Penal provisions of Bioethics Law: problems and improvements

Chapter 9 of the Bioethics Law has several problems due to strict research standards and strong penalties. Therefore, biomedical researchers in Korea have raised several objections to this Law. To make matters worse, the normative power of the Law is significantly diminished because norms and penalties are divergent. Articles 2, 24, 26, 27, 28, and 32 of the Law require amendment because the current regulations on sperm retrieval, sperm management, and sperm use are insufficient. At a minimum, legislation for artificial insemination and in vitro fertilization should be consolidated. It is also necessary for sperm researchers and donors to be notified of their rights and duties. Section 9 of the Bioethics Law should therefore be amended. In particular, its legal formulation should be modified in order to enhance the effectiveness of bioethics law. This is in accord with the spirit of the Constitution. The principle of proportionality should be maintained. The statutory form should be revised to the level of abortion. Not only are the actors in embryo research diverse, including medical personnel, medical institutions, donors, veterans, and mediators, but embryo research involves multiple behavioral aspects, including intentional acts and negligence (violation of state duty). Excessively free-form activity is prescribed. Although the value of life is important, heavy punishment violates human dignity and human values. This legislation should not reflect to be grounded in emotional reactions such as anger.

Penal provisions of Bioethics Law: problems and improvements

Chapter 9 of the Bioethics Law has several problems due to strict research standards and strong penalties. Therefore, biomedical researchers in Korea have raised several objections to this Law. To make matters worse, the normative power of the Law is significantly diminished because norms and penalties are divergent. Articles 2, 24, 26, 27, 28, and 32 of the Law require amendment because the current regulations on sperm retrieval, sperm management, and sperm use are insufficient. At a minimum, legislation for artificial insemination and in vitro fertilization should be consolidated. It is also necessary for sperm researchers and donors to be notified of their rights and duties. Section 9 of the Bioethics Law should therefore be amended. In particular, its legal formulation should be modified in order to enhance the effectiveness of bioethics law. This is in accord with the spirit of the Constitution. The principle of proportionality should be maintained. The statutory form should be revised to the level of abortion. Not only are the actors in embryo research diverse, including medical personnel, medical institutions, donors, veterans, and mediators, but embryo research involves multiple behavioral aspects, including intentional acts and negligence (violation of state duty). Excessively free-form activity is prescribed. Although the value of life is important, heavy punishment violates human dignity and human values. This legislation should not reflect to be grounded in emotional reactions such as anger.

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic beta-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic beta-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

Liver Transplantation in Patients over Sixty Years of Age

PURPOSE: Orthotopic liver transplantation is considered a standard procedure for patients with end-stage liver disease. Liver transplantation in older patients has increased, with generally acceptable results. In Korea we have an aging population. In this study, we retrospectively reviewed the results of liver transplantation in patients more than 60 years of age at Asan Medical Center. METHODS: Fifty-four patients, age 60 and over, received a liver transplantation at Asan Medical Center between January 1998 and June 2005. We retrospectively reviewed the medical records of these patients. All patients were assessed according to the following variables: age, gender, clinical features, indications for transplantation, surgical findings, the hospital stay following liver transplantation, days in the intensive care unit, complications, and survival. RESULTS: The mean age of the recipients was 62.4 years. The transplant indications were 28 cases of hepatocellular carcinoma and 15 of HBV related cirrhosis. There was postoperative mortality (up to 3 months) in seven patients (13.21%). The mean ICU and hospital stays were 8.04 and 36.8 days, respectively. Overall, the patient survival rates at 1, 3 and 5 years was 83.02%, 75.47% and 75.47%, respectively. CONCLUSIONS: The results of this study showed that chronologic age should not be a contraindication to liver transplantation, especially if the pretransplant evaluation shows no comorbid disease that could increase the mortality rate.

Tetanus trismus associated with facial eletrical burn

Tetanus is rare in Korea due to the introduction of vaccination programs and the advancement in public health. Its common signs are trismus, voice disturbance, neck stiffness, and difficulty in swallowing, etc. A 56 years old man was injured by grasping a high voltage electric cable. After the accident, he fell down on a steel plate and had a head trauma. When he visited Emergency Department, there was multiple electric burn wound on left arm and left facial area. He was hospitalized on a department of neurosurgery, because intra cranial hemorrhage was presumed. 12 days later, he was referred to department of OMFS with developed painful masseter spasms and trismus. That night he violently bit his tongue with his denture. Because masseter muscle and temporal muscle constriction was involuntary, tongue was lacerated and denture was distorted. At first we supposed that the symptom was related with neurologic disturbance following head trauma or electric shock. But it was revealed that trismus was caused by tetanus on an electrophysiological test. By using mechanical ventilation and administration of tetanus immunoglobulin, muscle-relaxant, and sedatives at ICU, symptoms had subsided (4-weeks). Because tetanus is rare disease, we rarely suppose tetanus infection to be a cause of a trismus. Especially it is more difficult to diagnose in patient who has head trauma, burn and neurologic problem as in this case.

Analysis of Relationship between Positive T Lymphocytotoxic and/or B Lympocytotoxic Cross- Match and Acute Rejection in Adult-to-Adult Living Donor Liver Transplantation / 대한이식학회지

PURPOSE: The influences of lymphocytotoxic cross-match on survival or acute rejection after adult-to-adult living donor liver transplantation (LDLT) have not been fully studied and there have been some arguments about its influence. In this study, we retrospectively investigated the influence of lymphocytotoxic cross-match in LDLT and assessed the survival of recipients and the incidence of acute rejection. METHODS: 142 adult-to-adult LDLT were performed in adult patients in our institution between January 2003 and December 2003. Among them, HLA cross-matching tests were done in 78 cases and we analyzed their data of HLA cross-match. Recipients were 62 males and 16 females, and their mean age was 50 7 years. Most of the donors were genetically related to the recipients. Lymphocyototxic cross-match was performed according to the standard National Institutes of Health technique. The cross-match test was interpreted as positive when more than 20% of the donor lymphocytes were killed by the recipient serum, Acute cellular rejection was defined as a biopsy-proven episode and graded according to the Banff schema. RESULTS: The results of positive T and/or B cell cross-match observed in only 5 cases (6.4%). In this series, there were episodes of acute rejection in 10 recipients (13.6%) after 1~9 months, but all of 10 had revealed negative results of T and B cell cross-match. Additionally, the results of positive T and/or B cell cross-match did not change the incidence of acute rejection. All of the recipients undergone acute rejection were treated successfully using steroid bolus therapy and survive to date. CONCLUSION: According to our preliminary results, positive T and/or B cell cross-match did not give significant impact upon either the incidence of acute rejection or the survival rate in our series with 13% incidence of acute rejection and 5% mortality.

Scoring Method for Predicting the Mortality of Premature Infants: Comparison with CRIB

PURPOSE: To develop a new scoring method for predicting the mortality at 28 days of life in premature infants. METHODS: From January 2000 to August 2001 (period I), medical records of 138 premature infants less than 32 weeks' gestation admitted at Asan Medical Center were reviewed retrospectively, and a predictive model (named as KCRIB28) was developed based on several steps of regression analysis. From January 2001 to December 2002 (period II), KCRIB28 was validated for 99 premature infants admitted at Ulsan University Hospital using retrospective cohort study, and compared with results of CRIB score for those infants. The primary outcome variable was death at 28 days of life. RESULTS: One hundred twenty seven (92%) of 138 infants during period I and 86 (86.9%) of 99 infants during period II survived over 28 days of life (P=0.07). The mean gestational age and birth weight (+/-SD) were 29.1+/-2.0 weeks and 1.23+/-0.35 kg, respectively, during period I, and 29.6+/-2.0 weeks and 1.37+/-0.46 kg, respectively, during period II. Gestational age, birth weight, 5-min. Apgar score and peak inspiratory pressure divided by birth weight at 12 hours of age were selected as parameters of KCRIB 28. Areas under the receiver operator characteristic curves (AUCs) were 0.84 (SEM, 0.08; 95%CI, 0.77-0.90) during period I and 0.89 (SEM, 0.06; 95%CI, 0.81-0.94) during period II. No differences in AUCs were found between KCRIB 28 and CRIB for patients during period II (P=0.75). CONCLUSION: KCRIB 28 can be used as a valuable measurement to predict the mortality of premature infants at 28 days of life.

Regulation of Prolactin Gene Expression by Hypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Female Rat Pituitary Gland / 대한내분비학회지

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays the role of a hypophysiotropic factor, which regulates the synthesis and secretion of pituitary hormones through the hypothalamo-hypophysial portal system. No clear evidence has yet been reported regarding the regulation of prolactin (PRL) by PACAP. In the present study, we tested a hypothesis that PACAP regulates the synthetic machinery of PRL during the estrus cycle and pubertal process using intracerebroventricular (i.c.v.) injection of an antisense oligodeoxynucleotide (ODN) against type I PACAP receptor (PAC1). METHODS: An RNase protection assay (RPA) was used to determine the pattern of hypothalamic PACAP and PAC1 mRNA expressions during the estrus cycle. Antisense PAC1 ODN was administered via i.c.v. injection to the female rats in normal estrus cycle of pubertal process. Northern blot analysis was used to determine the mRNA ievel of PRL in the pituitary gland. RESULTS: 1) PACAP mRNA in the medial basal hypothalamus was significantly increased at the diestrus I, while PAC1 mRNA showed no significant change. 2) PRL mRNA level of pituitary was increased by an injection of antisense PAC1 ODN at the proestrus and estrus stages. 3) PRL mRNA level of pituitary was significantly decreased by antisense PAC1 ODN injection at stage of prepuberty and initiate puberty, while its level was increased at stage of puberty. CONCLUSION: These data suggest that PACAP suppresses PRL mRNA synthesis through the PAC1 signaling pathway in the certain estrus cycle environments. It may be also involved in the regulation of pituitary PRL gene expression during the pubertal process

Development of Hepatoma-Specific Replication Competent Adenovirus

A prerequisite for the development of a cancer cell selective targeting adenovirus is the generation of adenoviral vectors that lack native receptor binding ability and additionally contain domains redirecting the vector to cancer cell specific receptors. Towards this goal, we have generated an E1B 55kDa-deleted oncolytic and coxoackie and adenovirus receptor (CAR)-binding ablated adenovirus, YKL-K420A. This newly engineered adenovirus resulted in a dramatic reduction of transduction efficiency compared to the control adenovirus, YKL-1, in all of the cell lines tested. The malaria circumsporozoite (CS) protein interacts with glycosaminoglycans (GAG) present on the liver cell surface, and plays a prominent role in sporozoite attachment and invasion into hepatocytes. To redirect the CAR binding ablated adenovirus YKL-K420A to hepatocytes, CS protein epitope (EWSPCSVTCGNGIQVRIK) was incorporated onto the C-terminus of the YKL-K420A fiber protein, generating an YKL-K420A-hepa. The In vitro efficacy and specificity of YKL-K420A-hepa was then evaluated by comparing the cytopathic effect in hepatoma and other cancer cells from different origins. In hepatoma cells, YKL-K420A-hepa exerted upto 20-fold higher cytolytic ability compared to the control adenovirus, YKL-1, in hepatoma cell lines. Treatment with YKL-K420A-hepa also significantly suppressed tumor growth in a hepatoma xenograft tumor model when compared to YKL-1. Taken together, these studies demonstrate that the strategy to alter adenovirus tropism may greatly improve adenoviral utilities in gene therapy applications.

A Clinical Study of Aseptic Meningitis in Ulsan from May to July, 2002

PURPOSE: There occurred an explosive outbreak of aseptic meningitis in Ulsan, in the year of 2002. In this study, we report clinical manifestations, laboratory data and causative viruses of the outbreak. METHODS: Were assessed 371 children with aseptic meningitis who were admitted to the Department of Pediatrics, Ulsan University Hospital in Ulsan between May and July, 2002. We reviewed the sex, age, clinical manifestations, peripheral blood examinations and CSF examinations of the patients. Virus isolation and serotype identification were performed by cell cultures of cerebrospinal fluid and stool. RESULTS: The ratio of males to females was 1.9:1. The majority of aseptic meningitis occurred in children between 1 and 5 years of age with a mean age of 6.8+/-5.1 years. The clinical manifestations was fever, headache, vomiting, and abdominal pain and 16.2% of the patients developed neck stiffness. The mean duration of fever was 3.2 days. The mean value of peripheral blood leukocytes was 10,355+/-4,800/mm3 and the mean value of CRP was 0.96+/-1.67 mg/dL. Initial CSF findings revealed leukocytes 212+/-385/mm3, protein 37.0+/-18.9 mg/dL and glucose 68.3+/-17.6 mg/dL. Viruses were isolated 67(18.1%) out of 371 patients and the serotypes were echovirus 6 in 10 cases, echovirus 9 in 15 cases, echovirus 11 in 4 cases, echovirus 13 in 18 cases, and unclassified enterovirus in 20 cases. CONCLUSION: Aseptic meningitis was prevalent in Ulsan, in the year of 2002. The clinical manifestations and the laboratory findings of the patients were compatible with those of previous reports. The causative viruses were echovirus 6, echovirus 9, echovirus 11, echovirus 13 and unclassified enterovirus.

A Case of Transfusion Transmitted Malaria Infection in Extremely Low Bith Weight Infant

The incidence of malaria in Korea is significantly on the rise since its reemergence in 1993 and no screening test that can prevent the infection has been available. Very low birth weight infants are especially susceptible to malaria infection due to transfusions from multiple donors. We report a case of transfusion transmitted Plasmodium vivax infection in a 120-day-old infant of a gestational age 24 weeks with birth weight of 700 gm who was successfully treated with hydroxychloroquine.

Histochemical Detection of Glycoconjugates in the Male Reproductive System of the Horse

Lectins are glycoproteins of plant and animal origin that have the ability to bind specific carbohydrate residues of cell glycoconjugates, particularly in terminal positions. In this study, the binding of lectins, Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), Bandeiraea simplicifolia BS-1 (isolectin B4), Triticum vulgaris (WGA), Arachis hypogaea (PNA), and Ulex europaeus (UEA-I), was studied in the reproductive systems of male thoroughbred horses.DBA was detected in the stereocilia of the caput and corpus epididymis, and in the vas deferens. It was weakly detected in connective tissue of the corpus epididymis. Strong SBA staining was seen in epithelial cells in the testis, stereocilia of the corpus and cauda epididymis, and in the vas deferens. There were intense positive reactions for isolectin B4 in interstitial cells in all tissue and serosa of the vas deferens. PNA staining was seen only in stereocilia in the caput and corpus epididymis, and in the vas deferens. Strong WGA staining was seen throughout the testis, except in Sertoli cells, stereocilia, and connective tissue. UEA-I was detected in secondary spermatids, stereocilia, and epithelial cells of the cauda epididymis.These results show that degenerating cells in the testis, epididymal tubules, and vas deferens have differential affinities for lectins, and suggest that lectins play a role in the reproductive system of the horse. The heterogeneity of the lectin staining pattern in the reproductive tubules of adult horses suggests that the carbohydrate composition of each cell type is region specific.

A Case of Primary Epiploic Appendagitis

Epiploic appendages are small, 0.5-5 cm long, peritoneal pouches containing small vessels and fat, located on the serous surface of the colon, from the cecum to the rectosigmoid junction. Pathologic states are rare in these appendages, the most frequent being is infarction either due to torsion or spontaneous. As a result of subsequent inflammatory reaction, the condition has been termed primary epiploic appendagitis. The condition is manifested by localized abdominal pain, which is often mistaken for appendicitis or diverticulitis and is usually diagnosed at surgery. With the aid of comtemporary imaging modalities, however, the diagnosis of epiploic appendagitis need no longer hinge on the pathologic specimen but may be established by the clinician. As this disorder recently has been demonstrated to be predominantly self-limited, laparotomy is no longer considered necessary. Conservative management has been shown to be safe. We report a 5-year-old male patient with epiploic appendagitis who presented with acute abdominal pain.

Stimulation of Bactericidal and Fungicidal Activity of Neonatal Monocytes by Immunoactivating Peptide

PURPOSE: To evaluate the function of Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) in human neonatal monocytes. METHODS: The peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), was synthesized, purified, and prepared in the Peptide Library Support Facility at Pohang University of Science and Technology. Female Sprague-Dawley rats (200+/-10 g) were preinfected with S. aureus and treated with WKYMVm through femoral vein. At various time points, blood samples were obtained by puncture of femoral artery and the serum was plated on the nutrient agar plate. The number of viable bacteria was determined by counting the number of bacterial colonies. In addition, using S. aureus and C. albicans, we evaluated the bactericidal and fungicidal activities of neonatal monocytes, which were separated from umbilical cord blood by Ficoll gradient. RESULTS: The numbers of bacteria in the blood of WKYMVm-treated rats were rapidly decreased with time, as compared with those of the untreated rats. The peptide treatment enhanced the bactericidal activity in vivo within 10 minutes. In neonatal monocytes, WKYMVm stimulated the intracellular killing of S. aureus in a dose dependent manner, showing the maximum effect at 100 nM. WKYMVm stimulated the phagocytic and fungicidal activities against C. albicans in a dose dependent manner, with the maximum effect at the 100 nM. CONCLUSION: These results suggest that WKYMVm may be an effective agent against the neonatal infections.