Core Elements for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals / 감염과화학요법

Currently, antimicrobial resistance (AMR) is a major threat to global public health. The antimicrobial stewardship program (ASP) has been proposed as an important approach to overcome this crisis. ASP supports the optimal use of antimicrobials, including appropriate dosing decisions, administration duration, and administration routes. In Korea, efforts are being made to overcome AMR using ASPs as a national policy. The current study aimed to develop core elements of ASP that could be introduced in domestic medical facilities. A Delphi survey was conducted twice to select the core elements through expert consensus.The core elements for implementing the ASP included (1) leadership commitment, (2) operating system, (3) action, (4) tracking, (5) reporting, and (6) education. To ensure these core elements are present at medical facilities, multiple departments must collaborate as teams for ASP operations. Establishing a reimbursement system and a workforce for ASPs are prerequisites for implementing ASPs. To ensure that ASP core elements are actively implemented in medical facilities, it is necessary to provide financial support for ASPs in medical facilities, nurture the healthcare workforce in performing ASPs, apply the core elements to healthcare accreditation, and provide incentives to medical facilities by quality evaluation criteria.

Mitochondrial and DNA damage in bovine somatic cell nuclear transfer embryos

The generation of reactive oxygen species (ROS) and subsequent mitochondrial and DNA damage in bovine somatic cell nuclear transfer (SCNT) embryos were examined. Bovine enucleated oocytes were electrofused with donor cells and then activated by a combination of Ca-ionophore and 6-dimethylaminopurine culture. The H2O2 and .OH radical levels, mitochondrial morphology and membrane potential (DeltaPsi), and DNA fragmentation of SCNT and in vitro fertilized (IVF) embryos at the zygote stage were analyzed. The H2O2 (35.6 +/- 1.1 pixels/embryo) and .OH radical levels (44.6 +/- 1.2 pixels/embryo) of SCNT embryos were significantly higher than those of IVF embryos (19.2 +/- 1.5 and 23.8 +/- 1.8 pixels/embryo, respectively, p < 0.05). The mitochondria morphology of SCNT embryos was diffused within the cytoplasm. The DeltaPsi of SCNT embryos was significantly lower (p < 0.05) than that of IVF embryos (0.95 +/- 0.04 vs. 1.21 +/- 0.06, red/green). Moreover, the comet tail length of SCNT embryos was longer than that of IVF embryos (515.5 +/- 26.4 microm vs. 425.6 +/- 25.0 microm, p < 0.05). These results indicate that mitochondrial and DNA damage increased in bovine SCNT embryos, which may have been induced by increased ROS levels.

Microtubule distribution in somatic cell nuclear transfer bovine embryos following control of nuclear remodeling type

This study was conducted to evaluate the microtubule distribution following control of nuclear remodeling by treatment of bovine somatic cell nuclear transfer (SCNT) embryos with caffeine or roscovitine. Bovine somatic cells were fused to enucleated oocytes treated with either 5 mM caffeine or 150 micrometer roscovitine to control the type of nuclear remodeling. The proportion of embryos that underwent premature chromosome condensation (PCC) was increased by caffeine treatment but was reduced by roscovitine treatment (p < 0.05). The microtubule organization was examined by immunostaining beta- and gamma-tubulins at 15 min, 3 h, and 20 h of fusion using laser scanning confocal microscopy. The gamma-tubulin foci inherited from the donor centrosome were observed in most of the SCNT embryos at 15 min of fusion (91.3%) and most of them did not disappear until 3 h after fusion, regardless of treatment (82.9-87.2%). A significantly high proportion of embryos showing an abnormal chromosome or microtubule distribution was observed in the roscovitine-treated group (40.0%, p < 0.05) compared to the caffeine-treated group (22.1%). In conclusion, PCC is a favorable condition for the normal organization of microtubules, and inhibition of PCC can cause abnormal mitotic division of bovine SCNT embryos by causing microtubule dysfunction.

Combination treatment with leflunomide and methotrexate in patients with rheumatoid arthritis: the efficacy, safety, and predisposing factors for treatment response / 대한내과학회지

BACKGROUND: Leflunomide, a novel immunoregulatory drug, has been shown to be effective in rheumatoid arthritis (RA) as monotherapy and as combination therapy with methotrexate (MTX). The aims of this study were to investigate the efficacy and safety of combination therapy with leflunomide and MTX in active RA patients and to identify the patients with a better response to this combination. METHODS: The patients received a maintenance dose of 20 mg of leflunomide with or without a loading dose. Parameters for disease activity in RA were measured at baseline and at 12 and 24 weeks after initiation of leflunomide. At 24 weeks, the baseline data from the patients classified as leflunomide responders were compared with data from nonresponders and analyzed to determine the potential predisposing factors for treatment response. RESULTS: A total of 103 patients with RA were included and 93 (90.3%) patients received leflunomide for 24 weeks. At 24 weeks, 67 (65.1%) patients were DAS28 responders; 14 (13.6%) were good responders and 53 (51.5%) moderate responders. At 12 weeks, significant improvements were noticeable in the individual efficacy measures of diseases activity. There were also significant improvements between 12 and 24 weeks in swollen joint count, tender joint count, HAQ disability index, and patients' and physicians' global assessments of diseases activity; but no further improvements in ESR or CRP could be seen after the first 12 weeks. When comparing the baseline data from responders with the nonresponders, patients on a higher MTX dose and patients with a higher disease activity at baseline responded better to leflunomide. However, age, sex, disease duration of RA, functional status, loading dosage of leflunomide, and previous number of DMARDs used did not affect the patients' response to leflunomide. CONCLUSION: Combination therapy with leflunomide and MTX is effective and safe across a wide range of patients, especially those with a high disease activity in spite of treatment with other traditional DMARDs.

Binding of Lectins to the Zona Pellucida on Sperm-oocytes Interaction in the Pig / 대한불임학회지

OBJECTIVE: Lectins are cell-agglutinating and sugar specific proteins or glycoproteins of non-immune origin that precipitate glycoconjugates having saccharides of appropriate complementarity. Because of these properties, plant lectins have been used to help characterize the carbohydrate moieties of glycoproteins in the zona pellucida (ZP) of several mammalian species including pigs. Treatment of oocytes with various lectins blocks sperm binding to the ZP in various mammalian species. This study was undertaken to examine the distribution of sugar residues in the ZP of pig oocytes matured in vitro and the ability of spermatozoa to bind to ZP and in vitro penetration in oocytes treated with fluorescein isothiocyanate (FITC)-labelled lectins. MATERIALS AND METHODS: The lectins of Banderiaea simplicifolia (BS-II, bind to beta-D-Nacetylglucosamine), Canavalin ensiformis (Con A, bind to alpha-D-Mannose), Lens culinaris (LCA, bind to alpha-D-Mannose), Ricinus communis (RCA-I, bind to beta-D-Galactose) and Ulex europaeus (UEA-I, bind to alpha-L-Fucose) were examined for spermatozoa penetration, binding capacity to ZP and distribution of lectins. RESULTS: The penetration rates were significantry (p<0.05) higher in control oocytes (63%) than those treated with all lectins, but penetration rates (40~49%) were simililar in group treated with lectins. The incidence of monospermy was similar in oocytes untreated and UEA-I, but it was higher in oocytes treated with BS-II, Con A, RCA-I and LCA. The porcine oocytes cultured for 48 h in TC-199 medium were freed from cumulus cells and treated for 30 min with fluorescein isothiocyanate-labelled lectins. When examined under fluorescein illumination, higher (p<0.001) proportions of oocytes showed fluorescein of zona pellucida after treatment with Con A (93%), LCA (93%) and RCA-I (100%) than BS-II (37%) and UEA-I (50%). All of the oocytes treated with RCA-I exhibited strong fluorescein in the outer region of the zona pellucida while those treated with LCA exhibited strong fluorescein throughout the zona pellucida. BS-II bounded mainly to the outer region and UEA-I bounded mainly to the inner region of the zona pellucida, with either strong or weak fluorescein. At 120 min after insemination in vitro, fewer spermatozoa were bound to the zona pellucida of the oocytes treated with BS-II, Con-A and RCA-I. Of the lectins, Con A most inhibited sperm binding. CONCLUSIONS: These results suggest that beta-D-Galactose residues in the porcine zona pellucida may act as primary sperm receptors and inducers of the sperm acrosome reaction and these sugar residues may be involved in the block to polyspermy.

A Case of Treatment of Acute Renal Failure due to Bilateral Ureter Injuries after Bilateral Inguinal Herniorrhaphy / 대한신장학회잡지

Inguinal herniorrhaphy is the most frequent general surgical operation performed by pediatric surgeons, but some complications can usually be attributed to inappropriate approach and traumatic dissection. We experienced a case of acute renal failure due to bilateral ureter injuries after bilateral inguinal hernia repairs. The patient was a 3 month old male infant who presented as anuria and generalized edema after bilateral herniorrhaphy and was treated with peritoneal dialysis for 2 weeks. After 4 days of peritoneal dialysis, general conditions and symptoms were improved, but anuria persisted for 2 weeks. We performed IVP and abdominal CT. Both studies showed abnormal dye accumulation in peritoneal cavity. Ureteroneocystostomy on right and segmental resection of ureter and end to end anastomosis of left ureter were done without any complications. He has been doing well and has had normal kidney function. Therefore we report a case of acute renal failure due to bilateral ureter injuries after both inguinal herniorrhaphy with a brief review of literatures.