Kang-ju Chou - Academia.edu (original) (raw)
Papers by Kang-ju Chou
International Journal of Environmental Research and Public Health
Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-assoc... more Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patient...
International Journal of Molecular Sciences
We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured... more We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and...
Experimental Cell Research, 2017
The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchy... more The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24h after injury and reduced lung stasis. An in vitro adhesion assay revealed that transfection enhanced the association between MSCs and hypoxic endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at the renal capsule, and some MSCs later migrated inward between tubules. Most homing MSCs were in close contact with inflammatory cells without tubular transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated renal injury, partly by enhancing the polarization of infiltrating macrophages. In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection might enhance renotropism and the regenerating ability of MSCs in ischemic kidney injury.
PloS one, 2016
Cardiovascular disease remains the most common cause of death for patients on chronic dialysis. E... more Cardiovascular disease remains the most common cause of death for patients on chronic dialysis. End stage renal disease patients undergoing dialysis imposed to reduce phosphorus intake, which likely contributes to development of vegetarian diet behaviors. Vegetarian diets are often lower in protein content, in contradiction to the recommendation that a high protein diet is followed by patients undergoing dialysis. The purpose of the study was to investigate the effects of a vegetarian diet on the nutritional and cardiovascular status of dialysis patients. A study of 21 vegetarian dialysis patients and 42 age- and sex-matched non-vegetarian dialysis patients selected as controls was conducted in the Kaohsiung Veterans General Hospital. Brachial-ankle pulse wave velocity and biochemistry data including total homocysteine levels, serum lipid profiles, high-sensitivity C-reactive protein, vitamin D levels, albumin, and normalized protein catabolic rate were measured. Compared with the n...
BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with hemodialysis in patie... more BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with hemodialysis in patients with severe azotemia remains obscure. To investigate whether either interstitial or cytotoxic edema is responsible for dialysis disequilibrium syndrome (DDS), we used diffusion-weighted MR imaging (DWI) to measure the apparent diffusion coefficient (ADC), which is sensitive for detecting tissue water dynamics. METHODS: Eight consecutive patients with end
PloS one, 2015
Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objec... more Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD. We conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed. There were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48....
Nephrology (Carlton, Vic.), Jan 19, 2015
Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-a... more Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-abdominal complications despite removal of the peritoneal catheter. Repeated percutaneous drainage or open laparotomy is often required, and mortality is not uncommon. The benefits of pelvic drainage placement during catheter removal in decreasing these complications and interventions remain unproven. Forty-six patients with refractory peritonitis who underwent removal of a Tenckhoff catheter between 1991 and 2013 were reviewed retrospectively. Twelve patients had pelvic drainage using closed active suction devices during catheter removal (drainage group). The remaining 34 patients underwent catheter removal without drainage (non-drainage group). The outcomes measured were the development of intra-abdominal complications and the requirement for repeated percutaneous drainage or open laparotomy within 90 days after the catheter removal. Baseline characteristics were similar with the except...
The Journal of clinical endocrinology and metabolism, Jan 8, 2015
Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal... more Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. To evaluate the short-term effect of co-administration of calcitriol and denosumab on parathyroid hormone secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. A 24-week, open-label study. Kaohsiung Veterans General Hospital. Dialysis patients with SHPT (intact parathyroid hormone [iPTH] >800 pg/mL) and low bone mass (T score <-2.5) were enrolled. Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH <300 pg/mL. Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (day 7, 14, and 21 and every month thereafter). iPTH significantly decreased (mean decrease, 58.28%±6.12%) with denosumab/calcitriol administration (P<0.01) but not ...
BMC cardiovascular disorders, Jan 4, 2014
There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. H... more There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. However, the relation of location-specific epicardial adipose tissue (EAT) thickness to coronary atherosclerotic burden is still unclear. This meta-analysis was used to study the relations between location-specific EAT thickness and obstructive coronary artery disease (CAD). A systemic literature search to identify eligible studies that met the inclusion criteria from the beginning until January 2014 was made. We conducted the meta-analysis of all included 10 published studies. Pre-specified subgroup analyses were performed according to ethnicity, body mass index, diagnostic tools for CAD, and measurement tool if presence of high heterogeneity between studies. Potential publication bias was also assessed. We identified ten observed studies with a total of 1625 subjects for planned comparison. With regard to the association between obstructive CAD and location-specific EAT thickness at the...
Nephron, 2015
Ultrafiltration is an adjunctive treatment for decompensated heart failure patients with cardiore... more Ultrafiltration is an adjunctive treatment for decompensated heart failure patients with cardiorenal syndrome. The efficacy and safety of ultrafiltration in the patient cohort are still unknown. We systematically reviewed and evaluated randomized controlled trials, comparing diuretics with ultrafiltration in adult patients with decompensated heart failure and cardiorenal syndrome through January 2014. The primary outcomes were body weight loss and total fluid removal. We identified 8 trials including 608 patients. In a random-effects model, the pooled difference of body weight loss was 1.44 kg between patients receiving ultrafiltration and diuretics (95% CI, 0.29-2.59; p = 0.01). The difference of fluid removal was 1.28 l between groups (95% CI, 0.43-2.12; p = 0.003). The RR for mortality was 0.90 for ultrafiltration compared with diuretics (95% CI, 0.61-1.33; p = 0.60) and the RR for renal function deterioration was 1.29 (95% CI, 0.90-1.85; p = 0.17). There is a trend toward reducing readmission rate in ultrafiltration group. Ultrafiltration is a safe and effective strategy in the treatment of cardiorenal syndrome without increasing the risk of renal deterioration. © 2015 S. Karger AG, Basel.
The American journal of tropical medicine and hygiene, 2005
We report an outbreak of ciguatoxin poisoning after barracuda fish ingestion in southern Taiwan. ... more We report an outbreak of ciguatoxin poisoning after barracuda fish ingestion in southern Taiwan. Three members of a family developed nausea, vomiting, watery diarrhea, and myalgias about 1 hour after eating three to ten eggs of a barracuda fish. Numbness of the lips and extremities followed the gastrointestinal symptoms about 2 hours after ingestion. Other manifestations included hyperthermia, hypotension, bradycardia, and hyperreflexia. Bradycardia persisted for several days, and one patient required a continuous infusion of intravenous atropine totaling 40 mg over 2 days. Further follow-up of the patients disclosed improvement of neurologic sequelae and bradycardia, but sensory abnormalities resolved several months later. In conclusion, ciguatoxin poisoning causes mainly gastrointestinal and neurologic effects of variable severity. In two patients with ciguatoxin poisoning after barracuda fish egg ingestion, persistent bradycardia required prolonged atropine infusion.
Korean Journal of Radiology, 2006
Objective: We wanted to report our experience of metallic stent placement after insufficient ball... more Objective: We wanted to report our experience of metallic stent placement after insufficient balloon dilation in graft hemodialysis patients. Materials and Methods: Twenty-three patients (13 loop grafts in the forearm and 10 straight grafts in the upper arm) underwent metallic stent placement due to insufficient flow after urokinase thrombolysis and balloon dilation. The indications for metallic stent deployment included 1) recoil and/or kinked venous stenosis in 21 patients (venous anastomosis: 17 patients, peripheral outflow vein: four patients); and 2) major vascular rupture in two patients. Metallic stents 8 10mm in diameter and 40 80 mm in length were used. Of them, eight stents were deployed across the elbow crease. Access patency was determined by clinical follow-up and the overall rates were calculated by Kaplan-Meier survival analysis. Results: No procedure-related complications (stent fracture or central migration) were encountered except for a delayed Wallstent shortening/migration at the venous anastomosis, which resulted in early access failure. The overall primary and secondary patency rates (standard error) of all the vascular accesses in our 23 patients at 3, 6, 12 and 24 months were 69% 9 and 88% 6, 41% 10 and 88% 6, 30% 10 and 77% 10, and 12% 8 and 61% 13, respectively. For the forearm and upper-arm grafts, the primary and secondary patency rates were 51% 16 and 86% 13 vs 45% 15 and 73% 13 at 6 months, and 25% 15 and 71% 17 vs 23% 17 and 73% 13 at 12 months (p = .346 and .224), respectively. Conclusion: Metallic stent placement is a safe and effective means for treating peripheral venous lesions in dialysis graft patients after insufficient balloon dilation. No statistically difference in the patency rates between the forearm and upper-arm patient groups was seen.
International journal of immunopharmacology, 2000
The effect of NPC-14686 (Fmoc-L-homophenylalanine), a novel anti-inflammatory agent on intracellu... more The effect of NPC-14686 (Fmoc-L-homophenylalanine), a novel anti-inflammatory agent on intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darby canine kidney (MDCK) renal tubular cells, was investigated, using fura-2 as a Ca(2+) dye. At concentrations between 10 and 200 microM NPC-14686 increased [Ca(2+)](i) concentration dependently. The [Ca(2+)](i) signal comprised an initial rise and a sustained phase. Ca(2+) removal inhibited the Ca(2+) signals by 90%. In Ca(2+)-free medium, pretreatment with 100 microM NPC-14686 nearly abolished the [Ca(2+)](i) increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and abolished the [Ca(2+)](i) increase induced by 2 microM carbonylcyanide m-chlorophenylhydrazone (CCCP) (a mitochondrial uncoupler). NPC-14686 (100 microM) induced a slight [Ca(2+)](i) increase after pretreatment with 2 microM CCCP and 1 microM thapsigargin. Addition of 3 mM Ca(2+) elicited a [Ca(2+)](i) increase in cells pretreated ...
Toxicon, 2002
The effect of gossypol, a compound found in cottonseed, on intracellular free Ca2+ levels ([Ca2+]... more The effect of gossypol, a compound found in cottonseed, on intracellular free Ca2+ levels ([Ca2+](i)) in Chang liver cells were evaluated using fura-2 as a fluorescent Ca2+ indicator. Gossypol (0.2-5microM) increased [Ca2+](i) in a concentration-dependent manner with an EC(50) value of 1.5microM. The [Ca2+](i) response was composed of an initial rise and a slow decay to a sustained phase within 5min after drug application. Removal of extracellular Ca2+ markedly reduced the [Ca2+](i) signals by 80+/-2%. Preincubation with 0.1mM La3+ or 10microM nimodipine abolished the Ca2+ influx. Gossypol (5microM)-induced release of intracellular Ca2+ was reduced by 75% by pretreatment with 1microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+. Conversely, pretreatment with gossypol abolished thapsigargin-induced Ca2+ release. After pretreatment with 5microM gossypol in Ca2+-free medium for several min, addition of 3mM Ca2+ induced a [Ca2+](i) increase of a magnitude nine-fold greater than control. Gossypol (5microM)-induced Ca2+ release was not affected by inhibiting phospholipase C with 2microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Together, this study shows that gossypol induced significant [Ca2+](i) increases in Chang liver cells by releasing Ca2+ from intracellular pools in a phospholipase C-dissociated fashion and by causing La3+- and nimodipine-sensitive Ca2+ influx.
Toxicology Letters, 2001
The effect of fendiline, an anti-anginal drug, on cytosolic free Ca 2 + levels ([Ca 2 + ] i) in M... more The effect of fendiline, an anti-anginal drug, on cytosolic free Ca 2 + levels ([Ca 2 + ] i) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca 2 + indicator. Fendiline at concentrations between 1 and 200 mM increased [Ca 2 + ] i in a concentration-dependent manner and the signal saturated at 100 mM. The Ca 2 + signal was inhibited by 65 9 5% by Ca 2 + removal and by 38 95% by 10 mM nifedipine, but was unchanged by 10 mM La 3 + or verapamil. In Ca 2 +-free medium, pre-treatment with 1 mM thapsigargin (an endoplasmic reticulum Ca 2 + pump inhibitor) to deplete the endoplasmic reticulum Ca 2 + store inhibited fendiline-induced intracellular Ca 2 + release. The Ca 2 + release induced by 50 mM fendiline appeared to be independent of IP 3 because the [Ca 2 + ] i increase was unaltered by inhibiting phospholipase C with 2 mM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca 2 + ] i by inducing Ca 2 + influx and Ca 2 + release in an IP 3-independent manner.
Toxicology and Applied Pharmacology, 2000
The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cel... more The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Tamoxifen evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 1 and 50 microM with an EC50 of 10 microM. The response was decreased by extracellular Ca(2+) removal. In Ca(2+)-free medium, pretreatment with 5 microM tamoxifen abolished the [Ca(2+)](i) increase induced by the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM), but pretreatment with brefeldin A (50 microM; a Ca(2+) mobilizer of the Golgi complex), thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) pump), and carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), only partly inhibited tamoxifen-induced [Ca(2+)](i) increases. This suggests that tamoxifen released Ca(2+) from multiple pools. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) rise after pretreatment with 5 microM tamoxifen in Ca(2+)-free medium. Inhibiting inositol 1,4,5-trisphosphate formation with the phospholipase C inhibitor U73122 (2 microM) did not alter 5 microM tamoxifen-induced Ca(2+) release. The [Ca(2+)](i) increase induced by 5 microM tamoxifen was not altered by La(3+), nifedipine, verapamil, or diltiazem. Tamoxifen (1-10 microM) decreased cell viability in a concentration- and time-dependent manner. Tamoxifen (5 microM) also increased [Ca(2+)](i) in neutrophils, bladder cancer cells, and prostate cancer cells from humans and glioma cells from rats. Collectively, it was found that tamoxifen increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from multiple Ca(2+) stores in a manner independent of the production of inositol 1,4, 5-trisphosphate and also by triggering Ca(2+) influx from extracellular space. The [Ca(2+)](i) increase was accompanied by cytotoxicity.
Thrombosis and Haemostasis, 2004
SummaryIt is known that thrombosis is a leading cause of vascular access failure and that the for... more SummaryIt is known that thrombosis is a leading cause of vascular access failure and that the formation of thrombus requires platelets. The activation of platelets induces the increase in intracellular Ca2+ levels ([Ca2+]i) leading to aggregation and thrombosis. We compared the platelet [Ca2+]i before and after stimulation between the patients with and without easily occluded vascular access. Our study included two groups of hemodialysis patients. Group 1 consisted of 21 patients who had received chronic hemodialysis therapy for more than 6 months. They had had more than three events (including three) of vascular access failures during the past year. Group 2 consisted of 21 hemodialysis patients with age, sex, and diabetes mellitus matched who had never suffered from any event of vascular access failure. We measured the basal and stimulated platelet [Ca2+]i after stimulation with 1 U/ml thrombin, 1 µM arachidonic acid, 1 µM platelet activation factor (PAF), and 10 µM adenosine dipho...
Nephron, 2001
In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in... more In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in dialysis patients previously found only in a small number of cases. We collected the cases of newly diagnosed TB patients in Taiwan during 1997. Simultaneously, all dialysis patients were collected and matched with the TB cases to identify the dialysis patients who had also contracted TB. The annual incidence of the dialysis population was 493.4/100,000, 6.9 times that of the general population (71.1/100,000). The annual incidence for the male dialysis population was 573.3, the incidence was 479.2 for the female dialysis population. The incidence for the general population was 97.1 and 43.7/100,000, respectively. Although the 1-year mortality rate due to TB (1.7 vs. 1.9%, p > 0.05) was similar in both populations, the non-TB mortality was much higher in the dialysis population than that in the general population (25.6 vs. 11.1%, p < 0.05). Finally, the 1-year mortality rate of dialysis patients with TB is 3.3 times higher than that in dialysis patients without TB (27.3 vs. 8.3%, p < 0.05). The findings suggest that uremia modifies the behavior of TB, jeopardizes female and younger dialysis patients, poses a higher risk of extrapulmonary dissemination, and predicts a higher overall mortality.
Steroids, 2001
The effect of the estrogen diethylstilbestrol (DES) on intracellular Ca 2ϩ concentrations ([Ca 2ϩ... more The effect of the estrogen diethylstilbestrol (DES) on intracellular Ca 2ϩ concentrations ([Ca 2ϩ ] i) in Madin Darby canine kidney (MDCK) cells was investigated, using the fluorescent dye fura-2 as a Ca 2ϩ indicator. DES (10-50 M) evoked [Ca 2ϩ ] i increases in a concentrationdependent manner. Extracellular Ca 2ϩ removal inhibited 45 Ϯ 5% of the Ca 2ϩ response. In Ca 2ϩ-free medium, pretreatment with 50 M DES abolished the [Ca 2ϩ ] i increases induced by 2 M carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler) and 1 M thapsigargin (an endoplasmic reticulum Ca 2ϩ pump inhibitor); and pretreatment with CCCP and thapsigargin partly inhibited DES-induced [Ca 2ϩ ] i signals. Adding 3 mM Ca 2ϩ increased [Ca 2ϩ ] i in cells pretreated with 50 M DES in Ca 2ϩ-free medium, suggesting that DES may induce capacitative Ca 2ϩ entry. 17-Estradiol (2-20 M) increased [Ca 2ϩ ] i , but 100 M diethylstilbestrol dipropionate had no effect. Pretreatment with the phospholipase C inhibitor U73122 (1 M) to abolish inositol 1,4,5-trisphosphate formation inhibited 30% of DES-induced Ca 2ϩ release. DES (20 M) also increased [Ca 2ϩ ] i in human normal hepatocytes and osteosarcoma cells. Cumulatively, this study shows that DES induced rapid and sustained [Ca 2ϩ ] i increases by releasing intracellular Ca 2ϩ and triggering extracellular Ca 2ϩ entry in renal tubular cells.
Pharmacology, 2002
The effect of 17beta-estradiol on intracellular Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darb... more The effect of 17beta-estradiol on intracellular Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darby canine kidney cells was investigated by using the fluorescent dye fura-2. 17Beta-estradiol (5-100 micromol/l) induced instantaneous increases in [Ca(2+)](i) in a concentration-dependent manner. Ca(2+) removal inhibited 45 +/- 15% of the Ca(2+) signal. In Ca(2+)-free medium, pretreatment with 50 micromol/l 17beta-estradiol abolished the [Ca(2+)](i) increases induced by 2 micromol/l carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), 1 micromol/l thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and 50 micromol/l brefeldin A (an antibiotic which disperses the Golgi complex), but pretreatment with brefeldin A, CCCP and thapsigargin only partly inhibited the 17beta-estradiol-induced [Ca(2+)](i) signal. Adding 3 mmol/l Ca(2+) increased [Ca(2+)](i) in cells pretreated with 5-100 micromol/l 17beta-estradiol in Ca(2+)-free medium. Pretreatment with 1 micromol/l U73122 to abolish the formation of inositol-1,4,5-trisphosphate inhibited 50% of the Ca(2+) release induced by 50 micromol/l 17beta-estradiol. 17Beta-estradiol (20 micromol/l) also increased [Ca(2+)](i) in human bladder cancer cells and prostate cancer cells. Collectively, this study shows that 17beta-estradiol evoked a significant internal Ca(2+) release and external Ca(2+) entry possibly in a nongenomic manner.
International Journal of Environmental Research and Public Health
Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-assoc... more Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patient...
International Journal of Molecular Sciences
We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured... more We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and...
Experimental Cell Research, 2017
The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchy... more The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24h after injury and reduced lung stasis. An in vitro adhesion assay revealed that transfection enhanced the association between MSCs and hypoxic endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at the renal capsule, and some MSCs later migrated inward between tubules. Most homing MSCs were in close contact with inflammatory cells without tubular transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated renal injury, partly by enhancing the polarization of infiltrating macrophages. In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection might enhance renotropism and the regenerating ability of MSCs in ischemic kidney injury.
PloS one, 2016
Cardiovascular disease remains the most common cause of death for patients on chronic dialysis. E... more Cardiovascular disease remains the most common cause of death for patients on chronic dialysis. End stage renal disease patients undergoing dialysis imposed to reduce phosphorus intake, which likely contributes to development of vegetarian diet behaviors. Vegetarian diets are often lower in protein content, in contradiction to the recommendation that a high protein diet is followed by patients undergoing dialysis. The purpose of the study was to investigate the effects of a vegetarian diet on the nutritional and cardiovascular status of dialysis patients. A study of 21 vegetarian dialysis patients and 42 age- and sex-matched non-vegetarian dialysis patients selected as controls was conducted in the Kaohsiung Veterans General Hospital. Brachial-ankle pulse wave velocity and biochemistry data including total homocysteine levels, serum lipid profiles, high-sensitivity C-reactive protein, vitamin D levels, albumin, and normalized protein catabolic rate were measured. Compared with the n...
BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with hemodialysis in patie... more BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with hemodialysis in patients with severe azotemia remains obscure. To investigate whether either interstitial or cytotoxic edema is responsible for dialysis disequilibrium syndrome (DDS), we used diffusion-weighted MR imaging (DWI) to measure the apparent diffusion coefficient (ADC), which is sensitive for detecting tissue water dynamics. METHODS: Eight consecutive patients with end
PloS one, 2015
Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objec... more Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD. We conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed. There were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48....
Nephrology (Carlton, Vic.), Jan 19, 2015
Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-a... more Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-abdominal complications despite removal of the peritoneal catheter. Repeated percutaneous drainage or open laparotomy is often required, and mortality is not uncommon. The benefits of pelvic drainage placement during catheter removal in decreasing these complications and interventions remain unproven. Forty-six patients with refractory peritonitis who underwent removal of a Tenckhoff catheter between 1991 and 2013 were reviewed retrospectively. Twelve patients had pelvic drainage using closed active suction devices during catheter removal (drainage group). The remaining 34 patients underwent catheter removal without drainage (non-drainage group). The outcomes measured were the development of intra-abdominal complications and the requirement for repeated percutaneous drainage or open laparotomy within 90 days after the catheter removal. Baseline characteristics were similar with the except...
The Journal of clinical endocrinology and metabolism, Jan 8, 2015
Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal... more Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. To evaluate the short-term effect of co-administration of calcitriol and denosumab on parathyroid hormone secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. A 24-week, open-label study. Kaohsiung Veterans General Hospital. Dialysis patients with SHPT (intact parathyroid hormone [iPTH] >800 pg/mL) and low bone mass (T score <-2.5) were enrolled. Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH <300 pg/mL. Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (day 7, 14, and 21 and every month thereafter). iPTH significantly decreased (mean decrease, 58.28%±6.12%) with denosumab/calcitriol administration (P<0.01) but not ...
BMC cardiovascular disorders, Jan 4, 2014
There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. H... more There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. However, the relation of location-specific epicardial adipose tissue (EAT) thickness to coronary atherosclerotic burden is still unclear. This meta-analysis was used to study the relations between location-specific EAT thickness and obstructive coronary artery disease (CAD). A systemic literature search to identify eligible studies that met the inclusion criteria from the beginning until January 2014 was made. We conducted the meta-analysis of all included 10 published studies. Pre-specified subgroup analyses were performed according to ethnicity, body mass index, diagnostic tools for CAD, and measurement tool if presence of high heterogeneity between studies. Potential publication bias was also assessed. We identified ten observed studies with a total of 1625 subjects for planned comparison. With regard to the association between obstructive CAD and location-specific EAT thickness at the...
Nephron, 2015
Ultrafiltration is an adjunctive treatment for decompensated heart failure patients with cardiore... more Ultrafiltration is an adjunctive treatment for decompensated heart failure patients with cardiorenal syndrome. The efficacy and safety of ultrafiltration in the patient cohort are still unknown. We systematically reviewed and evaluated randomized controlled trials, comparing diuretics with ultrafiltration in adult patients with decompensated heart failure and cardiorenal syndrome through January 2014. The primary outcomes were body weight loss and total fluid removal. We identified 8 trials including 608 patients. In a random-effects model, the pooled difference of body weight loss was 1.44 kg between patients receiving ultrafiltration and diuretics (95% CI, 0.29-2.59; p = 0.01). The difference of fluid removal was 1.28 l between groups (95% CI, 0.43-2.12; p = 0.003). The RR for mortality was 0.90 for ultrafiltration compared with diuretics (95% CI, 0.61-1.33; p = 0.60) and the RR for renal function deterioration was 1.29 (95% CI, 0.90-1.85; p = 0.17). There is a trend toward reducing readmission rate in ultrafiltration group. Ultrafiltration is a safe and effective strategy in the treatment of cardiorenal syndrome without increasing the risk of renal deterioration. © 2015 S. Karger AG, Basel.
The American journal of tropical medicine and hygiene, 2005
We report an outbreak of ciguatoxin poisoning after barracuda fish ingestion in southern Taiwan. ... more We report an outbreak of ciguatoxin poisoning after barracuda fish ingestion in southern Taiwan. Three members of a family developed nausea, vomiting, watery diarrhea, and myalgias about 1 hour after eating three to ten eggs of a barracuda fish. Numbness of the lips and extremities followed the gastrointestinal symptoms about 2 hours after ingestion. Other manifestations included hyperthermia, hypotension, bradycardia, and hyperreflexia. Bradycardia persisted for several days, and one patient required a continuous infusion of intravenous atropine totaling 40 mg over 2 days. Further follow-up of the patients disclosed improvement of neurologic sequelae and bradycardia, but sensory abnormalities resolved several months later. In conclusion, ciguatoxin poisoning causes mainly gastrointestinal and neurologic effects of variable severity. In two patients with ciguatoxin poisoning after barracuda fish egg ingestion, persistent bradycardia required prolonged atropine infusion.
Korean Journal of Radiology, 2006
Objective: We wanted to report our experience of metallic stent placement after insufficient ball... more Objective: We wanted to report our experience of metallic stent placement after insufficient balloon dilation in graft hemodialysis patients. Materials and Methods: Twenty-three patients (13 loop grafts in the forearm and 10 straight grafts in the upper arm) underwent metallic stent placement due to insufficient flow after urokinase thrombolysis and balloon dilation. The indications for metallic stent deployment included 1) recoil and/or kinked venous stenosis in 21 patients (venous anastomosis: 17 patients, peripheral outflow vein: four patients); and 2) major vascular rupture in two patients. Metallic stents 8 10mm in diameter and 40 80 mm in length were used. Of them, eight stents were deployed across the elbow crease. Access patency was determined by clinical follow-up and the overall rates were calculated by Kaplan-Meier survival analysis. Results: No procedure-related complications (stent fracture or central migration) were encountered except for a delayed Wallstent shortening/migration at the venous anastomosis, which resulted in early access failure. The overall primary and secondary patency rates (standard error) of all the vascular accesses in our 23 patients at 3, 6, 12 and 24 months were 69% 9 and 88% 6, 41% 10 and 88% 6, 30% 10 and 77% 10, and 12% 8 and 61% 13, respectively. For the forearm and upper-arm grafts, the primary and secondary patency rates were 51% 16 and 86% 13 vs 45% 15 and 73% 13 at 6 months, and 25% 15 and 71% 17 vs 23% 17 and 73% 13 at 12 months (p = .346 and .224), respectively. Conclusion: Metallic stent placement is a safe and effective means for treating peripheral venous lesions in dialysis graft patients after insufficient balloon dilation. No statistically difference in the patency rates between the forearm and upper-arm patient groups was seen.
International journal of immunopharmacology, 2000
The effect of NPC-14686 (Fmoc-L-homophenylalanine), a novel anti-inflammatory agent on intracellu... more The effect of NPC-14686 (Fmoc-L-homophenylalanine), a novel anti-inflammatory agent on intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darby canine kidney (MDCK) renal tubular cells, was investigated, using fura-2 as a Ca(2+) dye. At concentrations between 10 and 200 microM NPC-14686 increased [Ca(2+)](i) concentration dependently. The [Ca(2+)](i) signal comprised an initial rise and a sustained phase. Ca(2+) removal inhibited the Ca(2+) signals by 90%. In Ca(2+)-free medium, pretreatment with 100 microM NPC-14686 nearly abolished the [Ca(2+)](i) increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and abolished the [Ca(2+)](i) increase induced by 2 microM carbonylcyanide m-chlorophenylhydrazone (CCCP) (a mitochondrial uncoupler). NPC-14686 (100 microM) induced a slight [Ca(2+)](i) increase after pretreatment with 2 microM CCCP and 1 microM thapsigargin. Addition of 3 mM Ca(2+) elicited a [Ca(2+)](i) increase in cells pretreated ...
Toxicon, 2002
The effect of gossypol, a compound found in cottonseed, on intracellular free Ca2+ levels ([Ca2+]... more The effect of gossypol, a compound found in cottonseed, on intracellular free Ca2+ levels ([Ca2+](i)) in Chang liver cells were evaluated using fura-2 as a fluorescent Ca2+ indicator. Gossypol (0.2-5microM) increased [Ca2+](i) in a concentration-dependent manner with an EC(50) value of 1.5microM. The [Ca2+](i) response was composed of an initial rise and a slow decay to a sustained phase within 5min after drug application. Removal of extracellular Ca2+ markedly reduced the [Ca2+](i) signals by 80+/-2%. Preincubation with 0.1mM La3+ or 10microM nimodipine abolished the Ca2+ influx. Gossypol (5microM)-induced release of intracellular Ca2+ was reduced by 75% by pretreatment with 1microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+. Conversely, pretreatment with gossypol abolished thapsigargin-induced Ca2+ release. After pretreatment with 5microM gossypol in Ca2+-free medium for several min, addition of 3mM Ca2+ induced a [Ca2+](i) increase of a magnitude nine-fold greater than control. Gossypol (5microM)-induced Ca2+ release was not affected by inhibiting phospholipase C with 2microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Together, this study shows that gossypol induced significant [Ca2+](i) increases in Chang liver cells by releasing Ca2+ from intracellular pools in a phospholipase C-dissociated fashion and by causing La3+- and nimodipine-sensitive Ca2+ influx.
Toxicology Letters, 2001
The effect of fendiline, an anti-anginal drug, on cytosolic free Ca 2 + levels ([Ca 2 + ] i) in M... more The effect of fendiline, an anti-anginal drug, on cytosolic free Ca 2 + levels ([Ca 2 + ] i) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca 2 + indicator. Fendiline at concentrations between 1 and 200 mM increased [Ca 2 + ] i in a concentration-dependent manner and the signal saturated at 100 mM. The Ca 2 + signal was inhibited by 65 9 5% by Ca 2 + removal and by 38 95% by 10 mM nifedipine, but was unchanged by 10 mM La 3 + or verapamil. In Ca 2 +-free medium, pre-treatment with 1 mM thapsigargin (an endoplasmic reticulum Ca 2 + pump inhibitor) to deplete the endoplasmic reticulum Ca 2 + store inhibited fendiline-induced intracellular Ca 2 + release. The Ca 2 + release induced by 50 mM fendiline appeared to be independent of IP 3 because the [Ca 2 + ] i increase was unaltered by inhibiting phospholipase C with 2 mM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca 2 + ] i by inducing Ca 2 + influx and Ca 2 + release in an IP 3-independent manner.
Toxicology and Applied Pharmacology, 2000
The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cel... more The effect of tamoxifen on Ca(2+) signaling and viability in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Tamoxifen evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 1 and 50 microM with an EC50 of 10 microM. The response was decreased by extracellular Ca(2+) removal. In Ca(2+)-free medium, pretreatment with 5 microM tamoxifen abolished the [Ca(2+)](i) increase induced by the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM), but pretreatment with brefeldin A (50 microM; a Ca(2+) mobilizer of the Golgi complex), thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) pump), and carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), only partly inhibited tamoxifen-induced [Ca(2+)](i) increases. This suggests that tamoxifen released Ca(2+) from multiple pools. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) rise after pretreatment with 5 microM tamoxifen in Ca(2+)-free medium. Inhibiting inositol 1,4,5-trisphosphate formation with the phospholipase C inhibitor U73122 (2 microM) did not alter 5 microM tamoxifen-induced Ca(2+) release. The [Ca(2+)](i) increase induced by 5 microM tamoxifen was not altered by La(3+), nifedipine, verapamil, or diltiazem. Tamoxifen (1-10 microM) decreased cell viability in a concentration- and time-dependent manner. Tamoxifen (5 microM) also increased [Ca(2+)](i) in neutrophils, bladder cancer cells, and prostate cancer cells from humans and glioma cells from rats. Collectively, it was found that tamoxifen increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from multiple Ca(2+) stores in a manner independent of the production of inositol 1,4, 5-trisphosphate and also by triggering Ca(2+) influx from extracellular space. The [Ca(2+)](i) increase was accompanied by cytotoxicity.
Thrombosis and Haemostasis, 2004
SummaryIt is known that thrombosis is a leading cause of vascular access failure and that the for... more SummaryIt is known that thrombosis is a leading cause of vascular access failure and that the formation of thrombus requires platelets. The activation of platelets induces the increase in intracellular Ca2+ levels ([Ca2+]i) leading to aggregation and thrombosis. We compared the platelet [Ca2+]i before and after stimulation between the patients with and without easily occluded vascular access. Our study included two groups of hemodialysis patients. Group 1 consisted of 21 patients who had received chronic hemodialysis therapy for more than 6 months. They had had more than three events (including three) of vascular access failures during the past year. Group 2 consisted of 21 hemodialysis patients with age, sex, and diabetes mellitus matched who had never suffered from any event of vascular access failure. We measured the basal and stimulated platelet [Ca2+]i after stimulation with 1 U/ml thrombin, 1 µM arachidonic acid, 1 µM platelet activation factor (PAF), and 10 µM adenosine dipho...
Nephron, 2001
In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in... more In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in dialysis patients previously found only in a small number of cases. We collected the cases of newly diagnosed TB patients in Taiwan during 1997. Simultaneously, all dialysis patients were collected and matched with the TB cases to identify the dialysis patients who had also contracted TB. The annual incidence of the dialysis population was 493.4/100,000, 6.9 times that of the general population (71.1/100,000). The annual incidence for the male dialysis population was 573.3, the incidence was 479.2 for the female dialysis population. The incidence for the general population was 97.1 and 43.7/100,000, respectively. Although the 1-year mortality rate due to TB (1.7 vs. 1.9%, p > 0.05) was similar in both populations, the non-TB mortality was much higher in the dialysis population than that in the general population (25.6 vs. 11.1%, p < 0.05). Finally, the 1-year mortality rate of dialysis patients with TB is 3.3 times higher than that in dialysis patients without TB (27.3 vs. 8.3%, p < 0.05). The findings suggest that uremia modifies the behavior of TB, jeopardizes female and younger dialysis patients, poses a higher risk of extrapulmonary dissemination, and predicts a higher overall mortality.
Steroids, 2001
The effect of the estrogen diethylstilbestrol (DES) on intracellular Ca 2ϩ concentrations ([Ca 2ϩ... more The effect of the estrogen diethylstilbestrol (DES) on intracellular Ca 2ϩ concentrations ([Ca 2ϩ ] i) in Madin Darby canine kidney (MDCK) cells was investigated, using the fluorescent dye fura-2 as a Ca 2ϩ indicator. DES (10-50 M) evoked [Ca 2ϩ ] i increases in a concentrationdependent manner. Extracellular Ca 2ϩ removal inhibited 45 Ϯ 5% of the Ca 2ϩ response. In Ca 2ϩ-free medium, pretreatment with 50 M DES abolished the [Ca 2ϩ ] i increases induced by 2 M carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler) and 1 M thapsigargin (an endoplasmic reticulum Ca 2ϩ pump inhibitor); and pretreatment with CCCP and thapsigargin partly inhibited DES-induced [Ca 2ϩ ] i signals. Adding 3 mM Ca 2ϩ increased [Ca 2ϩ ] i in cells pretreated with 50 M DES in Ca 2ϩ-free medium, suggesting that DES may induce capacitative Ca 2ϩ entry. 17-Estradiol (2-20 M) increased [Ca 2ϩ ] i , but 100 M diethylstilbestrol dipropionate had no effect. Pretreatment with the phospholipase C inhibitor U73122 (1 M) to abolish inositol 1,4,5-trisphosphate formation inhibited 30% of DES-induced Ca 2ϩ release. DES (20 M) also increased [Ca 2ϩ ] i in human normal hepatocytes and osteosarcoma cells. Cumulatively, this study shows that DES induced rapid and sustained [Ca 2ϩ ] i increases by releasing intracellular Ca 2ϩ and triggering extracellular Ca 2ϩ entry in renal tubular cells.
Pharmacology, 2002
The effect of 17beta-estradiol on intracellular Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darb... more The effect of 17beta-estradiol on intracellular Ca(2+) concentrations ([Ca(2+)](i)) in Madin Darby canine kidney cells was investigated by using the fluorescent dye fura-2. 17Beta-estradiol (5-100 micromol/l) induced instantaneous increases in [Ca(2+)](i) in a concentration-dependent manner. Ca(2+) removal inhibited 45 +/- 15% of the Ca(2+) signal. In Ca(2+)-free medium, pretreatment with 50 micromol/l 17beta-estradiol abolished the [Ca(2+)](i) increases induced by 2 micromol/l carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), 1 micromol/l thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and 50 micromol/l brefeldin A (an antibiotic which disperses the Golgi complex), but pretreatment with brefeldin A, CCCP and thapsigargin only partly inhibited the 17beta-estradiol-induced [Ca(2+)](i) signal. Adding 3 mmol/l Ca(2+) increased [Ca(2+)](i) in cells pretreated with 5-100 micromol/l 17beta-estradiol in Ca(2+)-free medium. Pretreatment with 1 micromol/l U73122 to abolish the formation of inositol-1,4,5-trisphosphate inhibited 50% of the Ca(2+) release induced by 50 micromol/l 17beta-estradiol. 17Beta-estradiol (20 micromol/l) also increased [Ca(2+)](i) in human bladder cancer cells and prostate cancer cells. Collectively, this study shows that 17beta-estradiol evoked a significant internal Ca(2+) release and external Ca(2+) entry possibly in a nongenomic manner.