• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.118-122
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• 2016

Integrin ${\alpha}_v{\beta}_3$ plays an important role in the tumor metastases and angiogenesis. Arginine-glycine-aspartate (RGD) peptide motif binds to the integrin ${\alpha}_v{\beta}_3$. General $^{68}Ga$-labeled cyclic RGD peptides was rapidly eliminated from the circulatory system by renal excretion because of its hydrophilic property. The purpose of this study was to develop a novel $^{68}Ga$-labeled cyclic RGD peptides, which could acquire enhanced PET tumor images with improved pharmacokinetics by adopting biphenyl group between chelator and RGD peptides. $^{68}Ga$-DOTA-2P-c(RGDyK) was demonstrated a 12% higher lipophilicity level than $^{68}Ga$-DOTA-c(RGDyK) as a reference compound. In the animal PET, $^{68}Ga$-DOTA-2P-c(RGDyK) represented relatively lower blood-clearance, and an increased signal to noise ratio compared to $^{68}Ga$-DOTA-c(RGDyK). From these perspective, $^{68}Ga$-DOTA-2P-c(RGDyK) could be a good candidate for in integrin ${\alpha}_v{\beta}_3$-expressed tumor imaging.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.42-47
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• 1999

Angiotensin-converting enzyme inhibitors lower urinary protein excretion in hypertensive and normotensive patients with renal disease. Most children with nephrotic syndrome have minimal change histology and the great majority of these patients respond to the treatment with oral prednisone. Here we have studied the effects of combination of Inhibace and oral prednisone in pediatric patients with nephrotic syndrome. 45 patients with nephrotic syndrome were selected. Of these, 29 patients were treated with prednisone(2mg/kg/day) and 16 children were treated with prednisone and Inhibace(2.5mg/day). Urinary protein, blood pressure, creatinine clearance, serum creatinine, serum albumin and serum cholesterol were measured in both control and Inhibace group. Also the duration to remission after treatment was compared in both groups. The amounts of proteinuria before and after treatment were not significantly different in both group. The duration to remission of proteinuria was significantly shorter in Inhibace group compared to that in control group. The changes of blood pressure and creatinine clearance were not significant in Inhibace group. In conclusion, the combination therapy of oral prednisone and ACE inhibitor have shortened the duration to remission of proteinuria in nephrotic syndrome of children.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.364-375
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• 2011

Given that single blockade with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can achieve only partial and undurable suppression of the Renin Angiotensin System (RAS), it has been hypothesized that dual blockage would be more beneficial in the management of blood pressure (BP) reduction and prevention of progressive chronic kidney disease (CKD) than either agent alone. Thus, it has been suggested that the combination of an ACEI and an ARB might provide renal benefits to hypertensive patients over and above BP reduction. However, this might also expose patients to additive or synergistic side effects. We attempted to conduct a systematic review to evaluate the benefits and harms of combination therapy in hypertensive patients with or without kidney diseases. MEDLINE and KoreaMed were searched for relevant randomized clinical trials in adult hypertensive patients with or without diabetes (restricted to 1997, limited to trials published in English). Results were summarized using the random-effects model, and between-studies heterogeneity was estimated with $I^2$. A final analysis of ten trials (23,928 patients) revealed that the combination of an ACEI and an ARB reduced blood pressure (SBP/DBP) by 3.95/2.02 mmHg (95% confidence interval [CI], -4.38 to -3.53/-2.33 to -1.71) compared with ACEI monotherapy, and 2.83/2.64 mmHg (95% CI, -3.25 to -2.41/-4.95 to -0.33) compared with ARB monotherapy. Eight trials (391 patients) demonstrated a significant reduction in 24h-proteinuria (weighted mean difference, 0.16 g/day, 95% CI, -0.26-0.05), but they did not translate into an improvement in GFR. Tests for heterogeneity showed no difference in effect among the studies. The combination therapy reduced proteinuria by 30% (95% CI, 23% to 37%) and 39% (95% CI, 31% to 48%) compared with ACEI monotherapy and ARB monotherapy, respectively. However, in patients who had proteinuria more than 0.5 g/day, the combination therapy failed to show significant reduction in urinary protein excretion. The current cumulative evidence suggests that diabetic patients with proteinuria on dual RAS blockade have an increase risk of adverse events such as hyperkalemia, hypotension, and so on, compared with ACEI or ARB alone. It is, therefore, proposed that the combination therapy should not be routinely used for the treatment of hypertension with or without compelling indications.

• Reproductive and Developmental Biology
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• v.30 no.3
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• pp.157-162
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• 2006

Endogenous 84 amino acid parathyroid hormone(PTH) is synthesized as a pre-pro hormone by the chief cells of the parathyroid glands. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. In addition, PTH stimulates new bone formation by extraordinary stimulation of osteoblastic activity and decreasing calcium excretion by the kidney. In this study, we constructed and tested retrovirus vectors designed to express the human parathyroid hormone(hPTH) gene under the control of the tetracycline-inducible promoters. To increase the hPTH gene expression at turn-on state, woodchuck hepatitis virus posttranscriptional regulatory element(WPRE) sequence was also introduced into retrovirus vector at downstream region of either the hPTH gene or the sequence encoding reverse tetracycline-controlled transactivator(rtTA). Transformed primary culture cells(porcine fetal fibroblast, PFF, chicken embryonic fibroblast, CEF) were cultured in the medium supplemented with or without doxycycline(tetracycline derivative) for 48 hours, and induction efficiency was measured by comparing the hPTH gene expression level using two step RT-PCR and ELISA Higher hPTH expression($3{\tims}10^4\;pg/ml,\;5.3{\times}10^4\;pg/ml$) and tighter expression control(up to 8 fold) were observed from the vector in which the WPRE sequence was placed at downstream of the hPTH gene. The resulting tetracycline inducible vector system may be helpful in solving serious physiological disturbance problems which have been a major obstacle in successful production of transgenic animals.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.3
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• pp.342-350
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• 2005

In the present work antidotal effect of dietary garlic was studied on lead-intoxicated rat. One of 5 groups of young Wistar sp. male rat, aged 4 weeks for control were fed only normal diet. Lead (25 ㎎/㎏.bw/week) was administered to other four groups for plumbism model over 4 weeks, of which three groups were supplemented with one of the following raw garlic juice: 1.10 (1% diet), 2.21 (2%) and 3.31 (3%) ㎎/㎏.bw/day respectively. Body weight gain rates in all garlic group significantly increased, especially in 2% garlic group that showed 9.8% net gain, as compared with only-lead treated group but lower values than control. The fecal and urinary lead excretion in all garlic groups significantly increased in a dose dependent fashion with highest value of 9.59% net gain in 3% garlic group as compared to lead treated control group. In comparison with lead treated control group, all garlic groups showed significantly increased hemoglobin contents, hematocrit values (Hct), red blood cell (RBC) count, mean corpuscular volume (MCV), and δ-amino levulinic acid dehydratase (δ-ALAD) activities. The values of 2% and 3% garlic groups remarkably increased while no significant difference between the values of 2% and 3% garlic groups was observed. The ALT activities, blood urea nitrogen (BUN) and creatinine (CR) in all garlic groups significantly decreased as compared with lead-treated control group. The values of 2% garlic group were the lowest and significantly different from the values of 1% and 3% garlic groups. The results showed that 2%-3% garlic juice in diet had obviously antidotal effects in lead-poisoned rats by promoting lead excretion. However, mega dose garlic such as in 3% garlic group might have some adverse effects on hepatic and renal functions in rats. In conclusion, the dietary habit to take ordinary garlic sauce in appropriate amount, may be helpful for preventing lead or other heavy metal intoxication.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.2
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• pp.9-13
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• 2016

Purpose PET-CT examinations using $^{18}F-FDG$ to treat urinary system cancer are limited in terms of anatomical structure and excretion route of $^{18}F-FDG$. But one of the ongoing examinations utilizing $^{11}C-Acetate$ can compensate for such defects. We would like to introduce a clinical application of $^{11}C-Acetate$ PET-CT in urinary cancer patients. Materials and Methods We conducted a clinical survey of 22 patients diagnosed with urinary cancer at our hospital, 10 prostate cancer patients, 10 renal cell carcinoma patients, and 2 bladder cancer patients. All patients were performed $^{18}F-FDG$ PET-CT examinations, $^{11}C-Acetate$ examinations were performed after two weeks on average. The equipment used to D-710 PET-CT in GE Company and we performed PET-CT procedures 15 minutes after injecting $^{11}C-Acetate$, and a medical doctor from the department of nuclear medicine appraised and compared images between $^{18}F-FDG$ and $^{11}C-Acetate$. Results According to our survey, prostate cancer patients generally had lower uptake of $^{18}F-FDG$ than other cancer patients did. In 2 out of 10 prostate cancer patients, metastasized cancer showed greater uptake in $^{11}C-Acetate$ than $^{18}F-FDG$. In renal cell carcinoma cases, 8 out of 10 patients displayed evidently greater uptake in $^{11}C-Acetate$ than $^{18}F-FDG$. We excluded bladder cancer cases in this study because uptake of $^{18}F-FDG$ in the bladder was too hot, the number of patients was insufficient, and the cases did not meet criteria such as the use of diuretics. Conclusion It is too premature to draw solid conclusions from the survey, since it involved only a small number of participants. However, there are a number of studies conducted abroad that prove the effectiveness of the $^{11}C-Acetate$ PET-CT examinations in treating urinary system cancer, and this study is still ongoing at our hospital. If the tests were to be conducted on a larger number of participants, this study could lead to numerous other potential research topics, such as the correlation between Prostatic specific antigen (PSA) values and $^{11}C-Acetate$ PET-CT, Gleason sum values from biopsy before surgery, Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) between $^{18}F-FDG$ PET-CT examinations and $^{11}C-Acetate$ PET-CT examinations in other urinary system cancers.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.183-192
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• 2005

Purpose : The long term disease course and prognostic factors were evaluated in childhood Henoch-$Sch{\ddot{o}}nlein$ puruura nephritis(HSPN). Methods : A total of 75 children(44 boys and 31 girls) with HSPN were included in this study. The onset age was $8.0{\pm}3.1$ years(2.3-l5.3 years), and the follow-up period was $4.3{\pm}3.6$ years(1.0-17.1 years). Kidney biopsy was done in 24 children(32$\%$). Initial clinical and laboratory findings were evaluated. In addition, polymorphisms of the renin angiotensin system(RAS) genes(insertion/deletion in intron 16 of ACE gene, M235T in AGT gene, and A1166C in AGTR gene) were analysed. The initial and last clinical states were classified into 4 groups as follows A, normal; B, minor urinary abnormalities; C, active renal disease (nephrotic-range proteinuria and/or hypertension with serum creatinine $\leq$1.5 mg/dL); D, renal insufficiency. Results : At the onset, the clinical states of the patients were B in 26(35$\%$), C in 46(61$\%$), and D, in 3(4$\%$). The distribution of the RAS gene polymorphism of HSPN were not different from that of 100 healthy control subjects. At the last follow-up, the clinical states of the patients were A in 23(31$\%$), B in 38(50$\%$), C in 9(12$\%$), and D in 5(7$\%$). A multiple logistic regression identified age at the onset and initial urine protein excretion as significant prognostic factors. Analysis of genotypes of the 3 RAS genes as prognostic values revealed no statistical significance. Conclusion : Older age at onset and severe proteinuria were identified as poor prognostic factors of childhood HSPN. Implication of the RAS gene polymorphism In HSPN could not be validated in this small-scale retrospective study. (J Korean Soc Pediatr Nephrol 2005;9:183-192)

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.48-55
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• 2002

Purpose: Thin glomerular basement membrane nephropathy (TGBMN) is recognized as the leading cause of microscopic hematuria in both children and adults. However thinning of glomerular basement membrane (TCBM) has been found in healthy adult and also is known to be associated with various renal diseases such as Alport syndronh, IgA nephropathy and mesangial proliferative glomerulonephritis. The association of TGBM with minimal change nephrotic syndrome (MCNS) has been very rare so that the present study was undertaken to determine the relationship between TGBM and MCNS. Methods: The study population consisted of 49 children with biopsy- proven MCNS who have been admitted to the pediatric department of Kyungpook University Hospital during the past 5 years from 1997 to 2001. Group I consisted of 8 children associated with TGBM and Group II 41 children without TCBM. Various parameters such as age of illness, duration from discovery of illness to the time of biopsy, family history of hematuria and other laboratory tests were compared between these two groups and the following results were obtained. Results: Age distribution showed slightly older age in Group I ($7.1{\pm}3.5$ years) compared to Group II ($4.8{\pm}2.9$ years). However this was not statistically different (P=0.056). Family history of hematuria was noted in 2 cases in Group II. Though statistically not significant, hematuria was seen in 2 out of 8 cases ($25\%$) in MCNS children with TGBM, compared to 7 out of 41 cases ($17\%$) with MCNS children without TGBM. Other parameters such as BUN, creatinine, 24 hours urine protein excretion, serum protein, albumin, cholesterol, and T4/T8 ratio, showed no difference. Also renal biopsy finding showed no significant difference and the thickness of glomerular basement membrane in Croup I was $188{\pm}30nm$. Conclusion: TGBM was found in 8 out of 49 children with MCNS ($16.3\%$). And this high frequency of occurrence indicates that these association is not an incidental findings. Typical clinical findings of TCBMN was not noted in all of the 8 children with MCNS associated with TGBM, suggesting that thinning of glomerular basement membrane (TCBN) is secondary to rather than the cause of MCNS. (J Korean Soc Pediatr Nephrol 2002;6: 48-55)

• The Korean Journal of Physiology
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• v.25 no.2
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• pp.189-200
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• 1991

During the past few years it has been proposed that lithium clearance can be used as a reliable measure for the outflow of tubular fluid from the proximal tubule. This study was aimed to characterize the inflow dependent reabsorption of Na in renal tubule beyond the proximal tubule. For this purpose, lithium clearance was used as a measure for the inflow from the proximal tubule and the changes in reabsorption fraction of Na and water were determined in rabbits. Rabbits were pretreated with hypotonic saline solutions for an hour (50 mM/L NaCl, 20 ml/hr/kg). And then a hypertonic solution of 500 mM/L NaCl (20 ml/kg) was administered intraperitoneally in conjunction with a bolus of LiCl solution (2 mM/kg, i.v.) for conditioning the $C_{Li}$ and urine flow rate. To rule out the effect of $Li^+$ on tubular functions, a bolus of NaCl solution (2 mM/kg, i.v.) was administered. Fifteen, thirty, and sixty minutes after injection of hypertonic saline arterial blood and urine samples were taken. Urinary and plasma concentrations as well as urinary output of $Li^+,\;Na^+\;and\;K^+$ were measured. From these $C_{Li},\;C_{Na}$ and the reabsorption fraction of Na and water $(Fr_{Na}\;&\;FrH_2O)$ were calculated. These results were compared with those from control groups in which the same amount of isotonic saline (145 mM/L NaCl) and of 15% dextran solution were administered in the same way as that in experimental group. Followings are the results obtained. 1) The plasma concentration of $Na^+$ in rabbits injected with hypertonic saline reached the peak value after 15 min and thereafter no significant change was observed. Hematocrit values did not show any change, while urinary excretion of $Na^+$ increased markedly during the first 15 min and decreased thereafter. These results were not affected by an injection of a small amount of LiCl. 2) The clearances of $Li^+,\;Na^+\;and\;K^+$ in rabbits injected with hypertonic saline and LiCl solution decreased. 3) In spite of the variation in $C_{Li},\;Fr_{Na}$ did not show any significant change while $FrH_2O$ increased gradually. 4) $C_{Li}$ decreased also in rabbits received isotonic saline. $Fr_{Na}$ tended to be higher than that in hypertonic saline group, while $FrH_2O\;and\;Fr_{Na}$ did not associated with the decrease in $C_{Li}$. 5) $C_{Li}$ of the rabbits received dextran solution fluctuated persistently and $Fr_{Na}\;and\;FrH_2O$ did not change in along with $C_{Li}$ although $Fr_{Na}$ had a tendency to be higher than that in hypertonic saline group. 6) From the above results it was concluded that: (a) In rabbits with normal body store of $Na^+$, the $Fr_{Na}$ of renal tubule beyond proximal tubule. calculated from $C_{Li}$ as a measure of inflow from proximal tubule is constant in spite of variations in $C_{Li}$. (b) The $FrH_2O$ calculated from $C_{Li}$ is dependent largely upon ADH rather than inflow from proximal tubule. (c) When there is a decrease in plasma $Na^+$ concentration or ineffective body fluid. $Li^+$ reabsorption may occur in the thick segnent of Henle's loop and hence the determination of $Fr_{Na}$ and $FrH_2O$ will not be easy one, but $Fr_{Na}$ is constant under the same experimental conditions.

• The Korean Journal of Physiology
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• v.24 no.2
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• pp.319-329
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• 1990

Effects of atrial natriuretic peptide (ANP) on blood pressure, plasma lenin activity, aldosterone and renal excretion were compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar rats fed low, medium or high sodium diet (2, 10, 25 mmol NaCl/100g diet) for 6 weeks. ANP infusion (380 ng/kg/min for 20 min) produced reductions in blood pressure, plasma renin activity, and aldosterone level, but marked increases in hematocrit, urine flow, and excretions of sodium and potassium. The low sodium group showed a significantly enhanced aldosterone lowering effect of ANP than the high sodium group. However, three salt groups showed no difference in effects of ANP on blood pressure, plasma renin activity, hematocrit and diuresis. Natriuretic response to ANP was significantly greater in the high salt-than in the low sait-SHR, but was not different between the Wistar salt groups. There were strain differences in effects of ANP: SHR showed greater responses of blood pressure and natriuresis than Wistar rats. Above results indicate that aldosterone-lowering and natriuretic effects of ANP were modifed by different dietary sodium intakes. However, blood pressure- and renin-lowering, or diuretic effects of ANP were not affected by dietary sodium intakes. The mechanisms whereby dietary sodium intakes alter the effects of ANP in the pathogenesis of hypertension are not clear.