OBJECTIVES: Regenerative treatment using stem cells may serve as treatment option for empty nose syndrome (ENS), which is caused by the lack of turbinate tissue and deranged nervous system in the nasal cavity. We aimed to assess the efficacy and safety of the autologous stromal vascular fraction (SVF) in the treatment of ENS. METHODS: In this prospective observational clinical study, we enrolled 10 ENS patients who volunteered to undergo treatment of ENS through the injection of autologous SVF. Data, including demographic data, pre- and postoperative Sino-Nasal Outcome Test-25 (SNOT-25) scores, overall patient satisfaction, and postoperative complications, were prospectively collected. Nasal secretion was assessed using the polyurethane foam absorption method, and the levels of biological markers were analyzed in both ENS group and control group using enzyme-linked immunosorbent assay. The SVF extracted from abdominal fat was diluted and injected into both inferior turbinates. RESULTS: Among the 10 initial patients, one was excluded from the study. Subjective satisfaction was rated as “much improved” in two and “no change” in seven. Among the improved patients, the mean preinjection SNOT-25 score was 55.0 and the score at 6 months after injection was 19.5. However, the average SNOT-25 score of nine participants at 6 months after injection (mean±standard deviation, 62.4±35.8) did not differ significantly from the baseline SNOT-25 score (70.1±24.7, P>0.05, respectively). Among the various inflammatory markers assessed, the levels of interleukin (IL)-1β, IL-8, and calcitonin gene-related peptide were significantly higher in ENS patients. Compared with preinjection secretion level, the nasal secretions from SVF-treated patients showed decreased expressions of IL-1β and IL-8 after injection. CONCLUSION: Although SVF treatment appears to decrease the inflammatory cytokine levels in the nasal mucosa, a single SVF injection was not effective in terms of symptom improvement and patient satisfaction. Further trials are needed to identify a more practical and useful regenerative treatment modality for patients with ENS.
Abdominal Fat ; Absorption ; Biomarkers ; Calcitonin Gene-Related Peptide ; Clinical Study ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-8 ; Interleukins ; Methods ; Nasal Cavity ; Nasal Mucosa ; Nervous System ; Nose* ; Patient Satisfaction ; Polyurethanes ; Postoperative Complications ; Prospective Studies ; Stem Cells ; Turbinates

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08–3.00 h, 0.03–0.10 h and 0.03–0.10 h, respectively) and were eliminated with mean half-lives of 9.29–10.44 h, 6.09–12.39 h and 0.25–47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250–750 µg and 50–150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.
Charcoal ; Fluticasone* ; Gastrointestinal Absorption ; Humans ; Inhalation* ; Lung Diseases, Obstructive ; Male ; Pharmacokinetics ; Plasma ; Pulmonary Disease, Chronic Obstructive ; Respiratory Tract Absorption ; Salmeterol Xinafoate* ; Tiotropium Bromide*

The lymphatic vasculature has been regarded as a passive conduit for interstitial fluid and responsible for the absorption of macromolecules such as proteins or lipids and transport of nutrients from food. However, emerging data show that the lymphatic vasculature system plays an important role in immune modulation. One of its major roles is to coordinate antigen transport and immune-cell trafficking from peripheral tissues to secondary lymphoid organs, lymph nodes. This perspective was recently updated with the notion that the interaction between lymphatic endothelial cells and leukocytes controls the immune-cell migration and immune responses by regulating lymphatic flow and various secreted molecules such as chemokines and cytokines. In this review, we introduce the lymphatic vasculature networks and genetic transgenic models for research on the lymphatic vasculature system. Next, we discuss the contribution of lymphatic endothelial cells to the control of immune-cell trafficking and to maintenance of peripheral tolerance. Finally, the physiological roles and features of the lymphatic vasculature system are further discussed regarding inflammation-induced lymphangiogenesis in a pathological condition, especially in mucosal tissues such as the gastrointestinal tract and respiratory tract.
Absorption ; Chemokines ; Cytokines ; Endothelial Cells ; Endothelium ; Extracellular Fluid ; Gastrointestinal Tract ; Leukocytes ; Lymph Nodes ; Lymphangiogenesis ; Mucous Membrane ; Peripheral Tolerance ; Respiratory System

OBJECTIVES/HYPOTHESIS: Prostasin is a protease that activates epithelial sodium channels (ENaC), which mediate Na+ absorption across epithelial surfaces. Human nasal polyps absorb more ENaC-mediated Na+ than normal mucosa. We investigated the expression and distribution of prostasin in normal mucosa and nasal polyp. STUDY DESIGN: This was a controlled, prospective study. METHODS: The distribution patterns and levels of expression of prostasin in normal sinus mucosa and nasal polyps were evaluated using real-time polymerase chain reaction (PCR), immunohistochemical staining and western blotting. RESULTS: Real-time PCR revealed that the mRNA expression of prostasin was higher in nasal polyps than in normal sinus mucosa. The expression of prostasin was faint in immunohistochemical staining of superficial epithelial cells and submucosal glandular epithelial cells of normal sinus mucosa, but was intense in superficial epithelial cells and submucosal glandular epithelial cells in nasal polyps. Inflammatory cells infiltrating into the nasal mucosa also showed prostasin immunoreactivity in nasal polyps. Western blot analysis with prostasin antiserum detected prostasin protein in normal sinus mucosa and nasal polyps. The expression levels of prostasin were increased in nasal polyps compared with normal sinus mucosa. CONCLUSIONS: The levels of expression of prostasin were upregulated in nasal polyps compared to normal sinus mucosa, suggesting a role in the pathogenesis of nasal polyps. However, the exact pathophysiologic function of prostasin in nasal epithelium warrants further investigation.
Absorption ; Blotting, Western ; Epithelial Cells ; Epithelial Sodium Channels ; Humans ; Mucous Membrane ; Nasal Mucosa ; Nasal Polyps ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Serine Endopeptidases ; Up-Regulation

PURPOSE: In order to maintain corrected nasal tip projection, strong support is important. Authors used calvarial bone graft method for this purpose. Patients were followed up about permanency of the bone graft for a long time. METHODS: From 1995 to 1998, author performed calvarial bone graft on 30 adult patients with secondary cleft lip and nose deformity. Patients were observed for 34 months. There were no specific complications, and results were satisfactory. We could confirm the permanence of the calvarial bone graft in 3 patients by photography and radiologic studies for 10 years follow-up. RESULTS: None of the patients showed size change or displacement. But the portion of graft facing the tip was absorbed resulting in loss of tip projection and short nose in two patients. One patient had fracture on the middle of the graft. This caused depression from lower portion of the dorsum to the tip. CONCLUSION: Despite of autogenous grafts such as calvarial bone, absorption of the bone may occur when compressed with tension for a long period. And the graft in the nasal tip not having any contact with the nasal bone may cause absorption of the graft.
Absorption ; Adult ; Cleft Lip ; Congenital Abnormalities ; Depression ; Displacement (Psychology) ; Follow-Up Studies ; Humans ; Nasal Bone ; Nose ; Photography ; Transplants

OBJECTIVETo observe the influence of natural borneol and synthetic borneol on mucosal permeability of Gardenia extract.

METHODTaken frog skin as a vitro model to study the vitro mucosal permeation the impacts of the natural borneols and synthetic borneols on the P(app) of the Jasminoidin were studied, and the effect of different borneols on the stability of Jasminoidin were investigated. Compared the 10 h accumulated infiltration rate of each group the effects of influence factors,such as C(Ge), C(B) and rotation speed on P(app) were investigated by using response surface method.

RESULTThe P(app) of Jasminoidin of natural borneol and synthetic borneol group were 1.44 fold and 1.77 fold of control group (P < 0.01). For two borneol groups, the results also showed a significant difference too (P < 0.05). Jasminoidin began to degrade about 8 h after the effect of frog skin for control group and synthetic borneol group, but was stable within 12 h for natural borneol group. The accumulated permeation rate of 10 h was same for different borneol groups. It was about 1.3 fold of control group. The C(Ge) had a salinence influence on the P(app) (P < 0.01) and C(B) had a salience influence on time-lag (P < 0.01).

CONCLUSIONBoth the natural borneol and synthetic borneol can accelerate the permeation of Jasminoidin and the synthetic borneol has stronger effect on the P(app). Both two different borneol can reduce the degradation effect of frog skin to Jasminoidin, but the natural borneol has a better protect effect on it. By using more natural borneol, the mucosal permeability of Gardenia extract can be increased, the time-lag can be reduced, and Jasminoidin has better stability.

Administration, Cutaneous ; Bornanes ; chemical synthesis ; pharmacokinetics ; Dosage Forms ; Drugs, Chinese Herbal ; chemistry ; Gardenia ; chemistry ; Iridoids ; pharmacology ; Mucous Membrane ; metabolism ; Nasal Mucosa ; metabolism ; Permeability ; Skin ; metabolism ; Skin Absorption

OBJECTIVETo investigate the absorption enhancen effect of borneol/mentholum eutectic mixture (BO/ME) on nasal-brain delivery of neurotoxin loaded nanoparticles.

METHODUsing microdialysis sampling technique in awake freely-moving rats, the counter per minute (cpm) of dialysates in right PAG of NT-loaded nanoparticles with the BO/ME (BO/ME-NT-NP), radiolabeled with sodium 125I-Iodide, were measured in a gamma-counter for radioactivity. After converting cpm into corresponding concentrations of NT byin vivorecovery of microdialysis probes, the pharmacokinetic parameters were calculated.

RESULTThe BO/ME-NT-NP could be absorbed into the brain, much better to NT-NP and the nanoparticles with borneol or menthdlum only, and the pharmacokinetics accorded with the two-compartment model. The parameters tmax, cmax, AUC, t 1/2(beta) were 0.68 h, 27.32 ng x mL(-1), 132.68 ng x h x mL(-1), 3.1076 h.

CONCLUSIONWith adding BO/ME as absorption enhancer, NT could be significantly increased in the brain with the help of nanopartilces as carriers, and the time to maximal concentration was short, the elimination process was prolonged.

Absorption ; drug effects ; Animals ; Bornanes ; chemistry ; pharmacology ; Brain ; metabolism ; Drug Carriers ; pharmacokinetics ; Male ; Menthol ; chemistry ; pharmacology ; Microdialysis ; Nanoparticles ; Nasal Cavity ; metabolism ; Neurotoxins ; administration & dosage ; pharmacokinetics ; Rats

BACKGROUND AND OBJECTIVES: Nasal mucosal pH have a direct effect on the alteration of the physio-chemical characteristics of the nasal mucosa. Previous studies have reported the normal mucosal pH to be within the range of 5.3-7.0, mucosal pH with sinusitis to be within 6.8-7.6 and mucosal pH with rhinitis to be within 7.2-8.3. However, no consideration was paid to the conditions that influence the pH and there were no measured pH value by different methods. This study was therefore designed with the latest trend method in pH measurement with the purpose of evaluating pH in nasal secretion and creating an objective parameter for a beneficial manifestation of mucosa. MATERIALS AND METHODS: We measured the pH values from 30 normal control group (group 1), 30 patients with chronic sinusitis (group 2), and 30 patients with allergic rhinitis (group 3). Nasal secretion was obtained through filter paper absorption method and, using a micro pH electrode with pH meter, pH was measured in nasal secretion. RESULTS: pH in nasal secretion in this study was higher than the nasal mucosal pH from previously reported studies. pH values in nasal secretion showed a significant difference between three groups (group 1:7.86, group2:8.06, group 3:8.24) in this study (p<0.01). CONCLUSION: The measurement of pH in nasal secretion seems to be a useful parameter for monitoring and assessing the state of nasal mucosa. And we recommend this study as a method for obtaining an objective parameter for pH measurement in nasal cavity.
Absorption ; Electrodes ; Humans ; Hydrogen-Ion Concentration ; Nasal Cavity ; Nasal Mucosa ; Rhinitis ; Rhinitis, Allergic, Perennial ; Sinusitis

The aim of this study is to investigate absorption-promoting mechanism of enhancers and the transport pathway of large hydrophilous molecular across rat nasal epithelium by electron spin resonance (ESR) and confocal laser scanning microscopy (CLSM) technologies. In the experiment, recombinant hirudin-2 (rHV2) was chosen as a large hydrophilic molecular model drug. After nasal administration in rats the bioavailability of rHV2 with or without various enhancers was compared. The effects of enhancers on membrane lipid fluidity and protein conformation were measured with 5-deoxyl-stearic acid (5-DSA), 16-deoxyl-stearic acid (16-DSA) and 3-maleidoproxyl (MSL) labeling ESR. The effects of enhancers on cytoskeletal F-actin of rat nasal epithelium and FITC-rHV2 transport pathway across rat nasal epithelium were performed by CLSM combined with fluorescence labeling. 0.5% Chitosan (CS), 5% hydroxyl-propyl-beta-cyclodextrin ( HP-beta-CD) and 1% ammonium glycyrrhizinate (AMGZ) were all able to significantly increase the nasal absorption of rHV2. CS could result in the paracellular pathway transport of FITC-rHV2 which seemed related to a transient effect on tight junctions. HP-beta-CD could cause paracellular and transcellular route transport of FITC-rHV2 by influencing upon membrane protein as well as lipid fluidity. AMGZ seemed to enhance the transcellular route transport of FITC-rHV2, and could exert some influence on membrane protein but not on lipid fluidity. So how it brought out this result needs further research. Present experiment may become a useful reference for promoting mechanism of enhancers and the transport pathway of large hydrophilic molecular across nasal epithelium research.
2-Hydroxypropyl-beta-cyclodextrin ; Absorption ; Administration, Intranasal ; Animals ; Area Under Curve ; Biological Availability ; Biological Transport ; drug effects ; Chitosan ; pharmacology ; Electron Spin Resonance Spectroscopy ; Glycyrrhizic Acid ; pharmacology ; Hirudins ; blood ; pharmacokinetics ; Male ; Microscopy, Confocal ; Nasal Cavity ; Nasal Mucosa ; metabolism ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; blood ; pharmacokinetics ; beta-Cyclodextrins ; pharmacology

OBJECTIVETo study Xionggui nasal sprays and its evaluation in release in vitro and absorption in vivo.

METHODEstablishing the best prescription of Xionggui nasal sprays through orthogonal design methods, The in vitro release action of Xionggui nasal sprays was studied using dynamic dialyse method. The in vivo rat nasal recirculation methods were used to study the rule of Xionggui nasal sprays absorption.

RESULTThe optimum prescription was: Pemulen TR-1 0.35%, EDTA 0.2%, PEG400 1%, xanthan gum 0.2%; trolamine: right amount(adjust pH). Its release in vitro and absorption in vivo meet to Higuchi distribution.

CONCLUSIONThe preparation method of Xionggui nasal sprays was appropriate. The release of drug and its uptake was well correlated.

Absorption ; Administration, Intranasal ; Aerosols ; Angelica sinensis ; chemistry ; Animals ; Drug Carriers ; Drug Combinations ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Edetic Acid ; Emulsions ; Ethanolamines ; Female ; Ligusticum ; chemistry ; Male ; Nasal Mucosa ; metabolism ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; Polysaccharides, Bacterial ; Rats ; Rats, Sprague-Dawley