It is well known that renal cell carcinoma shows poor responses upon chemotherapy, and a multidrug-resistance has been suggested as one of the possible mechanisms of these resistances to chemotherapeutics of renal cell carcinoma as well as other malignancies. We tried to measure the expressions of the multidrug resistance gene and p-glycoprotein in human renal cell carcinoma cell lines, and to evaluate whether various multidrug resistance modulators could enhance the cytotoxicity of adriamycin. Four human renal cell carcinoma cell lines, A-498, A-704, Caki-1, Caki -2, were used and verapamil, cyclosporin A, cefoperazone, quinidine were used as the multidrug resistance modulating agents. Polymerase chain reaction was used to detect the expression of MDR1 mRNA, and measurement of p-glycoprotein was done by FACScan using JSB-1 monoclonal antibody. Cytotoxicity of adriamycin was measured by MTT colorimetric assay. Expression of MDR1 mRNA was observed in A-704, and A-498, but was not detected in Caki-1 and Caki-2. Expression of p-glycoprotein was found in A-498 and A-704, but not in Caki-1 and Caki-2. The relative expression rates of MDR1 and p-glycoprotein in A-498, A-704, Caki-1 and Caki-2 comparing to KB-3-1, the negative control cell line were 1.75, 2.44, 0.98, 0.97 and 1.31, 1.12, 1.08, 0.78 respectively. From these observations, A-498 was selected as MDR positive cell line and Caki-2 as MDR negative cell line, and then a study was performed to evaluate the effect of multidrug resistance modulators on the cytotoxicity of adriamycin upon these cell lines. Verapamil, in concentration of 0.1/microM, did not enhance the anticancer effect of adriamycin on A -498 cells, but with the concentration of 1 microM and 10microM, it decreased IC(50) of adriamycin from 0.43 microgram/ml when only adriamycin was used to 0.21 and 0.16, showing the dose modification effect of 2. 05 and 2.68 respectively (p<0.05, by Mann Whitney test). Cyclosporin A, in all the concentration of 0.3, 1, 3 microM, also decreased IC(50) of adriamycin on A-498 cells to 0.17, 0.14, 0.15 microgram/ml respectively, showing the dose modification effect of 2.53 to 3.07 (p<0.05, by Mann Whitney test). But the cytotoxicity of adriamycin was not influenced by cefoperazone and quinidine. In Caki-2 cells, in which MDR1 and p-glycoprotein expression were barely detected, verapamil and cyclosporin A as well as cefoperazone and quinidine did not show any effect upon the cytotoxicity of adriamycin. Considering above results, verapamil and cyclosporin A seem to be an effective multidrug resistance modulating agents to enhance the cytotoxicity of adriamycin in renal cell carcinoma showing MDR1 and p-glycoprotein expression, and further studies including in vivo study are needed before clinical trials to improve chemotherapeutic effect upon renal cell carcinoma.
Carcinoma, Renal Cell* ; Cefoperazone ; Cell Line* ; Cyclosporine ; Doxorubicin* ; Drug Resistance, Multiple* ; Drug Therapy ; Genes, MDR ; Humans* ; P-Glycoprotein ; Polymerase Chain Reaction ; Quinidine ; RNA, Messenger ; Verapamil

Glutathione based detoxification system in tumor cells was proposed as one of the drug resistance mechanisms and appeared to play as an obstacle in anticancer chemotherapy. It was evaluated that depletion of glutathione content in MBT-2, murine bladder tumor cells by buthionine sulfoximine could enhance the chemotherapeutic effect of carboplatin. Glutathione contents were measured by an enzymatic assay and chemosensitivity was assessed by MTT colorimetric test. Twenty-four hours exposure to 1, 2.5, 5 and 10uM buthionine sulfoximine reduced intracellular glutathione levels to 84.9, 24.8, 18.3 and 11.0% of the control level, respectively, in MBT-2 tumor cell line. Pretreatment with 2.5, 5 and 10uM buthionine sulfoximine for 24 hours and continuous exposure to buthionine sulfoximine and carboplatin for 72 hours potentiated the carboplatin cytotoxicity by 1.26, 1.56 and 1.90 folds, respectively. The potentiation of antitumor effect of carboplatin in C3H/He mice MBT-2 tumor by buthionine sulfoximine was evaluated with the use of tumor growth and tumor volume-doubling time. Glutathione contents in the tumor and liver were reduced to 12.8 and 21.8% of the control level by oral administration of 30mM buthionine sulfoximine for 5 days. No significant change in serum creatinine levels and renal histology was found in the mice treated with buthionine sulfoximine. Combination of carboplatin and buthionine sulfoximine significantly reduced tumor growth rate and delayed tumor volume-doubling time compared to carboplatin alone(p <0.05), while buthionine sulfoximine alone did not influence the tumor growth(p >0.05). Weight loss or mortality due to carboplatin and buthionine sulfoximine administration was not noted. Since buthionine sulfoximine significantly enhanced the effect of carboplatin on murine bladder tumor without apparent toxicity, combination of buthionine sulfoximine and carboplatin could be a new strategy in chemotherapy against advanced bladder cancer.
Administration, Oral ; Animals ; Buthionine Sulfoximine* ; Carboplatin* ; Cell Line, Tumor ; Creatinine ; Drug Resistance ; Drug Therapy ; Enzyme Assays ; Glutathione ; Liver ; Mice ; Mortality ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Weight Loss

OBJECTIVES: Although risk factors for coronary artery disease are also associated with increased carotid intima-media thickness (IMT), there is little information available on the asymptomatic, young adult population. We examined the association between multiple cardiovascular risk factors and the common carotid IMT in 280 young Korean adults. METHODS: The data used for this study was obtained from 280 subjects (130 men and 150 women) aged 25 years who participated in the Kangwha Study follow-up examination in 2005. We measured cardiovascular risk factors, including anthropometrics, blood pressure, blood chemistry, carotid ultrasonography, and reviewed questionnaires on health behaviors. Risk factors were defined as values above the sex-specific 75th percentile of systolic blood pressure, body mass index, total cholesterol/high-density lipoprotein cholesterol ratio, fasting blood glucose and smoking status. RESULTS: The mean carotid IMT+/-standard deviation observed was 0.683+/-0.079 mm in men and 0.678+/-0.067 mm in women (p=0.567) and the evidence of plaque was not observed in any individuals. Mean carotid IMT increased with an increasing number of risk factors(p for trend <0.001) and carotid IMT values were 0.665 mm, 0.674 mm, 0.686 mm, 0.702 mm, and 0.748 mm for 0, 1, 2, 3, and 4 to 5 risk factors, respectively. The odds ratio for having the top quartile carotid IMT in men with 3 or more risk factors versus 0-2 risk factors was 5.09 (95% CI, 2.05-12.64). CONCLUSIONS: Current findings indicate the need for prevention and control of cardiovascular risk factors in young adults and more focus on those with multiple cardiovascular risk factors.
Adult ; Blood Pressure ; Body Weights and Measures ; Cardiovascular Diseases/*epidemiology ; Carotid Arteries/*physiopathology/ultrasonography ; Female ; Health Behavior ; Hematologic Tests ; Humans ; Korea/epidemiology ; Male ; Risk Factors ; Tunica Intima/*physiopathology

PURPOSE: To determine the efficacy of photodynamic therapy (PDT) with verteporfin (Visudyne(R), Norvatis Ophthalmics AG, Hettingen, Switzerland), a benzoporphyrin derivative, in the treatment of corneal neo-vascularization (CN) in a rabbit eye model. METHODS: CN was induced by placing instrastromal sutures in the cornea. Two weeks after suturing, verteporfin was administrated intravenously and 1 hour later, the right eye (treated group) was exposed to a laser with a 689 nm wavelength, and the left eye was used as the control. The changes in CN were analyzed using biomicroscopy and optical microscopy in twelve rabbits. RESULTS: The mean percentages of the neovascular area in the control and treated groups were 96.4 +/- 1.9% and 90.3 +/- 3.5% (P=0.009) at three days after the PDT, 88.6 +/- 4.6% and 71.6 +/- 6.2% (P<0.001) at one week, and 76.8 +/- 4.4% and 43.6 +/- 15.1% (P<0.001) at two weeks, respectively. Optical microscopy showed significant differences between the control and treated group in terms of the area and number of CN (P<0.05). CONCLUSIONS: PDT with verteporfin is a safe and effective procedure for regressing CN. However, a further study will be necessary.
Animals* ; Cornea ; Corneal Neovascularization* ; Microscopy ; Photochemotherapy* ; Rabbits ; Sutures

BACKGROUND AND OBJECTIVES: The study investigated the effect of mesenchymal stem cells (MSCs) or fibrin glue on tunnel widening after anterior cruciate ligament (ACL) reconstruction compared with biologic free control without any biologic agents in the rabbit model. METHODS AND RESULTS: ACL reconstructions were performed in 18 New Zealand white rabbits. All animals were divided into 3 groups according to the following reconstruction conditions and euthanized 12 weeks postoperatively for radiologic and histologic analyses. Thirty-two knees (control group=10; fibrin group=11; MSCs group=11) were finally evaluated. On micro-CT scan, mean femoral tunnel widening on oblique-sagittal image was 0.7±0.4 mm in the control group, 0.22±0.1 mm in the fibrin group and 0.25±0.1 mm in the MSCs group (p=0.001). Fibrin group and MSCs group showed significant differences compared with control group (p=0.002, 0.002). Mean tibial tunnel widening on oblique-sagittal image was 0.76±0.5 mm, 0.27±0.1 mm and 0.29±0.2 mm in the control, fibrin and MSCs group. Fibrin and MSCs group showed significant differences compared with control group (p=0.017, 0.014). Hounsfield Units (HU) were not significantly different between 3 groups (p>0.05). Histological analysis revealed that the architecture of graft in the MSCs group featured hypercellularity and compact collagen deposit. CONCLUSION: ACL reconstruction using MSCs seemed decrease tunnel widening in rabbit model. Further study with large animals is required to confirm efficacy on decreasing tunnel widening.
Animals ; Anterior Cruciate Ligament Reconstruction ; Anterior Cruciate Ligament ; Biological Factors ; Collagen ; Fibrin ; Fibrin Tissue Adhesive ; Knee ; Mesenchymal Stromal Cells ; Rabbits ; Transplants

Purpose: Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma. Methods: We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy. Results: Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each. Conclusions Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.

BACKGROUND: Dyslipidemia is a disorder of lipid metabolism, including elevated total cholesterol, elevated triglyceride, elevated low density lipoprotein cholesterol (LDL-C), and decreased high density lipoprotein cholesterol (HDL-C). The objective of this study was to investigate recent changes in the prevalence of dyslipidemia and also the rates of awareness, treatment, and control of dyslipidemia among Korean adults. METHODS: Dyslipidemia is defined according to the National Cholesterol Education Program-Adult Treatment Panel III as total cholesterol > or =240 mg/dL, LDL-C > or =160 mg/dL, HDL-C <40 mg/dL, and triglyceride > or =200 mg/dL. The prevalence of dyslipidemia was estimated for adults aged > or =20 years using the Korea National Health and Nutrition Survey (KNHANES) in 1998 (n=6,923), 2001 (n=4,882), and 2005 (n=5,323). Rates of awareness, treatment and control of dyslipidemia were calculated for adults aged > or =30 years using the KNHANES in 2005 (n=4,654). RESULTS: The prevalence of dyslipidemia (aged > or =20 years) increased from 32.4% in 1998 to 42.6% in 2001 and 44.1% in 2005. Compared with the KNHANES in 1998, the prevalence of dyslipidemia was 47% (95% confidence interval [CI], 35% to 59%) higher in 2001 and 61% (95% CI, 49% to 75%) higher in 2005. In 2005, only 9.5% of people with dyslipidemia were aware of the disease, 5.2% used lipid-lowering medication, and 33.2% of patients with treatment reached treatment goals. CONCLUSION: The prevalence of dyslipidemia in Korea gradually increased between 1998 and 2005. These findings suggest that more intense efforts for the prevention and treatment of dyslipidemia may lead to further improvement in the management of dyslipidemia.
Adult ; Aged ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Dyslipidemias ; Humans ; Korea ; Lipid Metabolism ; Lipoproteins ; Nutrition Surveys ; Prevalence

PURPOSE: To investigate surgical outcomes between retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) groups for a main stone sized 15 to 30 mm and located in the lower-pole calyx. MATERIALS AND METHODS: Patients who underwent PNL or RIRS for a main stone sized 15 to 30 mm and located in the lower-pole calyx were retrospectively reviewed. Each patient in the RIRS group was matched to one in the PNL group on the basis of calculated propensity scores by use of age, sex, body mass index, previous treatment history, stone site, maximum stone size, and stone volume. We compared perioperative outcomes between the unmatched and matched groups. RESULTS: Patients underwent PNL (n=87, 66.4%) or RIRS (n=44, 33.6%). After matching, 44 patients in each group were included. Mean patient age was 54.4+/-13.7 years. Perioperative hemoglobin drop was significantly higher and the hospital stay was longer in the PNL group than in the RIRS group. The operative time was significantly longer in the RIRS group than in the PNL group. Stone-free rates were higher and complications rates were lower in the RIRS group than in the PNL group without statistical significance. The presence of a stone located in the lower-anterior minor calyx was a predictor of stone-free status. CONCLUSIONS: RIRS and single-session PNL for patients with a main stone of 15 to 30 mm located in the lower-pole calyx showed comparable surgical results. However, RIRS can be performed more safely than PNL with less bleeding. Stones in the lower-anterior minor calyx should be carefully removed during these procedures.
Adult ; Aged ; Female ; Hemoglobins/metabolism ; Humans ; Kidney Calculi/pathology/*surgery ; Length of Stay/statistics & numerical data ; Male ; Middle Aged ; Nephrectomy/adverse effects/*methods ; Nephrostomy, Percutaneous/adverse effects/*methods ; Prognosis ; Propensity Score ; Retrospective Studies ; Treatment Outcome

Although a paradoxical response of tuberculosis to antituberculous therapy is not a rare phenomenon, it can be a clinical challenge to differentiate a paradoxical response from treatment failure. A 25-year-old woman was admitted for miliary lung nodules and multiple intracranial nodules. Antituberculous treatment was started with a preliminary diagnosis of tuberculosis based on the history and clinical findings. After one month, the miliary lung nodules improved while the intracranial nodules increased in size and number. Based on a stereotactic biopsy, it was confirmed that the intracranial lesions were tuberculomas. Although the therapeutic regimen was not changed, the symptoms eventually were ameliorated and the intracranial nodules improved two months later.
Adult ; Biopsy ; Female ; Humans ; Lung ; Treatment Failure ; Tuberculoma ; Tuberculoma, Intracranial ; Tuberculosis

Pancreatic duct stones are commonly associated with recurrent pancreatitis. They are believed to develop as a result of the calcification of an intraductal protein plug. A choledochal cyst is a relatively rare anomaly usually presenting with abdominal pain, jaundice and palpable mass. APBDU (anomalous pancreaticobiliary ductal union) is frequently associated with various pancreatobiliary diseases, including choledochal cyst, biliary tumor, pancreatitis and pancreas divisum. We report a 48-year-old woman who presented with right upper quadrant pain with a pancreatic duct stone, a choledochal cyst and APBDU. She underwent endoscopic pancreatic sphincterotomy, a surgical choledochal cyst excision and Roux-en-Y choledochojejunostomy.
Female ; Humans ; Cysts