In the present work zirconia-nanoparticles were dispersed in epoxy matrix to form epoxy-zirconia polymer nanocomposites using ultrasonication and viscoelastic properties of nanocomposites were investigated. For the same spherical zirconia-nanoparticles (45 nm) were dispersed in weight fraction of 2, 4, 6 and 8 % to reinforce the epoxy. DMA results show the significant enhancement in viscoelastic properties with the dispersion of zirconia nanoparticles in the epoxy matrix. The value of storage modulus and glass transition temperature increases from 179 MPa (pristine) to 225 MPa (6 wt.% ZrO2) and 61 °C (pristine) to 70 °C (6 wt.% ZrO2) respectively with the dispersion of zirconia nanoparticles in the epoxy.

  11. Effect of nanoparticles dispersion on viscoelastic properties of epoxy-zirconia polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Singh, Sushil Kumar; Kumar, Abhishek; Jain, Anuj

    2018-03-01

    In the present work zirconia-nanoparticles were dispersed in epoxy matrix to form epoxy-zirconia polymer nanocomposites using ultrasonication and viscoelastic properties of nanocomposites were investigated. For the same spherical zirconia-nanoparticles (45 nm) were dispersed in weight fraction of 2, 4, 6 and 8 % to reinforce the epoxy. DMA results show the significant enhancement in viscoelastic properties with the dispersion of zirconia nanoparticles in the epoxy matrix. The value of storage modulus and glass transition temperature increases from 179 MPa (pristine) to 225 MPa (6 wt.% ZrO2) and 61 °C (pristine) to 70 °C (6 wt.% ZrO2) respectively with the dispersion of zirconia nanoparticles in the epoxy.

  12. Systematic investigation of structural and morphological studies on doped TiO2 nanoparticles for solar cell applications

    NASA Astrophysics Data System (ADS)

    Murugadoss, G.; Jayavel, R.; Rajesh Kumar, M.

    2014-12-01

    Optical, structural and thermal properties of the doped with different ions (transition metals, other metals or post transition metals, non-metals, alkali metals and lanthanides) in TiO2 nanocrystals were investigated. The doped nanoparticles were synthesized by modified chemical method. Ethanol-deionised water mixer (20:1) was used as solvent for synthesize of the undoped and doped TiO2 nanoparticles. Systematic studies on structural and morphological changes by thermal treatment on TiO2 were examined. It has been observed that with Eu and Al doping TiO2, the phase transition temperature for anatase to rutile phase increased. Blue and red shifting absorptions were observed for doped TiO2 in visible region. Among the dopant, significant blue shift was obtained for Cu, Cd, Ag, Y, Ce and In doped TiO2 and red shift was obtained for Zr, Sm, Al, Na, S, Fe, Ni, Eu and Gd doped TiO2 nanoparticles.

  13. Intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.

    PubMed

    Wu, Shipo; Zhang, Zhe; Yu, Rui; Zhang, Jun; Liu, Ying; Song, Xiaohong; Yi, Shaoqiong; Liu, Ju; Chen, Jianqin; Yin, Ying; Xu, Junjie; Hou, Lihua; Chen, Wei

    2014-02-01

    Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

  14. Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

    PubMed Central

    Wu, Shipo; Zhang, Zhe; Yu, Rui; Zhang, Jun; Liu, Ying; Song, Xiaohong; Yi, Shaoqiong; Liu, Ju; Chen, Jianqin; Yin, Ying; Xu, Junjie

    2014-01-01

    Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 108 infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD50) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax. PMID:24307239

  15. Two Glass Transitions Associated to Different Dynamic Disorders in the Nematic Glassy State of a Non-Symmetric Liquid Crystal Dimer Dopped with γ-Alumina Nanoparticles

    PubMed Central

    Diez-Berart, Sergio; López, David O.; Salud, Josep; Diego, José Antonio; Sellarès, Jordi; Robles-Hernández, Beatriz; de la Fuente, María Rosario; Ros, María Blanca

    2015-01-01

    In the present work, the nematic glassy state of the non-symmetric LC dimer α-(4-cyanobiphenyl-4′-yloxy)-ω-(1-pyrenimine-benzylidene-4′-oxy) undecane is studied by means of calorimetric and dielectric measurements. The most striking result of the work is the presence of two different glass transition temperatures: one due to the freezing of the flip-flop motions of the bulkier unit of the dimer and the other, at a lower temperature, related to the freezing of the flip-flop and precessional motions of the cyanobiphenyl unit. This result shows the fact that glass transition is the consequence of the freezing of one or more coupled dynamic disorders and not of the disordered phase itself. In order to avoid crystallization when the bulk sample is cooled down, the LC dimer has been confined via the dispersion of γ-alumina nanoparticles, in several concentrations.

  16. DNA hydrogel as a template for synthesis of ultrasmall gold nanoparticles for catalytic applications.

    PubMed

    Zinchenko, Anatoly; Miwa, Yasuyuki; Lopatina, Larisa I; Sergeyev, Vladimir G; Murata, Shizuaki

    2014-03-12

    DNA cross-linked hydrogel was used as a matrix for synthesis of gold nanoparticles. DNA possesses a strong affinity to transition metals such as gold, which allows for the concentration of Au precursor inside a hydrogel. Further reduction of HAuCl4 inside DNA hydrogel yields well dispersed, non-aggregated spherical Au nanoparticles of 2-3 nm size. The average size of these Au nanoparticles synthesized in DNA hydrogel is the smallest reported so far for in-gel metal nanoparticles synthesis. DNA hybrid hydrogel containing gold nanoparticles showed high catalytic activity in the hydrogenation reaction of nitrophenol to aminophenol. The proposed soft hybrid material is promising as environmentally friendly and sustainable material for catalytic applications.

  17. Intranasal abuse of prescription hydrocodone/acetaminophen results in oronasal fistula: a case report.

    PubMed

    Sloan, Paul A; Klimkina, Oksana

    2009-01-01

    Opioids are becoming more common in the treatment of chronic nonmalignant pain. With increased availability of opioids for chronic pain we may expect an increased misuse of these as analgesics as well. The authors describe the case report of a young woman with chronic back pain and intranasal abuse of prescribed hydrocodone/acetaminophen who was diagnosed after presenting for hypernasal speech and foreign body in the nose. This case report highlights the need for vigilance on the part of the physician for any aberrant drug-related behaviors. Any unusual symptoms or signs such as hypernasal speech, chronic nasal infection, or unexplained foreign body sensation in the nose should be thoroughly investigated.

  18. Control of DNA-Functionalized Nanoparticle Assembly

    NASA Astrophysics Data System (ADS)

    Olvera de La Cruz, Monica

    Directed crystallization of a large variety of nanoparticles, including proteins, via DNA hybridization kinetics has led to unique materials with a broad range of crystal symmetries. The nanoparticles are functionalized with DNA chains that link neighboring functionalized units. The shape of the nanoparticle, the DNA length, the sequence of the hybridizing DNA linker and the grafting density determine the crystal symmetries and lattice spacing. By carefully selecting these parameters one can, in principle, achieve all the symmetries found for both atomic and colloidal crystals of asymmetric shapes as well as new symmetries, and drive transitions between them. A scale-accurate coarse-grained model with explicit DNA chains provides the design parameters, including degree of hybridization, to achieve specific crystal structures. The model also provides surface energy values to determine the shape of defect-free single crystals with macroscopic anisotropic properties, as well as the parameters to develop colloidal models that reproduce both the shape of single crystals and their growth kinetics.

  19. Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

    PubMed

    Rando, Jessica; Broering, Derek; Olson, James E; Marco, Catherine; Evans, Stephen B

    2015-09-01

    This study sought to answer the question, "Can police officers administer intranasal naloxone to drug overdose victims to decrease the opioid overdose death rate?" This prospective interventional study was conducted in Lorain County, OH, from January 2011 to October 2014. Starting October 2013, trained police officers administered naloxone to suspected opioid overdose victims through a police officer naloxone prescription program (NPP). Those found by the county coroner to be positive for opioids at the time of death and those who received naloxone from police officers were included in this study. The rate of change in the total number of opioid-related deaths in Lorain County per quarter year, before and after initiation of the NPP, and the trend in the survival rate of overdose victims who were given naloxone were analyzed by linear regression. Significance was established a priori at P < .05. Data from 247 individuals were eligible for study inclusion. Opioid overdose deaths increased significantly before initiation of the police officer NPP with average deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the first 9 months of 2013. After initiation of the police officer NPP, the number of opioid overdose deaths decreased each quarter with an overall average of 13.4. Of the 67 participants who received naloxone by police officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up. Intranasal naloxone administration by police first responders is associated with decreased deaths in opioid overdose victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Visual systemizing preference in children with autism: A randomized controlled trial of intranasal oxytocin.

    PubMed

    Strathearn, Lane; Kim, Sohye; Bastian, D Anthony; Jung, Jennifer; Iyengar, Udita; Martinez, Sheila; Goin-Kochel, Robin P; Fonagy, Peter

    2018-05-01

    Several studies have suggested that the neuropeptide oxytocin may enhance aspects of social communication in autism. Little is known, however, about its effects on nonsocial manifestations, such as restricted interests and repetitive behaviors. In the empathizing-systemizing theory of autism, social deficits are described along the continuum of empathizing ability, whereas nonsocial aspects are characterized in terms of an increased preference for patterned or rule-based systems, called systemizing. We therefore developed an automated eye-tracking task to test whether children and adolescents with autism spectrum disorder (ASD) compared to matched controls display a visual preference for more highly organized and structured (systemized) real-life images. Then, as part of a randomized, double-blind, placebo-controlled crossover study, we examined the effect of intranasal oxytocin on systemizing preferences in 16 male children with ASD, compared with 16 matched controls. Participants viewed 14 slides, each containing four related pictures (e.g., of people, animals, scenes, or objects) that differed primarily on the degree of systemizing. Visual systemizing preference was defined in terms of the fixation time and count for each image. Unlike control subjects who showed no gaze preference, individuals with ASD preferred to fixate on more highly systemized pictures. Intranasal oxytocin eliminated this preference in ASD participants, who now showed a similar response to control subjects on placebo. In contrast, control participants increased their visual preference for more systemized images after receiving oxytocin versus placebo. These results suggest that, in addition to its effects on social communication, oxytocin may play a role in some of the nonsocial manifestations of autism.