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

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

BACKGROUND AND OBJECTIVES: Recent evidence has shown that nitric oxide (NO) levels are increased in allergic rhinitis. However, the role of this molecule in the pathophysiology of allergic rhinitis is still poorly understood. Peroxynitrite (OONO-), the reactive metabolites of NO, causes nitrotyrosine formation by the nitration of tyrosine residues, and promotes deleterious effects on protein function. We attempted in this study to clarify whether NO and nitrotyrosine in the nasal secretion could be increased in the early or the late phase reaction after allergen challenge. MATERIALS AND METHODS: Samples were obtained from thirteen patients with allergic rhinits to Dermatophagoides Pteronyssinus with the filter paper absorption method. The samples were collected right before, 30 minutes after, and 8 hours after the allergen challenge. Then we estimated the concentrations of nitrite (NO2-) and nitrate (NO3-). Nitrotyrosine in nasal secretions was determined by Western blot analysis in three patients. RESULTS: The nitrite/nitrate concentration in nasal secretions did not show significant changes between the baseline, the early, and the late phase (p>0.05). In the Western blot analysis, the concentration of nitrotyrosine was increased in the late phase. CONCLUSIONS: Although the NO was not increased after the allergen challenge, nitrotyrosine, the evidence of the peroxynitrite effect to tyrosine residues of the protein, was increased in the late phase of the reaction rather than the early phase. Because the peroxynitrite is an metabolite of NO, we can estimate that the overall NO effect has an influence on the late phase of the allergic reaction, and it can be presumed that NO has an influence on the long-term deterioration on the nasal mucosa by cytotoxic effect of peroxynitrite, rather than on the immediate reaction of allergic rhinitis.
Absorption ; Blotting, Western ; Dermatophagoides pteronyssinus ; Humans ; Hypersensitivity ; Nasal Mucosa ; Nitric Oxide* ; Peroxynitrous Acid* ; Rhinitis* ; Tyrosine

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

To investigate the possibility of utilizing of sister chromatid exchange(SCE) analysis in lymphocytes as an indicator which could evaluate the effects of mutagenicity after in vivo exposure to hexavalent chromium, this study was conducted using some of chromium plating workers occupationally exposed to hexavalent chromium, chromium trioxide (CrO3) in Taegu city. The study population was 12 Cr platers with perforation of nasal septum, 12 Cr platers without perforation of nasal septum and 20 controls. The SCE in peripheral blood lymphocytes of the subjects was analyzed and blood chromium concentration was estimated using the atomic absorption spectrophotometer (IL 551) equipped with furnace atomizer (IL 755). The mean SCE frequencies for Cr platers with and without perforation of nasal septum were statistically higher than those for control. The difference in SCE frequencies by age, smoking habits were not statistically significant both in Cr platers and controls. There was no difference in SCE frequencies by career of Cr platers workers. In Cr platers, the correlation between the mean SCE frequencies and chromium concentration in blood was not statistically significant. Using the transformation y=(sum SCE)1/2+(sum SCE+1)1/2, when the data was studied by multiple regression, it appeared that the influence of the occupation was the most important. Age, smoking, occupation and CrB(blood chromium concentration) together explain only 32.3% of interpersonal variation on SCE. The results in this study suggest that a genetic risk due to occupationally exposure to hexavalent chromium is clearly inferable and thus, SCE analysis in human lymphocytes may be used indicator of biological toxic effects of chromium. Further, populatio analysis studies are required before SCE frequency can be used as a mutagenic indicator in human population.
Absorption ; Chromatids ; Chromium* ; Daegu ; Humans ; Lymphocytes* ; Nasal Septum ; Nebulizers and Vaporizers ; Occupations ; Siblings* ; Sister Chromatid Exchange* ; Smoke ; Smoking

Nasal dorsal suppor may be weakened or lost during the corrective rhinoplasty procedures such as resection of dorsal deviation, osteotomies and reposition of deviated nasal bones, and incision, fracture, resection or scoring of the dorsal septal strut especially in the small flat noses. Partial or total augmentation of the nasal dorsum has an important role in the correction of asymmetry and restoration of aesthetic balance in the considerable amount of traumatic nasal deformities. We reviewed medical records, pre- and postoperative photographs of 53 patients with traumatic nasal deformities, which had been corrected by augmentation rhinoplasties. The majority of the patients were male (70%), ages of twenties and thirties (79%), injection by automobile accident, fist blows, and sports activities (76%), and were operated more than 3 years after injury (74%). Types of deformities were deviation only (47%), depression only (23%), deviation and depression (19%), deviation and hump (8%), and depression and widening (6%). At least two corrective procedures were needed in the deviated deformities and one procedure in the depressed deformities. Materials for augmentation were silicone implants in 55% and autogenous tissues in 45%. In terms of postoperative complications, displacement and/or absorption were observed in 6 of 24 (25%) autogenous augmentations and displacement and/or swelling in 8 of 29 (27.6%) silicone augmentations.
Absorption ; Automobiles ; Congenital Abnormalities* ; Depression ; Humans ; Male ; Medical Records ; Nasal Bone ; Nose ; Osteotomy ; Postoperative Complications ; Rhinoplasty* ; Silicones ; Sports

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

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