Biomedical subjects

Jin Kim

Publications and source records attributed to Jin Kim.

At least 73 records · Page 4Linked to original sources

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↗

PubMed2004

Odontogenic ghost cell tumour with clear cell components: clear cell odontogenic ghost cell tumour?

A case of odontogenic ghost cell tumour (OGCT) with clear cell components was encountered in the mandible of a 63-year-old man. The tumour revealed ameloblastomatous-type epithelial components accompanied by clusters of ghost cells and dentinoid juxtaposed to the odontogenic epithelium. In addition, some areas of the tumour tissue showed sheets and islands of clear, glycogen containing epithelial cells, which were separated by a thin fibrous connective tissue stroma. Both ameloblastic and clear cells exhibited positive immunoreactivities for cytokeratin 19 and AE1/3. It is not known whether this tumour represents a clear cell change of a pre-existing OGCT or a separate and distinct neoplasm derived de novo from the odontogenic epithelium. This tumour was given the term 'clear cell OGCT' because it captures the clear cell components, which is one of the most prominent distinguishing features of the tumour.

Diagnosis, Differential↗

PubMed2004

Diminished expression of sodium transporters in the ureteral obstructed kidney in rats.

BACKGROUND/AIMS: Whether the postobstructive natriuresis and diuresis is related with an altered regulation of sodium transporters in the kidney was examined. METHODS: Male Sprague-Dawley rats underwent either bilateral (BUO) or unilateral obstruction (UUO) of the proximal ureters for 24 h. The expression of Na,K-ATPase, type-3 sodium-hydrogen exchanger (NHE3), type-1 bumetanide-sensitive sodium cotransporter (BSC1), and thiazide-sensitive sodium cotransporter (TSC) proteins was determined in the obstructed kidney by Western blot analysis and immunohistochemistry. Catalytic activity of Na,K-ATPase was also determined. RESULTS: The expression of alpha1 and beta1 subunit proteins and the catalytic activity of Na,K-ATPase were significantly decreased in the obstructed kidney in BUO. The expressions of NHE3, BSC1 and TSC proteins were also significantly decreased. Immunohistochemistry confirmed the downregulation of these sodium transporters in the obstructed kidney. In UUO, the expression of sodium transporters was similarly decreased in the obstructed kidney. CONCLUSION: The postobstructive natriuresis and diuresis may in part be accounted for by a reduced abundance of sodium transporters in the kidney.

Animals↗

PubMed2004

Use of complementary and alternative medicine among Korean cancer patients.

BACKGROUND: Complementary and alternative medicine (CAM) is now being increasingly used among cancer patients. The objectives of our study were to assess the prevalence, types, cost, subjective effects, and side effects of CAM use, reasons for CAM use, characteristics of CAM users compared to those of nonusers, and patients' expectations of doctors regarding their CAM use among Korean cancer patients at a single cancer center. METHODS: From April to August, 2003, we interviewed 186 cancer patients hospitalized in the Korea Cancer Center Hospital using a structured questionnaire, and analyzed the data. RESULTS: 78.5% of experimental subjects (146 patients) had been treated with at least one type of CAM, in addition to conventional Western treatment, with a mean monthly cost of 1,380,000 Won/person (approximately, 1,100 U.S. dollars on July, 2004). The most prevalent types of CAM used by these patients included medicinal mushrooms (67.1%), herbs (54.1%), vegetable diets (50.6%), and ginseng (46.5%). The main reported reasons for the use of CAM in addition to conventional medicine were nutritional support (19.1%) and physical strengthening (17.8%). 5% of CAM users experienced side effects. The younger and more educated the patients were, the more likely they were to employ CAM. 66% of CAM users wanted to discuss CAM techniques with their doctors. CONCLUSION: More than two-thirds of cancer patients used various kinds of CAM, incurring considerable costs. Therefore, in order to help patients make informed decisions, medical society should be open to communication with patients. Not only the scientific aspects, but also the economic aspects of CAM usage should be examined more thoroughly, in order to ensure proper distribution of medical resources.

Complementary Therapies↗

PubMed2004

Expression of apoptosis-related factors in chronic cyclosporine nephrotoxicity after cyclosporine withdrawal.

AIM: To examine whether the reversibility of chronic cyclosporine A (CsA) nephrotoxicity is associated with apoptotic cell death and its regulatory factors. METHODS: Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg, sc) for 5 weeks, and then withdrawing it for 5 or 10 weeks. The effect of CsA withdrawal on apoptotic cell death was evaluated by an in situ TdT-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and the expression of pro-apoptotic [transforming growth factor-beta 1 (TGF-beta 1) and Fas] and anti-apoptotic [epidermal growth factors (EGF) and Bcl-2] factors. RESULTS: Discontinuation of CsA induced significant decreases in TUNEL-positive cells in a time-dependent manner and the reduction in TUNEL-positive cells was correlated with the tubulointerstitial fibrosis score (r=0.919, P<0.01). Upregulation of TGF-beta and Fas expression in CsA-treated rat kidneys was decreased significantly after withdrawal of CsA. In contrast, downregulated EGF and Bcl-2 expression returned to normal or supernormal levels. CONCLUSION: CsA withdrawal is associated with a decrease in apoptotic cell death and with changes in the expression of pro-apoptotic and anti-apoptotic molecules involved in renal wound repair. This may constitute one of the mechanisms underlying the reversibility of chronic CsA nephrotoxicity.

Animals↗

PubMed2004

[Positron emission tomography with fluorine-18-fluorodeoxyglucose is useful for predicting the prognosis of patients with hepatocellular carcinoma].

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is heterogenous in terms of its glucose metabolism. Positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) shows various levels of FDG uptake for patients with HCC. This study was designed to assess the usefulness of FDG-PET for predicting the outcome of the patients with HCC. METHODS: FDG-PET was performed for 27 patients with HCC. The standardized uptake value (SUV) and SUV ratio (defined as the tumor-to-nontumor ratio of SUV) was calculated for each patient. The clinical factors of the outcome were analyzed by regression analysis using Cox's multivariate proportional hazard model. The survival rate was calculated by the Kaplan-Meier method. RESULTS: Among the analyzed clinical factors including tumor size, number of tumors, AFP, involvement of major vessels, presence of systemic metastases, Child-Pugh class the SUV and SUV ratio, only the SUV was the only significant independent prognostic factor (p=0.001). On the basis of the SUV, the patients were divided into two groups of roughly equal size: group A, SUV of <7; group B, SUV > or =7. The cumulative survival rate was significantly lower for group B than for group A, and the median survival time was significantly different (4 months vs 15 months, respectively) (p=0.003). CONCLUSIONS: These results suggest that FDG-PET is useful to predict the outcome for patients with hepatocellular carcinoma.

Adult↗

PubMed2003

Comparative Ki-67 expression and apoptosis in the odontogenic keratocyst associated with or without an impacted tooth in addition to unilocular and multilocular varieties.

It is not known whether the presence of an impacted tooth or the radiographic types in an odontogenic keratocyst (OKC) change the clinical biologic behavior and therapeutic approaches. This study evaluated the comparative proliferative activity and apoptosis in OKC associated with or without an impacted tooth, as well as between the unilocular and multilocular OKC varieties. Immunohistochemical expression of Ki-67 as a proliferation marker and the apoptotic reactions were assessed by the TUNEL method for 32 cases of OKC (OKC with impacted tooth, n=16; OKC without impacted tooth, n=16) and 10 cases of dentigerous cyst (DC). OKC showed a greater proliferative potential and more apoptotic reactions than DC. In particular, OKC contained proliferating and apoptotic cells situated predominantly in the suprabasal and superficial layers, respectively. However, no significant difference was found between OKC associated with or without impacted tooth, or between the unilocular and multilocular OKC varieties, in terms of proliferative activity or apoptosis. In conclusion, OKC is characterized by an increase in both cell proliferation and apoptosis, suggesting a unique proliferative and differentiation process. It is believed that incomplete removal or other contributing factors, rather than intrinsic growth or apoptosis, may be the main reasons for the aggressive biologic behavior or recurrence in multilocular OKC.

Adult↗

PubMed2003

Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy.

We investigated the effects of pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on interstitial inflammation and fibrosis, using an animal model of chronic cyclosporine A (CsA)-induced nephropathy. Sprague-Dawley rats were maintained on a low-salt diet (0.05% sodium) and treated daily for 1 or 4 wk with vehicle (olive oil; 1 ml/kg sc), CsA (15 mg/kg sc), or both CsA and pravastatin (5 or 20 mg/kg in the drinking water). Anti-inflammatory and antifibrotic effects of pravastatin were studied by evaluating the concentrations of the inflammatory mediators osteopontin (OPN) and C-reactive protein (CRP), of fibrotic cytokine-transforming growth factor (TGF)-beta1, and the presence of ED-1-positive cells (macrophages). In addition, renal function, serum lipid levels, histopathology (arteriolopathy and tubulointerstitial fibrosis), and the expression of the vasoactive factors endothelial nitric oxide synthase (eNOS) and renin protein were also compared for different treatment groups. Pravastatin induced dose-dependent decreases in the expression of OPN, intrarenal CRP, and TGF-beta1, and in the numbers of ED-1-positive cells at 1 and 4 wk. These were accompanied by a significant attenuation of tubulointerstitial fibrosis at 4 wk. The downregulation of eNOS protein expression in CsA-treated rat kidney was markedly upregulated by pravastatin treatment, although intrarenal renin expression was unaffected. Renal dysfunction induced by CsA significantly improved with administration of pravastatin at a dose of 20 mg/kg. Neither CsA nor pravastatin influenced serum lipid or high-sensitivity CRP levels in the treatment groups. Thus in chronic CsA nephropathy, pravastatin effectively abrogates the progression of tubulointerstitial inflammation and fibrosis. This may support the clinical use of pravastatin.

Animals↗

PubMed2003

Expression of urea transporters in potassium-depleted mouse kidney.

Urea transport in the kidney is mediated by a family of transporter proteins that include the renal urea transporter (UT-A) and the erythrocyte urea transporter (UT-B). The purpose of this study was to determine the location of the urea transporter isoforms in the mouse kidney and to examine the effects of prolonged potassium depletion on the expression and distribution of these transporters by ultrastructural immunocytochemistry. C57BL6 mice were fed a low-potassium diet for 2 wk, and control animals received normal chow. After 2 wk on a low-potassium diet, urinary volume increased and urinary osmolality decreased (833 +/- 30 vs. 1,919 +/- 174 mosmol/kgH2O), as previously demonstrated. Kidneys were processed for immunocytochemistry with antibodies against UT-A1 (L446), UT-A1 and UT-A2 (L194), UT-A3 (Q2), and UT-B. In normal mice, UT-A1 and UT-A3 were expressed mainly in the cytoplasm of the terminal inner medullary collecting duct (IMCD). UT-A2 immunoreactivity was observed mainly on the basolateral membrane of the type 1 epithelium of the descending thin limb (DTL) of short-looped nephrons. The intensity of UT-A1 and UT-A3 immunoreactivity in the IMCD was markedly reduced in potassium-depleted mice. In contrast, there was a significant increase in UT-A2 immunoreactivity in the DTL. The intensity of UT-B immunoreactivity in the descending vasa recta (DVR) was reduced in potassium-depleted animals compared with controls. In control animals, UT-B immunoreactivity was predominantly observed in the plasma membrane, whereas in potassium-depleted mice, it was mainly observed in cytoplasmic granules in endothelial cells of the DVR. In summary, potassium depletion is associated with reduced expression of UT-A1, UT-A3, and UT-B but increased expression of UT-A2. We conclude that reduced expression of urea transporters may play a role in the impaired urine-concentrating ability associated with potassium deprivation.

Animals↗

PubMed2003

Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization.

Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of this study was to identify unique oncogenes that are differentially expressed in human cancers and characterize their functions in tumorigenesis. To discover new putative oncogenes, the differential display RT-PCR method was applied using normal cervical tissues, cervical cancer cell lines, cervical cancer tissues, and metastatic tissues. We identified a new human cervical cancer oncogene HCCR-2 that was overexpressed in various human tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon, and uterine cervix. Ectopic expression of HCCR-2 resulted in direct tumorigenic conversions of NIH/3T3 and Rat1 fibroblasts. Nude mice injected with NIH/3T3 cells stably transfected with HCCR-2 formed tumors in 4 weeks. The resultant tumors display characteristics of an epithelial carcinoma. In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of p53-induced p21(WAF1), MDM2, and bax. These results indicate that HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor.

3T3 Cells↗

PubMed2003

Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney.

Improving the ability of the kidney to tolerate ischemic injury has important implications. We investigated the effect of recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) injury and evaluated the role of heat shock protein (HSP) 70 in rHuEPO-induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, and rats were killed at 24, 48, and 72 h after I/R injury. Pretreatment of rHuEPO resulted in the following: i) decreased serum creatinine level; ii) decreased tubular cell apoptosis and necrosis, measured by DNA fragmentation analysis and TUNEL staining and histomorphological criteria; iii) decreased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; iv) increased bcl-2 protein and decreased caspase 3 activity; and v) decreased JNK expression. rHuEPO treatment increased HSP70 expression in a dose-dependent manner in normal rat kidneys, and inhibition of HSP70 expression by quercetin eliminated the renoprotective effect of rHuEPO in ischemic kidneys. Our study demonstrates that rHuEPO has a protective effect on subsequent I/R injury and that this effect is associated with induction of HSP70. Our study provides a new avenue for therapy to prevent renal damage after I/R injury.

Animals↗

PubMed2003

Adenovirus serotype 5 fiber shaft influences in vivo gene transfer in mice.

Adenoviral vectors used in gene therapy are predominantly derived from adenovirus serotype 5 (Ad5), which infects a broad range of cells. Ad5 cell entry involves interactions with the coxsackie-adenovirus receptor (CAR) and integrins. To assess these receptors in vivo, we mutated amino acid residues in fiber and penton that are involved in receptor interaction and showed that CAR and integrins play a minor role in hepatic transduction but that integrins can influence gene delivery to other tissues. These data suggest that an alternative entry pathway exists for hepatocyte transduction in vivo that is more important than CAR or integrins. In vitro data suggest a role for heparan sulfate glycosaminoglycans (HSG) in adenovirus transduction. The role of the fiber shaft in liver uptake was examined by introducing specific amino acid changes into a putative HSG-binding motif contained within the shaft or by preparing fiber shaft chimeras between Ad5 and Ad35 fibers. Results were obtained that demonstrate that the Ad5 fiber shaft can influence gene transfer both in vitro and to the liver in vivo. These observations indicate that the currently accepted two-step entry pathway, which involves CAR and integrins, described for adenoviral infection in vitro, is not used for hepatic gene transfer in vivo. In contrast, alpha(v) integrins influence gene delivery to the lung, spleen, heart, and kidney. The detargeted vector constructs described here may provide a foundation for the development of targeted adenoviral vectors.

Adenoviridae↗

PubMed2003

Increased expression of H+-ATPase in inner medullary collecting duct of aquaporin-1-deficient mice.

Phenotype analysis has demonstrated that aquaporin-1 (AQP1) null mice are polyuric and manifest a urinary concentrating defect because of an inability to create a hypertonic medullary interstitium. We report here that deletion of AQP1 is also associated with a decrease in urinary pH from 6.15 +/- (SE) 0.1 to 5.63 +/- 0.07. To explore the mechanism of the decrease in urinary pH, we examined the expression of H+-ATPase in kidneys of AQP1 null mice. There was strong labeling for H+-ATPase in intercalated cells and proximal tubule cells in both AQP1 null and wild-type mice. Strong H+-ATPase immunostaining was also present in the apical plasma membrane of inner medullary collecting duct (IMCD) cells in AQP1 null mice, whereas no H+-ATPase labeling was observed in IMCD cells in wild-type mice. In addition, there was an increase in the prevalence of type A intercalated cells in the IMCD of AQP1 null mice, suggesting that the deletion of intercalated cells from the IMCD, which normally occurs during postnatal kidney development, was impaired. Western blot analysis of H+-ATPase expression in the different regions of the kidney demonstrated a significant increase in H+-ATPase protein in the inner medulla of AQP1 null mice compared with wild-type mice. There were no changes in H+-ATPase expression in the cortex or outer medulla. These results represent the first demonstration of apical H+-ATPase immunoreactivity in IMCD cells in vivo and suggest that the decrease in urinary pH observed in AQP1 null mice is due to upregulation of H+-ATPase in the IMCD. The induction of H+-ATPase expression in IMCD cells of AQP1 null mice may be related to the chronically low interstitial osmolality in these animals. The challenge will be to identify the molecular signal(s) responsible for the de novo H+-ATPase expression.

Animals↗

PubMed2003

Synergistic effects of mycophenolate mofetil and losartan in a model of chronic cyclosporine nephropathy.

BACKGROUND: Combined treatments of mycophenolate mofetil (MMF) and losartan (LSRT) have synergistic effects on various renal diseases through their hemodynamic and anti-inflammatory effects. This study investigated whether MMF treatment is effective in inhibiting inflammatory processes in chronic cyclosporine A (CsA) nephrotoxicity, and whether combined treatment using MMF and LSRT affords superior protection compared with the respective monotherapies. METHODS: Rats on a low-salt diet were given vehicle (VH group, olive oil, 1 mg/kg per day), CsA (15 mg/kg per day), CsA and LSRT (CsA+LSRT group, 100 mg/L per day), CsA and MMF (CsA+MMF group; 40 mg/kg per day), or CsA, LSRT and MMF (CsA+LSRT MMF group). Control groups received each drug without CsA treatment. Renal function, histologic parameters (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and mediators of CsA-induced nephrotoxicity (angiotensin-II, osteopontin, and transforming growth factor [TGF]-beta1) were studied. RESULTS: The CsA-treated rats showed decreased renal function and increased histologic parameters compared with the VH-treated rats. The CsA+MMF treatment significantly improved renal function and histopathologic parameters compared with the CsA group, and combined treatment with MMF and LSRT further improved those parameters compared with the CsA+LSRT and CsA+MMF groups. At a molecular level, increased expression of angiotensin II protein, osteopontin, and TGF-beta1 mRNAs in the CsA group were significantly decreased with MMF, and further decrease was observed with the combined treatment using MMF and LSRT. CONCLUSIONS: MMF treatment decreases CsA-induced nephrotoxicity, and combined treatment with LSRT has a synergistic effect in preventing chronic CsA nephrotoxicity.

Angiotensin II↗

PubMed2003

Physicochemical characterization of solid dispersion of furosemide with TPGS.

The D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used to increase the aqueous solubility and dissolution rate of furosemide. The solid dispersion of furosemide with TPGS was prepared by solvent method using methanol. The aqueous solubility and the dissolution rate of furosemide were rapid and markedly enhanced from the 1:2 furosemide-TPGS solid dispersion. The X-ray diffractometry showed that pure furosemide and furosemide contained within the physical mixture were crystalline in nature, whereas furosemide in the solid dispersion was not in crystalline form. The infrared spectroscopic analysis showed that an interaction, in the solid dispersion, such as an association between the functional groups of furosemide and TPGS might occur in the molecular level. The infrared spectroscopy and differential thermal analysis showed the physicochemical modifications of the furosemide from the solid dispersion. The solid dispersion technique with TPGS provides a promising way to increase the solubility and dissolution rate of poorly soluble drugs.

Chemical Phenomena↗

PubMed2003

Aerobic soil metabolism of a new herbicide, LGC-42153.

To elucidate the fate of a new sulfonylurea herbicide, LGC-42153 [N-((4,6-dimethoxypyrimidin-2-yl)aminocarbonyl)-2-(1-methoxyacetoxy-2-fluoropropyl)-3-pyridinesulfonamide], in soil, an aerobic soil metabolism study was carried out for 120 days with [(14)C]LGC-42153 applied to a loamy soil. The material balance ranged from 90.7 to 101.5% of applied herbicide. The half-life of [(14)C]LGC-42153 was calculated to be approximately 9.0 days. The degradation products resulted from the cleavage of the sulfonylurea bridge. The metabolites identified during the study were N-((4,6-dimethoxypyrimidin-2-yl)aminocarbonyl)-2-(1-hydroxy-2-fluoropropyl)-3-pyridinesulfonamide, 2-(1-hydroxy-2-fluoropropyl)-3-pyridinesulfonamide, and 4,6-dimethoxy-2-aminopyrimidine. No significant volatile products or [(14)C]carbon dioxide was observed during the study. Nonextractable (14)C-residue reached 14.4-30.5% of applied material at 120 days after treatment, and radioactivity was distributed mostly in the humin and fulvic acid fractions.

Aerobiosis↗

PubMed2003

Preconditioning with cyclosporine A or FK506 differentially regulates mitogen-activated protein kinase expression in rat kidneys with ischemia/reperfusion injury.

BACKGROUND: The signaling pathways of mitogen-activated protein kinases (MAPKs) are important molecular components responsible for ischemia/reperfusion (I/R) injury in the kidneys. Preconditioning with cyclosporine A (CsA) or FK506 reduces subsequent I/R injury. We studied the effect of preconditioning with CsA or FK506 on MAPK expression in ischemic rat kidneys. METHODS: Two separate studies were performed using Sprague-Dawley rats. First, MAPK (extracellular signal-regulated kinase [ERK], jun N-terminal kinase [JNK], p38) expressions were observed at 0, 10, 20, 30, 60, 120, and 1,440 min after I/R injury. Second, the effects of preconditioning with CsA or FK506 on MAPK expressions were observed in rat kidneys with I/R injury. I/R injury was induced by clamping both renal arteries for 45 min. Rats were pretreated with intravenous (IV) CsA (3 mg/kg) or IV FK506 (0.3 mg/kg) 6 hr before I/R injury and killed 30 min later. Expression of MAPK was measured using immunoblot and immunohistochemistry. RESULTS: MAPK (ERK, JNK, p38) expressions were significantly increased in kidneys with I/R injury compared with sham-operated controls, and immunohistochemistry revealed increased MAPK immunoreactivity in renal tubules of the outer medulla. Kidneys preconditioned with low-dose CsA or FK506 showed significantly increased ERK expression compared with kidneys with I/R injury alone (CsA, 9.5- vs. 4.5-fold; FK506 10.4- vs. 4.5-fold: P<0.05) but showed decreased JNK (CsA, 3.8- vs. 5.3-fold; FK506, 3.4- vs. 5.3-fold: P<0.05) and p38 expression (CsA, 2.5- vs. 3.7-fold; FK506, 2.1- vs. 3.7-fold: P<0.05). CONCLUSIONS: Preconditioning with CsA or FK506 differentially regulates the expression of MAPK in rat kidneys with I/R injury, and this may explain the remarkable protective effects of these agents.

Animals↗

PubMed2003

Degradation of the sulfonylurea herbicide LGC-42153 in flooded soil.

LGC-42153, 2-fluoro-1-[3-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)pyridin-2-yl] propyl methoxyacetate, is a new sulfonylurea herbicide for use in rice. Its breakdown and metabolism was studied in soil under flooded conditions using two radioactive tracer compounds labelled at either the propyl group or the pyrimidine ring. The half-life of LGC-42153 was approximately 3.0 days. The mass balance over 120 days ranged from 94.0 to 104.2% of applied radiocarbon, and no significant amount of volatiles or [14C]carbon dioxide were observed. Solvent non-extractable radiocarbon reached about 11-14% of applied radiocarbon at 120 days after treatment. The major metabolic reaction was the cleavage of the carboxyl ester bond to give 1-(4,6-dimethoxypyrimidin-2-yl)-3-[2-(1-hydroxy-2-fluoropropyl)pyridine-3-sulfonyl]urea, which underwent hydrolysis of the sulfonylurea bridge giving 2-(1-hydroxy-2-fluoro)propyl-3-pyridinesulfonamide and 4,6-dimethoxy-2-aminopyrimidine.

Carbon Radioisotopes↗