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Sample records for human nasal tissue

  1. Effects of endogenous formaldehyde in nasal tissues on inhaled formaldehyde dosimetry predictions in the rat, monkey, and human nasal passages.

    PubMed

    Schroeter, Jeffry D; Campbell, Jerry; Kimbell, Julia S; Conolly, Rory B; Clewell, Harvey J; Andersen, Melvin E

    2014-04-01

    Formaldehyde is a nasal carcinogen in rodents at high doses and is an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde have relied on internal dose estimates in the upper respiratory tract. Dosimetry calculations are complicated by the presence of endogenous formaldehyde concentrations in the respiratory mucosa. Anatomically accurate computational fluid dynamics (CFD) models of the rat, monkey, and human nasal passages were used to simulate uptake of inhaled formaldehyde. An epithelial structure was implemented in the nasal CFD models to estimate formaldehyde absorption from air:tissue partitioning, species-specific metabolism, first-order clearance, DNA binding, and endogenous formaldehyde production. At an exposure concentration of 1 ppm, predicted formaldehyde nasal uptake was 99.4, 86.5, and 85.3% in the rat, monkey, and human, respectively. Endogenous formaldehyde in nasal tissues did not significantly affect wall mass flux or nasal uptake predictions at exposure concentrations > 500 ppb; however, reduced nasal uptake was predicted at lower exposure concentrations. At an exposure concentration of 1 ppb, predicted nasal uptake was 17.5 and 42.8% in the rat and monkey; net desorption of formaldehyde was predicted in the human model. The nonlinear behavior of formaldehyde nasal absorption will affect the dose-response analysis and subsequent risk estimates at low exposure concentrations. Updated surface area partitioning of nonsquamous epithelium and average flux values in regions where DNA-protein cross-links and cell proliferation rates were measured in rats and monkeys are reported for use in formaldehyde risk models of carcinogenesis.

  2. Swelling of Erectile Nasal Tissue Induced by Human Sexual Pheromone.

    PubMed

    Mazzatenta, Andrea; De Luca, C; Di Tano, A; Cacchio, M; Di Giulio, C; Pokorski, Mieczyslaw

    2016-01-01

    Most chemically mediated sexual communication in humans remains uncharacterized. Yet the study of sexual communication is decisive for understanding sexual behavior and evolutive mechanisms in our species. Here we provide the evidence to consider 4,16-androstadien-3-one (AND) as a man's sexual pheromone. Our experiment provides support for the physiological effect of AND on nasal airway resistance (Rna) in women, as assessed by anterior rhinomanometry. We found that AND administration increased the area of turbinate during the ovulatory phase, resulting in an increase of Rna. Thus, we discovered that minute amounts of AND, acting through neuroendocrine brain control, regulate Rna and consequently affect the sexual physiology and behavior. Fascinatingly, this finding provides the evidence of the preservation of chemosexual communication in humans, which it has been largely neglected due to its unconscious perception and concealed nature. Therefore, chemical communication is a plesiomorphic evolutive phenomenon in humans.

  3. Volume Expansion of Tissue Engineered Human Nasal Septal Cartilage

    PubMed Central

    Reuther, Marsha S; Briggs, Kristen K; Neuman, Monica K; Masuda, Koichi; Sah, Robert L; Watson, Deborah

    2014-01-01

    Importance Cartilaginous craniofacial defects range in size and autologous cartilaginous tissue is preferred for repair of these defects. Therefore, it is important to have the ability to produce large size cartilaginous constructs for repair of cartilaginous abnormalities. Objectives To produce autologous human septal neocartilage constructs substantially larger in size than previously produced constructs To demonstrate that volume expanded neocartilage constructs possess comparable histological and biochemical properties to standard size constructs To show that volume expanded neocartilage constructs retain similar biomechanical properties to standard size constructs Design Prospective, basic science Setting Laboratory Participants The study used remnant human septal specimens removed during routine surgery at the University of California, San Diego Medical Center or San Diego Veterans Affairs Medical Center. Cartilage from a total of 8 donors was collected. Main Outcomes Measured Human septal chondrocytes from 8 donors were used to create 12mm and 24mm neocartilage constructs. These were cultured for a total of 10 weeks. Photo documentation, histological, biochemical, and biomechanical properties were measured and compared. Results The 24mm diameter constructs were qualitatively similar to the 12mm constructs. They possessed adequate strength and durability to be manually manipulated. Histological analysis of the constructs demonstrated similar staining patterns in standard and volume expanded constructs. Proliferation, as measured by DNA content, was similar in 24mm and 12mm constructs. Additionally, glycosaminoglycan (GAG) and total collagen content did not significantly differ between the two construct sizes. Biomechanical analysis of the 24mm and 12mm constructs demonstrated comparable compressive and tensile properties. Conclusion and Relevance Volume expanded human septal neocartilage constructs are qualitatively and histologically similar to standard 12mm

  4. Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering.

    PubMed

    Griffin, M F; Premakumar, Y; Seifalian, A M; Szarko, M; Butler, P E M

    2016-01-01

    Nasal reconstruction is currently performed using autologous grafts provides but is limited by donor site morbidity, tissue availability and potentially graft failure. Additionally, current alternative alloplastic materials are limited by their high extrusion and infection rates. Matching mechanical properties of synthetic materials to the native tissue they are replacing has shown to be important in the biocompatibility of implants. To date the mechanical properties of the human nasal cartilages has not been studied in depth to be able to create tissue-engineered replacements with similar mechanical properties to native tissue. The young's modulus was characterized in compression on fresh-frozen human cadaveric septal, alar, and lateral cartilage. Due to the functional differences experienced by the various aspects of the septal cartilage, 16 regions were evaluated with an average elastic modulus of 2.72 ± 0.63 MPa. Furthermore, the posterior septum was found to be significantly stiffer than the anterior septum (p < 0.01). The medial and lateral alar cartilages were tested at four points with an elastic modulus ranging from 2.09 ± 0.81 MPa, with no significant difference between the cartilages (p < 0.78). The lateral cartilage was tested once in all cadavers with an average elastic modulus of 0.98 ± 0.29 MPa. In conclusion, this study provides new information on the compressive mechanical properties of the human nasal cartilage, allowing surgeons to have a better understanding of the difference between the mechanical properties of the individual nasal cartilages. This study has provided a reference, by which tissue-engineered should be developed for effective cartilage replacements for nasal reconstruction.

  5. Tissue engineering of human nasal alar cartilage precisely by using three-dimensional printing.

    PubMed

    Xu, Yihao; Fan, Fei; Kang, Ning; Wang, Sheng; You, Jianjun; Wang, Huan; Zhang, Bo

    2015-02-01

    Tissue engineering strategies hold promise for the restoration of damaged cartilage. However, the results of most studies report irregularly shaped beads of cartilage, which are not precise enough. Thus, a precise shape of cartilage graft must be taken into consideration. The goal of this study was to develop a simple method of creating a precisely predetermined nasal alar shape with the aid of three-dimensional printing. Lower lateral cartilage from cadavers was observed and scanned by computed tomography. Molds of the lower lateral cartilage were achieved by using three-dimensional printing. Human nasal cartilage was obtained and chondrocytes were harvested. Then, the mixture of cells and poly(glycolic acid)/poly-L-lactic acid was cultured in vitro and implanted into the subcutaneous tissue of nude mice. After subcutaneous implantation, the length and width of the samples were measured, and the results were not statistically significantly different from the native lower lateral cartilage (p > 0.05). Their thickness was measured and the results were statistically different from the native lower lateral cartilage (p < 0.05). Histologic examination of the engineered constructs revealed that both the cell and tissue morphologic features of engineered cartilage were similar to those of native lower lateral cartilage. The biomechanical properties of the engineered cartilage exceeded those of native cartilage. This study demonstrates that three-dimensional printing-aided tissue engineering can achieve precise three-dimensional shapes of human nasal alar cartilage. To our knowledge, this is the first reported creation of a precise nasal alar cartilage with a tissue-engineering strategy and three-dimensional printing technique.

  6. Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix.

    PubMed

    Liese, Juliane; Marzahn, Ulrike; El Sayed, Karym; Pruss, Axel; Haisch, Andreas; Stoelzel, Katharina

    2013-06-01

    Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.

  7. Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue cultures in vitro.

    PubMed

    Jiao, Jian; Meng, Na; Wang, Hong; Zhang, Luo

    2013-12-01

    The purpose of this study was to compare cell growth characteristics, ciliated cell differentiation, and function of human nasal epithelial cells established as explant outgrowth cultures or dissociated tissue cultures. Human nasal mucosa of the uncinate process was obtained by endoscopy and epithelial cell cultures were established by explant outgrowth or dissociated tissue culture methods. Epithelial cell growth characteristics were observed by inverted phase contrast microscopy. Ciliated cell differentiation was detected by β-tubulin IVand ZO-1 immunocytochemistry. Basal and ATP-stimulated ciliary beat frequency (CBF) was measured using a highspeed digital microscopic imaging system. Both the explant and dissociated tissue cultures established as monolayers with tight junctions and differentiated cell composition, with both types of cultures comprising ciliated and non-ciliated epithelial cells. Fibroblasts were also frequently found in explant cultures but rarely seen in dissociated tissue cultures. In both culture systems, the highest ciliated cell density appeared at 7th-10th culture day and declined with time, with the lifespan of ciliated cells ranging from 14 to 21 days. Overall, 10% of the cells in explant cultures and 20% of the cells in the dissociated tissue cultures were ciliated. These two cultures demonstrated similar ciliary beat frequency values at baseline (7.78 ± 1.99 Hz and 7.91 ± 2.52 Hz, respectively) and reacted equivalently following stimulation with 100 μM ATP. The results of this study indicate that both the explant outgrowth and dissociated tissue culture techniques are suitable for growing well-differentiated nasal ciliated and non-ciliated cells, which have growth characteristics and ciliary activity similar to those of nasal epithelial cells in vivo.

  8. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    EPA Science Inventory

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  9. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    EPA Science Inventory

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  10. [Differential proteins analysis among human nasal inverted papilloma and nasal polyposis and normal nasal mucosa].

    PubMed

    Meng, Qing-shu; Jin, Sheng; Zhang, Qiu-hang; Zhang, Man

    2010-04-01

    Proteomics-based approach was applied to analyze and compare the difference of proteins among human nasal inverted papilloma (NIP), nasal polyposis and normal nasal mucosa, in order to screen different proteins as marker. The total proteins of NIP, nasal polyposis and normal nasal mucosa were separated by two-dimensional gel electrophoresis (2-DE). Protein image obtained by using the gel of Calibrated GS-800 Densitometer system, and determined different protein spots. Six differential proteins between NIP and nasal polyp tissue were identified, which were galectin-1, Manganese-superoxide dismutase, galectin-7, trichostatin A, prohibitin and transferring. All of them were increased in NIP. Six differential proteins were possibly involved in NIP, which provided a new way for discriminating NIP from nasal polyposis. The data would be good for the establishment of NIP protein 2-DE map.

  11. Simulation modeling of the tissue disposition of formaldehyde to predict nasal DNA-protein cross-links in Fischer 344 rats, rhesus monkeys, and humans.

    PubMed

    Conolly, R B; Lilly, P D; Kimbell, J S

    2000-10-01

    Formaldehyde inhalation causes formation of DNA-protein cross-links (DPX) in the nasal mucosa of Fischer 344 (F344) rats and rhesus monkeys. DPX are considered to be part of the mechanism by which cytotoxic and carcinogenic effects of formaldehyde in laboratory animals are exerted, and DPX data have been used as a measure of tissue dose in cancer risk assessments for formaldehyde. Accurate prediction of DPX concentrations in humans is therefore desirable. The goal of this work was to increase confidence in the prediction of human DPX by refining earlier models of formaldehyde disposition and DPX kinetics in the nasal mucosa. Anatomically accurate, computational fluid dynamics models of the nasal airways of F344 rats, rhesus monkeys, and humans were used to predict the regional flux of formaldehyde to the respiratory and olfactory mucosa. A previously developed model of the tissue disposition of formaldehyde and of DPX kinetics was implemented in the graphical simulation tool SIMULINK and linked to the regional flux predictions. Statistical optimization was used to identify parameter values, and good simulations of the data were obtained. The parameter estimates for rats and monkeys were used to guide allometric scale-up to the human case. The relative levels of nasal mucosal DPX in rats, rhesus monkeys, and humans for a given inhaled concentration of formaldehyde were predicted by the model to vary with concentration. This modeling approach reduces uncertainty in the prediction of human nasal mucosal DPX resulting from formaldehyde inhalation.

  12. Reconstruction of Small Soft Tissue Nasal Defects

    PubMed Central

    Wolfswinkel, Erik M.; Weathers, William M.; Cheng, David; Thornton, James F.

    2013-01-01

    Nasal defect repair has been one of the more challenging areas of reconstructive surgery due to the lack of uniform nasal skin thickness and complex contours. Currently, algorithms for medium to large nasal soft tissue defects have been well defined by various authors. Small defects, arbitrarily defined as 1 cm or less, still present significant challenges. In this article, the authors examine the options available to repair small soft tissue nasal defects and the appropriate situations in which each method is best suited. PMID:24872751

  13. Advancing nasal reconstructive surgery: the application of tissue engineering technology.

    PubMed

    Oseni, Adelola; Crowley, Claire; Lowdell, Mark; Birchall, Martin; Butler, Peter E; Seifalian, Alexander M

    2012-11-01

    Cartilage tissue engineering is a rapidly progressing area of regenerative medicine with advances in cell biology and scaffold engineering constantly being investigated. Many groups are now capable of making neocartilage constructs with some level of morphological, biochemical, and histological likeness to native human cartilage tissues. The application of this useful technology in articular cartilage repair is well described in the literature; however, few studies have evaluated its application in head and neck reconstruction. Although there are many studies on auricular cartilage tissue engineering, there are few studies regarding cartilage tissue engineering for complex nasal reconstruction. This study therefore highlighted the challenges involved with nasal reconstruction, with special focus on nasal cartilage tissue, and examined how advancements made in cartilage tissue engineering research could be applied to improve the clinical outcomes of total nasal reconstructive surgery. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    PubMed

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

  15. Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo

    PubMed Central

    Zhang, Nan; Van Crombruggen, Koen; Holtappels, Gabriele; Lan, Feng; Katotomichelakis, Michail; Zhang, Luo; Högger, Petra; Bachert, Claus

    2014-01-01

    Background Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse. Objective To compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa. Methods We used an ex-vivo human nasal mucosal tissue model and employed pre- and post- Staphylococcus aureus enterotoxin B (SEB)-challenge incubations with various time intervals and drug concentrations to mimic typical clinical situations of preventive or therapeutic use. Results At a fixed concentration of 10−10 M, FF had significantly higher suppressive effects on interferon (IFN)-γ, interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-α, vs. MF. While the maximal suppressive activity was maintained when FF was added before or after tissue stimulation, the cytokine suppression capacity of MF appeared to be compromised when SEB-induced cell activation preceded the addition of the drug. In a pre-challenge incubation setting with removal of excess drug concentrations, MF approached inhibition of IL-5 and TNF-α after 6 and 24 hours while FF maximally blocked the release of these cytokines right after pre-incubation. Furthermore, FF suppressed a wider range of T helper cytokines compared to MF. Conclusion The study demonstrates the potential of our human mucosal model and shows marked differences in the ability to suppress the release of various cytokines in pre- and post-challenge settings between FF and MF mimicking typical clinical situations of preventive or therapeutic use. PMID:24710117

  16. A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal tissue metabolism and cross-species dosimetry.

    PubMed

    Campbell, Jerry L; Andersen, Melvin E; Clewell, Harvey J

    2014-05-01

    A PBPK model for naphthalene in the rat and human that incorporates a hybrid CFD-PBPK description of the upper respiratory tract was developed to support cross-species dosimetry comparisons of naphthalene concentrations and tissue normalized rate of metabolism in the nasal respiratory and olfactory epithelium, lung and liver. In vitro measurements of metabolic rates from microsomal incubations published for rat and monkey (surrogate for human) were scaled to the specific tissue based on the tissue microsomal content and volume of tissue. The model reproduces time courses for naphthalene blood concentrations from intravenous and inhalation exposures in rats and upper respiratory tract extraction data in both naïve rats and rats pre-treated to inhibit nasal metabolism. This naphthalene model was applied to estimate human equivalent inhalation concentrations (HECs) corresponding to several NOAELs or LOAELs for the non-cancer effects of naphthalene in rats. Two approaches for cross-species extrapolation were compared: (1) equivalence based on tissue naphthalene concentration and (2) equivalence based on amount metabolized per minute (normalized to tissue volume). At the NOAEL of 0.1 ppm, the regional gas dosimetry ratio (RGDR) based on naphthalene concentration was 0.18 for the dorsal olfactory region; however, the RGDR rises to 5.4 when based on the normalized amount metabolized due to the lower of expression of CYP isozymes in the nasal epithelium of primates and humans. The resulting HEC is 0.12 ppm (0.63 mg/m(3)) continuous exposure at the rat NOAEL of 0.1 ppm (6 h/day, 5 days/week).

  17. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

    PubMed

    Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

    2016-10-22

    Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm(2)) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

  18. Air pollutants cause release of hydrogen peroxide and interleukin-8 in a human primary nasal tissue culture model.

    PubMed

    Cho, Do-Yeon; Le, Wei; Bravo, Dawn T; Hwang, Peter H; Illek, Beate; Fischer, Horst; Nayak, Jayakar V

    2014-12-01

    A component of primary innate defense of the nasal mucosa against inhaled pathogens includes continuous, low-level release of hydrogen peroxide (H2 O2 ) into luminal secretions. Epidemiologically, an association exists between poor air quality and increased prevalence of sinonasal disease. To understand the effects of particulate matter (PM) in nasal mucosa, we studied the release of H2 O2 and interleukin 8 (IL-8) after PM exposure. Human nasal specimens were collected from surgery and cultured in serum-free growth medium. Cell integrity and recovery during culture was monitored by lactate dehydrogenase (LDH) release into the medium. Cultures were exposed to PM for 24 hours in the presence/absence of diphenyleneiodonium sulfate (DPI; a nicotinamide adenine dinucleotide phosphate [NADPH] oxidase inhibitor). Luminex cytokine and Amplex-Red H2 O2 assays were performed. LDH levels dropped rapidly within 2 days, indicative of stabilization and cell recovery after harvest. All cultures released H2 O2 into the medium. Exposure to PM (20 μg/cm(2) ) increased H2 O2 levels significantly (94.6 ± 7.7 nM) compared to untreated controls (55.8 ± 4.0 nM; p = 0.001). PM-induced H2 O2 production was partially inhibited by DPI (80.1 ± 3.8nM), indicating that cellular NADPH oxidase may be a primary source of H2 O2 production. Exposure to PM increased IL-8 levels in a dose-dependent fashion (control = 2301 ± 412 MFI; 20 μg/cm(2) = 5002 ± 1327 MFI; 40 μg/cm(2) = 8219 ± 1090 MFI; p = 0.022). PM increases the quantity of H2 O2 released by nasal epithelial cells, indicating that PM can contribute to oxidative stress in part by activating a normal cellular defense mechanism. Exposure to PM resulted in elevated IL-8 levels and mucin production in explants. Efforts to reduce airborne PM may lead to reduced H2 O2 and mucin production in sinonasal epithelium. © 2014 ARS-AAOA, LLC.

  19. A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.

    PubMed

    Frederick, C B; Gentry, P R; Bush, M L; Lomax, L G; Black, K A; Finch, L; Kimbell, J S; Morgan, K T; Subramaniam, R P; Morris, J B; Ultman, J S

    2001-05-01

    To assist in interspecies dosimetry comparisons for risk assessment of the nasal effects of organic acids, a hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of inhaled vapors in the rat and human nasal cavity. Application to a specific vapor would involve the incorporation of the chemical-specific reactivity, metabolism, partition coefficients, and diffusivity (in both air and tissue phases) of the vapor. This report describes the structure of the CFD-PBPK model and its application to a representative acidic vapor, acrylic acid, for interspecies tissue concentration comparisons to assist in risk assessment. By using the results from a series of short-term in vivo studies combined with computer modeling, regional nasal tissue dose estimates were developed and comparisons of tissue doses between species were conducted. To make these comparisons, the assumption was made that the susceptibilities of human and rat olfactory epithelium to the cytotoxic effects of organic acids were similar, based on similar histological structure and common mode of action considerations. Interspecies differences in response were therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The results of simulations with the seven-compartment CFD-PBPK model suggested that the olfactory epithelium of the human nasal cavity would be exposed to tissue concentrations of acrylic acid similar to that of the rat nasal cavity when the exposure conditions are the same. Similar analysis of CFD data and CFD-PBPK model simulations with a simpler one-compartment model of the whole nasal cavities of rats and humans provides comparable results to averaging over the compartments of the seven-compartment model. These

  20. Air flow in the human nasal cavity

    NASA Astrophysics Data System (ADS)

    Fomin, V. M.; Vetlutsky, V. N.; Ganimedov, V. L.; Muchnaya, M. I.; Shepelenko, V. N.; Melnikov, M. N.; Savina, A. A.

    2010-03-01

    A mathematical model of the air flow in the human nasal cavity is developed under the assumption of a turbulent viscous air flow. The shape of the nasal cavity is modeled with the use of the Gambit graphical software system and tomography data. A numerical solution is obtained by using the Fluent commercial software system. Calculations are performed for various variants of construction of the human nasal cavity.

  1. Nasal obstruction and human communication.

    PubMed

    Malinoff, R; Moreno, C

    1989-04-01

    Nasal obstruction may cause a variety of communication disorders, particularly in children. The effects of nasal obstruction on hearing, speech, language, and voice are examined. Methods for assessing the effects of nasal obstruction are delineated, and recommendations for therapeutic interventions are described.

  2. Nasal cytochrome P4502A: Identification in rats and humans

    SciTech Connect

    Thornton-Manning, J.R.; Hotchkiss, J.A.; Ding, Xinxin

    1995-12-01

    The nasal mucosa, the first tissue of contact for inhaled xenobiotics, possesses substantial enobiotic-metabolizing capacti. Enzymes of the nasal cavity may metabolize xenobiotics to innocuous, more water-soluble compounds that are eliminated from the body, or they may bioactivate them to toxic metabolites. These toxic metabolites may find to cellular macromolecules in the nasal cavity or be transported to other parts of the body where they may react. Nasal carcinogenesis in rodents often results from bioactivation of xenobiotics. The increased incidences of nasal tumors associated with certain occupations suggest that xenobiotic bioactivation may be important in human nasal cancer etiology, as well. The increasing popularity of the nose as a route of drug administration makes information concerning nasal drug metabolism and disposition vital to accomplish therapeutic goals. For these reasons, the study of xenobiotic-met abolizing capacity of the nasal cavity is an important area of health-related research. In the present study, we have confirmed the presence of CYP2A6 mRNA in human respiratory mucosa.

  3. Exploring the bacterial assemblages along the human nasal passage.

    PubMed

    Wos-Oxley, Melissa L; Chaves-Moreno, Diego; Jáuregui, Ruy; Oxley, Andrew P A; Kaspar, Ursula; Plumeier, Iris; Kahl, Silke; Rudack, Claudia; Becker, Karsten; Pieper, Dietmar H

    2016-07-01

    The human nasal passage, from the anterior nares through the nasal vestibule to the nasal cavities, is an important habitat for opportunistic pathogens and commensals alike. This work sampled four different anatomical regions within the human nasal passage across a large cohort of individuals (n = 79) comprising individuals suffering from chronic nasal inflammation clinically known as chronic rhinosinusitis (CRS) and individuals not suffering from inflammation (CRS-free). While individuals had their own unique bacterial fingerprint that was consistent across the anatomical regions, these bacterial fingerprints formed into distinct delineated groups comprising core bacterial members, which were consistent across all four swabbed anatomical regions irrespective of health status. The most significant observed pattern was the difference between the global bacterial profiles of swabbed and tissue biopsy samples from the same individuals, being also consistent across different anatomical regions. Importantly, no statistically significant differences could be observed concerning the global bacterial communities, any of the bacterial species or the range of diversity indices used to compare between CRS and CRS-free individuals, and between two CRS phenotypes (without nasal polyps and with nasal polyps). Thus, the role of bacteria in the pathogenesis of sinusitis remains uncertain. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Nasal chondrocytes and fibrin sealant for cartilage tissue engineering.

    PubMed

    Vinatier, C; Gauthier, O; Masson, M; Malard, O; Moreau, A; Fellah, B H; Bilban, M; Spaethe, R; Daculsi, G; Guicheux, J

    2009-04-01

    Hybrid constructs associating a biodegradable matrix and autologous chondrocytes hold promise for the treatment of articular cartilage defects. In this context, our objective was to investigate the potential use of nasal chondrocytes associated with a fibrin sealant for the treatment of articular cartilage defects. The phenotype of primary nasal chondrocytes (NC) from human (HNC) and rabbit (RNC) origin were characterized by RT-PCR. The ability of constructs associating fibrin sealant and NC to form a cartilaginous tissue in vivo was investigated, firstly in a subcutaneous site in nude mice and secondly in an articular cartilage defect in rabbit. HNC express type II collagen and aggrecan, the two major hallmarks of a chondrocytic phenotype. Furthermore, when injected subcutaneously into nude mice within a fibrin sealant, these chondrocytes were able to form a cartilage-like tissue. Our data indicate that RNC also express type II collagen and aggrecan and maintained their phenotype in three-dimensional culture within a fibrin sealant. Moreover, treatment of rabbit articular cartilage defects with autologous RNC embedded in a fibrin sealant led to the formation of a hyalin-like repair tissue. The use of fibrin sealant containing hybrid autologous NC therefore appears as a promising approach for cell-based therapy of articular cartilage. Copyright 2008 Wiley Periodicals, Inc.

  5. Hypoxia Increases Epithelial Permeability in Human Nasal Epithelia

    PubMed Central

    Min, Hyun Jin; Kim, Tae Hoon; Yoon, Joo-Heon

    2015-01-01

    Purpose The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells. Materials and Methods The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting. Results Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control. Conclusion Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens. PMID:25837192

  6. Measuring and Characterizing the Human Nasal Cycle

    PubMed Central

    Kahana-Zweig, Roni; Geva-Sagiv, Maya; Weissbrod, Aharon; Secundo, Lavi; Soroker, Nachum; Sobel, Noam

    2016-01-01

    Nasal airflow is greater in one nostril than in the other because of transient asymmetric nasal passage obstruction by erectile tissue. The extent of obstruction alternates across nostrils with periodicity referred to as the nasal cycle. The nasal cycle is related to autonomic arousal and is indicative of asymmetry in brain function. Moreover, alterations in nasal cycle periodicity have been linked to various diseases. There is therefore need for a tool allowing continuous accurate measurement and recording of airflow in each nostril separately. Here we provide detailed instructions for constructing such a tool at minimal cost and effort. We demonstrate application of the tool in 33 right-handed healthy subjects, and derive several statistical measures for nasal cycle characterization. Using these measures applied to 24-hour recordings we observed that: 1: subjects spent slightly longer in left over right nostril dominance (left = 2.63 ± 0.89 hours, right = 2.17 ± 0.89 hours, t(32) = 2.07, p < 0.05), 2: cycle duration was shorter in wake than in sleep (wake = 2.02 ± 1.7 hours, sleep = 4.5 ± 1.7 hours, (t(30) = 5.73, p < 0.0001). 3: slower breathing was associated with a more powerful cycle (the extent of difference across nostrils) (r = 0.4, p < 0.0001), and 4: the cycle was influenced by body posture such that lying on one side was associated with greater flow in the contralateral nostril (p < 0.002). Finally, we provide evidence for an airflow cycle in each nostril alone. These results provide characterization of an easily obtained measure that may have diagnostic implications for neurological disease and cognitive state. PMID:27711189

  7. Measuring and Characterizing the Human Nasal Cycle.

    PubMed

    Kahana-Zweig, Roni; Geva-Sagiv, Maya; Weissbrod, Aharon; Secundo, Lavi; Soroker, Nachum; Sobel, Noam

    2016-01-01

    Nasal airflow is greater in one nostril than in the other because of transient asymmetric nasal passage obstruction by erectile tissue. The extent of obstruction alternates across nostrils with periodicity referred to as the nasal cycle. The nasal cycle is related to autonomic arousal and is indicative of asymmetry in brain function. Moreover, alterations in nasal cycle periodicity have been linked to various diseases. There is therefore need for a tool allowing continuous accurate measurement and recording of airflow in each nostril separately. Here we provide detailed instructions for constructing such a tool at minimal cost and effort. We demonstrate application of the tool in 33 right-handed healthy subjects, and derive several statistical measures for nasal cycle characterization. Using these measures applied to 24-hour recordings we observed that: 1: subjects spent slightly longer in left over right nostril dominance (left = 2.63 ± 0.89 hours, right = 2.17 ± 0.89 hours, t(32) = 2.07, p < 0.05), 2: cycle duration was shorter in wake than in sleep (wake = 2.02 ± 1.7 hours, sleep = 4.5 ± 1.7 hours, (t(30) = 5.73, p < 0.0001). 3: slower breathing was associated with a more powerful cycle (the extent of difference across nostrils) (r = 0.4, p < 0.0001), and 4: the cycle was influenced by body posture such that lying on one side was associated with greater flow in the contralateral nostril (p < 0.002). Finally, we provide evidence for an airflow cycle in each nostril alone. These results provide characterization of an easily obtained measure that may have diagnostic implications for neurological disease and cognitive state.

  8. [Predictive significance of tissue eosinophilia for nasal polyp recurrence].

    PubMed

    Wang, C S; Lou, H F; Meng, Y F; Piao, Y S; Zhang, L

    2016-04-07

    To evaluate the association between clinical parameters, especially tissue eosinophilia, and chronic sinusitis with nasal polyps (CRSwNP) recurrence. To identify optimal criteria of tissue eosinophilia as a predictor for recurrence. Two hundred and forty-eight CRSwNP patients were enrolled in this study. The demographic and clinical features were compared between recurrence and no recurrence groups. Mucosal specimens were assessed for the presence of tissue inflammatory cells. Factors associated with polyp recurrence were analyzed by Logistic regression analysis and optimal cutoff point of the predictor for nasal polyp recurrence was determined by receiver operating characteristic curve. SPSS 19.0 software was used to analyze the data. The recurrence rate was 55.6%(138/248 patients) in this cohort. Tissue and peripheral eosinophilia, comorbid asthma, olfactory score and Lund-Mackay score were significantly correlated with polyp recurrence(all P<0.01). As a predictor for recurrence, tissue eosinophil accumulation outweighed other parameters. A cutoff value of 27% for tissue eosinophil percentage was able to predict recurrence with 96.4% sensitivity and 92.7% specificity (AUC=0.971, P<0.001). Tissue eosinophilia provides valuable information regarding to polyp recurrence. Tissue eosinophil proportion equal to or over 27% may be regarded as the prognostic criterion for nasal polyp recurrence.

  9. Enhanced release of IgE-dependent early phase mediators from nasal polyp tissue

    PubMed Central

    Patou, Joke; Holtappels, Gabriele; Affleck, Karen; Gevaert, Philippe; Perez-Novo, Claudina; Van Cauwenberge, Paul; Bachert, Claus

    2009-01-01

    Background The mast cell is a crucial effector cell in allergic rhinitis and other inflammatory diseases. During the acute allergic reaction preformed mediators such as histamine, but also de novo produced mediators such as leukotrienes (LTC4/D4/E4) and prostaglandins (PGD2) are released. Mast cells represent targets for therapeutic intervention, and thus a human ex-vivo model to stimulate mast cells taken from mucosal sites would be instrumental for drug intervention studies. We have aimed to activate mast cells within ex-vivo human nasal tissue by IgE/anti-IgE specific (ε chain specific) stimulations and in this respect to test the usability of nasal polyps versus inferior turbinates Methods Biopsy samples were collected from patients with nasal polyps and inferior turbinates from patients who underwent sinus or septal surgery. Tissue fragments were primed with IgE 1 μg/ml for 60 minutes and then stimulated for 30 minutes with tissue culture medium (negative control), anti-IgE 10 μg/ml, anti-IgE 30 μg/ml and ionomycin 10 μM (positive control). Histamine, leukotrienes and PGD2 were measured in supernatants. To help provide an understanding of the extent of the response, the number of tryptase and FcεRIα positive cells was evaluated by means of immunohistochemistry and the FcεRIα-chain was measured by means of quantitative PCR in the nasal polyp and inferior turbinate tissues. Finally, the correlation between IgE concentrations in the nasal tissue and the release of mediators was analysed. Results Stimulations with anti-IgE on IgE-primed nasal tissue fragments lead to a concentration-dependent release of histamine, leukotrienes and PGD2. The release of these early phase mediators was significantly higher in nasal polyps compared to inferior turbinates, although tryptase, FcεRIα positive cells and FcεRIα-chain transcripts were equally present in both groups. No correlation was found between baseline concentrations of IgE, and the release of histamine

  10. Airflow patterns in a human nasal model

    SciTech Connect

    Hornung, D.E.; Leopold, D.A.; Youngentob, S.L.; Sheehe, P.R.; Gagne, G.M.; Thomas, F.D.; Mozell, M.M.

    1987-02-01

    Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

  11. Characterizing human nasal airflow physiologic variables by nasal index.

    PubMed

    Patki, Aniruddha; Frank-Ito, Dennis O

    2016-10-01

    Although variations in nasal index (NI) have been reported to represent adaptation to climatic conditions, assessments of NI with airflow variables have not been rigorously investigated. This study uses computational fluid dynamics modeling to investigate the relationship between NI and airflow variables in 16 subjects with normal nasal anatomy. Airflow simulations were conducted under constant inspiratory pressure. Nasal resistance (NR) against NI showed weak association from nostrils to anterior inferior turbinate (R(2)=0.26) and nostril to choanae (R(2)=0.12). NI accounted for 38% and 41% of the respective variation in wall shear stress (WSS) and heat flux (HF) at the nasal vestibule, and 52% and 49% of variability in WSS and HF across the entire nose. HF and WSS had strong correlation with NI<80, and weakly correlated with NI>80; these differences in HF and WSS for NI<80 and NI>80 were not statistically significant. Results suggest strong relationship between NI and both WSS and HF but not NR, particularly in subjects with NI<80. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Nasal Soft-Tissue Triangle Deformities.

    PubMed

    Foda, Hossam M T

    2016-08-01

    The soft-tissue triangle is one of the least areas attended to in rhinoplasty. Any postoperative retraction, notching, or asymmetries of soft triangles can seriously affect the rhinoplasty outcome. A good understanding of the risk factors predisposing to soft triangle deformities is necessary to prevent such problems. The commonest risk factors in our study were the wide vertical domal angle between the lateral and intermediate crura, and the increased length of intermediate crus. Two types of soft triangle grafts were described to prevent and treat soft triangle deformities. The used soft triangle grafts resulted in an excellent long-term aesthetic and functional improvement.

  13. Regulatory Adaptation of Staphylococcus aureus during Nasal Colonization of Humans

    PubMed Central

    Burian, Marc; Wolz, Christiane; Goerke, Christiane

    2010-01-01

    The nasopharynx is the main ecological niche of the human pathogen Staphylococcus aureus. Although colonization of the nares is asymptomatic, nasal carriage is a known risk factor for endogenous staphylococcal infection. We quantified S. aureus mRNA levels in nose swabs of persistent carriers to gain insight into the regulatory adaptation of the bacterium to the nasal environment. We could elucidate a general response of the pathogen to the surrounding milieu independent of the strain background or the human host. Colonizing bacteria preferentially express molecules necessary for tissue adherence or immune-evasion whereas toxins are down regulated. From the analysis of regulatory loci we found evidence for a predominate role of the essential two-component system WalKR of S. aureus. The results suggest that during persistent colonization the bacteria are metabolically active with a high cell surface turnover. The increased understanding of bacterial factors that maintain the colonization state can open new therapeutic options to control nasal carriage and subsequent infections. PMID:20386721

  14. Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

    SciTech Connect

    Rodgers, D.A.; Nikula, K.J.; Avila, K.

    1995-12-01

    The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models to human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.

  15. Toxicology of the nasal passages

    SciTech Connect

    Barrow, C.S.

    1986-01-01

    Contents of this work include: Comparative Anatomy and Function of the Nasal Passages; Light Microscopic Examination of the Rat Nasal Passages: Preparation and Morphologic Features; Histopathology of Acute and Subacute Nasal Toxicity; Pathology of Chronic Nasal Toxic Responses Including Cancer; Responses of the Nasal Mucociliary Apparatus to Airborne Irritants; Effects of Chemical Exposure on Olfaction in Humans, Possible Consequences of Cytochrome P-450-Dependent Monooxygenases in Nasal Tissues.

  16. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps.

    PubMed

    Kim, Dong-Young; Lee, Sun Hye; Carter, Roderick G; Kato, Atsushi; Schleimer, Robert P; Cho, Seong H

    2016-08-01

    Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs.

  17. Characterizing adult human nasal airway dimensions

    SciTech Connect

    Guilmette, R.A.; Griffith, W.C.

    1994-11-01

    Respiratory tract models used in calculating radiation dose from exposure to inhaled radioactive aerosols have only recently focused attention on the importance of the nasal airways (NAs). Because the NAs are the first tissues of the respiratory tract available for aerosol deposition in normally nose-breathing people, any deposition of aerosol in this anatomical structure will reduce the amounts available to be deposited in the remainder of the respiratory tract. Thus, uncertainties in estimating the deposition fractions in the NAs will propagate throughout the remainder of the respiratory tract, creating errors in the calculated dose estimates. Additionally, there is evidence that the NAs are also at risk for induction of cancer from exposure to certain occupational aerosols such as wood dust, leather dust, chromium, and nickel. The purpose of this investigation was to conduct an anatomical study to assess the variabilities in NA dimensions.

  18. Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

    PubMed Central

    Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-01-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

  19. Marine collagen scaffolds for nasal cartilage repair: prevention of nasal septal perforations in a new orthotopic rat model using tissue engineering techniques.

    PubMed

    Bermueller, Christian; Schwarz, Silke; Elsaesser, Alexander F; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-10-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair.

  20. Nasal Soft Tissue Change Following Bimaxillary Orthognathic Surgery.

    PubMed

    Jeong, Hye-In; Lee, Ho-Sung; Jung, Young-Soo; Park, Hyung-Sik; Jung, Hwi-Dong

    2017-05-31

    The purpose of this study is to identify the correlation between maxillary movement and nasal soft tissue changes on three-dimensional reconstructed cone beam computed tomography (CBCT) images after Le Fort I osteotomy. The authors also investigate the long-term change of alar base width (ABW) to determine the effect of cinch suture. The authors retrospectively studied 52 subjects (14 males and 38 females) who were treated by bimaxillary orthognathic surgery including Le Fort I osteotomy and mandibular ramus surgery. The landmarks and planes were established on three-dimensional reconstructed CBCT images. The authors measured each parameters preoperatively, 1 month postoperatively, and 1 year postoperatively. There was no significant correlation between the horizontal movement of A-point and the widening of ABW (P < 0.038), nor was there a significant correlation between the vertical movement of A-point and the change of ABW (P < 0.61). There was no significant correlation between horizontal and vertical movement of anterior nasal spine and the widening of ABW, nor was there a significant correlation between the nasal tip length and the vector of maxillary movement. There was no significant correlation between the ABW widening and the vector of surgical maxillary movement. The effect and stability of the alar base cinch suture is difficult to determine and require further investigation.

  1. Heavy metals in normal mucosa and nasal polyp tissues from Tunisian patients.

    PubMed

    Khlifi, Rim; Olmedo, Pablo; Gil, Fernando; Chakroun, Amine; Hammami, Boutheina; Hamza-Chaffai, Amel

    2015-01-01

    Despite growing evidence that bacteria, fungi, allergens, and superantigens play a prominent role in the pathophysiology of nasal polyps (NP), the exact cause of polyposis is still unknown. The etiology of NP is considered multifactorial. Until now, there is no information on the presence of heavy metals, such as cadmium (Cd), chromium (Cr), nickel (Ni), and arsenic (As) or of their role, in the pathogenesis of NP disease. In this study, concentrations of these four metals in tissue of NP were determined using Atomic Absorption Spectrometry. The Ni, Cr, and As levels in NP tissues were 2.1-, 3.2-, and 8.0-fold higher than those of normal mucosa (p < 0.05), respectively. A strong effect of cumulative smoking as expressed in the number of pack per year (PY), Ni, As, and Cd levels in NP tissue samples of patients ever-smokers (1-20 and >20 PY) are significantly higher than those of non-smokers (p = 0.006, 0.002, and < 0.001, respectively). The highest As concentrations among patients lived at polluted areas (1-25 and > 25 years) were observed in both nasal mucosa and NP tissues. The Ni and As in both nasal mucosa and NP tissues of patients occupationally exposed were significantly higher than non-exposed group. Cr and As levels were found to be associated with NP stage classification (p < 0.05). This is the first report to describe an association between concentrations of metals (Cr, As, and Ni) in human NP tissues and the risk of NP disease. Tissue metal levels have increased due to smoking, environmental, and occupational exposure. Therefore, heavy metal exposure may increase the risk of NP in the Tunisian population. The considerable risk in the category of highest cumulative exposure argues for an association between heavy metals exposure and nasal polyposis risk. Future investigations with larger samples should better elucidate this association.

  2. [Establishment of 2-dimensional gel electrophoresis map and analysis of proteomics from human nasal polyps].

    PubMed

    He, Guang-xiang; Sun, Hong; Wang, Tian-sheng; Li, Gui; Liu, Huo-wang; Chen, Yu

    2006-08-01

    To establish 2-dimensional polyacrylamide gel electrophoresis (2-DE) map from human nasal polyps and normal nasal mucosa, and to identify differential expression proteins of 2-DE map. Samples of nasal polyps and nasal mucosa (each sample group containing 7 cases) were obtained. The total proteins were extracted and separated by immobilized pH gradient (IPG)-based 2-DE. The silver-stained 2-DE was scanned with digital Imagescanner and analyzed with ImageMaster 2-DE Elite 4.01 software. To obtain peptide mass fingerprint (PMF) of differential protein spots, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used. The PMF was searched in Swiss-Prot and TreMBL database by Pept-Ident software, to identify differential expression proteins. The well-resolved, reproducible 2-DE maps of nasal polyps and nasal mucosa were established. For the polyps tissues, the average proteins spot of three 2-DE maps was 825+/-78; and 682+/-96 spot was matched with the average matching rate of 82.7%. The average deviations of matched spot position were (1.13+/-0.16) mm in IEF direction and (1.45+/-0.21) mm in SDS-PAGE direction, respectively. For the nasal mucosa tissues, the average proteins spot of three 2-DE maps was 936+/-62; and 821+/-78 spots were matched with the average matching rate of 87.7%. After comparing the 2-DE maps of nasal polyps and nasal mucosa tissues, the protein spots were 1,458 and 1,617 respectively; and 1,026 protein spots were matched. Forty differential expression protein spots were incised from silver staining gel randomly and digested in the gel by TPCK-Trypsin. Thirty-four PMFs were obtained by MALDI-TOF-MS and 24 differential proteins were identified. The well-resolved, reproducible 2-DE maps of human nasal polyps and nasal mucosa have been successfully established. Certain differential proteins related to the pathogenesis of human nasal polyps are identified.

  3. The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

    PubMed

    Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

    2016-02-17

    The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

  4. Air-conditioning in the human nasal cavity.

    PubMed

    Elad, David; Wolf, Michael; Keck, Tilman

    2008-11-30

    Healthy humans normally breathe through their nose even though its complex geometry imposes a significantly higher resistance in comparison with mouth breathing. The major functional roles of nasal breathing are defense against infiltrating particles and conditioning of the inspired air to nearly alveolar conditions in order to maintain the internal milieu of the lung. The state-of-the-art of the existing knowledge on nasal air-conditioning will be discussed in this review, including in vivo measurements in humans and computational studies on nasal air-conditioning capacity. Areas where further studies will improve our understanding and may help medical diagnosis and intervention in pathological states will be introduced.

  5. Ecogeographic variation in human nasal passages.

    PubMed

    Yokley, Todd R

    2009-01-01

    Theoretically, individuals whose ancestors evolved in cold and/or dry climates should have greater nasal mucosal surface area relative to air volume of the nasal passages than individuals whose ancestors evolved in warm, humid climates. A high surface-area-to-volume (SA/V) ratio allows relatively more air to come in contact with the mucosa and facilitates more efficient heat and moisture exchange during inspiration and expiration, which would be adaptive in a cold, dry environment. Conversely, a low SA/V ratio is not as efficient at recapturing heat and moisture during expiration and allows for better heat dissipation, which would be adaptive in a warm, humid environment. To test this hypothesis, cross-sectional measurements of the nasal passages that reflect surface area and volume were collected from a sample of CT scans of patients of European and African ancestry. Results indicate that individuals of European descent do have higher SA/V ratios than individuals of African descent, but only when decongested. Otherwise, the two groups show little difference. This pattern of variation may be due to selection for different SA/V configurations during times of physical exertion, which has been shown to elicit decongestion. Relationships between linear measurements of the skeletal nasal aperture and cavity and cross-sectional dimensions were also examined. Contrary to predictions, the nasal index, the ratio of nasal breadth to nasal height, is not strongly correlated with internal dimensions. However, differences between the nasal indices of the two groups are highly significant. These results may be indicative of different adaptive solutions to the same problem.

  6. [Relationship between nasal inverted papilloma and human papillomavirus subtypes].

    PubMed

    Sun, Pu; Chen, Xiao-ping; Pei, Fei; Ma, Rui-xia; Zhang, Yi; Chen, Qun; Dong, Wei-gang; Chen, Wei-xiang; Huang, Hui-li

    2010-04-01

    To study the distribution of human papillomavirus (HPV) subtypes in nasal inverted papilloma (NIP), and to evaluate the relationship between HPV and NIP. Twenty-one HPV subtypes were detected in paraffin-embedded tissues of 101 cases of NIP by flow through hybridization and gene chip (HybriMax), 24 cases of normal nasal mucosa were used as controls. HPV positive rates of NIP were 64.36% (65/101). Benign NIP group, NIP with atypical hyperplasia group, NIP with cancerous group of HPV positive rates were 59.7% (46/77), 81.8% (18/22) and 50% (1/2) respectively. The control group was negative (0/24). The comparison between NIP group and control group was statistically significant (chi(2) = 32.178, P < 0.05). Benign NIP group and NIP with atypical hyperplasia group were compared, but no statistically significance (chi(2) = 3.649, P = 0.056) was found. The constituent ratio of benign NIP group and NIP with atypical hyperplasia group in high, low-risk HPV subtypes infections was compared, a statistically significance (chi(2) = 10.412, P < 0.05) was found. The occurrence of NIP was related with HPV infection. High-risk HPV subtype infections or multiple infections will prompt benign NIP to NIP with atypical hyperplasia. Understanding the distribution of HPV subtypes in the NIP is helpful to predict the clinical behavior.

  7. Mechanics of airflow in the human nasal airways.

    PubMed

    Doorly, D J; Taylor, D J; Schroter, R C

    2008-11-30

    The mechanics of airflow in the human nasal airways is reviewed, drawing on the findings of experimental and computational model studies. Modelling inevitably requires simplifications and assumptions, particularly given the complexity of the nasal airways. The processes entailed in modelling the nasal airways (from defining the model, to its production and, finally, validating the results) is critically examined, both for physical models and for computational simulations. Uncertainty still surrounds the appropriateness of the various assumptions made in modelling, particularly with regard to the nature of flow. New results are presented in which high-speed particle image velocimetry (PIV) and direct numerical simulation are applied to investigate the development of flow instability in the nasal cavity. These illustrate some of the improved capabilities afforded by technological developments for future model studies. The need for further improvements in characterising airway geometry and flow together with promising new methods are briefly discussed.

  8. Utility of human amniotic membrane allograft in re-epithelialization of the nasal tip

    PubMed Central

    Dennis, D'Antonio C.; Turnock, Adam R.; Sutton, Collin; Chastant, Bradley; Vanderlan, Wesley B.

    2016-01-01

    Variations in skin thickness and contours pose significant challenges to reconstruction of the lower third of the nose. Human amniotic membrane allograft offers a potential alternative to tissue transfer in reconstruction of the lower third of the nose. We reviewed the procedure and photographs of a healthy 56-year-old male with a 22 × 18 mm lower third nasal defect involving full thickness skin and subcutaneous tissue. Following preparation for grafting, dehydrated human amniotic membrane was fashioned to the dimensions of the defect and applied. No further surgical intervention was provided for 3 months. Complete re-epithelialization of the nasal and adjacent defects was achieved with minimal scar formation. Human amniotic membrane allograft provides an efficacious and cosmetically acceptable alternative to local and regional tissue transfer.

  9. Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections

    PubMed Central

    Johnson, Ryan C.; Ellis, Michael W.; Lanier, Jeffrey B.; Schlett, Carey D.; Cui, Tianyuan

    2014-01-01

    The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization with Staphylococcus aureus is an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance of Proteobacteria in the anterior nares in non-SSTI participants (P < 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation between Corynebacterium spp. and S. aureus (P = 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI. PMID:25486991

  10. Correlation between nasal microbiome composition and remote purulent skin and soft tissue infections.

    PubMed

    Johnson, Ryan C; Ellis, Michael W; Lanier, Jeffrey B; Schlett, Carey D; Cui, Tianyuan; Merrell, D Scott

    2015-02-01

    The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization with Staphylococcus aureus is an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance of Proteobacteria in the anterior nares in non-SSTI participants (P < 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation between Corynebacterium spp. and S. aureus (P = 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Shape of the human nasal cavity promotes retronasal smell

    NASA Astrophysics Data System (ADS)

    Trastour, Sophie; Melchionna, Simone; Mishra, Shruti; Zwicker, David; Lieberman, Daniel E.; Kaxiras, Efthimios; Brenner, Michael P.

    2015-11-01

    Humans are exceptionally good at perceiving the flavor of food. Flavor includes sensory input from taste receptors but is dominated by olfactory (smell) receptors. To smell food while eating, odors must be transported to the nasal cavity during exhalation. Olfactory performance of this retronasal route depends, among other factors, on the position of the olfactory receptors and the shape of the nasal cavity. One biological hypothesis is that the derived configuration of the human nasal cavity has resulted in a greater capacity for retronasal smell, hence enhanced flavor perception. We here study the air flow and resulting odor deposition as a function of the nasal geometry and the parameters of exhalation. We perform computational fluid dynamics simulations in realistic geometries obtained from CT scans of humans. Using the resulting flow fields, we then study the deposition of tracer particles in the nasal cavity. Additionally, we derive scaling laws for the odor deposition rate as a function of flow parameters and geometry using boundary layer theory. These results allow us to assess which changes in the evolution of the human nose led to significant improvements of retronasal smell.

  12. Human nasal mucosal changes after exposure to urban pollution.

    PubMed Central

    Calderon-Garcidueñas, L; Rodriguez-Alcaraz, A; Garcia, R; Sanchez, G; Barragan, G; Camacho, R; Ramirez, L

    1994-01-01

    Millions of people worldwide are living in areas where ozone (O3) concentrations exceed health standards (an hourly average of 235 micrograms/m3/0.12 ppm, not to be exceeded more than once per year). Ozone induces acute nasal inflammatory responses and significant epithelial lesions in experimental animals and humans. To determine the nasal effects of a 15-day exposure to an urban polluted atmosphere with O3 as the main pollutant, we studied a population of healthy, young males newly arrived to southwest metropolitan Mexico City (SWMMC). The study included 49 non-smoking residents in an unpolluted port, Veracruz City; 14 subjects stayed in the port and served as controls, while 35 subjects traveled to SWMMC and had serial nasal lavages at different times after arriving in SWMMC. Subjects had exposures to ambient O3 an average of 10.2 hr/day, with a total cumulative O3 exposure of 10.644 ppm.hr. Nasal inflammatory responses, polymorphonuclear leukocyte PMN-CD11b surface expression, rhinoscopic changes, and respiratory symptoms were evaluated. Exposed subjects had massive nasal epithelial shedding and significant responses in PMN nasal influx (p < 0.00001) and in PMN-CD11b expression (p < 0.05). Cumulative O3 exposure correlated with respiratory symptoms, PMNs (rs = 0.2374, p < 0.01), and CD11b (rs = 0.3094, p < 0.01); 94% of exposed subjects experienced respiratory symptoms, and 97% left the city with an abnormal nasal mucosa by rhinoscopy. Nasal epithelial changes persisted 2 weeks after the exposed subjects returned to their nonpolluted environment. Exposure to an urban polluted atmosphere induces significant and persistent nasal epithelial alterations in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 2. D Figure 2. E Figure 2. F Figure 3. A Figure 3. B Figure 4. A Figure 4. B Figure 5. A Figure 5. B PMID:7713020

  13. Fibrotic Tissue and Middle Turbinate Exhibit Similar Mechanical Properties. Is Fibrosis a Solution in Nasal Polyposis?

    PubMed Central

    Gregório, Luciano; Pezato, Rogério; Felici, Rafael Souza; Kosugi, Eduardo Macoto

    2016-01-01

    Introduction Nasal polyposis (NP) is a chronic inflammatory condition of the upper airway characterized by overgrowth of nasal mucosa. Recent studies have shown a mechanical dysfunction in the nasal polyp tissue. Objective This study aims to evaluate the mechanical properties of nasal fibrotic tissue. Method This study was an institutional review board approved translational study in 20 participants (8 patients with NP, 7 patients with nasal synechiae, and 5 subjects without sinus disease (control group). We used Controlled Disc Stimulation equipment to compare the curve Pressure/Volume created during the saline solution infusion. Results The increase of pressure in response to solution injection was lower in the nasal polyp group when compared with control middle turbinate group and fibrotic group. No significant difference was found in the pressure response during solution injection between fibrotic group and control middle turbinate group. Inferior turbinate group showed significant difference when compared with control middle turbinate group. Conclusion The mechanical dysfunction found in the nasal mucosa of patients with NP provides new insight into this condition. These data allow the belief that the fibrosis has a potential role in increasing interstitial hydrostatic pressure and, consequently, mitigating edema formation in NP.

  14. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

    PubMed

    Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

    2016-10-01

    In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Clearance concepts applied to the metabolism of inhaled vapors in tissues lining the nasal cavity.

    PubMed

    Andersen, M E; Sarangapani, R

    1999-10-01

    Some inhaled vapors are metabolized by tissues in the nasal cavity or carried away in nasal venous blood after diffusing from the lumen through the nasal epithelial tissues. These processes remove chemical from the airstream. Clearance (volume/time) is the volumetric airflow from which chemical would have to be completely removed to account for the net loss. We present here a steady-state analysis of a series of physiologically based clearance-extraction (PBCE) models for nasal clearance of inhaled vapors, consisting of one, two, three, or four subcompartments. A two-compartment model is the simplest representation of tissues in the nasal cavity, with an air and a tissue compartment. The three-compartment model had air, mucus, and tissue phases. The four-compartment model included both epithelial and submucosal tissues in addition to the air and mucus compartments. For the two-, three-, and four-compartment models, the airstream clearance (Cl(sys)) equation has a common form. Cl(sys) = Cl(tot)H(m:a)PA(gas)Q divided by Cl(tot)H(m:a)(Q + PA(gas)) + PA(gas)Q. In this equation, Cl(tot) is the total tissue clearance, PA(gas) is the gas-phase diffusional clearance, Q is the airflow, and H(muc:a) is the mucus air partition coefficient. Cl(tot) varies in complexity for the different models since it encompasses tissue diffusion, tissue clearance due to metabolism, and blood flow. A physiologically based clearance-extraction (PBCE) model for the whole nose with three nasal tissue regions, each containing a four-compartment tissue stack, was used to simulate nasal uptake of three vapors-acetone, methyl methacrylate (MMA), and vinyl acetate (VA)-to show the dependence of clearance on different parameters for specific compounds. Acetone is not metabolized in the nose, MMA is metabolized at a moderate rate by nasal tissues, and VA is metabolized at a high rate in mucus and tissues. Equations derived from steady-state analyses show the importance of the specific biochemical and

  16. Physiologically based pharmacokinetic (PBPK) models for nasal tissue dosimetry of organic esters: assessing the state-of-knowledge and risk assessment applications with methyl methacrylate and vinyl acetate.

    PubMed

    Andersen, Melvin E; Green, Trevor; Frederick, Clay B; Bogdanffy, Matthew S

    2002-12-01

    Mathematical models have been developed to describe nasal epithelial tissue dosimetry with two compounds, vinyl acetate (VA) and methyl methacrylate (MMA), that cause toxicity in these tissues These models couple computational fluid dynamics (CFD) calculations that map airflow patterns within the nose with physiologically based pharmacokinetic (PBPK) models that integrate diffusion, metabolism, and tissue interactions of these compounds. Dose metrics estimated in these models for MMA and VA, respectively, were rates of MMA metabolism per volume of tissue and alterations in pH in target tissues associated with VA hydrolysis and metabolism. In this article, four scientists who have contributed significantly to development of these models describe the many similarities and relatively few differences between the MMA and VA models. Some differences arise naturally because of differences in target tissues, in the calculated measures of tissue dose, and in the modes of action for highly extracted vapors (VA) compared with poorly extracted vapors (MMA). A difference in the approach used to estimate metabolic parameters from human tissues provides insights into interindividual extrapolation and identifies opportunities for studies with human nasal tissues to enhance current risk assessments. In general, the differences in model structure for these two esters were essential for describing the biology of the observed responses and in accounting for the different measures of target tissue dose. This article is intended to serve as a guide for understanding issues of optimum model structure and optimal data sources for these nasal tissue dosimetry models. We also hope that it leads to greater international acceptance of these hybrid CFD/PBPK modeling approaches for improving risk assessment for many nasal toxicants. In general, these models predict either equivalent (VA) or lower (MMA) nasal tissue doses in humans compared with tissue doses at equivalent exposure concentrations

  17. Particle Image Velocimetry Measurements Inside the Human Nasal Passage

    NASA Astrophysics Data System (ADS)

    Kelly, James; Hopkins, Lisa; Sreenivas, K. R.; Wexler, Anthony; Prasad, Ajay

    1998-11-01

    In some applications (such as biological flows) the flow passage exhibits a highly complex geometry. A method is described by which such a flow passage is rendered as a three-dimensional model. A computer model of an adult human nasal cavity was generated from digitized computed tomography (CT) scan images, using the I-DEAS modeling package, and was converted to a stereolithographic file for rapid prototyping. Rapid prototyping yielded a water soluble negative of the airway. Silicone elastomer was poured over the negative, which was washed out after the silicone hardened. This technique can be used to obtain an accurate, transparent, silicone, replicate model of any arbitrary geometry. If the working fluid is refractive-index matched to the silicone, it is possible to obtain PIV measurements in any cross-section. We demonstrate the technique by creating a double-scale model of the human nasal passage, and obtaining PIV measurements.

  18. Comparison of serologic evaluation via agar gel immunodiffusion and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs.

    PubMed

    Pomrantz, Jill S; Johnson, Lynelle R; Nelson, Richard W; Wisner, Erik R

    2007-05-01

    To compare the sensitivity and specificity of serologic evaluation and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs. Prospective study. 58 dogs with nasal discharge and 26 healthy dogs. Dogs with nasal discharge were anesthetized and underwent computed tomography and rhinoscopy; nasal tissues were collected for histologic examination and fungal culture. Sera were assessed for antibodies against Aspergillus spp (healthy dog sera were used as negative control specimens). Nasal aspergillosis was diagnosed in dogs that had at least 2 of the following findings: computed tomographic characteristics consistent with aspergillosis, fungal plaques detected during rhinoscopy, and histologically detectable fungal hyphae in nasal tissue. Histologic characteristics of malignancy were diagnostic for neoplasia. Without evidence of neoplasia or fungal disease, nonfungal rhinitis was diagnosed. Among the 58 dogs, 21 had nasal aspergillosis, 25 had nonfungal rhinitis, and 12 had nasal neoplasia. Fourteen aspergillosis-affected dogs and 1 dog with nonfungal rhinitis had serum antibodies against Aspergillus spp. Fungal culture results were positive for Aspergillus spp only for 17 dogs with aspergillosis. With regard to aspergillosis diagnosis, sensitivity, specificity, and positive and negative predictive values were 67%, 98%, 93%, and 84%, respectively, for serum anti-Aspergillus antibody determination and 81%, 100%, 100%, and 90%, respectively, for fungal culture. Results suggest that seropositivity for Aspergillus spp and identification of Aspergillus spp in cultures of nasal tissue are highly suggestive of nasal aspergillosis in dogs; however, negative test results do not rule out nasal aspergillosis.

  19. An effective manual deboning method to prepare intact mouse nasal tissue with preserved anatomical organization.

    PubMed

    Dunston, David; Ashby, Sarah; Krosnowski, Kurt; Ogura, Tatsuya; Lin, Weihong

    2013-08-10

    The mammalian nose is a multi-functional organ with intricate internal structures. The nasal cavity is lined with various epithelia such as olfactory, respiratory, and squamous epithelia which differ markedly in anatomical locations, morphology, and functions. In adult mice, the nose is covered with various skull bones, limiting experimental access to internal structures, especially those in the posterior such as the main olfactory epithelium (MOE). Here we describe an effective method for obtaining almost the entire and intact nasal tissues with preserved anatomical organization. Using surgical tools under a dissecting microscope, we sequentially remove the skull bones surrounding the nasal tissue. This procedure can be performed on both paraformaldehyde-fixed and freshly dissected, skinned mouse heads. The entire deboning procedure takes about 20-30 min, which is significantly shorter than the experimental time required for conventional chemical-based decalcification. In addition, we present an easy method to remove air bubbles trapped between turbinates, which is critical for obtaining intact thin horizontal or coronal or sagittal sections from the nasal tissue preparation. Nasal tissue prepared using our method can be used for whole mount observation of the entire epithelia, as well as morphological, immunocytochemical, RNA in situ hybridization, and physiological studies, especially in studies where region-specific examination and comparison are of interest.

  20. Substance P and neurokinin A in human nasal mucosa

    SciTech Connect

    Baraniuk, J.N.; Lundgren, J.D.; Okayama, M.; Goff, J.; Mullol, J.; Merida, M.; Shelhamer, J.H.; Kaliner, M.A. )

    1991-03-01

    The tachykinins substance P (SP) and neurokinin A (NKA) were studied in human inferior turbinate nasal mucosa by radioimmunoassay, immunohistochemistry, and autoradiography and for their effect upon mucus release in an in vitro culture system in order to infer their potential functions in the upper respiratory tract. Similar amounts of SP (1.03 +/- 0.12 pmol/g wet weight; mean +/- SEM; n = 26) and NKA (0.76 +/- 0.23; n = 7) were found. NKA and SP immunoreactive nerve fibers were found in the walls of arterioles, venules, and sinusoids and as individual fibers in gland acini, near the basement membrane, and in the epithelium. ({sup 125}I)SP bound to arterioles, venules, and glands. ({sup 125}I)NKA bound only to arterioles. In short-term explant culture of fragments of human nasal mucosa, both 1 microM SP and 1 microM NKA stimulated release of ({sup 3}H)glucosamine-labeled respiratory glycoconjugates. These results indicate that SP and NKA have similar distributions in nociceptive sensory nerves in human nasal mucosa. The distribution of ({sup 125}I)SP binding sites is consistent with a role for SP as a vasodilator and mucous secretagogue. The presence of ({sup 125}I) NKA binding sites on vessels suggests a primary role for NKA in regulating vasomotor tone.

  1. Cryosurgical posterior nasal tissue ablation for the treatment of rhinitis.

    PubMed

    Hwang, Peter H; Lin, Bryant; Weiss, Raymond; Atkins, James; Johnson, Jacob

    2017-08-11

    Endoscopic posterior nasal nerve (PNN) resection has been described as an efficacious surgical treatment of allergic and nonallergic rhinitis, but the requirement for surgery under general anesthesia has limited its acceptance. We report the first series of patients treated for chronic rhinitis using a novel device designed for office-based cryosurgical ablation of the PNN. Twenty-seven patients with chronic rhinorrhea and/or nasal congestion for >3 months were recruited (allergic or nonallergic rhinitis), with minimum rhinorrhea and/or congestion subscores of 2 as part of the Total Nasal Symptom Score [TNSS]). Under local anesthesia, the cryotherapy device was applied endoscopically to the posterior middle meatus and was used to freeze the PNN region bilaterally. Patients were followed up after 7, 30, 90, 180, and 365 days to assess TNSS. The procedure was successfully completed in 100% of patients, with no complications; 74% reported no or mild discomfort by the first postprocedure day. TNSS was reduced significantly at 30 days (mean ± standard deviation: 6.2 ± 0.5 at baseline, 2.6 ± 0.3 at 30 days, n = 27, p < 0.001), with continued reduction at 90 (2.7 ± 0.4, n = 24, p < 0.001), 180 (2.3 ± 0.5, n = 21, p < 0.001), and 365 days (1.9 ± 0.3, n = 15, p < 0.001). Both rhinorrhea and congestion subscores decreased significantly at 30, 90, 180, and 365 days compared to baseline (p < 0.001). Allergic and nonallergic subcohorts both appeared to benefit from treatment. Office-based cryotherapy of the PNN region is safe and well tolerated. Symptom scores were significantly decreased by 7 days postprocedure and remained lower at 30, 90, 180, and 365 days. © 2017 The Authors International Forum of Allergy & Rhinology, published by ARSAAOA, LLC.

  2. Computational fluid dynamics simulations of respiratory airflow in human nasal cavity and its characteristic dimension study

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Liu, Yingxi; Sun, Xiuzhen; Yu, Shen; Yu, Chi

    2008-04-01

    To study the airflow distribution in human nasal cavity during respiration and the characteristic parameters of nasal structure, three-dimensional, anatomically accurate representations of 30 adult nasal cavity models were reconstructed based on processed tomography images collected from normal people. The airflow fields in nasal cavities were simulated by fluid dynamics with finite element software ANSYS. The results showed that the difference of human nasal cavity structure led to different airflow distribution in the nasal cavities and variation of the main airstream passing through the common nasal meatus. The nasal resistance in the regions of nasal valve and nasal vestibule accounted for more than half of the overall resistance. The characteristic model of nasal cavity was extracted on the basis of characteristic points and dimensions deduced from the original models. It showed that either the geometric structure or the airflow field of the two kinds of models was similar. The characteristic dimensions were the characteristic parameters of nasal cavity that could properly represent the original model in model studies on nasal cavity.

  3. Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke

    PubMed Central

    Kuehn, Diana; Majeed, Shoaib; Guedj, Emmanuel; Dulize, Remi; Baumer, Karine; Iskandar, Anita; Boue, Stephanie; Martin, Florian; Kostadinova, Radina; Mathis, Carole; Ivanov, Nikolai V.; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C.

    2015-01-01

    Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers. PMID:25741927

  4. Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption.

    PubMed

    Al-Ghabeish, Manar; Scheetz, Todd; Assem, Mahfoud; Donovan, Maureen D

    2015-08-03

    Mice and rats are commonly used to investigate in vivo nasal drug absorption, yet their small nasal cavities limit their use for in vitro investigations. Bovine tissue explants have been used to investigate drug transport through the nasal respiratory and olfactory mucosae, yet limited information is available regarding the similarities and differences among these animal models compared to humans. The aim of this study was to compare the presence of a number of important drug transporters in the nasal mucosa of these species. DNA microarray results for nasal samples from humans, rats, and mice were obtained from GenBank, while DNA microarray and RT-PCR were performed on bovine nasal explants. The drug transporters of interest include multidrug resistance, cation, anion, peptide, and nucleoside transporters. Each of the species (mouse, rat, cattle, and human) shows similar patterns of expression for most of the important drug transporters. Several transporters were highly expressed in all the species, including MRP1, OCTN2, PEPT2, and y+LAT2. While some differences in transporter mRNA and protein expression were observed, the transporter expression patterns were quite similar among the species. The differences suggest that it is important to be aware of any specific differences in transporter expression for a given compound being investigated, yet the similarities support the continued use of these animal models during preclinical investigation of intranasally administered therapeutics.

  5. Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption

    PubMed Central

    Al-Ghabeish, Manar; Scheetz, Todd; Assem, Mahfoud; Donovan, Maureen D.

    2015-01-01

    Purpose Mice and rats are commonly used to investigate in vivo nasal drug absorption, yet their small nasal cavities limit their use for in vitro investigations. Bovine tissue explants have been used to investigate drug transport through the nasal respiratory and olfactory mucosae, yet limited information is available regarding the similarities and differences among these animal models compared to humans. The aim of this study was to compare the presence of a number of important drug transporters in the nasal mucosa of these species. Methods DNA microarray results for nasal samples from humans, rats and mice were obtained from GenBank, while DNA microarray and RT-PCR were performed on bovine nasal explants. The drug transporters of interest include multidrug resistance, cation, anion, peptide, and nucleoside transporters. Results Each of the species (mouse, rat, cow and human) shows similar patterns of expression for most of the important drug transporters. Several transporters were highly expressed in all the species, including MRP1, OCTN2, PEPT2 and y+LAT2. Conclusion While some differences in transporter mRNA and protein expression were observed, the transporter expression patterns were quite similar among the species. The differences suggest that it is important to be aware of any specific differences in transporter expression for a given compound being investigated, yet the similarities support the continued use of these animal models during preclinical investigation of intranasally administered therapeutics. PMID:26106909

  6. Nasal mucosa: a new site for tissue biopsy to diagnose hereditary TTR amyloidosis.

    PubMed

    Munar-Qués, Miguel; Solé, Manel; Martínez-Nadal, Jacinto; Murcia-Sáiz, Antonio; Mas-Degano, José Manuel

    2014-11-07

    We report 2 carriers of the TTRV30M mutation and its plasmatic biochemical marker with clinical symptoms compatible with hereditary TTR amyloidosis. Based on our previously reported casual finding of amyloid TTR in nasal mucosa (2008), we requested biopsy of this tissue to search for amyloid with Congo red staining and TTR immunohistochemical analysis. The histological diagnosis was achieved by retrospective analysis of surgical sinonasal biopsy in the first patient and prospective biopsy of inferior nasal concha in the second. Large interstitial deposits of ATTR were observed in both cases. We suggest nasal mucosa as a suitable site for tissue biopsy in patients with suspected hereditary TTR amyloidosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  7. [Comparison of biomechanical properties between human nasal periosteum and fascia].

    PubMed

    Zeng, Yanjun; Wu, Weihua; Yang, Jian; Li, Zhen; Yu, Hongmei

    2002-09-01

    There has been a lot of controversies on which layer the silastic implants should be inserted in the augmentation rhinoplasty, i.e. subperiosteal or deep subfascial. This study is to investigate the biomechanical properties of human nasal periosteum and deep fascia, including tensile strength, stress-strain and stress relaxation characters under uniaxial tension system. The periosteum is stronger in tensile strength than that of the fascia, but it is less elastic. Under a sudden increase of load, the periosteum relaxes far less than the fasia. Therefore, in view of biomechanics, the periosteum is thicker, tougher, stiffer and less relaxation than facia, thus has a better fixation effect.

  8. [Regulation of the swelling mechanism in the inferior turbinate of human nasal mucosa].

    PubMed

    Riederer, A; Knipping, S; Toleti, Birgit

    2002-07-01

    The swelling mechanism of human nasal mucosa is based on a complicated vascular system and regulated by a variety of classical and peptidergic transmitters as well as by endothelial transmitters. The aim of this study was to elucidate this mechanism taking into account the distribution of these substances and the morphology of the different vessels. Tissue specimens of human inferior turbinates were evaluated by light and electron microscopy. We used frozen sections to localize enzymes of the transmitter synthesis by histochemical and immunocytochemical methods. The distribution of classical neurotransmitters, neuropeptides (calcitonin-gene-related-peptide, neuropeptide Y, substance P and vasoactive intestinal polypeptide), enzymes producing neuronal NO (neuronal nitric oxide synthase, nicotine-amid-adenine-dinucleotide-phosphate-diaphorase) as well as endothelial transmitters such as endothelin and endothelial nitric oxide were examined. For ultrastructal examination the specimens were fixed in glutaraldehyde und osmium tetroxide, embedded in araldide, cut and double contrasted. Most of the axons and immunoreactivity of transmitters were located in the arterial part of the human nasal vascular system. In venous vessels only a spare innervation was observed, whereas in the subendothelial muscular bolsters of the cushion veins a rich nerve supply could be detected. Near the fenestrated subendothelial and periglandular capillaries no axons were found. Nasal vasculature is supplied by a equilibrated aminergic and cholinergic innervation. Mainly arterial vessels showed reactions to antibodies directed against endothelial transmitters. Because of the dense innervation of arteries and subendothelial venous muscular bolsters we conclude that the swelling mechanism of human nasal mucosa is mainly regulated by these structures. A dual (endothelial and neuronal) control exists in arterioles whereas the control in the subendothelial muscular swellings of the cushion veins

  9. The early interferon response of nasal-associated lymphoid tissue to Streptococcus pyogenes infection.

    PubMed

    Hyland, Kendra A; Brennan, Robert; Olmsted, Stephen B; Rojas, Eduardo; Murphy, Ellen; Wang, Beinan; Cleary, P Patrick

    2009-04-01

    Streptococcus pyogenes is a major causative agent of tonsillitis or pharyngitis in children. Streptococcus pyogenes can persist in tonsils, and one-third of children treated with antibiotics continue to shed streptococci and have recurrent infections. Mouse nasal-associated lymphoid tissue (NALT) is functionally analogous to human oropharyngeal lymphoid tissues, and serves as a model for characterization of the mucosal innate immune response to S. pyogenes. Wild-type S. pyogenes induces transcription of both type I and interferon-gamma (IFN-gamma)-responsive genes, proinflammatory genes and acute-phase response proteins 24 h after intranasal infection. Invasion of NALT and the induction of the interferon response were not dependent on expression of antiphagocytic M protein. Intranasal infection induces a substantial influx of neutrophils into NALT at 24 h, which declines by 48 h after infection. Infection of IFN-gamma(-/-) [IFN-gamma knock-out mouse (GKO)] C57BL/6 mice with wild-type S. pyogenes resulted in local dissemination of bacteria to draining lymph nodes (LN), but did not lead to systemic infection by 48 h after infection. Infected GKO mice had an increased influx of neutrophils into NALT compared with immunocompetent mice. Thus, IFN-gamma-induced responses are required to prevent local dissemination of streptococci to the draining LN.

  10. Unsteady flow characteristics through a human nasal airway.

    PubMed

    Lee, Jong-Hoon; Na, Yang; Kim, Sung-Kyun; Chung, Seung-Kyu

    2010-07-31

    Time-dependent characteristics of the flow in a human nasal airway constructed from the CT image of a healthy volunteer were investigated using a computational fluid dynamics (CFD) technique. To capture the time-varying nature of the flow as well as pressure and temperature fields, the large eddy simulation (LES) technique instead of the RANS (Reynolds Averaged Navier-Stokes) approach was adopted. To make the present analysis more relevant to a real human breathing cycle, the flow was designed to be induced by the pressure difference and the time-varying pressure at the end of trachea was described to reproduce the flow rate data from the measurement. Comparison of the present results with those of typical steady simulations showed that the difference in flow characteristics is magnified in the expiration phase. This fact may suggest that the inertial effect associated with unsteady flow is more important during the expiration period. Also, the fact that the distribution of the flow rate in a given cross-section of the airway changes significantly with time implies the importance of unsteady data for clinical decision. The wall shear stress was found to have relatively high values at the locations near nasopharynx and larynx but the magnitude changes with time during the whole respiratory cycle. Analysis of the temperature field showed that most of the temperature change occurs in the nasal cavity when the air is incoming and thus, the nasal cavity acts as a very efficient heat exchanger during an inspiration period. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Hypoxia depresses nitric oxide output in the human nasal airways.

    PubMed

    Haight, J S; Qian, W; Daya, H; Chalmers, P; Zamel, N

    2000-03-01

    The role of oxygen in the nasal air on nasal nitric oxide (NO) output was studied in 13 adult volunteers. Nasal NO was measured while air containing oxygen (0%-100% in nitrogen) was aspirated through the nasal airway before and after the topical application of xylometazoline. The mean nasal NO output of the untreated nose was 507.8 +/- 161.9 nL/min (mean +/- SD) when 21% oxygen was aspirated through the nasal cavities in series and remained unaltered by 100% O2 (P = .79). Below 10% oxygen the reduction in nasal NO output correlated positively and significantly with the decrease in oxygen concentration (r2 = 0.14). NO output was 245.2 +/- 153.4 nL/min at 0% oxygen, a significant decline from 21% oxygen (P < .0001). Nasal vasoconstriction induced by xylometazoline and alterations in the blood oxygen content by a maximal breath-holding or breathing 100% oxygen did not alter nasal NO in hypoxia (P = .41). Nasal NO output is markedly depressed in hypoxia and is oxygen dependent at concentrations of less than 10%. Approximately 50% of nasally generated NO is produced from oxygen in nasal air or regulated by it.

  12. Exhaled nasal nitric oxide output is reduced in humans at night during the sleep period.

    PubMed

    O'Hearn, Daniel J; Giraud, George D; Sippel, Jeffrey M; Edwards, Chad; Chan, Benjamin; Holden, William E

    2007-04-16

    The physiologic function of nasal nitric oxide (NO) release is unknown. In prior experiments, topical NG-nitro-L-arginine methyl ester (L-NAME) on nasal mucosa reduced exhaled nasal NO output and caused daytime sleepiness. We hypothesized that nasal NO output is reduced at night during the sleep period. We measured exhaled nasal NO concentration and minute ventilation and calculated nasal NO output in humans over 24 h. Daytime awake NO output was greater than NO output at night during sleep or transient wakefulness. Exhaled NO concentration decreased during sleep along with minute ventilation. A daytime voluntary reduction in minute ventilation also decreased nasal NO output but exhaled NO concentration increased. Nasal NO output was not changed by body position. We conclude that exhaled nasal NO output is decreased at night due to decreased mass flow of NO into nasal air in addition to decreased minute ventilation. Our findings suggest a role of nasal NO in sleep or in the physiologic processes accompanying sleep.

  13. Early depictions of the human anterior nasal septum.

    PubMed

    Pirsig, Wolfgang; Sokiranski, Roman

    2006-06-01

    In the literature, remarks on the depiction of the anterior nasal septum in prehistoric times cannot be found. Studying works of art from some archaeological sites of Asia, Asia Minor, Near East, Egypt, and Southeastern Europe the anatomical depiction of the columella and the nostrils in human figures are shown. These figures or heads, partly appearing as masks, were made of ivory, stone, marble, terracotta, steatite, reeds and clay, or of burned limestone. Faces and figures sculpted in the time between the Upper Palaeolithic (30,000 - 25,000 BC) and the Early Bronze Age (3,300 - 2,400 BC) are presented as examples of our ancestors' outstanding skill to create works of art with an astonishing ability to observe anatomical details. The tendency to create a human nose in a natural manner can already be recognized in the figurines of the Upper Palaeolithic.

  14. Nasal spreader grafts: a comparison of medpor to autologous tissue reconstruction.

    PubMed

    Reiffel, Alyssa J; Cross, Kevin J; Spinelli, Henry M

    2011-01-01

    Reconstruction of the damaged nasal vault is challenging. Limited available autologous tissue has lead surgeons to pursue alloplastic alternatives. A retrospective review comparing 18 patients who underwent secondary rhinoplasty with internal nasal valve reconstruction with spreader graft (SG) implants using either autologous tissue or high-density porous polyethylene (Medpor) was performed. All underwent bilateral SG reconstruction of the internal nasal valve with Medpor (10 cases) or autologous cartilage (8 cases). Mean follow-up was 26 months for the autologous group and 29 months for the Medpor group. Functional performance and aesthetic results were identical. Complications were few: 1 case of unilateral infection in the Medpor group treated with partial excision, and 1 case of erythema at the auricular donor site for the autologous tissue group. For patients who have exhausted autologous tissue options or are unwilling to tolerate potential donor-site morbidity, the Medpor SG is an appropriate option that allows for excellent aesthetic and functional results that remains stable over time.

  15. Effect of nitrogen dioxide on human nasal epithelium

    SciTech Connect

    Carson, J.L.; Collier, A.M.; Hu, S.C.; Delvin, R.B. )

    1993-09-01

    The nasal epithelium of young adult white men in good health was evaluated by electron microscopy in a condition blind fashion relative to exposures of 2 ppm nitrogen dioxide (NO2) or clean air for 4 h. The exposure protocol involved two separate exposures of the same individuals to NO2 or clean air approximately 3 wk apart. We found qualitative and quantitative evidence that luminal border membranes of ciliated cells were ultrastructurally altered in six of seven samples of nasal epithelium obtained following NO2 exposures, although subsequent morphometric statistical analyses were not significant. This alteration was characterized by cilia containing excess matrix in which individual or, more commonly, multiple ciliary axonemes were embedded, and by vesiculations of luminal border ciliary membranes, a pattern less common in clean air-exposed control specimens. Although these patterns were not widespread, their morphology was consistent with findings of previous animal studies involving acute and chronic exposure to NO2. Our findings suggest that adverse effects on mucociliary function in normal humans due to acute exposure to low levels of NO2 are most likely minimal. However, in view of other reports of NO2 exposure in laboratory animals documenting ciliary injury, our observations support a view that similar patterns might appear more prominently with higher NO2 levels and/or more extended exposure intervals.

  16. Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

    PubMed Central

    Giannasca, P J; Boden, J A; Monath, T P

    1997-01-01

    The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal

  17. Generation and characterization of osteochondral grafts with human nasal chondrocytes.

    PubMed

    Barandun, Marina; Iselin, Lukas Daniel; Santini, Francesco; Pansini, Michele; Scotti, Celeste; Baumhoer, Daniel; Bieri, Oliver; Studler, Ueli; Wirz, Dieter; Haug, Martin; Jakob, Marcel; Schaefer, Dirk Johannes; Martin, Ivan; Barbero, Andrea

    2015-08-01

    We investigated whether nasal chondrocytes (NC) can be used to generate composite constructs with properties necessary for the repair of osteochondral (OC) lesions, namely maturation, integration and capacity to recover from inflammatory burst. OC grafts were fabricated by combining engineered cartilage tissues (generated by culturing NC or articular chondrocytes - AC - onto Chondro-Gide® matrices) with devitalized spongiosa cylinders (Tutobone®). OC tissues were then exposed to IL-1β for three days and cultured for additional 2 weeks in the absence of IL-1β. Cartilage maturation extent was assessed (immune) histologically, biochemically and by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) while cartilage/bone integration was assessed using a peel-off mechanical test. The use of NC as compared to AC allowed for more efficient cartilage matrix accumulation and superior integration of the cartilage/bone layers. dGEMRIC and biochemical analyzes of the OC constructs showed a reduced glycosaminoglycan (GAG) contents upon IL-1β administration. Cartilaginous matrix contents and integration forces returned to baseline up on withdrawal of IL-1β. By having a cartilage layer well developed and strongly integrated to the subchondral layer, OC tissues generated with NC may successfully engraft in an inflammatory post-surgery joint environment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Association between cigarette smoking and interleukin-17A expression in nasal tissues of patients with chronic rhinosinusitis and asthma

    PubMed Central

    Huang, Chien-Chia; Wang, Chun-Hua; Fu, Chia-Hsiang; Huang, Chi-Che; Chang, Po-Hung; Chen, Yi-Wei; Wu, Chia-Chen; Wu, Pei-Wen; Lee, Ta-Jen

    2016-01-01

    Abstract Cigarette smoke plays a substantial role in the development of airway inflammatory diseases, including asthma and chronic rhinosinusitis (CRS). Interleukin (IL)-17A might contribute to cigarette smoke-related inflammation of the airway. This study aimed to investigate the association between cigarette smoking and IL-17A expression in the nasal tissues of patients with CRS and asthma. We prospectively recruited 24 patients (13 smokers, 11 nonsmokers) with CRS and asthma and 6 patients with asthma but without CRS (control group) in a tertiary medical center. Nasal mucosa was obtained as part of the nasal surgery. Protein and mRNA levels of IL-17A in the nasal tissues were determined by immunostaining and real-time polymerase chain reaction. The number of unexpected emergency clinic visits for acute asthma attacks were higher among smokers than among nonsmokers. Interleukin-17A protein and mRNA levels in the nasal tissues of smokers were greater compared to those in the nasal tissues of nonsmokers (P = 0.02 both) and control patients (P = 0.05 and 0.04, respectively). Cigarette smoking was associated with an increase in the number of unexpected emergency clinic visits due to acute asthma attack and in the expression of IL-17A in the nasal tissues of patients with airway inflammatory diseases. PMID:27893686

  19. Dexamethasone-induced apoptosis of freshly isolated human nasal epithelial cells concomitant with abrogation of IL-8 production.

    PubMed

    Bobic, S; van Drunen, C M; Callebaut, I; Hox, V; Jorissen, M; Fokkens, W J; Hellings, P W

    2010-12-01

    Human nasal epithelial cells (hNECs) are the first line of immune defense and are able to produce mediators that recruit, activate and prolong survival of immune cells, among which IL-8 takes an important place. Studies on IL-8 and effects of dexamethasone on hNECs have been hampered by methodological shortcomings. The purpose of the study is to investigate the contribution of freshly isolated hNECs to IL-8 production in chronic rhinosinusitis with nasal polyps (CRSwithNP). Secondly, the effects of dexamethasone treatment on hNEC apoptosis and IL-8 production are investigated. hNECs were freshly isolated from nasal polyp tissue and healthy inferior turbinate of NP patients (n=12) and from inferior turbinates of healthy donors (n=19) by protease treatment and two negative selection procedures. hNECs were incubated with IL-1β (10ng/ml), TNFα (10ng/ml) or dexamethasone (10, 100 and 1000 Amicrog/ml). After 24h, IL-8 levels were determined in the supernatants by ELISA. Finally, hNECs were incubated with increasing doses of dexamethasone and stained with trypan-blue and annexin-FITC/PI to study apoptosis. hNECs isolated from nasal turbinates of healthy and NP patients and polyp tissue from NP patients produced similar levels of IL-8. IL-1β induced higher levels of IL-8 production in all types of hNECs without differences between control and NP tissue. Dexamethasone induced apoptosis of hNECs concomitant with abrogation of IL-8 production by hNECs. IL-8 production by human nasal epithelial cells does not differ between NP and healthy tissue under baseline nor stimulatory conditions. Dexamethasone induces apoptosis of hNECs and abrogates IL-8 production.

  20. Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function

    PubMed Central

    Jiang, Heidi; Zhou, Guangyu; Arora, Nikita; Schuele, Stephan; Rosenow, Joshua; Gottfried, Jay A.

    2016-01-01

    The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2–12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16–0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior. SIGNIFICANCE STATEMENT Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence

  1. Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function.

    PubMed

    Zelano, Christina; Jiang, Heidi; Zhou, Guangyu; Arora, Nikita; Schuele, Stephan; Rosenow, Joshua; Gottfried, Jay A

    2016-12-07

    The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2-12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16-0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior. Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment

  2. Comparison of cadmium cytotoxicity in human versus rat nasal epithelial cells in vitro

    SciTech Connect

    Morgan, D.L.; Humphreys, J.E.; Bilotta, J.M.; Nixon, J.C.; Hatch, G.E.

    1990-01-01

    Quantitative extrapolation of toxicity data from animals to humans will allow more accurate assessments of human health risks. The overall objective of this investigation is to provide the tissue sensitivity data necessary to extrapolate quantitatively the toxic effects of inhaled particles from animals to humans. In the initial study, cadmium sulfate (CdSO4) toxicity for human and Fischer 344 rat nasal turbinate epithelial (NTE) cells was evaluated in vitro. The studies were unique in that both rat and human NTE cells were obtained from fresh, normal tissue. Methods were developed for isolating and culturing NTE cells from rat and human tissue using identical procedures, and for measuring the cellular nucleotides by HPLC. Changes in adenylate energy charge (EC) and nucleotide levels were used as toxicity endpoints. Cellular Cd levels were measured by graphite furnace atomic absorption spectrometry and expressed as microgram Cd/microgram DNA. Using these methods, the cellular Cd dose and the toxic effect in each cell type were measured and compared.

  3. Herpes viruses and human papilloma virus in nasal polyposis and controls.

    PubMed

    Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

    2015-01-01

    Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  4. Implications of Airflow Dynamics and Soft-Tissue Reconstructions for the Heat Exchange Potential of Dinosaur Nasal Passages

    NASA Astrophysics Data System (ADS)

    Bourke, Jason Michael

    This study seeks to restore the internal anatomy within the nasal passages of dinosaurs via the use of comparative anatomical methods along with computational fluid dynamic simulations. Nasal airway descriptions and airflow simulations are described for extant birds, crocodylians, and lizards. These descriptions served as a baseline for airflow within the nasal passages of diapsids. The presence of shared airflow and soft-tissue properties found in the nasal passages of extant diapsids, were used to restore soft tissues within the airways of dinosaurs under the assumption that biologically unfeasible airflow patterns (e.g., lack of air movement in olfactory recess) can serve as signals for missing soft tissues. This methodology was tested on several dinosaur taxa. Restored airways in some taxa revealed the potential presence and likely shape of nasal turbinates. Heat transfer efficiency was tested in two dinosaur species with elaborated nasal passages. Results of that analysis revealed that dinosaur noses were efficient heat exchangers that likely played an integral role in maintaining cephalic thermoregulation. Brain cooling via nasal expansion appears to have been necessary for dinosaurs to have achieved their immense body sizes without overheating their brains.

  5. Incorporation of tissue reaction kinetics in a computational fluid dynamics model for nasal extraction of inhaled hydrogen sulfide in rats.

    PubMed

    Schroeter, Jeffry D; Kimbell, Julia S; Bonner, Anna M; Roberts, Kay C; Andersen, Melvin E; Dorman, David C

    2006-03-01

    Rodents exposed to hydrogen sulfide (H2S) develop olfactory neuronal loss. This lesion has been used by the risk assessment community to develop occupational and environmental exposure standards. A correlation between lesion locations and areas of high H2S flux to airway walls has been previously demonstrated, but a quantitative dose assessment is needed to extrapolate dose at lesion sites to humans. In this study, nasal extraction (NE) of 10, 80, and 200 ppm H2S was measured in the isolated upper respiratory tract of anesthetized rats under constant unidirectional inspiratory flow rates of 75, 150, and 300 ml/min. NE was dependent on inspired H2S concentration and air flow rate: increased NE was observed when H2S exposure concentrations or inspiratory air flow rates were low. An anatomically accurate, three-dimensional computational fluid dynamics (CFD) model of rat nasal passages was used to predict NE of inhaled H2S. To account for the observed dependence of NE on H2S exposure concentration, the boundary condition used at airway walls incorporated first-order and saturable kinetics in nasal tissue to govern mass flux at the air:tissue interface. Since the kinetic parameters cannot be obtained using the CFD model, they were estimated independently by fitting a well-mixed, two-compartment pharmacokinetic (PK) model to the NE data. Predicted extraction values using this PK-motivated CFD approach were in good agreement with the experimental measurements. The CFD model provides estimates of localized H2S flux to airway walls and can be used to calibrate lesion sites by dose.

  6. Precultivation of engineered human nasal cartilage enhances the mechanical properties relevant for use in facial reconstructive surgery.

    PubMed

    Farhadi, Jian; Fulco, Ilario; Miot, Sylvie; Wirz, Dieter; Haug, Martin; Dickinson, Sally C; Hollander, Anthony P; Daniels, A U; Pierer, Gerhard; Heberer, Michael; Martin, Ivan

    2006-12-01

    To investigate if precultivation of human engineered nasal cartilage grafts of clinically relevant size would increase the suture retention strength at implantation and the tensile and bending stiffness 2 weeks after implantation. SUMMARY BACKGROUND INFORMATION: To be used for reconstruction of nasal cartilage defects, engineered grafts need to be reliably sutured at implantation and resist to bending/tension forces about 2 weeks after surgery, when fixation is typically removed. Nasal septum chondrocytes from 4 donors were expanded for 2 passages and statically loaded on 15 x 5 x 2-mm size nonwoven meshes of esterified hyaluronan (Hyaff-11). Constructs were implanted for 2 weeks in nude mice between muscle fascia and subcutaneous tissue either directly after cell seeding or after 2 or 4 weeks of preculture in chondrogenic medium. Engineered tissues and native nasal cartilage were assessed histologically, biochemically, and biomechanically. Engineered constructs reproducibly developed with culture time into cartilaginous tissues with increasing content of glycosaminoglycans and collagen type II. Suture retention strength was significantly higher (3.6 +/- 2.2-fold) in 2-week precultured constructs than in freshly seeded meshes. Following in vivo implantation, tissues further developed and maintained the original scaffold size and shape. The bending stiffness was significantly higher (1.8 +/- 0.8-fold) if constructs were precultured for 2 weeks than if they were directly implanted, whereas tensile stiffness was close to native cartilage in all groups. In our experimental setup, preculture for 2 weeks was necessary to engineer nasal cartilage grafts with enhanced mechanical properties relevant for clinical use in facial reconstructive surgery.

  7. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    SciTech Connect

    Yeh, Hsu-Chi; Swift, D.L.; Simpson, S.Q.

    1995-12-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

  8. Effects of cold dry air nasal stimulation on airway mucosal blood flow in humans.

    PubMed

    Le Merre, C; Isber, J; Chediak, A D; Wanner, A

    2003-10-01

    Several studies have demonstrated that nasal challenges can induce reflex responses in the respiratory system. Some authors have described bronchoconstriction and modification of the pattern of breathing following nasal challenges by irritants and cold air. We propose to determine the effect of nasal stimulation with cold dry air on airway mucosal blood flow (Qaw) in the proximal tracheal bronchial tree of healthy humans. Nine healthy subjects participated in the study. Baseline measurement Qaw, nasal airway resistance (NAR) and airway caliber by specific airways conductance (SGaw) were followed by nasal challenge with cold dry air. Qaw, NAR and Sgaw were determined after the challenge. In those subjects in which a significant decline in Qaw was recorded the protocol was repeated after pretreatment with nasal anesthesia using topical lidocaine. Cold dry air challenge produced a significant decrease in mean Qaw for the nine subjects and this response was abolished by pretreatment with nasal anesthesia using topical lidocaine. There was no significant change in Sgaw and NAR after the challenge and topical lidocaine anesthesia. Our data indicates that nasal stimulation with cold dry air leads to a reduction in Qaw and that this effect may be mediated by a nasal reflex.

  9. Breathing life into dinosaurs: tackling challenges of soft-tissue restoration and nasal airflow in extinct species.

    PubMed

    Bourke, Jason M; Porter, W M Ruger; Ridgely, Ryan C; Lyson, Tyler R; Schachner, Emma R; Bell, Phil R; Witmer, Lawrence M

    2014-11-01

    The nasal region plays a key role in sensory, thermal, and respiratory physiology, but exploring its evolution is hampered by a lack of preservation of soft-tissue structures in extinct vertebrates. As a test case, we investigated members of the "bony-headed" ornithischian dinosaur clade Pachycephalosauridae (particularly Stegoceras validum) because of their small body size (which mitigated allometric concerns) and their tendency to preserve nasal soft tissues within their hypermineralized skulls. Hypermineralization directly preserved portions of the olfactory turbinates along with an internal nasal ridge that we regard as potentially an osteological correlate for respiratory conchae. Fossil specimens were CT-scanned, and nasal cavities were segmented and restored. Soft-tissue reconstruction of the nasal capsule was functionally tested in a virtual environment using computational fluid dynamics by running air through multiple models differing in nasal soft-tissue conformation: a bony-bounded model (i.e., skull without soft tissue) and then models with soft tissues added, such as a paranasal septum, a scrolled concha, a branched concha, and a model combining the paranasal septum with a concha. Deviations in fluid flow in comparison to a phylogenetically constrained sample of extant diapsids were used as indicators of missing soft tissue. Models that restored aspects of airflow found in extant diapsids, such as appreciable airflow in the olfactory chamber, were judged as more likely. The model with a branched concha produced airflow patterns closest to those of extant diapsids. These results from both paleontological observation and airflow modeling indicate that S. validum and other pachycephalosaurids could have had both olfactory and respiratory conchae. Although respiratory conchae have been linked to endothermy, such conclusions require caution in that our re-evaluation of the reptilian nasal apparatus indicates that respiratory conchae may be more widespread

  10. The effects of coronavirus on human nasal ciliated respiratory epithelium.

    PubMed

    Chilvers, M A; McKean, M; Rutman, A; Myint, B S; Silverman, M; O'Callaghan, C

    2001-12-01

    Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.

  11. Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population.

    PubMed

    Lou, Hongfei; Meng, Yifan; Piao, Yingshi; Wang, Chengshuo; Zhang, Luo; Bachert, Claus

    2015-01-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging clinical entity with its propensity for recurrence. Tissue eosinophilia is a hallmark of CRSwNP, and its role in polyp recurrence is a subject of much investigation. The aim of this study was to evaluate the association between clinical parameters, especially tissue eosinophilia and polyp recurrence, and to identify the optimal cutoff value of tissue eosinophilia as a predictor for polyp recurrence in Chinese subjects. Overall, 387 patients with CRSwNP were enrolled in this retrospective analysis and postoperative follow-up for polyp recurrence was over a period that lasted >24 months (mean [standard deviation], 34.03 ± 4.95 months). The baseline demographic and clinical features and the preoperative computed tomography were compared, and mucosal specimens obtained at endoscopic sinus surgery were assessed for inflammatory cells by using histocytologic staining. Predictive factors associated with polyp recurrence were analyzed by logistic regression analysis, and optimal cutoff points of the predictors were determined by receiver operating characteristic curves and the Youden index. A total of 55.3% patients (214/387) experienced recurrence. Tissue eosinophilia markedly outweighed other parameters and correlated with polyp recurrence. Receiver operating characteristic curves indicated that a cutoff value of 27% tissue eosinophils predicted recurrence with 96.7% sensitivity and 92.5% specificity (area under the curve = 0.969; p < 0.001); and an absolute count of 55 eosinophils per high power field predicted recurrence with 87.4% sensitivity and 97.1% specificity (area under the curve = 0.969; p < 0.001). A tissue eosinophil proportion of >27% of total cells or a tissue eosinophil absolute count of >55 eosinophils per high power field may act as a reliable prognostic indicator for nasal polyp recurrence within 2 years after surgery.

  12. Ocular surface reconstruction with a tissue-engineered nasal mucosal epithelial cell sheet for the treatment of severe ocular surface diseases.

    PubMed

    Kobayashi, Masakazu; Nakamura, Takahiro; Yasuda, Makoto; Hata, Yuiko; Okura, Shoki; Iwamoto, Miyu; Nagata, Maho; Fullwood, Nigel J; Koizumi, Noriko; Hisa, Yasuo; Kinoshita, Shigeru

    2015-01-01

    Severe ocular surface diseases (OSDs) with severe dry eye can be devastating and are currently some of the most challenging eye disorders to treat. To investigate the feasibility of using an autologous tissue-engineered cultivated nasal mucosal epithelial cell sheet (CNMES) for ocular surface reconstruction, we developed a novel technique for the culture of nasal mucosal epithelial cells expanded ex vivo from biopsy-derived human nasal mucosal tissues. After the protocol, the CNMESs had 4-5 layers of stratified, well-differentiated cells, and we successfully generated cultured epithelial sheets, including numerous goblet cells. Immunohistochemistry confirmed the presence of keratins 3, 4, and 13; mucins 1, 16, and 5AC; cell junction and basement membrane assembly proteins; and stem/progenitor cell marker p75 in the CNMESs. We then transplanted the CNMESs onto the ocular surfaces of rabbits and confirmed the survival of this tissue, including the goblet cells, up to 2 weeks. The present report describes an attempt to overcome the problems of treating severe OSDs with the most severe dry eye by treating them using tissue-engineered CNMESs to supply functional goblet cells and to stabilize and reconstruct the ocular surface. The present study is a first step toward assessing the use of tissue-engineered goblet-cell transplantation of nonocular surface origin for ocular surface reconstruction.

  13. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    PubMed

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Measurement of multiple microcirculatory parameters in human nasal mucosa using laser-Doppler velocimetry.

    PubMed

    Druce, H M; Kaliner, M A; Ramos, D; Bonner, R F

    1989-09-01

    LDV has been modified to measure four microcirculatory responses in human nasal mucosa. Resting nasal blood flow was measured in 115 observations in 23 nonatopic subjects and 111 observations in 21 atopic subjects with allergic nasal disease. Other parameters measured concurrently were the number density of moving red blood cells (RBC), mean RBC speed, and flow pulsatility. Challenges with aerosolized buffered saline or water had no significant effect on any parameter. By contrast, nasal application of alpha-adrenergic agonists, oxymetazoline and phenylephrine, produced significant dose-dependent reductions in flow without any significant change in RBC number density. These results suggest a selective alpha-agonist effect on resistance vessels but not on capacitance vessels. Topical cholinergic stimulation with methacholine selectively reduced the RBC number density without affecting other parameters. These modifications of LDV may prove useful in analyzing nasal responses to provocation and determining the sites of action of vasoactive agents on the microcirculation.

  15. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

    PubMed

    Guastella, Adam J; Hickie, Ian B; McGuinness, Margaret M; Otis, Melissa; Woods, Elizabeth A; Disinger, Hannah M; Chan, Hak-Kim; Chen, Timothy F; Banati, Richard B

    2013-05-01

    A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans.

  16. A review of the morphology of human nasal mast cells as studied by light and electron microscopy.

    PubMed

    Drake-Lee, A B; Price, J

    1992-12-01

    This review discusses the distribution and classification of human nasal mast cells after the use of different fixatives, and some of their staining characteristics, both at the light- and electron-microscopical level. The problems encountered with alcoholic and formaldehyde fixation are discussed as well as the limitations of different stains (including the basic aniline dyes), esterase cytochemistry and immunological techniques. Also, the respective limitations of light and electron microscopy are compared. Cells studied by means of electron microscopy are much more difficult to quantify objectively. It is concluded that classification of mast cells--by means of their morphology, fixation and staining characteristics--into two categories (mucosal vs. connective tissue; T-vs. T/C cells) is simplistic, especially since human nasal mast cells are both heterogeneous and pleomorphic.

  17. Numerical study on the air conditioning characteristics of the human nasal cavity.

    PubMed

    Kim, Da-Woon; Chung, Seung-Kyu; Na, Yang

    2017-07-01

    The air-conditioning characteristics of the human nasal cavity were investigated using computational fluid dynamics. The wall layer was modeled as a heat conducting layer consisting of water with constant thickness placed on top of epithelial cells. By assuming constant tissue temperature, prescribed to be 36 (°)C, which is close to the alveolar condition, the proposed wall model yielded a spatially varying surface temperature distribution that is in reasonable agreement with the measurement studies in the literature. The results show that the regions of the main airway between the nasal valve, and the anterior of the middle turbinate were shown to have relatively low temperatures, whereas the superior meatus exhibited relatively high temperature. Water vapor flux evaluated at the surface of the mucus layer was found to be quite large in the region between the posterior of the vestibule and the anterior of the middle turbinate. Comparing the results obtained from the present model to those obtained with a constant surface temperature boundary condition of 32.6 °C or 34 °C revealed that temperature, and absolute humidity of the airflow increased faster through the turbinated airway passage. Even in the presence of sizable differences in the distributions of surface temperature and water vapor concentration, distributions of relative humidity of the air were found to be quite similar regardless of temperature boundary conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Regenerative Potential of Tissue-Engineered Nasal Chondrocytes in Goat Articular Cartilage Defects.

    PubMed

    Mumme, Marcus; Steinitz, Amir; Nuss, Katja M; Klein, Karina; Feliciano, Sandra; Kronen, Peter; Jakob, Marcel; von Rechenberg, Brigitte; Martin, Ivan; Barbero, Andrea; Pelttari, Karoliina

    2016-11-01

    Nasal chondrocytes (NC) were previously demonstrated to remain viable and to participate in the repair of articular cartilage defects in goats. Here, we investigated critical features of tissue-engineered grafts generated by NC in this large animal model, namely cell retention at the implantation site, architecture and integration with adjacent tissues, and effects on subchondral bone changes. In this study, isolated autologous goat NC (gNC) and goat articular chondrocytes (gAC, as control) were expanded, green fluorescent protein-labelled and seeded on a type I/III collagen membrane. After chondrogenic differentiation, tissue-engineered grafts were implanted into chondral defects (6 mm in diameter) in the stifle joint for 3 or 6 months. At the time of explantation, surrounding tissues showed no or very low (only in the infrapatellar fat pad <0.32%) migration of the grafted cells. In repair tissue, gNC formed typical structures of articular cartilage, such as flattened cells at the surface and column-like clusters in the middle layers. Semi-quantitative histological evaluation revealed efficient integration of the grafted tissues with the adjacent native cartilage and underlying subchondral bone. A significantly increased subchondral bone area, as a sign for the onset of osteoarthritis, was observed following treatment of cartilage defects with gAC-, but not with gNC-grafts. Our results reinforce the use of NC-based engineered tissue for articular cartilage repair and preliminarily indicate their potential for the treatment of early osteoarthritic defects.

  19. [Human brown adipose tissue].

    PubMed

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  20. Analysis of rapid maxillary expansion effects on nasal soft tissues widths.

    PubMed

    Santariello, C; Nota, A; Baldini, A; Ballanti, F; Cozza, P

    2014-09-01

    The aim of this study was to analyze the variations in nasal dimensions in prepubertal patients associated with RME therapy compared with an untreated age matched control group. A group of 61 subjects (26 F, 35 M; mean age 10.5±1.8 years) was enrolled in the study to undergo a rapid maxillary expansion therapy; 41 subjects (26 F, 15 M; mean age 10.7±2.2 years) were enrolled as a control group. Both groups underwent nasal soft tissues width measurements using a caliper at three separate time points: T0 - prior to the placement of RME; T1 - after completion of active expansion phase; T2 - at the removal of the expander (nearly 6 months after T1). The ANOVA showed statistically significant increments (P<0.0001) of the greater alar cartilage (GAC) measurement (0.8±0.2 mm) in the study group, differences for the AB measurements were not statistically significant (P=0.0784). The treatment of rapid maxillary expansion can induce an increase in GAC soft tissues width of about 1 mm in prepubertal patients. This increase could not be considered of clinical impact. The alar base width increase less than GAC, this increase is without statistical significance.

  1. Effects of a honeybee lactic acid bacterial microbiome on human nasal symptoms, commensals, and biomarkers.

    PubMed

    Mårtensson, Anders; Greiff, Lennart; Lamei, Sepideh S; Lindstedt, Malin; Olofsson, Tobias C; Vasquez, Alejandra; Cervin, Anders

    2016-09-01

    Lactic acid bacteria (LAB) can restore commensal microbiomes and prevent infections. Arguably, nasal administrations of LAB may therefore be beneficial in chronic rhinosinusitis (CRS). Previous studies have examined effects of topical/nasal LAB in children with secretory otitis media, but little is as yet known about their effects on the human nasal airway. The aim of this pilot study was to examine effects on nasal symptoms and commensal bacteria in healthy subjects of nasal administration of a honeybee LAB microbiome; ie, a mixture of 9 Lactobacillus spp. and 4 Bifidobacterium spp. obtained from the honeybee Apis mellifera. Furthermore, we aimed to assess whether or not the honeybee LAB produced a local inflammatory response. Twenty-two healthy subjects received a single administration of honeybee LAB in a sham-controlled, double-blinded, and crossover design. Using questionnaires, microbiological methods, and nasal lavages, they were assessed regarding symptoms, changes to commensal bacteria, and inflammatory products in nasal lavage fluids. The honeybee LAB did not produce any symptoms or other untoward effects. No changes were observed of commensal bacteria by the honeybee LAB, and no inflammatory response was detected (compared to sham); ie, unaffected nasal lavage fluid levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), monokine induced by interferon-γ (MIG), interleukin-15 (IL-15), epidermal growth factor (EGF), eotaxin, interferon gamma-induced protein-10 (IP-10), and interleukin-1 receptor antagonist (IL-1RA). A single human nasal administration of a honeybee LAB microbiome is well tolerated. Specifically, it does not affect commensal bacteria and does not produce an inflammatory response. © 2016 ARS-AAOA, LLC.

  2. A low percentage of autologous serum can replace bovine serum to engineer human nasal cartilage.

    PubMed

    Wolf, F; Haug, M; Farhadi, J; Candrian, C; Martin, I; Barbero, A

    2008-02-05

    For the generation of cell-based therapeutic products, it would be preferable to avoid the use of animal-derived components. Our study thus aimed at investigating the possibility to replace foetal bovine serum (FBS) with autologous serum (AS) for the engineering of cartilage grafts using expanded human nasal chondrocytes (HNC). HNC isolated from 7 donors were expanded in medium containing 10% FBS or AS at different concentrations (2%, 5% and 10%) and cultured in pellets using serum-free medium or in Hyaff(R)-11 meshes using medium containing FBS or AS. Tissue forming capacity was assessed histologically (Safranin O), immunohistochemically (type II collagen) and biochemically (glycosaminoglycans -GAG- and DNA). Differences among experimental groups were assessed by Mann Whitney tests. HNC expanded under the different serum conditions proliferated at comparable rates and generated cartilaginous pellets with similar histological appearance and amounts of GAG. Tissues generated by HNC from different donors cultured in Hyaff(R)-11 had variable quality, but the accumulated GAG amounts were comparable among the different serum conditions. Staining intensity for collagen type II was consistent with GAG deposition. Among the different serum conditions tested, the use of 2% AS resulted in the lowest variability in the GAG contents of generated tissues. In conclusion, a low percentage of AS can replace FBS both during the expansion and differentiation of HNC and reduce the variability in the quality of the resulting engineered cartilage tissues.

  3. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey.

    PubMed

    Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent Km, Vmax, and catalytic efficiency (Vmax/Km) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar Km and Vmax appeared to metabolize naphthalene. The rank order of Vmax (rat olfactory epithelium>mouse olfactory epithelium>murine airways>rat airways) correlated well with tissue susceptibility to naphthalene. The Vmax in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. A model for the central control of airflow patterns within the human nasal cycle.

    PubMed

    Williams, M; Eccles, R

    2016-01-01

    The nasal cycle exhibits mainly reciprocal changes in nasal airflow that may be controlled from centres in the hypothalamus and brainstem. This study aims to gather new knowledge about the nasal cycle to help develop a control model. Right and left nasal airflow was measured in healthy human subjects by rhinomanometry. This was performed over 7-hour periods on 2 study days separated by approximately 1 week. The correlation coefficient for nasal airflow was calculated for day 1 and day 2. Thirty subjects (mean age, 22.7 years) completed the study. The correlation coefficient for nasal airflow varied between r = 0.97 with in-phase changes in airflow and r = -0.89 with reciprocal changes in airflow. The majority of r values were negative, indicating reciprocal changes in airflow (50 out of 60). There was a tendency for r values to become more negative between day 1 and day 2 (p < 0.001). A control model involving a hypothalamic centre and two brainstem half centres is proposed to explain both the in-phase and reciprocal changes in airflow associated with the nasal cycle.

  5. Development of T Lymphocytes in the Nasal-associated Lymphoid Tissue (NALT) from Growing Wistar Rats

    PubMed Central

    Sosa, Gustavo A.

    2004-01-01

    The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT) of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8α+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1) the predominance of TCRγδ+ and CD8α+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2) that TCRγβ+ outnumbered TCRαβ+ T cells from 7 to 45 days postpartum whereas αβ T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRγ+, CD8+, as well as the population coexpressing both phenotypes (TCRγδ+CD8α+), were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of γδ+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats. PMID:15154609

  6. LPS may enhance expression and release of HMGB1 in human nasal epithelial cells in vitro.

    PubMed

    Chen, D; Bellussi, L M; Passali, D; Chen, L

    2013-12-01

    Chronic rhinosinusitis with nasal polyps is a common disease with still unclear pathophysiologic mechanisms. The airway epithelial barrier has been shown to be involved in different chronic disorders, including rhinitis, nasal polyposis and asthma. High mobility group box 1 (HMGB1), a primarily nuclear protein, is involved in the induction of airway inflammation in patients with chronic rhinosinusitis, allergy, asthma and COPD. Pathogen-derived lipopolysaccharide is widely used as a trigger for inflammation. However, the molecular dialogue between LPS and HMGB1 in the delayed inflammatory processes remains to be explored, and the regulation of HMGB1 release through LPS from epithelial cells has not been extensively studied in patients with chronic rhinosinusitis and nasal polyps. The objective of the present study was to investigate the relocation of HMGB1 in LPS-induced human nasal epithelial cells in vitro. We obtained epithelial cells of nasal polyps from 10 patients requiring surgery for sinusitis at the ENT Department of the Chinese PLA General Hospital. The primary cultured human nasal epithelial (HNE) cells were stimulated with LPS. The expression and translocation of HMGB1 in intracellular and culture supernatants were determined using Western blot and immunofluorescence assay. HMGB1 protein was released in a time-dependent fashion in culture supernatants: in fact, expression of HMGB1 protein in HNE cells showed no significant changes at 0-24 h after exposure to 100 μg/ml LPS, but increased significantly at 48 and 72 hr. Immunofluorescence analysis revealed the transfer of HMGB1 from nuclei to cytoplasm in response to LPS exposure after 24 hr. These data reveal a hitherto unrecognized association between HMGB1 and LPS in human nasal epithelial cells. LPS can affect HMGB1 translocation and release, suggesting the involvement of HMGB1, through inflammatory mediators, in chronic rhinosinusitis with nasal polyps.

  7. Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction.

    PubMed

    Varty, LoriAnn M; Gustafson, Eric; Laverty, Maureen; Hey, John A

    2004-01-19

    The peripheral histamine H3 receptor is a presynaptic heterologous receptor located on postganglionic sympathetic nerve fibers innervating sympathetic effector systems such as blood vessels and the heart. An extensive body of evidence shows that activation of the histamine H3 receptor attenuates sympathetic tone by presynaptic inhibition of noradrenaline release. It is proposed that this sympathoinhibitory action, in vivo, leads to reduced vasoconstriction, thereby eliciting a vasodilatory effect. In humans, the peripheral histamine H3 receptor has also been shown to exert a sympathoinhibitory function on specific peripheral autonomic effector systems. For example, human saphenous vein and heart possess functional presynaptic histamine H3 receptors on the sympathetic nerve terminals that upon activation decrease the sympathetic tone to these respective organs. The present studies were conducted to define the role of histamine H3 receptors on neurogenic sympathetic vasoconstrictor responses in human nasal turbinate mucosa. Contractility studies were conducted to evaluate the effect of histamine H3 receptor activation on sympathetic vasoconstriction in surgically isolated human nasal turbinate mucosa. We found that the histamine H3 receptor agonist, (R)-alpha-methylhistamine (30 and 300 nM), inhibited electrical field stimulation-induced (neurogenic) sympathetic vasoconstriction in a concentration-dependent fashion. Pretreatment with the selective histamine H3 receptor antagonist, clobenpropit (100 nM), blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine on the neurogenic sympathetic vasoconstriction. In addition, analysis of Taqman mRNA expression studies showed a specific, high level of distribution of the histamine H3 receptor localized in the human nasal mucosa. Taken together, these studies indicate that histamine H3 receptors modulate vascular contractile responses in human nasal mucosa most likely by inhibiting noradrenaline release from

  8. A guide to practical aspects of measurement of human nasal airflow by rhinomanometry.

    PubMed

    Eccles, R

    2011-03-01

    The guide is intended for all those interested in measuring human nasal airflow by rhinomanometry, either for clinical or research purposes. The guide is written in non-technical language so that it may be understood by nursing and support staff who may need to make measurements using rhinomanometry. It is not a systematic review of the literature but a personal view based on over 40 years experience of measuring nasal airflow. The guide introduces the basic principles of nasal airflow and pressure and their measurement. The following topics are discussed: anterior and posterior rhinomanometry and their relative problems and benefits, control of errors in measurement, standard operating procedures, calibration of equipment, measurement of the totally obstructed nose, reproducibility and sensitivity of rhinomanometry, hygiene, factors influencing nasal airflow such as rest and exercise, alcohol, medicines, temperature and humidity and diseases such as common cold and allergy.

  9. Local deposition fractions of ultrafine particles in a human nasal-sinus cavity CFD model.

    PubMed

    Ge, Qin Jiang; Inthavong, Kiao; Tu, Ji Yuan

    2012-07-01

    Ultrafine particle deposition studies in the human nasal cavity regions often omit the paranasal sinus regions. Because of the highly diffusive nature of nanoparticles, it is conjectured that deposition by diffusion may occur in the paranasal sinuses, which may affect the residual deposition fraction that leaves the nasal cavity. Two identical CFD models of a human nasal cavity, one with sinuses and one without, were reconstructed from CT-scans to determine the uptake of ultrafine particles. In general, there was little flow passing through the paranasal sinuses. However, flow patterns revealed that some streamlines reached the upper nasal cavity near the olfactory regions. These flow paths promote particle deposition in the sphenoid and ethmoid sinuses. It was found that there were some differences in the deposition fractions and patterns for 5 and 10 nm particles between the nasal-sinus and the nasal cavity models. This difference is amplified when the flow rate is decreased and at a flow rate of 4 L/min the maximum difference was 17%. It is suggested that evaluations of nanoparticle deposition should consider some deposition occurring in the paranasal sinuses especially if flow rates are of concern.

  10. Clinical Examination of Tissue Eosinophilia in Patients with Chronic Rhinosinusitis and Nasal Polyposis.

    PubMed

    Gitomer, Sarah A; Fountain, Cynthia R; Kingdom, Todd T; Getz, Anne E; Sillau, Stefan H; Katial, Rohit K; Ramakrishnan, Vijay R

    2016-07-01

    (1) Describe clinical and histopathologic findings in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). (2) Determine if tissue and serum eosinophilia predicts disease severity in CRSwNP. Case series with chart review. Academic hospital specializing in respiratory and allergic disease. Patients with CRSwNP treated from 2008 to 2010. Clinical data were collected; sinus computed tomography (CT) scans were scored according to the Lund-Mackay system; and surgical specimens were evaluated for degree of tissue eosinophilia. Statistical analysis was performed to compare eosinophilia with indicators of disease severity. Seventy CRSwNP patients were included, with a mean Lund-Mackay score of 16.7; 62.1% of patients had severe asthma, and 62.9% were aspirin sensitive. Elevated tissue eosinophil level did not correlate with medication usage, olfactory symptoms, or Lund-Mackay scores, nor did it correlate with presence of asthma or aspirin-sensitivity (P = .09). Patients with mild asthma had significantly more tissue eosinophils versus patients with severe asthma, possibly because of the high amount of chronic corticosteroid use in severe asthmatics. There was no correlation between tissue and serum eosinophil counts (P = .97), but there was a significant positive correlation between CT score and peripheral eosinophil level (P < .05). Higher serum eosinophil levels may indicate more extensive mucosal disease as measured on CT scan. Neither serum nor tissue eosinophilia predicted disease severity in our retrospective analysis of CRSwNP patients, and serum eosinophil level did not serve as a marker of tissue eosinophilia. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  11. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

    SciTech Connect

    Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

  12. Human Tissue Stimulator

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Neurodyne Corporation Human Tissue Stimulator (HTS) is a totally implantable system used for treatment of chronic pain and involuntary motion disorders by electrical stimulation. It was developed by Pacesetter Systems, Inc. in cooperation with the Applied Physics Laboratory. HTS incorporates a nickel cadmium battery, telemetry and command systems technologies of the same type as those used in NASA's Small Astronomy Satellite-3 in microminiature proportions so that the implantable element is the size of a deck of cards. The stimulator includes a rechargeable battery, an antenna and electronics to receive and process commands and to report on its own condition via telemetry, a wireless process wherein instrument data is converted to electrical signals and sent to a receiver where signals are presented as usable information. The HTS is targeted to nerve centers or to particular areas of the brain to provide relief from intractable pain or arrest involuntary motion. The nickel cadmium battery can be recharged through the skin. The first two HTS units were implanted last year and have been successful. Extensive testing is required before HTS can be made available for general use.

  13. Morphological interaction between the nasal septum and nasofacial skeleton during human ontogeny.

    PubMed

    Goergen, Matthew J; Holton, Nathan E; Grünheid, Thorsten

    2017-05-01

    The nasal septal cartilage is thought to be a key growth center that contributes to nasofacial skeletal development. Despite the developmental influence of the nasal septum however, humans often exhibit a high frequency of septal deviation suggesting discordance in the growth between the septum and surrounding nasofacial skeleton. While there are numerous etiological factors that contribute to septal deviation, the surrounding nasofacial skeleton may also act to constrain the septum, resulting in altered patterns of growth. That is, while the nasal septum has a direct morphogenetic influence on aspects of the nasofacial skeleton, other nasofacial skeletal components may restrict septal growth resulting in deviation. Detailing the developmental relationship between these structures is important not only for understanding the causal determinants of nasal septal deviation, but also for developing a broader understanding of the complex interaction between the facial skeleton and chondrocranium. We selected 66 non-syndromic subjects from the University of Minnesota Orthodontic Clinic who ranged from 7 to 18 years in age and had an existing pretreatment cone-beam computed tomography (CBCT) scan. Using CBCT data, we examined the developmental relationship between nasal septal deviation and the surrounding nasofacial skeleton. We measured septal deviation as a percentage of septal volume relative to a modeled non-deviated septum. We then collected a series of coordinate landmark data in the region immediately surrounding the nasal septum in the midsagittal plane representing the nasofacial skeleton. First, we examined ontogenetic changes in the magnitude of nasal septal deviation relative to chronological age and nasofacial size. Next, using Procrustes-based geometric morphometric techniques, we assessed the morphological relationship between nasal septal deviation and nasofacial skeletal shape. Our results indicate that variation in the magnitude of nasal septal

  14. Effects of mucokinetic drugs on rheological properties of reconstituted human nasal mucus.

    PubMed

    Rhee, C S; Majima, Y; Cho, J S; Arima, S; Min, Y G; Sakakura, Y

    1999-01-01

    To investigate the effects of mucokinetic drugs on the rheological properties of human nasal mucus in patients with chronic sinusitis. We reconstituted human nasal mucus obtained from 74 patients with chronic sinusitis and determined the effects of 4 mucokinetic drugs, including acetylcysteine, deoxynuclease I, 2% sodium bicarbonate, and a combination product containing tyloxapol (Alevaire), on rheological properties of reconstituted human nasal mucus (RHNM). We used 5% RHNM dissolved in phosphate-buffered solution as the optimal buffer and concentration of RHNM for the study because it showed a viscoelastic response similar to that of freshly collected nasal mucus from patients with chronic sinusitis. Four experiments were performed to determine the influence of each drug on dynamic viscosity and elasticity of 5% RHNM. Distilled water was used as a control. Acetylcysteine and deoxynuclease I significantly decreased both dynamic viscosity and elastic modulus, while distilled water had no effect on rheological properties of 5% RHNM in vitro. Alevaire significantly reduced both dynamic viscosity and elastic modulus. Sodium bicarbonate significantly reduced elastic modulus but not dynamic viscosity. Reduction of elastic modulus by Alevaire was significantly greater than that by sodium bicarbonate, while there was no difference in reduction of dynamic viscosity between them. Our results indicate that RHNM may be useful for studying the topical effects of various drugs on nasal mucus from patients with chronic sinusitis.

  15. Effects of Ginkgo biloba on exhaled nasal nitric oxide during normobaric hypoxia in humans.

    PubMed

    Jowers, Casey; Shih, Richard; James, Jim; Deloughery, Thomas G; Holden, William E

    2004-01-01

    Ginkgo biloba, an extract of the ginkgo tree, may prevent or lessen symptoms of acute mountain sickness in humans. The mechanism of this effect is poorly understood. One hypothesis is that ginkgo alters nitric oxide (NO) metabolism, possibly by scavenging NO or altering nitric oxide synthase expression and thereby lessening the vasodilatory effects of NO. To date, an effect of Ginkgo biloba on NO metabolism has not been demonstrated in humans. We measured exhaled nasal NO output in humans (n = 9) during normoxia and then during acute normobaric hypoxia (goal oxyhemoglobin saturation 75% to 85%) before and after administration of a standardized extract of Ginkgo biloba (120 mg twice daily for 5 days). Oxygen saturation, heart rate, and minute ventilation were similar before and after Ginkgo biloba administration. Exhaled nasal NO output was increased during normoxia following ginkgo (p < 0.02) and reduced during normobaric hypoxia both before (p < 0.02) and following (p < 0.003) ginkgo. Exhaled nasal NO output during normobaric hypoxia was lowest following ginkgo (p < 0.003). We conclude that Ginkgo biloba increases exhaled nasal NO output during normoxia and enhances reduced exhaled nasal NO output during normobaric hypoxia. Our results suggest that Ginkgo biloba may act to reduce AMS through an effect on NO metabolism.

  16. Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues.

    PubMed

    Iskandar, Anita R; Martin, Florian; Talikka, Marja; Schlage, Walter K; Kostadinova, Radina; Mathis, Carole; Hoeng, Julia; Peitsch, Manuel C

    2013-01-01

    Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue.

  17. Nasal Anatomy

    MedlinePlus

    ... Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure Statement CONDITIONS Adult ... Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure Statement Printer Friendly ...

  18. Expression of survivin and enhanced polypogenesis in nasal polyps.

    PubMed

    Qiu, Zhe-Fu; Han, De-Min; Zhang, Luo; Zhang, Wei; Fan, Er-Zhong; Cui, Shun-Jiu; Huang, Qian; Wang, Xiang-Dong

    2008-01-01

    The pathogenesis of nasal polyps still is not clear. This disease is believed to be inflammation related. Previous research has indicated that apoptosis in inflammatory cells is an important factor in the resolution of inflammation. Survivin is regarded as a novel member of the group of inhibitors of apoptosis proteins. It is overexpressed in a number of tumor types. The objective of this study was to investigate the expression of the survivin gene in human nasal polyps. We investigated the expression of survivin in nasal polyps of adult patients with chronic rhinosinusitis. Specimens of nasal polyps were harvested during endonasal sinus surgery (n=22), and the normal mucosa surrounding the nasal polyp tissues or inferior turbinate tissues served as control (n=7). Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR), and Western blotting were performed for detecting the expression of survivin in the nasal polyps. This study has clearly shown that immunoreactivity of survivin significantly increased in the nasal polyp compared with nasal mucosa specimens surrounding nasal polyps (p<0.001). The higher expression of survivin Western blotting and RT-PCR also was observed in the nasal polyp but not in normal nasal mucosa. With a markedly increased expression of survivin in nasal polyps at both the mRNA and the protein levels, we believe the elevated expression of survivin might play an important role of development in nasal polyps.

  19. Optimization of human nasal epithelium primary culture conditions for optimal proton oligopeptide and organic cation transporters expression in vitro.

    PubMed

    Shao, Di; Massoud, Emad; Clarke, David; Cowley, Elizabeth; Renton, Ken; Agu, Remigius U

    2013-01-30

    To investigate the effect of key tissue culture conditions on cell growth, gene expression and functional uptake of peptide and organic cation transporter substrates in the human nasal epithelium (HNE). HNE were cultured on different growth surfaces (polystyrene plastic, collagen film, and hydrated collagen gel) and were maintained with three popular nasal tissue culture media supplements [DMEM/F12 supplemented with Ultroser(®) G (2%), FBS (10%) and NuSerum(®) (10%)], respectively. The expression of gene transcripts for organic cation and peptide transporters were screened using qPCR and substrate uptake studies. Cell growth surface (polystyrene plastic surface, dried collagen film and hydrated collagen gel) did not significantly alter gene expression levels. However, Ultroser(®) G and FBS caused significant increase in PEPT1, PEPT2, PHT1, OCT3, and OCTN1 levels (~/=2-5-fold for FBS and 2-8-fold for Ultroser(®) G). In terms of the degree to which the supplements affected gene expression, the following observations were made: effect on OCTN1>PEPT2>OCT3>PHT1>PEPT1. Functional uptake of organic cation (4-Di-1-ASP) and peptide [β-Ala-Lys (AMCA)] transporter substrates was significantly lower in cells cultured with NuSerum(®) compared to Ultroser(®) G and FBS cultured cells (p>0.05). Tissue culture media had a major effect on SLC gene expression levels of the human nasal epithelium in primary culture. Ultroser(®) G was identified as the most efficient culture supplement in maintaining SLC transporter expression under most culture conditions, whereas FBS appears to be an economical choice. We do not recommend the use of NuSerum(®) as a supplement for growing HNE for transport studies involving SLC transporters. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Use of a pharmacokinetic-driven computational fluid dynamics model to predict nasal extraction of hydrogen sulfide in rats and humans.

    PubMed

    Schroeter, Jeffry D; Kimbell, Julia S; Andersen, Melvin E; Dorman, David C

    2006-12-01

    Hydrogen sulfide (H2S) is a naturally occurring and industrially generated gas. Human exposure to H2S results in dose-related neurological, respiratory, and cardiovascular effects. Subchronic exposure of rats to 30 or 80 ppm H2S results in olfactory neuron loss and basal cell hyperplasia. Olfactory lesions commonly border main airflow streams in the rat, indicating an influence of airflow on H2S-induced lesion locations. In this study, anatomically accurate computational fluid dynamics (CFD) models were used to quantitatively predict H2S tissue dose in rat and human nasal passages. Air-tissue flux was defined in terms of H2S solubility, diffusivity, and reaction kinetics in nasal tissue. Kinetic parameters for the rat were estimated from an air-tissue pharmacokinetic (PK) model that was fit to experimental nasal extraction (NE) data. Using this PK-driven CFD model, predicted flux at the mid-dorsomedial meatus and the middle portion of the ethmoid recess showed a good correlation with olfactory lesion incidence. Scaled kinetic parameters were incorporated into a human CFD model to predict H2S flux in human nasal passages. Assuming that equivalent H2S flux values will induce similar responses in the olfactory regions of rats and humans, a no-observed-adverse-effect-level human-equivalent concentration was estimated to be 5 ppm. This estimate was based on quantitative tissue dose estimates extrapolated from both lesion and NE data in rats and represents a risk estimate that is science based and does not rely on simplified dosimetric assumptions for interspecies extrapolation.

  1. [Computational fluid dynamics simulations of the airflow in the human nasal cavity].

    PubMed

    Castro Ruiz, P; Castro Ruiz, F; Costas López, A; Cenjor Español, C

    2005-11-01

    This study represents an attempt to simulate the complex three-dimensional airflow pattern in the human nasal passageways. In the present study the computational Fluid Dynamics (CFD) have been used. The CFD solved numerically the flow governing equations. The CFD demonstrated to be a very efficient tool for researching on nasal flow. By means of CT scan, an anatomic accurate three-dimensional representation of the human nasal cavity was obtained. Based on this model the influence of the inspiration and at the expiration at the flow pattern has been reviewed. The flow pattern is visualized by the velocity, pressure and turbulence intensity fields. The flow patterns show the channel effect of turbinates and the influence of the breathing phase.

  2. Characterisation of Regulatory T Cells in Nasal Associated Lymphoid Tissue in Children: Relationships with Pneumococcal Colonization

    PubMed Central

    Zhang, Qibo; Leong, Samuel C.; McNamara, Paul S.; Mubarak, Ayman; Malley, Richard; Finn, Adam

    2011-01-01

    Regulatory T cells (Treg) diminish immune responses to microbial infection, which may contribute to preventing inflammation-related local tissue damage and autoimmunity but may also contribute to chronicity of infection. Nasopharyngeal carriage of pneumococcus is common in young children and can persist for long periods but it is unknown whether the presence of Treg in the nasopharynx contributes to this persistence. We have investigated the numbers and activities of Foxp3+Treg in adenoidal tissues and their association with pneumococcal carriage in children. Expression of Treg cell-related markers including Foxp3, CD25, CD39, CD127 and CLTA4 were analysed by flow-cytometry in adenoidal mononuclear cells (MNC) and PBMC from children. Unfractionated MNC or Treg-depleted MNC were stimulated with a pneumococcal whole cell antigen (WCA) and T cell proliferation measured. Cytokine production by MNC was measured using a cytometric bead array. Higher numbers of CD25highFoxp3high Treg expressing higher CD39 and CTLA4 were found in adenoidal MNC than in PBMC. Children with pneumococcus positive nasopharyngeal cultures had higher proportions of Treg and expressed higher levels of CD39 and CTLA-4 than those who were culture negative (−). WCA induced adenoidal Treg proliferation which produce IL10 but not IL17, and CD4 T cell proliferation in Treg-depleted MNC was greater in pneumococcal culture positive than negative children. Significant numbers of Treg with an effector/memory phenotype which possess a potent inhibitory effect, exist in adenoidal tissue. The association of pneumococcal carriage with an increased frequency of adenoidal Treg suggests that Treg in nasal-associated lymphoid tissue (NALT) may contribute to the persistence of pneumococcus in children. Further studies to determine what component and mechanisms are involved in the promotion of Treg in NALT may lead to novel therapeutic or vaccination strategy against upper respiratory infection. PMID:21852948

  3. Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: utility and limitation of the surrogate tissues in research for brain disorders.

    PubMed

    Horiuchi, Yasue; Kano, Shin-Ichi; Ishizuka, Koko; Cascella, Nicola G; Ishii, Seiji; Talbot, C Conover; Jaffe, Andrew E; Okano, Hideyuki; Pevsner, Jonathan; Colantuoni, Carlo; Sawa, Akira

    2013-12-01

    Human olfactory cells obtained by rapid nasal biopsy have been suggested to be a good surrogate system to address brain disease-associated molecular changes. Nonetheless, whether use of this experimental strategy is justified remains unclear. Here we compared expression profiles of olfactory cells systematically with those from the brain tissues and other cells. Principal component analysis indicated that the expression profiles of olfactory cells are very different from those of blood cells, but are closer to those of stem cells, in particular mesenchymal stem cells, that can be differentiated into the cells of the central nervous system.

  4. Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: utility and limitation of the surrogate tissues in research for brain disorders

    PubMed Central

    Horiuchi, Yasue; Kano, Shin-ichi; Ishizuka, Koko; Cascella, Nicola G.; Ishii, Seiji; Talbot, C. Conover; Jaffe, Andrew E.; Okano, Hideyuki; Pevsner, Jonathan; Colantuoni, Carlo; Sawa, Akira

    2014-01-01

    Human olfactory cells obtained by rapid nasal biopsy have been suggested to be a good surrogate system to address brain disease-associated molecular changes. Nonetheless, whether use of this experimental strategy is justified remains unclear. Here we compared expression profiles of olfactory cells systematically with those from the brain tissues and other cells. Principal component analysis indicated that the expression profiles of olfactory cells are very different from those of blood cells, but are closer to those of stem cells, in particular mesenchymal stem cells, that can be differentiated into the cells of the central nervous system. PMID:24120685

  5. Expression and distribution of epithelial sodium channel in nasal polyp and nasal mucosa.

    PubMed

    Jiang, Yiming; Xu, Ji; Chen, Yanqing; Shi, Jiali; Zhang, Chun; Li, Jiping

    2015-11-01

    To evaluate the expression and location of epithelial sodium channels (ENaCs) in human nasal polyp and normal nasal mucosa, and to characterize the relevance of ENaCs to the development of NPs. Nasal polyp tissue from 17 patients and nasal mucosa from ten patients were obtained through endoscopic sinus surgery. The mRNA concentrations of ENaC-α, β, and γ were detected by real-time polymerase chain reaction. The expression of ENaC-α was detected using western blot and immunofluorescence techniques. The distribution of ENaC-α in mucosal tissue was observed using a laser scanning confocal microscope. The transcriptional expression of three subunits of ENaC was in the following order: α > β > γ, in both groups. The transcriptional expression of α, β, and γ subunits of ENaC was elevated in nasal polyp compared to nasal mucosa (p < 0.01). ENaC-α expression was higher in nasal polyp than in nasal mucosa (p < 0.05). Immunofluorescent staining indicated that ENaC-α protein was distributed in the epithelial cell apical membrane. The expression of ENaC is upregulated in human nasal polyp, which might in turn facilitate the formation and development of nasal polyp.

  6. Aspects of nitrogen dioxide toxicity in environmental urban concentrations in human nasal epithelium

    SciTech Connect

    Koehler, C.; Ginzkey, C.; Friehs, G.; Hackenberg, S.; Froelich, K.; Scherzed, A.; Burghartz, M.; Kessler, M.; Kleinsasser, N.

    2010-06-01

    Cytotoxicity and genotoxicity of nitrogen dioxide (NO{sub 2}) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO{sub 2} in realistic environmental concentrations with respect to the current limit values in a human target tissue of volatile xenobiotics, the epithelium of the upper aerodigestive tract. Nasal epithelial cells of 10 patients were cultured as an air-liquid interface and exposed to 0.01 ppm NO{sub 2}, 0.1 ppm NO{sub 2}, 1 ppm NO{sub 2}, 10 ppm NO{sub 2} and synthetic air for half an hour. After exposure, genotoxicity was evaluated by the alkaline single-cell microgel electophoresis (Comet) assay and by induction of micronuclei in the micronucleus test. Depression of proliferation and cytotoxic effects were determined using the micronucleus assay and trypan blue exclusion assay, respectively. The experiments revealed genotoxic effects by DNA fragmentation starting at 0.01 ppm NO{sub 2} in the Comet assay, but no micronucleus inductions, no changes in proliferation, no signs of necrosis or apoptosis in the micronucleus assay, nor did the trypan blue exclusion assay show any changes in viability. The present data reveal a possible genotoxicity of NO{sub 2} in urban concentrations in a screening test. However, permanent DNA damage as indicated by the induction of micronuclei was not observed. Further research should elucidate the effects of prolonged exposure.

  7. Capsaicin-desensitization to the human nasal mucosa selectively reduces pain evoked by citric acid.

    PubMed Central

    Geppetti, P; Tramontana, M; Del Bianco, E; Fusco, B M

    1993-01-01

    1. Kallidin (5-500 nmol), hypertonic saline (0.9-20% NaCl) or low pH medium (citric acid: pH 2.5-1) applied (50 microliters) to the human nasal mucosa produced a pain response (evaluated by a visual analogue scale) that was related to the concentration of the peptide, NaCl or hydrogen ions, respectively. 2. Application (50 microliters) of capsaicin (50 nmol) to the human nasal mucosa produced overt pain. After repeated administrations (once a day for 5-7 days) to one nostril this effect underwent almost complete desensitization, while in the contralateral nostril, treated with the vehicle, the response to capsaicin was unaffected. 3. The pain response produced in the human nasal mucosa by topical application (50 microliters) or kallidin (50-500 nmol), NaCl (10-20%) or citric acid (pH 1.5-1) solutions was then studied before and after local capsaicin desensitization. 4. The pain response to pH 1.5 or 1 citric acid was markedly reduced (by 60% and 75%, respectively) in the capsaicin-treated nostril. However, the pain response to 10% or 20% NaCl or the mild pain response to 50 or 500 nmol kallidin were unaffected by capsaicin pre-treatment. 5. The present results suggest that prolonged topical capsaicin treatment to the human nasal mucosa may lead to selective desensitization to certain algesic stimuli such as capsaicin itself and hydrogen ions. PMID:8443036

  8. The nasal complex of Neanderthals: an entry portal to their place in human ancestry.

    PubMed

    Márquez, Samuel; Pagano, Anthony S; Delson, Eric; Lawson, William; Laitman, Jeffrey T

    2014-11-01

    Neanderthals are one of the most intensely studied groups of extinct humans, as aspects of their phylogeny and functional morphology remain controversial. They have long been described as cold adapted but recent analyses of their nasal anatomy suggest that traits formerly considered adaptations may be the result of genetic drift. This study performs quantitative and qualitative analysis of aspects of the nasal complex (NC) in Neanderthals and other later Pleistocene fossils from Europe and Africa. A geographically diverse sample of modern human crania was used to establish an anatomical baseline for populations inhabiting cold and tropical climates. Nasofrontal angle, piriform aperture dimensions, and relative maxillary sinus volume were analyzed along with qualitative features of the piriform aperture rim. Results indicate that Neanderthals and other later Pleistocene Homo possessed NC's that align them with tropical modern humans. Thus comparison of Neanderthal nasal morphology with that of modern humans from cold climates may not be appropriate as differences in overall craniofacial architecture may constrain the narrowing of the piriform apertures in Neanderthals. They retain primitively long, low crania, large maxillary sinuses, and large piriform aperture area similar to mid-Pleistocene Homo specimens such as Petralona 1 and Kabwe 1. Adaptation to cold climate may have necessitated other adaptations such as bony medial projections at the piriform aperture rim and, potentially, midfacial prognathism. Nasal complex components of the upper respiratory tract remain a critical but poorly understood area that may yet offer novel insight into one of the greatest continuing controversies in paleoanthropology.

  9. From the Cover: Comparative Numerical Modeling of Inhaled Nanoparticle Deposition in Human and Rat Nasal Cavities.

    PubMed

    Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan; Chen, Rui; Bai, Ru; Wang, Dongliang; Chen, Chunying

    2016-08-01

    To gain a better understanding of nanoparticle exposure in human nasal cavities, laboratory animals (e.g. rat) are used for in vivo studies. However, due to anatomical differences between human and rodent nasal cavities, direct particle deposition comparisons between species are difficult. This paper presents a comparative nanoparticle (1 nm, 10 nm, and 100 nm) deposition study using anatomically realistic models of a human and rat nasal cavity. The particle deposition fraction was highest consistently in the main nasal passage, for all nanoparticles tested, in the human model; whereas this was only the case for 10 nm, and 100 nm particles for the rodent model, where greater deposition was found in the anterior nose for 1 nm particles. A deposition intensity (DI) term was introduced to represent the accumulated deposition fraction on cross-sectional slices. A common and preferential deposition site in the human model was found for all nanoparticles occurring at a distance of 3.5 cm inside the nasal passage. For the rodent model maximum DI occurred in the vestibule region at a distance of 0.3 cm, indicating that the rodent vestibule produces exceptionally high particle filtration capability. We also introduced a deposition flux which was a ratio of the regional deposition fraction relative to the region's surface area fraction. This value allowed direct comparison of deposition flux between species, and a regional extrapolation scaling factor was found (e.g. 1/10 scale for vestibule region for rat to human comparison). This study bridges the in vitro exposure experiments and in vivo nanomaterials toxicity studies, and can contribute towards improving inter-species exposure extrapolation studies in the future. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data.

    PubMed

    Hinderliter, P M; Thrall, K D; Corley, R A; Bloemen, L J; Bogdanffy, M S

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  11. Validation of Human Physiologically Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data

    SciTech Connect

    Hinderliter, Paul M.; Thrall, Karla D.; Corley, Rick A.; Bloemen, Louis J.; Bogdanffy, M S.

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13 C1 , 13 C2 vinyl acetate via inhalation. A probe inserted into thenasopharyngeal region sampled both 13 C1 , 13 C2 vinyl acetate and the major metabolite 13 C1 , 13 C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  12. A Real-time Method to Evaluate the Nasal Deposition and Clearance of Acetone in the Human Volunteer

    SciTech Connect

    Thrall, Karla D. ); Schwartz, Ronald E.; Weitz, Karl K. ); Soelberg, Jolen J. ); Foureman, Gary L.; Prah, James D.; Timchalk, Charles

    2003-05-01

    Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled 13C-acetone at approximately 1 ppm concentration for 30 minutes under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 sec. A second ion-trap mass spectrometer simultaneously sampled from the volunteer?s exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the 13C-acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in 13C-acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analysis of 13C-acetone concentrations indicate that between 40-75% of the compound is absorbed upon inhalation and nearly all of that absorbed released back into the breath stream during exhalation.

  13. Polyvinylidene fluoride film based nasal sensor to monitor human respiration pattern: an initial clinical study.

    PubMed

    Roopa Manjunatha, G; Rajanna, K; Mahapatra, D Roy; Nayak, M M; Krishnaswamy, Uma Maheswari; Srinivasa, R

    2013-12-01

    Design and development of a piezoelectric polyvinylidene fluoride (PVDF) thin film based nasal sensor to monitor human respiration pattern (RP) from each nostril simultaneously is presented in this paper. Thin film based PVDF nasal sensor is designed in a cantilever beam configuration. Two cantilevers are mounted on a spectacle frame in such a way that the air flow from each nostril impinges on this sensor causing bending of the cantilever beams. Voltage signal produced due to air flow induced dynamic piezoelectric effect produce a respective RP. A group of 23 healthy awake human subjects are studied. The RP in terms of respiratory rate (RR) and Respiratory air-flow changes/alterations obtained from the developed PVDF nasal sensor are compared with RP obtained from respiratory inductance plethysmograph (RIP) device. The mean RR of the developed nasal sensor (19.65 ± 4.1) and the RIP (19.57 ± 4.1) are found to be almost same (difference not significant, p > 0.05) with the correlation coefficient 0.96, p < 0.0001. It was observed that any change/alterations in the pattern of RIP is followed by same amount of change/alterations in the pattern of PVDF nasal sensor with k = 0.815 indicating strong agreement between the PVDF nasal sensor and RIP respiratory air-flow pattern. The developed sensor is simple in design, non-invasive, patient friendly and hence shows promising routine clinical usage. The preliminary result shows that this new method can have various applications in respiratory monitoring and diagnosis.

  14. DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution

    SciTech Connect

    Calderon-Garciduenas, L.; Osnaya-Brizuela, N.; Ramirez-Martinez, L.

    1996-02-01

    All organisms have the ability to respond and adapt to a myriad of environmental insults. The human respiratory epithelium, when exposed to oxidant gases in photochemical smog, is at risk of DNA damage and requires efficient cellular adaptative responses to resist the environmentally induced cell damage. Ozone and its reaction products induce in vitro and in vivo DNA single strand breaks (SSBs) in respiratory epithelial cells and alveolar macrophages. To determine if exposure to a polluted atmosphere with ozone as the main criteria pollutant of 19 children and 13 adult males who lived in a low-polluted Pacific port, 69 males and 16 children who were permanent residents of Southwest Metropolitan Mexico City (SWMMC), and 22 young males newly arrived to SWMMC and followed for 12 weeks. Respiratory symptoms, nasal cytology and histopathology, cell viabilities, and single-cell gel electrophoresis were investigated. Atmospheric pollutant data were obtained from a fixed-site monitoring station. SWMMC volunteers spent >7 hr/day outdoors and all had upper respiratory symptoms. A significant difference in the numbers of DNA-damaged nasal cells was observed between control and chronically exposed subjects, both in children (p<0.00001) and in adults (p>0.01). SSBs in newly arrived subjects quickly increased upon arrival to the city, from 39.8 {+-}8.34% in the first week to 67.29 {+-}2.35 by week 2. Thereafter, the number of cells with SSBs remained stable in spite of the continuous increase in cumulative ozone, suggesting a threshold for cumulative DNA nasal damage. Exposure to a polluted urban atmosphere induces SSBs in human nasal respiratory epithelium, and nasal SSBs could serve as a biomarker of ozone exposure. Further, because DNA strand breaks are a threat to cell viability and genome integrity and appear to be a critical lesion responsible for p53 induction, nasal SSBs should be evaluated in ozone-exposed individuals. 43 refs., 5 figs., 4 tabs.

  15. [Electron microscopy studies of vascular innervation of nasal mucosa in the human].

    PubMed

    Riederer, A; Grevers, G; Welsch, U; Herzmann, S

    1997-07-01

    The distribution of neural structures in human nasal vasculature is still not completely understood. To date, immunocytochemical and histochemical studies of the innervation pattern and neurotransmitter distribution have only been performed using light microscopy. The aim of this study was to verify these results by electron microscopy and to obtain new knowledge of the innervation of the individual vessel types. The target was to determine the role of the different vessels in the swelling mechanism in human nasal mucosa. Specimens were prefixed in glutaraldehyde and postfixed in osmium tetroxide. After dehydration they were embedded in araldite. Ultrathin sections were cut, contrasted with uranylacetate and lead citrate, and studied under EM. Nasal vasculature is controlled by a dense innervation. Amyelinated longitudinal nerve bundles and smaller axon conglomerates are detected in the arterial adventitia. Capacitance vessels (veins) in general show few nerve structures, which, in contrast to arteries, are also located between the smooth muscle cells. Cushion veins, however, reveal a stronger innervation pattern especially in their muscular swelling. In contrast to smaller arterioles, no axons can de demonstrated in capillaries. The density of innervation in arteries and cushion veins seems to indicate that these vessel types are the central neural control point for the swelling mechanism in human nasal mucosa. Capillary function, however, does not seem to be directly influenced by the autonomic nervous system.

  16. Decellularization of Human Nasal Septal Cartilage for the Novel Filler Material of Vocal Fold Augmentation.

    PubMed

    Kang, Dae-Woon; Shin, Sung-Chan; Jang, Jeon-Yeob; Park, Hee-Young; Lee, Jin-Choon; Wang, Soo-Geun; Lee, Byung-Joo

    2017-01-01

    The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method. Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment. A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes. Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  17. Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position.

    PubMed

    Sánchez Crespo, Alejandro; Hallberg, Jenny; Lundberg, Jon O; Lindahl, Sten G E; Jacobsson, Hans; Weitzberg, Eddie; Nyrén, Sven

    2010-01-01

    There are a number of evidences suggesting that lung perfusion distribution is under active regulation and determined by several factors in addition to gravity. In this work, we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. In 15 healthy volunteers, we used single-photon emission computed tomography technique and two tracers (99mTc and 113mIn) labeled with human macroaggregated albumin to assess pulmonary blood flow distribution. In the sitting upright position, subjects first breathed NO free air through the mouth followed by the administration of the first tracer. Subjects then switched to either nasal breathing or oral breathing with the addition of exogenous NO-enriched air followed by the administration of the second tracer. Compared with oral breathing, nasal breathing induced a blood flow redistribution of approximately 4% of the total perfusion in the caudal to cranial and dorsal to ventral directions. For low perfused lung regions like the apical region, this represents a net increase of 24% in blood flow. Similar effects were obtained with the addition of exogenous NO during oral breathing, indicating that NO and not the breathing condition was responsible for the blood flow redistribution. In conclusion, these results provide evidence that autoinhalation of endogenous NO from the nasal airways may ameliorate the influence of gravity on pulmonary blood flow distribution in the upright position. The presence of nasal NO only in humans and higher primates suggest that it may be an important part of the adaptation to bipedalism.

  18. Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

    PubMed

    Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

    2015-04-01

    The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

  19. [Adult of Drosophila melanogaster parasitized in human nasal cavity: a case report].

    PubMed

    Zhan, Xiaodong; Tang, Xiaoniu; Wang, Shaosheng

    2015-05-01

    We reported a case of adult Drosophila melanogaster parasitized in nasal cavity of a 81-year-old woman who was living in Xuancheng City, Anhui Province now. She was admitted for treatment of cerebral infarction and water accumulation in the lungs in 2014 June. The patient was also suffering from secretory otitis media, a history of hypertension and heart stents were placed in 2007. A foreign body was found in the left nasal cavity during the preoperative examination process, and then the part of the inflammatory tissue was removed through the nasal endoscopy, and sent to our department for identification. There are three adults of Drosophila in paraffin-embedded biopsy specimens. The parasites length is approximately 3mm, with huge red compound eyes. The end of the body is tip, with 5 ring lines in back, has no dark spots. The abdomen of the parasites have seven sections. Tarsus of foot I have no sex comb on base, and they are male adult of Drosophila melanogaster after identification. After a thorough reviewing of medical history, we knew the patient began to sneeze violently and frequently six years ago. But there was no clear or purulent nasal discharge flowing, therefore did not attract attention. After removing the parasites the sneezing symptoms were relieved, and had no abnormal symptoms in the follow-up 6 months.

  20. Comparative numerical modeling of inhaled micron-sized particle deposition in human and rat nasal cavities.

    PubMed

    Shang, Yidan; Dong, Jingliang; Inthavong, Kiao; Tu, Jiyuan

    2015-01-01

    Micron-sized particle deposition in anatomically realistic models of a rat and human nasal cavity was numerically investigated. A steady laminar inhalation flow rate was applied and particles were released from the outside air. Particles showing equivalent total particle deposition fractions were classified into low, medium and high inertial particle. Typical particle sizes are 2.5, 9 and 20 μm for the human model and 1, 2 and 3 μm for the rat model, respectively. Using a surface-mapping technique the 3D nasal cavity surface was "unwrapped" into a 2D domain and the particle deposition locations were plotted for complete visual coverage of the domain surface. The total surface area comparison showed that the surface area of the human nasal model was about ten times the size of the rat model. In contrast, the regional surface area percentage analysis revealed the olfactory region of the rat model was significantly larger than all other regions making up ∼55.6% of the total surface area, while that of the human nasal model only occupying 10.5%. Flow pattern comparisons showed rapid airflow acceleration was found at the nasopharynx region and the nostril region for the human and rat model, respectively. For the human model, the main passage is the major deposition region for micro-particles. While for the rat model, it is the vestibule. Through comparing the regional deposition flux between human and rat models, this study can contribute towards better extrapolation approach of inhalation exposure data between inter-subject species.

  1. Yield Strength Testing in Human Cadaver Nasal Septal Cartilage and L-Strut Constructs.

    PubMed

    Liu, Yuan F; Messinger, Kelton; Inman, Jared C

    2017-01-01

    To our knowledge, yield strength testing in human nasal septal cartilage has not been reported to date. An understanding of the basic mechanics of the nasal septum may help surgeons decide how much of an L-strut to preserve and how much grafting is needed. To determine the factors correlated with yield strength of the cartilaginous nasal septum and to explore the association between L-strut width and thickness in determining yield strength. In an anatomy laboratory, yield strength of rectangular pieces of fresh cadaver nasal septal cartilage was measured, and regression was performed to identify the factors correlated with yield strength. To measure yield strength in L-shaped models, 4 bonded paper L-struts models were constructed for every possible combination of the width and thickness, for a total of 240 models. Mathematical modeling using the resultant data with trend lines and surface fitting was performed to quantify the associations among L-strut width, thickness, and yield strength. The study dates were November 1, 2015, to April 1, 2016. The factors correlated with nasal cartilage yield strength and the associations among L-strut width, thickness, and yield strength in L-shaped models. Among 95 cartilage pieces from 12 human cadavers (mean [SD] age, 67.7 [12.6] years) and 240 constructed L-strut models, L-strut thickness was the only factor correlated with nasal septal cartilage yield strength (coefficient for thickness, 5.54; 95% CI, 4.08-7.00; P < .001), with an adjusted R2 correlation coefficient of 0.37. The mean (SD) yield strength R2 varied with L-strut thickness exponentially (0.93 [0.06]) for set widths, and it varied with L-strut width linearly (0.82 [0.11]) or logarithmically (0.85 [0.17]) for set thicknesses. A 3-dimensional surface model of yield strength with L-strut width and thickness as variables was created using a 2-dimensional gaussian function (adjusted R2 = 0.94). Estimated yield strengths were generated from the model to allow

  2. The effects of injection modes on instantaneous particle deposition in a realistic human nasal cavity.

    PubMed

    Wen, Jian; Gu, Xin; Wang, Mengmeng; Jian, Guanping; Wang, Simin; Zheng, Guoxi

    2017-03-01

    To understand the instantaneous particle deposition in nasal cavity, effects of two injection models on particle deposition characteristic were discussed in this paper. Based on a realistic human nasal cavity geometry obtained from CT scans, a comparison of deposition pattern in the nasal cavity between single injection and continuous injection was investigated through the Lagrangian approach. The instantaneous airflow field was simulated with the tidal volume of 159 and 318 mL by two sine wave curves at inlet. For the case of single injection, particles have finished deposition in the first half of inhalation, and a negative correlation between the tidal volumes and deposition can be observed when the particle diameter was larger than 10 µm. Moreover, particles were mainly deposited in the turbinate area that was beneficial for aerosol therapy. The inertial parameter was not suitable to predict the particle deposition in the case of single injection. With respect to continuous injection, a reduction in total deposition caused by the deceleration process of inhalation can be observed after 1.5 s. The deposition was closely associated with the time-varying flow field, and particles were mainly deposited in the anterior region and turbinate area. Besides, the particle deposition increased with the inertial parameter for continuous injection. The results indicated that the injection modes had an influence on both the total deposition and local deposition pattern in the nasal cavity. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Surface mapping for visualization of wall stresses during inhalation in a human nasal cavity.

    PubMed

    Inthavong, Kiao; Shang, Yidan; Tu, Jiyuan

    2014-01-01

    Airflow analysis can assist in better understanding the physiology however the human nasal cavity is an extremely complicated geometry that is difficult to visualize in 3D space, let alone in 2D space. In this paper, an anatomically accurate 3D surface of the nasal passages derived from CT data was unwrapped and transformed into a 2D space, into a UV-domain (where u and v are the coordinates) to allow a complete view of the entire wrapped surface. This visualization technique allows surface flow parameters to be analyzed with greater precision. A UV-unwrapping tool is developed and a strategy is presented to allow deeper analysis to be performed. This includes (i) the ability to present instant comparisons of geometry and flow variables between any number of different nasal cavity models through normalization of the 2D unwrapped surface; (ii) visualization of an entire surface in one view and; (iii) a planar surface that allows direct 1D and 2D analytical solutions of diffusion of inhaled vapors and particles through the nasal walls. This work lays a foundation for future investigations that correlates adverse and therapeutic health responses to local inhalation of gases and particles. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution.

    PubMed Central

    Calderon-Garciduenas, L; Osnaya-Brizuela, N; Ramirez-Martinez, L; Villarreal-Calderon, A

    1996-01-01

    All organisms have the ability to respond and adapt to a myriad of environmental insults. The human respiratory epithelium, when exposed to oxidant gases in photochemical smog, is at risk of DNA damage and requires efficient cellular adaptative responses to resist the environmentally induced cell damage. Ozone and its reaction products induce in vitro and in vivo DNA single strand breaks (SSBs) in respiratory epithelial cells and alveolar macrophages. To determine if exposure to a polluted atmosphere with ozone as the main criteria pollutant induces SSBs in nasal epithelium, we studied 139 volunteers, including a control population of 19 children and 13 adult males who lived in a low-polluted Pacific port, 69 males and 16 children who were permanent residents of Southwest Metropolitan Mexico City (SWMMC), and 22 young males newly arrived to SWMMC and followed for 12 weeks. Respiratory symptoms, nasal cytology and histopathology, cell viabilities, and single-cell gel electrophoresis were investigated. Atmospheric pollutant data were obtained from a fixed-site monitoring station. SWMMC volunteers spent >7 hr/day outdoors and all had upper respiratory symptoms. A significant difference in the numbers of DNA-damaged nasal cells was observed between control and chronically exposed subjects, both in children (p<0.00001) and in adults (p<0.01). SSBs in newly arrived subjects quickly increased upon arrival to the city, from 39.8 +/- 8.34% in the first week to 67.29 +/- 2.35 by week 2. Thereafter, the number of cells with SSBs remained stable in spite of the continuous increase in cumulative ozone, suggesting a threshold for cumulative DNA nasal damage. Exposure to a polluted urban atmosphere induces SSBs in human nasal respiratory epithelium, and nasal SSBs could serve as a biomarker of ozone exposure. Further, because DNA strand breaks are a threat to cell viability and genome integrity and appear to be a critical lesion responsible for p53 induction, nasal SSBs should be

  5. DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution.

    PubMed

    Calderon-Garciduenas, L; Osnaya-Brizuela, N; Ramirez-Martinez, L; Villarreal-Calderon, A

    1996-02-01

    All organisms have the ability to respond and adapt to a myriad of environmental insults. The human respiratory epithelium, when exposed to oxidant gases in photochemical smog, is at risk of DNA damage and requires efficient cellular adaptative responses to resist the environmentally induced cell damage. Ozone and its reaction products induce in vitro and in vivo DNA single strand breaks (SSBs) in respiratory epithelial cells and alveolar macrophages. To determine if exposure to a polluted atmosphere with ozone as the main criteria pollutant induces SSBs in nasal epithelium, we studied 139 volunteers, including a control population of 19 children and 13 adult males who lived in a low-polluted Pacific port, 69 males and 16 children who were permanent residents of Southwest Metropolitan Mexico City (SWMMC), and 22 young males newly arrived to SWMMC and followed for 12 weeks. Respiratory symptoms, nasal cytology and histopathology, cell viabilities, and single-cell gel electrophoresis were investigated. Atmospheric pollutant data were obtained from a fixed-site monitoring station. SWMMC volunteers spent >7 hr/day outdoors and all had upper respiratory symptoms. A significant difference in the numbers of DNA-damaged nasal cells was observed between control and chronically exposed subjects, both in children (p<0.00001) and in adults (p<0.01). SSBs in newly arrived subjects quickly increased upon arrival to the city, from 39.8 +/- 8.34% in the first week to 67.29 +/- 2.35 by week 2. Thereafter, the number of cells with SSBs remained stable in spite of the continuous increase in cumulative ozone, suggesting a threshold for cumulative DNA nasal damage. Exposure to a polluted urban atmosphere induces SSBs in human nasal respiratory epithelium, and nasal SSBs could serve as a biomarker of ozone exposure. Further, because DNA strand breaks are a threat to cell viability and genome integrity and appear to be a critical lesion responsible for p53 induction, nasal SSBs should be

  6. [Immunocytochemical detection of caspase 3 in various diseases of human nasal mucosa].

    PubMed

    Hirt, R; Paulsen, F; Neumann, K; Knipping, S

    2009-05-01

    Inflammatory processes play a central role in the pathogenesis of chronic rhinosinusitis (CRS), however, the impact of apoptosis in CRS in unclear. The aim of this study was a comparison of caspase 3 activity, a key enzyme in the apoptosis cascade, in samples of nasal tissue from patients with different types of rhinosinusitis. Immunohistochemical analyses were carried out to detect caspase 3 in samples of nasal tissue from patients with CRS and nasal polyps (NP), allergic rhinitis (AR), rhinitis medicamentosa (RM) and atrophic rhinitis. Evidence of increased apoptosis was found in the epithelium, submucosal glands and blood vessels in NP samples. Samples of RM showed strong caspase 3 activity in the endothelial cells and the lamina muscularis of blood vessels. In atrophic rhinitis the epithelium and subepithelial glands showed increased caspase 3 activity. In samples of patients with allergic rhinitis caspase 3 activity could not be detected. Activated apoptosis seems to play an important role in the pathogenesis of different types of rhinosinusitis. Further investigations on the induction of caspase 3 are necessary for the development of new therapeutic strategies to influence the regulation of apoptosis.

  7. Cocaine inhibits extraneuronal O-methylation of exogenous norepinephrine in nasal and oral tissues of the rabbit

    SciTech Connect

    de la Lande, I.S.; Parker, D.A.S.; Proctor, C.H.; Marino, V.; Mackay-Sim, A.

    1987-11-30

    Nasal mucosa (respirator and olfactory) and lingual gingiva of the rabbit were depleted of their sympathetic nerves by superior cervical ganglionectomy. In the innervated nasal mucosa, exogenous tritiated norepinephrine (/sup 3/H-NE) was metabolized mainly to tritiated 3,4-dihydroxyphenylethylene glycol (/sup 3/HDOPEG) and 3,4-dihydroxy mandelic acid (/sup 3/HDOMA), whereas after denervation it was metabolized mainly to tritiated normetanephrine (/sup 3/HNMN). In the denervated mucosa, cocaine(30umol/l) inhibited /sup 3/HNMN formation by 50-60%. Cocaine also inhibited /sup 3/HNMN formation by 60% in the denervated lingual gingiva. It is concluded that the tissues metabolize /sup 3/H-NE via a cocaine-sensitive extraneuronal uptake and O-methylating system similar to that which has been shown to be present in dental pulp. 17 references, 1 table.

  8. Lack of DNA binding in the rat nasal mucosa and other tissues of the nasal toxicants roflumilast, a phosphodiesterase 4 inhibitor, and a metabolite, 4-amino-3,5-dichloropyridine, in contrast to the nasal carcinogen 2,6-dimethylaniline.

    PubMed

    Jeffrey, Alan M; Luo, Feng-Qi; Amin, Shantilal; Krzeminski, Jacek; Zech, Karl; Williams, Gary M

    2002-02-01

    The phosphodiesterase 4 inhibitor Roflumilast (B9302-107) (RF) and its metabolite 4-amino-3,5-dichloropyridine (ADCP) produced nasal toxicity in preclinical safety studies with rats. The purpose of this study was to assess the possible formation of DNA adducts, by RF and ADCP, in the nasal mucosa, liver and testes of male rats using the 32P-postlabeling assay. For comparison, rats were exposed to the DNA-reactive carcinogens 2,6-dimethylaniline (DMA), also known as 2,6-xylidine, a nasal carcinogen, and the aromatic amine carcinogens 4,4'-methylene-bis(2-chloroaniline) (MOCA), which yields monocyclic DNA adducts, and 2-acetylaminofluorene (2-AAF). In the case of RF, possible sources of DNA adducts include the parent molecule and its ADCP moiety by enzymatic N-hydroxylation and sulfation, reactions typical of carcinogenic aromatic amines. 4-Acetoxylamino-3,5-dichloropyridine (N-acetoxy-ADCP), a chemically activated derivative of ADCP, was prepared and used to modify DNA which was then used to establish the chromatographic conditions with which to reliably detect whether or not such adducts were formed metabolically from RF and ADCP. Similarly, a standard N-hydroxy-DMA was prepared, but the corresponding N-acetoxy derivative was unstable and decomposed during synthesis. Both N-hydroxy-DMA and N-acetoxy-ADCP were mutagenic in the Salmonella typhimurium Ames assay using strain TA100 without an exogenous bioactivation system, with the former being more potent. N-hydroxy-ADCP was essentially inactive in this assay. For the 32P-postlabeling assay, male Wistar rats were exposed to the test substances and carrier control compounds by intragastric instillation at the selected dose levels for 7 days. Subsequently, the nasal mucosa, liver, and testes of the rats exposed to the test or control compounds were extirpated, the DNA extracted and the samples postlabeled. The patterns of adducts formed with the test compounds were compared to those formed in N-acetoxy-ADCP- and N

  9. Characterization of human tissue carnosinase.

    PubMed Central

    Lenney, J F; Peppers, S C; Kucera-Orallo, C M; George, R P

    1985-01-01

    Human tissue carnosinase (EC 3.4.13.3) had optimum activity at pH9.5 and was a cysteine peptidase, being activated by dithiothreitol and inhibited by p-hydroxymercuribenzoate. By optimizing assay conditions, the activity per g of tissue was increased 10-fold compared with values in the literature. The enzyme was present in every human tissue assayed and was entirely different from serum carnosinase. Highly purified tissue carnosinase had a broader specificity than hog kidney carnosinase. Although tissue carnosinase was very strongly inhibited by bestatin, it did not hydrolyse tripeptides, and thus appears to be a dipeptidase rather than an aminopeptidase. It had a relative molecular mass of 90 000, an isoelectric point of 5.6, and a Km value of 10 mM-carnosine. Two forms of kidney and brain carnosinase were separated by high-resolution anion-exchange chromatography, although only one form was detected by various electrophoretic methods. Homocarnosinase and Mn2+-independent carnosinase were not detected in human tissues, although these enzymes are present in rat and hog kidney. PMID:4026801

  10. Pilot study to establish a nasal tip prediction method from unknown human skeletal remains for facial reconstruction and skull photo superimposition as applied to a Japanese male populations.

    PubMed

    Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko; Sakurada, Koichi; Uemura, Koichi

    2016-02-01

    Skull-photo superimposition is a technique used to identify the relationship between the skull and a photograph of a target person: and facial reconstruction reproduces antemortem facial features from an unknown human skull, or identifies the facial features of unknown human skeletal remains. These techniques are based on soft tissue thickness and the relationships between soft tissue and the skull, i.e., the position of the ear and external acoustic meatus, pupil and orbit, nose and nasal aperture, and lips and teeth. However, the ear and nose region are relatively difficult to identify because of their structure, as the soft tissues of these regions are lined with cartilage. We attempted to establish a more accurate method to determine the position of the nasal tip from the skull. We measured the height of the maxilla and mid-lower facial region in 55 Japanese men and generated a regression equation from the collected data. We obtained a result that was 2.0±0.99mm (mean±SD) distant from the true nasal tip, when applied to a validation set consisting of another 12 Japanese men.

  11. Human parvovirus 4 in nasal and fecal specimens from children, Ghana.

    PubMed

    Drexler, Jan Felix; Reber, Ulrike; Muth, Doreen; Herzog, Petra; Annan, Augustina; Ebach, Fabian; Sarpong, Nimarko; Acquah, Samuel; Adlkofer, Julia; Adu-Sarkodie, Yaw; Panning, Marcus; Tannich, Egbert; May, Jürgen; Drosten, Christian; Eis-Hübinger, Anna Maria

    2012-10-01

    Nonparenteral transmission might contribute to human parvovirus 4 (PARV4) infections in sub-Saharan Africa. PARV4 DNA was detected in 8 (0.83%) of 961 nasal samples and 5 (0.53%) of 943 fecal samples from 1,904 children in Ghana. Virus concentrations ≤ 6-7 log(10) copies/mL suggest respiratory or fecal-oral modes of PARV4 transmission.

  12. Human Parvovirus 4 in Nasal and Fecal Specimens from Children, Ghana

    PubMed Central

    Drexler, Jan Felix; Reber, Ulrike; Muth, Doreen; Herzog, Petra; Annan, Augustina; Ebach, Fabian; Sarpong, Nimarko; Acquah, Samuel; Adlkofer, Julia; Adu-Sarkodie, Yaw; Panning, Marcus; Tannich, Egbert; May, Jürgen; Drosten, Christian

    2012-01-01

    Nonparenteral transmission might contribute to human parvovirus 4 (PARV4) infections in sub-Saharan Africa. PARV4 DNA was detected in 8 (0.83%) of 961 nasal samples and 5 (0.53%) of 943 fecal samples from 1,904 children in Ghana. Virus concentrations ≤6–7 log10 copies/mL suggest respiratory or fecal–oral modes of PARV4 transmission. PMID:23018024

  13. Micro and nanoparticle deposition in human nasal passage pre and post virtual maxillary sinus endoscopic surgery.

    PubMed

    Abouali, Omid; Keshavarzian, Erfan; Farhadi Ghalati, Pejman; Faramarzi, Abolhasan; Ahmadi, Goodarz; Bagheri, Mohammad Hadi

    2012-05-31

    Realistic 3-D models of the human nasal passages were developed pre and post virtual uncinectomy and Middle Meatal Antrostomy. A 3-D computational domain was constructed by a series of coronal CT scan images from a healthy subject. Then a virtual uncinectomy intervention and maxillary antrostomy were performed on the left nasal passage by removing the uncinate process and exposing the maxillary sinus antrum. For several breathing rates corresponding to low or moderate activities, the airflows in the nasal passages were simulated numerically pre and post virtual routine maxillary sinus endoscopic surgery. The airflow distribution in the nasal airway, maxillary and frontal sinuses were analyzed and compared between pre and post surgery cases. A Lagrangian trajectory analysis approach was used for evaluating the path and deposition of microparticles in the nasal passages and maxillary sinuses. A diffusion model was used for nanoparticle transport and deposition analysis. The deposition rate of the inhaled micro and nanoparticles in the sinuses were evaluated and compared for pre and post operation conditions. The results showed that after maxillary sinus endoscopic surgery, the inhaled nano and microparticles can easily enter this sinus due to penetration of the airflow into the sinus cavity. This was in contrast to the preoperative condition in which almost no particles entered the sinuses. These results could be of importance for a better understanding of the effect of sinus endoscopic surgery on patient exposure to particulate pollution and inhalation drug delivery. The significantly higher airflow rate and particle deposition in the sinus could be a reason for the discomfort reported by some patient after maxillary sinus endoscopic surgery. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Nasalance, nasality, voice, and articulation after uvulopalatopharyngoplasty.

    PubMed

    Van Lierde, Kristiane M; Van Borsel, John; Moerman, Mieke; Van Cauwenberge, Paul

    2002-05-01

    The main purpose of the study was to determine the impact of uvulopalatopharyngoplasty (UPPP) on nasalance and nasality. It was hypothesized that nasalance would change from the presurgical to the postsurgical condition because the surgical protocol involves removal of palatal tissue. An additional objective of the study was to provide objective and subjective data about changes in voice and articulation after UPPP. Because the surgical procedure of UPPP does not involve laryngeal tissue, it was hypothesized that the voice characteristics remain relatively stable. Because of removal of effective velar length, articulation problems of the uvular /R/ can occur in the Dutch language. Prospective study in which 26 men were studied before (1 week before UPPP) and after (3 weeks after UPPP) surgery. The Nasometer was used to obtain nasalance scores. The mirror-fogging test, a perceptual evaluation of each subject's readings, and the Gutzmann and the Bzoch hypernasality tests were used for the assessment of nasality. For the assessment of articulation, a phonetic analysis was performed. Voice assessment included a perceptual rating of the voice and a determination of fundamental frequency. No significant differences were found between the conditions before and after surgery regarding nasalance (except for the vowel /i/), nasality, and voice. Regarding articulation, only 1 patient showed a derhotacized /R/. The findings of the study indicate that UPPP does not have an impact on nasality, voice, and articulation. Regarding nasalance, no significant nasalance change occurred after UPPP, except for the high vowel /i/.

  15. Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage

    PubMed Central

    Cole, Amy L.; Muthukrishnan, Gowrishankar; Chong, Christine; Beavis, Ashley; Eade, Colleen R.; Wood, Matthew P.; Deichen, Michael G.; Cole, Alexander M.

    2016-01-01

    Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Ten out of 15 studies resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not IL-17. Nasal SA persistence corresponded with elevated baseline levels of MIP-1β, IL-1β, and IL-6, no induction of inflammatory factors post-inoculation, and decreased IL-1RA:IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild-type only in participants with upregulated inflammatory markers post-inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial co-determinant of SA nasal carriage. PMID:26838052

  16. Spontaneous Nasal Septal Abscess Presenting as a Soft Tissue Mass in a Child.

    PubMed

    Cai, Yi; Saqi, Anjali; Haddad, Joseph

    2017-04-01

    Nasal septal abscess (NSA) is a rare condition most commonly seen as a complication of nasal trauma. The diagnosis of NSA requires emergent treatment, because delayed management can result in significant morbidity. Typically, NSA presents as a purulent collection that can be managed with drainage, either surgically or at bedside. We report an unusual presentation of a spontaneous NSA in a 7-year-old boy as a solid nasal mass eroding the nasal septum. The solid, tumor-like nature of the mass necessitated intervention beyond drainage and was ultimately excised. Imaging initiated in the emergency department revealed a partially cystic mass and erosion of the septum, which was key to the diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given the ease with which a diagnosis of NSA may be missed and the need for urgent management upon diagnosis of a NSA, we aim to highlight the clinical, radiologic, and histopathologic aspects that aid in diagnosis of NSA. Imaging, obtaining culture results, and initiation of antibiotics are paramount in management. In addition, NSAs may also necessitate bedside drainage given their emergent nature. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Amoebae-resisting bacteria isolated from human nasal swabs by amoebal coculture.

    PubMed

    Greub, Gilbert; La Scola, Bernard; Raoult, Didier

    2004-03-01

    Amoebae feed on bacteria, and few bacteria can resist their microbicidal ability. Amoebal coculture could therefore be used to selectively grow these amoebae-resisting bacteria (ARB), which may be human pathogens. To isolate new ARB, we performed amoebal coculture from 444 nasal samples. We recovered 7 (1.6%) ARB from 444 nasal swabs, including 4 new species provisionally named Candidatus Roseomonas massiliae, C. Rhizobium massiliae, C. Chryseobacterium massiliae, and C. Amoebinatus massiliae. The remaining isolates were closely related to Methylobacterium extorquens, Bosea vestrii, and Achromobacter xylosoxidans. Thus, amoebal coculture allows the recovery of new bacterial species from heavily contaminated samples and might be a valuable approach for the recovery of as-yet unrecognized emerging pathogens from clinical specimens.

  18. Hyperresponsiveness in the human nasal airway: new targets for the treatment of allergic airway disease.

    PubMed Central

    Turner, P J; Foreman, J C

    1999-01-01

    Allergic rhinitis is a condition which affects over 15% of the population in the United Kingdom. The pathological process involves two stages: nasal inflammation, and the development of nasal airway hyperresponsiveness (AHR) to allergen and a number of other stimuli. This results in the amplification of any subsequent allergic reaction, contributing to the chronic allergic state. A number of different hypotheses have been proposed to explain the underlying mechanism of AHR, including a role for eosinophil-derived proteins, free radicals and neuropeptides. While there may be a number of independent pathways which can result in AHR, evidence obtained from both animal models and in vivo experiments in humans indicate that some mediators may interact with one another, resulting in AHR. Further research into these interactions may open new avenues for the pharmacological treatment of chronic allergic rhinitis, and possibly other allergic airway diseases. PMID:10704051

  19. Nasal polyps

    MedlinePlus

    ... get rid of nasal polyps. Nasal steroid sprays shrink polyps. They help clear blocked nasal passages and ... is stopped. Corticosteroid pills or liquid may also shrink polyps, and can reduce swelling and nasal congestion. ...

  20. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species.

    PubMed

    Johnston, Miles; Zakharov, Andrei; Papaiconomou, Christina; Salmasi, Giselle; Armstrong, Dianna

    2004-12-10

    BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. METHODS: Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. RESULTS: In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. CONCLUSIONS: The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit.

  1. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

    PubMed Central

    Johnston, Miles; Zakharov, Andrei; Papaiconomou, Christina; Salmasi, Giselle; Armstrong, Dianna

    2004-01-01

    Background The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. Methods Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. Results In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. Conclusions The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit. PMID:15679948

  2. [Specific clinical and immunological features of chronic diseases of the nasal-associated lymphoid tissue in the children].

    PubMed

    Beniova, S N; Taranova, S V; Babko, S V

    2014-01-01

    The objective of the present work was to study the structure, clinical, and immunological features of various etiological variants of chronic diseases of the nasal-associated lymphoid tissue in the children. A total of 142 children at the age from 3 to 7 years presenting with this pathological condition were available for the observation. The study revealed differences in the clinical course of the disease and the cytokine response (IL-6, Ril-6, TNF, sYNFR55, sTNFR75) at the local and systemic levels for different pathogens (S. aureus, S. pneumoniae, S. pyrogenes).

  3. Tissue Engineered Human Skin Equivalents

    PubMed Central

    Zhang, Zheng; Michniak-Kohn, Bozena B.

    2012-01-01

    Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed. PMID:24300178

  4. Tissue engineering a human phalanx.

    PubMed

    Landis, W J; Chubinskaya, S; Tokui, T; Wada, Y; Isogai, N; Jacquet, R

    2016-03-21

    A principal purpose of tissue engineering is the augmentation, repair or replacement of diseased or injured human tissue. This study was undertaken to determine whether human biopsies as a cell source could be utilized for successful engineering of human phalanges consisting of both bone and cartilage. This paper reports the use of cadaveric human chondrocytes and periosteum as a model for the development of phalanx constructs. Two factors, osteogenic protein-1 [OP-1/bone morphogenetic protein-7 (BMP7)], alone or combined with insulin-like growth factor (IGF-1), were examined for their potential enhancement of chondrocytes and their secreted extracellular matrices. Design of the study included culture of chondrocytes and periosteum on biodegradable polyglycolic acid (PGA) and poly-l-lactic acid (PLLA)-poly-ε-caprolactone (PCL) scaffolds and subsequent implantation in athymic nu/nu (nude) mice for 5, 20, 40 and 60 weeks. Engineered constructs retrieved from mice were characterized with regard to genotype and phenotype as a function of developmental (implantation) time. Assessments included gross observation, X-ray radiography or microcomputed tomography, histology and gene expression. The resulting data showed that human cell-scaffold constructs could be successfully developed over 60 weeks, despite variability in donor age. Cartilage formation of the distal phalanx models enhanced with both OP-1 and IGF-1 yielded more cells and extracellular matrix (collagen and proteoglycans) than control chondrocytes without added factors. Summary data demonstrated that human distal phalanx models utilizing cadaveric chondrocytes and periosteum were successfully fabricated and OP-1 and OP-1/IGF-1 accelerated construct development and mineralization. The results suggest that similar engineering and transplantation of human autologous tissues in patients are clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes.

    PubMed

    Bardsley, Katie; Kwarciak, Agnieska; Freeman, Christine; Brook, Ian; Hatton, Paul; Crawford, Aileen

    2017-01-01

    The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification. Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5-10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation. The temporal changes in the genes measured reflected the temporal changes observed in the growth plate. Collagen II gene expression increased 6 fold by day 7 and was then significantly downregulated from day 14 onwards. Conversely, collagen X gene expression was detectable by day 14 and increased 100-fold by day 35. The temporal increase in collagen X expression was mirrored by increases in alkaline phosphatase gene expression which also was detectable by day 14 with a 30-fold increase in gene expression by day 35. Histological and immunohistochemical analysis of the engineered constructs showed increased chondrocyte cell volume (31-45 μm), deposition of collagen X in the extracellular matrix and expression of alkaline phosphatase activity. However, no cartilage mineralisation was observed in in vitro culture of up to 10 weeks. On subcutaneous implantation of the hypertrophic engineered constructs, the grafts became vascularised, cartilage mineralisation occurred and loss of the proteoglycan in the matrix was observed. Implantation of the hypertrophic engineered constructs into a rat cranial defect resulted in angiogenesis, mineralisation and remodelling of the cartilage tissue into bone. Micro-CT analysis indicated that defects which received the engineered hypertrophic constructs showed 38.48% in bone volume

  6. Flow modeling of actual human nasal cavity for various breathing conditions

    NASA Astrophysics Data System (ADS)

    Mokhtar, Nur Hazwani; Yaakob, Muhammad Syauki; Osman, Kahar; Kadir, Mohammed Rafiq Abdul; Abdullah, Wan Kamil Wan; Haron, Juhara

    2012-06-01

    Flow in the human nasal cavity varies when the body is under various physical activities. However, in order to visualize the flow pattern, traditional in-vivo technique may disturb the flow patterns. In this study, computational method was used to model the flow in the nasal cavity under various breathing conditions. Image from CT-Scan was used to mimic the actual cavity geometry. The image was computationally constructed and EFD. Lab was used to predict the flow behavior. Steady incompressible flow was considered for all case studies. The result shows that, for all breathing conditions, vortices were observed in the turbinate region which confirms the turbinate functions as a filter before the flow reaches the olfactory area. Larger vortices were detected when the flow rates were higher. In the olfactory region, the flow velocities were shown to be dramatically dropped to the ideal odorant uptake velocity range for all cases studied. This study had successfully produced visual description of air flow pattern in the nasal cavity.

  7. Computational modeling and validation of human nasal airflow under various breathing conditions.

    PubMed

    Li, Chengyu; Jiang, Jianbo; Dong, Haibo; Zhao, Kai

    2017-09-05

    The human nose serves vital physiological functions, including warming, filtration, humidification, and olfaction. These functions are based on transport phenomena that depend on nasal airflow patterns and turbulence. Accurate prediction of these airflow properties requires careful selection of computational fluid dynamics models and rigorous validation. The validation studies in the past have been limited by poor representations of the complex nasal geometry, lack of detailed airflow comparisons, and restricted ranges of flow rate. The objective of this study is to validate various numerical methods based on an anatomically accurate nasal model against published experimentally measured data under breathing flow rates from 180 to 1100ml/s. The numerical results of velocity profiles and turbulence intensities were obtained using the laminar model, four widely used Reynolds-averaged Navier-Stokes (RANS) turbulence models (i.e., k-ε, standard k-ω, Shear Stress Transport k-ω, and Reynolds Stress Model), large eddy simulation (LES) model, and direct numerical simulation (DNS). It was found that, despite certain irregularity in the flow field, the laminar model achieved good agreement with experimental results under restful breathing condition (180ml/s) and performed better than the RANS models. As the breathing flow rate increased, the RANS models achieved more accurate predictions but still performed worse than LES and DNS. As expected, LES and DNS can provide accurate predictions of the nasal airflow under all flow conditions but have an approximately 100-fold higher computational cost. Among all the RANS models tested, the standard k-ω model agrees most closely with the experimental values in terms of velocity profile and turbulence intensity. Copyright © 2017. Published by Elsevier Ltd.

  8. Polyhexanide-containing solution reduces ciliary beat frequency of human nasal epithelial cells in vitro.

    PubMed

    Birk, Richard; Aderhold, C; Stern-Sträter, J; Hörmann, K; Stuck, B A; Sommer, J U

    2015-02-01

    In ENT, polyhexanide-containing solutions are used to treat nasal infections caused by multiresistant bacteria like methicillin-resistant Staphylococcus aureus. Many forms of commercial nasal solutions containing polyhexanide exist, such as gels or solutions for topical use. Data regarding the influence of polyhexanide on ciliary beat frequency (CBF) are lacking to date. We tested the CBF of nasal ciliated epithelial cells under the influence of a commercially available polyhexanide-containing solution (Lavasept(®) Concentrate) in a therapeutic concentration (0.04, 0.02%). In addition, we tested the concentrations of 0.1 and 0.01%. Cells were visualized with a phase contrast microscope, and the CBF was measured with the SAVA system's region of interest method. Ringer's solution and macrogol served as negative controls. A therapeutic concentration of Lavasept significantly reduced CBF in a time- and concentration-dependent manner. After 1 min, the CBF was reduced from 8.90 ± 1.64 to 5.00 ± 3.72 Hz with a concentration of 0.04% (p value = 0.001). After 10 min, all cilia stopped beating. After 5 min, a 0.02% solution of Lavasept concentrate decreased CBF significantly from 8.64 ± 1.71 to 3.30 ± 3.27 Hz (p value < 0.001). In conclusion, CBF of human nasal epithelia is significantly reduced with the use of the polyhexanide-containing solution Lavasept in some therapeutic concentrations. Due to our findings in this study, Lavasept should be used on ciliated mucosa only with caution and in a concentration of 0.02%.

  9. Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

    PubMed

    Tian, Lin; Inthavong, Kiao; Lidén, Göran; Shang, Yidan; Tu, Jiyuan

    2016-07-01

    Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition

  10. Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model.

    PubMed

    Schroeter, Jeffry D; Kimbell, Julia S; Asgharian, Bahman

    2006-01-01

    The human nasal passages effectively filter particles from inhaled air. This prevents harmful pollutants from reaching susceptible pulmonary airways, but may leave the nasal mucosa vulnerable to potentially injurious effects from inhaled toxicants. This filtering property may also be strategically used for aerosolized nasal drug delivery. The nasal route has recently been considered as a means of delivering systemically acting drugs due to the large absorptive surface area available in close proximity to the nostrils. In this study, a computational fluid dynamics (CFD) model of nasal airflow was used with a particle transport and deposition code to predict localized deposition of inhaled particles in human nasal passages. The model geometry was formed from MRI scan tracings of the nasal passages of a healthy adult male. Spherical particles ranging in size from 5 to 50 microm were released from the nostrils. Particle trajectories and deposition sites were calculated in the presence of steady-state inspiratory airflow at volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and olfactory region were defined in the CFD model so that particles depositing in these regions could be identified and correlated with their release positions on the nostril surfaces. When plotted against impaction parameter, deposition efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%, respectively. Analysis of preferential deposition patterns and nostril release positions under natural breathing scenarios can be used to determine optimal particle size and flow rate combinations to selectively target drug particles to specific regions of the nose.

  11. Analysis of the size variability of the human normal and cleft palate fetal nasal capsule by means of three-dimensional computer reconstruction of histologic preparations.

    PubMed

    Siegel, M I; Mooney, M P; Kimes, K R; Todhunter, J

    1987-07-01

    As part of an ongoing study of cleft palate fetal morphology, normal and dysmorphic development of the human fetal nasal capsule was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft), ranging in age from 8 to 21 postmenstrual weeks. The specimens were celloidin embedded, sectioned at 20 microns, and every tenth section stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the nasal capsule, nasal septal cartilage, and nasal airway. Qualitatively, the cleft palate nasal capsule exhibited gross abnormalities including cartilaginous nasal septum deformities, abnormal septal volume and hypertrophy, reduced nasal airway and capsule volumes, and abnormal spatial relationships between the nasal capsule components. These results suggest that the reduced nasal airways, noted clinically in cleft perinates, may be a function of an interaction of nasal capsule deficiency and nasal septum hypertrophy. However, when lengths and volumes were plotted against fetal postmenstrual age, producing fetal "growth" curves, no significant differences (p greater than 0.05) were noted for growth rates (slopes) or nasal capsule size between the normal and cleft palate fetal samples. Curvilinear regression analysis revealed that both normal and cleft palate nasal capsule and septum lengths changed in a sigmoidal fashion, with the steepest increases from 13 to 17 weeks. In contrast, nasal capsule, airway, and septum volumes changed curvilinearly, showing slow relative growth rates from 8 to 17 weeks, which increased sharply from 18 to 21 weeks. Results suggest that from 8 to 21 weeks prenatally, normal and cleft palate specimens exhibited a similar pattern of fetal nasal capsule development that was characterized by an initial anteroposterior elongation followed by circumferential (i.e., volumetric) growth.

  12. Geno- and cytotoxicity of salinomycin in human nasal mucosa and peripheral blood lymphocytes.

    PubMed

    Scherzad, Agmal; Hackenberg, Stephan; Schramm, Carolin; Froelich, Katrin; Ginzkey, Christian; Hagen, Rudolf; Kleinsasser, Norbert

    2015-06-01

    Salinomycin is usually applied in stock breading but has also been described as a promising agent against cancer stem cells (CSC). However, knowledge about the toxicity of this ionophor substance is incomplete. The aim of this study was to investigate cyto- and genotoxic effects of salinomycin in human non-malignant cells. Primary human nasal mucosa cells (monolayer and mini organ cultures) and peripheral blood lymphocytes from 10 individuals were used to study the cytotoxic effects of salinomycin (0.1-175 μM) by annexin-propidiumiodide- and MTT-test. The comet assay was performed to evaluate DNA damage. Additionally, the secretion of interleukin-8 was analyzed by ELISA. Flow cytometry and MTT assay revealed significant cytotoxic effects in nasal mucosa cells and lymphocytes at low salinomycin concentrations of 10-20 μM. No genotoxic effects could be observed. IL-8 secretion was elevated at 5 μM. Salinomycin-induced cytotoxic and pro-inflammatory effects were seen at concentrations relevant for anti-cancer treatment. Concurrent to the evaluation of salinomycin application in experimental oncology, adverse effects in non-malignant cells need to be monitored and reduced as much as possible. Further studies are also warranted to evaluate the toxic effects in a variety of human cell systems, e.g., liver, kidney and muscle cells.

  13. Classification of chronic rhinosinusitis according to a nasal polyp and tissue eosinophilia: limitation of current classification system for Asian population

    PubMed Central

    Cho, Sung-Woo; Kim, Dae Woo; Kim, Jeong-Whun; Lee, Chul Hee

    2017-01-01

    Chronic rhinosinusitis (CRS) can be classified according to the presence of a nasal polyp (NP): CRS with NP (CRSwNP) and CRS without NP (CRSsNP). CRSwNP has characteristics with high infiltration of tissue eosinophilia with a burst of Th2 inflammatory cytokine. However recent findings in Eastern Asia countries suggest that CRSwNP can be divided according to the presence of tissue eosinophilia. Thus, CRSwNP can be classified into eosinophilic and noneosinophilic. Eosinophilic CRSwNP seems to have different immunological and clinical feature compared to noneosinophilic CRSwNP. From the same point of view, CRSsNP can also be divided according to tissue eosinophilia. However, the meaning of this dichotomous categorization in CRS seems to be not quite clear. This review focus on the limitations in current subclassification of CRS according to the presence of NP and tissue eosinophilia and discuss other factors related to tissue remodeling and NP generation which may provide clues for the further understanding of CRS pathogenesis. PMID:28765816

  14. Phenotype and function of nasal dendritic cells

    PubMed Central

    Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

    2015-01-01

    Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

  15. Cloning and expression of odorant-binding proteins Ia and Ib from mouse nasal tissue.

    PubMed

    Pes, D; Mameli, M; Andreini, I; Krieger, J; Weber, M; Breer, H; Pelosi, P

    1998-05-28

    We had previously reported the purification and partial characterisation of four distinct odorant-binding proteins from male mouse nasal epithelium. One of these, named OBP-I appeared to be a heterodimer, whose subunits, Ia and Ib showed significant similarity in their N-terminal amino acid sequences with hamster aphrodisin. In this paper, we report the complete amino acid sequences of these two polypeptide chains, as deduced from nucleotide sequences of their relative cDNA. These data confirm the high similarity of both proteins with hamster aphrodisin. A comparison with the sequences of other known OBPs indicate that they are more closely related to members of class I, including bovine OBP, rat OBP-I and pig OBP-I. A putative odorant-binding site is indicated by the presence of amino acid residues conserved with respect to the bovine protein, whose three-dimensional structure has been recently resolved. In-situ hybridisation has revealed identical expression patterns for the two proteins, further supporting the heterodimeric structure of these proteins in the nasal mucus.

  16. Radiation Effect on Human Tissue

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered

  17. Radiation Effect on Human Tissue

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered

  18. Microbiota of Human Breast Tissue

    PubMed Central

    Urbaniak, Camilla; Cummins, Joanne; Brackstone, Muriel; Macklaim, Jean M.; Gloor, Gregory B.; Baban, Chwanrow K.; Scott, Leslie; O'Hanlon, Deidre M.; Burton, Jeremy P.; Francis, Kevin P.; Tangney, Mark

    2014-01-01

    In recent years, a greater appreciation for the microbes inhabiting human body sites has emerged. In the female mammary gland, milk has been shown to contain bacterial species, ostensibly reaching the ducts from the skin. We decided to investigate whether there is a microbiome within the mammary tissue. Using 16S rRNA sequencing and culture, we analyzed breast tissue from 81 women with and without cancer in Canada and Ireland. A diverse population of bacteria was detected within tissue collected from sites all around the breast in women aged 18 to 90, not all of whom had a history of lactation. The principal phylum was Proteobacteria. The most abundant taxa in the Canadian samples were Bacillus (11.4%), Acinetobacter (10.0%), Enterobacteriaceae (8.3%), Pseudomonas (6.5%), Staphylococcus (6.5%), Propionibacterium (5.8%), Comamonadaceae (5.7%), Gammaproteobacteria (5.0%), and Prevotella (5.0%). In the Irish samples the most abundant taxa were Enterobacteriaceae (30.8%), Staphylococcus (12.7%), Listeria welshimeri (12.1%), Propionibacterium (10.1%), and Pseudomonas (5.3%). None of the subjects had signs or symptoms of infection, but the presence of viable bacteria was confirmed in some samples by culture. The extent to which these organisms play a role in health or disease remains to be determined. PMID:24610844

  19. Deposition of fractal-like aerosol aggregates in a model of human nasal cavity.

    PubMed

    Moskal, Arkadiusz; Makowski, Lukasz; Sosnowski, Tomasz R; Gradoń, Leon

    2006-09-01

    Toxicity of diesel exhaust is related to the inhalation of nano-sized fractal-like aerosol aggregates. Their complex behavior (in comparison to spherical particles) should be taken into account in deposition modeling. The deposition of aerosol fractal-like aggregates in the model of a human nose was studied numerically for the flow rate corresponding to breathing conditions. The simplified geometry of the human nasal replica was implemented in the computational fluid dynamics (CFD) code (FLUENT) used for calculation of the three-dimensional airflow structure. A Brownian dynamic (BD) algorithm was applied for determination of the aggregates deposition in the nasal cavity during inhalation. These calculations were carried out for several populations of aggregates. The values of parameters used in the BD simulations for characterization of fractal-like aggregates, that is, fractal dimension (Df) and the radius of gyration (Rg), were in the range of 1.7-2.1 and 0.24-0.36 microm, respectively. These are the representative values for soot aggregates emitted from diesel engines. The results of computation show approximately 20% penetration of submicrometer aggregates through the nose and a weak dependence of deposition efficiency on Df and Rg values. The proposed methodology may lead to a more realistic description of deposition of nonspherical aerosol particles in the respiratory system. A more sophisticated approach for description of fractal-like aggregates dynamics is suggested for future studies.

  20. Effect of mitomycin-C on contraction and migration of human nasal mucosa fibroblasts: implications in dacryocystorhinostomy.

    PubMed

    Kumar, Vinay; Ali, Mohammad Javed; Ramachandran, Charanya

    2015-09-01

    To determine the effect of mitomycin-C (MMC) on the contraction and migration of human nasal mucosal fibroblasts (HNMFs) in vitro in order to identify the least concentration of MMC required to prevent cicatrix development following dacryocystorhinostomy (DCR). Primary cultures of HNMFs were established from nasal mucosal tissues of patients undergoing DCR. Myofibroblast transformation of HNMFs was induced using transforming growth factor-β (TGF-β1) and confirmed by immunostaining for α-smooth muscle actin (α-SMA). Collagen gel contraction assay was employed to study contraction in the presence or absence of TGF-β1 (5 and 10 ng/mL) and MMC (0.2 and 0.4 mg/mL). Scratch wound assay was employed to determine the influence of MMC treatment on cell migration. Quantification of gel contraction and wound closure was done using Image J software. α-SMA expression increased with TGF-β1 treatment in a time- and dose-dependent manner indicating myofibroblast transformation of HNMFs. MMC inhibited TGF-β1- induced collagen gel contraction in a dose-dependent manner (0.4 mg/mL>0.2 mg/mL). Further, there was a decrease in the migration of MMC-treated HNMFs, resulting in delayed wound closure that corroborated with the loss of actin stress fibres. MMC successfully inhibited TGF-β1-induced myofibroblast transformation, collagen gel contraction and significantly reduced the migration of HNMFs to cover the wound even at a low concentration of 0.2 mg/mL. This study provides evidence that low concentration and short duration of MMC treatment is efficient in reducing increased contraction and migration of HMNFs in response to injury. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

    PubMed Central

    Xiao, Li; Jia, Lei; Bai, Lu; He, Long; Yang, Binyan; Wu, Changyou; Li, Huabin

    2016-01-01

    Although CD4+ T cells are recognized to play an important role in the inflammatory response of nasal polyps (NPs), the biological functions of CD8+ T cells in polypogenesis remain unclear. In this study, we analyzed cell markers, cytokine expression and transcription factors in IL-21-expressing CD8+ T cells in polyp tissues of NP patients. The results showed that the majority of IL-21-producing CD8+ T cells were effector memory cells and they co-expressed IFN-γ. IL-21-expressing CD8+ T cells in polyp tissues expressed higher CXCR5, PD-1, and ICOS levels than cells in control tissues and showed significantly higher T-bet and Bcl-6 expression levels compared with IL-21−CD8+ T cells. Purified polyp CD8+ T cells promoted IgG production from isolated polyp B cells in vitro, and recombinant IL-12 modulated the expression of IL-21, IFN-γ and CD40L in purified polyp CD8+ T cells. Moreover, the percentage of IL-21+CD8+ T cells in polyp tissues was positively correlated with endoscopic and CT scan scores in NP patients. These findings indicated that polyp CD8+ T cells, by co-expressing IL-21 and IFN-γ and other markers, display a Tfh cell functionality, which is associated with the clinical severity of NP patients. PMID:27468819

  2. In vivo microvascular imaging of human oral and nasal cavities using swept-source optical coherence tomography with a single forward/side viewing probe

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Ruikang K.

    2015-03-01

    We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1.3 μm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm x 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions.

  3. Numerical simulation of airflow and micro-particle deposition in human nasal airway pre- and post-virtual sphenoidotomy surgery.

    PubMed

    Bahmanzadeh, Hojat; Abouali, Omid; Faramarzi, Mohammad; Ahmadi, Goodarz

    2015-06-01

    In the present study, the effects of endoscopic sphenoidotomy surgery on the flow patterns and deposition of micro-particles in the human nasal airway and sphenoid sinus were investigated. A realistic model of a human nasal passage including nasal cavity and paranasal sinuses was constructed using a series of CT scan images of a healthy subject. Then, a virtual sphenoidotomy by endoscopic sinus surgery was performed in the left nasal passage and sphenoid sinus. Transient airflow patterns pre- and post-surgery during a full breathing cycle (inhalation and exhalation) were simulated numerically under cyclic flow condition. The Lagrangian approach was used for evaluating the transport and deposition of inhaled micro-particles. An unsteady particle tracking was performed for the inhalation phase of the breathing cycle for the case that particles were continuously entering into the nasal airway. The total deposition pattern and sphenoid deposition fraction of micro-particles were evaluated and compared for pre- and post-surgery cases. The presented results show that sphenoidotomy increased the airflow into the sphenoid sinus, which led to increased deposition of micro-particles in this region. Particles up to 25 μm were able to penetrate into the sphenoid in the post-operation case, and the highest deposition in the sphenoid for the resting breathing rate occurred for 10 μm particles at about 1.5%. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Comparison of exhaled nitric oxide and cardiorespiratory indices between nasal and oral breathing during submaximal exercise in humans.

    PubMed

    Yasuda, Y; Itoh, T; Miyamura, M; Nishino, H

    1997-10-01

    In order to examine the origin and role of nitric oxide (NO) in exhaled air during exercise, exhaled NO outputs of 8 healthy human subjects were compared using different breathing methods, through the mouth or nose, at two intensities of bicycle exercise. The concentration of NO in the exhaled air and ventilatory gas exchange variables were measured by a chemiluminescence analyzer and a mixing chamber method, respectively. The concentration and total output of NO in the expired air was significantly higher under nasal breathing than under oral breathing for both exercise intensities, whereas no significant difference was observed in cardiorespiratory variables between them. NO output increased significantly when exercise intensity was increased from unloaded (0 W) to 60 W under nasal breathing, but not under oral breathing. A negative correlation among subjects was found between NO output and minute ventilation in both breathing methods only for unloaded exercise. Data indicate that nasal airways have a large contribution, at least 50% of total NO output in the exhaled air during nasal breathing, but this nasal NO may have no further modulation on respiratory function during submaximal exercise by healthy humans.

  5. A preliminary 3D computed tomography study of the human maxillary sinus and nasal cavity.

    PubMed

    Butaric, Lauren N; McCarthy, Robert C; Broadfield, Douglas C

    2010-11-01

    Despite centuries of investigation, the function of the maxillary sinus (MS) and underlying patterns governing its form remain elusive. In this study, we articulate a methodology for collecting volumetric data for the MS and nasal cavity (NC) from computed tomography (CT) scans and report details for a small sample of 39 dried human crania of known ecogeographic provenience useful for assessing variation in MS size and shape. We use scaling analyses to preliminarily test the hypothesis that volumes of the nasal cavity (NCV) and maxillary sinus (MSV) are inversely correlated such that the NC covaries with size of the face, whereas the MS "fills in" the leftover space [proposed by Shea: Am J Phys Anthropol 47 (1977):289-300]. Against expectation, MSV is not significantly correlated with NCV or any cranial size variable. NCV, on the other hand, scales isometrically with facial size. The results of this pilot study suggest that NCV covaries with facial size, but that the MS does not simply fill in the leftover space in the face. The role, if any, of the MSs in midfacial function and architecture remains unclear. Larger sample sizes, additional environmental variables, and assessment of MS and NC shape are necessary to resolve this issue.

  6. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection.

  7. Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage

    SciTech Connect

    Koren, H.S.; Devlin, R.B.

    1992-01-01

    A set of symptoms has been described during the past two decades which has been called the sick building syndrome. These symptoms include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that volatile organic compounds (VOC) present in synthetic materials used in homes and office buildings contribute to these symptoms. However, there have been few studies in which humans have been exposed to known amounts of VOC under carefully controlled conditions. In the study 14 subjects have been exposed to a mixture of VOC (25 mg/cu m total hydrocarbon) representative of what is found in new homes and office buildings. Since irritation of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, the authors have used nasal lavage to monitor neutrophil (PMN) influx into the nasal passages following exposure to VOC. The authors report statistically significant increases in PMNs both immediately after a four hour exposure to VOC, as well as 18 hours later.

  8. Neural net applied to anthropological material: a methodical study on the human nasal skeleton.

    PubMed

    Prescher, Andreas; Meyers, Anne; Gerf von Keyserlingk, Diedrich

    2005-07-01

    A new information processing method, an artificial neural net, was applied to characterise the variability of anthropological features of the human nasal skeleton. The aim was to find different types of nasal skeletons. A neural net with 15*15 nodes was trained by 17 standard anthropological parameters taken from 184 skulls of the Aachen collection. The trained neural net delivers its classification in a two-dimensional map. Different types of noses were locally separated within the map. Rare and frequent types may be distinguished after one passage of the complete collection through the net. Statistical descriptive analysis, hierarchical cluster analysis, and discriminant analysis were applied to the same data set. These parallel applications allowed comparison of the new approach to the more traditional ones. In general the classification by the neural net is in correspondence with cluster analysis and discriminant analysis. However, it goes beyond these classifications because of the possibility of differentiating the types in multi-dimensional dependencies. Furthermore, places in the map are kept blank for intermediate forms, which may be theoretically expected, but were not included in the training set. In conclusion, the application of a neural network is a suitable method for investigating large collections of biological material. The gained classification may be helpful in anatomy and anthropology as well as in forensic medicine. It may be used to characterise the peculiarity of a whole set as well as to find particular cases within the set.

  9. Lateralization in human nasal chemoreception: differences in bilateral electrodermal responses related to olfactory and trigeminal stimuli.

    PubMed

    Brand, G; Millot, J L; Saffaux, M; Morand-Villeneuve, N

    2002-07-18

    The study of olfactory lateralization in humans has given rise to many publications, but the findings have often been contradictory. There is growing evidence to suggest that the nature of the olfactory stimulus influences the processes of lateralization. An important factor could be the trigeminal component. Indeed, most odorants simultaneously stimulate both olfactory (CN I) and trigeminal (CN V) systems which differ in terms of their central projections, ipsilaterally for CN I and contralaterally for CN V. The aim of this study was to investigate variations in psychophysiological measurements between a nasal input with low (phenyl ethyl alcohol (PEA)) and high (allyl isothiocyanate (AIC)) intranal trigeminal stimulation. In a first experiment (20 subjects), the intensity, hedonicity and irritation levels of stimulus were tested with a psychophysical evaluation to study the possible influences of perceptual characteristics. A second experiment (37 subjects) used bilateral electrodermal recordings and compared the skin conductance responses (SCRs) for both nasal inputs on either monorhinal and birhinal stimulations. Firstly, the electrodermal activity (EDA) results showed no differences between the two nostrils for PEA as well as AIC, but differences in relation to the type of stimulus, e.g. higher amplitude in response to AIC versus PEA. Secondly, the results indicated bilateral differences in EDA recordings related to the nature of the stimulus and are discussed in terms of hemispheric asymmetric activation.

  10. Nonneoplastic nasal lesions in rats and mice.

    PubMed Central

    Monticello, T M; Morgan, K T; Uraih, L

    1990-01-01

    Rodents are commonly used for inhalation toxicology studies, but until recently the nasal passages have often been overlooked or only superficially examined. The rodent nose is a complex organ in which toxicant-induced lesions may vary, depending on the test compound. A working knowledge of rodent nasal anatomy and histology is essential for the proper evaluation of these responses. Lack of a systematic approach for examining rodent nasal tissue has led to a paucity of information regarding nonneoplastic lesions in the rodent nose. Therefore, slides from the National Toxicology Program (NTP) and the Chemical Industry Institute of Toxicology (CIIT) were examined, and the literature was reviewed to assemble the spectrum of nonneoplastic rodent nasal pathology. Presented are lesions associated with the various types of epithelia lining the rodent nasal cavity plus lesions involving accessory nasal structures. Even though there are anatomic and physiologic differences between the rodent and human nose, both rats and mice provide valuable animal models for the study of nasal epithelial toxicity, following administration of chemical compounds. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PLATE 24. PLATE 25. PLATE 26. PLATE 27. PLATE 28. PLATE 29. PLATE 30. PLATE 31. PLATE 32. PLATE 33. PLATE 34. PLATE 35. PLATE 36. PLATE 37. PLATE 38. PMID:2200665

  11. Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

    PubMed Central

    de Borja Callejas, Francisco; Martínez-Antón, Asunción; Alobid, Isam; Fuentes, Mireya; Cortijo, Julio; Picado, César

    2014-01-01

    Background Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described. Objectives 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function. Methods Epithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array). Results In both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia. Conclusion Reconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model

  12. Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells.

    PubMed

    Kojima, Takashi; Kondoh, Masuo; Keira, Takashi; Takano, Ken-Ichi; Kakuki, Takuya; Kaneko, Yakuto; Miyata, Ryo; Nomura, Kazuaki; Obata, Kazufumi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo

    2016-10-01

    Intranasal insulin administration has therapeutic potential for Alzheimer's disease and in intranasal administration across the nasal mucosa, the paracellular pathway regulated by tight junctions is important. The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) binds the tight junction protein claudin and disrupts the tight junctional barrier without a cytotoxic effect. The C-CPE mutant called C-CPE 194 binds only to claudin-4, whereas the C-CPE 194 mutant called C-CPE m19 binds not only to claudin-4 but also to claudin-1. In the present study, to investigate the effects of C-CPE mutants on the tight junctional functions of human nasal epithelial cells (HNECs) and on the permeability of human recombinant insulin across the cells, HNECs were treated with C-CPE 194 and C-CPE m19. C-CPE 194 and C-CPE m19 disrupted the barrier and fence functions without changes in expression of claudin-1, -4, -7, and occludin or cytotoxicity, whereas they transiently increased the activity of ERK1/2 phosphorylation. The disruption of the barrier function caused by C-CPE 194 and C-CPE m19 was prevented by pretreatment with the MAPKK inhibitor U0126. Furthermore, C-CPE 194 and C-CPE m19 significantly enhanced the permeability of human recombinant insulin across HNECs and the permeability was also inhibited by U0126. These findings suggest that C-CPE mutants 194 and m19 can regulate the permeability of insulin across HNECs via the MAPK pathway and may play a crucial role in therapy for the diseases such as Alzheimer's disease via the direct intranasal insulin administration.

  13. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    PubMed Central

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  14. Dosimetry of nasal uptake of soluble and reactive gases: A first study of inter-human variability (Journal Article)

    EPA Science Inventory

    Anatomically accurate human child and adult nasal tract models will be used in concert with computationally simulated air flow information to investigate the influence of age-related differences in anatomy on inhalation dosimetry in the upper and lower airways. The findings of t...

  15. Dosimetry of nasal uptake of soluble and reactive gases: A first study of inter-human variability (Journal Article)

    EPA Science Inventory

    Anatomically accurate human child and adult nasal tract models will be used in concert with computationally simulated air flow information to investigate the influence of age-related differences in anatomy on inhalation dosimetry in the upper and lower airways. The findings of t...

  16. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; hide

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  17. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; Romeo, V. D.; Behl, C. R.

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  18. Lysosomal exoglycosidases in nasal polyps.

    PubMed

    Chojnowska, Sylwia; Minarowska, Alina; Knaś, Małgorzata; Niemcunowicz-Janica, Anna; Kołodziejczyk, Paweł; Zalewska-Szajda, Beata; Kępka, Alina; Minarowski, Łukasz; Waszkiewicz, Napoleon; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

    2013-01-01

    Nasal polyps are smooth outgrowths assuming a shape of grapes, formed from the nasal mucosa, limiting air flow by projecting into a lumen of a nasal cavity. Up to now the surgical resection is the best method of their treatment, but etiology and pathogenesis of the nasal polyps is not yet fully established. The aim of the study was the assessment of the selected lysosomal exoglycosidases activity in the nasal polyps. In this study the activity of β-galactosidase, α-mannosidase and α-fucosidase was determined in the tissue of the nasal polyps obtained from 40 patients (10F, 30M) and control tissues derived from mucosa of lower nasal conchas obtained during mucotomy from 20 patients (10F, 10M). We observed significant lower values of GAL, FUC and tendency to decrease of MAN and GLU concentration in nasal polyps (P) in comparison to control healthy nasal mucosa (C). In nasal polyp tissue (P) no differences of GAL, MAN and FUC specific activity in comparison to control mucosa (C) were found. Our research supports bioelectrical theory of the nasal polyps pathogenesis and directs attention at research on glycoconjugates and glycosidases of the nasal mucosa extracellular matrix. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

  19. Simulation of convective flows in irregular channels on the example of the human nasal cavity and paranasal sinuses

    NASA Astrophysics Data System (ADS)

    Lukyanov, G. N.; Voronin, A. A.; Rassadina, A. A.

    2017-03-01

    Here we explore possibilities of the detached eddy simulation models (DES-models) in relation to a human nasal cavity as to a complicated structure of variable section with several bulges and irregularities (paranasal sinuses and turbinate). The three-dimensional geometric model (3D-model) of nasal cavity is perfomed on the results of the computer tomography with the Mercury Amira soft. The convective flows in the 3D-model are given with the Ansys Icem CFD soft. First-ever the nonstationary flow calculations for the 3D-model simulated nasal cavity are performed which aren't averaged in time, and consider the function of pressure drop in breathing. The results of the simulation are compared with the experimental data obtained for the analogous solid 3D-model.

  20. Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction.

    PubMed

    Zhao, Kai; Scherer, Peter W; Hajiloo, Shoreh A; Dalton, Pamela

    2004-06-01

    Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (nasal CT scans from an individual patient into an anatomically accurate 3-D numerical nasal model that can be used to predict airflow and odorant transport, which may ultimately determine olfactory sensitivity. The 3-D model can be also be rapidly modified to depict various anatomical deviations, such as polyps and their removal, that may alter nasal airflow and impair olfactory ability. To evaluate the degree to which variations in critical nasal areas such as the olfactory slit and nasal valve can alter airflow and odorant transport, inspiratory and expiratory airflow with odorants were simulated using numerical finite volume methods. Results suggest that anatomical changes in the olfactory region (upper meatus below the cribriform plate) and the nasal valve region will strongly affect airflow patterns and odorant transport through the olfactory region, with subsequent effects on olfactory function. The ability to model odorant transport through individualized models of the nasal passages holds promise for relating anatomical deviations to generalized or selective disturbances in olfactory perception and may provide important guidance for treatments for nasal-sinus disease, occupational rhinitis and surgical interventions that seek to optimize airflow and improve deficient olfactory function.

  1. Characterization of postoperative changes in nasal airflow using a cadaveric computational fluid dynamics model: supporting the internal nasal valve.

    PubMed

    Shadfar, Scott; Shockley, William W; Fleischman, Gita M; Dugar, Anand R; McKinney, Kibwei A; Frank-Ito, Dennis O; Kimbell, Julia S

    2014-01-01

    Collapse or compromise of the internal nasal valve (INV) results in symptomatic nasal obstruction; thus, various surgical maneuvers are designed to support the INV. To determine the effect on nasal airflow after various surgical techniques focused at the level of the INV and lateral nasal sidewall. A fresh cadaver head was obtained and underwent suture and cartilage graft techniques directed at the level of the INV using an external approach. Preoperative and postoperative digital nasal models were created from the high-resolution, fine-cut, computed tomographic imaging after each intervention. Isolating the interventions to the level of the INV, we used computational fluid dynamic techniques to calculate nasal resistance, nasal airflow, and nasal airflow partitioning for each intervention. Suture and cartilage graft techniques. Nasal airflow, nasal resistance, and partitioning of airflow. Using the soft-tissue elevation model as baseline, computational fluid dynamic analysis predicted that most of the suture and cartilage graft techniques directed toward the nasal valve improved nasal airflow and partitioning while reducing nasal resistance. Specifically, medial and modified flare suture techniques alone improved nasal airflow by 16.9% and 15.1%, respectively. The combination of spreader grafts and modified flare suture improved nasal airflow by 13.2%, whereas spreader grafts alone only improved airflow by 5.9%. The largest improvements in bilateral nasal resistance were achieved using the medial and modified flare sutures, outperforming the combination of spreader grafts and modified flare suture. Techniques directed at supporting the INV have tremendous value in the treatment of nasal obstruction. The use of flare sutures alone can address dynamic valve collapse or upper lateral cartilage incompetence without gross disruption of the nasal architecture. Using computational fluid dynamic techniques, this study suggests that flare sutures alone may improve flow and

  2. Silver resistance in MRSA isolated from wound and nasal sources in humans and animals.

    PubMed

    Loh, Jia V; Percival, Steven L; Woods, Emma J; Williams, Nicola J; Cochrane, Christine A

    2009-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonises skin, nasal passages and dermal wounds. Methods used to manage wounds infected and colonised with MRSA often include the use of topical antiseptics such as ionic silver and iodine. The objectives of this study were to determine the prevalence of silver-resistance (sil) genes in MRSA and methicillin-resistant coagulase-negative staphylococci (MR-CNS) isolated from wounds and nasal cavities of humans and animals, and also to determine the susceptibility of sil-positive and sil-negative MRSA isolates to a silver-containing Hydrofiber (SCH) wound dressing, on planktonic silE-positive and silE-negative MRSA. Polymerase chain reaction was used to determine the presence of three silver-resistance (sil) genes, silE, silP and silS in 33 MRSA and 8 methicillin-resistant staphylococci (MR-CNS). SilP and silS genes were absent in all isolates tested; however, two MRSA strains were found to contain the silE gene, together with one isolate of MR-CNS. Phenotypic resistance of the silE-positive strains and their susceptibility to the SCH dressing was evaluated using the zone of inhibition test on Mueller Hinton agar, and confocal laser microscopy using a live/dead fluorescent stain. Results confirmed that the SCH dressing was effective in killing all MRSA strains with and without the silE gene. First, this study showed that the prevalence of sil genes was low in the isolates investigated; and secondly, that the presence of a silver-resistance gene (silE) in MRSA and MR-CNS did not afford protection to the organism in the presence of a SCH wound dressing. The use of topical antiseptics in chronic wound care should be considered before the use of antibiotics that can result in their overuse and the risk of further resistance.

  3. Pharmacokinetics of a Novel Zolpidem Nasal Spray for Rapid Management of Insomnia: First Trial in Humans

    PubMed Central

    Li, Cheng-Tai; Su, Tung-Ping; Wang, Yanfeng; Lee, Benjamin; Toh, Melvin; Ho, Tony

    2016-01-01

    Study Objectives: The present single-dose, parallel-group, randomized, double-blind, placebo-controlled study is to evaluate the pharmacokinetics, tolerability and safety of zolpidem tartrate nasal spray (ZNS) as compared to placebo in healthy subjects. Methods: Thirty-six healthy subjects participated in this study, with 19 male and 17 female subjects in 3 cohorts (12 subjects per cohort), who were randomly assigned to receive either an intranasal dose of ZNS 1.75 mg, 3.5 mg, 5.0 mg (n = 10 per dose), or an intranasal placebo (n = 2). Multiple venous blood samples were collected for pharmacokinetic analyses. Results: Plasma zolpidem concentrations rapidly increased after intranasal ZNS 1.75, 3.5, and 5.0 mg with mean Tmax of 0.42, 0.76 and 0.50 h, respectively, followed by rapid decreases at all three doses. Cmax, AUC0-t, and AUC0-∞ were found to increase in a dose-proportional manner. Female subjects had generally higher AUC0-t, AUC0-∞, and lower weight-normalized clearance rate (CL/F) than male subjects. In this study, ZNS was safe and well tolerated over the evaluated dose range. There were no serious adverse events. Conclusions: Zolpidem was rapidly absorbed and eliminated after intranasal administration of ZNS. Dose proportionality was found at the doses ranged from 1.75 mg to 5.0 mg. Intranasal exposure of zolpidem was generally higher in female subjects than that in male subjects. It could be concluded that ZNS is safe and well tolerated over the evaluated range of intranasal doses. Citation: Li CT, Su TP, Wang Y, Lee B, Toh M, Ho T. Pharmacokinetics of a novel zolpidem nasal spray for rapid management of insomnia: first trial in humans. J Clin Sleep Med 2016;12(11):1453–1459. PMID:27568900

  4. Human dignity and human tissue: a meaningful ethical relationship?

    PubMed

    Kirchhoffer, David G; Dierickx, Kris

    2011-09-01

    Human dignity has long been used as a foundational principle in policy documents and ethical guidelines intended to govern various forms of biomedical research. Despite the vast amount of literature concerning human dignity and embryonic tissues, the majority of biomedical research uses non-embryonic human tissue. Therefore, this contribution addresses a notable lacuna in the literature: the relationship, if any, between human dignity and human tissue. This paper first elaborates a multidimensional understanding of human dignity that overcomes many of the shortcomings associated with the use of human dignity in other ethical debates. Second, it discusses the relationship between such an understanding of human dignity and 'non-embryonic' human tissue. Finally, it considers the implications of this relationship for biomedical research and practice involving human tissue. The contribution demonstrates that while human tissue cannot be said to have human dignity, human dignity is nevertheless implicated by human tissue, making what is done with human tissue and how it is done worthy of moral consideration.

  5. Absolute humidity and the human nose: A reanalysis of climate zones and their influence on nasal form and function.

    PubMed

    Maddux, Scott D; Yokley, Todd R; Svoma, Bohumil M; Franciscus, Robert G

    2016-10-01

    Investigations into the selective role of climate on human nasal variation commonly divide climates into four broad adaptive zones (hot-dry, hot-wet, cold-dry, and cold-wet) based on temperature and relative humidity. Yet, absolute humidity-not relative humidity-is physiologically more important during respiration. Here, we investigate the global distribution of absolute humidity to better clarify ecogeographic demands on nasal physiology. We use monthly observations from the Climatic Research Unit Timeseries 3 (CRU TS3) database to construct global maps of average annual temperature, relative humidity and absolute humidity. Further, using data collected by Thomson and Buxton (1923) for over 15,000 globally-distributed individuals, we calculate the actual amount of heat and water that must be transferred to inspired air in different climatic regimes to maintain homeostasis, and investigate the influence of these factors on the nasal index. Our results show that absolute humidity, like temperature, generally decreases with latitude. Furthermore, our results demonstrate that environments typically characterized as "cold-wet" actually exhibit low absolute humidities, with values virtually identical to cold-dry environments and significantly lower than hot-wet and even hot-dry environments. Our results also indicate that strong associations between the nasal index and absolute humidity are, potentially erroneously, predicated on individuals from hot-dry environments possessing intermediate (mesorrhine) nasal indices. We suggest that differentially allocating populations to cold-dry or cold-wet climates is unlikely to reflect different selective pressures on respiratory physiology and nasal morphology-it is cold-dry, and to a lesser degree hot-dry environments, that stress respiratory function. Our study also supports assertions that demands for inspiratory modification are reduced in hot-wet environments, and that expiratory heat elimination for thermoregulation is a

  6. Lipids Including Cholesteryl Linoleate and Cholesteryl Arachidonate Contribute to the Inherent Antibacterial Activity of Human Nasal Fluid1

    PubMed Central

    Do, Thai Q.; Moshkani, Safiehkhatoon; Castillo, Patricia; Anunta, Suda; Pogosyan, Adelina; Cheung, Annie; Marbois, Beth; Faull, Kym F.; Ernst, William; Chiang, Su Ming; Fujii, Gary; Clarke, Catherine F.; Foster, Krishna; Porter, Edith

    2008-01-01

    Mucosal surfaces provide first-line defense against microbial invasion through their complex secretions. The antimicrobial activities of proteins in these secretions have been well delineated, but the contributions of lipids to mucosal defense have not been defined. We found that normal human nasal fluid contains all major lipid classes (μg/ml), as well as lipoproteins and apolipoprotein AI. The predominant less polar lipids were myristic, palmitic, palmitoleic, stearic, oleic, and linoleic acid, cholesterol, and cholesteryl palmitate, -linoleate, and -arachidonate. Normal human bronchioepithelial cell secretions exhibited a similar lipid composition. Removal of less-polar lipids significantly decreased the inherent antibacterial activity of nasal fluid against Pseudomonas aeruginosa, which was in part restored after replenishing the lipids. Furthermore, lipids extracted from nasal fluid exerted direct antibacterial activity in synergism with the antimicrobial peptide HNP-2 and liposomal formulations of cholesteryl linoleate and cholesteryl arachidonate were active against P. aeruginosa at physiological concentrations as found in nasal fluid and exerted inhibitory activity against other gram negative and gram positive bacteria. These data suggest that host-derived lipids contribute to mucosal defense. The emerging concept of host-derived antimicrobial lipids unveils novel roads to a better understanding of the immunology of infectious diseases. PMID:18768875

  7. Double-layered reconstruction of the nasal floor in complete cleft deformity of the primary palate using superfluous lip tissue.

    PubMed

    Park, Young-Wook; Kwon, Kwang-Jun; Kim, Min-Keun

    2015-12-01

    After cleft lip repair, many patients suffer from nasolabial fistulas, asymmetrical nasal floor, or an indistinct nostril sill, as well as intraoral wound dehiscence and subsequent scar contracture of surgical wounds leading to vestibular stenosis. For successful primary nasolabial repair of complete cleft deformity of the primary palate, cleft surgeons need special care in reconstructing the sound nasal floor. Especially when the cleft gap is wide or when any type of nasoalveolar molding therapy was not performed, three-dimensional reconstruction of the nasal floor is critical for a balanced nasal shape. In this study, the author describes an effective method for reconstructing a double-layered nasal floor using two mucosal flaps from both sides of the fissured upper lip. This is a report of six patients with unilateral or bilateral complete cleft of the primary palate with a detailed description of the surgical technique and a literature review.

  8. Airflow, gas deposition, and lesion distribution in the nasal passages

    SciTech Connect

    Morgan, K.T.; Monticello, T.M. )

    1990-04-01

    The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. 61 references.

  9. Airflow, gas deposition, and lesion distribution in the nasal passages.

    PubMed Central

    Morgan, K T; Monticello, T M

    1990-01-01

    The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. Images FIGURE 4. FIGURE 6. FIGURE 7. PMID:2200663

  10. EFFECT OF DIESEL EXHAUST PARTICLES ON HUMAN NASAL LAVAGE CELLS AND DNA ADDUCTS

    EPA Science Inventory

    The overall aim of this study is to determine (using a nasal challenge model) the effect of diesel exhaust particles (DEP) on nasal responses including induction of inflammation, immune changes and DNA damage. We are also examining how treatment of DEP with ozone (oz-DEP)modify ...

  11. Effects of Surface Smoothness on Inertial Particle Deposition in Human Nasal Models

    PubMed Central

    Schroeter, Jeffry D.; Garcia, Guilherme J. M.; Kimbell, Julia S.

    2010-01-01

    Computational fluid dynamics (CFD) predictions of inertial particle deposition have not compared well with data from nasal replicas due to effects of surface texture and the resolution of tomographic images. To study effects of geometric differences between CFD models and nasal replicas, nasal CFD models with different levels of surface smoothness were reconstructed from the same MRI data used to construct the nasal replica used by Kelly et al. (2004) [Aerosol Sci. Technol. 38:1063–1071]. One CFD model in particular was reconstructed without any surface smoothing to preserve the detailed topology present in the nasal replica. Steady-state inspiratory airflow and Lagrangian particle tracking were simulated using Fluent software. Particle deposition estimates from the smoother models under-predicted nasal deposition from replica casts, which was consistent with previous findings. These discrepancies were overcome by including surface artifacts that were not present in the reduced models and by plotting deposition efficiency versus the Stokes number, where the characteristic diameter was defined in terms of the pressure-flow relationship to account for changes in airflow resistance due to wall roughness. These results indicate that even slight geometric differences have significant effects on nasal deposition and that this information should be taken into account when comparing particle deposition data from CFD models with experimental data from nasal replica casts. PMID:21339833

  12. EFFECT OF DIESEL EXHAUST PARTICLES ON HUMAN NASAL LAVAGE CELLS AND DNA ADDUCTS

    EPA Science Inventory

    The overall aim of this study is to determine (using a nasal challenge model) the effect of diesel exhaust particles (DEP) on nasal responses including induction of inflammation, immune changes and DNA damage. We are also examining how treatment of DEP with ozone (oz-DEP)modify ...

  13. Effects of Surface Smoothness on Inertial Particle Deposition in Human Nasal Models.

    PubMed

    Schroeter, Jeffry D; Garcia, Guilherme J M; Kimbell, Julia S

    2011-01-01

    Computational fluid dynamics (CFD) predictions of inertial particle deposition have not compared well with data from nasal replicas due to effects of surface texture and the resolution of tomographic images. To study effects of geometric differences between CFD models and nasal replicas, nasal CFD models with different levels of surface smoothness were reconstructed from the same MRI data used to construct the nasal replica used by Kelly et al. (2004) [Aerosol Sci. Technol. 38:1063-1071]. One CFD model in particular was reconstructed without any surface smoothing to preserve the detailed topology present in the nasal replica. Steady-state inspiratory airflow and Lagrangian particle tracking were simulated using Fluent software. Particle deposition estimates from the smoother models under-predicted nasal deposition from replica casts, which was consistent with previous findings. These discrepancies were overcome by including surface artifacts that were not present in the reduced models and by plotting deposition efficiency versus the Stokes number, where the characteristic diameter was defined in terms of the pressure-flow relationship to account for changes in airflow resistance due to wall roughness. These results indicate that even slight geometric differences have significant effects on nasal deposition and that this information should be taken into account when comparing particle deposition data from CFD models with experimental data from nasal replica casts.

  14. Livestock-Associated, Antibiotic-Resistant Staphylococcus aureus Nasal Carriage and Recent Skin and Soft Tissue Infection among Industrial Hog Operation Workers

    PubMed Central

    Nadimpalli, Maya; Stewart, Jill R.; Pierce, Elizabeth; Pisanic, Nora; Love, David C.; Hall, Devon; Larsen, Jesper; Carroll, Karen C.; Tekle, Tsigereda; Perl, Trish M.

    2016-01-01

    Swine production work is a risk factor for nasal carriage of livestock-associated (LA-) Staphylococcus aureus and also for skin and soft tissue infection (SSTI). However, whether LA-S. aureus nasal carriage is associated with increased risk of SSTI remains unclear. We aimed to examine S. aureus nasal carriage and recent (≤3 months prior to enrollment) SSTI symptoms among industrial hog operation (IHO) workers and their household contacts. IHO workers and their household contacts provided a nasal swab and responded to a questionnaire assessing self-reported personal and occupational exposures and recent SSTI symptoms. Nasal swabs were analyzed for S. aureus, including methicillin-resistant S. aureus (MRSA), multidrug-resistant-S. aureus (MDRSA), absence of scn (livestock association), and spa type. S. aureus with at least one indicator of LA was observed among 19% of 103 IHO workers and 6% of 80 household members. Prevalence of recent SSTI was 6% among IHO workers and 11% among 54 minor household members (0/26 adult household members reported SSTI). Among IHO workers, nasal carriers of MDRSA and scn-negative S. aureus were 8.8 (95% CI: 1.8, 43.9) and 5.1 (95% CI: 1.2, 22.2) times as likely to report recent SSTI as non-carriers, respectively. In one household, both an IHO worker and child reported recent SSTI and carried the same S. aureus spa type (t4976) intranasally. Prevalence of scn-negative S. aureus (PR: 5.0, 95% CI: 1.2, 21.4) was elevated among IHO workers who reported never versus always wearing a face mask at work. Although few SSTI were reported, this study of IHO workers and their household contacts is the first to characterize a relation between nasal carriage of antibiotic-resistant LA-S. aureus and SSTI. The direction and temporality of this relation and IHO workers’ use of face masks to prevent nasal carriage of these bacteria warrant further investigation. PMID:27851746

  15. Livestock-Associated, Antibiotic-Resistant Staphylococcus aureus Nasal Carriage and Recent Skin and Soft Tissue Infection among Industrial Hog Operation Workers.

    PubMed

    Nadimpalli, Maya; Stewart, Jill R; Pierce, Elizabeth; Pisanic, Nora; Love, David C; Hall, Devon; Larsen, Jesper; Carroll, Karen C; Tekle, Tsigereda; Perl, Trish M; Heaney, Christopher D

    2016-01-01

    Swine production work is a risk factor for nasal carriage of livestock-associated (LA-) Staphylococcus aureus and also for skin and soft tissue infection (SSTI). However, whether LA-S. aureus nasal carriage is associated with increased risk of SSTI remains unclear. We aimed to examine S. aureus nasal carriage and recent (≤3 months prior to enrollment) SSTI symptoms among industrial hog operation (IHO) workers and their household contacts. IHO workers and their household contacts provided a nasal swab and responded to a questionnaire assessing self-reported personal and occupational exposures and recent SSTI symptoms. Nasal swabs were analyzed for S. aureus, including methicillin-resistant S. aureus (MRSA), multidrug-resistant-S. aureus (MDRSA), absence of scn (livestock association), and spa type. S. aureus with at least one indicator of LA was observed among 19% of 103 IHO workers and 6% of 80 household members. Prevalence of recent SSTI was 6% among IHO workers and 11% among 54 minor household members (0/26 adult household members reported SSTI). Among IHO workers, nasal carriers of MDRSA and scn-negative S. aureus were 8.8 (95% CI: 1.8, 43.9) and 5.1 (95% CI: 1.2, 22.2) times as likely to report recent SSTI as non-carriers, respectively. In one household, both an IHO worker and child reported recent SSTI and carried the same S. aureus spa type (t4976) intranasally. Prevalence of scn-negative S. aureus (PR: 5.0, 95% CI: 1.2, 21.4) was elevated among IHO workers who reported never versus always wearing a face mask at work. Although few SSTI were reported, this study of IHO workers and their household contacts is the first to characterize a relation between nasal carriage of antibiotic-resistant LA-S. aureus and SSTI. The direction and temporality of this relation and IHO workers' use of face masks to prevent nasal carriage of these bacteria warrant further investigation.

  16. Biomarkers of inflammation in ozone-exposed humans: Comparison of the nasal and bronchoalveolar lavage

    SciTech Connect

    Graham, D.E.; Koren, H.S.

    1989-06-01

    An influx of neutrophils (PMNs), a primary feature of acute inflammation, has been associated with the development of lower lung disorders, such as emphysema and idiopathic fibrosis, as well as airway hyperreactivity and increased mucus secretion. It was previously established that an acute inflammatory response in the upper respiratory tract of humans could be studied by analysis of nasal lavages (NL), which is inexpensive, non-invasive, and atraumatic. However, the relationship of the cellular changes in the upper respiratory tract to changes in the lower airways has not been thoroughly investigated in humans. Here the cellular changes detected in the NL with those detected in the bronchoalveolar lavage (BAL) taken from the same individual have been compared. Ten subjects were exposed to either filtered air or 0.4 ppm ozone (O3), with exercise, for 2 hrs. The NL was done prior to, immediately following an 18 hr post exposure, while the BAL was done only at 18 hr post exposure. A significant increase in PMNs was detected in the NL immediately post exposure to 03, (7.7-fold increase; p=.003), and remained elevated in the 18 hr post-03 NL (6.1-fold increase; p<.001).

  17. Nasal Cancer

    MedlinePlus

    ... the way to your throat as you breathe. Cancer of the nasal cavity and paranasal sinuses is ... be like those of infections. Doctors diagnose nasal cancer with imaging tests, lighted tube-like instruments that ...

  18. Numerical simulations for detailed airflow dynamics in a human nasal cavity.

    PubMed

    Wen, Jian; Inthavong, Kiao; Tu, Jiyuan; Wang, Simin

    2008-04-30

    Nasal physiology is dependent on the physical structure of the nose. Individual aspects of the nasal cavity such as the geometry and flow rate collectively affect nasal function such as the filtration of foreign particles by bringing inspired air into contact with mucous-coated walls, humidifying and warming the air before it enters the lungs and the sense of smell. To better understand the physiology of the nose, this study makes use of CFD methods and post-processing techniques to present flow patterns between the left and right nasal cavities and compared the results with experimental and numerical data that are available in literature. The CFD simulation adopted a laminar steady flow for flow rates of 7.5 L/min and 15 L/min. General agreement of gross flow features were found that included high velocities in the constrictive nasal valve area region, high flow close to the septum walls, and vortex formations posterior to the nasal valve and olfactory regions. The differences in the left and right cavities were explored and the effects it had on the flow field were discussed especially in the nasal valve and middle turbinate regions. Geometrical differences were also compared with available models.

  19. A critical review of the influence of oxytocin nasal spray on social cognition in humans: evidence and future directions.

    PubMed

    Guastella, Adam J; Graustella, Adam J; MacLeod, Colin

    2012-03-01

    The past eight years of research has demonstrated that oxytocin nasal spray has a significant impact on human social cognition. The aim of this review is to provide critical comment on the literature using an information-processing framework. We provide a summary of fundamental assumptions of information-processing models and highlight an impressive range of consistent findings that demonstrate the impact of oxytocin nasal spray on social information processing. These findings include that oxytocin nasal spray improves the early conceptual detection of affect from social cues and improves the accurate appraisal of affect from social cues at elaborate and strategic levels of processing. There is some evidence that these effects may be particularly powerful for positive social cues. This review comments on inconsistent results that have been reported. We argue that such inconsistencies can, in part, be explained by variability across experiments in the degree to which potential extraneous confounds have been controlled, the different methods upon which studies assessed cognition, and the extent to which the focus of investigation has been on group-based outcomes. Finally, we argue that sound cognitive experimental methods can provide powerful tools to identify markers of response to oxytocin nasal spray that can be integrated into more complex circuitry models. The identification of robust markers has particular value in predicting behavioral and therapeutic response to intervention. This should now be a major focus for future research. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

  20. Humanized mice and tissue transplantation

    PubMed Central

    Kenney, Laurie L; Shultz, Leonard D.; Greiner, Dale L; Brehm, Michael A.

    2017-01-01

    Our understanding of the molecular pathways that control immune responses, particularly immunomodulatory molecules that control the extent and duration of an immune response, have led to new approaches in the field of transplantation immunology to induce allograft survival. These molecular pathways are being defined precisely in murine models, and are now being translated into clinical practice. However, many of the newly available drugs are human-specific reagents and furthermore, there exist many species-specific differences between mouse and human immune systems. Recent advances in the development of humanized mice, i.e., immunodeficient mice engrafted with functional human immune systems, have led to the availability of a small animal model for the study of human immune responses. Humanized mice represent an important pre-clinical model system for evaluation of new drugs as well as identification of the mechanisms underlying human allograft rejection without putting patients at risk. This review highlights recent advances in the development of humanized mice and their use as pre-clinical models for the study of human allograft responses. PMID:26588186

  1. Human Nasal Myiasis Caused by Oestrus ovis in the Highlands of Cusco, Peru: Report of a Case and Review of the Literature.

    PubMed

    Hoyer, P; Williams, R R; Lopez, M; Cabada, M M

    2016-01-01

    Myiasis is the infestation by dipterous larvae. The larvae can infect intact or decaying tissue including the skin or epithelial surfaces of the orbits, nose, and genitourinary and gastrointestinal tracts. We report a case of primary obligatory nasal myiasis by Oestrus ovis in a 56-year-old man from Cusco in Peru. He presented with nasal pruritus, congestion, and sneezing white "cottony" material. The material was identified as O. ovis larvae. A literature review of publications reporting nasal myiasis caused by O. ovis is presented.

  2. Human Nasal Myiasis Caused by Oestrus ovis in the Highlands of Cusco, Peru: Report of a Case and Review of the Literature

    PubMed Central

    Lopez, M.

    2016-01-01

    Myiasis is the infestation by dipterous larvae. The larvae can infect intact or decaying tissue including the skin or epithelial surfaces of the orbits, nose, and genitourinary and gastrointestinal tracts. We report a case of primary obligatory nasal myiasis by Oestrus ovis in a 56-year-old man from Cusco in Peru. He presented with nasal pruritus, congestion, and sneezing white “cottony” material. The material was identified as O. ovis larvae. A literature review of publications reporting nasal myiasis caused by O. ovis is presented. PMID:28116184

  3. Metabolic activation of the tobacco carcinogen 4-(methylnitrosamino)-(3-pyridyl)-1-butanone by cytochrome P450 2A13 in human fetal nasal microsomes.

    PubMed

    Wong, Hansen L; Zhang, Xiuling; Zhang, Qing-Yu; Gu, Jun; Ding, Xinxin; Hecht, Stephen S; Murphy, Sharon E

    2005-06-01

    Among human P450s studied to date, P450 2A13 is the most efficient catalyst of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-hydroxylation. This reaction is a key bioactivation pathway in NNK-induced carcinogenesis. P450 2A13 mRNA has been detected in human tissues, but it is unknown whether the enzyme is functional in vivo. Therefore, we studied NNK alpha-hydroxylation in human fetal nasal mucosal microsomes, which have been shown to contain high levels of P450 2A protein, presumed to be a mixture of P450 2A6 and 2A13. The microsomes efficiently catalyzed NNK alpha-hydroxylation at the methylene and methyl carbons, as well as carbonyl reduction. Antibodies against mouse P450 2A5 inhibited alpha-hydroxylation by these microsomes greater than 90%. K(m) and V(max) values for alpha-methylene hydroxylation were 6.5 +/- 1.1 muM and 3.0 +/- 0.1 pmol/min/mg; for alpha-methyl hydroxylation, they were 6.7 +/- 0.8 microM and 0.85 +/- 0.03 pmol/min/mg. The K(m) values agree closely with those for NNK metabolism by P450 2A13. Using a new technique, we separated P450 2A13 from P450 2A6 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Quantitative immunoblot analysis indicated that the level of P450 2A13 in the pooled fetal nasal microsome sample used for kinetic analysis was approximately 1.6 pmol/mg protein. In the same sample, P450 2A6 was not detected (detection limit, 67 fmol/mg protein). These kinetic, immunoinhibition, and immunoblot data confirm that P450 2A13 is a functional enzyme and the catalyst of NNK alpha-hydroxylation in human fetal nasal mucosa. The results are also the first to demonstrate high efficiency NNK alpha-hydroxylation in a human tissue.

  4. Tissue Specificity of Human Disease Module

    PubMed Central

    Kitsak, Maksim; Sharma, Amitabh; Menche, Jörg; Guney, Emre; Ghiassian, Susan Dina; Loscalzo, Joseph; Barabási, Albert-László

    2016-01-01

    Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue. Driven by this hypothesis, we conducted a systematic study of the expression patterns of disease genes within the human interactome. We find that genes expressed in a specific tissue tend to be localized in the same neighborhood of the interactome. By contrast, genes expressed in different tissues are segregated in distinct network neighborhoods. Most important, we show that it is the integrity and the completeness of the expression of the disease module that determines disease manifestation in selected tissues. This approach allows us to construct a disease-tissue network that confirms known and predicts unexpected disease-tissue associations. PMID:27748412

  5. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A nasal... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external...

  6. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A nasal... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external...

  7. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans.

    PubMed

    Johansson, E L; Wassén, L; Holmgren, J; Jertborn, M; Rudin, A

    2001-12-01

    Sexually transmitted diseases are a major health problem worldwide, but there is still a lack of knowledge about how to induce an optimal immune response in the genital tract of humans. In this study we vaccinated 21 volunteers nasally or vaginally with the model mucosal antigen cholera toxin B subunit and determined the level of specific immunoglobulin A (IgA) and IgG antibodies in vaginal and cervical secretions as well as in serum. To assess the hormonal influence on the induction of antibody responses after vaginal vaccination, we administered the vaccine either independently of the stage in the menstrual cycle or on days 10 and 24 in the cycle in different groups of subjects. Vaginal and nasal vaccinations both resulted in significant IgA and IgG anti-cholera toxin B subunit responses in serum in the majority of the volunteers in the various vaccination groups. Only vaginal vaccination given on days 10 and 24 in the cycle induced strong specific antibody responses in the cervix with 58-fold IgA and 16-fold IgG increases. In contrast, modest responses were seen after nasal vaccination and in the other vaginally vaccinated group. Nasal vaccination was superior in inducing a specific IgA response in vaginal secretions, giving a 35-fold increase, while vaginal vaccination induced only a 5-fold IgA increase. We conclude that a combination of nasal and vaginal vaccination might be the best vaccination strategy for inducing protective antibody responses in both cervical and vaginal secretions, provided that the vaginal vaccination is given on optimal time points in the cycle.

  8. Grating-based tomography of human tissues

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Schulz, Georg; Mehlin, Andrea; Herzen, Julia; Lang, Sabrina; Holme, Margaret; Zanette, Irene; Hieber, Simone; Deyhle, Hans; Beckmann, Felix; Pfeiffer, Franz; Weitkamp, Timm

    2012-07-01

    The development of therapies to improve our health requires a detailed knowledge on the anatomy of soft tissues from the human body down to the cellular level. Grating-based phase contrast micro computed tomography using synchrotron radiation provides a sensitivity, which allows visualizing micrometer size anatomical features in soft tissue without applying any contrast agent. We show phase contrast tomography data of human brain, tumor vessels and constricted arteries from the beamline ID 19 (ESRF) and urethral tissue from the beamline W2 (HASYLAB/DESY) with micrometer resolution. Here, we demonstrate that anatomical features can be identified within brain tissue as well known from histology. Using human urethral tissue, the application of two photon energies is compared. Tumor vessels thicker than 20 μm can be perfectly segmented. The morphology of coronary arteries can be better extracted in formalin than after paraffin embedding.

  9. Acute reinforcing effects of low-dose nicotine nasal spray in humans.

    PubMed

    Perkins, K A; Grobe, J E; Caggiula, A; Wilson, A S; Stiller, R L

    1997-02-01

    Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers.

  10. Enhancing effect of borneol and muscone on geniposide transport across the human nasal epithelial cell monolayer.

    PubMed

    Chen, Zhenzhen; Gong, Xin; Lu, Yang; Du, Shouying; Yang, Zhihui; Bai, Jie; Li, Pengyue; Wu, Huichao

    2014-01-01

    Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases.

  11. Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage

    SciTech Connect

    Koren, H.S.; Devlin, R.B. )

    1992-04-30

    A set of symptoms has been described during the past two decades. These symptoms, which have been called the sick building syndrome, include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that VOCs present in synthetic materials used in homes and office buildings contribute to these symptoms. There have been few studies, however, in which humans have been exposed to known amounts of VOCs under carefully controlled conditions. In this study, 14 subjects have been exposed to a mixture of VOCs (25 mg/m3 total hydrocarbon) representative of what is found in new homes and office buildings. Because irritation of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, we have used NAL to monitor PMN influx into the nasal passages following exposure to VOCs. We report statistically significant increases in PMNs both immediately after a 4-hr exposure to VOCs, as well as 18 hr later.

  12. Enhancing Effect of Borneol and Muscone on Geniposide Transport across the Human Nasal Epithelial Cell Monolayer

    PubMed Central

    Chen, Zhenzhen; Gong, Xin; Lu, Yang; Du, Shouying; Yang, Zhihui; Bai, Jie; Li, Pengyue; Wu, Huichao

    2014-01-01

    Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases. PMID:24992195

  13. Comparison of micron- and nanoparticle deposition patterns in a realistic human nasal cavity.

    PubMed

    Wang, S M; Inthavong, K; Wen, J; Tu, J Y; Xue, C L

    2009-05-15

    Knowledge regarding particle deposition processes in the nasal cavity is important in aerosol therapy and inhalation toxicology applications. This paper presents a comparative study of the deposition of micron and submicron particles under different steady laminar flow rates using a Lagrangian approach. A computational model of a nasal cavity geometry was developed from CT scans and the simulation of the fluid and particle flow within the airway was performed using the commercial software GAMBIT and FLUENT. The air flow patterns in the nasal cavities and the detailed local deposition patterns of micron and submicron particles were presented and discussed. It was found that the majority of micron particles are deposited near the nasal valve region and some micron particles are deposited on the septum wall in the turbinate region. The deposition patterns of micron particles in the left cavity are different compared with that in the right one especially in the turbinate regions. In contrast, the deposition for nanoparticles shows a moderately even distribution of particles throughout the airway. Furthermore the particles releasing position obviously influences the local deposition patterns. The influence of the particle releasing position is mainly shown near the nasal valve region for micron particle deposition, while for submicron particles deposition, both the nasal valve and turbinate region are influenced. The results of the paper are valuable in aerosol therapy and inhalation toxicology.

  14. Effects of experimental nasal obstruction on human masseter and suprahyoid muscle activities during sleep.

    PubMed

    Hiyama, Shigetoshi; Ono, Takashi; Ishiwata, Yasuo; Kuroda, Takayuki; Ohyama, Kimie

    2003-04-01

    The effect of nasal obstruction on nocturnal masseter and suprahyoid muscle activities using a newly developed portable electromygram (EMG)-recording unit was examined. Ten healthy Japanese males participated in this study. EMG activities of both the right masseter and bilateral suprahyoid muscles were recorded with a portable EMG-recording unit. At midnight, the subject was asked to lie on a bed after complete preparation with surface electrodes. After maximal clenching and jaw-opening effort (100% maximum voluntary contribution), the subject was allowed to fall asleep. In the first half of the night, EMG activities were recorded for about three hours of sleep without nasal obstruction. In the second half of the night, EMG activities were recorded for about three hours of sleep with nasal obstruction. In both muscles, there were no significant changes in either the maximal EMG activities or the number of events beyond 40% MVC with nasal obstruction. But in an evaluation based on the distribution of muscle activities, the EMG activity of the masseter muscle tended to decrease (P = .07) and that of the suprahyoid muscles increased significantly (P = .02) with nasal obstruction. These results suggest that nasal obstruction could modulate the activities of the masseter and suprahyoid muscles during sleep.

  15. NCI’s Cooperative Human Tissue Network

    Cancer.gov

    Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

  16. Melanin content of hamster tissues, human tissues, and various melanomas

    SciTech Connect

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  17. Variation in alternative splicing across human tissues

    PubMed Central

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. Conclusions This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells. PMID:15461793

  18. Characterization of nasal methicillin-resistant Staphylococcus aureus isolated from international human and veterinary surgeons.

    PubMed

    Post, Virginia; Harris, Llinos G; Morgenstern, Mario; Geoff Richards, R; Sheppard, Samuel K; Fintan Moriarty, T

    2017-03-01

    Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is poorly described for surgeons, despite the increased exposure to nosocomial pathogens and at-risk patients. This study investigated the molecular epidemiology and antimicrobial resistance of 26 MRSA isolates cultured from the nares of an international cross-sectional study of 1166 human and 60 veterinary surgeons. All isolates were subjected to agr, spa and multilocus sequence typing, and the presence of 22 virulence factors was screened for by PCR. Additionally, biofilm-forming ability, haemolytic activity, staphyloxanthin production and antibiotic resistance were determined. The genome of a rifampicin-resistant MRSA was sequenced. Approximately half of the isolates belonged to well-described clonal lineages, ST1, ST5, ST8, ST45 and ST59, that have previously been associated with severe infections and increased patient mortality. Two of the three veterinarian MRSA belonged to epidemic livestock-associated MRSA clonal lineages (ST398 and ST8) previously associated with high transmission potential between animals and humans. The isolates did not display any consistent virulence gene pattern, and 35 % of the isolates carried at least one of the Panton-Valentine leukocidin (lukFS-PV), exfoliative toxin (eta) or toxic shock syndrome (tst) genes. Resistance to rifampicin was detected in one veterinarian isolate and was found to be due to three mutations in the rpoB gene. Surgeons occupy a critical position in the healthcare profession due to their close contact with patients. In this study, surgeons were found to be colonized with MRSA at low rates, similar to those of the general population, and the colonizing strains were often common clonal lineages.

  19. Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

    USGS Publications Warehouse

    Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, William D.; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

    2016-01-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

  20. Nasal packing and stenting

    PubMed Central

    Weber, Rainer K.

    2011-01-01

    Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

  1. Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

    PubMed

    Liu, Shao-Cheng; Lin, Chun-Shu; Chen, Shyi-Gen; Chu, Yueng-Hsiang; Lee, Fei-Peng; Lu, Hsuan-Hsuan; Wang, Hsing-Won

    2017-02-01

    Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

  2. N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

    PubMed

    Rochat, Thierry; Lacroix, Jean-Silvain; Jornot, Lan

    2004-10-01

    N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport.

  3. Human histocultures (tissue explants) in retrovirology

    PubMed Central

    Arakelyan, Anush; Fitzgerald, Wendy; Grivel, Jean-Charles; Vanpouille, Christophe; Margolis, Leonid

    2014-01-01

    Summary Viral pathogenesis is studied predominantly in cultures of primary isolated cells or cell lines. Many retroviruses efficiently replicate only in activated cells. Therefore, in order to become efficient viral producers cells should be artificially activated, a procedure which significantly changes cell physiology. However, for many viral diseases, like HIV-1 and other retroviruses’ diseases, critical pathogenic events occur in tissues and cell isolation from their native microenvironment prevents single cell cultures from faithfully reflecting important aspects of cell-cell and cell-pathogen interactions that occur in the context of complex tissue cytoarchitecture. Tissue explants (histocultures) that retain tissue cytoarchitecture and many aspects of cell-cell interactions more faithfully represent in vivo tissue features. Human histocultures constitute an adequate model for studying viral pathogenesis under controlled laboratory conditions. Protocols for various human histocultures as applied to study retroviral pathogenesis, in particular of HIV-1, have been refined by our laboratory and are described in the present publication. Human histocultures of human tonsils and lymph nodes, as well as of recto-sigmoid and cervico-vaginal tissues can be used to study viral transmission, pathogenesis and as a pre-clinical platform for antivirals evaluation. PMID:24158827

  4. Effect of nasal sprays on an in vitro survival and morphology of nasoseptal cartilage.

    PubMed

    Stoelzel, Katharina; Kohl, Benjamin; Hoyer, Mariann; Meier, Carola; Szczepek, Agnieszka J; Olze, Heidi; Schulze-Tanzil, Gundula

    2015-04-01

    Nasal sprays were introduced several years ago to support the treatment of allergic rhinitis. These sprays may come in direct contact with directly exposed nasoseptal cartilage (e.g. is case of nasoseptal perforation). To date, no studies investigated the effects of nasal sprays on cartilage tissues and cells. Therefore, our aim was to analyze the influence of two different nasal spray types (thixotropic and liposomal) on the vitality of nasoseptal chondrocytes. Human chondrocytes were isolated from surgically dissected tissues. Alternatively, nasal septa (porcine and human) tissue explants were used. The cell or explant cultures were treated with nasal sprays for 4-24 h. As a read-out, cell vitality and gene and protein expression profiles of type I and II collagen, SOX 9 and matrix metalloproteinase MMP-1 were compared to the untreated controls by means of real-time RT-PCR and immunostaining. Using the liposomal, but not thixotropic nasal spray in an explant or chondrocyte in vitro culture led to increased cell death, as compared to the untreated controls. A trend towards suppression of type II collagen and SOX 9 on protein level was found in cultures exposed to liposomal nasal spray, as compared to the controls. The thixotropic nasal spray has not affected the nasoseptal chondrocytes. Further studies with the use of viable nasoseptal cartilage explants and particularly using an in vivo animal model of exposed nasoseptal cartilage are necessary to clear the effect of liposomal spray on chondrocytes.

  5. Accumulation of perfluoroalkyl substances in human tissues.

    PubMed

    Pérez, Francisca; Nadal, Martí; Navarro-Ortega, Alícia; Fàbrega, Francesc; Domingo, José L; Barceló, Damià; Farré, Marinella

    2013-09-01

    Perfluoroalkyl substances (PFASs) are environmental pollutants with an important bioaccumulation potential. However, their metabolism and distribution in humans are not well studied. In this study, the concentrations of 21 PFASs were analyzed in 99 samples of autopsy tissues (brain, liver, lung, bone, and kidney) from subjects who had been living in Tarragona (Catalonia, Spain). The samples were analyzed by solvent extraction and online purification by turbulent flow and liquid chromatography coupled to tandem mass spectrometry. The occurrence of PFASs was confirmed in all human tissues. Although PFASs accumulation followed particular trends depending on the specific tissue, some similarities were found. In kidney and lung, perfluorobutanoic acid was the most frequent compound, and at highest concentrations (median values: 263 and 807ng/g in kidney and lung, respectively). In liver and brain, perfluorohexanoic acid showed the maximum levels (median: 68.3 and 141ng/g, respectively), while perfluorooctanoic acid was the most contributively in bone (median: 20.9ng/g). Lung tissues accumulated the highest concentration of PFASs. However, perfluorooctane sulfonic acid and perfluorooctanoic acid were more prevalent in liver and bone, respectively. To the best of our knowledge, the accumulation of different PFASs in samples of various human tissues from the same subjects is here reported for the very first time. The current results may be of high importance for the validation of physiologically based pharmacokinetic models, which are being developed for humans. However, further studies on the distribution of the same compounds in the human body are still required.

  6. Beneficial effect of antibiotics on ciliary beat frequency of human nasal epithelial cells exposed to bacterial toxins.

    PubMed

    Mallants, Roel; Jorissen, Mark; Augustijns, Patrick

    2008-04-01

    In the present study, we explored whether the cilio-inhibitory effect induced by toxins derived from bacterial infections could be compensated for by a cilio-stimulatory effect of antibiotics. Human nasal epithelial cells (HNEC) expressing beating cilia were grown as monolayers. Ciliary beat frequency (CBF) was determined using an inverted microscope coupled with a high-speed digital camera. Clarithromycin and neomycin did not influence ciliary activity. Bacitracin, clindamycin, gramicidin and roxithromycin increased CBF significantly: by 50 +/- 12%, 54 +/- 16%, 31 +/- 16% and 31 +/- 18%, respectively. A 30 min exposure to Staphylococcus aureus enterotoxin B (SEB) and Pseudomonas aeruginosa lipopolysaccharide (PAL) decreased CBF significantly, by 37 +/- 16 and 28 +/- 12%, respectively. In contrast with exposure to the toxin alone, co-incubation of the nasal monolayer cells with PAL and bacitracin or clindamycin did not result in a decrease in CBF after 30 and 60 min. The effect of SEB could be compensated for by bacitracin but not by clindamycin. After a 12 h preincubation period with SEB, co-incubation with either bacitracin or clindamycin resulted in the complete recovery of CBF. This study suggests that topical antibiotic treatment of nasal infections could result in a dual positive effect, namely treatment of the bacterial infection and recovery of ciliary activity.

  7. Humanized mice with ectopic artificial liver tissues.

    PubMed

    Chen, Alice A; Thomas, David K; Ong, Luvena L; Schwartz, Robert E; Golub, Todd R; Bhatia, Sangeeta N

    2011-07-19

    "Humanized" mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury but these methods have not gained widespread use due to the duration and variability of hepatocyte repopulation. In light of the significant progress that has been achieved in clinical cell transplantation through tissue engineering, we sought to develop a humanized mouse model based on the facile and ectopic implantation of a tissue-engineered human liver. These human ectopic artificial livers (HEALs) stabilize the function of cryopreserved primary human hepatocytes through juxtacrine and paracrine signals in polymeric scaffolds. In contrast to current methods, HEALs can be efficiently established in immunocompetent mice with normal liver function. Mice transplanted with HEALs exhibit humanized liver functions persistent for weeks, including synthesis of human proteins, human drug metabolism, drug-drug interaction, and drug-induced liver injury. Here, mice with HEALs are used to predict the disproportionate metabolism and toxicity of "major" human metabolites using multiple routes of administration and monitoring. These advances may enable manufacturing of reproducible in vivo models for diverse drug development and research applications.

  8. Nasal commensal Staphylococcus epidermidis counteracts influenza virus

    PubMed Central

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T.; Rohde, Holger; Gallo, Richard L.; Huang, Chun-Ming

    2016-01-01

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection. PMID:27306590

  9. Nasal commensal Staphylococcus epidermidis counteracts influenza virus.

    PubMed

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T; Rohde, Holger; Gallo, Richard L; Huang, Chun-Ming

    2016-06-16

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection.

  10. The Ramathibodi nasal filter in a simulated human airway: evaluated with laser smoke particles and a laser diode dust portable monitor.

    PubMed

    Tanpowpong, K; Chiratthiti, C

    2001-12-01

    The Ramathibodi nasal filter was specially designed as a personal respiratory protective device. It was attached to a simulated human airway composed of a nasal and pharyngeal model, airway passage and lung model machine. The system was run in a laser smoke particles environment. The laser smoke particles with suspended particulate matter size of less than 15, 10 and 2.5 microns (PM15, PM10 and PM2.5) were selected. The amount of each particle size in the simulated human airway with and without the Ramathibodi nasal filter was measured continuously by a laser diode portable dust monitor. One hundred sample sizes were analyzed by a descriptive statistical method at the Department of Otolaryngology, Ramathibodi Hospital from January to November 1999. The graphic distribution patterns of each residual particle size in the simulated human airway with and without the Ramathibodi nasal filter were compared. The filtration efficacy of the Ramathibodi nasal filter should be tested further by this experimental model. The device could be applied intermittently in adult nasal vestibules.

  11. [Human lung connective tissue in postnatal ontogeny].

    PubMed

    Kasimtsev, A A; Nikolaev, V G

    1993-01-01

    Changes of the connective tissue structures, appearing during all postnatal ontogenesis stages were studied in 147 human lung specimens of different age groups (from newborns up to 82-year-olds). Qualitative and quantitative composition of connective tissue structures changes with the age which leads to the lateral aggregation of the fibers and growth of the general mass of the connective tissue. Heterochronia of the age variability manifestations in different regions of the lung framework was demonstrated. The original age transformations of connective tissue structures are characteristic for the basal lung regions. With the exception of perivasal connective tissue, similar changes in the region of the lung apexes appear 3-5 years later. This gives an opportunity to distinguish three anatomic zones in the lungs in an apico-basal direction, characterising the local nature of the age changes manifestations.

  12. Airflow in the Human Nasal Passage and Sinuses of Chronic Rhinosinusitis Subjects.

    PubMed

    Kumar, Haribalan; Jain, Ravi; Douglas, Richard G; Tawhai, Merryn H

    2016-01-01

    Endoscopic surgery is performed on patients with chronic inflammatory disease of the paranasal sinuses to improve sinus ventilation. Little is known about how sinus surgery affects sinonasal airflow. In this study nasal passage geometry was reconstructed from computed tomographic imaging from healthy normal, pre-operative, and post-operative subjects. Transient air flow through the nasal passage during calm breathing was simulated. Subject-specific differences in ventilation of the nasal passage were observed. Velocity magnitude at ostium was different between left and right airway. In FESS, airflow in post-surgical subjects, airflow at the maxillary sinus ostium was upto ten times higher during inspiration. In a Lothrop procedure, airflow at the frontal sinus ostium can be upto four times higher during inspiration. In both post-operative subjects, airflow at ostium was not quasi-steady. The subject-specific effect (of surgery) on sinonasal interaction evaluated through airflow simulations may have important consequences for pre- and post-surgical assessment and surgical planning, and design for improvement of the delivery efficiency of nasal therapeutics.

  13. Airflow in the Human Nasal Passage and Sinuses of Chronic Rhinosinusitis Subjects

    PubMed Central

    Kumar, Haribalan; Jain, Ravi; Douglas, Richard G.; Tawhai, Merryn H.

    2016-01-01

    Endoscopic surgery is performed on patients with chronic inflammatory disease of the paranasal sinuses to improve sinus ventilation. Little is known about how sinus surgery affects sinonasal airflow. In this study nasal passage geometry was reconstructed from computed tomographic imaging from healthy normal, pre-operative, and post-operative subjects. Transient air flow through the nasal passage during calm breathing was simulated. Subject-specific differences in ventilation of the nasal passage were observed. Velocity magnitude at ostium was different between left and right airway. In FESS, airflow in post-surgical subjects, airflow at the maxillary sinus ostium was upto ten times higher during inspiration. In a Lothrop procedure, airflow at the frontal sinus ostium can be upto four times higher during inspiration. In both post-operative subjects, airflow at ostium was not quasi-steady. The subject-specific effect (of surgery) on sinonasal interaction evaluated through airflow simulations may have important consequences for pre- and post-surgical assessment and surgical planning, and design for improvement of the delivery efficiency of nasal therapeutics. PMID:27249219

  14. Pathophysiology of nasal congestion

    PubMed Central

    Naclerio, Robert M; Bachert, Claus; Baraniuk, James N

    2010-01-01

    Nasal congestion is a common symptom in rhinitis (both allergic and nonallergic), rhinosinusitis and nasal polyposis. Congestion can also be caused by physical obstruction of nasal passages and/or modulation of sensory perception. Mucosal inflammation underlies many of the specific and interrelated factors that contribute to nasal congestion, as well as other symptoms of both allergic rhinitis and rhinosinusitis. A wide range of biologically active agents (eg, histamine, tumor necrosis factor-α, interleukins, cell adhesion molecules) and cell types contribute to inflammation, which can manifest as venous engorgement, increased nasal secretions and tissue swelling/edema, ultimately leading to impaired airflow and the sensation of nasal congestion. Inflammation-induced changes in the properties of sensory afferents (eg, expression of peptides and receptors) that innervate the nose can also contribute to altered sensory perception, which may result in a subjective feeling of congestion. Increased understanding of the mechanisms underlying inflammation can facilitate improved treatment selection and the development of new therapies for congestion. PMID:20463823

  15. Nasal polyposis

    PubMed Central

    Brown, Gerald A.

    1969-01-01

    A review of 313 cases of nasal polyposis indicates that there is a high incidence of recurrence in this disease. Other nasal pathology affects a significant number of these patients. Simple surgical removal of the polypi by a transnasal route is the common mode of treatment. PMID:4187956

  16. Viscoelastic Properties of Human Tracheal Tissues.

    PubMed

    Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

    2017-01-01

    The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

  17. [Lymphatic tissue of the nose (NALT) and larynx (LALT) in species comparison: human, rat, mouse].

    PubMed

    Pabst, R

    2010-07-01

    Nose- and larynx associated lymphatic tissues (NALT and LALT) vary markedly between humans, rats and mice. NALT of rats and mice is formed by paired lymphoid aggregates in the nasal cavity, while it consists of individual mucosa associated lymphoid follicles throughout the nose in humans. In addition to NALT, tonsils are present in humans, but not in rats and mice. In the larynx, LALT can be found in humans, but not in rats. Size and functionality of NALT, tonsils and LALT vary with age. The extrapolation of data obtained from rodents to humans should be carefully evaluated due to these differences. The term common mucosal immune system should replaced by the term "integrated" MALT and the immunological differences between respiratory and digestive tract should always be considered.

  18. Scaffold-free cartilage tissue engineering with a small population of human nasoseptal chondrocytes.

    PubMed

    Chiu, Loraine L Y; To, William T H; Lee, John M; Waldman, Stephen D

    2017-03-01

    Cartilage tissue engineering is a promising approach to provide suitable materials for nasal reconstruction; however, it typically requires large numbers of cells. We have previously shown that a small number of chondrocytes cultivated within a continuous flow bioreactor can elicit substantial tissue growth, but translation to human chondrocytes is not trivial. Here, we aimed to demonstrate the application of the bioreactor to generate large-sized tissues from a small population of primary human nasoseptal chondrocytes. Experimental study. Chondrocytes were cultured in the bioreactor using different medium compositions, with varying amounts of serum and with or without growth factors. Resulting engineered tissues were analyzed for physical properties, biochemical composition, tissue microstructure, and protein localization. Bioreactor-cultivated constructs grown with serum and growth factors (basic fibroblast growth factor and transforming growth factor beta 2) had greater thickness, as well as DNA and glycosaminoglycan (GAG) contents, compared to low serum and no growth factor controls. These constructs also showed the most intense proteoglycan and collagen II staining. The combination of bioreactor conditions, serum, and growth factors allowed the generation of large, thick scaffold-free human cartilaginous tissues that resembled the native nasoseptal cartilage. There also may be implications for patient selection in future clinical applications of these engineered tissues because their GAG content decreased with donor age. NA. Laryngoscope, 127:E91-E99, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Optical recordings from the human nasal mucosa in response to olfactory stimulation.

    PubMed

    Ishimaru, Tadashi; Reden, Jens; Krone, Franziska; Scheibe, Mandy

    2007-08-23

    Using the intrinsic optical signal the present study aimed to investigate changes in blood flow at the nasal epithelium in response to specific olfactory stimulation. Recording equipment included an endoscope, a CCD camera, and a light source of 617 nm. Two concentrations of the specific olfactory stimulant H(2)S (2.8 and 5.6 ppm), generated by a computer-controlled olfactometer, were used for olfactory stimulation. Eight healthy normosmic volunteers participated. Using 5.6 ppm H(2)S stimuli, responses were typically recorded from the olfactory cleft, middle turbinate, and middle meatus while responses were less pronounced for 2.8 ppm H(2)S stimuli. Response areas were significantly larger for the 5.6 ppm H(2)S stimuli. While further experiments are needed, recordings of the intrinsic optical signal may be used to obtain responses from the nasal cavity to specific olfactory stimuli.

  20. Three Dimension Filamentous Human Cardiac Tissue Model

    PubMed Central

    Ma, Zhen; Koo, Sangmo; Finnegan, Micaela A.; Loskill, Peter; Huebsch, Nathaniel; Marks, Natalie C.; Conklin, Bruce R.; Grigoropoulos, Costas P.; Healy, Kevin E.

    2013-01-01

    A human in vitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an in vitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity. PMID:24268663

  1. Frequency domain optical tomography in human tissue

    NASA Astrophysics Data System (ADS)

    Yao, Yuqi; Wang, Yao; Pei, Yaling; Zhu, Wenwu; Hu, Jenhun; Barbour, Randall L.

    1995-10-01

    In this paper, a reconstruction algorithm for frequency-domain optical tomography in human tissue is presented. A fast and efficient multigrid finite difference (MGFD) method is adopted as a forward solver to obtain the simulated detector responses and the required imaging operator. The solutions obtained form MGFD method for 3D problems with weakly discontinuous cocoefficients are compared with analyzed solutions to determine the accuracy of the numerical method. Simultaneous reconstruction of both absorption and scattering coefficients for tissue-like media is accomplished by solving a perturbation equation using the Born approximation. This solution is obtained by a conjugate gradient descent method with Tikhonov regularization. Two examples are given to show the quality of the reconstruction results. Both involve the examination of anatomically accurate optical models of tissue derived from segmented 3D magnetic resonance images to which have been assigned optical coefficients to the designated tissue types. One is a map of a female breast containing two small 'added pathologies', such as tumors. The other is a map of the brain containing a 'local bleeding' area, representing a hemorrhage. The reconstruction results show that the algorithm is computationally practical and can yield qualitatively correct geometry of the objects embedded in the simulated human tissue. Acceptable results are obtaiend even when 10% noise is present in the data.

  2. Impacts of fluid dynamics simulation in study of nasal airflow physiology and pathophysiology in realistic human three-dimensional nose models.

    PubMed

    Wang, De Yun; Lee, Heow Peuh; Gordon, Bruce R

    2012-12-01

    During the past decades, numerous computational fluid dynamics (CFD) studies, constructed from CT or MRI images, have simulated human nasal models. As compared to rhinomanometry and acoustic rhinometry, which provide quantitative information only of nasal airflow, resistance, and cross sectional areas, CFD enables additional measurements of airflow passing through the nasal cavity that help visualize the physiologic impact of alterations in intranasal structures. Therefore, it becomes possible to quantitatively measure, and visually appreciate, the airflow pattern (laminar or turbulent), velocity, pressure, wall shear stress, particle deposition, and temperature changes at different flow rates, in different parts of the nasal cavity. The effects of both existing anatomical factors, as well as post-operative changes, can be assessed. With recent improvements in CFD technology and computing power, there is a promising future for CFD to become a useful tool in planning, predicting, and evaluating outcomes of nasal surgery. This review discusses the possibilities and potential impacts, as well as technical limitations, of using CFD simulation to better understand nasal airflow physiology.

  3. Impacts of Fluid Dynamics Simulation in Study of Nasal Airflow Physiology and Pathophysiology in Realistic Human Three-Dimensional Nose Models

    PubMed Central

    Lee, Heow Peuh; Gordon, Bruce R.

    2012-01-01

    During the past decades, numerous computational fluid dynamics (CFD) studies, constructed from CT or MRI images, have simulated human nasal models. As compared to rhinomanometry and acoustic rhinometry, which provide quantitative information only of nasal airflow, resistance, and cross sectional areas, CFD enables additional measurements of airflow passing through the nasal cavity that help visualize the physiologic impact of alterations in intranasal structures. Therefore, it becomes possible to quantitatively measure, and visually appreciate, the airflow pattern (laminar or turbulent), velocity, pressure, wall shear stress, particle deposition, and temperature changes at different flow rates, in different parts of the nasal cavity. The effects of both existing anatomical factors, as well as post-operative changes, can be assessed. With recent improvements in CFD technology and computing power, there is a promising future for CFD to become a useful tool in planning, predicting, and evaluating outcomes of nasal surgery. This review discusses the possibilities and potential impacts, as well as technical limitations, of using CFD simulation to better understand nasal airflow physiology. PMID:23205221

  4. Beta adrenergic receptors in human cavernous tissue

    SciTech Connect

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  5. Characterization of Postoperative Changes in Nasal Airflow Using a Cadaveric Computational Fluid Dynamics Model

    PubMed Central

    Shadfar, Scott; Shockley, William W.; Fleischman, Gita M.; Dugar, Anand R.; McKinney, Kibwei A.; Frank-Ito, Dennis O.; Kimbell, Julia S.

    2015-01-01

    IMPORTANCE Collapse or compromise of the internal nasal valve (INV) results in symptomatic nasal obstruction; thus, various surgical maneuvers are designed to support the INV. OBJECTIVE To determine the effect on nasal airflow after various surgical techniques focused at the level of the INV and lateral nasal sidewall. DESIGN AND SETTING A fresh cadaver head was obtained and underwent suture and cartilage graft techniques directed at the level of the INV using an external approach. Preoperative and postoperative digital nasal models were created from the high-resolution, fine-cut, computed tomographic imaging after each intervention. Isolating the interventions to the level of the INV, we used computational fluid dynamic techniques to calculate nasal resistance, nasal airflow, and nasal airflow partitioning for each intervention. INTERVENTION Suture and cartilage graft techniques. MAIN OUTCOMES AND MEASURES Nasal airflow, nasal resistance, and partitioning of airflow. RESULTS Using the soft-tissue elevation model as baseline, computational fluid dynamic analysis predicted that most of the suture and cartilage graft techniques directed toward the nasal valve improved nasal airflow and partitioning while reducing nasal resistance. Specifically, medial and modified flare suture techniques alone improved nasal airflow by 16.9% and 15.1%, respectively. The combination of spreader grafts and modified flare suture improved nasal airflow by 13.2%, whereas spreader grafts alone only improved airflow by 5.9%. The largest improvements in bilateral nasal resistance were achieved using the medial and modified flare sutures, outperforming the combination of spreader grafts and modified flare suture. CONCLUSIONS AND RELEVANCE Techniques directed at supporting the INV have tremendous value in the treatment of nasal obstruction. The use of flare sutures alone can address dynamic valve collapse or upper lateral cartilage incompetence without gross disruption of the nasal

  6. Efficacy of the ramathibodi nasal filter in a simulated human airway evaluated by a laser diode portable dust monitor under low laser smoke particle concentration.

    PubMed

    Tanpowpong, Kunchitthape; Chiratthiti, Chumroon

    2002-02-01

    The Ramathibodi nasal filter attached to a simulated human airway was proposed to filter laser smoke particles. The simulated human airway composed of nasal and pharyngeal model, airway passage and lung model machine which mimicked the human respiratory system. The laser smoke particles represented a suspended particulate matter in a highly air-pollutted area such as at a main roadside in Bangkok. The experiment was done in the Department of Otolaryngology, Ramathibodi Hospital, from January to March 2000. The simulated human airway got an equal amount of laser smoke particles in a sealed plastic box for 1 min. The residual amount of laser smoke particles in a closed system of the simulated human airway was measured by a laser diode portable dust monitor for 1 min in each cycle and calculated as a mean and standard deviation. Without the Ramathibodi nasal filter of 39 sample pairs, the amounts of PM15, PM10 and PM2.5 were 52.3 +/- 6.8, 43.0 +/- 4.9 and 37.0 +/- 3.5 mcg/m3 respectively. With the Ramathibodi nasal filter of 39 pairs sample, the amounts of PM15, PM10 and PM2.5 were 48.1 +/- 9.9, 39.1 +/- 9.1 and 33.2 +/- 7.2 mcg/m3 respectively. Ramathibodi nasal filter efficacy for all laser smoke particle sizes evaluated statistically using t-test showed significant differences from those without the filter. Filtration efficacy should be tested further in higher concentrations of laser smoke particles and applied in human nasal vestibules under a critical air-polluted condition.

  7. Increased expression of intelectin-1 in nasal polyps.

    PubMed

    Park, Il-Ho; Park, Se-Jin; Cho, Jung-Sun; Moon, You-Mi; Kim, Tae Hoon; Lee, Sang Hag; Lee, Heung-Man

    2012-01-01

    Intelectin-1 is a new type of Ca(2+)-dependant soluble lectin in humans that has affinity for galactofuranose in carbohydrate chains of bacterial cell walls, indicating that intelectin-1 may play a role in immune defense against bacteria. The purpose of the current study was to determine the expression of intelectin-1 mRNA and protein and to localize intelectin-1 protein in nasal polyps and tissues from control subjects. Normal sphenoid sinus mucosa was obtained from 10 patients undergoing surgery for pituitary tumor. Nasal polyp samples were obtained from 10 patients undergoing endoscopic sinus surgery for chronic polypoid rhinosinusitis. Real-time polymerase chain reaction (PCR) was performed for intelectin-1 mRNA. Immunofluorescent staining was done for localization of intelectin-1 and quantitatively analyzed using computer-based image analysis. Western blot analysis was performed. Real-time PCR and Western blot analysis showed that intelectin-1 expression in nasal polyps was increased compared with normal sinus mucosa. Using immunofluorescent staining, intelectin-1 was strongly stained in epithelium and submucosa of nasal polyps, and faint staining was found in normal sinus mucosa. Intelectin-1 is expressed in human sinus mucosa and is increased in patients with nasal polyps. These results suggest a possible contribution for intelectin-1 in the pathophysiology of nasal polyps.

  8. Desmopressin Nasal

    MedlinePlus

    ... stop some types of bleeding in people with hemophilia (condition in which the blood does not clot ... When desmopressin nasal (Stimate®) is used to treat hemophilia and von Willebrand's disease, 1 to 2 spray(s) ...

  9. Alpha-dispersion in human tissue

    NASA Astrophysics Data System (ADS)

    Grimnes, Sverre; Martinsen, Ørjan G.

    2010-04-01

    Beta dispersion is found in living tissue in the kilohertz - megahertz range and is caused by the cellular structure of biological materials with low frequency properties caused by cell membranes. Alpha dispersion is found in the hertz range and the causes are not so well known. Alpha dispersions are the first to disappear when tissue dies. Tissue data have often been based upon excised specimen from animals and are therefore not necessarily representative for human tissue alpha dispersions. Here we present data obtained with non-invasive skin surface electrodes for different segments of the living human body. We found alpha dispersions in all cases; the ankle-wrist results had the smallest. Large alpha dispersions were found where the distance between the electrodes and muscle masses was small, e.g. on the calf. Further studies on electrode technique and reciprocity, electrode positioning, statistical variations, gender, age and bodily constitutions are necessary in order to reveal more about the alpha dispersion, its appearance and disappearance.

  10. Rheological characterization of human brain tissue.

    PubMed

    Budday, S; Sommer, G; Haybaeck, J; Steinmann, P; Holzapfel, G A; Kuhl, E

    2017-09-15

    The rheology of ultrasoft materials like the human brain is highly sensitive to regional and temporal variations and to the type of loading. While recent experiments have shaped our understanding of the time-independent, hyperelastic response of human brain tissue, its time-dependent behavior under various loading conditions remains insufficiently understood. Here we combine cyclic and relaxation testing under multiple loading conditions, shear, compression, and tension, to understand the rheology of four different regions of the human brain, the cortex, the basal ganglia, the corona radiata, and the corpus callosum. We establish a family of finite viscoelastic Ogden-type models and calibrate their parameters simultaneously for all loading conditions. We show that the model with only one viscoelastic mode and a constant viscosity captures the essential features of brain tissue: nonlinearity, pre-conditioning, hysteresis, and tension-compression asymmetry. With stiffnesses and time constants of μ∞=0.7kPa, μ1=2.0kPa, and τ1=9.7s in the gray matter cortex and μ∞=0.3kPa, μ1=0.9kPa and τ1=14.9s in the white matter corona radiata combined with negative parameters α∞ and α1, this five-parameter model naturally accounts for pre-conditioning and tissue softening. Increasing the number of viscoelastic modes improves the agreement between model and experiment, especially across the entire relaxation regime. Strikingly, two cycles of pre-conditioning decrease the gray matter stiffness by up to a factor three, while the white matter stiffness remains almost identical. These new insights allow us to better understand the rheology of different brain regions under mixed loading conditions. Our family of finite viscoelastic Ogden-type models for human brain tissue is simple to integrate into standard nonlinear finite element packages. Our simultaneous parameter identification of multiple loading modes can inform computational simulations under physiological conditions

  11. Nitric oxide in exhaled and aspirated nasal air as an objective measure of human response to indoor air pollution.

    PubMed

    Kolarik, B; Lagercrantz, L; Sundell, J

    2009-04-01

    The concentration of nitric oxide (NO) in exhaled and aspirated nasal air was used to objectively assess human response to indoor air pollutants in a climate chamber exposure experiment. The concentration of NO was measured before exposure, after 2, and 4.5 h of exposure, using a chemiluminescence NO analyzer. Sixteen healthy female subjects were exposed to two indoor air pollutants and to a clean reference condition for 4.5 h. Subjective assessments of the environment were obtained by questionnaires. After exposure (4.5 h) to the two polluted conditions a small increase in NO concentration in exhaled air was observed. After exposure to the reference condition the mean NO concentration was significantly reduced compared to pre-exposure. Together these changes resulted in significant differences in exhaled NO between exposure to reference and polluted conditions. NO in nasal air was not affected by the exposures. The results may indicate an association between polluted indoor air and subclinical inflammation. Measurement of nitric oxide in exhaled air is a possible objective marker of subclinical inflammation in healthy adults.

  12. The Impact of Pepsin on Human Nasal Epithelial Cells In Vitro: A Potential Mechanism for Extraesophageal Reflux Induced Chronic Rhinosinusitis.

    PubMed

    Southwood, Jessica E; Hoekzema, Craig R; Samuels, Tina L; Wells, Clive; Poetker, David M; Johnston, Nikki; Loehrl, Todd A

    2015-12-01

    To describe potential mechanisms by which pepsin induces inflammation in refractive chronic rhinosinusitis (CRS). Our hypothesis was that pepsin induces mitochondrial damage and cytokine expression in human nasal epithelial cells (HNEpC) in vitro. Western blot was used to detect pepsin in sinus lavages from patients with CRS and controls. The HNEpC cells were treated with pepsin (pH 7; 0.1 mg/mL) for 1 or 16 hours and routine electron microscopy (EM) and MTT assay were performed. Cytokine ELISA was performed on media collected from HNEpC cells 16 hours following a 1-hour pepsin treatment. Pepsin was detected in sinus lavages from 4 out of 6 CRS patients and 0 out of 3 controls. The EM showed mitochondrial damage in pepsin-treated HNEpC cells but not in control cells. The MTT assay demonstrated reduced mitochondrial activity in pepsin-treated HNEpC cells compared to controls (P < .001). Pepsin increased IL-1A (P = .003) and IL-6 (P = .04) expression in HNEpC cells. Pepsin in sinus lavages from patients with CRS is consistent with previous studies. This study reveals the damaging effect of pepsin on mitochondria in nasal epithelial cells in vitro. Cytokines previously associated with CRS were elevated following pepsin treatment of HNEpC cells in vitro. These results demonstrate mechanisms by which pepsin may potentiate CRS. © The Author(s) 2015.

  13. Ethyl acrylate risk assessment with a hybrid computational fluid dynamics and physiologically based nasal dosimetry model.

    PubMed

    Sweeney, Lisa M; Andersen, Melvin E; Gargas, Michael L

    2004-06-01

    Cytotoxicity in the nasal epithelium is frequently observed in rodents exposed to volatile organic acids and esters by inhalation. An interspecies, hybrid computational fluid dynamics and physiologically based pharmacokinetic (CFD-PBPK) dosimetry model for inhaled ethyl acrylate (EA) is available for estimating internal dose measures for EA, its metabolite acrylic acid (AA), and EA-mediated reductions in tissue glutathione (GSH). Nasal tissue concentrations of AA were previously used as the dose metric for a chronic Reference Concentration (RfC) calculation with this compound. However, EA was more toxic than expected, based on calculated tissue AA concentrations. Unlike AA, EA causes depletion of tissue GSH. We have developed an RfC for EA using tissue GSH depletion in the olfactory epithelium as the primary measure of nasal tissue dose. The hybrid CFD-PBPK model was refined to improve the accuracy of simulations for GSH in rat olfactory tissues. This refined model was used to determine the concentration for continuous human exposures to EA predicted to reduce nasal GSH levels to the same extent as seen in rats exposed to EA at the no-observed-effect level (NOEL). Importantly, AA concentrations in the human nasal olfactory epithelium at the proposed chronic RfC were predicted to be lower than the AA concentrations estimated in the rat at the NOEL. Thus, a chronic RfC based on maintaining GSH in the human nasal olfactory epithelium at levels equivalent to the rat NOEL would also provide an adequate margin of safety with respect to AA concentrations in nasal tissues.

  14. Formation of in vivo tissue engineered human hyaline cartilage in the shape of a trachea with internal support.

    PubMed

    Ruszymah, Binti Haji Idrus; Chua, Kienhui; Latif, Mazlyzam Abdul; Hussein, Fuzina Nor; Saim, Aminuddin Bin

    2005-11-01

    Treatment and management of congenital as well as post-traumatic trachea stenosis remains a challenge in pediatric surgery. The aim of this study was to reconstruct a trachea with human nasal septum chondrocytes by using the combination of biodegradable hydrogel and non-biodegradable high-density polyethylene (HDP) as the internal predetermined shape scaffold. Human nasal septum cartilage was harvested as excessive tissue after elective septoplasty and digested in 0.6% collagenase II. Chondrocytes were cultured in an equal volume mix of Ham's F12 medium and Dulbecco's modified eagle medium added with 10% fetal bovine serum and basic fibroblast growth factor. After two passages, the cultured chondrocytes were trypsinized and mixed with biodegradable hydrogel Pluronic F127. The chondrocytes-hydrogel admixture was then painted over the HDP as the internal support in a predetermined trachea shape. The composite was then implanted subcutaneously in athymic mice. After 8 weeks of in vivo implantation, the tissue engineered trachea constructs were harvested. Macroscopic appearance of the tissue engineered trachea constructs demonstrated that the HDP were 80-90% covered with yellowish glistering cartilage like tissue without any sign of inflammation. The tissue engineered trachea cartilage consisted of evenly spaced lacunae embedded in basophilic matrix and stained red with Safranin-O staining denoting abundant proteoglycans production. Type II collagen gene which was expressed in native cartilage was highly expressed in this tissue engineered trachea cartilage. We have successfully reconstructed a trachea in vivo with human nasal septum chondrocytes using HDP as the internal support. This construct has the advantage of bio-inert and strength in which both are important properties in tracheal reconstruction.

  15. Tissue microarray profiling in human heart failure.

    PubMed

    Lal, Sean; Nguyen, Lisa; Tezone, Rhenan; Ponten, Fredrik; Odeberg, Jacob; Li, Amy; Dos Remedios, Cristobal

    2016-09-01

    Tissue MicroArrays (TMAs) are a versatile tool for high-throughput protein screening, allowing qualitative analysis of a large number of samples on a single slide. We have developed a customizable TMA system that uniquely utilizes cryopreserved human cardiac samples from both heart failure and donor patients to produce formalin-fixed paraffin-embedded sections. Confirmatory upstream or downstream molecular studies can then be performed on the same (biobanked) cryopreserved tissue. In a pilot study, we applied our TMAs to screen for the expression of four-and-a-half LIM-domain 2 (FHL2), a member of the four-and-a-half LIM family. This protein has been implicated in the pathogenesis of heart failure in a variety of animal models. While FHL2 is abundant in the heart, not much is known about its expression in human heart failure. For this purpose, we generated an affinity-purified rabbit polyclonal anti-human FHL2 antibody. Our TMAs allowed high-throughput profiling of FHL2 protein using qualitative and semiquantitative immunohistochemistry that proved complementary to Western blot analysis. We demonstrated a significant relative reduction in FHL2 protein expression across different forms of human heart failure. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Post Septorhinoplasty Custom-Made Unilateral Nasal Stent for Nasal Cleft Deformity

    PubMed Central

    Rathee, Manu; Bhoria, Mohaneesh; Boora, Priyanka

    2015-01-01

    Context: Nasal cleft deformity is a complicated problem. Utilization of nasal stent in post septorhinoplastyaims at establishing and maintaining airway patency, tissue position, and reduces tissue contracture after surgery. Case Report: A 16-year-old female patient presented with history of surgical reconstruction of congenital cleft lip and cleft palate with secondary septorhinoplasty of nasal cleft deformity. Patient was referred for nasal stent 1 week after septorhinoplasty. This case report provides a novel technique for fabrication of esthetic nasal stent after postseptorhinoplasty for secondary cleft nose deformity correction. Conclusion: This case report presents a simple, convenient technique for nasal stent fabrication for prevention of restenosis for cleft nose deformity post secondary septorhinoplasty. Provision of nasal stent allows breathing, maintains esthetics, comfort, nasal patency, and contour with minimal discomfort. PMID:25789253

  17. UWB pulse propagation into human tissues

    NASA Astrophysics Data System (ADS)

    Cavagnaro, Marta; Pittella, Erika; Pisa, Stefano

    2013-12-01

    In this paper the propagation of a UWB pulse into a layered model of the human body is studied to characterize absorption and reflection of the UWB signal due to the different body tissues. Several time behaviours for the incident UWB pulse are considered and compared with reference to the feasibility of breath and heartbeat activity monitoring. Results show that if the UWB source is placed far from the human body, the reflection coming from the interface between air and skin can be used to detect the respiratory activity. On the contrary, if the UWB source is placed close to the human body, a small reflection due to the interface between the posterior lung wall and the bone, which is well distanced in time from the reflections due to the first layers of the body model, can be used to detect lung and heart changes associated with the cardio-respiratory activity.

  18. Bone tissue engineering with human stem cells

    PubMed Central

    2010-01-01

    Treatment of extensive bone defects requires autologous bone grafting or implantation of bone substitute materials. An attractive alternative has been to engineer fully viable, biological bone grafts in vitro by culturing osteogenic cells within three-dimensional scaffolds, under conditions supporting bone formation. Such grafts could be used for implantation, but also as physiologically relevant models in basic and translational studies of bone development, disease and drug discovery. A source of human cells that can be derived in large numbers from a small initial harvest and predictably differentiated into bone forming cells is critically important for engineering human bone grafts. We discuss the characteristics and limitations of various types of human embryonic and adult stem cells, and their utility for bone tissue engineering. PMID:20637059

  19. Mechanical characterization of human brain tissue.

    PubMed

    Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

    2017-01-15

    Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed

  20. Sorption studies of human keratinized tissues

    NASA Astrophysics Data System (ADS)

    Johnsen, G. K.; Martinsen, Ø. G.; Grimnes, Sverre

    2010-04-01

    Water content is known to be the most important single parameter for keratinized tissue to remain its vital functions. In that sense, a general knowledge of the water binding properties is of great interest, and a reliable measurement setup must be found. Also, revealing the sorption properties of human keratinized tissues is vital towards a calibration of susceptance based skin hydration measurements that already is an important diagnostic tool in clinical dermatology, and we will see that any hysteresis will complicate such a calibration further. In this study we investigated the sorption properties of keratinized tissues such as human epidermal stratum corneum (SC), hair and nail. The study was performed under controlled environmental conditions with a dynamic vapor sorption (DVS) instrument, and the water uptake of the keratinized test samples was measured as the relative humidity in the ambient air was altered step-wisely. In this study, vital and characteristic water sorption properties such as the isotherm, relative water uptake, and hysteresis were investigated and will be discussed.

  1. Effect of High, Medium, and Low Molecular Weight Hyaluronan on Inflammation and Oxidative Stress in an In Vitro Model of Human Nasal Epithelial Cells.

    PubMed

    Albano, Giusy Daniela; Bonanno, Anna; Cavalieri, Luca; Ingrassia, Eleonora; Di Sano, Caterina; Siena, Liboria; Riccobono, Loredana; Gagliardo, Rosalia; Profita, Mirella

    2016-01-01

    IL-17A is involved in the activation of oxidative stress and inflammation in nasal epithelial cells. Hyaluronan (HA) in its high molecular weight form (HMW-HA) shows anti-inflammatory responses in contrast to low and medium molecular weight HA (LMW-HA and MMW-HA). The aim of this study was to investigate the pro- or anti-inflammatory biologic function of HA at different molecular weight in an in vitro model of nasal inflammation IL-17A mediated. We evaluated the ERK1/2 and IκBα phosphorylation, NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 protein, and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rh) IL-17A. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA, and U0126. Our results showed that rhIL-17A increased the ERK1/2, IκBα phosphorylation and NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 proteins, and mRNA levels. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. IL-17A is able to generate oxidative stress and inflammation via the activation of ERK1/2/NF-κB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/antioxidative treatment of nasal epithelial cells during IL-17A nasal inflammation.

  2. Effect of High, Medium, and Low Molecular Weight Hyaluronan on Inflammation and Oxidative Stress in an In Vitro Model of Human Nasal Epithelial Cells

    PubMed Central

    Albano, Giusy Daniela; Bonanno, Anna; Cavalieri, Luca; Ingrassia, Eleonora; Di Sano, Caterina; Siena, Liboria; Riccobono, Loredana; Gagliardo, Rosalia; Profita, Mirella

    2016-01-01

    IL-17A is involved in the activation of oxidative stress and inflammation in nasal epithelial cells. Hyaluronan (HA) in its high molecular weight form (HMW-HA) shows anti-inflammatory responses in contrast to low and medium molecular weight HA (LMW-HA and MMW-HA). The aim of this study was to investigate the pro- or anti-inflammatory biologic function of HA at different molecular weight in an in vitro model of nasal inflammation IL-17A mediated. We evaluated the ERK1/2 and IκBα phosphorylation, NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 protein, and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rh) IL-17A. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA, and U0126. Our results showed that rhIL-17A increased the ERK1/2, IκBα phosphorylation and NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 proteins, and mRNA levels. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. IL-17A is able to generate oxidative stress and inflammation via the activation of ERK1/2/NF-κB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/antioxidative treatment of nasal epithelial cells during IL-17A nasal inflammation. PMID:27212811

  3. Human Nasopharyngeal-Associated Lymphoreticular Tissues

    PubMed Central

    Boyaka, Prosper N.; Wright, Peter F.; Marinaro, Mariarosaria; Kiyono, Hiroshi; Johnson, Joyce E.; Gonzales, Ricardo A.; Ikizler, Mine R.; Werkhaven, Jay A.; Jackson, Raymond J.; Fujihashi, Kohtaro; Di Fabio, Simonetta; Staats, Herman F.; McGhee, Jerry R.

    2000-01-01

    Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic immune responses. The distribution of T and B cell subsets, cytokine patterns, and antibody (Ab) isotype profiles were similar for adenoids and tonsils. Both tissues contained predominantly B cells (∼65%), approximately 5% macrophages, and 30% CD3+ T cells. The T cells were primarily of the CD4+ subset (∼80%). Tonsillar intraepithelial lymphocytes were also enriched in B cells. The analysis of dispersed cells revealed a higher frequency of cells secreting IgG than IgA and the predominant Ig subclass profiles were IgG1 > IgG3 and IgA1 > IgA2, respectively. In situ analysis also revealed higher numbers of IgG- than IgA-positive cells. These IgG-positive cells were present in the epithelium and in the subepithelial zones of both tonsils and adenoids. Mitogen-triggered T cells from tonsils and adenoids produced both Th1- and Th2-type cytokines, clearly exhibiting their pluripotentiality for support of cell-mediated and Ab responses. Interestingly, antigen-specific T cells produced interferon-γ and lower levels of interleukin-5. These results suggest that adenoids and tonsils of the nasopharyngeal-associated lymphoreticular tissues represent a distinct component of the mucosal-associated lymphoreticular tissues with features of both systemic and mucosal compartments. PMID:11106575

  4. Triloculotrema euzeti n. sp. (Monogenea, Monocotylidae) from the nasal tissues of the blackspotted smooth-hound Mustelus punctulatus (Carcharhiniformes, Triakidae) from off Tunisia

    PubMed Central

    2016-01-01

    Triloculotrema euzeti n. sp. (Monogenea, Monocotylidae, Merizocotylinae) is described from the nasal tissues of the blackspotted smooth-hound Mustelus punctulatus collected from the coastal marine waters off Tunisia. The new parasite species is distinguished from the other two species of the genus, T. japanicae Kearn, 1993 and T. chisholmae Justine, 2009, by the morphology of the sclerotised male copulatory organ which has longitudinal ridges. The species is also characterised by its oötype with short descending and ascending limbs (long and more convoluted in the other two species). The presence of three peripheral loculi, which is the main characteristic of the genus Triloculotrema Kearn, 1993, is unconfirmed. This is the first description of a species of this genus in the Mediterranean Sea and the first record from a coastal shark. PMID:28008824

  5. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features.

    PubMed

    Yu, Guoqin; Gail, Mitchell H; Consonni, Dario; Carugno, Michele; Humphrys, Michael; Pesatori, Angela C; Caporaso, Neil E; Goedert, James J; Ravel, Jacques; Landi, Maria Teresa

    2016-07-28

    The human lung tissue microbiota remains largely uncharacterized, although a number of studies based on airway samples suggest the existence of a viable human lung microbiota. Here we characterized the taxonomic and derived functional profiles of lung microbiota in 165 non-malignant lung tissue samples from cancer patients. We show that the lung microbiota is distinct from the microbial communities in oral, nasal, stool, skin, and vagina, with Proteobacteria as the dominant phylum (60 %). Microbiota taxonomic alpha diversity increases with environmental exposures, such as air particulates, residence in low to high population density areas, and pack-years of tobacco smoking and decreases in subjects with history of chronic bronchitis. Genus Thermus is more abundant in tissue from advanced stage (IIIB, IV) patients, while Legionella is higher in patients who develop metastases. Moreover, the non-malignant lung tissues have higher microbiota alpha diversity than the paired tumors. Our results provide insights into the human lung microbiota composition and function and their link to human lifestyle and clinical outcomes. Studies among subjects without lung cancer are needed to confirm our findings.

  6. Application of physiological computational fluid dynamics models to predict interspecies nasal dosimetry of inhaled acrolein.

    PubMed

    Schroeter, Jeffry D; Kimbell, Julia S; Gross, Elizabeth A; Willson, Gabrielle A; Dorman, David C; Tan, Yu-Mei; Clewell, Harvey J

    2008-02-01

    Acrolein is a highly soluble and reactive aldehyde and is a potent upper-respiratory-tract irritant. Acrolein-induced nasal lesions in rodents include olfactory epithelial atrophy and inflammation, epithelial hyperplasia, and squamous metaplasia of the respiratory epithelium. Nasal uptake of inhaled acrolein in rats is moderate to high, and depends on inspiratory flow rate, exposure duration, and concentration. In this study, anatomically accurate three-dimensional computational fluid dynamics (CFD) models were used to simulate steady-state inspiratory airflow and to quantitatively predict acrolein tissue dose in rat and human nasal passages. A multilayered epithelial structure was included in the CFD models to incorporate clearance of inhaled acrolein by diffusion, blood flow, and first-order and saturable metabolic pathways. Kinetic parameters for these pathways were initially estimated by fitting a pharmacokinetic model with a similar epithelial structure to time-averaged acrolein nasal extraction data and were then further adjusted using the CFD model. Predicted air:tissue flux from the rat nasal CFD model compared well with the distribution of acrolein-induced nasal lesions from a subchronic acrolein inhalation study. These correlations were used to estimate a tissue dose-based no-observed-adverse-effect level (NOAEL) for inhaled acrolein. A human nasal CFD model was used to extrapolate effects in laboratory animals to human exposure conditions on the basis of localized tissue dose and tissue responses. Assuming that equivalent tissue dose will induce similar effects across species, a NOAEL human equivalent concentration for inhaled acrolein was estimated to be 8 ppb.

  7. Nickel content of human palatine tonsils: analysis of small tissue samples by flameless atomic absorption spectrophotometry.

    PubMed

    Torjussen, W; Andersen, I; Zachariasen, H

    1977-06-01

    We describe a method for determining the nickel content of small tissue samples by flameless atomic absorption spectrophotometry in this case biopsy specimens from human palatine tonsils. Contact between tissue samples and metallic objects was avoided, except for the use of biopsy forceps (Type No. 8150.00 Wolf, stainless steel) for collecting samples, to imitate the actual procedure when small biopsy specimens are removed from the nasal mucosal membranes in nickel workers for histopathological and chemical investigations. Nickel contamination from this instrument was insignificant at the precision of the present procedures. The mean concentration of nickel in 15 tonsils was 13.5 +/- 7.0 (SD) microng/100g (wet wt). The mean nickel concentration in eight different samples of the same tonsil was 5.6 +/- 2.7 (SD microng/100 g.

  8. Osseous differentiation of human fat tissue grafts: From tissue engineering to tissue differentiation

    PubMed Central

    Bondarava, Maryna; Cattaneo, Chiara; Ren, Bin; Thasler, Wolfgang E.; Jansson, Volkmar; Müller, Peter E.; Betz, Oliver B.

    2017-01-01

    Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9. Ca2+ depositions were observed after two weeks of osteogenic induction which visibly increased when either type of BMP was added. mRNA levels of alkaline phosphatase (ALP) and osteocalcin (OCN) increased when cultured in OM alone but addition of BMP-2, BMP-7 or BMP-9 caused significantly higher expression levels of ALP and OCN. Immunofluorescent staining for OCN, osteopontin and sclerostin supported the observed real-time-PCR data. BMP-9 was the most effective osteogenic inducer in this system. Our findings reveal that tissue regeneration can be remarkably simplified by omitting prior cell isolation and propagation, therefore removing significant obstacles on the way to clinical applications of much needed regeneration treatments. PMID:28054585

  9. Proteomic analysis of human nasal mucosa: different expression profile in rhino-pathologic states.

    PubMed

    Gelardi, M; Siciliano, R A; Papa, F; Mazzeo, M F; De Nitto, E; Quaranta, N; Lippolis, R

    2014-09-01

    Rhinitis comprises several diseases with varying causes and different clinical manifestations and pathological features, but treated as a single clinical disorder. As heterogeneous disease, proper differential diagnosis is useful to delineate appropriate therapeutic intervention. Comparative proteomic investigation was aimed to provide information for specific differentially expressed proteins in rhino pathologic state, that could be used for diagnostic purpose and therapeutic monitoring. Proteins extracted from nasal mucosa cells of patients with different features of rhinitis and from control subjects, were separated by 2-DE. Proteins differentially expressed were identified by mass spectrometry (MS). Comparative proteomic analyses led to the identification of eighteen proteins differentially expressed in patients with rhinitis, mainly related to cell defense and innate and acquired immunity. From that, at least one protein can be a possible candidate as biomarker of disease.

  10. Analysis of the human osseous nasal shape--population differences and sexual dimorphism.

    PubMed

    Schlager, Stefan; Rüdell, Alexandra

    2015-08-01

    In this study, the shape of the outer osseous nose in a German and a Chinese sample is analyzed using a dense set of semi-landmarks. Shape differences related to population and sex as well as directional and fluctuating asymmetry were statistically evaluated and also visualized. Shape differences in the bony nose were investigated between a large sample of CT scans of German (140 ♀, 127 ♂) and Chinese (135 ♀, 132 ♂) crania. We used semi-automatic methods to represent the shape of this region as a dense point-cloud, consisting of 370 three-dimensional bilateral coordinates. Both the symmetric and asymmetric modes of shape variation were addressed. Strong differences in nasal shape were found between the two populations, while sex was found to play a minor role in explaining the observed shape variation. The expression of sexual dimorphism was similar in both populations. Differences attributed to population affinity and to sexual dimorphism were both found to affect the shape of the ossa nasalia and the projection of the spina nasalis. The correlation with population/sex was weak for directional asymmetry, but strong for fluctuating asymmetry. The nasal region is more asymmetric in Germans than in Chinese, with males displaying more asymmetry than females in both populations. While the bony nose is well suited for predicting population affinity, regarding the populations under investigation, its value for sexing unknown individuals is rather moderate. The similar expression of sexual dimorphism in those otherwise very dissimilar populations indicates common factors responsible for these differences. © 2015 Wiley Periodicals, Inc.

  11. Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures.

    PubMed

    Franco, I; Ortiz-López, L; Roque-Ramírez, B; Ramírez-Rodríguez, G B; Lamas, M

    2017-05-01

    Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2-P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs). We evaluated and compared cellular morphology, proliferation rates and the expression pattern of pluripotency-associated markers and DNA methylation-associated gene expression in these cultures. Neuronal differentiation was induced by exposure to all-trans retinoic acid and forskolin for 7 days and evaluated by morphological analysis and immunofluorescence against neuronal markers MAP2, NSE and MAP1B. In response to the inductive cues mNOS/PCs expressed NSE (75.67%) and MAP2 (35.34%); whereas the majority of the hNOS/PCs were immunopositive to MAP1B. Treatment with procainamide, a specific inhibitor of DNA methyltransferase 1 (DNMT1), increases in the number of forskolin'/retinoic acid-induced mature neuronal marker-expressing mNOS/PCs cells and enhances neurite development in hNOS/PCs. Our results indicate that mice and human nasal olfactory stem/progenitors cells share pluripotency-related gene expression suggesting that their application for stem cell therapy is worth pursuing and that DNA methylation inhibitors could be efficient tools to enhance neuronal differentiation from these cells.

  12. Proton-coupled oligopeptide transporter (POT) family expression in human nasal epithelium and their drug transport potential.

    PubMed

    Agu, Remigius; Cowley, Elizabeth; Shao, Di; Macdonald, Christopher; Kirkpatrick, David; Renton, Ken; Massoud, Emad

    2011-06-06

    The molecular and functional expression of peptide transporters (PEPT1 and PEPT2, PHT1, PHT2) in human nasal epithelium was investigated. Quantitative/reverse transcriptase polymerase chain reaction (qPCR/RT-PCR), Western blotting and indirect immuno-histochemistry were used to investigate the functional gene and protein expression for the transporters. Uptake and transport studies were performed using metabolically stable peptides [β-alanyl-L-lysyl-Nε-7-amino-4-methyl-coumarin-3-acetic acid (β-Ala-Lys-AMCA) and β-alanyl-L-histidine (carnosine)]. The effects of concentration, temperature, polarity, competing peptides, and inhibitors on peptide uptake and transport were investigated. PCR products corresponding to PEPT1 (150 bp), PEPT2 (127 bp), PHT1 (110 bp) and PHT2 (198 bp) were detected. Immunohistochemistry and Western blotting confirmed the functional expression of PEPT1 and PEPT2 genes. The uptake of β-Ala-Lys-AMCA was concentration-dependent and saturable (Vmax =4.1 ( 0.07 μmol/min/mg protein, Km = 0.6 ( 0.07 μM). The optimal pH for intracellular accumulation of β-Ala-Lys-AMCA was 6.5. Whereas dipeptides and carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly inhibited peptide uptake and transport, L-Phe had no effect on peptide transport. The permeation of β-alanyl-L-histidine was concentration-, direction-, and temperature-dependent. The uptake, permeation, qPCR/RT-PCR and protein expression data showed that the human nasal epithelium functionally expresses proton-coupled oligopeptide transporters.

  13. Critical factors in assessing risk from exposure to nasal carcinogens.

    PubMed

    Bogdanffy, M S; Mathison, B H; Kuykendall, J R; Harman, A E

    1997-10-31

    Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.

  14. Autologous human nasal epithelial cell sheet using temperature-responsive culture insert for transplantation after middle ear surgery.

    PubMed

    Hama, Takanori; Yamamoto, Kazuhisa; Yaguchi, Yuichiro; Murakami, Daisuke; Sasaki, Hiroyuki; Yamato, Masayuki; Okano, Teruo; Kojima, Hiromi

    2017-04-01

    Postoperative mucosal regeneration of the middle ear cavity and the mastoid cavity is of great importance after middle ear surgery. However, the epithelialization of the mucosa in the middle ear is retarded because chronic inflammation without epithelialization aggravates gas exchange and clinical function. These environmental conditions in the middle ear lead to postoperative retraction and adhesion of the newly-formed tympanic membrane. Therefore, if the mucosa on the exposed middle ear bone surface can be rapidly regenerated after surgery, the surgical treatments for cholesteatoma and adhesive middle ear disease can potentially be improved. In this study, we successfully generated a cell sheet designed for the postoperative treatment of cholesteatoma. We used nasal cells to create an artificial middle ear mucosal cell sheet with a three-dimensional (3D) configuration similar to that of the middle ear mucosa. The sheets consisted of multi-layered mucosal epithelia and lower connective tissue and were similar to normal middle ear mucosa. This result indicates that tissue-engineered mucosal cell sheets would be useful to minimize complications after surgical operations in the middle ear and future clinical applications are expected. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques

    SciTech Connect

    Carey, Stephen A.; Minard, Kevin R.; Trease, Lynn L.; Wagner, James G.; Garcia, Guilherme M.; Ballinger, Carol A.; Kimbell, Julia; Plopper, Charles G.; Corley, Rick A.; Postlewait, Ed; Harkema, Jack R.

    2007-03-01

    ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.

  16. Hippocampus and epilepsy: findings from human tissues

    PubMed Central

    Huberfeld, Gilles; Blauwblomme, Thomas; Miles, Richard

    2015-01-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including (1) temporal lobe epilepsies with hippocampal sclerosis, (2) cortical dysplasias, (3) epilepsies associated with tumors and (4) developmental malformations. Slices of tissue from patient with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum an output region which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide, restores intracellular chloride and thus hyperpolarizing GABAergic actions so suppressing interictal activity. PMID

  17. Visual exploration of nasal airflow.

    PubMed

    Zachow, Stefan; Muigg, Philipp; Hildebrandt, Thomas; Doleisch, Helmut; Hege, Hans-Christian

    2009-01-01

    Rhinologists are often faced with the challenge of assessing nasal breathing from a functional point of view to derive effective therapeutic interventions. While the complex nasal anatomy can be revealed by visual inspection and medical imaging, only vague information is available regarding the nasal airflow itself: Rhinomanometry delivers rather unspecific integral information on the pressure gradient as well as on total flow and nasal flow resistance. In this article we demonstrate how the understanding of physiological nasal breathing can be improved by simulating and visually analyzing nasal airflow, based on an anatomically correct model of the upper human respiratory tract. In particular we demonstrate how various Information Visualization (InfoVis) techniques, such as a highly scalable implementation of parallel coordinates, time series visualizations, as well as unstructured grid multi-volume rendering, all integrated within a multiple linked views framework, can be utilized to gain a deeper understanding of nasal breathing. Evaluation is accomplished by visual exploration of spatio-temporal airflow characteristics that include not only information on flow features but also on accompanying quantities such as temperature and humidity. To our knowledge, this is the first in-depth visual exploration of the physiological function of the nose over several simulated breathing cycles under consideration of a complete model of the nasal airways, realistic boundary conditions, and all physically relevant time-varying quantities.

  18. Nasal bots...a fascinating world!

    PubMed

    Angulo-Valadez, Carlos E; Scholl, Philip J; Cepeda-Palacios, Ramón; Jacquiet, Philippe; Dorchies, Philippe

    2010-11-24

    Larvae causing obligatory myiasis are numerous and they may affect cutaneous and subcutaneous tissues, wounds, nasopharyngeal cavities (nasal bots), internal organs and the digestive tract (bots) of domestic and wild animals and humans as well. Nasal bots belong to the Family Oestridae, Subfamily Oestrinae, which includes several important genera: Oestrus, Kirkioestrus, and Gedoelstia infecting Artiodactyla (except Cervidae) in Africa and Eurasia, Cephenemyia and Pharyngomyia infecting Cervidae, Rhinoestrus infecting horses, Cephalopina infecting camels, Pharyngobolus infecting African elephants, and Tracheomyia infecting Australian kangaroos. Nasal bots are widespread in Mediterranean and tropical areas and in affected animals they induce sneezing and nasal discharge which may become caked with dust making breathing very difficult. The aforementioned species of larvae are host-specific but sometimes the may be deposited in human eyes inducing a painful opthalmomyiasis of short duration. The first fascinating trait of these parasites is the very efficient morphological and biological adaptations to parasitism they show either as larvae or as adults, in order to facilitate their survival and search for a suitable host. Nasal bots have reached different degrees of complexity in their life cycles. Indeed, while for some species (e.g., Oestrus ovis, Rhinoestrus usbekistanicus) larvae are injected by flies directly into nostrils and develop in the sinuses before being ejected for external pupation, some other species migrate from eyes to blood before returning to nasal cavities either through the ethmoid bone (Gedoelstia hässleri) or via lungs and bronchi (Gedoelstia cristata). Moreover, larvae are very well-adapted to their environment being able to undergo through hypobiosis either inside or outside the host, according to the climatic environmental conditions and seasonality. The second fascinating trait of nasal bots is related to host behavioural and immune

  19. The nose revisited: a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium.

    PubMed

    Harkema, Jack R; Carey, Stephan A; Wagner, James G

    2006-01-01

    The nose is a very complex organ with multiple functions that include not only olfaction, but also the conditioning (e.g., humidifying, warming, and filtering) of inhaled air. The nose is also a "scrubbing tower" that removes inhaled chemicals that may be harmful to the more sensitive tissues in the lower tracheobronchial airways and pulmonary parenchyma. Because the nasal airway may also be a prime target for many inhaled toxicants, it is important to understand the comparative aspects of nasal structure and function among laboratory animals commonly used in inhalation toxicology studies, and how nasal tissues and cells in these mammalian species may respond to inhaled toxicants. The surface epithelium lining the nasal passages is often the first tissue in the nose to be directly injured by inhaled toxicants. Five morphologically and functionally distinct epithelia line the mammalian nasal passages--olfactory, respiratory, squamous, transitional, and lymphoepithelial--and each nasal epithelium may be injured by an inhaled toxicant. Toxicant-induced epithelial lesions in the nasal passages of laboratory animals (and humans) are often site-specific and dependent on the intranasal regional dose of the inhaled chemical and the sensitivity of the nasal epithelial tissue to the specific chemical. In this brief review, we present examples of nonneoplastic epithelial lesions (e.g., cell death, hyperplasia, metaplasia) caused by single or repeated exposure to various inhaled chemical toxicants. In addition, we provide examples of how nasal maps may be used to record the character, magnitude and distribution of toxicant-induced epithelial injury in the nasal airways of laboratory animals. Intranasal mapping of nasal histopathology (or molecular and biochemical alterations to the nasal mucosa) may be used along with innovative dosimetric models to determine dose/response relationships and to understand if site-specific lesions are driven primarily by airflow, by tissue

  20. [Localization and distribution of human olfactory mucosa in the nasal cavities].

    PubMed

    Escada, Pedro

    2013-01-01

    Introdução: A distribuição da mucosa olfactiva humana só pode ser determinada em estudos que avaliem a totalidade da região olfactiva. O objectivo deste trabalho é determinar a distribuição da mucosa olfactiva humana a partir do estudo histológico, por microscopia óptica, de peças anatómicas da região olfactiva obtidas do cadáver.Material e Métodos: Utilizaram-se peças anatómicas da região olfactiva colhidas durante a autópsia de cadáveres recentes. Em cada uma das peças foi determinada a distância entre a lâmina crivosa e o limite inferior da região olfactiva em três localizações diferentes da parede septal e da parede lateral.Resultados: das 230 peças anatómicas disponíveis, 217 foram excluídas por razões clínicas ou técnicas. Realizaram-se estudosmorfométricos em 13 peças num total de 156 medições. O limite inferior da mucosa olfactiva no septo nasal estava a 15,9 ± 3,2 mm, a 15,3 ± 3 mm e a 16 ± 2,8 mm nas porções anterior, média e posterior da região olfactiva. O limite inferior da mucosa olfactiva na parede turbinal estava a 15,3 ± 2,4 mm, a 14,8 ± 2,3 mm e a 12,3 ± 1,9 mm nas mesmas localizações. O valor mínimo observado foi de 12 mm.Conclusões: A mucosa olfactiva estende-se pelo corneto superior e médio e pelo septo nasal confrontante numa distância que nunca é inferior a 12 mm e que pode ultrapassar os 16 mm. O conhecimento da distribuição exacta da mucosa olfactiva nas fossas nasais pode ser útil para orientar a colheita em seres humanos, com propósitos diagnósticos ou terapêuticos.

  1. Responses of primary human nasal epithelial cells to EDIII-DENV stimulation: the first step to intranasal dengue vaccination.

    PubMed

    Nantachit, Nattika; Sunintaboon, Panya; Ubol, Sukathida

    2016-08-18

    About half of the world's population are living in the endemic area of dengue viruses implying that a rapid-mass vaccination may be required. In addition, a major target of dengue vaccine are children, thus, a needle-free administration is more attractive. These problems may be overcome by the alternative route of vaccination such as topical, oral and intranasal vaccination. Here, we investigated the possibility to deliver a dengue immunogen intranasally, a painless route of vaccination. The tested immunogen was the domain III of dengue serotype-3 E protein (EDIII-D3) loaded into trimethyl chitosan nanoparticles (EDIII-D3 TMC NPs). The primary human nasal epithelial cells, HNEpCs, were used as an in vitro model for nasal responses. At tested concentrations, EDIII-D3 TMC NPs not only exerted no detectable toxicity toward HNEpC cultures but also efficiently delivered EDIII-D3 immunogens into HNEpCs. Moreover, HNEpCs quickly and strongly produced proinflammatory cytokines (IL-1β, IL-6, TNF-α), type-I IFN, the growth factors (GM-CSF, IL-7), the chemokines (MCP-1, MIP-1β, IL-8), Th1-related cytokines (IL-2, IL-12p70, IL-17, IFN-γ) and Th2-related cytokine (IL-4) in response to EDIII-D3 TMC NPs treatment. A potential mucosal delivery system for dengue immunogens was revealed and found to stimulate a strong local innate antiviral response which possibly leading to a systemic adaptive immunity.

  2. The reconstruction and analysis of tissue specific human metabolic networks.

    PubMed

    Hao, Tong; Ma, Hong-Wu; Zhao, Xue-Ming; Goryanin, Igor

    2012-02-01

    Human tissues have distinct biological functions. Many proteins/enzymes are known to be expressed only in specific tissues and therefore the metabolic networks in various tissues are different. Though high quality global human metabolic networks and metabolic networks for certain tissues such as liver have already been studied, a systematic study of tissue specific metabolic networks for all main tissues is still missing. In this work, we reconstruct the tissue specific metabolic networks for 15 main tissues in human based on the previously reconstructed Edinburgh Human Metabolic Network (EHMN). The tissue information is firstly obtained for enzymes from Human Protein Reference Database (HPRD) and UniprotKB databases and transfers to reactions through the enzyme-reaction relationships in EHMN. As our knowledge of tissue distribution of proteins is still very limited, we replenish the tissue information of the metabolic network based on network connectivity analysis and thorough examination of the literature. Finally, about 80% of proteins and reactions in EHMN are determined to be in at least one of the 15 tissues. To validate the quality of the tissue specific network, the brain specific metabolic network is taken as an example for functional module analysis and the results reveal that the function of the brain metabolic network is closely related with its function as the centre of the human nervous system. The tissue specific human metabolic networks are available at .

  3. Depicting the inner and outer nose: the representation of the nose and the nasal mucosa on the human primary somatosensory cortex (SI).

    PubMed

    Gastl, Mareike; Brünner, Yvonne F; Wiesmann, Martin; Freiherr, Jessica

    2014-09-01

    The nose is important not only for breathing, filtering air, and perceiving olfactory stimuli. Although the face and hands have been mapped, the representation of the internal and external surface of the nose on the primary somatosensory cortex (SI) is still poorly understood. To fill this gap functional magnetic resonance imaging (fMRI) was used to localize the nose and the nasal mucosa in the Brodman areas (BAs) 3b, 1, and 2 of the human postcentral gyrus (PG). Tactile stimulation during fMRI was applied via a customized pneumatically driven device to six stimulation sites: the alar wing of the nose, the lateral nasal mucosa, and the hand (serving as a reference area) on the left and right side of the body. Individual representations could be discriminated for the left and right hand, for the left nasal mucosa and left alar wing of the nose in BA 3b and BA 1 by comparing mean activation maxima and Euclidean distances. Right-sided nasal conditions and conditions in BA 2 could further be separated by different Euclidean distances. Regarding the alar wing of the nose, the results concurred with the classic sensory homunculus proposed by Penfield and colleagues. The nasal mucosa was not only determined an individual and bilateral representation, its position on the somatosensory cortex is also situated closer to the caudal end of the PG compared to that of the alar wing of the nose and the hand. As SI is commonly activated during the perception of odors, these findings underscore the importance of the knowledge of the representation of the nasal mucosa on the primary somatosensory cortex, especially for interpretation of results of functional imaging studies about the sense of smell.

  4. Coefficient of Friction of Human Corneal Tissue.

    PubMed

    Wilson, Tawnya; Aeschlimann, Rudolf; Tosatti, Samuele; Toubouti, Youssef; Kakkassery, Joseph; Osborn Lorenz, Katherine

    2015-09-01

    A novel property evaluation methodology was used to determine the elusive value for the human corneal coefficient of friction (CoF). Using a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF was determined in 4 test solutions (≥5 corneas/solution): tear-mimicking solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid in PBS (TLF-PBS). Mean (SD) CoF values ranged from 0.006 to 0.015 and were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS-HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P = 0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). Successful measurement of the fresh human corneal tissue CoF was demonstrated, with values differing in the evaluated buffer solutions, within this limited sample size.

  5. [Microbiocenosis of the human nasal mucous membrane in the conditions of industrial city].

    PubMed

    Voĭtovich, A V

    2013-12-01

    In this work we studied the effect of industrial pollution on the mechanisms involved in the adaptation of the nasal microbiocenosis of healthy residents of the industrial city to external influences. In the given biotop composition of the microbiota and its biological properties, as well as the specific indicators of rhinocytogram and expression of TLR-2 and TLR-4 cells of the mucous membranes have been studied. Accommodation in relatively polluted industrial areas of the city induces an increase in the population of coagulase positive staphylococci and improve their adhesion activity, as well as strengthens destructive processes in the epithelium. Analysis of resistance phenotypes of staphylococcus showed that around 30 % of the strains of coagulase negative staphylococci and about 20 % of the strains of coagulase positive staphylococci have phenotype mecA. Among coagulase negative staphylococci higher number of strains with multiple resistance to β- lactams, aminoglycosides, and antibiotics of MLS group have been revealed. To such changes in the components of microbiocenosis the cells of the mucous membrane of the nose react by increasing the numbers of TLR-2+ epithelial cells, increased expression of TLR-2 by epithelial cells and reduced expression of TLR-4 by neutrophils.

  6. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

    PubMed

    Rygg, Alex; Hindle, Michael; Longest, P Worth

    2016-04-01

    The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  7. Immunoglobulins in Nasal Secretions of Healthy Humans: Structural Integrity of Secretory Immunoglobulin A1 (IgA1) and Occurrence of Neutralizing Antibodies to IgA1 Proteases of Nasal Bacteria

    PubMed Central

    Kirkeby, Line; Rasmussen, Trine Tang; Reinholdt, Jesper; Kilian, Mogens

    2000-01-01

    Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro. Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11 healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and, subsequently, concentrations in undiluted secretions could thereby be calculated. IgA, mainly in the secretory form, was found by enzyme-linked immunosorbent assay to be the dominant isotype in all subjects, and the vast majority of IgA (median, 91%) was of the A1 subclass, corroborating results of previous analyses at the level of immunoglobulin-producing cells. Levels of serum-type immunoglobulins were low, except for four subjects in whom levels of IgG corresponded to 20 to 66% of total IgA. Cumulative levels of IgA, IgG, and IgM in undiluted secretions ranged from 260 to 2,494 (median, 777) μg ml−1. IgA1 protease-producing bacteria (Haemophilus influenzae, Streptococcus pneumoniae, or Streptococcus mitis biovar 1) were isolated from the nasal cavities of seven subjects at 2.1 × 103 to 7.2 × 106 CFU per ml of undiluted secretion, corresponding to 0.2 to 99.6% of the flora. Nevertheless, α-chain fragments characteristic of IgA1 protease activity were not detected in secretions from any subject by immunoblotting. Neutralizing antibodies to IgA1 proteases of autologous

  8. Rapid Chondrocyte Isolation for Tissue Engineering Applications: The Effect of Enzyme Concentration and Temporal Exposure on the Matrix Forming Capacity of Nasal Derived Chondrocytes

    PubMed Central

    Vedicherla, Srujana

    2017-01-01

    Laboratory based processing and expansion to yield adequate cell numbers had been the standard in Autologous Disc Chondrocyte Transplantation (ADCT), Allogeneic Juvenile Chondrocyte Implantation (NuQu®), and Matrix-Induced Autologous Chondrocyte Implantation (MACI). Optimizing cell isolation is a key challenge in terms of obtaining adequate cell numbers while maintaining a vibrant cell population capable of subsequent proliferation and matrix elaboration. However, typical cell yields from a cartilage digest are highly variable between donors and based on user competency. The overall objective of this study was to optimize chondrocyte isolation from cartilaginous nasal tissue through modulation of enzyme concentration exposure (750 and 3000 U/ml) and incubation time (1 and 12 h), combined with physical agitation cycles, and to assess subsequent cell viability and matrix forming capacity. Overall, increasing enzyme exposure time was found to be more detrimental than collagenase concentration for subsequent viability, proliferation, and matrix forming capacity (sGAG and collagen) of these cells resulting in nonuniform cartilaginous matrix deposition. Taken together, consolidating a 3000 U/ml collagenase digest of 1 h at a ratio of 10 ml/g of cartilage tissue with physical agitation cycles can improve efficiency of chondrocyte isolation, yielding robust, more uniform matrix formation. PMID:28337445

  9. Variation in tissue outcome of ovine and human engineered heart valve constructs: relevance for tissue engineering.

    PubMed

    van Geemen, Daphne; Driessen-Mol, Anita; Grootzwagers, Leonie G M; Soekhradj-Soechit, R Sarita; Riem Vis, Paul W; Baaijens, Frank P T; Bouten, Carlijn V C

    2012-01-01

    Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and tissue properties of ovine (n = 8) and human (n = 7) tissue engineered heart valve constructs to quantify variations in tissue outcome within species, study the differences between species and determine possible indicators of tissue outcome. Tissue constructs consisted of polyglycolic acid/poly-4-hydroxybutyrate scaffolds, seeded with myofibroblasts obtained from the jugular vein (sheep) or the saphenous vein (from humans undergoing cardiac surgery) and cultured under static conditions. Prior to seeding, protein expression of α-smooth muscle actin, vimentin, nonmuscle myosin heavy chain and heat shock protein 47 were determined to identify differences at an early stage of the tissue engineering process. After 4 weeks of culture, tissue composition and mechanical properties were quantified as indicators of tissue outcome. After 4 weeks of tissue culture, tissue properties of all ovine constructs were comparable, while there was a larger variation in the properties of the human constructs, especially the elastic modulus and collagen content. In addition, ovine constructs differed in composition from the human constructs. An increased number of α-smooth muscle actin-positive cells before seeding was correlated with the collagen content in the engineered heart valve constructs. Moreover, tissue stiffness increased with increasing collagen content. The results suggest that the culture process of ovine tissues can be controlled, whereas the mechanical properties, and hence functionality, of tissues originating from human material are more difficult to control. On-line evaluation of tissue properties during culture or more early cellular markers to predict the properties of autologous

  10. 2010 Great Lakes Human Health Fish Tissue Study Fish Tissue Data Dictionary

    EPA Pesticide Factsheets

    The Office of Science and Technology (OST) is providing the fish tissue results from the 2010 Great Lakes Human Health Fish Tissue Study (GLHHFTS). This document includes the “data dictionary” for Mercury, PFC, PBDE and PCBs.

  11. Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells.

    PubMed

    Khoufache, Khaled; Puel, Olivier; Loiseau, Nicolas; Delaforge, Marcel; Rivollet, Danièle; Coste, André; Cordonnier, Catherine; Escudier, Estelle; Botterel, Françoise; Bretagne, Stéphane

    2007-01-23

    The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds. We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model. The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10(-8) M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts. Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined.

  12. Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells

    PubMed Central

    Khoufache, Khaled; Puel, Olivier; Loiseau, Nicolas; Delaforge, Marcel; Rivollet, Danièle; Coste, André; Cordonnier, Catherine; Escudier, Estelle; Botterel, Françoise; Bretagne, Stéphane

    2007-01-01

    Background The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds. Results We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model. The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10-8 M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts. Conclusion Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined. PMID:17244350

  13. Assessment of nasal spray deposition pattern in a silicone human nose model using a color-based method.

    PubMed

    Kundoor, Vipra; Dalby, Richard N

    2010-01-01

    To develop a simple and inexpensive method to visualize and quantify droplet deposition patterns. Deposition pattern was determined by uniformly coating the nose model with Sar-Gel (a paste that changes from white to purple on contact with water) and subsequently discharging sprays into the nose model. The color change was captured using a digital camera and analyzed using Adobe Photoshop. Several tests were conducted to validate the method. Deposition patterns of different nasal sprays (Ayr, Afrin, and Zicam) and different nasal drug delivery devices (Afrin nasal spray and PARI Sinustar nasal nebulizer) were compared. We also used the method to evaluate the effect of inhaled flow rate on nasal spray deposition. There was a significant difference in the deposition area for Ayr, Afrin, and Zicam. The deposition areas of Afrin nasal spray and PARI Sinustar nasal nebulizer (2 min and 5 min) were significantly different. Inhaled flow rate did not have a significant effect on the deposition pattern. Lower viscosity formulations (Ayr, Afrin) provided greater coverage than the higher viscosity formulation (Zicam). The nebulizer covered a greater surface area than the spray pump we evaluated. Aerosol deposition in the nose model was not affected by air flow conditions.

  14. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  15. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  16. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED...

  17. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED...

  18. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED...

  19. Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures.

    PubMed

    Fischer, William A; Chason, Kelly D; Brighton, Missy; Jaspers, Ilona

    2014-03-26

    Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent

  20. Staphylococcus aureus enterotoxins induce IL-8 secretion by human nasal epithelial cells

    PubMed Central

    O'Brien, Garrett J; Riddell, Gareth; Elborn, J Stuart; Ennis, Madeleine; Skibinski, Grzegorz

    2006-01-01

    Background Staphylococcus aureus produces a set of proteins which act both as superantigens and toxins. Although their mode of action as superantigens is well understood, little is known about their effects on airway epithelial cells. Methods To investigate this problem, primary nasal epithelial cells derived from normal and asthmatic subjects were stimulated with staphylococcal enterotoxin A and B (SEA and SEB) and secreted (supernatants) and cell-associated (cell lysates) IL-8, TNF-α, RANTES and eotaxin were determined by specific ELISAs. Results Non-toxic concentrations of SEA and SEB (0.01 μg/ml and 1.0 μg/ml) induced IL-8 secretion after 24 h of culture. Pre-treatment of the cells with IFN-γ (50 IU/ml) resulted in a further increase of IL-8 secretion. In cells from healthy donors pretreated with IFN-γ, SEA at 1.0 μg/ml induced release of 1009 pg/ml IL-8 (733.0–1216 pg/ml, median (range)) while in cells from asthmatic donors the same treatment induced significantly higher IL-8 secretion – 1550 pg/ml (1168.0–2000.0 pg/ml p = 0.04). Normal cells pre-treated with IFN-γ and then cultured with SEB at 1.0 μg/ml released 904.6 pg/ml IL-8 (666.5–1169.0 pg/ml). Cells from asthmatics treated in the same way produced significantly higher amounts of IL-8 – 1665.0 pg/ml (1168.0–2000.0 pg/ml, p = 0.01). Blocking antibodies to MHC class II molecules added to cultures stimulated with SEA and SEB, reduced IL-8 secretion by about 40% in IFN-γ unstimulated cultures and 75% in IFN-γ stimulated cultures. No secretion of TNF-α, RANTES and eotaxin was noted. Conclusion Staphylococcal enterotoxins may have a role in the pathogenesis of asthma. PMID:16952309

  1. The Effect of Menstrual Cycle on Nasal Resonance Characteristics in Females

    ERIC Educational Resources Information Center

    Kumar, Suman; Basu, Shriya; Sinha, Anisha; Chatterjee, Indranil

    2012-01-01

    The purpose of this study was to analyze resonance characteristics (nasality and nasalance values) during the menstrual cycle. Previous studies indicate changes in voice quality and nasal mucosa due to temporary falling estrogen levels in human females during their menstrual cycle. The present study compared the nasality and "nasalance scores"…

  2. The Effect of Menstrual Cycle on Nasal Resonance Characteristics in Females

    ERIC Educational Resources Information Center

    Kumar, Suman; Basu, Shriya; Sinha, Anisha; Chatterjee, Indranil

    2012-01-01

    The purpose of this study was to analyze resonance characteristics (nasality and nasalance values) during the menstrual cycle. Previous studies indicate changes in voice quality and nasal mucosa due to temporary falling estrogen levels in human females during their menstrual cycle. The present study compared the nasality and "nasalance scores"…

  3. Enoxacin penetration into human prostatic tissue.

    PubMed Central

    Bergeron, M G; Roy, R; Lessard, C; Foucault, P

    1988-01-01

    Concurrent enoxacin concentrations in serum and prostatic tissue were determined in 14 patients. The mean ratios of enoxacin concentration in tissue over concentration in serum were 1.4 +/- 0.2 (standard error of the mean). The levels in serum and prostatic tissue were above the MICs for most urinary pathogens. PMID:3196004

  4. Hormone Receptor Expression in Human Fascial Tissue

    PubMed Central

    Fede, C.; Albertin, G.; Petrelli, L.; Sfriso, M.M.; Biz, C.; De Caro, R.

    2016-01-01

    Many epidemiologic, clinical, and experimental findings point to sex differences in myofascial pain in view of the fact that adult women tend to have more myofascial problems with respect to men. It is possible that one of the stimuli to sensitization of fascial nociceptors could come from hormonal factors such as estrogen and relaxin, that are involved in extracellular matrix and collagen remodeling and thus contribute to functions of myofascial tissue. Immunohistochemical and molecular investigations (real-time PCR analysis) of relaxin receptor 1 (RXFP1) and estrogen receptor-alpha (ERα) localization were carried out on samples of human fascia collected from 8 volunteers patients during orthopedic surgery (all females, between 42 and 70 yrs, divided into pre- and post-menopausal groups), and in fibroblasts isolated from deep fascia, to examine both protein and RNA expression levels. We can assume that the two sex hormone receptors analyzed are expressed in all the human fascial districts examined and in fascial fibroblasts culture cells, to a lesser degree in the post-menopausal with respect to the pre-menopausal women. Hormone receptor expression was concentrated in the fibroblasts, and RXFP1 was also evident in blood vessels and nerves. Our results are the first demonstrating that the fibroblasts located within different districts of the muscular fasciae express sex hormone receptors and can help to explain the link between hormonal factors and myofascial pain. It is known, in fact, that estrogen and relaxin play a key role in extracellular matrix remodeling by inhibiting fibrosis and inflammatory activities, both important factors affecting fascial stiffness and sensitization of fascial nociceptors. PMID:28076930

  5. The transmission of masticatory forces and nasal septum: structural comparison of the human skull and Gothic cathedral.

    PubMed

    Hilloowala, Rumy; Kanth, Hrishi

    2007-07-01

    This study extrapolates the transmission of masticatory forces to the cranium based on the architectural principles of Gothic cathedrals. The most significant finding of the study, obtained by analysis of coronal CT scans, is the role of the hard palate, and especially the vomer and the perpendicular plate of the ethmoid in masticatory force transmission. The study also confirms, experimentally, the paths of masticatory forces, cited in literature but based purely on morphological observations. Human skulls and Gothic cathedrals have similar morphological and functional characteristics. The load exerted by the roof of the cathedral is transmitted to the ground by piers and buttresses. These structures also resist the shearing forces exerted by high winds. Similarly, the mid-facial bones of the skull transmit the vertical as well as the lateral masticatory forces from the maxillary dentition to the skull base. The nonload bearing walls and stained glass windows of the cathedral correspond to the translucent wall of the maxilla. The passageway between the aisle and the nave of the cathedral is equivalent to the meatal openings in the lateral wall of the nasal cavity.

  6. Assessing the residual CFTR gene expression in human nasal epithelium cells bearing CFTR splicing mutations causing cystic fibrosis

    PubMed Central

    Masvidal, Laia; Igreja, Susana; Ramos, Maria D; Alvarez, Antoni; de Gracia, Javier; Ramalho, Anabela; Amaral, Margarida D; Larriba, Sara; Casals, Teresa

    2014-01-01

    The major purpose of the present study was to quantify correctly spliced CFTR transcripts in human nasal epithelial cells from cystic fibrosis (CF) patients carrying the splicing mutations c.580-1G>T (712-1G>T) and c.2657+5G>A (2789+5G>A) and to assess the applicability of this model in CFTR therapeutic approaches. We performed the relative quantification of CFTR mRNA by reverse transcription quantitative PCR (RT-qPCR) of these splicing mutations in four groups (wild type, CF-F508del controls, CF patients and CF carriers) of individuals. In addition, in vitro assays using minigene constructs were performed to evaluate the effect of a new CF complex allele c.[2657+5G>A; 2562T>G]. Ex vivo qPCR data show that the primary consequence of both mutations at the RNA level is the skipping of their neighboring exon (6 and 16, respectively). The CFTR minigenes results mimicked the ex vivo data, as exon 16 skipping is the main aberrant transcript, and the correctly spliced transcript level was observed in a similar proportion when the c.2657+5G>A mutation is present. In summary, we provide evidence that ex vivo quantitative transcripts analysis using RT/qPCR is a robust technology that could be useful for measuring the efficacy of therapeutic approaches that attempt to achieve an increase in CFTR gene expression. PMID:24129438

  7. A comparison of natural and passive methods to measure nasal deposition of utrafline aerosols using replicate human upper airway casts

    SciTech Connect

    Cheng, Kuo-Hsi; Swift, D.L.; Cheng, Yung-Sung; Yeh, Hsu-Chi

    1994-11-01

    The risk of lung cancer associated with exposure to radon progeny in underground miners has been investigated extensively by epidemiological studies. Results indicate that exposure to relatively high concentrations of radon progeny in mines is closely linked to an increased occurrence of lung cancer. Current risk estimates for the general population exposed to indoor radon are primarily based on extrapolations from studies of underground miners. To extend these data to radon exposures of the general population in homes, dosimetric modeling is being used to assess the differences in exposure-dose relationships between the mining and home environments. The human upper airways are the first filter against inhaled particles that would otherwise penetrate into the more distal respiratory tract. Understanding of nasal and oral filtration efficiency is the first step in evaluating dose to the lung from exposure to radon progeny. Of the many factors considered in assessing health effects from exposure to radon progeny, particle size and breathing rate are two important parameters that influence deposition patterns in the respiratory tract.

  8. LL-37 causes cell death of human nasal epithelial cells, which is inhibited with a synthetic glycosaminoglycan.

    PubMed

    Thomas, Andrew J; Pulsipher, Abigail; Davis, Brock M; Alt, Jeremiah A

    2017-01-01

    LL-37 is an immune peptide that regulates innate and adaptive immune responses in the upper airways. Elevated levels of LL-37 have been linked to cell death and inflammatory diseases, such as chronic rhinosinusitis (CRS). Glycosaminoglycans (GAGs) are polysaccharides that are found on respiratory epithelial cells and serve important roles in mucosal surface repair. Recent findings suggest that a synthetic glycosaminoglycan (GM-0111) can protect against LL-37-induced sinonasal mucosal inflammation and cell death in a murine model of acute RS. Herein, we elucidated the mechanisms by which LL-37 causes sinonasal inflammation and how GM-0111 can prevent these mechanisms. When challenged with LL-37, human nasal epithelial cells (HNEpCs) and mouse macrophages (J774.2) demonstrated increased release of adenosine triphosphate (ATP) and interleukin (IL)-6 and -8, as well as cell death and lysis. These cellular responses were all blocked dose-dependently by pre-treatment with GM-0111. We identified that LL-37-induced cell death is associated with caspase-1 and -8 activation, but not activation of caspase-3/7. These responses were again blocked by GM-0111. Our data suggest that LL-37 causes cellular death of HNEpCs and macrophages through the pro-inflammatory necrotic and/or pyroptotic pathways rather than apoptosis, and that a GM-0111 is capable of inhibiting these pro-inflammatory cellular events.

  9. Three new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae) from the nasal tissues of dasyatid rays collected off Malaysian and Indonesian Borneo.

    PubMed

    Chisholm, Leslie A; Whittington, Ian D

    2012-06-01

    Three new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae) are described from the nasal tissues of stingrays collected off Borneo. Merizocotyle macrostrobus n. sp. is described from the dwarf whipray Himantura walga (Müller & Henle) collected in shallow waters off Sematan, Sarawak, Malaysia. This species can be distinguished from the other members of the genus by the morphology of the sclerotised male copulatory organ, which is long with many twists and loops. The vaginae of this species are also long and looped. Merizocotyle papillae n. sp. is described from the roughnose stingray Pastinachus solocirostris Last, Manjaji & Yearsley collected off Sematan and Mukah, Sarawak, Malaysia. It is distinguished from the other species of Merizocotyle by the morphology of the male copulatory organ, which is a sclerotised tube that expands slightly and then tapers at the distal end, and by the presence of papillae on the dorsal edge of the haptor. Merizocotyle rhadinopeos n. sp. is described from the whitenose whip ray Himantura uarnacoides (Bleeker) collected off Manggar, East Kalimantan, Indonesia. It can be differentiated by the male copulatory organ, which is a short, narrow, curved, sclerotised tube tapering distally, and the path of the ovary, which runs anteriorly to the base of the oötype. We also provide details of new host and/or locality records for M. australensis (Beverley-Burton & Williams, 1989) Chisholm, Wheeler & Beverley-Burton, 1995, M. icopae Beverley-Burton & Williams, 1989 and M. pseudodasybatis (Hargis, 1955) Chisholm, Wheeler & Beverley-Burton, 1995.

  10. Merizocotyle euzeti sp. n. (Monogenea: Monocotylidae) from the nasal tissue of three deep sea skates (Rajidae) in the southwestern Atlantic Ocean.

    PubMed

    Irigoitia, Manuel M; Cantatore, Delfina M P; Delpiani, Gabriela E; Incorvaia, Inés S; Lanfranchi, Ana L; Timi, Juan T

    2014-06-01

    A new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae) is described from the nasal tissues of three deep sea rajid skates: the southern thorny skate, Amblyraja doellojuradoi (Pozzi), broadnose skate, Bathyraja brachyurops (Fowler), and yellownose skate, Zearaja chilensis (Guichenot), collected off Buenos Aires Province, Argentina, southwest Atlantic Ocean. Two additional species of sympatric rajid, the white-dotted skate, Bathyraja albomaculata (Norman), and the Patagonian skate, Bathyraja macloviana (Norman), were also examined but no merizocotylines were found. The taxonomy of the Merizocotylinae is not widely accepted and, as a result, the status of Thaumatocotyle and Mycteronastes, and their proposed synonymy with Merizocotyle are currently under discussion. The new species differs from its congeners by having a unique haptoral structure, 6 peripheral loculi that are asymmetrically arranged (one much smaller, indistinctly located in the left or right side of the haptor). The presence of the new species in three sympatric species of Rajidae belonging to distinct genera and subfamilies, as well as its absence in sympatric congenerics indicates the lack of phylogenetic host specificity. Host ecology and geographical distribution appear to be more important than host phylogeny in determining the distribution of this parasite across potential hosts in the region. This constitutes the first record of Merizocotyle in the southwestern Atlantic Ocean.

  11. Nasal ventilation.

    PubMed Central

    Simonds, A. K.

    1998-01-01

    Nasal intermittent positive pressure ventilation is likely to have an increasing role in the management of acute ventilatory failure, weaning, and chronic ventilatory problems. Further improvements in ventilator and mask design will be seen. Appropriate application is likely to reduce both mortality and admissions to intensive care, while domiciliary use can improve life expectancy and/or quality of life in chronic ventilatory disorders. As with any new technique, enthusiasm should not outweigh clear outcome information, and possible new indications should always be subject to careful assessment. Images Figure 2 PMID:9799887

  12. Hemoglobin Promotes Staphylococcus aureus Nasal Colonization

    PubMed Central

    Schwartz, Kelly; Hernandez, Margarita; Boles, Blaise R.

    2011-01-01

    Staphylococcus aureus nasal colonization is an important risk factor for community and nosocomial infection. Despite the importance of S. aureus to human health, molecular mechanisms and host factors influencing nasal colonization are not well understood. To identify host factors contributing to nasal colonization, we collected human nasal secretions and analyzed their ability to promote S. aureus surface colonization. Some individuals produced secretions possessing the ability to significantly promote S. aureus surface colonization. Nasal secretions pretreated with protease no longer promoted S. aureus surface colonization, suggesting the involvement of protein factors. The major protein components of secretions were identified and subsequent analysis revealed that hemoglobin possessed the ability to promote S. aureus surface colonization. Immunoprecipitation of hemoglobin from nasal secretions resulted in reduced S. aureus surface colonization. Furthermore, exogenously added hemoglobin significantly decreased the inoculum necessary for nasal colonization in a rodent model. Finally, we found that hemoglobin prevented expression of the agr quorum sensing system and that aberrant constitutive expression of the agr effector molecule, RNAIII, resulted in reduced nasal colonization of S. aureus. Collectively our results suggest that the presence of hemoglobin in nasal secretions contributes to S. aureus nasal colonization. PMID:21750673

  13. Unilateral nasal resistance and asymmetrical body pressure.

    PubMed

    Haight, J S; Cole, P

    1986-08-01

    Lateral recumbency causes ipsilateral nasal congestion and contralateral decongestion. Nasal resistances were measured before, during and after the application of pressure either regionally or by lateral recumbency. In some experiments an attempt was made to block the response by local anesthetic injection, splinting the nasal vestibules, or topical decongestants. In others an electric blanket was employed as a stimulus instead of pressure. It was concluded that the nasal resistance changes during lateral recumbency are due to pressure receptors in the pelvic and pectoral girdles, and thorax. These adapt slowly. They are probably situated in the intercostal spaces, parietal pleura, or sterno-costal joints. Their centripetal fibers probably travel in the intercostal nerves, and their efferents in the cervical sympathetic outflow to the nasal erectile tissue. Lateral recumbency of 12 minutes' duration induces changes in nasal resistance which persist after the pressure asymmetry has been terminated. This may be due to temporal summation.

  14. Tissue-specific expression and promoter analyses of the human tissue kallikrein gene in transgenic mice.

    PubMed Central

    Xiong, W; Wang, J; Chao, L; Chao, J

    1997-01-01

    The expression of the tissue kallikrein gene is tissue-specific and exhibits a complex pattern of transcriptional and post-translational regulation. Information concerning the mechanism of its tissue-specific expression has been limited owing to the lack of suitable cell lines for the expression study. We approached this problem by introducing human tissue kallikrein gene constructs into mouse embryos, creating transgenic lines carrying its coding sequence with varying lengths of the promoter region. One construct (PHK) contained 801 bp in the 5'-flanking region and two deletion constructs contained either 302 bp (D300) or 202 bp (D200) of the promoter region. The expression of human tissue kallikrein in these transgenic mice was monitored by Northern blot, reverse transcriptase-PCR followed by Southern blot, and radioimmunoassay. In all three lines, human tissue kallikrein was expressed predominantly in the pancreas and at lower levels in other tissues, including salivary gland, kidney and spleen. This pattern was similar to that of tissue kallikrein expression in human tissues. The D300 line has higher levels of transgene expression than the D200 and PHK lines. The results indicate that the 202 bp segment immediately upstream of the translation starting site is sufficient to direct a tissue-specific expression pattern of the human tissue kallikrein gene, and that regulatory elements might exist between -801 and -202. PMID:9224635

  15. Seroprevalence of human T lymphtropic virus (HTLV) among tissue donors in Iranian tissue bank.

    PubMed

    Arjmand, Babak; Aghayan, Seyed Hamidreza; Goodarzi, Parisa; Farzanehkhah, Mohammad; Mortazavi, Seyed Mohamadjavad; Niknam, Mohamad Hossein; Jafarian, Ali; Arjmand, Farzin; Jebelly far, Soheyla

    2009-08-01

    Iranian Tissue Bank prepares a wide range of human tissue homografts such as; heart valve, bone, skin, amniotic membrane and other tissues for different clinical applications. The purpose of this study was to determine the seroprevalence of HTLV in tissue donors. About 1,548 tissue donors were studied during a 5-years period by ELISA assays. HTLV(1,2)-antibodies were tested for all of donors with other tests upon American Association of Tissue Banks (AATB) standards. About 25 (1.61%) out of 1,548 tissue donors were HTLV positive that 17 donors were male and 8 were female (female/male ratio was approximately 47%). Regarding to the prevalence of HTLV among tissue donors and importance of cell and tissue safety and quality assurance, we recommend that all blood, cell and tissue banks should be involved both routine serological methods and other complementary tests such as polymerase chain reaction (PCR) for diagnosis of HTLV.

  16. Reconstruction of Alar Nasal Cartilage Defects Using a Tissue Engineering Technique Based on a Combined Use of Autologous Chondrocyte Micrografts and Platelet-rich Plasma: Preliminary Clinical and Instrumental Evaluation

    PubMed Central

    Scioli, Maria G.; Bielli, Alessandra; Orlandi, Augusto; Cervelli, Valerio

    2016-01-01

    Background: Developing cartilage constructs with injectability, appropriate matrix composition, and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. The combined use of autologous chondrocyte micrografts and platelet-rich plasma (PRP) is an alternative that opens a new era in this field. Methods: At the Department of Plastic and Reconstructive Surgery, University of Rome Tor Vergata, Italy, 11 patients underwent nasal alar reconstruction with chondrocyte micrografts gently poured onto PRP in solid form. A computed tomographic scan control was performed after 12 months. Pearson’s Chi-square test was used to investigate difference in cartilage density between native and newly formed cartilages. Results: The constructs of chondrocyte micrografts–PRP that were subcutaneously injected resulted in a persistent cartilage tissue with appropriate morphology, adequate central nutritional perfusion without central necrosis or ossification, and further augmented nasal dorsum without obvious contraction and deformation. Conclusion: This report demonstrated that chondrocyte micrografts derived from nasal septum poured onto PRP in solid form are useful for cartilage regeneration in patients with external nasal valve collapse. PMID:27826462

  17. The use of animal tissues alongside human tissue: Cultural and ethical considerations.

    PubMed

    Kaw, Anu; Jones, D Gareth; Zhang, Ming

    2016-01-01

    Teaching and research facilities often use cadaveric material alongside animal tissues, although there appear to be differences in the way we handle, treat, and dispose of human cadaveric material compared to animal tissue. This study sought to analyze cultural and ethical considerations and provides policy recommendations on the use of animal tissues alongside human tissue. The status of human and animal remains and the respect because of human and animal tissues were compared and analyzed from ethical, legal, and cultural perspectives. The use of animal organs and tissues is carried out within the context of understanding human anatomy and function. Consequently, the interests of human donors are to be pre-eminent in any policies that are enunciated, so that if any donors find the presence of animal remains unacceptable, the latter should not be employed. The major differences appear to lie in differences in our perceptions of their respective intrinsic and instrumental values. Animals are considered to have lesser intrinsic value and greater instrumental value than humans. These differences stem from the role played by culture and ethical considerations, and are manifested in the resulting legal frameworks. In light of this discussion, six policy recommendations are proposed, encompassing the nature of consent, respect for animal tissues as well as human remains, and appropriate separation of both sets of tissues in preparation and display.

  18. Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells

    PubMed Central

    2014-01-01

    Background Pseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown. Methods To investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-κB, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function. Results PE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and β-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-κB pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs. Conclusions PE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight

  19. Pseudomonas aeruginosa elastase causes transient disruption of tight junctions and downregulation of PAR-2 in human nasal epithelial cells.

    PubMed

    Nomura, Kazuaki; Obata, Kazufumi; Keira, Takashi; Miyata, Ryo; Hirakawa, Satoshi; Takano, Ken-ichi; Kohno, Takayuki; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

    2014-02-18

    Pseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown. To investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-κB, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function. PE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and β-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-κB pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs. PE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight junctions by PE might occur repeatedly

  20. A computational analysis of nasal vestibule morphologic variabilities on nasal function.

    PubMed

    Ramprasad, Vaibhav H; Frank-Ito, Dennis O

    2016-02-08

    Although advances in computational modeling have led to increased understanding of nasal airflow, not much is known about the effects of normal sinonasal anatomic variabilities on nasal function. In this study, three distinct variations in the human nasal vestibule airspace that have not been previously described were identified. Computational fluid dynamics modeling of nasal airflow profile in each identified variation of nasal vestibule phenotype was conducted to assess the role of these phenotypes on nasal physiology. Three-dimensional reconstructions of the nasal geometry in sixteen subjects with normal radiographic sinonasal images were created and each respective unilateral nasal cavity was classified as Notched, Standard, or Elongated phenotype based nasal vestibule morphology. Steady state, laminar and incompressible flow simulations were performed in the nasal geometries under physiological, pressure-driven conditions with constant inspiratory pressure. Results showed that at localized regions of the unilateral nasal cavity, average resistance was significantly different among nasal vestibule phenotypes. However, global comparison from nostril to choana showed that average resistance was not significantly different across phenotypes; suggesting that with normal anatomic variations, the nose has a natural compensatory mechanism that modulates localized airflow in order to achieve a desired amount of global airflow. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Successful cryopreservation of human ovarian cortex tissues using supercooling.

    PubMed

    Moriguchi, Hisashi; Zhang, Yue; Mihara, Makoto; Sato, Chifumi

    2012-01-01

    The development of new method to cryopreserve human ovarian cortex tissues without damage is needed for the improvement of quality of life (QOL) of female cancer patients. Here we show novel cryopreservation method of human ovarian cortex tissues by using supercooling (S.C.) procedure. Our method will be helpful in order to preserve fertility of female cancer patients.

  2. Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation

    DTIC Science & Technology

    2012-05-01

    hypofractionated ionizing radiation. PRINCIPAL INVESTIGATOR: Thomas C. Sroka, M.D., Ph.D...April 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Response of human prostate tissue to hypofractionated ionizing radiation. 5b. GRANT NUMBER...of this proposal was to determine the differences in radiobiological response of human prostate tissue to conventional and hypofractionated

  3. Successful cryopreservation of human ovarian cortex tissues using supercooling

    PubMed Central

    Moriguchi, Hisashi; Zhang, Yue; Mihara, Makoto; Sato, Chifumi

    2012-01-01

    The development of new method to cryopreserve human ovarian cortex tissues without damage is needed for the improvement of quality of life (QOL) of female cancer patients. Here we show novel cryopreservation method of human ovarian cortex tissues by using supercooling (S.C.) procedure. Our method will be helpful in order to preserve fertility of female cancer patients. PMID:22844578

  4. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia.

    PubMed

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J

    2015-10-01

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss.

  5. Nasal glioma or nasal glial heterotopia? Morphological, immunohistochemical and ultrastructural study of two cases.

    PubMed

    Cerdá-Nicolás, M; Sanchez Fernandez de Sevilla, C; Lopez-Ginés, C; Peydro-Olaya, A; Llombart-Bosch, A

    2002-01-01

    The term nasal glioma has been used to describe a congenital benign tumor of the nasal region containing neural tissue. The nature of these lesions remains open to controversy, because of the different locations of the heterotopic neural tissue involved, the deficient development of the bony structures and the persistence or not of the structural relations with the central nervous system. More recent terms define these lesions as ectopic nervous tissue. A clinical, morphological, ultrastructural and immunohistochemical study is made of two cases of nasal glioma, one associated with agenesis of the corpus callosum. In this case, the mother had been treated with clomiphene. In such cases, morphological and immunohistochemical findings support that "nasal glioma" remain valid as a descriptive term defining a congenital benign tumor composed of heterotopic neural tissue within the nasal region and covered by skin, that may recur following incomplete surgical resection.

  6. Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation

    DTIC Science & Technology

    2011-07-01

    Summary01-07-2011 Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation Dr. Thomas Sroka University of Arizona Tucson, AZ 85719 The aim...of this proposal is to determine the differences in radiobiological response of human prostate tissue to conventional and hypofractionated ...conventional and hypofractionated ionizing radiation. Data generated in the first year of study has shown that normal prostate tissue and prostate

  7. Fundamentals of gas phase plasmas for treatment of human tissue.

    PubMed

    Kushner, Mark J; Babaeva, Natalia Yu

    2011-01-01

    The use of gas phase plasmas for treating human tissue is at the intersection of two disciplines - plasma physics and engineering, and medicine. In this paper, a primer will be provided for the medical practitioner on the fundamentals of generating gas phase plasmas at atmospheric pressure in air for the treatment of human tissue. The mechanisms for gas phase plasmas interacting with tissue and biological fluids will also be discussed using results from computer modeling.

  8. [The influence of nasal flow aerodynamics on the nasal physiology].

    PubMed

    Betlejewski, Stanisław; Betlejewski, Andrzej

    2008-01-01

    The ability of the human nose to warm and humidify the respiratory air is important to maintaining the internal environment of the lungs, since ambient air is conditioned to nearly alveolar conditions (body temperature and fully saturated with water vapour) upon reaching the nasopharynx. Because of very short time of the inspiratory phase duration, as well as expiratory phase, only the rich vascularization of the nasal mucosa and specific organization of the submucosal vessels are not able to assure such effective physiological activity. Therefore the type of airflow during the respiration is essential to understanding the functional possibilities of the nasal mucosa. Most studies have investigated the airflow only in steady-flow conditions, where the laminar flow was observed. Anatomically accurate physical models of real nasal cavities and particle image velocimetry allow evaluation of the entire flow field in the nasal cavity. In these investigations a partially turbulent flow was observed even at low air velocities in most part of the nasal cavity. From a physiological perspective, a turbulent flow would seem sensible, since it enhances contact between air and the mucosal layer. By doing so, the nasal physiological functions - humidification, cleaning and warming are optimized.

  9. Nasal Reconstruction and Repair of Secondary Nasal Deformities Following Treatment of Nasal Hemangiomas.

    PubMed

    Lu, Xiaona; Fan, Fei; Wang, Huan; You, Jianjun

    2017-03-01

    Secondary nasal deformities and retardation of development due to treatment of nasal hemangioma during infancy are a challenge when it comes to nasal reconstruction. In order to evaluate nasal repair and reconstruction in these patients, the authors compared the ease and outcomes of using expanded forehead, nasolabial sulcus, and medial upper arm tube flaps. According to the deformities and patients' wishes, flaps were selected; using autogeneic rib cartilage, auricle cartilage, or silica gel as a scaffold or without framework; the inner lining were made by the residual scar tissue or the distal end of transferred flap. The esthetical and functional scores were recorded by the Nasal Appearance and Function Evaluation Questionnaire score to evaluate the effectiveness of the methods. From January 2010 to December 2015, 34 patients were included. Postoperative follow-up went for 12 to 36 months. The expanded forehead flap was used in 28 patients, the nasolabial sulcus flap in 5 patients, and the medial upper arm tube flap in 1 patient. Regarding framework, 20 patients used rib cartilage, 8 patients used auricle cartilage, 1 patient used silicone, and 5 patients did not use any framework. All patients reported the increasing nasal appearance and function evaluation. Repair of secondary nasal defects following treatment of hemangiomas in infants and young children using an expanded frontal flap and autogenous cartilage framework is a reliable method with great long-term esthetic results. The nasolabial sulcus flap is a relatively simple method, especially for patients with a unilateral nasal alar defect. Supporting structure is needed and appropriate overcorrection is necessary.

  10. Predicting DNA methylation level across human tissues

    PubMed Central

    Ma, Baoshan; Wilker, Elissa H.; Willis-Owen, Saffron A. G.; Byun, Hyang-Min; Wong, Kenny C. C.; Motta, Valeria; Baccarelli, Andrea A.; Schwartz, Joel; Cookson, William O. C. M.; Khabbaz, Kamal; Mittleman, Murray A.; Moffatt, Miriam F.; Liang, Liming

    2014-01-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  11. Mesenchymal Stem Cell Levels of Human Spinal Tissues.

    PubMed

    Harris, Liam; Vangsness, C Thomas

    2017-09-06

    .: Systematic Review. .: The aim of this study was to investigate, quantify, compare and compile the various mesenchymal stem cell tissue sources within human spinal tissues to act as a compendium for clinical and research application. .: Recent years have seen a dramatic increase in academic and clinical understanding of human mesenchymal stem cells (MSCs). Previously limited to cells isolated from bone marrow, the past decade has illicited the characterization and isolation of human MSCs from adipose, bone marrow, synovium, muscle, periosteum, peripheral blood, umbilical cord, placenta and numerous other tissues. As researchers explore practical applications of cells in these tissues, the absolute levels of MSCs in specific spinal tissue will be critical to guide future research. .: The PubMED, MEDLINE, EMBASE and Cochrane databases were searched for articles relating to the harvest, characterization, isolation and quantification of human mesenchymal stem cells from spinal tissues. Selected articles were examined for relevant data, categorized according to type of spinal tissue, and when possible, standardized to facilitate comparisons between sites. .: Human mesenchymal stem cell levels varied widely between spinal tissues. Yields for Intervertebral disc demonstrated roughly 5% of viable cells to be positive for MSC surface markers. Cartilage endplate cells yielded 18,500- 61,875 cells/ 0.8 mm thick sample of cartilage end plate. Ligamentum flavum yielded 250,000- 500,000 cells per gram of tissue. Annulus fibrosus FACS treatment found 29% of cells positive for MSC marker Stro-1. Nucleus pulposus yielded mean tissue samples of 40,584-234,137 MSCs/gram of tissue. .: Numerous tissues within and surrounding the spine represent a consistent and reliable source for the harvest and isolation of human mesenchymal stem cells. Among the tissues of the spine, the annulus fibrosus and ligamentum flavum each offer considerable levels of mesenchymal stem cells, and may

  12. Brown adipose tissue as an anti-obesity tissue in humans.

    PubMed

    Chechi, K; Nedergaard, J; Richard, D

    2014-02-01

    During the 11th Stock Conference held in Montreal, Quebec, Canada, world-leading experts came together to present and discuss recent developments made in the field of brown adipose tissue biology. Owing to the vast capacity of brown adipose tissue for burning food energy in the process of thermogenesis, and due to demonstrations of its presence in adult humans, there is tremendous interest in targeting brown adipose tissue as an anti-obesity tissue in humans. However, the future of such therapeutic approaches relies on our understanding of the origin, development, recruitment, activation and regulation of brown adipose tissue in humans. As reviewed here, the 11th Stock Conference was organized around these themes to discuss the recent progress made in each aspect, to identify gaps in our current understanding and to further provide a common groundwork that could support collaborative efforts aimed at a future therapy for obesity, based on brown adipose tissue thermogenesis.

  13. The use of functional human tissues in drug development.

    PubMed

    Bunton, David

    2011-02-01

    Fresh, functional human tissues have long been considered the closest possible model of human in vivo function and can be used to measure a wide range of pharmacological responses. Despite this, relatively little drug development is conducted using fresh human tissue because of the logistical and ethical difficulties surrounding the availability of tissue and practicalities of experimental work. Most tests of drug activity require a living test system comprising cells, tissues or whole organisms. In some instances, "living" (fresh) human tissues have the potential to reduce or replace animal tests through superior prediction of drug safety and efficacy. Before functional human tissue tests become a routine part of drug development, two factors must co-exist. Firstly, organisations such as Biopta must continue to create compelling evidence that human tissues are more predictive than alternative models; such evidence will drive demand from the pharmaceutical industry for human tissue-based tests. Secondly, the vast number of tissues and organs residual to surgery or unsuitable for transplant must be routinely consented for medical research and made available to all researchers in an equitable and timely manner. This requires a concerted effort throughout the NHS and consistent demand as well as financial support from researchers, particularly within industry. It is our view that the next 5-10 years will generate compelling evidence of the value of functional human tissue-based tests and recognition that more efficient use of residual or non-transplantable tissues and organs is an urgent priority for the development of new medicines.

  14. Exploring the role of intra-nasal oxytocin on the partner preference effect in humans.

    PubMed

    Liu, Jean C J; Guastella, Adam J; Dadds, Mark R

    2013-04-01

    Previous studies with prairie voles suggest that the hormone oxytocin is crucial for bond formation - indicated when a partner preference is formed towards the target vole. In this study, we conduct the first empirical test of whether oxytocin likewise promotes partner preferences in humans. Seventy-six undergraduate students received either oxytocin or placebo before being introduced to a male and female persona (via pre-recorded videoclips). One day later, participants were assessed for a partner preference towards the personae: across three situations, participants were asked to choose as company one of the personae they had been introduced to, or an opposite- or same-gendered person they had not been introduced to before; participants were additionally offered a choice to have no company. We found evidence suggesting oxytocin increases preference for persons introduced under the influence of oxytocin; however, this was not targeted at persons of the opposite-gender, and was found in only one aspect of social interaction (finding out more information about the person, but not in choice of company to work with or for a date). Taken together, our findings suggest that oxytocin might not promote human bond formation in ways analogous to prairie voles - that is, by inducing a partner preference effect.

  15. Decellularized extracellular matrix derived from human adipose tissue as a potential scaffold for allograft tissue engineering.

    PubMed

    Choi, Ji Suk; Kim, Beob Soo; Kim, Jun Young; Kim, Jae Dong; Choi, Young Chan; Yang, Hyun-Jin; Park, Kinam; Lee, Hee Young; Cho, Yong Woo

    2011-06-01

    Decellularized tissues composed of extracellular matrix (ECM) have been clinically used to support the regeneration of various human tissues and organs. Most decellularized tissues so far have been derived from animals or cadavers. Therefore, despite the many advantages of decellularized tissue, there are concerns about the potential for immunogenicity and the possible presence of infectious agents. Herein, we present a biomaterial composed of ECM derived from human adipose tissue, the most prevalent, expendable, and safely harvested tissue in the human body. The ECM was extracted by successive physical, chemical, and enzymatic treatments of human adipose tissue isolated by liposuction. Cellular components including nucleic acids were effectively removed without significant disruption of the morphology or structure of the ECM. Major ECM components were quantified, including acid/pepsin-soluble collagen, sulfated glycosaminoglycan (GAG), and soluble elastin. In an in vivo experiment using mice, the decellularized ECM graft exhibited good compatibility to surrounding tissues. Overall results suggest that the decellularized ECM containing biological and chemical cues of native human ECM could be an ideal scaffold material not only for autologous but also for allograft tissue engineering.

  16. Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre

    PubMed Central

    Gould, Victoria M. W.; Francis, James N.; Anderson, Katie J.; Georges, Bertrand; Cope, Alethea V.; Tregoning, John S.

    2017-01-01

    In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines. PMID:28567036

  17. In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells

    PubMed Central

    Jukosky, James; Gosselin, Benoit J.; Foley, Leah; Dechen, Tenzin; Fiering, Steven; Crane-Godreau, Mardi A.

    2016-01-01

    Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual’s susceptibility to pathogen infection. PMID:26793127

  18. Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre.

    PubMed

    Gould, Victoria M W; Francis, James N; Anderson, Katie J; Georges, Bertrand; Cope, Alethea V; Tregoning, John S

    2017-01-01

    In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines.

  19. Expression and distribution of endocan in human tissues.

    PubMed

    Zhang, S M; Zuo, L; Zhou, Q; Gui, S Y; Shi, R; Wu, Q; Wei, W; Wang, Y

    2012-04-01

    Endocan is a novel human endothelial cell specific molecule. Its expression is regulated by cytokines and vascular endothelial growth factor (VEGF). The distribution of endocan in normal human tissues, however, remains unclear. We examined the expression of endocan in normal human tissue using immunohistochemical stains. Endocan was expressed in actively proliferative or neogeneic tissues and cells such as glandular tissues, endothelium of neovasculature, bronchial epithelium, germinal centers of lymph nodes etc. Endocan was not present in silent or resting tissues or cells such as endothelium of great arteries and spleen etc. Our findings suggest that endocan may act as a marker for angiogenesis or oncogenesis and could be regarded as a candidate gene for inflammatory tissue, neoplasia, tumor development and metastasis. The expression level of endocan may assist early diagnosis and prognosis of some tumors.

  20. Macrophages modulate engineered human tissues for enhanced vascularization and healing

    PubMed Central

    Spiller, Kara L.; Freytes, Donald O.; Vunjak-Novakovic, Gordana

    2014-01-01

    Tissue engineering is increasingly based on recapitulating human physiology, through integration of biological principles into engineering designs. In spite of all progress in engineering functional human tissues, we are just beginning to develop effective methods for establishing blood perfusion and controlling the inflammatory factors following implantation into the host. Functional vasculature largely determines tissue survival and function in vivo. The inflammatory response is a major regulator of vascularization and overall functionality of engineered tissues, through the activity of different types of macrophages and the cytokines they secrete. We discuss cell-scaffold-bioreactor systems for harnessing the inflammatory response for enhanced tissue vascularization and healing. To this end, inert scaffolds that have been considered for many decades a “gold standard” in regenerative medicine are beginning to be replaced by a new generation of “smart” tissue engineering systems designed to actively mediate tissue survival and function. PMID:25331098

  1. Diagnose human colonic tissues by terahertz near-field imaging

    NASA Astrophysics Data System (ADS)

    Chen, Hua; Ma, Shihua; Wu, Xiumei; Yang, Wenxing; Zhao, Tian

    2015-03-01

    Based on a terahertz (THz) pipe-based near-field imaging system, we demonstrate the capability of THz imaging to diagnose freshly surgically excised human colonic tissues. Through THz near-field scanning the absorbance of the colonic tissues, the acquired images can clearly distinguish cancerous tissues from healthy tissues fast and automatically without pathological hematoxylin and eosin stain diagnosis. A statistical study on 58 specimens (20 healthy tissues and 38 tissues with tumor) from 31 patients (mean age: 59 years; range: 46 to 79 years) shows that the corresponding diagnostic sensitivity and specificity on colonic tissues are both 100%. Due to its capability to perform quantitative analysis, our study indicates the potential of the THz pipe-based near-field imaging for future automation on human tumor pathological examinations.

  2. Determination of thiocyanate (biomarkers of ETS) and other inorganic ions in human nasal discharge samples using ion chromatography.

    PubMed

    Narkowicz, Sylwia; Polkowska, Żaneta; Marć, Mariusz; Simeonov, Vasil; Namieśnik, Jacek

    2013-10-01

    Environmental tobacco smoke (ETS) is a mixture of air and tobacco smoke containing more than 4000 chemical substances. In view of the health risks of many of these substances, studies are needed to determine biomarkers of exposure to ETS constituents in people who actively or passively are exposed to the toxic compounds. The methodologies for determining most biomarkers from saliva, urine and blood samples are known, but methods for analyzing these compounds in nasal discharges are not available. The objective of this work was to develop an analytical procedure for the determination of thiocyanate and other biomarker compounds in samples of nasal discharge using ion chromatography.

  3. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    SciTech Connect

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.

    2015-10-15

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  4. Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans

    PubMed Central

    Malis, Didier-David; Grouzmann, Eric; Morel, Denis R; Mutter, Manfred; Lacroix, Jean-Silvain

    1999-01-01

    In nine anaesthetized pigs we have studied the influence of intranasal or intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP), on the functional responses to subsequent intranasal or intrabronchial histamine challenge. In a parallel study, subjective and objective nasal airway resistance (NAR) increase following intranasal histamine challenge was evaluated in 11 healthy volunteers after TASP-V or placebo pretreatment. In pigs, increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal spray (0.25 mg kg−1 in 3 ml of saline) was significantly reduced by 65% (P<0.05) following intranasal pretreatment with 10 μg kg−1 of TASP-V. Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg−1 in 3 ml of saline) was significantly attenuated by 25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 and 20 μg kg−1, respectively. In healthy volunteers, objective increase in NAR and reduction in nasal minimal cross section area (MCSA) induced by intranasal spray of histamine dihydrochloride (15 μg kg−1 in 200 μl of saline) were significantly attenuated by 50% following local pretreatment with 1.275 μg kg−1 of TASP-V when compared with saline. It is concluded that intranasal or intrabronchial pretreatment with TASP-V reduced nasal obstruction and bronchoconstriction evoked by histamine challenge in the pig. In healthy human volunteers, this agent attenuated NAR increase and MCSA reduction induced by intranasal application of histamine. PMID:10193779

  5. VR-based interactive CFD data comparison of flow fields in a human nasal cavity

    NASA Astrophysics Data System (ADS)

    Gerndt, Andreas; Kuhlen, Torsten; van Reimersdahl, Thomas; Haack, Matthias; Bischof, Christian

    2004-05-01

    The Virtual Reality Center Aachen is developing a Virtual Reality based operation planning system in cooperation with aerodynamics scientists and physicians of several clinical centers. This system is meant to help the preparation of nose surgeries aimed at the elimination of respiratory diseases. A core part is the interactive comparison of experimental data and simulation data in the area of fluid dynamics. In a first step, data comparison is to depict the differences between healthy noses and diseased noses. Later on, data comparison should supply evidence for successful virtual surgeries, which finally results in guidance on the real operation. During virtual surgery sessions, scientists can interactively explore, analyze, annotate, and compare various medical and aerodynamics data sets. Image-based methods are used to extract several features in one image and between compared data sets. The determination of linked features between different data sets is a particular challenge because of their different time frames, scales, and distortions. An optimized human computer interface enables the user to interact intuitively within a virtual environment in order to select and deal with these data sets. Additionally to this interactive exploration, the system also allows automatic searches for cut plane and key frame candidates corresponding to given feature patterns. The comparison system makes use of an already implemented parallelized Computational Fluid Dynamics (CFD) postprocessing, which also extracts enhanced flow features that allow automatic detection of relevant flow regions. Beside vortex detection, the computation of critical points including flow field segmentation is a current research activity. These flow features are favored characteristics for the comparison and help considerably to classify different nose geometries and operation recommendations.

  6. Depth-resolved fluorescence of human ectocervical tissue

    NASA Astrophysics Data System (ADS)

    Wu, Yicong; Xi, Peng; Cheung, Tak-Hong; Yim, So Fan; Yu, Mei-Yung; Qu, Jianan Y.

    2005-04-01

    The depth-resolved autofluorescence of normal and dysplastic human ectocervical tissue within 120um depth were investigated utilizing a portable confocal fluorescence spectroscopy with the excitations at 355nm and 457nm. From the topmost keratinizing layer of all ectocervical tissue samples, strong keratin fluorescence with the spectral characteristics similar to collagen was observed, which created serious interference in seeking the correlation between tissue fluorescence and tissue pathology. While from the underlying non-keratinizing epithelial layer, the measured NADH fluorescence induced by 355nm excitation and FAD fluorescence induced by 457nm excitation were strongly correlated to the tissue pathology. The ratios between NADH over FAD fluorescence increased statistically in the CIN epithelial relative to the normal and HPV epithelia, which indicated increased metabolic activity in precancerous tissue. This study demonstrates that the depth-resolved fluorescence spectroscopy can reveal fine structural information on epithelial tissue and potentially provide more accurate diagnostic information for determining tissue pathology.

  7. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  8. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  9. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  10. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques

    PubMed Central

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-01-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [18F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [18F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  11. Transcriptomics resources of human tissues and organs.

    PubMed

    Uhlén, Mathias; Hallström, Björn M; Lindskog, Cecilia; Mardinoglu, Adil; Pontén, Fredrik; Nielsen, Jens

    2016-04-04

    Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large-scale transcriptomics studies have analyzed the expression of protein-coding genes across tissues. These datasets provide a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue-restricted manner. Here, we review publicly available human transcriptome resources and discuss body-wide data from independent genome-wide transcriptome analyses of different tissues. Gene expression measurements from these independent datasets, generated using samples from fresh frozen surgical specimens and postmortem tissues, are consistent. Overall, the different genome-wide analyses support a distribution in which many proteins are found in all tissues and relatively few in a tissue-restricted manner. Moreover, we discuss the applications of publicly available omics data for building genome-scale metabolic models, used for analyzing cell and tissue functions both in physiological and in disease contexts.

  12. Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion.

    PubMed

    Haley, Nicholas J; Siepker, Chris; Hoon-Hanks, Laura L; Mitchell, Gordon; Walter, W David; Manca, Matteo; Monello, Ryan J; Powers, Jenny G; Wild, Margaret A; Hoover, Edward A; Caughey, Byron; Richt, Jürgen A

    2016-04-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni;n= 323), and nasal brush samples were collected from a subpopulation of these animals (n= 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both thePRNPgenotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

  13. Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion

    PubMed Central

    Siepker, Chris; Hoon-Hanks, Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen A.

    2016-01-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD. PMID:26888899

  14. Natural Rubber Nanocomposite with Human-Tissue-Like Mechanical Characteristic

    NASA Astrophysics Data System (ADS)

    Murniati, Riri; Novita, Nanda; Sutisna; Wibowo, Edy; Iskandar, Ferry; Abdullah, Mikrajuddin

    2017-07-01

    The blends of synthetic rubber and natural rubber with nanosilica were prepared using a blending technique in presence of different filler volume fraction. The effect of filler on morphological and mechanical characteristics was studied. Utilization of human cadaver in means of medical study has been commonly used primarily as tools of medical teaching and training such as surgery. Nonetheless, human cadaver brought inevitable problems. So it is necessary to find a substitute material that can be used to replace cadavers. In orthopaedics, the materials that resemble in mechanical properties to biological tissues are elastomers such as natural rubber (latex) and synthetic rubber (polyurethanes, silicones). This substitution material needs to consider the potential of Indonesia to help the development of the nation. Indonesia is the second largest country producer of natural rubber in the world. This paper aims to contribute to adjusting the mechanical properties of tissue-mimicking materials (TMMs) to the recommended range of biological tissue value and thus allow the development of phantoms with greater stability and similarity to human tissues. Repeatability for the phantom fabrication process was also explored. Characteristics were then compared to the control and mechanical characteristics of different human body part tissue. Nanosilica is the best filler to produce the best nanocomposite similarities with human tissue. We produced composites that approaching the properties of human internal tissues.

  15. Distribution of miRNA expression across human tissues

    PubMed Central

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-01-01

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas). PMID:26921406

  16. Distribution of miRNA expression across human tissues.

    PubMed

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-05-05

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

  17. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  18. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  19. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  20. Bovine Leukemia Virus DNA in Human Breast Tissue

    PubMed Central

    Shen, Hua Min; Jensen, Hanne M.; Choi, K. Yeon; Sun, Dejun; Nuovo, Gerard

    2014-01-01

    Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease. PMID:24750974

  1. Bovine leukemia virus DNA in human breast tissue.

    PubMed

    Buehring, Gertrude Case; Shen, Hua Min; Jensen, Hanne M; Choi, K Yeon; Sun, Dejun; Nuovo, Gerard

    2014-05-01

    Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease.

  2. Dosimetry modeling of inhaled formaldehyde: binning nasal flux predictions for quantitative risk assessment.

    PubMed

    Kimbell, J S; Overton, J H; Subramaniam, R P; Schlosser, P M; Morgan, K T; Conolly, R B; Miller, F J

    2001-11-01

    Interspecies extrapolations of tissue dose and tumor response have been a significant source of uncertainty in formaldehyde cancer risk assessment. The ability to account for species-specific variation of dose within the nasal passages would reduce this uncertainty. Three-dimensional, anatomically realistic, computational fluid dynamics (CFD) models of nasal airflow and formaldehyde gas transport in the F344 rat, rhesus monkey, and human were used to predict local patterns of wall mass flux (pmol/[mm(2)-h-ppm]). The nasal surface of each species was partitioned by flux into smaller regions (flux bins), each characterized by surface area and an average flux value. Rat and monkey flux bins were predicted for steady-state inspiratory airflow rates corresponding to the estimated minute volume for each species. Human flux bins were predicted for steady-state inspiratory airflow at 7.4, 15, 18, 25.8, 31.8, and 37 l/min and were extrapolated to 46 and 50 l/min. Flux values higher than half the maximum flux value (flux median) were predicted for nearly 20% of human nasal surfaces at 15 l/min, whereas only 5% of rat and less than 1% of monkey nasal surfaces were associated with fluxes higher than flux medians at 0.576 l/min and 4.8 l/min, respectively. Human nasal flux patterns shifted distally and uptake percentage decreased as inspiratory flow rate increased. Flux binning captures anatomical effects on flux and is thereby a basis for describing the effects of anatomy and airflow on local tissue disposition and distributions of tissue response. Formaldehyde risk models that incorporate flux binning derived from anatomically realistic CFD models will have significantly reduced uncertainty compared with risk estimates based on default methods.

  3. Altered autophagy in human adipose tissues in obesity

    USDA-ARS?s Scientific Manuscript database

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  4. Tissue-Based Imaging Model of Human Trabecular Meshwork

    PubMed Central

    Chu, Edward R.; Gonzalez, Jose M.

    2014-01-01

    Abstract We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM. PMID:24517246

  5. Microwave non-contact imaging of subcutaneous human body tissues.

    PubMed

    Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-10-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated.

  6. Microwave non-contact imaging of subcutaneous human body tissues

    PubMed Central

    Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-01-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated. PMID:26609415

  7. Distribution of arsenic in human tissues and milk.

    PubMed

    Dang, H S; Jaiswal, D D; Somasundaram, S

    1983-07-01

    Using neutron activation followed by radiochemical separations, the arsenic contents of various human tissues and milk were determined. The reliability of analysis was established by analysing a number of standard reference materials. The concentrations in different human tissues range from 1.6 ng As/g (fresh weight) in kidneys to 2140 ng As/g in hair. The mean arsenic levels are compared with those reported from other countries.

  8. Deprojecting the nasal profile.

    PubMed

    Papel, I D; Mabrie, D C

    1999-02-01

    The nose is the most prominent aesthetic feature of the facial profile. Nasal length, tip rotation, and tip projection are integral aspects in analysis of the nasal profile. In most rhinoplasties the surgeon has the difficult task of increasing or maintaining tip projection of an underprojected or normally projected nasal tip. Less commonly, the rhinoplastic surgeon is presented with an overprojected nasal tip, and efforts are focused on deprojecting the nasal profile. In this article, the authors present a discussion of the overprojected tip, elucidating strategies of analysis, etiologies, and management of the nasal profile and give clinical examples.

  9. Nasal Injuries in Sports.

    PubMed

    Marston, Alexander P; O'Brien, Erin K; Hamilton, Grant S

    2017-04-01

    Nasal trauma is a common consequence of athletic competition. The nasal bones are the most commonly fractured facial bone and are particularly at risk during sports participation. Acute management of trauma to the nose includes thorough evaluation of all injuries and may require immediate management for repair of facial lacerations, epistaxis control, or septal hematoma drainage. Nasal fractures can often be addressed with closed reduction techniques; however, in the setting of complex nasal trauma, an open approach may be indicated. Using appropriate treatment techniques, posttraumatic nasal sequelae can be minimized; most patients report satisfactory long-term nasal form and function.

  10. Total DDT and dieldrin content of human adipose tissue

    SciTech Connect

    Ahmad, N.; Harsas, W.; Marolt, R.S.; Morton, M.; Pollack, J.K.

    1988-12-01

    As far as the authors could ascertain only 4 well-documented analytical studies have been carried out in Australia determining the total DDT and dieldrin content of human adipose tissue. The latest of these studies was published over 16 years ago. Therefore it is timely and important to re-examine the total DDT and dieldrin concentration within the adipose tissue of the Australian population. The present investigation has analyzed 290 samples of human adipose tissue obtained from Westmead Hospital situated in an outer suburb of Sydney, New South Wales for their content of total DDT and dieldrin.

  11. Mesenchymal Stem Cells Derived from Human Adipose Tissue.

    PubMed

    Mahmoudifar, Nastaran; Doran, Pauline M

    2015-01-01

    Human adult mesenchymal stem cells are present in fat tissue, which can be obtained using surgical procedures such as liposuction. The multilineage capacity of mesenchymal stem cells makes them very valuable for cell-based medical therapies. In this chapter, we describe how to isolate mesenchymal stem cells from human adult fat tissue, propagate the cells in culture, and cryopreserve the cells for tissue engineering applications. Flow cytometry methods are also described for identification and characterization of adipose-derived stem cells and for cell sorting.

  12. Characterization of Human Papillomavirus Type 154 and Tissue Tropism of Gammapapillomaviruses

    PubMed Central

    Ure, Agustín Enrique; Forslund, Ola

    2014-01-01

    The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus. PMID:24551244

  13. Vibrational Micro-Spectroscopy of Human Tissues Analysis: Review.

    PubMed

    Bunaciu, Andrei A; Hoang, Vu Dang; Aboul-Enein, Hassan Y

    2017-05-04

    Vibrational spectroscopy (Infrared (IR) and Raman) and, in particular, micro-spectroscopy and micro-spectroscopic imaging have been used to characterize developmental changes in tissues, to monitor these changes in cell cultures and to detect disease and drug-induced modifications. The conventional methods for biochemical and histophatological tissue characterization necessitate complex and "time-consuming" sample manipulations and the results are rarely quantifiable. The spectroscopy of molecular vibrations using mid-IR or Raman techniques has been applied to samples of human tissue. This article reviews the application of these vibrational spectroscopic techniques for analysis of biological tissue published between 2005 and 2015.

  14. Characterization of a simplified method of cryopreserving human parathyroid tissue.

    PubMed

    Saxe, A W; Gibson, G W; Kay, S

    1990-12-01

    Cryopreservation of human parathyroid tissue plays an important role in managing difficult parathyroid disease. It also can permit investigators to conduct experiments without dependence on the operating room schedule. Availability of cryopreservation has been limited by the perceived need for expensive, complex equipment. We adapted a simple method of freezing cell suspensions to freezing human parathyroid tissue. Vials containing human parathyroid in culture media, dimethylsulfoxide, and patient serum were placed in a plastic rack in a metal pan containing prechilled (4 degrees C) ethanol and placed in a -70 degrees C freezer. We compared viability (trypan blue dye exclusion by collagenase dispersed cells) of tissue frozen in this manner to that of tissue frozen in a programmable liquid nitrogen freezer at 1 degrees C per minute, a cooling rate recommended for human parathyroid tissue. The viability of 30 patients' samples cooled in liquid nitrogen (average length of storage 5 months) was 74% +/- 15% and that of 64 patients' samples cooled in ethanol (average length of storage 26 months) was 71% +/- 15%. Viability of 19 samples of fresh tissue was 79% +/- 10%. Neither method had a statistically significant correlation between length of storage and viability. Successful cryopreservation with simplified technology may expand the availability of parathyroid tissue to meet both clinical and investigative requirements.

  15. Efficient In Vitro Electropermeabilization of Reconstructed Human Dermal Tissue.

    PubMed

    Madi, Moinecha; Rols, Marie-Pierre; Gibot, Laure

    2015-10-01

    DNA electrotransfer is a successful technic for gene delivery. However, its use in clinical applications is limited since little is known about the mechanisms governing DNA electrotransfer in the complex environment occurring in a tissue. The objectives of this work were to investigate the role of the extracellular matrix (ECM) in that process. Tumor ECM composition was shown to modulate in vivo gene electrotransfer efficiency. In order to assess the effects of ECM composition and organization, as well as intercellular junctions and communication, in normal tissue response to electric pulses, we developed an innovative three-dimensional (3D) reconstructed human connective tissue model. 3D human dermal tissue was reconstructed in vitro by a tissue engineering approach and was representative of in vivo cell organization since cell-cell contacts were present as well as complex ECM. This human cell model presented multiple layers of primary dermal fibroblasts embedded in a native, collagen-rich ECM. This dermal tissue could become a useful tool to study skin DNA electrotransfer mechanisms. As proof of the concept, we show here that the cells within this standardized 3D tissue can be efficiently electropermeabilized by milliseconds electric pulses. We believe that a better comprehension of gene electrotransfer in such a model tissue would help improve electrogene therapy approaches such as the systemic delivery of therapeutic proteins and DNA vaccination.

  16. Elevated homocysteine in human abdominal aortic aneurysmal tissues.

    PubMed

    Chan, Crystal Yin Tung; Cheng, Stephen Wing Keung

    2017-10-01

    An abnormally high level of homocysteine (Hcy) has been consistently observed in the blood of abdominal aortic aneurysm (AAA) patients. However, the expression of Hcy in human AAA tissues has not been investigated. In this study, the expression of Hcy in aneurysmal tissues from AAA patients ( n=30) was compared with non-aneurysmal tissues from organ donors ( n=31) by dot blotting and immunohistochemistry. A significantly higher expression of Hcy was observed in AAA than control tissues ( p<0.001). Furthermore, the associations of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, detected by polymerase chain reaction-restriction fragment length polymorphism, with both AAA and tissue Hcy expression were evaluated. Our results showed MTHFR C677T polymorphism was not significantly associated with AAA or tissue Hcy expression. Lastly, the expression of Hcy in vascular smooth muscle cells (VSMCs), which were isolated from human aortic tissues by explant culture, and their release to cultured media was investigated by dot blotting. The AAA VSMCs expressed and released a significantly higher level of Hcy than the control VSMCs ( p<0.001). In summary, our novel findings showed Hcy expression was abnormally elevated in human AAA tissues, which may not be dependent on MTHFR C677T polymorphism.

  17. Decellularization of human and porcine lung tissues for pulmonary tissue engineering.

    PubMed

    O'Neill, John D; Anfang, Rachel; Anandappa, Annabelle; Costa, Joseph; Javidfar, Jeffrey; Wobma, Holly M; Singh, Gopal; Freytes, Donald O; Bacchetta, Matthew D; Sonett, Joshua R; Vunjak-Novakovic, Gordana

    2013-09-01

    The only definitive treatment for end-stage organ failure is orthotopic transplantation. Lung extracellular matrix (LECM) holds great potential as a scaffold for lung tissue engineering because it retains the complex architecture, biomechanics, and topologic specificity of the lung. Decellularization of human lungs rejected from transplantation could provide "ideal" biologic scaffolds for lung tissue engineering, but the availability of such lungs remains limited. The present study was designed to determine whether porcine lung could serve as a suitable substitute for human lung to study tissue engineering therapies. Human and porcine lungs were procured, sliced into sheets, and decellularized by three different methods. Compositional, ultrastructural, and biomechanical changes to the LECM were characterized. The suitability of LECM for cellular repopulation was evaluated by assessing the viability, growth, and metabolic activity of human lung fibroblasts, human small airway epithelial cells, and human adipose-derived mesenchymal stem cells over a period of 7 days. Decellularization with 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best maintenance of both human and porcine LECM, with similar retention of LECM proteins except for elastin. Human and porcine LECM supported the cultivation of pulmonary cells in a similar way, except that the human LECM was stiffer and resulted in higher metabolic activity of the cells than porcine LECM. Porcine lungs can be decellularized with CHAPS to produce LECM scaffolds with properties resembling those of human lungs, for pulmonary tissue engineering. We propose that porcine LECM can be an excellent screening platform for the envisioned human tissue engineering applications of decellularized lungs. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. A family of hyperelastic models for human brain tissue

    NASA Astrophysics Data System (ADS)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  19. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    PubMed

    Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

    2017-06-22

    Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Nutritional regulation of lipid metabolism in human adipose tissue.

    PubMed

    Coppack, S W; Patel, J N; Lawrence, V J

    2001-01-01

    Pfeiffer and colleagues years ago pointed out that different distributions and amounts of adipose tissue are associated with abnormalities of lipolysis and lipoprotein metabolism. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6. These adipose tissue actions are crucially regulated by nutrition. The review considers the existence of metabolic pathways and modes of regulation within adipose tissue, and how such metabolic activity can be quantitated in humans. Nutrition can influence adipose tissue at several 'levels'. Firstly the level of obesity or malnutrition has important effects on many aspects of adipose tissue metabolism. Secondly short-term overfeeding, underfeeding and exercise have major impacts on adipose tissue behaviour. Lastly, specific nutrients are capable of regulating adipose tissue metabolism. Recently there have been considerable advances in understanding adipose tissue metabolism and in particular its regulation. This review discusses the behaviour of adipose tissue under various nutritional conditions. There is then a review of recent work examining the ways in which nutritional influences act via intra-cellular mechanisms, insulin and the sympathetic innervation of adipose tissue.

  1. Meeting report: human fetal tissue transplantation research panel.

    PubMed

    Barnes, D W; Stevenson, R E

    1989-01-01

    On September 14 through 16, 1988, a meeting on the use of human fetal tissue in transplantation was held at the National Institutes of Health, Bethesda Maryland, USA. The meeting sponsored by NIH for the Human Fetal Tissue Transplantation Research Panel, a consultant group to the Advisory Committee to the Director. The consultant group was convened to deal with the scientific, judicial and moral questions associated with research involving transplantation of human fetal tissue obtained after induced abortions. The first day of the meeting was devoted to presentations addressing scientific issues. Included among the speakers was Dr. Lars Olson, Professor of Neurobiology, Karolinska Institute, Stockholm, who described the use of transplanted human fetal tissue in the treatment of patients with Parkinson's disease and Dr. Eugene Redmond, Professor of Psychiatry, Yale University School of Medicine, who showed results of work with transplantation of tissue to correct induced Parkinson-like disease in monkeys. Other speakers addressed the present, past or potential use of fetal tissue in the treatment of diabetes, immune disorders, and other diseases, as well as the use of fetal cells in the production of biologicals. At the conclusion of the meeting the panel did not recommend that research be halted on fetal tissue within the context discussed, although the recommendation of the committee is not binding, and an additional assembly of the panel will probably occur before the final recommendation to an NIH advisory committee is made in November. Other meetings on this subject include a meeting on the use of fetal tissue sponsored by the American Association of Tissue Banks, March 6-7, 1989, in Washington D. C. (Crystal City) and a meeting June 10, 1989, the day before the annual meeting of the Tissue Culture Association, USA, in Orlando, Florida, on fetal cells and ownership of cultured cells and products derived from clinical specimens. Following are statements to the

  2. Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population

    PubMed Central

    Köck, R.; Werner, P.; Friedrich, A.W.; Fegeler, C.; Becker, K.; Bindewald, O.; Bui, T.T.; Eckhoff, C.; Epping, R.; Kähmann, L.; Meurer, M.; Steger, J.; von Auenmüller, L.

    2015-01-01

    The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4–6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin-resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum β-lactamase–producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin-resistant S. aureus carriage was rare but highly associated with occupational livestock contact. PMID:26862431

  3. Beclomethasone Nasal Spray

    MedlinePlus

    ... the lining of the nose) after nasal polyp removal surgery. Beclomethasone nasal spray should not be used ... room temperature and away from excess heat and moisture (not in the bathroom).Unneeded medications should be ...

  4. Triamcinolone Nasal Spray

    MedlinePlus

    ... itchy nose and itchy, watery eyes caused by hay fever or other allergies. Triamcinolone nasal spray should not ... germs.Triamcinolone nasal spray controls the symptoms of hay fever and allergies but does not cure these conditions. ...

  5. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell culture...

  6. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell culture...

  7. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell culture...

  8. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell culture...

  9. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell culture...

  10. [Nasal septum cartilage-silica gel complex for repairing nasal deformities of unilateral cleft lip].

    PubMed

    Li, Qingwei; Sheng, Zunqi; Tang, Shengjian; Yang, Biaobing; Yu, Xiaohua

    2009-07-01

    To evaluate the operative methods and therapeutic effects of nasal septum cartilage-silica gel complex for two-stage repair of nasal deformities of unilateral cleft lip. From June 2001 to June 2007, 38 cases of secondary nasal deformity and septum deviation of cleft lip were treated with transplanting nasal septum cartilage-silica gel complex. Among of them, there were 21 males and 17 females, aging 14-23 years with an average of 17.6 years. All cases were with nasal deformities of unilateral cleft lip, including 21 cases of complete cleft lip and 17 cases of incomplete cleft lip. The locations were left side in 26 cases and right side in 12 cases. Nasal deformities were columella nasi deflexion, flattened nasal tip, pteleorrhine and alanasi collapse. The patients received 1-4 times operations, and the interval of two operations was 3-10 years (mean 5.5 years). According to nasal deformity, the nasal septum cartilage of 1.8 cm x 1.2 cm was cut, and transplanted into the nose point phantom surface forming "the shield" to extend nose column and to raise the tip of the nose. At the same time the nasal tip fat-connective tissue flap graft with fat knot was given. After fixation, the nasal alar cartilage and soft tissues were reduced to normal position. Primary healing of the incisions was achieved in all cases. The nasal deformity was corrected. The postoperative follow-up period was 12-18 months with an average of 15.6 months. All the patients of regional cartilage scars had no complication. The figure of nose was slinky, the height of apex of nose and the shape of nose was natural, the apex of nose, nasal ala, nostrils and nasal columella were satisfactory [(the results were satisfactory in 30 cases (78.9%), general in 8 cases (21.1%)]. The nose department overall esthetics shape was improved in all the patients, no complications of the phantom sliding, shifting and exposure, hemorrhage and infection occurred. The nasal septum cartilage-silica gel complex to repair

  11. [Exhaled and nasal nitric oxide in patients with Japanese cedar pollinosis and effects of nasal steroids].

    PubMed

    Miyazaki, Y

    1999-12-01

    Nitric oxide (NO) is produced by the action of NO synthase (NOS) using L-arginine as a substrate in various cells and found in air exhaled by humans. Previous studies suggest that almost all exhaled NO is derived from the upper airways and increases in patients with untreated asthma and allergic rhinitis. Exhaled NO is inhibited by treatment with inhalation of steroids that may be caused by inhibition of inducible nitric oxide synthase (iNOS). The purpose of this study is to determine whether exhaled and nasal NO increases in patients with Japanese cedar pollinosis compared with nonallergic healthy subjects, and whether it is affected by treatment with nasal steroids. Furthermore, we investigated its relation to nasal function and allergic rhinitis. 10 patients with Japanese cedar pollinosis and 5 healthy normal subjects were tested. All subjects had no history of respiratory infection for at least 2 weeks and did not smoke. Exhaled NO was collected in a sampling bag from oral and nasal breathing, and nasal NO was sampled directly from the nasal cavity. Both were measured by a chemiluminescence NO analyzer, ML9841, at a detection limit of 1 part per billion (ppb). Subjects used nasal steroids for 2 weeks and were measured similarly afterwards. NO concentrations in nasal air and air exhaled from the nose in patients with Japanese cedar pollinosis (277.9 +/- 59.5 ppb, 34.4 +/- 3.9 ppb, n = 10) were higher than the normal subjects (153.3 +/- 30.6 ppb, 19.9 +/- 3.4 ppb, n = 5) (p < 0.05). NO exhaled from the mouth was not significantly different between patients (20.5 +/- 4.9 ppb) and normal subjects (23.7 +/- 2.6 ppb). In patients with Japanese cedar pollinosis, the concentration of nasal NO and nasal exhaled NO were significantly decreased after treatment with nasal steroids (144.0 +/- 21.0 ppb, 26.1 +/- 3.0 ppb) (p < 0.01, p < 0.05), but there was no change in oral exhaled NO (17.2 +/- 3.3 ppb). In normal subjects, oral (22.5 +/- 5.3 ppb), nasal exhaled NO (19

  12. A New Antigen Retrieval Technique for Human Brain Tissue

    PubMed Central

    Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

    2008-01-01

    Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

  13. Nasal Harmony in Aguaruna.

    ERIC Educational Resources Information Center

    Moon, Gui-Sun

    A discussion of the nasal harmony of Aguaruna, a language of the Jivaroan family in South America, approaches the subject from the viewpoint of generative phonology. This theory of phonology proposes an underlying nasal consonant, later deleted, that accounts for vowel nasalization. Complex rules that suppose a complex system of vowel and…

  14. Nasal Harmony in Aguaruna.

    ERIC Educational Resources Information Center

    Moon, Gui-Sun

    A discussion of the nasal harmony of Aguaruna, a language of the Jivaroan family in South America, approaches the subject from the viewpoint of generative phonology. This theory of phonology proposes an underlying nasal consonant, later deleted, that accounts for vowel nasalization. Complex rules that suppose a complex system of vowel and…

  15. Nasal septal hematoma.

    PubMed

    Ginsburg, C M

    1998-04-01

    Nasal septal hematoma is a rare but potentially serious complication of nasal trauma. Proper management consists of early recognition, prompt surgical evacuation of the hematoma, and antimicrobial therapy if a secondary nasal septal abscess is suspected. Clindamycin is recommended as initial therapy until the results of cultures and susceptibility studies are available.

  16. Nasal computed tomography.

    PubMed

    Kuehn, Ned F

    2006-05-01

    Chronic nasal disease is often a challenge to diagnose. Computed tomography greatly enhances the ability to diagnose chronic nasal disease in dogs and cats. Nasal computed tomography provides detailed information regarding the extent of disease, accurate discrimination of neoplastic versus nonneoplastic diseases, and identification of areas of the nose to examine rhinoscopically and suspicious regions to target for biopsy.

  17. Human natural killer cell development in secondary lymphoid tissues

    PubMed Central

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  18. Mechanized syringe homogenization of human and animal tissues.

    PubMed

    Kurien, Biji T; Porter, Andrew C; Patel, Nisha C; Kurono, Sadamu; Matsumoto, Hiroyuki; Scofield, R Hal

    2004-06-01

    Tissue homogenization is a prerequisite to any fractionation schedule. A plethora of hands-on methods are available to homogenize tissues. Here we report a mechanized method for homogenizing animal and human tissues rapidly and easily. The Bio-Mixer 1200 (manufactured by Innovative Products, Inc., Oklahoma City, OK) utilizes the back-and-forth movement of two motor-driven disposable syringes, connected to each other through a three-way stopcock, to homogenize animal or human tissue. Using this method, we were able to homogenize human or mouse tissues (brain, liver, heart, and salivary glands) in 5 min. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometric enzyme assay for prolidase, we have found that the homogenates obtained were as good or even better than that obtained used a manual glass-on-Teflon (DuPont, Wilmington, DE) homogenization protocol (all-glass tube and Teflon pestle). Use of the Bio-Mixer 1200 to homogenize animal or human tissue precludes the need to stay in the cold room as is the case with the other hands-on homogenization methods available, in addition to freeing up time for other experiments.

  19. Human natural killer cell development in secondary lymphoid tissues.

    PubMed

    Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A

    2014-04-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field.

  20. The TissueNet v.2 database: A quantitative view of protein-protein interactions across human tissues

    PubMed Central

    Basha, Omer; Barshir, Ruth; Sharon, Moran; Lerman, Eugene; Kirson, Binyamin F.; Hekselman, Idan; Yeger-Lotem, Esti

    2017-01-01

    Knowledge of the molecular interactions of human proteins within tissues is important for identifying their tissue-specific roles and for shedding light on tissue phenotypes. However, many protein–protein interactions (PPIs) have no tissue-contexts. The TissueNet database bridges this gap by associating experimentally-identified PPIs with human tissues that were shown to express both pair-mates. Users can select a protein and a tissue, and obtain a network view of the query protein and its tissue-associated PPIs. TissueNet v.2 is an updated version of the TissueNet database previously featured in NAR. It includes over 40 human tissues profiled via RNA-sequencing or protein-based assays. Users can select their preferred expression data source and interactively set the expression threshold for determining tissue-association. The output of TissueNet v.2 emphasizes qualitative and quantitative features of query proteins and their PPIs. The tissue-specificity view highlights tissue-specific and globally-expressed proteins, and the quantitative view highlights proteins that were differentially expressed in the selected tissue relative to all other tissues. Together, these views allow users to quickly assess the unique versus global functionality of query proteins. Thus, TissueNet v.2 offers an extensive, quantitative and user-friendly interface to study the roles of human proteins across tissues. TissueNet v.2 is available at http://netbio.bgu.ac.il/tissuenet. PMID:27899616

  1. Staphylococcus aureus nasal carriage, virulence traits, antibiotic resistance mechanisms, and genetic lineages in healthy humans in Spain, with detection of CC398 and CC97 strains.

    PubMed

    Lozano, Carmen; Gómez-Sanz, Elena; Benito, Daniel; Aspiroz, Carmen; Zarazaga, Myriam; Torres, Carmen

    2011-08-01

    S. aureus nasal carriage was investigated in 278 healthy humans, determining the antibiotic resistance mechanisms, virulence traits, and genetic lineages of recovered isolates. Nasal samples were cultured in specific media for S. aureus and methicillin-resistant S. aureus (MRSA) recovery. S. aureus was detected in 53 of 278 nasal samples (19.1%): MRSA was found in one sample (0.4%) and methicillin-susceptible S. aureus (MSSA) in the remaining 52 samples. The MRSA isolate was typed as ST1649-t701-agrI-SCCmec-IVc and only exhibited resistance to beta-lactams. A high diversity of spa types (n=37) was identified among the 52 MSSA, identifying 5 new spa-types. Multi-locus sequence typing (MLST) typing was performed in 30 selected MSSA, detecting 16 different sequence types, 2 of them being new. MSSA strains presented agr types I (30.2%), II (30.2%), III (34%), and IV (5.6%). Eleven strains showed erythromycin resistance and harbored different combinations of erm(A), erm(B), erm(C), erm(T), and msr(A) genes. Two strains exhibited ciprofloxacin resistance, and one of them presented amino acid changes in GyrA and GrlA proteins. The presence of 28 genes encoding staphylococcal toxins was investigated by PCR in all 53 S. aureus isolates. The toxic shock syndrome toxin 1 (TSST-1) gene was detected in 15 MSSA isolates (11 of them typed within the clonal complex CC30) and the gene of exfoliative toxin A in 2 strains. Different combinations of enterotoxin genes were identified among S. aureus strains. None of the S. aureus isolates harbored the Panton-Valentine leukocidin gene. Two MSSA presented the sequence-type ST398 [harboring erm(T) gene], and 2 additional isolates were typed as ST97. Interestingly, MSSA CC398 and CC97 isolates were detected. These clonal complexes are associated with food-producing animals.

  2. Genetic effects on gene expression across human tissues.

    PubMed

    Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

    2017-10-11

    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

  3. Predicting Tissue-Specific Enhancers in the Human Genome

    SciTech Connect

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  4. Absorption and metabolism of the absorption enhancer didecanoylphosphatidylcholine in rabbit nasal epithelium in vivo.

    PubMed

    Vermehren, C; Johansen, P B; Hansen, H S

    1997-09-01

    The absorption enhancer, didecanoylphosphatidylcholine (DDPC), improves the nasal absorption of human growth hormone in rabbits. We elucidated the uptake and the metabolism of 1,2-di[1-14C]decanoyl-L-3-phosphatidylcholine and 1,2-didecanoyl-L-3-phosphatidyl[N-methyl-3H]choline in rabbit nasal mucosa in vivo. One minute after nasal application of DDPC, 4.4-7.5% of the applied dose was found absorbed into the mucosa. The retained radioactivity left the tissue in <2 hr. The lipophilic tissue extract revealed that, at t = 1 min, only 1.1-1.4% of the applied dose was found as intact DDPC in the nasal mucosa. The other labeled compounds were decanoic acid, DDPC reacylated with endogenous fatty acids, a neutral lipid, and very small amounts of lyso-DDPC and phosphatidylethanolamine. The water-soluble metabolites revealed formation of phosphorylcholine, glycerophosphorylcholine, cytidinediphosphatecholine, and a slight amount of choline. The detection of these metabolites suggests that DDPC was rapidly cleared from the nasal mucosa, partly by degradation by phospholipases. In addition, data illustrated reutilization of DDPC metabolites in the formation of cytidinediphosphatecholine and phosphatidylethanolamine, together with DDPC being reacylated with endogenous fatty acids. The rapid formation of decanoic acid raises the possibility that this acid may contribute significantly to the drug-enhancing properties of DDPC.

  5. High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers.

    PubMed

    Chew, G L; Huang, D; Lin, S J; Huo, C; Blick, T; Henderson, M A; Hill, P; Cawson, J; Morrison, W A; Campbell, I G; Hopper, J L; Southey, M C; Haviv, I; Thompson, E W

    2012-08-01

    Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

  6. Characterization of muscarinic receptor subtypes in human tissues

    SciTech Connect

    Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

    1988-01-01

    The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with (/sup 3/H)Pirenzepine and (/sup 3/H)N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M/sub 1/ neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M/sub 1/, the cardiac M/sub 2/ and the glandular M/sub 3/.

  7. Ethics, public policy, and human fetal tissue transplantation research.

    PubMed

    Childress, James F

    1991-06-01

    This article focuses on the deliberations of the National Institutes of Health Human Fetal Tissue Transplantation Research Panel in 1988. It explores various arguments for and against the use of fetal tissue for transplantation research, following elective abortion, and for and against the use of federal funds for such research. After examining the relevance of various positions on the moral status of the fetus and the morality of abortion, the article critically examines charges that such research, especially with federal funds, would involve complicity in the moral evil of abortion, would legitimate abortion practices, and would provide incentives for abortions. Finally, it considers whether the donation model is appropriate for the transfer of human fetal tissue and whether the woman who chooses to have an abortion is the apppropriate donor of the tissue.

  8. Dynamic transcriptional and epigenomic reprogramming from pediatric nasal epithelial cells to induced pluripotent stem cells

    PubMed Central

    Ji, Hong; Zhang, Xue; Oh, Sunghee; Mayhew, Christopher N.; Ulm, Ashley; Somineni, Hari K.; Ericksen, Mark; Wells, James M.; Khurana Hershey, Gurjit K.

    2014-01-01

    Background Induced pluripotent stem cells (iPSCs) hold tremendous potential, both as a biological tool to uncover the pathophysiology of disease by creating relevant human cell models, and as a source of cells for cell-based therapeutic applications. Studying the reprogramming process will also provide significant insight into tissue development. Objective We sought to characterize the derivation of iPSC lines from nasal epithelial cells isolated from the nasal mucosa samples of children, a highly relevant and easily accessible tissue for pediatric populations. Methods We performed detailed comparative analysis on the transcriptomes and methylomes of nasal epithelial cells, iPSCs derived from nasal epithelial cells (NEC-iPSCs), and ESCs. Results NEC-iPSCs express pluripotent cell markers, can differentiate into all three germ layers in vivo and in vitro, and have a transcriptome and methylome remarkably similar to ESCs. However, residual DNA methylation marks exist, which are differentially methylated between NEC-iPSCs and ESCs. A subset of these methylation markers related to epithelium development and asthma and specific to iPSCs generated from nasal epithelial cells persisted after several passages in vitro, suggesting the retention of an epigenetic memory of their tissue of origin. Our analysis also identified novel candidate genes with dynamic gene expression and DNA methylation changes during reprogramming, indicative of possible roles in airway epithelium development. Conclusion Nasal epithelial cells are an excellent tissue source to generate iPSCs in pediatric asthmatics, and detailed characterization of the resulting iPSC lines would help us better understand the reprogramming process and retention of epigenetic memory. PMID:25441642

  9. Photoacoustic characterization of human ovarian tissue

    NASA Astrophysics Data System (ADS)

    Aguirre, Andres; Ardeshirpour, Yasaman; Sanders, Mary M.; Brewer, Molly; Zhu, Quing

    2010-02-01

    Ovarian cancer has a five-year survival rate of only 30%, which represents the highest mortality of all gynecologic cancers. The reason for that is that the current imaging techniques are not capable of detecting ovarian cancer early. Therefore, new imaging techniques, like photoacoustic imaging, that can provide functional and molecular contrasts are needed for improving the specificity of ovarian cancer detection and characterization. Using a coregistered photoacoustic and ultrasound imaging system we have studied thirty-one human ovaries ex vivo, including normal and diseased. In order to compare the photoacoustic imaging results from all the ovaries, a new parameter using the RF data has been derived. The preliminary results show higher optical absorption for abnormal and malignant ovaries than for normal postmenopausal ones. To estimate the quantitative optical absorption properties of the ovaries, additional ultrasound-guided diffuse optical tomography images have been acquired. Good agreement between the two techniques has been observed. These results demonstrate the potential of a co-registered photoacoustic and ultrasound imaging system for the diagnosis of ovarian cancer.

  10. Large-scale discovery of enhancers from human heart tissue.

    PubMed

    May, Dalit; Blow, Matthew J; Kaplan, Tommy; McCulley, David J; Jensen, Brian C; Akiyama, Jennifer A; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Afzal, Veena; Simpson, Paul C; Rubin, Edward M; Black, Brian L; Bristow, James; Pennacchio, Len A; Visel, Axel

    2011-12-04

    Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

  11. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  12. Engineered human broncho-epithelial tissue-like assemblies

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor)

    2012-01-01

    Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

  13. Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants

    SciTech Connect

    Harkema, J.R. )

    1990-04-01

    The nasal cavity is susceptible to chemically induced injury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have a good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicant-induced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway.

  14. An improved cryopreservation procedure for human fetal pancreas tissues.

    PubMed

    Shiogama, T; Mullen, Y; Klandorf, H; Terada, M; Clark, W R

    1987-11-01

    Improved viability and function of insulin-producing beta (B) cells of frozen-stored human fetal pancreatic tissue was obtained by a two-step method utilizing high concentrations of dimethyl sulfoxide (DMSO). Human fetal pancreata (14-23-week gestation) obtained from pathologic abortions were teased and cultured overnight. Prior to freezing the tissues were immersed in 0.9% saline containing 0.5 M DMSO for 30 min (room temperature) and then placed in 2.1 M DMSO on ice for 5 min. The tissues were frozen by the method previously developed in our laboratory and stored at -196 degrees C. The frozen-stored tissues were subsequently thawed at 24 degrees C and cultured overnight before viability testing. Viability and function of the B cells were assessed by several specific assay methods; glucose plus theophylline-induced insulin release during static incubation and perifusion, 3H-leucine incorporation into insulin, and insulin content of the tissue grown in athymic mice for 7 days. The response to glucose plus theophylline stimulation, measured on the frozen-thawed tissue one day after thawing, was 80% of the level measured in control tissue maintained in organ culture. Frozen-thawed tissues maintained in organ culture for 1 week responded comparably in the in vitro assay systems. The insulin content of frozen-thawed pancreatic tissue removed from athymic mice 1 week after transplantation was approximately 60% of the amount measured in the control grafts. These results demonstrate the utility of our procedure in the maintenance of the viability and function of frozen-stored human B cells both in culture and after transplantation.

  15. Solubility of Freon 22 in human blood and lung tissue

    SciTech Connect

    Varene, N.; Choukroun, M.L.; Marthan, R.; Varene, P.

    1989-05-01

    The solubility of Freon 22 in human blood and lung tissue was determined using the chromatographic method of Wagner et al. In normal human blood, the mean Bunsen coefficient of solubility (alpha B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased with hematocrit (Hct) according to the equation alpha B = 0.274 Hct + 0.691. Tissue homogenates were prepared from macroscopically normal lung pieces obtained at thoracotomy from eight patients undergoing resection for lung carcinoma. The Bunsen solubility coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed and unwashed lung, respectively. These values can be used in the determination of both cardiac output and pulmonary tissue volume in humans by use of the rebreathing technique.

  16. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  17. [A case of neurinoma of the nasal septum].

    PubMed

    Sakamoto, Kikuo; Gondo, Kyujiro; Tomita, Kazuhide; Kasuya, Takao

    2003-05-01

    Neurinoma grows in the modulated nerve with Schwann cells, and is observed for all positions of the body. It is comparatively rare for neurinoma to grow in the nasal cavity and paranasal sinuses, however. We report a case of neurinoma of the nasal septum. A 24-year-old man seen for nasal obstruction was found in anterior rhinoscopy to have a tumor of the bilateral nasal cavity. Computed tomography (CT) showed a soft tissue density mass in the anterior part of the nasal cavity. Because we suspected neurinoma from biopsy, we resected the tumor by Denker's operation under general anesthesia. We found that it originated from the nasal septum. Histopathological findings of the tumor indicated an Antoni A type neurinoma. After surgery, cartilago costalis was transplanted the plastic surgery to correct the defect in the nasal septum. The post operative course was good and no signs of recurrence were seen. This is the 19th case found in the literature.

  18. Advancing biomaterials of human origin for tissue engineering

    PubMed Central

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  19. Advancing biomaterials of human origin for tissue engineering.

    PubMed

    Chen, Fa-Ming; Liu, Xiaohua

    2016-02-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  20. Glomus tissue in the vicinity of the human carotid sinus.

    PubMed Central

    Garfia, A

    1980-01-01

    Three of 60 cadavers have shown, in the adventitia or in the adipose tissue from the human carotid sinus region, small islands of tissue richly and typically vascularized and with nerve endings contacting cells like the tissue of the principal carotid body. In two of the cases such 'miniglomera' were single but in the third there were several all on the same side. A modified en bloc silver nitrate reduction stain was used to demonstrate the microvascular arrangements and the nerve endings by light microscopy of serial tangential sections of the carotid bifurcation. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7364653

  1. Immunohistochemical characterization of FHIT expression in normal human tissues

    PubMed Central

    Kujan, Omar; Abuderman, Abdulwahab; Al-Shawaf, Ahmad Zahi

    2016-01-01

    Background Fragile histidine triad (FHIT) is a tumor suppressor gene that is commonly inactivated in human tumors. Interestingly, the normal pattern of FHIT expression is largely unknown. Aim This study is aimed to characterize the expression of FHIT protein in normal human tissues. Materials and methods A total of 119 normal human tissue specimens were analyzed for the FHIT expression using immunohistochemistry technique. The inclusion criteria included: normal/inflammatory tissue with no evidence of cellular atypia. Results All studied specimens were stained positively with FHIT and showed either nuclear or cytoplasmic expression. Interestingly, the pattern of FHIT staining was similar among different specimens from each organ. FHIT is located predominantly in the nucleus, although cytoplasmic staining is also present in some cell types. Oral squamous epithelium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and bronchial epithelia all strongly expressed the nuclear protein. In connective tissue, FHIT has shown strong cytoplasmic expression in histocytes including macrophages and dendritic cells, fibroblasts, and myofibroblasts. Conclusion Documentation of the pattern of FHIT expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered FHIT expression in human tumors. PMID:28250975

  2. Biomechanical behavior of pericardial human tissue: a constitutive formulation.

    PubMed

    Pavan, Piero G; Pachera, Paola; Tiengo, Cesare; Natali, Arturo N

    2014-09-01

    This work aims to present a constitutive model suitable to interpret the biomechanical response of human pericardial tissues. The model is consistent with the need of describing large strains, anisotropy, almost incompressibility, and time-dependent effects. Attention is given to human pericardial tissue because of the increased interest in its application as a substitute in reconstructive surgery. Specific, even limited, experimental investigation has been performed on human samples taken from surgical grafts in order to verify the capability of the constitutive model in supplying a correct description of tissue mechanical response. Experimental data include uni-axial tensile tests and stress relaxation tests up to 300 s, developed along different directions of the tissue. The grafts tested show different mechanical characteristics for what concern the level of anisotropy of the tissue. The constitutive model proposed shows to adapt to the different configurations of the human pericardium grafts, as emerged by experimental data considered, and it is capable to describe the variability of the mechanical characteristics.

  3. Isolation and molecular characterization of methicillin-resistant coagulase-negative staphylococci from nasal flora of healthy humans at three community institutions in Rio de Janeiro City.

    PubMed Central

    Silva, F. R.; Mattos, E. M.; Coimbra, M. V.; Ferreira-Carvalho, B. T.; Figueiredo, A. M.

    2001-01-01

    We describe the isolation and molecular characterization of methicillin-resistant coagulase-negative staphylococci (MRCNS) from the nasal flora of healthy humans from three institutions located in Rio de Janeiro City. Swabs were obtained from the nares of students attending a non-residential public school and adults from two military quarters. Isolates of staphylococci were tested for the presence of the mecA gene by hybridization with a specific probe. S. epidermidis was the most frequent MRCNS (38 of the total 45 CNS isolated). Twenty-five percent of nasal staphylococcal carriers studied were colonized with MRCNS. Pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA was carried out to study the clonality of the methicillin-resistant S. epidermidis (MRSE) isolates. In addition to cross-colonization among individuals belonging to the same institution, familial cross-colonization appeared to contribute to the spread of the methicillin-resistant isolates among two inter-communicable institutions. Indeed, the wide genomic diversity among the MRSE flora suggests that the spread of the mecA gene among these isolates might also have occurred via horizontal transmission. Despite the limited number of institutions analysed, it is reasonable to conclude that our data do not represent a situation unique to the three organizations but may reflect other communities in Rio with respect to transmission of MRCNS. PMID:11561975

  4. Low prevalence of oral and nasal human papillomavirus in employees performing CO2-laser evaporation of genital warts or loop electrode excision procedure of cervical dysplasia.

    PubMed

    Kofoed, Kristian; Norrbom, Christina; Forslund, Ola; Møller, Charlotte; Frøding, Ligita P; Pedersen, Anders Elm; Markauskas, Algirdas; Blomberg, Maria; Baumgartner-Nielsen, Jane; Madsen, Jakob Torp; Strauss, Gitte; Madsen, Klaus G; Sand, Carsten

    2015-02-01

    Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p = 0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p = 0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.

  5. Near Infrared Spectral Determination of Human Tissue pH.

    DTIC Science & Technology

    1995-10-01

    Continuous Tissue pH Monitory in the Human Fetus During Labor", Obstet . Gynecol ., 55:523, 1980. 23. [Lemer 82] Lemer, H., et al., "Measurement of Glucose...Umbilical Blood pH", Am. J. Obstet . Gynecol ., 128: 901-903, 1977. 38. [Weyer 85] Weyer, L G., "Near Infrared Spectroscopy of Organic Substances," Applied...Patterns and Tissue pH in the Human Fetus", Am. J. Obstet . Gynecol ., 134:685-690, 1979. 24 Appendix I An Estimation Extension of the FKNN Algorithm In

  6. Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.

    PubMed

    Hubbard, Dallin; Enda, Michael; Bond, Tanner; Moghaddam, Seyyed Pouya Hadipour; Conarton, Josh; Scaife, Courtney; Volckmann, Eric; Ghandehari, Hamidreza

    2015-11-02

    Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.

  7. Discordance of DNA Methylation Variance Between two Accessible Human Tissues

    PubMed Central

    Jiang, Ruiwei; Jones, Meaghan J.; Chen, Edith; Neumann, Sarah M.; Fraser, Hunter B.; Miller, Gregory E.; Kobor, Michael S.

    2015-01-01

    Population epigenetic studies have been seeking to identify differences in DNA methylation between specific exposures, demographic factors, or diseases in accessible tissues, but relatively little is known about how inter-individual variability differs between these tissues. This study presents an analysis of DNA methylation differences between matched peripheral blood mononuclear cells (PMBCs) and buccal epithelial cells (BECs), the two most accessible tissues for population studies, in 998 promoter-located CpG sites. Specifically we compared probe-wise DNA methylation variance, and how this variance related to demographic factors across the two tissues. PBMCs had overall higher DNA methylation than BECs, and the two tissues tended to differ most at genomic regions of low CpG density. Furthermore, although both tissues showed appreciable probe-wise variability, the specific regions and magnitude of variability differed strongly between tissues. Lastly, through exploratory association analysis, we found indication of differential association of BEC and PBMC with demographic variables. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and helps guide decisions on the suitability of buccal epithelial or peripheral mononuclear cells for the biological questions explored by epigenetic studies in human populations. PMID:25660083

  8. Use of computational fluid dynamics models for dosimetry of inhaled gases in the nasal passages.

    PubMed

    Kimbell, J S; Subramaniam, R P

    2001-05-01

    Computational fluid dynamics (CFD) models of the nasal passages of a rat, monkey, and human are being used (1) to determine important factors affecting nasal uptake, (2) to make interspecies dosimetric comparisons, (3) to provide detailed anatomical information for the rat, monkey, and human nasal passages, and (4) to provide estimates of regional air-phase mass transport coefficients (a measure of the resistance to gas transport from inhaled air to airway walls) in the nasal passages of all three species. For many inhaled materials, lesion location in the nose follows patterns that are both site and species specific. For reactive, water-soluble (Category 1) gases, regional uptake can be a major factor in determining lesion location. Since direct measurement of airflow and uptake is experimentally difficult, CFD models are used here to predict uptake patterns quantitatively in three-dimensional reconstructions of the F344 rat, rhesus monkey, and human nasal passages. In formaldehyde uptake simulations, absorption processes were assumed to be as rapid as possible, and regional flux (transport rate) of inhaled formaldehyde to airway walls was calculated for rats, primates, and humans. For uptake of gases like vinyl acetate and acrylic acid vapors, physiologically based pharmacokinetic uptake models incorporating anatomical and physical information from the CFD models were developed to estimate nasal tissue dose in animals and humans. The use of biologically based models in risk assessment makes sources of uncertainty explicit and, in doing so, allows quantification of uncertainty through sensitivity analyses. Limited resources can then be focused on reduction of important sources of uncertainty to make risk estimates more accurate.

  9. Evaluation of nasal IgA secretion in normal subjects by nasal spray and aspiration.

    PubMed

    Fujimoto, Chisa; Kido, Hiroshi; Sawabuchi, Takako; Mizuno, Dai; Hayama, Masaki; Yanagawa, Hiroaki; Takeda, Noriaki

    2009-06-01

    Nasal washing (NW) is a popular method for collecting human nasal lavage fluid. However, for NW the subject must be trained, and the method is unsuitable for field studies on untrained subjects. To overcome this problem, we have developed an easy and painless method, a nasal spray and aspiration (NSA) method. This method is different from NW in that the nasal cavity is misted over with saline, and the nasal lavage fluid is aspirated from the nostrils through a silicon tube. First, nasal lavage fluid was obtained twice by NSA with an interval of a week between lavages to evaluate intraindividual variability, and the IgA and protein levels in the nasal lavage fluid were measured by enzyme-linked immunosorbent assay and bicinchoninic acid assay, respectively. Next, the IgA value determined by NSA was compared with that by NW in another 12 normal subjects 2 days after NSA. In 10 normal subjects, mean volume of saline sprayed into the nose was 0.46+/-0.15 ml (mean+/-S.D.). Mean volume of aspirated nasal lavage fluid containing both sprayed saline and nasal secretion was 0.44+/-0.37 ml. The mean IgA level/mg protein in the nasal lavage fluid determined by NSA was 112+/-18 microg/mg protein at the first and 99+/-20 at the second times of measurement, being highly reproducible. The mean value by NSA was 114+/-19 microg/mg protein, being almost the same as that by NW of 99+/-27. These findings suggest that the IgA level/mg protein in nasal lavage fluid determined by NSA instead of NW might be useful for assessing the variability of nasal IgA secretion.

  10. Cortisol in human tissues at different stages of life.

    PubMed

    Costa, A; Benedetto, C; Fabris, C; Giraudi, G F; Testori, O; Bertino, E; Marozio, L; Varvello, G; Arisio, R; Ariano, M; Emanuel, A

    1996-01-01

    Aim of the work was to measure the cortisol level in human tissues at different stages of life, by means of radioimmunoassay and by chromatography. Viable samples of 13 different tissues were obtained during surgical intervention from 30 to 70 years old patients of either sex. Mean tissue cortisol concentration was 78 +/- 35 ng/g, ranging from 20 +/- 10 ng/g in the thyroid to 124 +/- 76 ng/g in the kidney. Similar values were measured in the corresponding tissues from not decayed corpses, so that paired values could be mediated. However the pancreas, and corrupted autopsy tissues, gave nil or exceedingly high cortisol concentration values; in some cases, opposite extreme values were measured in different organs of the same body. Cortisol concentration was also measured in 11 sound different tissues of spontaneously aborted or stillbirth fetuses, between 16 and 36 weeks of gestation. Mean value was 63 +/- 27 ng/g, ranging from 30 +/- 25 ng/g in the liver to 104 +/- 52 ng/g in the lungs. Also in fetuses nil or exceedingly high cortisol values occurred in altered tissues. One hundred and fourteen samples of limbs and carcasses of 7 to 12 gestational weeks embryos, obtained from voluntary abortions, were also examined: 20% gave nil result, in the remaining mean cortisol concentration was 32 ng/g. In 33 samples of embryos' mixed viscera, RIA and chromatography gave unreliable exceedingly high values. The nil and the exceedingly high values measured in the altered autoptic tissue specimens were inconsistent with the cortisol blood level measured in the patients, as were those measured in embryonic tissues with the acknowledged blood and adrenals cortisol levels at that stage of life. Thus cortisol may be measured by RIA and by chromatography in sound tissues, while the values obtained in the pancreas, in corrupted tissues, and in embryonal viscera do not represent the hormonal milieu, but are likely artifacts due to impeachment of the diagnostic system.

  11. Inhaled cellulosic and plastic fibers found in human lung tissue.

    PubMed

    Pauly, J L; Stegmeier, S J; Allaart, H A; Cheney, R T; Zhang, P J; Mayer, A G; Streck, R J

    1998-05-01

    We report the results of studies undertaken to determine whether inhaled plant (i.e., cellulosic; e.g., cotton) and plastic (e.g., polyester) fibers are present in human lungs and, if so, whether inhaled fibers are also present in human lung cancers. Specimens of lung cancer of different histological types an