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1.
Hypertens Pregnancy ; 42(1): 2232029, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37417251

ABSTRACT

OBJECTIVE: To assess changes in expression of renal epithelial sodium channel (ENaC) and NEDD4L, a ubiquitin ligase, in urinary extracellular vesicles (UEV) of pre-eclamptic women compared to normal pregnant controls. METHODS: Urine was collected from pre-eclamptic women (PE, n = 20) or during normal pregnancy (NP, n = 20). UEV were separated by differential ultracentrifugation. NEDD4L, α-ENaC and γ-ENaC were identified by immunoblotting. RESULTS: There was no difference in the expression of NEDD4L (p = 0.17) and α-ENaC (p = 0.10). PE subjects showed increased expression of γ-ENaC by 6.9-fold compared to NP (p < 0.0001). CONCLUSION: ENaC expression is upregulated in UEV of pre-eclamptic subjects but was not associated with changes in NEDD4L.


Subject(s)
Extracellular Vesicles , Nedd4 Ubiquitin Protein Ligases , Pre-Eclampsia , Female , Humans , Pregnancy , Epithelial Sodium Channels/metabolism , Extracellular Vesicles/metabolism , Kidney , Pre-Eclampsia/metabolism , Nedd4 Ubiquitin Protein Ligases/genetics
2.
J Med Econ ; 20(5): 541-548, 2017 May.
Article in English | MEDLINE | ID: mdl-28277030

ABSTRACT

BACKGROUND: EOX (epirubicin, oxaliplatin, Xeloda; capecitabine) and FOLFOX4 (5-fluorouracil (5-FU), leucovorin, oxaliplatin) are the common chemotherapy regimens used in the treatment of advanced gastric cancer (aGC) in Hong Kong. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. It should be noted that, while FOLFOX4 is routinely administered in an outpatient setting in North America and Europe, inpatient setting is adopted in Hong Kong instead, incurring hospitalization cost as a result. METHODS: Fifty-eight patients were identified from the electronic records in two public tertiary hospitals, with 45 and 13 receiving EOX and FOLFOX4 regimens, respectively. Healthcare cost was direct medical costs including drugs, clinic follow-up, hospitalization, diagnostic laboratories, and radiographs. Societal cost refers to indirect costs such as patient time and travel costs. Cost items were further classified as "expected" or "unexpected". All cost data was expressed in US dollars. RESULTS: Patients in the EOX and FOLFOX4 arm received an average of 5.3 and 7.8 cycles of treatment, respectively. The capecitabine-based regimen group had a higher expected medication cost per cycle when compared to the 5-FU-based treatment group (US$290.3 vs US$66.9, p < .001), but lower expected hospitalization costs (US$76.9 vs US$1,269.2, p < .001). The total healthcare cost and total societal cost per patient was reduced by 67.2% (US$5,691.9 vs US$17,357.4, p < .001) and 25.3% (US$3,090.5 vs US$4,135.1, p = .001), respectively, in the capecitabine-based regimen group. Sensitivity analyses based on full cycle regimen costs and net capecitabine or 5-FU/leucovorin costs still showed EOX to be less costly than FOLFOX4. CONCLUSION: The capecitabine-based regimen, EOX, was found to generate significant cost saving from both the healthcare and societal perspectives in regions in which FOLFOX4 is given in an inpatient setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/economics , Capecitabine/economics , Fluorouracil/economics , Stomach Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/therapeutic use , Cost of Illness , Cost-Benefit Analysis , Female , Fluorouracil/therapeutic use , Health Expenditures/statistics & numerical data , Health Services/economics , Health Services/statistics & numerical data , Hong Kong , Humans , Male , Middle Aged , Models, Econometric , Neoplasm Staging , Retrospective Studies
3.
Physiol Rep ; 5(6)2017 Mar.
Article in English | MEDLINE | ID: mdl-28320891

ABSTRACT

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18-60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18-60 years; (2) combine these data with those for healthy children (aged 0-12), adolescents (aged 12-18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population-based cross-sectional observational study of healthy Chinese subjects aged 0.5-89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5-89; 52% male). From previous studies, 1197 children (aged 0-12, 55% male), 590 adolescents (aged 12-18, 49% male), and 77 elderly (aged 60-89, 55% male) were included. New data were collected from 354 adults aged 18-60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly.


Subject(s)
Cardiac Output/physiology , Hemodynamics/physiology , Stroke Volume/physiology , Vascular Resistance/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Child , Child, Preschool , Cross-Sectional Studies , Female , Hong Kong , Humans , Infant , Male , Middle Aged , Reference Values , Ultrasonography , Young Adult
4.
Environ Pollut ; 194: 188-195, 2014 11.
Article in English | MEDLINE | ID: mdl-25150452

ABSTRACT

Fifteen polycyclic aromatic hydrocarbons (PAHs) in PM2.5 samples collected in five different cities (Hong Kong (HK), Guangzhou (GZ), Xiamen (XM), Xi'an (XA) and Beijing (BJ)) in China in the winter 2012-13 [corrected] were analyzed by gas chromatography-mass spectrometry. The biological effects of organic extracts were assayed using the human bronchial epithelial cells BEAS-2B. All sixteen priority PAHs can be found in the PM2.5 samples of XA and BJ, but not in HK, GZ and XM, demonstrating the differential spatial source and distribution of PAHs. Our results showed that the total PAHs ranged from 3.35 to 80.45 ng/m(3) air, leading by BJ, followed by XA, XM, GZ and HK. In the cell culture study, transcript levels of pro-inflammatory cytokine interleukin-6 (IL-6), CYP1A1 and CYP1B1 were found to be induced in the treatment. The cells exposed to extracts from XA and BJ demonstrated significant migratory activities, indicating a sign of increase of tumorigenicity.


Subject(s)
Air Pollutants/analysis , Environmental Monitoring , Particulate Matter/analysis , Air/analysis , Air Pollution/analysis , Air Pollution/statistics & numerical data , China , Cities/statistics & numerical data , Gas Chromatography-Mass Spectrometry , Humans , Polycyclic Aromatic Hydrocarbons/analysis , Seasons
5.
Emerg Med J ; 31(7): 541-544, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23585576

ABSTRACT

BACKGROUND: In paediatric resuscitation, for a rapid and accurate estimate of children's weight, the Broselow tape can be used in children who are 46-144 cm tall. The Broselow tape has previously been found to provide the most accurate estimate of children's weight internationally, but it is not known how many fall outside the range of the tape, or whether such children can be assumed to be of adult weight, or how otherwise to estimate the weight of these children. OBJECTIVES: To determine what proportion of children in different age groups falls outside the limits of the Broselow tape, how their weight compares with that of the adults and what correlates most strongly with weight in these children. METHODS: This was a population-based prospective observational study of Chinese children up to 12 years old, from schools in Hong Kong. Weight was measured to the nearest 0.2 kg, and the height, foot-length and mid-arm circumference (MAC) were measured to the nearest 0.1 cm. RESULTS: 40% of 10-year olds and 70% of 11-year olds were too tall for the tape. Their median weight was 41.9 kg. This was significantly less than the median weight of 18-year olds (55 kg, p<0.0001) in Hong Kong. The strongest correlate with weight in these children was MAC. CONCLUSIONS: The Broselow tape is inappropriate for use in most children over 10 years old. Children too tall for the tape cannot be assumed to be of adult weight; to do so would imply an average overestimate of 30%. Weight estimates in older children could be based on MAC.


Subject(s)
Anthropometry/instrumentation , Body Height , Body Weight , Resuscitation , Child , Child, Preschool , Female , Hong Kong , Humans , Infant , Male , Prospective Studies
7.
J Hazard Mater ; 261: 763-9, 2013 Oct 15.
Article in English | MEDLINE | ID: mdl-23411151

ABSTRACT

In this study we report the human plasma concentrations of some common endocrine disrupting chemicals (EDCs) in the Hong Kong population. We have analyzed 153 plasma samples for the contaminants by methods involving labeled standards spiked into the samples. Quantification was performed using high performance liquid chromatography tandem mass spectrometry for bisphenol-A (BPA) and perfluorinated compounds (PFCs), and gas chromatography mass spectrometry methods for phthalates. We found BPA, several types of PFCs and phthalates in over 90% of the plasma samples. Perfluorooctane sulfonate (PFOS) was the dominant PFC, followed by perfluroroctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS). Eight out of ten phthalates were detected, with bis(2-ethylhexyl) phthalate (DEHP) as the most abundant, followed by bis(2-methoxyethyl) phthalate (DMEP) and dioctyl phthalate (DnOP). The levels of PFOS, PFOA, PFHxS and perfluorohexanoic acid (PFHxA) were significantly higher in the male plasma samples (p<0.05), while the mean plasma levels of DEHP and n-butyl benzyl phthalate (BBP) were significantly higher in the young age group (p<0.02). The presence of the selected EDCs in human blood plasma indicates common exposure routes among different population cohorts. Although the plasma levels of the EDCs were comparable to other countries, regular monitoring of human blood EDC contamination levels is necessary to provide a time-trend database for the estimation of exposure risk and to formulate appropriate public health policy.


Subject(s)
Benzhydryl Compounds/blood , Endocrine Disruptors/blood , Environmental Pollutants/blood , Fluorocarbons/blood , Phenols/blood , Phthalic Acids/blood , Adolescent , Adult , Environmental Monitoring , Female , Hong Kong , Humans , Male , Middle Aged , Young Adult
8.
Resuscitation ; 82(7): 891-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21507547

ABSTRACT

UNLABELLED: Reference ranges for vital signs may differ significantly among children of different ethnic origins. AIM: (1) To validate the Advanced Paediatric Life Support (APLS) age-based vital signs reference ranges in Chinese children in Hong Kong. (2) To derive age-based centile curves for systolic blood pressure, heart rate and respiratory rate for Chinese children. (3) To summarize the reference ranges in a table format appropriate for applying APLS to ethnic Chinese patients. METHOD: A cross-sectional study was performed on a population of healthy Chinese children recruited from 8 kindergartens and 6 primary schools in Hong Kong. Trained operators visit the sites to obtain measurements. Age-groups: small toddlers (12-23 months); pre-school (24-59 months); and school (60-143 months). Z-test was used to assess statistical significance for proportions of each parameter falling outside the APLS reference range. One-sample t-test was used for comparison with APLS means according to age-groups. LMS Chartmaker Pro v2.3 software was used to describe the data in centile curves. RESULTS: A total of 1353 patients (55.1% boys) were included. For heart rate, systolic blood pressure and respiratory rate respectively, 34.1%, 55.9% and 55.7% of corresponding measurements were outside the APLS age-based reference ranges. In the 'pre-school' and 'school' age-groups, the mean value for blood pressure is significantly higher, and the mean values for heart rate and respiratory rate significantly lower, in comparison to APLS mean values. CONCLUSION: Independently derived vital signs reference ranges are more appropriate for use when applying APLS to Chinese patients in Hong Kong.


Subject(s)
Advanced Cardiac Life Support/standards , Asian People , Hemodynamics/physiology , Vital Signs , Age Factors , Child , Child, Preschool , Cross-Sectional Studies , Female , Hong Kong , Humans , Infant , Male , Reference Values
9.
Resuscitation ; 81(9): 1105-10, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20619953

ABSTRACT

INTRODUCTION: Accurate measurement of children's weight is rarely possible in paediatric resuscitation, and rapid estimates are made to ensure appropriate drug and fluid doses and equipment selection. Weight is commonly estimated from formulae based on children's age, or from their height using the Broselow tape. Foot-length and mid-arm circumference have also been suggested as the basis of weight-estimation formulae. OBJECTIVES: To determine which of age, height, foot-length or mid-arm circumference had the strongest relationship with weight in healthy children, to derive a simple weight-estimation formula from the strongest correlate, and to compare its performance with existing weight-estimation tools. METHODS: This was a population-based prospective observational study of Hong Kong Chinese children aged 1-11 years old last birthday. Weight was measured to the nearest 0.2 kg; height, foot-length and mid-arm circumference to the nearest 0.1 cm. Multiple regression analysis was used to determine the strongest independent relationships with weight, and linear regression analysis derived a weight-estimation formula. Accuracy and precision of this formula were compared with standard age-based and height-based weight-estimation methods. RESULTS: Mid-arm circumference had the strongest relationship with weight, and this relationship grew stronger with age. The formula, weight [kg]=(mid-arm circumference [cm]-10) x 3, was at least as accurate and precise as the Broselow method and outperformed the age-based rule in school-age children, but was inadequate in pre-school children. CONCLUSION: This weight-estimation formula based on mid-arm circumference is reliable for use in school-age children, and an arm-tape could be considered as an alternative to the Broselow tape in this population.


Subject(s)
Anthropometry/methods , Arm/anatomy & histology , Body Weight , Child , Child, Preschool , Female , Humans , Infant , Male , Predictive Value of Tests , Prospective Studies , Reproducibility of Results
10.
Crit Care Med ; 38(9): 1875-81, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20562697

ABSTRACT

OBJECTIVE: The Ultrasonic Cardiac Output Monitor is a noninvasive method of hemodynamic assessment and monitoring in critically ill patients. There are no published reference ranges for normal values in children for this device. This study aimed to establish normal ranges for cardiovascular indices measured using Ultrasonic Cardiac Output Monitor in children aged 0-12 yrs old and to assess interobserver reliability. DESIGN: This was a population-based cross-sectional observational study. SETTING: Schools and kindergartens in Hong Kong. SUBJECTS: Chinese children aged up to 12 yrs old. INTERVENTIONS: Two operators performed Ultrasonic Cardiac Output Monitor scans on each child together with standard oscillometric measurement of blood pressure and heart rate. Software intrinsic to the Ultrasonic Cardiac Output Monitor device produces values for stroke volume, cardiac output, and systemic vascular resistance. For each parameter, normal ranges were defined as lying between the 2.5th and 97.5th percentiles. Interobserver reliability was assessed with Bland-Altman plots, coefficients of variation, and intraclass correlation. MEASUREMENTS AND MAIN RESULTS: A total of 1,197 Chinese children (55% boys) were scanned. Normal ranges of values for cardiac output, stroke volume, and systemic vascular resistance indices are presented. Interobserver reliability for Ultrasonic Cardiac Output Monitor was superior to that for standard blood pressure and heart rate measurement. CONCLUSIONS: This large study presents normal values for cardiovascular indices in children using the Ultrasonic Cardiac Output Monitor with good interobserver reliability.


Subject(s)
Cardiac Output , Echocardiography/standards , Heart Function Tests/standards , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Observer Variation , Reference Values
11.
Inflamm Res ; 55(7): 293-9, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16955392

ABSTRACT

OBJECTIVE: Synovial sarcoma (SS) is a malignant mesenchymal tumor that accounts for 5-10% of all soft tissue sarcoma. IL-1beta, a pleiotrophic cytokine, has been found in the tumor microenvironment which plays crucial roles in the pathogenesis of tumors. METHODS: In this study, we used Hs701.T as a cellular model to study the short-term (4-h) and long-term (48-h) stimulatory effect of IL-1beta on cell proliferation and differential gene expression. RESULTS: The results showed that IL-1beta can stimulate cell proliferation through activation of NF-kappaB and AP-1 transcription factors; sequentially triggers the expression of genes related to tumor progression. The microarray data indicated that most of the up-regulated genes were related to tumor progression. Five candidate genes which are involved in the mediation of proliferation (IL-6), apoptosis (Hsp27 and Daxx), and angiogenesis (PlGF and SPARC) were further validated by RT-PCR. CONCLUSION: These findings may be useful for understanding the pathogenesis of synovial sarcoma.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Interleukin-1beta/metabolism , Sarcoma, Synovial/metabolism , Synovial Membrane/pathology , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Proliferation , Disease Progression , Fibroblasts/metabolism , Humans , Neoplasms/blood supply , Neovascularization, Pathologic , Oligonucleotide Array Sequence Analysis , Time Factors
12.
Biochem Pharmacol ; 72(4): 437-45, 2006 Aug 14.
Article in English | MEDLINE | ID: mdl-16793023

ABSTRACT

Aberrant angiogenesis is an essential step for the progression of solid tumors. Thus anti-angiogenic therapy is one of the most promising approaches to control tumor growth. In this study, we examined the ability of 20(R)-ginsenoside Rg3 (Rg3), one of the active compounds present in ginseng root, to interfere with the various steps of angiogenesis. Rg3 was found to inhibit the proliferation of human umbilical vein endothelial cells (HUVEC) with an IC50 of 10 nM in Trypan blue exclusion assay. Rg3 (1-10(3) nM) also dose dependently suppressed the capillary tube formation of HUVEC on the Matrigel in the presence or absence of 20 ng/ml vascular endothelial growth factor (VEGF). The VEGF-induced chemoinvasion of HUVEC and ex vivo microvascular sprouting in rat aortic ring assay were both significantly attenuated by Rg3. In addition, Rg3 (150 and 600 nM) remarkably abolished the basic fibroblast growth factor (bFGF)-induced angiogenesis in an in vivo Matrigel plug assay. The Matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, which play an important role in the degradation of basement membrane in angiogenesis and tumor metastasis present in the culture supernatant of Rg3-treated aortic ring culture were found to decrease in their gelatinolytic activities. Taken together, these data underpin the anti-tumor property of Rg3 through its angiosuppressive activity.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Ginsenosides/pharmacology , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/chemistry , Animals , Aorta/drug effects , Aorta/enzymology , Aorta/growth & development , Capillaries/drug effects , Capillaries/growth & development , Cell Proliferation/drug effects , Collagen , Dose-Response Relationship, Drug , Drug Combinations , Drug Screening Assays, Antitumor/methods , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Ginsenosides/administration & dosage , Ginsenosides/chemistry , Humans , In Vitro Techniques , Injections, Subcutaneous , Laminin , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred C57BL , Molecular Structure , Neovascularization, Physiologic/drug effects , Proteoglycans , Rats , Vascular Endothelial Growth Factors/pharmacology
13.
Article in English | MEDLINE | ID: mdl-16634464

ABSTRACT

BACKGROUND: Although the significance of apolipoprotein E4 (Apo E4) in Alzheimer's disease (AD) has been well established in Caucasian populations, its role in determining the rate of cognitive decline in other ethnic groups has yet to be determined. This study examined the two-year progression of cognitive decline and its association with Apo E4 allelic status in a group of Chinese elderly subjects with AD. METHOD: One hundred and four Chinese subjects with mild and moderate AD as assessed by the Clinical Dementia Rating (CDR 1 and 2) were followed up at a mean (SD) duration of 22.53 (5.21) months. The rate of cognitive decline and its association with Apo E4 allelic status was evaluated RESULTS: At follow-up, 74 (73 percent) subjects were reassessed. Forty-nine remained stable at the same CDR and 25 had deteriorated. The mean (SD) deterioration in the Mini-Mental State Examination (MMSE) was 2.52 (4.38) and in the Mattis Dementia Rating Scale (DRS) was 9.03 (14.98) (paired t-test, p < 0. 001). There was no significant difference in the baseline MMSE and DRS scores between the "stable", "deteriorated", or "deceased" groups. Mildly demented subjects with the Apo E4 allele were more likely to have deteriorated to a more severe CDR than subjects without the Apo E4 allele (Pearson chi2 = 5.72, df 1, p = 0.017, Odds ratio = 6.3, CI 1.3 to 30.53). CONCLUSION: The presence of the Apo E4 allele may influence the rate of cognitive deterioration, particularly in subjects with mild AD.


Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Asian People/genetics , Gene Frequency , Aged , Aged, 80 and over , Disease Progression , Female , Follow-Up Studies , Hong Kong , Humans , Male , Neuropsychological Tests , Prospective Studies , Psychiatric Status Rating Scales , Severity of Illness Index
14.
Environ Health Perspect ; 112(15): 1550-6, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15531441

ABSTRACT

We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease "hot spots." Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.


Subject(s)
Disease Outbreaks , Geographic Information Systems , Population Surveillance , Severe Acute Respiratory Syndrome/epidemiology , Databases, Factual , Hong Kong/epidemiology , Humans
16.
Biol Reprod ; 68(1): 302-8, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12493726

ABSTRACT

The luminal fluid microenvironment of the uterus is important for sperm capacitation and embryo development. In an attempt to understand the possible role of Na(+)/H(+) exchangers (NHEs) in uterine function, the mRNAs of different NHE isoforms as well as their subcellular localization (apical versus basolateral) and functional activity were investigated in mouse endometrial epithelial cells using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and intracellular pH (pH(i)) measurement techniques. The presence of NHE1, NHE2, and NHE4, but not NHE3 mRNAs were revealed by RT-PCR. Immunostaining showed that NHE1, NHE2, and NHE4 were present in both apical and basolateral membranes. The pH(i) recovery from intracellular acidification was Na(+)-dependent; however, the rate of pH(i) recovery depending on basolateral Na(+) was 12.4 times faster than that depending on apical Na(+). The Na(+)-dependent rate of pH(i) recovery was also inhibited by amiloride, indicating H(+) extrusion through NHEs; however, the amiloride sensitivity of the apical membrane was less than that of the basolateral membrane, suggesting the involvement of different types of NHEs in the two membranes. The results indicate that the basolaterally located NHE1, NHE2, and NHE4, in addition to participating in the homeostatic control of intracellular pH, may play a role in H(+) extrusion in order to achieve transepithelial HCO(3)(-) secretion. The apically located NHEs may be involved in mediating Na(+) absorption as alternatives of or complementary to epithelial Na(+) channels.


Subject(s)
Endometrium/metabolism , Sodium-Hydrogen Exchangers/genetics , Sodium-Hydrogen Exchangers/metabolism , Animals , Base Sequence , DNA/genetics , Epithelium/metabolism , Female , Gene Expression , Hydrogen-Ion Concentration , Immunohistochemistry , Mice , Mice, Inbred ICR , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction
17.
Biol Reprod ; 62(3): 755-8, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10684820

ABSTRACT

Previous studies from our laboratory have provided evidence that the rat epididymis utilizes the Na(+)/H(+) exchanger to transport acid and base. The present study was undertaken to use immunohistochemistry for investigating the localization (apical versus basolateral) and distribution of NHE1 and NHE2 proteins along intact rat epididymis. Both proteins were found to be exclusively localized within the epithelium. Immunoreactivity for NHE1 was detected on the basolateral surface, whereas NHE2 immunoreactivity was detected on the apical side of the epithelium. Interestingly, NHE1 was found along the entire length of the epididymal tubule whereas NHE2 was absent in the initial segment but present in the caput, corpus, and cauda regions. These results, when interpreted along with those of previous functional studies, may suggest that the apical NHE2 is involved in Na(+) reabsorption and the basolateral NHE1 in HCO(3)(-) secretion in the rat epididymis.


Subject(s)
Epididymis/metabolism , Sodium-Hydrogen Exchangers/metabolism , Animals , Cell Membrane/metabolism , Immunoenzyme Techniques , Male , Rats , Rats, Sprague-Dawley , Sodium-Hydrogen Exchangers/immunology
18.
J Membr Biol ; 164(2): 155-67, 1998 Jul 15.
Article in English | MEDLINE | ID: mdl-9662559

ABSTRACT

The present study investigated both HCO-3 and Cl- secretions in a human pancreatic duct cell line, CAPAN-1, using the short-circuit current (Isc) technique. In Cl-/HCO-3-containing solution, secretin (1 microM) or forskolin (10 microM) stimulated a biphasic rise in the Isc which initially reached a peak level at about 3 min and then decayed to a plateau level after 7 min. Removal of external Cl- abolished the initial transient phase in the forskolin-induced Isc while the plateau remained. In HCO-3/CO2-free solution, on the contrary, only the initial transient increase in Isc was prominent. Summation of the current magnitudes observed in Cl--free and HCO-3-free solutions over a time course of 10 min gave rise to a curve which was similar, both in magnitude and kinetics, to the current observed in Cl-/HCO-3-containing solution. Removal of external Na+ greatly reduced the initial transient rise in the forskolin-induced Isc response, and the plateau level observed under this condition was similar to that obtained in Cl--free solution, suggesting that Cl--dependent Isc was also Na+-dependent. Bumetanide (50 microM), an inhibitor of the Na+-K+-2Cl- cotransporter, and Ba2+ (1 mm), a K+ channel blocker, could reduce the forskolin-induced Isc obtained in Cl-/HCO-3-containing or HCO-3-free solution. However, they were found to be ineffective when external Cl- was removed, indicating the involvement of these mechanisms in Cl- secretion. On the contrary, the HCO-3-dependent (in the absence of external Cl-) forskolin-induced Isc could be significantly reduced by carbonic anhydrase inhibitor, acetazolamide (45 microM). Basolateral application of amiloride (100 microM) inhibited the Isc; however, a specific Na+-H+ exchanger blocker, 5-N-methyl-N-isobutylamiloride (MIA, 5-10 microM) was found to be ineffective, excluding the involvement of the Na+-H+ exchanger. However, an inhibitor of H+-ATPase, N-ethylmaleimide did suppress the Isc (IC50 = 22 microM). Immunohistochemical studies also confirmed the presence of a vacuolar type of H+-ATPase in these cells. H2DIDS (100 microM), an inhibitor of Na+-HCO-3 cotransporter, was without effect. Apical addition of Cl- channel blocker, diphenylamine-2,2'-dicarboxylic acid (DPC, 1 mm), but not disulfonic acids, DIDS (100 microM) or SITS (100 microM), exerted an inhibitory effect on both Cl- and HCO-3-dependent forskolin-induced Isc responses. Histochemical studies showed discrete stainings of carbonic anhydrase in the monolayer of CAPAN-1 cells, suggesting that HCO-3 secretion may be specialized to a certain population of cells. The present results suggest that both HCO-3 and Cl- secretion by the human pancreatic duct cells may occur concurrently and independently.


Subject(s)
Antiporters/metabolism , Bicarbonates/metabolism , Chlorides/metabolism , Pancreatic Ducts/metabolism , Vacuolar Proton-Translocating ATPases , Biological Transport/physiology , Carbonic Anhydrases/metabolism , Cell Line , Chloride-Bicarbonate Antiporters , Humans , Pancreatic Ducts/cytology , Pancreatic Ducts/enzymology , Proton Pumps/metabolism , Proton-Translocating ATPases/metabolism , Sodium/physiology
19.
J Membr Biol ; 157(1): 97-103, 1997 May 01.
Article in English | MEDLINE | ID: mdl-9141362

ABSTRACT

Previous studies from our laboratory have provided evidence for the existence of a local renin-angiotensin system in the rat epididymis. Evidence has also accumulated, indicating that locally formed angiotensin II from the rat epididymis may play a paracrine and/or autocrine role in regulating epididymal electrolyte and fluid transport. In the present study, specific anti-peptide antibodies against the second extracellular loops of angiotensin II type I (AT1) and type II (AT2) receptors were used to localize immunocytochemically these receptors in the rat cauda epididymides of three developmental stages, namely, immature (2-week), early mature (6-week) and fully mature (10-week). The immunostaining intensity for AT1 receptors was found to be stronger than that for AT2 receptors throughout rat epididymides of all stages. However, the immunostaining for both AT1 and AT2 receptors observed in the fully mature rat epididymis was much more intense than that observed in the epididymides of the two younger stages. While the immunostaining for both AT1 and AT2 receptors in the younger rat epididymides appeared to be distributed in both basal and apical regions, the immunostaining in the fully mature epididymis was predominantly localized in the basal region. The present finding of the differential patterns of angiotensin II receptor immunoreactivity in three different stages of the rat epididymis may reflect the fine tuning of rat epididymal function by angiotensin II, acting as a paracrine or autocrine agent, during the course of development.


Subject(s)
Epididymis/metabolism , Receptors, Angiotensin/metabolism , Amino Acid Sequence , Animals , Cell Differentiation , Epididymis/cytology , Fluorescent Antibody Technique, Indirect , Humans , Male , Molecular Sequence Data , Rats , Rats, Sprague-Dawley
20.
Biochim Biophys Acta ; 1356(2): 140-8, 1997 Apr 24.
Article in English | MEDLINE | ID: mdl-9150272

ABSTRACT

A primary culture of mouse endometrial epithelium grown on permeable supports was established and the electrogenic ion transport across the endometrial epithelium was studied using the short-circuit current (I(SC)) technique. Enzymatically isolated mouse endometrial cells were immunostained with epithelial cells markers, cytokeratins, indicating an epithelial origin of the culture. Mouse endometrial epithelial cells grown on Millipore filters formed polarized monolayers with junctional complexes as revealed by light and electron microscopy. The cultured monolayers exhibited an average basal I(SC) of 4.6 +/- 0.3 microA/cm2, transepithelial voltage of 2.7 +/- 0.2 mV and transepithelial resistance of 599 +/- 30 omega cm2. The basal current was reduced by 85% in Na+-free solution and 13% in Cl(-)-free solution. The basal current could also be substantially (57.7%) blocked by an apical Na+ channel blocker, amiloride (10 microM), suggesting that Na+ absorption largely contributed to the basal current. Apical addition of Cl- channel blocker, DPC (2 mM), also exhibited an inhibitory effect, 19.4%, on the basal I(SC), indicating minor involvement of Cl- secretion as compared to that of Na+ absorption. The cultured endometrial epithelium also responded to a number of secretagogues including adrenaline and forskolin with increases in the I(SC), which could involve substantial Cl- secretion. The present study has established a culture of mouse endometrial epithelium exhibiting predominantly Na+ absorption under unstimulated condition, and Cl- secretion in response to various secretagogues. This culture may be useful for studying various regulatory mechanisms of electrogenic ion transport across the endometrial epithelium.


Subject(s)
Endometrium/metabolism , Ion Transport , Acetylcholine/pharmacology , Amiloride/pharmacology , Animals , Bumetanide/pharmacology , Cells, Cultured , Electric Impedance , Endometrium/cytology , Endometrium/ultrastructure , Epinephrine/pharmacology , Epithelium/metabolism , Female , Fluorescent Antibody Technique , Keratins/analysis , Mice , Mice, Inbred ICR , Vasopressins/pharmacology
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