BACKGROUND: Airway secretions partly arise from the interstitial fluid and partly from the secretory activities of respiratory epithelium and submucosal gland. The flow of water across the tracheobronchial epithelium is likely to be an important determinant of the efficiency of mucociliary clearance. Water movement across the epithelium is thought to follow active ion transport passively by means of the osmotic gradients created. OBJECTIVES: The aim of this study was to determine whether Na, K, and Cl are transported actively by the epithelium of nasal mucosa and to evaluate an effect of the tracheostomy on changes of pH and electrolytes in nasal secretum. MATERIALS AND METHODS: pH and Na, K, and Cl values were estimated in 35 samples (20 tracheostomized patients and 15 normal persons) of nasal secretum and plasma. RESULTS: On 15 normal persons, Mean pH value was 7.43, Na 143.2, K 4.2 and Cl 109.1(mEq/L) in plasma and Mean pH value was 7.81, Na 139.7, K 11.5 and Cl 127.5(mEq/L) in nasal secretion. On 20 tracheostomized patients, pH 7.49, Na 140.2, K 3.8, and Cl 108.7(mEq/L) in plasma were estimated, and pH 7.88, Na 128.5, K 12.0, and Cl 121.5(mEq/L) were estimated in nasal secretum. In nasal secretum pH, K, and Cl were higher than in plasma by +0.39, +8.2 and +12.8(mEq/L) respectively, while Na was lower -11.6(mEq/L). We had the same result on normal persons as on tracheostomized patients. The results show that pH, K and Cl were higher in nasal secretion and Na was lower than in plasma. CONCLUSION: Significant difference of pH and electrolyte values in nasal secretion was not observed between normal person and tracheostomized patient.
Biological Transport, Active ; Electrolytes ; Epithelium ; Extracellular Fluid ; Humans ; Hydrogen-Ion Concentration* ; Ion Transport ; Mucociliary Clearance ; Nasal Mucosa ; Plasma ; Respiratory Mucosa ; Tracheostomy ; Water Movements

The ionic quantity across the channel of the cell membrane decides the cell in a certain life state. The theory analysis that existed on the bio-effects of the electro-magnetic field (EMF) does not unveil the relationship between the EMF exerted on the cell and the ionic quantity across the cell membrane. Based on the cell construction, the existed theory analysis and the experimental results, an ionic probability wave theory is proposed in this paper to explain the biological window-effects of the electromagnetic wave. The theory regards the membrane channel as the periodic potential barrier and gives the physical view of the ion movement across cell-membrane. The theory revises the relationship between ion's energy in cell channel and the frequency exerted EMF. After the application of the concept of the wave function, the ionic probability across the cell membrane is given by the method of the quantum mechanics. The numerical results analyze the physical factors that influences the ion's movement across the cell membrane. These results show that the theory can explain the phenomenon of the biological window-effects.
Animals ; Biological Transport, Active ; Cell Membrane ; physiology ; radiation effects ; Cell Membrane Permeability ; physiology ; radiation effects ; Computer Simulation ; Electromagnetic Fields ; Ion Channels ; metabolism ; Ions ; metabolism ; Models, Biological

Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an active transport process mediated by the sodium-iodide symporter (NIS). The rat and human NIS-coding genes were cloned and identified in 1996. Evaluation of NIS gene and protein expression is critical for the management of thyroid cancer, and several approaches to increase NIS levels have been tried. Identification of the NIS gene has provided a means of expanding its role in radionuclide therapy and molecular target-specific theragnosis (therapy and diagnosis using the same molecular target). In this article, we describe the relationship between NIS expression and the thyroid carcinoma treatment using I-131 and alternative therapeutic approaches.
Animals ; Biological Transport, Active ; Clone Cells ; Diagnosis ; Humans ; Ion Transport ; Membranes ; Rats ; Thyroid Gland ; Thyroid Neoplasms*

Annexin A2, a multifunctional tumor associated protein, promotes nuclear factor-kappa B (NF-κB) activation by interacting with NF-κB p50 subunit and facilitating its nuclear translocation. Here we demonstrated that two ginsenosides Rg5 (G-Rg5) and Rk1 (G-Rk1), with similar structure, directly bound to Annexin A2 by molecular docking and cellular thermal shift assay. Both Rg5 and Rk1 inhibited the interaction between Annexin A2 and NF-κB p50 subunit, their translocation to nuclear and NF-κB activation. Inhibition of NF-κB by these two ginsenosides decreased the expression of inhibitor of apoptosis proteins (IAPs), leading to caspase activation and apoptosis. Over expression of K302A Annexin A2, a mutant version of Annexin A2, which fails to interact with G-Rg5 and G-Rk1, effectively reduced the NF-κB inhibitory effect and apoptosis induced by G-Rg5 and G-Rk1. In addition, the knockdown of Annexin A2 largely enhanced NF-κB activation and apoptosis induced by the two molecules, indicating that the effects of G-Rg5 and G-Rk1 on NF-κB were mainly mediated by Annexin A2. Taken together, this study for the first time demonstrated that G-Rg5 and G-Rk1 inhibit tumor cell growth by targeting Annexin A2 and NF-κB pathway, and G-Rg5 and G-Rk1 might be promising natural compounds for targeted cancer therapy.
Active Transport, Cell Nucleus ; drug effects ; Annexin A2 ; chemistry ; deficiency ; genetics ; metabolism ; Antineoplastic Agents ; chemistry ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Biological Products ; chemistry ; metabolism ; pharmacology ; Cell Nucleus ; drug effects ; metabolism ; Down-Regulation ; drug effects ; Drug Discovery ; Gene Knockdown Techniques ; Ginsenosides ; chemistry ; Hep G2 Cells ; Humans ; Molecular Docking Simulation ; Molecular Targeted Therapy ; NF-kappa B p50 Subunit ; metabolism ; Protein Conformation

Effects of cadmium (Cd) intoxication on renal endosomal accumulation of organic cations (OC ) were studied in rats using 14C-tetraethylammnium (TEA) as a substrate. Cd intoxication was induced by s.c. injections of 2 mg Cd/kg/day for 2-3 weeks. Renal cortical endosomes were isolated and the endosomal acidification (acridine orange fluorescence change) and TEA uptake (Millipore filtration technique) were assessed. The TEA uptake was an uphill transport mediated by H /OC antiporter driven by the pH gradient established by H -ATPase. In endosomes of Cd-intoxicated rats, the ATP-dependent TEA uptake was markedly attenuated due to inhibition of endosomal acidification as well as H /TEA antiport. In kinetic analysis of H /TEA antiport, Vmax was reduced and Km was increased in the Cd group. Inhibition of H /TEA antiport was also observed in normal endosomes directly exposed to free Cd (but not Cd-metallothionein complex, CdMt) in vitro. These data suggest that during chronic Cd exposure, free Cd ions liberated by lysosomal degradation of CdMt in proximal tubule cells may impair the endosomal accumulation of OC by directly inhibiting the H /OC antiporter activity and indirectly by reducing the intravesicular acidification, the driving force for H /OC exchange.
Animals ; Biological Transport, Active ; Cadmium ; Cations ; Citrus sinensis ; Endosomes* ; Filtration ; Fluorescence ; Ion Transport ; Ions ; Kidney ; Proton-Motive Force ; Rats* ; Tea ; Tetraethylammonium*

OBJECTIVETo explore the transmembrane transport and metabolism of diammonium glycyrrhizinate in intestines of rats.

METHODAn Ussing Chamber model were used to investigate the transmembrane transport of diammonium glycyrrhizinate (GZ), the concentrations of diammonium glycyrrhizinate and its two metabolites were determined by HPLC.

RESULTThe permeability coefficients of GZ in difference intestinal mucous membranes were ranged from 0.3 x 10(-6) cm x s(-1) to 1.1 x 10(-6) cm x s(-1). The metabolism of GZ in enterocytes during its transport process was negligible. The concentration of diammonium glycyrrhizinate and pH had limit effects on the transport amount and the permeability coefficients of GZ.

CONCLUSIONGZ is a low permeability drug, but it can be absorbed at all segments of the small intestine in rats. Ileum is the major absorption region of GZ.

Animals ; Biological Transport ; Cell Membrane Permeability ; Glycyrrhizic Acid ; metabolism ; pharmacokinetics ; Hydrogen-Ion Concentration ; Intestine, Small ; chemistry ; drug effects ; metabolism ; Male ; Models, Biological ; Rats ; Rats, Sprague-Dawley

1) A beta agonist stimulated Na+ transport and decreased the intracellular Cl concentration ([Cl]c) associated with cell shrinkage via an increase in cytosolic cAMP level by activating adenylate cyclase in rat fetal distal lung epithelial (FDLE) cells. 2) Lowering [Cl-]c activated a 28-pS nonselective cation (NSC) channel by elongating the open time of the channel. 3) cAMP signals were converted to a protein tyrosine kinase (PTK)-mediated signal. 4) The PTK-mediated signal was involved in the cAMP-stimulated Na+ transport in rat FDLE cells.
Adrenergic beta-Agonists/pharmacology* ; Animal ; Biological Transport/physiology ; Biological Transport/drug effects ; Cell Size/physiology ; Chlorides/metabolism* ; Cyclic AMP/metabolism ; Cytosol/metabolism ; Enzyme Inhibitors/pharmacology ; Female ; Fetus/cytology ; Forskolin/pharmacology ; Nitrobenzoates/pharmacology ; Pregnancy ; Protein-Tyrosine Kinase/metabolism* ; Rats ; Rats, Wistar ; Respiratory Mucosa/enzymology* ; Respiratory Mucosa/embryology ; Respiratory Mucosa/cytology ; Sodium/metabolism* ; Tyrphostins/pharmacology

BACKGROUND: The sodium-iodide-symporter (NIS) is a plasma membrane glycoprotein with 13 putative transmembrane domains, which is responsible for concentrating iodide into the thyroid by an active transport and provides the mechanism for radioactive-iodine (RAI) therapy for thyroid cancer. However, undifferentiated thyroid cancers and about 2050% of differentiated thyroid cancers do not take up the RAI at therapeutic dose. The NIS has been cloned from rat and human (hNIS) and characterized recently. In an attempt to develop a new therapeutic strategy using hNIS gene for improving the efficacy of RAI therapy in thyroid cancers, we have constructed a recombinant adenovirus encoding the hNIS (Ad-hNIS) and tested its function by an iodide uptake by infecting human thyroid cancer cells. METHODS: RT-PCR was performed to measure an intrinsic hNIS expression in thyroid cancer cell lines, such as NPA, FRO and ARO. To generate the hNIS adenovirus, hNIS cDNA was isolated and ligated into Swa I site of cosmid shuttle vector (pAxCAwt). We have produced recombinant adenovirus by co-transfecting the cosmid with DNA-TPC to 293 cell line. Adenovirus that express (beta-Galactosidase (LacZ) was also prepared by the similar strategy. Adenovirus infection efficiency was measured in three thyroid cancer cell lines. Finally, 24 hours after infection of ad-hNIS into the cells, I125-uptake was measured. RESULTS: Endogenous hNIS expression was detected only in FRO cells but not in NPA, ARO and Hela cells by RT-PCR. X-Gal staining after infection of Ad-LacZ to thyroid cancer cell (NPA, ARO, FRO) showed that an infection rate in ARO cells was 98.5+0.5%, 97.0+0.2% in FRO cells and 75.5+5.0% in NPA cells. We selected ARO cells for the infection of Ad-hNIS due to the highest infection efficiency and the absence of endogenous hNIS expression. When ARO cells were infected with the ad-hNIS, I125 uptake was increased 504+6.4%. CONCLUSION: Overexpression of hNIS gene in thyroid cancer cells elicited over 5 fold increase in I-uptake, suggesting that the Ad-hNIS infection to the thyroid cancer cells may improve the efficiency of radioactive iodine therapy.
Adenoviridae Infections ; Adenoviridae* ; Animals ; Biological Transport, Active ; Cell Line ; Cell Membrane ; Clone Cells ; Cosmids ; DNA, Complementary ; Genetic Therapy ; Genetic Vectors ; Glycoproteins ; HeLa Cells ; Humans* ; Iodine ; Ion Transport* ; Rats ; Sodium Iodide* ; Sodium* ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N-methyl-D-aspartate (NMDA) receptor-gated ion channels, which is usually blocked by a magnesium plug. Many studies have found that intrathecal or intraperitoneal magnesium suppress neuropathic pain. Therefore, it is possible that serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio are changed in neuropathic pain. The purpose of this study was evaluated changes in serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio in neuropathic rats. METHODS: Male Sprague-Dawley rats were prepared with tight ligation of the left lumbar 5th and 6th spinal nerves to produce neuropathic pain. The threshold of mechanical allodynia was evaluated by the up-down method using withdrawal response to a von Frey filaments stimulus on the 3rd, 7th, and 14th day. Rats with a threshold of less than 4 gram were selected as the experimental group. On the 16th day, serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio were measured. Experimental group data were then compared with those of an unoperated control group and an unligated sham group; each group contained 10 animals. RESULTS: No statistic differences were found between groups. CONCLUSIONS: Our results suggest that serum and cerebrospinal fluid Ca2+, Mg2+, and Ca2+/Mg2+ ratio in neuropathic rats do not differ from those of normal rats because of physiologic homeostasis is maintained by active transport through the blood-brain-barrier despite of activation of NMDA receptor-gated ion channels. However, we believe that the Mg2+ ion-dependent voltage-gating in rats with neuropathic pain may be deficient in a chronic condition due to a decreased Mg2+ binding affinity of the NMDA receptor-gated channel, as has been found in hippocampal granule cells in epileptic rats.
Animals ; Biological Transport, Active ; Calcium ; Central Nervous System Sensitization ; Cerebrospinal Fluid* ; Homeostasis ; Humans ; Hyperalgesia ; Ion Channels ; Ligation ; Magnesium ; Male ; N-Methylaspartate ; Neuralgia ; Rats* ; Rats, Sprague-Dawley ; Spinal Nerves

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.
Animals ; Ascorbic Acid Deficiency/*metabolism ; Biological Transport/drug effects ; Chlorides/*metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors/drug ; Forskolin/pharmacology ; Hyperbaric Oxygenation ; Hyperoxia/*physiopathology ; Ion Transport/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Knockout/metabolism ; Mice, Transgenic ; Microscopy, Fluorescence ; Oxidative Stress ; Oxygen/adverse effects/pharmacology ; Potassium Channels/metabolism ; Respiratory Mucosa/drug effects/*metabolism/secretion ; Sodium ; Sugar Acids/metabolism