Clinical Significance of Urine Dipstick Positive for Albuminuria in Urolithiasis / 계명의대학술지

Urolithiasis is suspected by flank pain, costovertebral angle tenderness, and hematuria, and confirmed by computed tomography (CT). Treatment strategy and likelihood of spontaneous passage of a stone were determined by size and position of ureteral calculi and complication detected by CT. In general, the purpose of urinalysis for urolithiasis is to confirm the hematuria and pyuria. However, sometimes albumin is detected by urine dipstick test in urolithiasis. Therefore, I performed this study to investigate the clinical significance of urine dipstick positive for albuminuria in urolithiasis. This study was a retrospective review of medical records of 150 patients who visited the emergency department and diagnosed with urolithiasis by CT between March 2010 and February 2014. The patients were divided into a albuminuria group and non-albuminuria group. General chracteristics, clinical features, laboratory results, and CT findings were compared. The incidence of stones >5 mm in diameter, hydronephrosis (≥grade 2) and upper ureter stone were significantly higher in albuminuria group than non-albuminuria group. In multivariate logistic regression analysis, hydronephrosis (≥grade 2) and upper ureter stone were significantly associated with albuminuria. Upper ureter stone and hydronephrosis (≥grade 2) are also known as predictors for failure of spontaneous passage of ureter calculi. If further studies are done, urine dipstick positive for albumin in urolithiasis can be used as a predictor for failure of spontaneous passage of ureter calculi.

Recent Insights into Insulin-Like Growth Factor Binding Protein 2 Transcriptional Regulation

Insulin-like growth factor binding proteins (IGFBPs) are major regulators of insulin-like growth factor bioavailability and activity in metabolic signaling. Seven IGFBP family isoforms have been identified. Recent studies have shown that IGFBPs play a pivotal role in metabolic signaling and disease, including the pathogenesis of obesity, diabetes, and cancer. Although many studies have documented the various roles played by IGFBPs, transcriptional regulation of IGFBPs is not well understood. In this review, we focus on the regulatory mechanisms of IGFBP gene expression, and we summarize the findings of transcription factor activity in the IGFBP promoter region.

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

BACKGROUND/AIMS: Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10(-/-)) mice. METHODS: Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. RESULTS: The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10(-/-) mice compared to IL-10(+/+) mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10(-/-) mice compared to IL-10(+/+) mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10(-/-) mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10(-/-) mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. CONCLUSIONS: These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

Effect of Green Tea Extract/Poly-gamma-Glutamic Acid Complex in Obese Type 2 Diabetic Mice

BACKGROUND: The increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with the rapid spread of obesity. Obesity induces insulin resistance, resulting in beta-cell dysfunction and thus T2DM. Green tea extract (GTE) has been known to prevent obesity and T2DM, but this effect is still being debated. Our previous results suggested that circulating green tea gallated catechins (GCs) hinders postprandial blood glucose lowering, regardless of reducing glucose and cholesterol absorption when GCs are present in the intestinal lumen. This study aimed to compare the effect of GTE with that of GTE coadministered with poly-gamma-glutamic acid (gamma-PGA), which is likely to inhibit the intestinal absorption of GCs. METHODS: The db/db mice and age-matched nondiabetic mice were provided with normal chow diet containing GTE (1%), gamma-PGA (0.1%), or GTE+gamma-PGA (1%:0.1%) for 4 weeks. RESULTS: In nondiabetic mice, none of the drugs showed any effects after 4 weeks. In db/db mice, however, weight gain and body fat gain were significantly reduced in the GTE+gamma-PGA group compared to nondrug-treated db/db control mice without the corresponding changes in food intake and appetite. Glucose intolerance was also ameliorated in the GTE+gamma-PGA group. Histopathological analyses showed that GTE+gamma-PGA-treated db/db mice had a significantly reduced incidence of fatty liver and decreased pancreatic islet size. Neither GTE nor gamma-PGA treatment showed any significant results. CONCLUSION: These results suggest that GTE+gamma-PGA treatment than GTE or gamma-PGA alone may be a useful tool for preventing both obesity and obesity-induced T2DM.

Alterations of Colonic Contractility in Long-term Diabetic Rat Model

BACKGROUND/AIMS: Dysfunction of the gastrointestinal tract occurs in about 76% of patients who are diabetic for more than 10 years. Although diabetes-related dysfunctions of the stomach such as gastroparesis have been extensively studied over the recent years, studies about the mechanism underlying colonic symptoms in long-term diabetes models are rare. Therefore, the goal of our study was to clarify the nature of colonic dysfunction in a long-term diabetic rat model. METHODS: The characteristics of colonic smooth muscle were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. These results were compared to those obtained from Long-Evans Tokushima Otsuka (LETO) control rats. RESULTS: Spontaneous contractility of the proximal colon was significantly decreased in the diabetic rats compared to the controls, while the spontaneous contractility of the distal colon was not. The number of interstitial cells of Cajal networks in the proximal colon was greatly decreased in diabetic rats compared to the controls. Contractility of the proximal colon in response to carbachol, an acetylcholine receptor agonist, was significantly weaker in the diabetic rats. In addition, the degree of relaxation in response to nitric oxide in the proximal colon of diabetic rats also appeared to be attenuated. CONCLUSIONS: The results from our study suggest that the decrease of interstitial cells of Cajal network, cholinergic receptors, and neuronal nitric oxide synthase in the proximal colon plays important roles in diabetes-related dysfunction of colon.

Increased Expression of ATP-sensitive K+ Channels Improves the Right Ventricular Tolerance to Hypoxia in Rabbit Hearts

ATP-sensitive K+ channels (KATP) are major component of preventing ischemia-reperfusion injury. However, there is little information regarding to the expressional difference of K(ATP) and its function between left and right ventricles. In this study, we measured the lactate dehydrogenase release of rabbit heart slices in vitro and determined the difference of the K(ATP) expression at the both ventricles by measuring the level of K(ATP)-forming Kir6.2 (OcKir6.2) mRNA using in situ hybridization. The hearts were preconditioned with 15 min hypoxia and reoxygenated for 15 min before a hypoxic period of 60 min, followed by reoxygenation for 180 min. With hypoxic preconditioning (100% N2) with 15 min, left ventricles (LV) showed higher release of LDH comparing with right ventricles (RV). Adding KATP blocker glibenclamide (10 microM) prior to a hypoxic period of 60 min, hypoxic preconditioning effect of RV was more abolished than LV. With in situ hybridization, the optical density of OcKir6.2 was higher in RV. Therefore, we suggest that different K(ATP) expression between LV and RV is responsible for the different response to hypoxia and hypoxic preconditioning of rabbit hearts.

ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity

BACKGROUND: The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight. METHODS: To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel. RESULTS: The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice. CONCLUSION: These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.

Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial K(ATP) Channel Activation in Isolated Rat Hearts

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 micrometer and 4.0+/-1.7% in EGCG 10 micrometer, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 micrometer GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 micrometer HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.

Characterization of Gentamicin-Induced Apoptosis in a Cochlear Cell Model / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Aminoglycoside antibiotics are ototoxic. Understanding of the molecular mechanisms underlying the drug-induced ototoxicity, however, has been hampered by limited cell availability. Recently, HEI-OC1 cells, which are of an immortalized cochlear cell line sensitive to ototoxic drugs, have been derived from the auditory sensory organ. This study was performed to confirm whether cultured HEI-OC1 cells can be used to evaluate aminoglycoside-induced ototoxicity and the effect of antioxidants against aminoglycoside-induced colchlear cell damage. MATERIALS AND METHOD: Gentamicin was administered for 3 days in the media containing HEI-OC1 cells. RESULTS: Cell viability was decreased by gentamicin in a dose-dependent manner. The cell number was decreased by 50% 3 days after the exposure to 2 mM gentamicin. Penicillin did not have any significant effect. Flow cytometric analysis revealed that sub G1 arrest representing cellular apoptosis was accelerated by gentamicin treatment but not by penicillin. Expression of p27Kip1, the cyclin-dependent kinase inhibitor, was exclusively increased by gentamicin. Reactive oxygen species were also increased by gentamicin when compared with those of the control or when penicillin was used. Caspase-3 activity became increased according to the elevation of gentamicin concentrations. N-acetyl cysteine, but not vitamin E or vitamin C, ameliorated cell survival dose-dependently against gentamicin. CONCLUSION:The present study reveals that the HEI-OC1 cell line is a good model to evaluate gentamicin-induced ototoxicity. The results suggest that gentamicin-induced apoptosis may be, at least partially, linked to the overproduction of a reactive oxygen species called. Nacetyl cysteine, a free radical scavenger, that decreases the gentamicin ototoxicity.

Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of KATP channels, insulin receptor beta-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that KATP-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on KATP channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

Induction of apoptosis by Hibiscus protocatechuic acid in human uterine leiomyoma cells / 부인종양

OBJECTIVE: Hibiscus protocatechuic acid (PCA) is a food-derived polyphenol antioxidants used as a food additive and a traditional herbal medicine. In this study, PCA was to determine its effect on cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. METHODS: The effect of PCA on cell proliferation and cell cycle progression was examined in the primary cultured human uterine leiomyoma cells. MTT reduction assay was carried out to determine the viability of uterine leiomyoma cells. Cell cycle analysis for Hibiscus protocatechuic acid treated leiomyoma cells was done by FACS analysis. DNA fragmentation assay was performed to determine fragmentation rate by PCA in leiomyoma cells. Western blot analysis was done using anti pRB, anti-p21(cip1/waf1), anti-p53, anti-p27(kip1), anti-cyclinE, anti CDK2 antibodies to detect the presence and expression of these proteins in PCA treated myoma cells. RESULTS: PCA induced growth inhibition in a dose dependent manner, treatment with 5 mmol/L PCA blocked 80% cell growth. FACS results showed that there was increased the percentage of cells in sub G1. DNA fragmentation assay by ELISA was done to find the rate of apoptosis. Apoptosis took place but in a dose dependent manner. From Western blot analysis it revealed PCA induced the expression of p21(cip1/waf1) and p27(kip1) increasingly and was not mediated by p53. Caspase-7 pathway was activated and dephosphorylation of pRB took place. CONCLUSION: In Conclusions, PCA, a polyphenol antioxidant, inhibited cell proliferation and induced cell cycle arrest at sub G1 phase by enhancing the production of p21cip1/waf1 and p27kip1. These results indicate that PCA will be a promising agent for use in chemopreventive or therapeutics against human uterine leiomyoma.

A Familial Case of Wiskott-Aldrich Syndrome with a Hotspot Mutation in Exon 2 of the WAS Gene

The Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder characterized classically by thrombocytopenia, immunodeficiency, and eczema. The phenotype observed in this syndrome is caused by mutation in the WAS gene. Peripheral blood DNAs were isolated from an 18-month-old boy with WAS and his mother, maternal uncle, and maternal grandmother. Genetic analysis for the detection of a mutation of WAS gene was performed by polymerase chain reaction-single strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing of the PCR product. In PCR-SSCP, the patient and his maternal uncle had an abnormal shift band, which was not found in normal controls, and his mother and maternal grandmother showed heterozygous bands. In direct sequencing analysis, the patient with WAS had CGC-->CAC point mutation in exon 2 that resulted in an amino acid change in codon 86 (Arg86His). The present study identified a gene mutation responsible for WAS at a mutation hotspot of the WAS gene in a Korean family.

Protective Effect of Melatonin on the Nephrotoxicity by Cisplatin / 대한신장학회잡지

BACKGROUND: Cisplatin (CP), an antitumor agent widely used in the treatment of cancers, has nephrotoxicity. This side effect is closely related to oxidative stress. In the present study, we attempted to reduce CP-induced nephrotoxicity in rats by administering melatonin, an antioxidant. METHODS: Male Sprague-Dawley rats were divided into different groups and were treated as follows: (1) saline control; (2) CP (16 mg/kg, i.p.); (3) CP plus melatonin (10 mg/kg, i.p.). The rats were sacrificed at the 6th day after CP treatment. To evaluate renal damage, BUN, serum creatinine, creatinine clearance and microscopic examination were done. Hydrogen peroxide which is one of the oxygen free radicals, and malondialdehyde which is known as a marker of the oxygen free radical mediated injury, and the activities of the antioxidant enzymes such as superoxied dismutase, catalase, and glutathione peroxidase were also measured. RESULTS: CP-treated rats showed the increase of BUN, serum creatinine, malondialdehyde, hydrogen peroxide and superoxide dismutase (SOD) in kidney. And CP-treated rats also showed the decrease of creatinine clearance and catalase levels. CP-treated rats showed severe tubular necrosis in proximal convoluted tubules under the light microscopic examination. The light microscopic finding and all of the parameters except SOD were restored in the rats injected with CP plus melatonin than those with CP alone. SOD level was higher in the rats injected with CP plus melatonin than that with CP alone. CONCIUSION: These results suggest that melatonin suppresses CP-induced nephrotoxicity by suppressing the production of reactive oxygen species via the activation of SOD and catalase.

Growth Inhibition of Human Uterine Leiomyoma Cells by Selective Estrogen Receptor Modulator / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to evaluate potential efficacy of selective estrogen receptor modulators (raloxifene and tamoxifen) to human uterine leiomyoma cells. METHODS: The samples were collected from ten hysterectomized specimen. we evaluated the estrogen-responsive growth of human uterine leiomyoma and normal myometrial cells. The potential efficacy of Selective Estrogen Receptor Modulators (SERMs: raloxifene and tamoxifen) to human uterine leiomyoma cells were conducted by MTS, cell count assay and Western-blot. RESULTS: Human uterine leiomyoma and normal myometrial cells that expressed estrogen receptor (ER) showed increases the cell number in the presence of estrogen compared with ER negative uterine leiomyoma cells. Raloxifene and tamoxifen inhibited estrogen-stimulated proliferation of ER-containing human uterine leiomyoma and normal myometrial cells. Raloxifene was more effective in inhibiting estrogen-induced increases of cell number compared with tamoxifen. CONCLUSION: The effect of SERMs on leiomyoma was inhibited the cell proliferation without apoptosis or cell cycle arrest. These data suggest that SERM should be examined as candidate of nonsurgical therapeutic agents for uterine leiomyoma.

Identification of ATP-sensitive K+ Channel in an Uterine Leiomyoma Cell / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to identify the ATP-sensitive potassium (K(ATP)) channel subtypes in uterine leiomyoma and normal myometrial cells, and to compare the difference in its expression between uterine leiomyoma and normal myometrial cells. METHODS: Fresh ten uterine leiomyomas and their adjacent normal myometrial tissues were obtained from hysterectomies that were conducted on benign diseases. With the use of reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, we analysed the expression of K(ATP) channel subtypes in tissues and primary cultured leiomyoma cells. To demonstrate the K(ATP) channel activity in uterine leiomyoma cells, whole cell patch-clamp recordings were made. RESULTS: The uterine leiomyoma and normal myometrial tissues contained Kir6.1/SUR2B and Kir6.2/ SUR2B mRNAs, although the expression of SUR1 and SUR2A mRNAs were not expressed in the uterine leiomyoma and normal myometrial tissues. Primary cultured uterine leiomyoma and normal myometrial cells demonstrated same patterns. To determine the expression levels of K(ATP) channel subunits, high levels of Kir6.1, Kir6.2, and SUR2B were detected by western-blot analysis in uterine leiomyoma compared with normal myometrial tissues. K(ATP) channel currents were increased by estrogen application in uterine leiomyoma cells. CONCLUSION: These studies provide new knowledge concerning K(ATP) channels in uterine leiomyoma and normal myomtrial cells. we demonstrated uterine leiomyoma and normal myometrial tissues contained Kir6.1/ SUR2B and Kir6.2/SUR2B subunits and showed an increased expression in uterine leiomyoma compared with normal myometrial tissues. These results suggest that K(ATP) channels are important elements in growth of uterine leiomyoma.

Changes in Hypothalamic Expressions of Natriuretic Peptide mRNA following Head-down Suspension in Rats

BACKGROUND: Head-down suspension (HDS) of rats has been used as a model for simulation of a microgravity environment. C-type natriuretic peptides (CNP) and atrial natriuretic peptide (ANP) are produced in the central nervous system, especially in hypothalamus, to complement their peripheral natriuretic effects. Therefore, this study investigated the changes in the central adaptations of hypothalamic ANP and CNP syntheses to 4 weeks of HDS in rats. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a -45 degrees head-down tilt using the tail-traction technique (HDS rats). We determined the hypothalamic syntheses of natriuretic peptides as an expression of ANP and CNP mRNA. The expression of natriuretic peptide mRNA was measured by reverse transcription-polymerase chain reaction with [32P]-dCTP following 4 weeks of HDS in the hypothalamus of control and HDS rats. RESULTS: After 4 weeks of HDS, the expression of ANP mRNA showed a decreasing trend in the hypothalamus of HDS rats. In contrast with ANP, CNP mRNA expression was significantly (p<0.01) increased in the hypothalamus of HDS rats. There were different changes in the hypothalamic CNP and ANP mRNA expressions of HDS rats compared with that of the control rats.CONCLUSION: These results represent that the hypothalamic syntheses of natriuretic peptides are differently responded and the role of CNP is augmented to compensate for the decrement of ANP action in the central nervous system following 4 weeks of HDS.

Effects of Long-Term Head-down Suspension on Changes in Body Weight, Daily Water Intake and Hematological Data in Rats

BACKGROUND: This study was aimed to observe the changes in body weight, water intake and hematological data during and after long-term head-down suspension (HDS) in rats. HDS rats induced by tail suspension has evolved as a useful model for the simulation of a microgravity or zero-gravity environment. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats, weighing 230-270 g, were subjected to either a hori-zontal position (control horizontal, CH rats) or a 45 degreeshead-down suspension (HDS rats) for 4 weeks. We deter-mined the body weight and daily water intake in both CH and HDS rats. Hematological data including white and red blood cell counts, hemoglobin concentration and hematocrit were measured. The characteristics of red blood cell were also calculated from above hematological data in the both rats after 4 weeks of observa-tion. RESULT: In CH rats, body weight was significantly increased (P<0.05) after 4 weeks of experiment, where-as the body weight of HDS rats was only showed a small increase but was significantly decreased (P<0.05) after 4 weeks of HDS compared with that of CH rats. Daily water intake was increased (P<0.05) after 2 week in HDS rats but the overall changes of the rest period were no difference between both CH and HDS rats. White blood cell counts did not show any changes in both rat groups while red blood cell counts showed a decreas-ing trend after 4 weeks HDS. After HDS, hemoglobin concentration, hematocrit and mean corpuscular hemoglobin were significantly decreased (P<0.05) compared with CH rats. CONCLUSION: These results represent that the long-term HDS could attenuate the increase in body weight of young rats and induce the decrease in hemato-logical data, especially in the characteristics of red blood cell.

Changes of mRNA and Plasma Levels of Atrial Natriuretic Peptide in Subtotal Nephrectomized Rats after High Salt Intake / 대한신장학회잡지

High salt intake produces volume expansion and electrolyte imbalance in chronic renal failure and modifies the synthesis and secretion of atrial natriuretic peptide(ANP) to compensate the abnormalities in fluid and sodium handling. This study was performed to investigate the effect of high salt intake on modulation of cardiac and noncardiac ANP mRNA as well as plasma ANP levels in 5/6 subtotal nephrectomized (NPX) rats as a model of chronic renal failure. Adult male Sprague-Dawley rats were divided into sham and NPX rats. NPX rats were induced by 2/3 pole ligation and contralateral nephrectomy. Sham and NPX rats had access to normal chow with tap water for 8 weeks or normal chow with 0.45% NaCl solution(HS) for last 2 weeks. Plasma ANP levels were measured by radioimmunoassay. ANP mRNA from the right atrium, left ventricle, hypothalamus and kidney were analyzed by RT-PCR with 32P-dCTP at 8 weeks after surgical operation in both sham and NPX rats. Blood urea nitrogen(BUN) was measured to evaluate impaired renal function. Body weight, daily water intake, hemoglobin, red blood cell, hematocrit, arterial pressure and heart rate were also monitored. Arterial pressure in NPX+HS rat was significantly increased. Both percent increase of body weight and hematologic findings were decreased in NPX rats. Daily water intake was increased in NPX rats, especially in NPX+HS rat. BUN also increased in NPX rats. Plasma ANP concentration was significantly increased in sham+HS rat, but other significant increases were not shown in NPX rats. The levels of right atrial ANP mRNA represented the increasing trend like as plasma ANP. Left ventricular ANP mRNA was increased in sham+HS rat, while the level in NPX+HS rat was decreased comparing with that of sham+HS rat. Hypothalamic ANP mRNA was decreased in NPX+HS rat. In the kidney, the level of ANP mRNA in sham+HS rat was increased comparing with sham rat, but ANP synthesis in NPX+HS rat was significantly lower than in sham, sham+HS and in NPX rats. These findings represent that the high salt intake in NPX rat does not alter the plasma levels and cardiac synthesis of ANP but suppresses the renal ANP mRNA. The diminished renal ANP synthesis may attenuate the regulatory role of ANP system in the kidney and result in volume expansion and hypertension.

Effect of propofol, an intravenous anesthetic agent, on KATP channels of pancreatic beta-cells in rats

ATP-sensitive potassium channels (KATP channels) play an important role in insulin secretion from pancreatic beta cells. We have investigated the effect of propofol on KATP channels in cultured single pancreatic beta cells of rats. Channel activity was recorded from membrane patches using the patch-clamp technique. In the inside-out configuration bath-applied propofol inhibited the KATP channel activities in a dose-dependent manner. The half-maximal inhibition dose (ED50) was 48.6+/-8.4 micrometer and the Hill coefficient was 0.73 0.11. Single channel conductance calculated from the slope of the relationship between single channel current and pipette potential (+20~+100 mV) was not significantly altered by propofol (control: 60.0+/-2.7 pS, 0.1 mM propofol: 58.7+/-3.5 pS). However, mean closed time was surely increased. Above results indicate that propofol blocks the KATP channels in the pancreatic beta cells in the range of its blood concentrations during anesthesia, suggesting a possible effect on insulin secretion and blood glucose level.

Mechanism of Renal Oxidative Damage following 4-week Head-down Suspension in Rats

The purpose of this study was to observe the variation of malondialdehyde (MDA), an indirect index of oxidative damage, following 4-week of head-down suspension (HDS) at -45degreein rats as a model of simulated weightlessness. We also measured the activities of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase for clarifying the mechanisms of renal oxidative damage. MDA was increased (p<0.05) at the 4th week of HDS rats compared to control horizontal positioned rats. Following HDS, the renal activity of SOD was also significantly increased (p<0.01) at the 4th week of HDS whereas the changes of renal GSH-Px and catalase activities were not significantly different from controls. The expression of renal SOD mRNA used by polymerase-chain reaction method showed the similar pattern with the change of renal SOD activity and was more increased (p<0.05) than control horizontal positioned rat. These results indicate that simulated weightlessness induces the augmented SOD gene expression in the kidney which results in increased SOD activity, and thus increased production of MDA due to increased production of hydrogen peroxide. And under this condition, GSH-Px and catalase do not play their protective roles against hydrogen peroxide.