• Journal of Veterinary Science
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• v.25 no.1
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• pp.12.1-12.10
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• 2024

Background: Staphylococcus aureus and S. pseudintermedius are the major etiological agents of staphylococcal infections in humans, livestock, and companion animals. The misuse of antimicrobial drugs has led to the emergence of antimicrobial-resistant Staphylococcus spp., including methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. pseudintermedius (MRSP). One novel therapeutic approach against MRSA and MRSP is a peptide nucleic acid (PNA) that can bind to the target nucleotide strands and block expression. Previously, two PNAs conjugated with cell-penetrating peptides (P-PNAs), antisense PNA (ASP)-cmk and ASP-deoD, targeting two essential genes in S. aureus, were constructed, and their antibacterial activities were analyzed. Objectives: This study analyzed the combined antibacterial effects of P-PNAs on S. aureus and S. pseudintermedius clinical isolates. Methods: S. aureus ATCC 29740 cells were treated simultaneously with serially diluted ASP-cmk and ASP-deoD, and the minimal inhibitory concentrations (MICs) were measured. The combined P-PNA mixture was then treated with S. aureus and S. pseudintermedius veterinary isolates at the determined MIC, and the antibacterial effect was examined. Results: The combined treatment of two P-PNAs showed higher antibacterial activity than the individual treatments. The MICs of two individual P-PNAs were 20 and 25 µM, whereas that of the combined treatment was 10 µM. The application of a combined treatment to clinical Staphylococcus spp. revealed S. aureus isolates to be resistant to P-PNAs and S. pseudintermedius isolates to be susceptible. Conclusions: These observations highlight the complexity of designing ASPs with high efficacy for potential applications in treating staphylococcal infections in humans and animals.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.83-91
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• 2024

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

• Archives of Craniofacial Surgery
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• v.25 no.2
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• pp.71-76
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• 2024

Background: The rising incidence of dialysis-dependent end-stage renal disease (ESRD) has underscored the need for collaboration between plastic surgeons and nephrologists, particularly concerning preoperative and postoperative management for facial reconstruction. This collaboration is essential due to a scarcity of comprehensive information in this domain. Methods: A study initiated in January 2015 involved 10 ESRD cases on dialysis undergoing Mohs micrographic surgery for facial skin cancer, followed by reconstructive surgery under general anesthesia. To ensure surgical safety, rigorous measures were enacted, encompassing laboratory testing, nephrology consultations, and preoperative dialysis admission. Throughout surgery, meticulous control was exercised over vital signs, electrolytes, bleeding risk, and pain management (excluding nonsteroidal anti-inflammatory drugs). Postoperative assessments included monitoring flap integrity, hematoma formation, infection, and cardiovascular risk through plasma creatinine levels. Results: Adherence to the proposed guidelines yielded a notable absence of postoperative wound complications. Postoperative plasma creatinine levels exhibited an average decrease of 1.10 mg/dL compared to preoperative levels, indicating improved renal function. Importantly, no cardiopulmonary complications or 30-day mortality were observed. In ESRD patients, creatinine levels decreased significantly postoperatively compared to the preoperative levels (p< 0.05), indicating favorable outcomes. Conclusion: The consistent application of guidelines for admission, anesthesia, and surgery yielded robust and stable outcomes across all patients. In particular, the findings support the importance of adjusting dialysis schedules. Despite the limited sample size in this study, these findings underscore the effectiveness of a collaborative and meticulous approach for plastic surgeons performing surgery on dialysis-dependent patients, ensuring successful outcomes.

• Pediatric Infection and Vaccine
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• v.13 no.2
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• pp.155-162
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• 2006

Purpose : Appropriate use of antimicrobials is an essential factor to treat infectious diseases and prevent acquisition of antimicrobial resistant pathogens. This study was undertaken to search that application of computerized management program for restriction of antimicrobials use in a hospital is helpful to decrease antimicrobial use density. Methods : Antibiotics utilization committee decided to restrict the use of 16 antimicrobials(14 expensive drugs having fear of drug resistance by pathogens and additional two drugs with inappropriate using tendency). Retrospective evaluation of antimicrobial user numbers between May and July of 2004 and 2005(study group) was conducted to compare with previous use density during same period of 2002 and 2003(control group). Results : Inpatients number of control group($823.5{\pm}37.1$ persons) was more than study group($809.2{\pm}39.3$ persons, P<0.001), but, outpatients number and hospitalized duration were equal in two groups. Antimicrobial user number/100 inpatients per day of glycopeptides and antifungal agents was equal in two groups, and study group was significantly higher density than control group in the use of carbapenems, piperacillin-tazobactam and quinolones(P<0.001). But study group was significantly lower density than control group in the use of drugs with inappropriately using tendency and expensive cephalosporins having broad antimicrobial spectrum(P<0.001). Conclusion : Application of computerized management program for restriction of antimicrobials use in a hospital is effective to decrease the use density of antimicrobials with inappropriately using tendency, but it is an insufficient measures for the restricted use of other antimicrobials on the whole.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1154-1166
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• 1998

Background : In the management of patients whose primary chemotherapy has failed, careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The purpose of present study is establishment of retreatment regimen for pulmonary tuberculosis. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Masan Tuberculosis Hospital. Methods : Retrospective cohort study was made of 104 drug-resistant pulmonary tuberculosis patients who were treated by five regimens between Jan. 1994 and Nov. 1996. All the patients taken medicine for second anti-tuberculosis regimens for the first time. We separated the patients by three groups(Group I ; OFX+PTA+CS+PAS+Aminoglycoside, Group II : PZA+PTA+CS+PAS+Aminoglycoside, Group III : PZA+OFX+PTA+PAS+Aminoglycoside). Results : The age distribution was most frequent in fourth decade(36patients, 34.6%) and the mean age was 42.6 year. The sex distribution was more frequent in the males(81 patients, 85.7%). There was 31 patients(29.8%) with combined diseaes, 18 patients with complication and 24 patients(27.9%) with family history. Primary chemotherapy regimens were HERZ(S or K) in 48 patients (46.2%), HER(S or K) in 41 patients(39.4%) and others in 15 patients(14.4%). Result of drug sensitivity test showed that the resistance to INH and RFP is in 68 patients(65.4%), RFP is 12 patients(11.5%), INH is in 3 patients(2.9%) and all sensitive to INH and RFP is 3 patients(2.9%). The clinical symptoms on admission were coughing(89.4%), sputum(69.2%), dyspnea on exertion(37.5%), weight loss(33.7%) blood tinged sputum(15.4%) and others. The extent of disease on the radiograph was far-advanced in 73 patients(70.2%), moderate in 28 patients(26.9%) and minimal in 3 patients(2.9%). The side effects for drugs were gastrointestinal troubles in 31 patients(29.8%), arthralgia in 22 patients(21.2%), skin rash in 12 patients(11.5%) and others. The negative conversion rate on sputum AFB smear was 85.6%(87.5% in Group I, 80.0% in Group II and 90.5% in Group III). The average negative conversion time on sputum was 4 month(4.0 month in Group I, 4.6 month in Group II and 3.0 month in Group III). Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and combination of PZA and OFX can be use effectively substituting for CS.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.61-67
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• 2009

Purpose : The rate of drug-resistant tuberculosis (DR-TB) in children is an indicator of the effectiveness of TB control programs in the community. This study aimed to assess the prevalence of DR-TB in children and evaluate TB management. Methods : Between January 1999 and July 2007, drug susceptibility tests for anti-TB drugs were employed for patients aged less than 19 years with culture-positive TB. Results : A total of 607 cases (16.6%) were resistant to at least one anti-TB drug as follows: isoniazid (INH; 13.8%), rifampin (8.9%), pyrazinamide (4.2%), streptomycin (3.7%), ethambutol (EMB; 5.9%), and para-aminosalicylic acid (PAS; 1.9%). Multidrug-resistant (MDR) TB was found in 276 cases (7.6%); extensive drug resistant (XDR) TB, in 5 cases (0.2%). The rate of resistance to at least one anti-TB drug in children aged >15 years (16.1%) was significantly lower than that in children aged <15 years (20.5%) (P=0.016). The rate of resistance to at least one anti-TB drug and multidrug-resistance in this survey decreased significantly (P<0.001) as compared to the previous survey (1987-1995). The rate of resistance to INH, EMB, and PAS also significantly decreased (P<0.05). Conclusion : The rate of DR-TB in children in Korea has decreased over time; however, it remains higher than that in other countries. MDR-TB and XDR-TB are the emerging problems in Korean children. Therefore, the selection of effective drugs through drug susceptibility tests and evaluating risk factors of resistant TB is essential to successful therapy and a decreased incidence of DR-TB.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.867-870
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• 2001

All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.188-195
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• 1993

In order to understand the machanism of action and regulation of ${\beta}$-adrenergic receptor in terms of molecular level, the purification of receptor protein has a fundamental importance. Moreover, species differences among avian, amphibian and mammalian ${\beta}$-adrenergic receptors make it more important to purify mammalian ${\beta}$-adrenergic receptor. Because ${\beta}$-adrenergic receptor is an integral membrane protein, it must be solubilized from the membrane for the purification. The purpose of the present study was to solubilize and characterize the mammalian $\beta$-adrenergic receptor from guinea pig lung in quantities by more efficient and practical method eventually to purify receptor. Guinea pig lung membrane preparation was solubilized by sequential treatment of buffers containing low and high concentration of digitonin which are 0.2 and 1.2% respectively. About 50% of the total receptor pool was released by this double extraction procedure. The $\beta$-adrenoceptors in the digitonin extract were identified using the ${\beta}$-adrenergic antagonist, (-)-[$^3H$]-dihydroalprenolol ([$^3H$]DHA). The solubilized receptor retained all of the essential characteristics of membrane-bound receptor, namely saturability; stereoselectivity; high affinity to ${\beta}$-adrenergic drugs. For the measurement of soluble receptor activity, Sephadex G-50 chromatography method has been widely used. Inspite of its accuracy and wide acceptance, this technique employed troublesome column work which required long time to assay the activity of receptor. We employed another methods to measure receptor activity. When using 0.5% polyethylenimine pretreated GF/B glass fiber filter, filtration technique could be used to measure soluble receptor activity. This technique enabled us to reduce the total amount of time to assay by a factor of 4 as well as to detect soluble receptor. In the present study, we could establish more efficient and practical solubilization method of mammalian $\beta$-adrenergic receptor. The rapidity and high yield of this solubilization scheme, together with the favorable recovery of the receptor activity, are significant steps toward the ultimate purification of the mammalian $\beta$-adrenergic receptor. The result of this study together with more convenient purification method could provide large amount of purified receptor with ease for various research purposes.

• Journal of Food Hygiene and Safety
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• v.5 no.3
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• pp.139-158
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• 1990

Heavy resposibility is placed on the veterinarian and the livestock and aquatic animal producers to observe the period for withdrawal of a drug prior to marketing to assure that illegal concentrations of drug residues in meat, milk, egg, fish and other animal foods do not occur. This is essential from a public health standpoint because levels of residues in excess of those legalIy permitted in edible tissues may produce injurious effects when consumed over a long time span. With greater use of animal drugs of chemicals required in production of food crops, livestock and aquatic animals, the possibility of human being continuously exposed to drug and chemical residues for a life time is unequivocally evident. Korean authorities concerned Ministry of Agriculture and Fishery and Ministry of Health and Social Affairs, have recenly made their own regulations to control chemical residues in beef, pork and chicken independently. Consequently, inspection for the chemical residues also have been or will be carried out by the two authorities concerned without any cooperations. It is undoubtfulI to have a single regulation and national residue program for control residual chemicals in animal foods and that the tolerance levels should be established in milk, egg, and freshwater fish. Besides, we have no complete standard methods to analyze the residual chemicals and the methods have not been evaluated their efficiency, precise, accuracy and limit of detection. In this paper, the analytical methods and national residue programs in foreign countries are introduced and discussed and the status of animal food safety in this country is also reviewed.

• Parasites, Hosts and Diseases
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• v.51 no.6
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• pp.711-717
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• 2013

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.