Biomedical subjects

Curie Ahn

Publications and source records attributed to Curie Ahn.

At least 37 records · Page 2Linked to original sources

PubMed2004

RETRACTED: Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst.

Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.

Animals↗

PubMed2004

Repair of transposition of the great arteries, ventricular septal defect and left ventricular outflow tract obstruction.

OBJECTIVES: This study was undertaken to compare the outcomes of the Lecompte procedure and Rastelli repair in the transposition of the great arteries (TGA) with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO) and to determine the risk factors associated with unfavorable events. METHODS: Over a 12-year period (April 1990-October 2002), 35 patients underwent complete repair for TGA, VSD, and LVOTO. Twenty-five patients (71%) underwent the Lecompte modification, and mean age and weight were 23.4+/-18.2 months and 10.2+/-3.0 kg. Ten patients (29%) underwent the Rastelli operation, and mean age and weight were 39.1+/-36.1 months and 13.8+/-6.8 kg. RESULTS: One early death (3%) occurred after the Lecompte procedure and no late death. The mean follow-up was 5.9+/-3.8 years. Eight patients in the Rastelli group (80%) underwent a late reoperation for obstruction of the extracardiac conduit, and in four of these patients, a reoperation for LVOTO was concomitantly required. Reoperation was also required in six patients of the Lecompte group (25%); five for right ventricular outflow tract obstruction (RVOTO) including one for LVOTO and two for VSD leakage, and one for mitral regurgitation and left pulmonary artery stenosis. The interval prior to reoperation ranged from 1.6 to 11.1 years, with a mean of 5.7+/-3.1 years. The actuarial figures for freedom from reoperation at 5 and 10 years were 40.0+/-15.5 and 26.7+/-15.0% after the Rastelli operation and 95.7+/-4.3 and 63.5+/-12.6% after the Lecompte procedure (P = 0.02). Multivariate analysis by Cox regression analysis revealed that the risk factors of RVOTO were a younger age at operation, the Rastelli operation, and ductus ligation during the operation. CONCLUSIONS: The Lecompte procedure and Rastelli repair provide satisfactory early and late results. However, substantial late morbidity is more associated with conduit obstruction, and LVOTO in Rastelli repair rather than Lecompte procedure.

Abnormalities, Multiple↗

PubMed2004

Characterization of microsatellite markers to diagnose ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) maps to chromosome 16p13.3 (PKD1) and to chromosome 4q21-23 (PKD2), with the likelihood of a third unmapped locus. The size and genomic complexity of the PKD1 gene make it impractical to detect mutations for prenatal diagnosis. Therefore, pedigree-based linkage analysis remains useful for diagnosis of ADPKD. Since, the complete genome sequences of chromosome 16p13.3 and 4q21-23 including PKD1 and PKD2, respectively, were reported very recently, in order to do more precise diagnosis of ADPKD, we tried to find microsatellite markers. We performed database searches of 2000 kb of genome sequence across the 16p13.3 and the 4q21-23. To determine the distribution of alleles and the degree of polymorphism of the microsatellites, genotyping experiments were performed on 48 Korean individuals. We found novel 14 microsatellite markers around ADPKD that are more polymorphic and closer to PKD1 or PKD2 than the known markers. The novel microsatellite markers were applied to diagnose ADPKD families. These novel microsatellite markers are not only useful for presymptomatic and prenatal diagnosis of ADPKD, but also applicable in the study of positional cloning, human evolution and tumor biology.

Chromosomes, Human, Pair 4↗

PubMed2004

Targeted gene disruption of the heat shock protein 72 gene (hsp70.1) in the donor tissue is associated with a prolonged rejection-free survival in the murine skin allograft model.

It is known that the expression level of the heat shock protein (HSP) is elevated in allograft tissues, but the specific role of the HSP in the acute rejection has not been elucidated. This study aims to determine how and when the HSP72 molecule works immunologically in the process of acute allograft rejection from a skin graft model in which HSP72 (hsp70.1 gene) knock out (KO) mice were adopted either as a donor or as a recipient. In experiment I, tail skin was grafted from either the HSP72 KO C57BL/6 mice or wild-type C57BL/6 mice--as the allograft control--onto the trunk of B10BR mice. The grafts were observed for any signs of rejection until the 14th day after the graft. The survival of the grafted skin from the two donor groups was analyzed by a log-rank method. The grafted skin was observed for the degree of rejection using light microscopy. In addition, the degree of apoptosis was assessed using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). A mixed lymphocyte reaction (MLR) was observed with HSP72 KO C57BL/6 splenocytes as the stimulator and B10BR mice lymphocytes as the responder cells. The cytokine levels, such as interleukin-2 (IL-2) and interferon-gamma, were measured from an MLR supernatant using enzyme-linked immunosorbent assay (ELISA). In experiment II, the tail skin was grafted in the opposite direction from the B10BR mice to the HSP72 KO or wild-type C57BL/6 mice, and the grafts were observed for any signs of rejection, as defined in experiment I. The absence of HSP72 expression was observed in the HSP72 KO mice lymphocytes after heat stress (42 degrees C) using Western blot analysis. In experiment I, the survival of the skin grafts from the HSP72 KO C57BL/6 mice was 12+/-1.3 days (median+/-S.E.), which was significantly longer than that from the allograft control donor (9+/-0.6 days; p=0.03). This coincided with the microscopic finding of the graft tissues. The MLR response of the CD4+ lymphocytes stimulated by HSP72 KO C57BL/6 splenocytes was lower, and the interferon-gamma concentration from the MLR supernatant was also lower. On Day 9, 3.7+/-1.1(mean+/-S.D.) TUNEL-positive cells per unit high-power field (HPF) were observed from the HSP72 KO C57BL/6 skin, which was significantly lower than that from the control skin (8.7+/-2.1 cells/HPF; p=0.045). In contrast, in experiment II, there was no difference in the survival of the skin graft either from the B10BR to HSP72 KO C57BL/6 mice or from the B10BR to the wild-type C57BL/6 mice. In summary, the survival of the skin grafts from the HSP72 KO C57BL/6 mice was prolonged, and the degree of rejection was lower than that from the allograft control. This means that the presence of HSP72 in the donor tissue is related to the up-regulation of acute rejection from the recipient immune system. The HSP72 KO mice as the donor were shown to have decreased level of antigen presentation to the recipient CD4+ lymphocytes. Therefore, the HSP72 molecule from the donor cells is believed to be related to the induction of the recipient immune reaction via alloantigen presentation.

Animals↗

PubMed2004

Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/S-phase transition.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of epithelial cells and the influx of cyst fluid. The 14-kb mRNA of the polycystic kidney disease gene, PKD1, encodes the polycystin-1 protein, whose function remains unknown. In this study, we observed that polycystin-1 localized in epithelial cell-cell contacts of 293 cells. We found, by bromodeoxyuridine (BrdU) incorporation experiments and Western blot analysis of S-phase-specific cyclins, that the depletion of polycystin-1 led to an increased cell proliferation rate and caused a premature G1/S-phase transition. In addition, we showed that the depletion of polycystin-1 reduced the amount of p53 in 293 cells irradiated by UV light, suggesting that polycystin-1 acts as a regulator of G1 checkpoint, which controls entry into the S phase and prevents the replication of damaged DNA. Our results might provide an insight into the formation and progression of ADPKD cysts.

Amino Acid Sequence↗

PubMed2004

Siah-1 interacts with the intracellular region of polycystin-1 and affects its stability via the ubiquitin-proteasome pathway.

Autosomal dominant polycystic kidney disease, characterized by extensive formation of renal cysts and progressive renal failure, is a genetic disorder caused by mutations in the PKD1 and PKD2 genes. The PKD1 gene product, polycystin-1, is a transmembrane protein with its N-terminus facing the extracellular region and C-terminus facing the cytoplasm. Polycystin-1 seems to be involved in regulating cell growth and maturation, but the precise mechanisms are not yet well defined. For investigating the function of the intracellular region of polycystin-1, the C-terminal cytoplasmic fragment of polycystin-1, PKD1-C, was used as bait in two-hybrid screening, and a polycystin-1-binding protein, the human homologue of Drosophila Seven in Absentia (Siah-1), which has a RING domain and promotes the ubiquitin-dependent proteasome pathway, was identified. It was shown that PKD1-C interacts with Siah-1 in vivo. In addition, interaction with Siah-1 induces the degradation of PKD1-C, shortening its half-life. PKD1-C and CD4 chimeric proteins, which are attached to the plasma membrane, also show similar results. Furthermore, ubiquitination and degradation of PKD1-C are increased in the presence of Siah-1, and overexpression of Siah-1 protein promotes the degradation of polycystin-1 via the ubiquitin-proteasome pathway. These results suggest that polycystin-1 is regulated by Siah-1 through the ubiquitin-dependent proteasome pathway.

Cell Line↗

PubMed2004

The urine-blood PCO gradient as a diagnostic index of H(+)-ATPase defect distal renal tubular acidosis.

BACKGROUND: Urine pH during acidemia and urine PCO2 upon alkalization both may be useful to indicate H+ secretion from collecting ducts. The urine anion gap has been used to detect urinary NH4+ for differential diagnosis of hyperchloremic metabolic acidosis. We have previously demonstrated that the lack of normal H(+)-ATPase may underlie secretory defect distal renal tubular acidosis (dRTA). In this study we evaluated the diagnostic value of the urine-blood (U-B) PCO2 in H(+)-ATPase defect dRTA, and compared it with that of urine pH and urine anion gap during acidemia. METHODS: In H(+)-ATPase defect dRTA, the diagnostic values of three urinary parameters were evaluated: (1) urine pH measured after acid (NH4Cl) loading; (2) urine-to-blood carbon dioxide tension gradient (U-B PCO2) during alkali (NaHCO3) loading; and (3) urine anion gap during acidemia. Seventeen patients were diagnosed as having H(+)-ATPase defect dRTA based on reduced urinary NH4+ and an absolute decrease in H(+)-ATPase immunostaining in intercalated cells on renal biopsy. Eight patients with non-dRTA renal disease served as control patients. RESULTS: Upon NaHCO3 loading, U-B PCO2 was < or =30 mm Hg in all 17 dRTA patients and >30 mm Hg in all 8 control patients. With NH4Cl loading, urine pH was >5.4 in 15 of 17 dRTA patients and < or =5.4 in 7 of 8 control patients, and the urine anion gap was >5 mmol/L in 13 of 17 dRTA patients and< or =5 mmol/L in 6 of 8 control patients. Therefore, the sensitivity and specificity of U-B PCO2 < or =30 mm Hg during NaHCO3 loading were both 100%, whereas those of urine pH >5.4 or urine anion gap >5 mmol/L during NH4Cl loading were below 90%. In control patients, the U-B PCO2 was found to be well correlated with the urinary NH4+ (r= 0.79, P < 0.05). CONCLUSION: The U-B PCO2 during NaHCO3 loading is an excellent diagnostic index of H(+)-ATPase defect dRTA.

Acidosis, Renal Tubular↗

PubMed2003

Synergistic immunosuppressive effects of rosmarinic acid and rapamycin in vitro and in vivo.

BACKGROUND: We previously demonstrated that rosmarinic acid (RosA) inhibits T-cell antigen receptor-induced T-cell activation and proliferation. In this study, we evaluated the ability of RosA alone and in conjunction with currently used immunosuppressive drugs to inhibit in vitro splenic T-cell proliferation and prolong skin graft survival in vivo. METHODS: Mouse splenic T-cell proliferation assays were performed in the presence of RosA alone or in combination with cyclosporine, rapamycin (Rapa), or prednisone (Pred). The in vivo synergistic efficacy of RosA and Rapa was evaluated in the mouse skin allograft model. RESULTS: RosA combined with Rapa or prednisone synergistically inhibited splenic T-cell proliferation, whereas the combination of RosA and cyclosporine additively inhibited T-cell proliferation. The combination of RosA and Rapa synergistically prolonged allograft survival. CONCLUSIONS: We conclude that the combination of RosA and Rapa promotes immunosuppressive effects.

Animals↗

PubMed2003

Clinicopathological correlation of intrarenal cytokines and chemokines in IgA nephropathy.

The pathogenetic mechanisms of IgA nephropathy are diverse and are not yet clearly elucidated. We believe pro-inflammatory cytokines, Th1/Th2, and chemokines would be involved in the pathogenetic pathways and would affect the functional and histological consequences of IgA nephropathy. By using semiquantitative reverse transcriptase-polymerase chain reactions (RT-PCR), we measured the level of intrarenal gene expression of various cytokines and chemokines in 61 renal core biopsy specimens confirmed as IgA nephropathy. And, by using immunohistochemistry (IHC), the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 of the above patients were attempted to be determined. In RT-PCR, the gamma-interferon (IFN-gamma)/interleukin-10 (IL-10) ratio was higher in patients with renal dysfunction than in those with normal renal function. The levels of pro-inflammatory cytokine gene transcripts (tumor necrosis factor-alpha (TNF-alpha), IL-1beta) were high in patients with significant proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high. The level of IL-10 gene transcript was related to the severity of tubular atrophy and interstitial fibrosis. The extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 gene transcript. The degree of IgA deposition in glomeruli was related to the expression of IL-15 and IL-6. In IHC, TNF-alpha, IFN-gamma and IL-2 were immunostained dominantly in the mesangial region, but not in the tubulointerstitial region. In contrast, positive reactions for IL-10 were observed primarily in tubules. Significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT-PCR and IHC showed positive relationships, but these were not statistically significant. This study suggests that pro-inflammatory, Th1/Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunological injury in IgA nephropathy.

Adolescent↗

PubMed2003

Renal cyst ablation with n-butyl cyanoacrylate and iodized oil in symptomatic patients with autosomal dominant polycystic kidney disease: preliminary report.

Fifty renal cysts in 14 patients with autosomal dominant polycystic kidney disease (ADPKD) were treated with percutaneous needle aspiration and intracystic injection of a mixture of n-butyl cyanoacrylate and iodized oil in a ratio of 1:2. At follow-up of 1-12 months, symptoms improved in 12 (86%) of 14 patients, and 25 (81%) of 31 cysts decreased more than 50% in diameter. This procedure appears to be feasible and may be an effective modality in ablation of renal cysts in patients with ADPKD.

Adult↗

PubMed2003

High incidence of tacrolimus-associated posttransplantation diabetes in the Korean renal allograft recipients according to American Diabetes Association criteria.

OBJECTIVE: The incidence of posttransplantation diabetes mellitus (PTDM) has been reported to vary according to different study populations or different definitions. In this study, using American Diabetes Association criteria, the incidence and clinical characteristics of PTDM in Korean renal allograft recipients undergoing tacrolimus-based immunosuppression were examined. RESEARCH DESIGN AND METHODS: A total of 21 patients taking tacrolimus as primary immunosuppressant were recruited and tested with a serial 75-g oral glucose tolerance test at 0, 1, 3, and 6 months after renal transplantation. RESULTS: The cumulative incidence of PTDM was 52.4% at 1 month and 57.1% at 3 and 6 months. The baseline characteristics of the PTDM group were old age (especially >40 years), a high BMI, a high fasting glucose level, a high plasma insulin level, and increased insulin resistance. Among these parameters, old age was the only independent risk factor. The insulin secretory capacity in the PTDM group was maximally suppressed 3 months after transplantation. Thereafter, it was gradually restored along with dose reduction of tacrolimus. CONCLUSIONS: Routine screening for PTDM is necessary in patients over 40 years of age who are undergoing a relatively higher dose tacrolimus therapy during the early course of postrenal transplantation.

Adult↗

PubMed2002

The --174 G to C polymorphism of interleukin-6 gene is very rare in koreans.

The proinflammatory cytokine, interleukin-6 (IL-6), seems to be involved in the pathogenesis and progression of IgA nephropathy. Moreover, the transcriptional activity of the IL-6 gene and the plasma levels of IL-6 protein are associated with a single G/C base exchange polymorphism at position -174 of the IL-6 gene promoter. Using PCR-RFLP and PCR product sequencing, we examined the -174 polymorphism in 104 IgA nephropathy patients and in 53 of the normal Korean population. Only 2 GC heterozygous variants and no CC homozygous variants were found (C allele frequency=0.006). These results suggest that the frequency of the C allele in the Korean population is considerably lower than in the Caucasian population, and it appears that the -174 G to C polymorphism of IL-6 is very rare in Eastern Asians. And, the IL-6 polymorphism at -174 is unlikely to contribute significantly to susceptibility to or the progression of IgA nephropathy in Koreans.

Alleles↗

PubMed2002

Secretory-defect distal renal tubular acidosis is associated with transporter defect in H(+)-ATPase and anion exchanger-1.

Recent progress in molecular physiology has permitted us to understand pathophysiology of various channelopathies at a molecular level. The secretion of H(+) from alpha-intercalated cells is mediated by apical plasma membrane H(+)-ATPase and basolateral plasma membrane anion exchanger-1 (AE1). Studies have demonstrated the lack of H(+)-ATPase immunostaining in the intercalated cells in a few patients with distal renal tubular acidosis (dRTA). Mutations in H(+)-ATPase and AE1 gene have recently been reported to cause dRTA. This study extends the investigation of the role of transporter defect in dRTA by using immunohistochemical methods. Eleven patients with hyperchloremic metabolic acidosis were diagnosed functionally to have secretory-defect dRTA: urine pH >5.5 during acidemia, normokalemia or hypokalemia, and urine-to-blood pCO(2) <25 mmHg during bicarbonaturia. Renal biopsy tissue was obtained from each patient, and immunohistochemistry was carried out using antibodies to H(+)-ATPase and AE1. For comparison, renal tissues from the patients who had no evidences of distal acidification defect by functional studies were used: four with glomerulopathy or tubulointerstitial nephritis (disease controls) and three from nephrectomized kidneys for renal cell carcinoma (normal controls). The H(+)-ATPase immunoreactivity in alpha-intercalated cells was almost absent in all of the 11 patients with secretory-defect dRTA. In addition, 7 of 11 patients with secretory-defect dRTA were accompanied by negative AE1 immunoreactivity. In both disease controls and normal controls, the immunoreactivity of H(+)-ATPase and AE1 was strong in alpha-intercalated cells. In conclusion, significant defect in acid-base transporters is the major cause of secretory-defect dRTA.

Acidosis, Renal Tubular↗

PubMedDate not supplied

IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo.

Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1beta, TNF-alpha and IFN-gamma. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or beta-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.

Animals↗

PubMedDate not supplied

The expression patterns of CD44 and CD45RB on peripheral blood T lymphocytes in the rejection of allogeneic murine skin transplantation.

Until now, the rejection was diagnosed through a biopsy, but this method of diagnosis reflected the advanced tissue damage of the transplanted organ and contained the innate problem of being invasive. In relation, our research attempted to evaluate the viability of analyzing the surface antigens of the peripheral blood activated T lymphocytes after murine skin transplantation as a non-invasive and early diagnostic tool for diagnosis of rejection. After mouse skin was transplanted, the expression patterns of activated T lymphocyte markers, CD44 and CD45RB were analyzed along with T lymphocyte markers, CD3, CD4 and CD8 using flow cytometry. The skins from the tails of allogeneic BALB/c(H2d) mice and syngeneic C57BL/6J mice were transplanted to C57BL/6J(H2b) mice as test and control groups, respectively. Peripheral blood, which was sampled from the tail every other day from day 3 to day 15 was stained with anti-CD44 (or CD45RB), anti-CD4 (or CD8) and anti-CD3 monoclonal antibodies simultaneously, and analyzed by 3-color FACS. Rejection occurred only in the test group from day 8 to day 13 (median: day 10). Although the proportions of CD3(+) lymphocytes, CD4(+) lymphocytes and CD8(+) lymphocytes showed no difference, the total number of peripheral blood lymphocytes and the number of CD3(+) lymphocytes and CD8(+) lymphocytes decreased more sharply in the control after day 7. The proportion and the number of CD44(+)CD3(+)-lymphocytes, CD44(+)CD4(+)-lymphocytes and CD44(+)CD4(+)CD3(+)-lymphocytes began to increase after day 7, to peak on day 11, and then to decrease, showing a significant difference. The proportion and number of CD44(+)CD8(+)-lymphocytes and CD44(+)CD8(+)CD3(+)-lymphocytes showed similar trends. No significant difference was observed in any subsets of the CD45RB antigen. The analysis of the expression patterns of surface antigen CD44 on peripheral blood T lymphocytes using flow cytometry is sensitive, safe, easily repeatable and controllable, and, therefore, can be considered a promising tool for the diagnosis of rejection. However, the clear change in CD44 occurred between day 9 and day 13, when rejection was observed grossly. Therefore, it is regarded more useful as a screening test or follow-up indicator rather than as an early diagnostic tool.

Animals↗

PubMedDate not supplied

Inducible nitric oxide synthase inhibitors prolonged the survival of skin xenografts through selective down-regulation of pro-inflammatory cytokine and CC-chemokine expressions.

To elucidate the possible immunoregulatory role of nitric oxide (NO) in cellular xenograft rejection we performed rat-to-mouse skin xenotransplantation. The rat skin engrafted mice were treated with the inducible NO synthase (iNOS) inhibitors, aminoguanidine (AMG, 200 mg/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg) every other day until rejection. Skin xenograft survival was monitored and immune cell infiltration and intragraft cytokine and chemokine mRNA expressions were analyzed 7 days after grafting. Compared with the control mice, the AMG- and L-NAME treated mice showed delayed xenograft rejection by approximately 3 days (8.9 +/- 0.7 days vs. 11.7 +/- 1.2 and 12.0 +/- 0.9 days, respectively). Infiltrations of CD11b+, MOMA-2+ cells and neutrophils were significantly reduced in both AMG- and L-NAME treated graft but CD4+ and CD8+ cells were not. The expression of cytokines such as IL-1beta, IL-2, IL-6, IL-12 and IFN-gamma in AMG- and L-NAME treated grafts were significantly decreased (P<0.01), whereas IL-10, TNF-alpha and TGF-beta1 were unchanged or enhanced. Additionally, the expressions of CC-chemokines, such as RANTES and MIP-1alpha, were significantly reduced (P<0.01) whereas the expressions of CXC-chemokines, such as IP-10 and MIG, were unchanged. These results imply that prolonged rat-to-mouse skin xenograft survival by iNOS inhibitors may be due to the selective inhibition of pro-inflammatory cytokines and chemokines and suggest the possible regulatory role of NO in cytokine and chemokine expressions during xenotransplant rejection.

Animals↗

PubMedDate not supplied

Effect of peritoneal dialysis on plasma and peritoneal fluid concentrations of isoniazid, pyrazinamide, and rifampin.

OBJECTIVE: This study was performed to elucidate the pharmacokinetic profiles of antimycobacterial regimens for peritoneal dialysis patients. PATIENTS: Nine patients on maintenance continuous ambulatory peritoneal dialysis (CAPD) were included in this study. METHODS: After administering a conventional oral dose of antituberculosis medications, we measured plasma and peritoneal fluid concentrations of isoniazid by fluorometry, and rifampin and pyrazinamide by high performance liquid chromatography. The assay data were subjected to pharmacokinetic analysis. RESULTS: Average peak plasma concentrations of isoniazid, rifampin, and pyrazinamide were 3.3 mg/L, 6.5 mg/L, and 30.9 mg/L, respectively, all of which much exceed the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. Peritoneal fluid concentrations of isoniazid and pyrazinamide were maintained well above the MICs for M. tuberculosis; however, peritoneal fluid concentration of rifampin was below the therapeutic range most of the time. CONCLUSION: For the treatment of systemic or pulmonary tuberculosis in CAPD patients, no dose adjustments are required for isoniazid, rifampin, or pyrazinamide. On the contrary, for the treatment of tuberculous peritonitis, oral rifampin therapy is not expected to be effective because of its low peritoneal fluid concentration.

Adult↗

PubMedDate not supplied

Two cases of pure red-cell aplasia due to anti-erythropoietin antibodies.

We report on two Korean patients who developed pure red-cell aplasia (PRCA) due to anti-erythropoietin (EPO) antibodies. The first patient became refractory to EPO treatment after a good response for an initial 26 months. Anti-EPO antibodies were detected by enzyme linked immunosorbent assay (ELISA) and by radioimmunoprecipitation (RIPA), and these were found to inhibit erythroid colony formation by in vitro bioassay. In the second patient, the anemia became aggravated, accompanied by thrombocytopenia and wheals appeared at the EPO injection site 3 months after the initiation of subcutaneous EPO treatment. Anti-EPO antibodies were detected by ELISA, and the patient showed a partial response to the second corticosteroid treatment course. Our cases demonstrate that PRCA due to anti-EPO antibodies becomes an important issue in Asians as well as in Caucasians.

Adult↗