Cyclosporine nephrotoxicity: the mechanisms of cell injury by cyclosporine A in renal proximal tubular cells.
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Animals↗
Biomedical subjects
D S Han
Publications and source records attributed to D S Han.
Hyperhomocysteinemia in renal transplant recipients with cyclosporine.
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Cyclosporine↗
Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats.
Keratinocyte growth factor-2 (KGF-2, repifermin) is a homolog of KGF-1 with epithelial mitogenic activities. We investigated the therapeutic role of KGF-2 in intestinal ulceration and its mechanisms of protection. KGF-2 (0.3-5 mg/kg) was administered before or after induction of small intestinal ulceration by indomethacin (Indo) in prevention and treatment protocols. In acute studies, KGF-2 was injected for up to 7 days before or daily for 5 days after Indo. In a 15-day chronic study, KGF-2 was injected intravenously daily beginning before or 7 days after Indo. Injury was evaluated by blinded macroscopic and microscopic inflammatory scores, epithelial BrdU staining, tissue IL-1beta, PGE(2), and hydroxyproline concentrations, and collagen type I RNA expression. In vitro effects of KGF-2 were evaluated by epithelial cellular proliferation, restitution of wounded monolayers, PGE(2) secretion, and expression of COX-2 and collagen mRNA. Intravenous KGF-2 significantly decreased acute intestinal injury by all parameters and significantly decreased chronic ulceration. Pretreatment, daily infusion, and delayed treatment were effective. KGF-2 promoted in vitro epithelial restitution with only modest effects on epithelial cell proliferation, stimulated COX-2 expression in cultured epithelial cells, and upregulated in vitro and in vivo PGE(2) production. KGF-2 did not affect in vivo fibrosis, although it induced collagen expression in cultured intestinal myofibroblasts. These results suggest that KGF-2 inhibits intestinal inflammation by stimulating epithelial restitution and protective PGs.
Acute Disease↗
The prevalence and associated risk factors of renal artery stenosis in patients undergoing cardiac catheterization.
Renal artery stenosis may be a cause of hypertension and a potential contributor to progressive renal insufficiency. However, the prevalence of renal artery disease in a general population is poorly defined. The purposes of this study were to evaluate the prevalence of angiographically-determined renal artery narrowing in a patient population undergoing routine cardiac catheterization, and to identify the risk factors for renal artery stenosis. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery stenosis. A total of 427 patients (274 males, 153 females) were studied and the mean age was 59 years. Renal artery narrowing was identified in 10.5% of patients. Significant (> or = 50% diameter narrowing) renal artery stenosis was found in 24 patients (5.6%) and insignificant stenosis was found in 21 patients (4.9%). Significant unilateral stenosis was present in 4.2% of patients and bilateral stenosis was present in 1.4%. The stem of the renal artery was a more common site of stenosis in 62.2% of patients than in the ostium (37.8%), but the severity of stenosis was not significantly different according to the site of stenosis. By univariate and multivariate logistic regression analysis, the association of clinical variables with renal artery stenosis was assessed. Multivariable predictors included age, hypertension and peripheral vascular disease (p < 0.05). The variables such as sex, smoking history, hyperlipidemia, renal insufficiency, as well as the presence of obesity, severity of coronary heart disease and D.M., were not associated. In conclusion, the prevalence of angiographically-determined renal artery narrowing in a patient population undergoing cardiac catheterization is 10.5%. Old age, hypertension and evidence of peripheral vascular disease represent the predictors of renal artery stenosis.
Adult↗
Gentamicin induced apoptosis of renal tubular epithelial (LLC-PK1) cells.
Nephrotoxicity is a major limiting factor in the use of aminoglycoside antibiotics, the mechanisms for which are still speculative. To clarify the mechanisms of renal tubular cell death induced by aminoglycosides, we examined the renal proximal tubule-like cell line, LLC-PK1, after inducing apoptosis through a chronic treatment with gentamicin (GM). Changes in the expression of the Fas were also investigated. On flow cytometric analysis, 5.7 +/- 3.3% of the control cells appeared in a region of decreased forward light scatter and increased side light scatter, where both indices represent the characteristics of apoptotic cell death. Compared to the control, treatment with 10 mM of GM for 15 days significantly increased the proportion of cells in the apoptotic region to 23.9 +/- 8.5%. This finding was supported by electrophoretic analysis of the DNA extracted from the GM-treated cells, where a series of bands corresponding to integer multiples of 180 to 200 base pairs was visualized. However, the 15-day GM treatment did not cause a significant elevation in the expression of the 45 kD Fas protein, the cell surface molecule that stimulates apoptosis, by Western blot analysis. In conclusion, long-term exposure to GM induces apoptosis of the renal tubular epithelial cells, and this process may contribute to some of the aminoglycoside nephrotoxicities. Further studies are needed on the mechanism(s) of apoptosis induced by GM.
Animals↗
Metabolic acidosis and composite nutritional index (CNI) in CAPD patients.
BACKGROUND: Metabolic acidosis (MA) has been recognized as an important stimulus for net protein catabolism. Continuous ambulatory peritoneal dialysis (CAPD) is regarded to have advantage in normalizing the acid-base homeostasis over hemodialysis due to continuous supply of buffer. However, many CAPD patients still remain acidotic and the clinical impact of this MA is uncertain. Recent studies revealed no specific correlation between a certain degree of MA and protein nutritional status while others showed that mild alkalosis is nutritionally beneficial to CAPD patients. A cross-sectional study evaluating acid-base and nutritional status was performed to examine the relationship between acid-base status and overall nutritional status assessed by composite nutritional index (CNI) and to get a basic information about the optimal pH/HCO3 in CAPD patients. PATIENTS AND METHODS: Total 198 clinically stable patients maintained on CAPD more than 6 months were evaluated. Each of 10 nutritional parameters of CNI consisting of clinical (subjective global assessment), biochemical (total lymphocyte count, albumin, prealbumin, insulin-like growth factor-1, transferrin) and anthropometric parameters (body mass index, % lean body mass, triceps skinfold thickness, midarm muscle circumference) was graded from 0 to 3 point (0; normal, 1; mildly decreased, 2; moderately decreased, 3; severely decreased). RESULTS: Mean CNI score was 8.2 +/- 5.2 with a range of 0 to 25. CNI was positively correlated with age, duration of peritoneal dialysis, incidence of peritonitis, C-reactive protein (CRP), HCO3 and dialytic protein loss whereas it was inversely correlated with hemoglobin and nPNA. In patients with MA (n = 25, mean arterial HCO3 19.5 +/- 1.9 mM/l), CNI score was significantly lower (6.3 +/- 3.5) compared to patients with normal acid-base status (n = 63, 9.5 +/- 5.9, p < 0.01) or metabolic alkalosis (n = 47, 10.1 +/- 4.6, p < 0.001). Multiple regression analysis revealed that the incidence of peritonitis, duration of dialysis, CRP and dialytic protein loss were the independent predictors of CNI. CONCLUSIONS: CAPD patients with mild to moderate degree of MA appear to be associated with more favorable overall nutritional status expressed as CNI. Prospective studies evaluating changes in the nutritional parameters with the correction of acid-base abnormality are needed to understand the real impact of acid-base status on nutritional status and to know the optimal pH/HCO3 in CAPD patients.
Acidosis↗
Characterization of the humoral and cellular immune responses against hepatitis C virus core induced by DNA-based immunization.
Hepatitis C Virus (HCV) causes most cases of posttransfusion hepatitis. Chronic HCV infection is highly related to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Current therapies are only minimally effective and no vaccine has been developed. DNA-based immunization could be of prophylactic and therapeutic value for HCV infection. By intramuscular inoculation in BALB/c mice with an HCV recombinant plasmid pCI-HCV-C, we found significant levels of IgM antibody, but no significant IgG rise. After boost the immunized mice with recombinant HCV-core protein (cp1-10; 1-164aa), the anticore IgG, verified by Western-blotting, rose rapidly, which was two weeks earlier than that with control plasmid. Spleen cells from pCI-HCV-C immunized mice gave higher proliferation index (PI) than control (P < 0.05). The PI of cp1-10 boosted mice was even higher. Proliferation blocking assay with mAb proved the responding cell to be of CD4+ CD8- phenotype, supporting specific priming of T helper cells. A 51Cr-releasing CTL assay specific for HCV-core was developed, and a specific CTL response against HCV-core was demonstrated in both pCI-HCV-C immunized mice and mice boosted with cp1-10. Strong cytotoxic activity against peptide-pulsed p815 cells (H-2d), but not EL-4 cells (H-2b), suggested MHC class I restriction of the CTL activity. Blocking of CTL with mAb proved the effector cells to be of CD4- CD8+. Three CTL epitopes in HCV-core protein were demonstrated. We failed to detect CTL when immunized only with core protein. The results suggested that vaccination with HCV-core derived DNA sequences could be an effective method to induce humoral and cellular immune responses to HCV.
Animals↗
Relationship of peritoneal membrane transport characteristics to the nutritional status in CAPD patients.
BACKGROUND: The study was carried out to evaluate the role of individual peritoneal membrane transport characteristics in the nutritional status expressed as the composite nutritional index (CNI) METHODS: Cross-sectional analyses of the overall nutritional status of 147 continuous ambulatory peritoneal dialysis (CAPD) patients were performed using the CNI. CNIs based on a scoring system of 10 nutritional indices including subjective global assessment, biochemical parameters and anthropometry were compared according to the results of a standard peritoneal equilibration test (PET) RESULTS: Patients were classified as low (n = 16, 10.9%), low average (n=59, 40.2%), high average (n=54, 36.7%) and high (n=18, 12.2%) transporters based on the D/P(Cr) after 4 h dwells. The mean 4 h D/P(Cr) was 0.65 +/- 0.12 (0.34-0.95), and there was no significant correlation between D/P(Cr) and other demographic parameters such as age, duration of peritoneal dialysis and body surface area. D/P(Cr) was correlated with dialytic albumin loss (r=0.47, P<0.001), serum albumin (r=-0.46, P<0.001), serum creatinine (r= -0.38, P<0.001), serum TGF-1 (r=-0.37, P<0.01) and LBM(Cr) (r= -0.26, P<0.05). In high transporters, the serum albumin was significantly lower while dialysate protein and albumin losses were significantly greater compared with low transporters. Serum creatinine and IGF-1 concentrations as well as LBM(Cr) were also decreased in higher transporters. The mean CNI score was 8.1 +/- 4.9, with a range of 0-24. CNI was positively correlated with age, duration of peritoneal dialysis, incidence of peritonitis, CRP and dialytic protein loss, whereas it was inversely correlated with ultrafiltration volume, haemoglobin and NPNA. The CNI score was significantly higher in high transporters compared with low transporters (11.7 +/- 4.3 vs. 5.9 +/- 1.6, P < 0.01). There was also a significant correlation between D/P(Cr) and CNI (r = 0.29, P < 0.05). Multiple regression analysis revealed that the incidence of peritonitis, duration of CAPD, CRP and D/P(Cr) were the independent factors affecting the CNI. CONCLUSION: Peritoneal membrane transport characteristics correlate with the overall nutritional status of peritoneal dialysis patients assessed by the scoring system of the CNI, although it is associated with a different impact on the individual nutritional indices. The results of this cross-sectional study also suggest that a high permeability state is a risk factor for malnutrition in CAPD patients. Prospective studies evaluating the changes in nutritional parameters among patients with different membrane transport rates are needed to understand better the relationship of peritoneal membrane characteristics to the nutritional status of CAPD patients.
Biological Transport↗
Association between apolipoprotein E polymorphism and macroalbuminuria in patients with non-insulin dependent diabetes mellitus.
OBJECTIVES: Apolipoprotein E (apo E) is known to play an important role in lipoprotein metabolism through its ability to bind to the receptors as a ligand. Three different apo E alleles (epsilon2, epsilon3 and epsilon4) produce six apo E genotypes (epsilon2/2, epsilon2/3, epsilon2/4, epsilon3/3, epsilon3/4 and epsilon4/4). The objective of this study was to investigate an association between apo E gene polymorphism and macroalbuminuria in 167 Korean patients with non-insulin dependent diabetes mellitus (NIDDM). METHODS: The patients in the macroalbuminuria group (n = 74) represent those in whom 24 h urinary albumin excretion was above 300 mg. The patients in the normoalbuminuria group (n = 93) represent those in whom 24 h urinary albumin excretion was below 30 mg and serum creatinine levels were less than 1.2 mg/dl. The duration of diabetes in all patients was at least 8 years. RESULTS: There were no significant differences in terms of age, sex, body mass index, HbA1c, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol between the two groups. In the macroalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 2 (2.7%), epsilon2/3 14 (18.9%), epsilon2/4 0 (0%), epsilon3/3 47 (63.5%), epsilon3/4 11 (14.9%) and epsilon4/4 0 (0%). In the normoalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 0 (0%), epsilon2/3 7 (7.5%), epsilon2/4 1 (1.1%), epsilon3/3 72 (77.4%), epsilon3/4 12 (12.9%) and epsilon4/4 1 (1.1%). There was no significant difference in the distribution of apo E genotypes between the two groups. However, there was a significant difference in the allele frequencies, epsilon2 frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (12.2% vs 4.3%, P<0.05). Also, we compared apo E carrier frequencies between the two groups. Epsilon2 carrier frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (21.6% vs 7.6%, P<0.05). In each group, there was no significant difference in the degree of lipid abnormalities between apo epsilon2 carrier (epsilon2/2, epsilon2/3 genotypes), epsilon3 carrier (epsilon3/3 genotype) and epsilon4 carrier (epsilon3/4, epsilon4/4 genotype). CONCLUSION: Apo epsilon2 allele and epsilon2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that epsilon2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.
Aged↗
Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of autoimmune cholangitis.
Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.
Autoantibodies↗
Current status of peritoneal dialysis in Korea: efforts to achieve optimal outcome.
Since its introduction in 1981, peritoneal dialysis (PD) has become firmly established as an effective mode of renal replacement therapy and serves an increasing patient population in Korea. The latest registry data indicate that about 3700 end-stage renal disease patients are maintained on chronic PD, representing 24.1% of the country's dialysis population. The majority (93.3%) of these patients are on continuous ambulatory peritoneal dialysis (CAPD) using the two-bag disconnect system, while only 3.3% are on automated PD. Under current renal reimbursement policies, most dialysis patients have to pay 20% of dialysis fees. Thus CAPD patients on 4 x 2-L daily exchanges pay about US$200 per month, not including medication and travel costs. Traditionally, most PD centers in Korea have used the "standard" prescription of 4 exchanges of 2 L of solution for most of their patients. A recent survey of 1467 patients who commenced CAPD in 1997 revealed that 84% of these patients were initially prescribed 4 x 2-L exchanges, while 12% were given a daily volume of 6 L. With this standard prescription, the percentages of Korean CAPD patients initially achieving the adequacy target of Kt/V urea > or = 2.0 and standardized creatinine clearance (SCCr) > or = 60 L/week/1.73 m2, were 74.4% and 82.1%, respectively. It is likely that, among current Korean CAPD patients, a much lower percentage will achieve the clearance targets compared to this initial outcome, but the precise data are not available. However, it is not clear whether the levels of small-solute clearance recommended for optimal PD outcomes, and proposed by the NKF-DOQI guidelines, will bring the expected benefits to Korean patients. Overall survival of Korean PD patients appears to be as good as, or even better than, that in most other countries. Recently, a single large PD center reported patient survival of 92.1%, 85.6%, 81.4%, and 67.6% at 1, 2, 3, and 5 years respectively. Other centers also reported similar outcomes. As in other countries, cardiovascular deaths predominate among Korean patients: death was due to cardiac causes in 29%, to vascular causes in 21%, and to infectious causes in 24%. Peritonitis is the most important barrier to prolonged use of CAPD in Korea, and more PD patients transfer to hemodialysis because of peritonitis than in other countries. To further reduce the morbidity and mortality of Korean PD patients, various control measures need to be implemented that can reduce or prevent peritonitis and other infectious complications. Also, to further improve long-term patient outcome, Korean nephrologists need to establish and practice optimal clearance targets in the chronic care of these patients.
Cause of Death↗
Influence of apolipoprotein E genotype on lipid and lipoprotein levels in continuous ambulatory peritoneal dialysis patients.
Apolipoprotein (Apo) E has an important role in triglyceride (TG)-rich lipoprotein metabolism, and the genotype of Apo E is associated with premature coronary artery disease. Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) develop various abnormalities of lipid metabolism and are prone to develop accelerated atherosclerosis. To investigate the distribution of Apo E genotype, and to evaluate the influence of Apo E polymorphism on lipid metabolism in CAPD patients, we measured Apo E genotypes, serum lipid, and lipoprotein levels in 54 CAPD patients (M:F = 1:1). The most common genotype of Apo E in the CAPD patients was E 3/3, found in 68.5%. The frequencies of the other genotypes were E 2/3, found in 14.8%, and E 4/3, found in 16.7%. No genotypic differences in Apo E were seen in the patients with regard to the presence of diabetes, the level of parathyroid hormone, or the transport characteristics of the peritoneal membrane. When comparing lipid levels by Apo E genotype, the total cholesterol and TG levels of E 2/3 patients were significantly higher than those of E 3/3 or E 4/3 patients. The differences in high-density or low-density lipoprotein cholesterol levels by Apo E genotype were not significant. In comparing lipoprotein levels by Apo E genotype, the Apo B and lipoprotein (a) levels of E 2/3 patients were significantly lower than those of E 3/3 or E 4/3 patients. In conclusion, the Apo E 3/3 genotype seems to be the most common genotype in CAPD patients, and the Apo E 2/3 genotype appears to be associated with high cholesterol and TG levels. These results demonstrate the need for further prospective studies in these subjects aimed at elucidating the impact of genetic variation at the Apo E locus on the development of atherosclerosis.
Apolipoproteins E↗
Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells.
Geraniol (1), olivetol (2), cannabinoids (3 and 4) and 5-fluorouracil (5) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) and NIH 3T3 fibroblasts using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. Cannabigerol (3) exhibited the highest growth-inhibitory activity against the cancer cell lines.
Antineoplastic Agents, Phytogenic↗
Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells.
BACKGROUND & AIMS: Regulatory cytokines mediate intestinal epithelial cell (IEC) participation in mucosal immune responses. The aim of this study was to investigate the expression of secretory and intracellular isoforms of interleukin 1 receptor antagonist (IL-1Ra) in human primary IECs and carcinoma-derived cell lines. METHODS: Primary IECs were isolated from patients with Crohn's disease or ulcerative colitis and from normal controls. Isoform-specific IL-1Ra messenger RNA (mRNA) and protein were assessed by reverse-transcription polymerase chain reaction and Western blot analysis. Expression during cellular differentiation was determined by in situ immunohistochemistry on sequentially released, native IECs and in vitro differentiated cell lines. Intracellular IL-1Ra I function was analyzed by permanent transfection of Caco-2 cells. RESULTS: Intracellular IL-1Ra I protein accumulated in surface IECs with extension to the crypts during inflammation. Secretory IL-1Ra and intracellular IL-1Ra II mRNA, but not the corresponding protein, was detected. Transcription of intracellular IL-1Ra I mRNA was significantly up-regulated with inflammation and in vitro by phorbol myristate acetate and interleukin 1beta. In vitro differentiated cells had higher constitutive intracellular IL-1Ra I protein content. Intracellular IL-1Ra I expression in Caco-2 cells decreased IL-1beta-stimulated interleukin 8 secretion. CONCLUSIONS: Native human IECs and certain cell lines constitutively express intracellular IL-1Ra type I, which is up-regulated by inflammation, inflammatory stimuli, and cellular differentiation. Constitutive expression of this anti-inflammatory cytokine may contribute to mucosal protection.
Cell Differentiation↗
Specific NF-kappaB blockade selectively inhibits tumour necrosis factor-alpha-induced COX-2 but not constitutive COX-1 gene expression in HT-29 cells.
Cyclo-oxygenase (COX) is the key regulatory enzyme of the prostaglandin/eicosanoid pathway. While COX-1 is mostly constitutively expressed, the COX-2 isoform is inducible by proinflammatory cytokines. We used an adenoviral vector containing an NF-kappaB super-repressor (Ad5IkappaB) to investigate the role of NF-kappaB in tumour necrosis factor-alpha (TNF-alpha)-mediated COX-2 gene expression in a colonic epithelial cell line. COX-1 mRNA and protein were constitutively expressed in uninfected, control Ad5LacZ- or Ad5IkappaB-infected HT-29 cells with no apparent change following TNF-alpha exposure. COX-2 mRNA and protein expression was undetectable in unstimulated cells but was strongly up-regulated after TNF-alpha stimulation in uninfected and Ad5LacZ-infected HT-29 cells. This induction was prevented in Ad5IkappaB cells. TNF-alpha increased prostaglandin E2 production by 20-fold in Ad5LacZ-infected HT-29 cells compared with uninfected cells and was significantly inhibited in Ad5IkappaB-infected cells in agreement with the COX-2 mRNA findings. We conclude that NF-kappaB activation is critical in mediating COX-2, but not COX-1 gene expression in HT-29 cells. Selective inhibition of COX-2 expression with the NF-kappaB super-repressor may be useful in distinguishing the role of inducible versus constitutive prostaglandins in intestinal function and provides greater specificity than pharmacological inhibitors.
Adenoviridae↗
Acute effects of recombinant human erythropoietin on plasma levels of proendothelin-1 and endothelin-1 in haemodialysis patients.
BACKGROUND: The pathogenesis of rHuEpo-induced hypertension in haemodialysis (HD) patients still remains uncertain. Endothelin-1 (ET-1) is produced from proendothelin-1 (proET-1) by an endothelin-converting enzyme. Since proET-1 is known to have approximately 1/100 the potency of ET-1 for contracting an isolated blood vessel, the change in the activity of endothelin-converting enzyme (ECE) has been proposed as an important factor in the pathophysiology of various hypertensive diseases. However there is no report on whether a change in the rate of conversion of proET-1 to ET-1 may be involved in the pathogenesis of rHuEpo-induced hypertension. The purpose of this study was to ascertain the potential role of ECE in the development of rHuEpo-induced hypertension. METHODS: The levels of plasma erythropoietin, proET-1, ET-1, and mean arterial blood pressure (MAP) were measured following a single dose of rHuEpo (100 U/kg) in HD patients with 24-h ambulatory blood pressure monitoring. Different routes of administration (19 intravenous group, 10 subcutaneous group) were compared to a placebo-injected control group (10 HD patients). RESULTS: Plasma erythropoietin levels reached maximal value 5 min after i.v. injection of rHuEpo (13.1+/-2.4 vs 2780.9+/-290.1 mU/ml, P<0.01), whereas it was 6 h in the s.c. group (14.7+/-3.8 vs 38.9+/-17.7 mU/ml, P<0.05). A significant increase in MAP was noted 30 min after rHuEpo injection, which lasted for 3 h in the i.v. group. However, no significant changes in MAP were noted in patients given rHuEpo subcutaneously. Both the plasma concentrations of proET-1 and ET-1 started to increase from 10 min after i.v. rHuEpo administration, with the proET-1 reaching a peak level at 30 min (13.5+/-7.4 vs 21.6+/-3.8 pg/ml, P<0.05) and the ET-1 at 1 h (4.2+/-2.6 vs 9.9+/-4.8 pg/ml, P<0.05). In patients with significant interdialysis hypertension following a single i.v. injection of rHuEpo, the molar ratio of ET-1 over proET-1 (ET-1/proET-1) was significantly higher than in patients without hypertension. In addition, the increase in ET-1 levels was significantly greater in patients with interdialysis hypertension, while changes in proET-1 level were similar in both hypertensive and non-hypertensive groups. Changes in interdialysis MAP (delta IDMAP) was significantly correlated with delta ET-1 during the interdialysis period, but not with delta proET-1. CONCLUSION: Differences in ET-1/proET-1 ratio in relation to changes in MAP after a single intravenous administration of rHuEpo suggest a potential role for ECE in the pathogenesis of rHuEpo-induced hypertension.
Adult↗
Combination chemotherapy of oral 5'-deoxy-5-fluorouridine and cisplatin in advanced gastric cancer: a phase II study.
This study was designed to test the activity and feasibility of 5'-deoxy-5-fluorouridine (5'-DFUR) and cisplatin combination therapy in the treatment of advanced gastric cancer. Nineteen patients with inoperable and/or metastatic gastric cancer, which was histologically proven, were orally administered 5'-DFUR 1,200 mg/m2 on days 1 to 4 and days 15-18 combined with 70 mg/m2 of cisplatin being repeated every 4 weeks. Five partial responses (PRs) were achieved. Seven patients had stable disease and 6 progressed on therapy. The overall response rate was 27.7% (95% confidence interval: 9.69% to 53.5%). The median survival duration of all 18 patients was 25 weeks (9-64). The majority of patients had WHO grade I/II toxicity, but there was no treatment-related death. These data support that the combinations of oral 5'-DFUR and cisplatin are well tolerable and have a moderate activity with low toxicity in the treatment of advanced gastric cancer.
Administration, Oral↗
Hepatitis G virus infection in hemodialysis and continuous ambulatory peritoneal dialysis patients.
To determine the prevalence and clinical relevance of HGV infection in dialysis patients, we performed a cross-sectional study of 61 HD patients and 79 Continuous Ambulatory Peritoneal Dialysis (CAPD) patients. HGV-RNA was identified by reverse-transcription (RT) polymerase chain reaction (PCR) assay with primers from the 5'-untranslated region of the viral genome. The prevalence of HGV infection was similar in HD and CAPD patients (9.8% vs. 12.7%), while that of HCV infection was significantly higher in HD patients compared to CAPD patients (16.4% vs. 1.3%, p < 0.05). The mean age (49.2 +/- 13.4 vs. 46.7 +/- 13.0 years), male to female ratio (2.4:1 vs. 1.3:1), history of transfusion (62.3% vs. 49.4%), history of hepatitis (27.9% vs. 26.6%), mean ALT level during the previous 6 months (22.4 +/- 37.9 vs. 14.0 +/- 7.4 IU/L), and the prevalence of HBsAg (8.2% vs. 6.3%) showed no difference between HD and CAPD patients. In both HD and CAPD patients, the presence of HGV RNA was not related to age, sex, duration of dialysis, history of transfusion, history of hepatitis, or to the presence of HBV or HCV markers. There was no significant difference in the clinical and biochemical data between patients with isolated HGV infection (n = 12) and patients without viremia (n = 106). The clinical feature of patients coinfected with HGV and HBV (n = 2), or HGV and HCV (n = 2) seemed to be similar to those of patients with isolated HBV (n = 8) or HCV (n = 9) infection. In conclusion, the prevalence of HGV infection was not different between HD and CAPD patients, and HGV infections did not seem to be associated with clinically significant hepatitis. The routes of HGV transmission, other than transfusion or contamination during HD procedure, were suspected.
Female↗