Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Development and implementation of standardized method for detecting immunogenicity of acellular pertussis vaccines in Korea

PURPOSE: There is no standard method for confirming the immunogenicity of acellular pertussis vaccines. We tried to develop a local standard method for evaluating the immunogenicity of the three-component of acellular pertussis vaccines which was developed by a Korean local company. MATERIALS AND METHODS: The developed pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) were evaluated by in-house enzyme-linked immunosorbent assay (ELISA) using 189 negative sera, 25 positive sera, and 73 paired sera (pre- and post-Tdap [tetanus, diphtheria, and acellular pertussis] vaccinated sera). ELISA units were calculated by the reference line method, compared with World Health Organization reference sera, and the cut-off value was calculated using negative sera. RESULTS: When compared to National Institute for Biological Standards and Control control antigen (NIBSC) control antigens, the developed pertussis toxin (PT) and filamentous haemagglutinin (FHA) antigens were 203.48 and 61.60 IU/µg, respectively. Each in-house ELISA was established by validating the coefficients of variation % (PT, 11.53%; FHA, 8.60%; pertactin [PRN], 9.86%) obtained from the results of inter- and intra-assay variation. Also, the cut-off values of PT, FHA, and PRN were 11.65, 38.95, and 5.66 EU/mL, respectively. The distributions of antibody levels in paired showed that 93.15% (68/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were higher than a 100% increase after vaccination. Additionally, the values of 89.04% (65/73) in anti-PT IgG, 97.26% (72/73) in anti-FHA IgG, and 100% in anti-PRN IgG were below each cut-off point. CONCLUSION: We established an in-house ELISA method using self-developed antigens, and these immunoassays have provided a way to standardize measuring the immunogenicity of newly developed vaccines, through single- and dual-serology.

Enzyme-linked immunosorbent assay for detecting anti-pertussis toxin antibody in mouse

PURPOSE: Although the DTaP and Tdap vaccines used to prevent pertussis have been used for a long time, there is no standard method for measuring pertussis antigens. Therefore, this preliminary study was conducted to develop an enzyme-linked immunosorbent assay method using an animal model for measuring antibodies against pertussis toxin, the most important pertussis pathogenic antigen, in the sera of vaccinated mice. MATERIALS AND METHODS: Bordetella pertussis Tohama phase I was cultured for 24–30 hours, and then pertussis toxin was purified from the culture medium by chromatography. Purified pertussis toxin was diluted in phosphate-buffered saline-coating buffer, and 100 µL of diluted pertussis toxin was added to each well and reacted at room temperature for 4 hours. Positive serum was diluted to 1/1,250–1/80,000 and negative serum was diluted to 1/50 to determine the coating concentration with the optimal signal/noise ratio. Optimal test conditions were confirmed from the dilution factors of the secondary antibody and streptavidin horseradish peroxidase (SA-HRP). RESULTS: Optimal conditions were as follows: 4 µg/mL for coating antigen; 1/40,000 for secondary antibody; and 1/1,000 for the SA-HRP dilution factor. Comparison of the sera obtained from mice treated with a developing vaccine and commercial vaccine with National Institute for Biological Standard and Control standard serum under the established conditions showed the following results: 1,300.62, 534.94, and 34.85, respectively. CONCLUSION: The method developed in this study is suitable for measuring anti-pertussis toxin antibodies and may be applicable for clinical sample analysis or indirect diagnosis of pertussis.

Amyloidosis in a Whooper swan (Cygnus cygnus)

Two Whooper swan (Cygnus cygnus) died after suffering from pododermatitis, lethargy, and ataxia; necropsy was performed. Grossly, the liver was swollen and firm. The kidney and spleen were also enlarged and a pale tan color. On histopathologic examination with Congo red staining, amyloidosis was noted in liver, spleen, and kidney. In addition, marked osseous metaplasia was present in the liver. Based on these results, systemic amyloidosis involving liver, spleen, and kidney with osseous metaplasia in the liver was diagnosed. Study results indicate that an inflammatory reaction associated with pododermatitis had a role in the amyloidosis in this particular case.

A Case of Acute Liver Failure Associated with Methimazole in Patient with Underlying Liver Disease

We report a case of methimazole-induced acute hepatic failure, which occurred 4 days after initiation of drug in a 51-year-old man with hyperthyroidism. Liver function was evaluated before taking methimazole, total bilirubin was 14.2 mg/dL. This finding suggested toxic hepatitis d/t herbal medication or unknown liver disease. He was treated with methimazole with increasing doses from 15 to 45 mg/day, he developed liver failure gradually, despite of suspending methimazole. From the time of admission, his liver function test was abnormal and liver cirrhosis was suspected by liver sonography. With aggravated liver function, he died of renal failure, sepsis of unknown origin and respiratory failure. Fulminant hepatitis rarely occurs in methimazole users, and spontaneous recovery is expected. But this case shows that methimazole-induced hepatotoxicity with possible underlying liver disease could increase the risk of poor outcomes. And in case of continued deterioration of liver function, prompt liver transplatation should be considered.

Effects of remifentanil on emergence characteristics from anesthesia in cervical spine surgery: a comparison of remifentanil- and sevoflurane-based anesthesia

BACKGROUND: Smooth and rapid emergence from anesthesia without bucking, agitation or pain is ideal in terms of neck stabilization and early neurological assessment on potential complications immediately after cervical spine surgery. This study was designed to compare the severity of bucking, the level of awakening, and pain during the emergence from anesthesia with sevoflurane, remifentanil supplemented with sevoflurane or remifentanil supplemented with propofol in patients undergoing cervical spine surgery. METHODS: Sixty American Society of Anesthesiologists physical status class I to II patients undergoing cervical spine surgery were randomized into one of three groups: maintenance solely with sevoflurane (group S, n = 20); maintenance with remifentanil and supplementation with less than 1% sevoflurane (group RS, n = 20); and maintenance of anesthesia with remifentanil and propofol target controlled infusion (TCI) (group RP, n = 20). The severity of bucking, the level of awakening, and the perception of pain during the emergence phase were assessed using predetermined scoring scales by a nurse blinded to the method of anesthesia. RESULTS: The bucking, level of awakening, pain score were significantly better in both group RP and group RS than in the group S. However there was no significant difference between group RP and group RS. CONCLUSIONS: The quality of emergence from anesthesia in patients with cervical spine surgery could be improved with remifentanil-based anesthesia, but no significant differences were found between the propofol TCI and less than 1% sevoflurane as a concomitant hypnotic adjunct.

Acute Pulmonary Edema after Simultaneous Bilateral Percutaneous Nephrolithotomy: A case report / 대한마취과학회지

Percutaneous nephrolithotomy (PCNL) is currently the procedure of choice for the removal of large and complex renal calculi. With recent developments in percutaneous access technique and in equipment for the disintegration of calculi, simultaneous bilateral PCNL has become safe. However the complications include hemorrhage, extravasation and absorption of large volumes of irrigation fluid, fever, infection, colonic perforation and pneumothorax. A 46-year-old, 59 kg, female patient in our care developed acute pulmonary edema after simultaneous bilateral PCNL under general anesthesia. The preoperative chest X-ray was normal. The patient recovered following 36 hours of intensive treatment involving fluid restriction, diuretics, sedation and continuous airway pressure ventilation.

Effect of Anti-inflammatory Drug on the Cyclooxygenase-2 Protein Expression in Lipopolysaccharide-Stimulated Amnion Cells in Culture / 대한주산의학회잡지

No abstract available.

Effect of Pyrimethamine on DNA Synthesis of Germ Cells in Mice Testis / 대한비뇨기과학회지

Pyrimethamine(PYR) produces reversible infertility in mice. The antifertility effect of PYR is due to its antifolate action. PYR causes male infertility in Balb C mice in a dose dependent manner. The present study was performed to determine DNA synthesis of germ cell in mice treated with PYR. For 6-8 weeks adult Balb C mice were administered a PYR dose of 100mg- 200mg/ kg/day suspended in vegetable oil.10 control mice received only vegetable oil without PYR. After 7 weeks administration 28.6% of mice(4/14) administered a PYR dosage of 100mg/kg were infertility, whereas all of those(4/4), 200mg/kg/day were infertile. Morphologic changes of the testis induced by orally administered PYR were spermatogenic arrest and depopulation of germ cell. The incorporation of thymidine into DNA of germ cells was studied by using autoradiography after intraperitoneal injection of 15 Ci of methyl-3H-thymidine. Synthesis of DNA takes place in interphase and early prophase of mitotic phase of germ cell. The synthesis of DNA in spermatogonia reduced in all stage of spermatogenesis in mice treated with PYR due to spermatogenic arrest, compared with that of control mice. These results suggest that reduced synthesis of DNA in spermatogonia by PYR administration caused hypospermatogenesis. PYR represents further approach toward development of male contraceptive.

Alteration of Nerve Growth Factor in the Penis of Rats with Streptozotocin-induced Diabetes / 대한비뇨기과학회지

Insulin and nerve growth factor (NGF) share several properties concerning physiological activity, molecular structure and site of synthesis. Considering the properties that NGF shares with insulin, and the important role it plays on nerve physiology, NGF may participate in the pathophysiology of diabetic neuropathy. We investigated the alterations of NGF in the penis of diabetic rats at 8-week after induction of diabetes with streptozotocin. NGF was determined by sandwich ELISA method. The weight gain reduced significantly in diabetic rats. Diabetic rats showed a significantly reduced NGF content in the penis (62.3% of control, p<0.05 at 8-week after induction of diabetes. These findings suggest that decreased NGF levels in the penis of diabetic rats may be involved in the development of the diabetic neuropathy regarded as important cause of diabetic impotence.

Treatment of Concealed Penis: Adjunctive Suprapubic Lipectomy / 대한비뇨기과학회지

The concealed penis is caused by a prominent suprapubic fat pad in addition to the restrictive fibrous bands of the dartos fascia fixing the shaft of the penis proximally. Anchoring of the skin of the base of the penis to the periosteum of the pubis only does not satisfy the obese patients with concealed penis because the suprapubic fat concealed the penis. We treated 4 obese patients with concealed penis by removing the suprapubic fat and anchoring the skin of the base of the penis to the pubic symphysis. All penes project adequately, and the patient's socialization status and self-image are improved. One patient felt moderate pain in the suprapubic area for 3 months after operation. Other complications such as infection, hemorrhage, and lymphorrhea have not been seen in our practice. We consider that excision of suprapubic fat with sectioning of the tethering dartos bands should be added to anchoring of the skin of the base of the penis to the periosteum of the pubis. Suprapubic lipectomy to excise suprapubic fat seems simple and satisfying. Additional liposuction may be valuable in contouring the adjacent abdominal fat.

A case of cushing's syndrome due to bilateral macronodular adrenocortical hyperplasia associated with empty sella syndrome / 대한내분비학회지

No abstract available.

Fungal peritonitis in patients with continuous ambulatory peritoneal dialysis / 대한신장학회잡지

No abstract available.

A case of cryptococcal peritonitis and meningitis in a CAPD patient with SLE / 대한신장학회잡지

No abstract available.

Four cases of primary malignant lymphoma of the breast / 대한암학회지

No abstract available.

Hemostatic Effect of Endoscopic Local Injection of Hypertonic Saline - Epinephrine Solution in Peptic Ulcer Bleeding / 대한소화기내시경학회지

To date several agents have been used to achieve hemostasis in patients with bleeding peptic ulcers using endoscopic sclerotherapy techniques. In this study, the efficacy of endoscopic local injections of hypertonie saline-epinephrine(HS-E) solution, consisting of 9 volume of 3% sodium chloride and 1 volume of 1: 1000 epinephrine, on the base of the ulcer around bleeding vessel was assessed. During the period between April 1989 and July l992, 127 patients were admitted to the study. Ninety-six of these patients underwent endoscopic treatmeat(endoscopic treatment group), while the other 31 cases received conservative treatment only(conservative treatment group). (continue...)

Scanning electron microscopy of Malassezia furfur in tinea versicolor

Morphologic features of Malassezia(M.) furfur in the horny layer from clinical lesions of tinea versicolor were examined by scanning electron microscopy and compared with the appearance of fungus in the horny layer from normal skin and in culture. In skin lesions of tinea versicolor, M. furfur showed a variety of growth and reproduction patterns. Although the main patterns were budding yeast forms, various patterns suggesting yeast-mycelial conversion were observed and mycelial hyphae were more prominent in the deeper horny layer than in the superficial layers. However, in the skin of normal persons and in culture, M. furfur existed only as yeast forms and no mycelial hyphae or yeast-mycelial conversion forms were seen. This suggests that the morphologic change of M. furfur, from a yeast form to a mycelial hypha one, may play a role in the induction of the clinical lesion of tinea versicolor.

Scanning electron microscopy of Malassezia furfur in tinea versicolor

Morphologic features of Malassezia(M.) furfur in the horny layer from clinical lesions of tinea versicolor were examined by scanning electron microscopy and compared with the appearance of fungus in the horny layer from normal skin and in culture. In skin lesions of tinea versicolor, M. furfur showed a variety of growth and reproduction patterns. Although the main patterns were budding yeast forms, various patterns suggesting yeast-mycelial conversion were observed and mycelial hyphae were more prominent in the deeper horny layer than in the superficial layers. However, in the skin of normal persons and in culture, M. furfur existed only as yeast forms and no mycelial hyphae or yeast-mycelial conversion forms were seen. This suggests that the morphologic change of M. furfur, from a yeast form to a mycelial hypha one, may play a role in the induction of the clinical lesion of tinea versicolor.

A Case of Fungal Granuloma Caused by Trichophyton violaceum / 대한피부과학회지

We report a patient with an unusual manifestation of Trichophyton violaceum infection, who lives in Seoul. An 8-year-old male presented an erythematous nodule on the lower eyelid of the left eye which had persisted for 10 weeks. On physical examination, there was no abnormality except a skin lesion on the eyelid. The skin biopsy of the nodule showed epidermal hyperplasia and granulomatous change in the upper dermis. The biopsy specimen yielded Trichophyton uiolaceum on culture. The skin lesion disappeared 2 months after administration of ketoconazole.