Current Status and Future Direction of Artificial Intelligence in Healthcare and Medical Education / 의학교육논단

The rapid development of artificial intelligence (AI), including deep learning, has led to the development of technologies that may assist in the diagnosis and treatment of diseases, prediction of disease risk and prognosis, health index monitoring, drug development, and healthcare management and administration. However, in order for AI technology to improve the quality of medical care, technical problems and the efficacy of algorithms should be evaluated in real clinical environments rather than the environment in which algorithms are developed. Further consideration should be given to whether these models can improve the quality of medical care and clinical outcomes of patients. In addition, the development of regulatory systems to secure the safety of AI medical technology, the ethical and legal issues related to the proliferation of AI technology, and the impacts on the relationship with patients also need to be addressed. Systematic training of healthcare personnel is needed to enable adaption to the rapid changes in the healthcare environment. An overall review and revision of undergraduate medical curriculum is required to enable extraction of significant information from rapidly expanding medical information, data science literacy, empathy/compassion for patients, and communication among various healthcare providers. Specialized postgraduate AI education programs for each medical specialty are needed to develop proper utilization of AI models in clinical practice.

Changes of academic performance by integration between basic and clinical medicine in pre-clerkship medical education / 한국의학교육

PURPOSE: The purpose of this study was to investigate the effect of curriculum revision on student performance in tests of the medical knowledge of students at Pusan National University. METHODS: Test scores of the Basic Medicine Comprehensive Examination (BMCE), conducted by the Medical Education Assessment Corporation, and internal clinical knowledge tests of the three integrated courses of the Pusan National University School of Medicine, during the last 3 years (2015–2017) were compared with an unpaired Student t-test and the results were considered to be significant at p < 0.05. RESULTS: Curriculum revision in 2017 introduced the integration of basic and clinical courses at the organ level of medical education. Scores of BMCE and internal clinical knowledge tests in three integrated courses after curriculum revision showed a statistically significant increase after curriculum revision. CONCLUSION: Curriculum revisions that integrated the basic and clinical courses in organ-level education improved student's academic performance significantly.

MicroRNA-103a-3p controls proliferation and osteogenic differentiation of human adipose tissue-derived stromal cells

The elucidation of the molecular mechanisms underlying the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs) represents a critical step in the development of hADSCs-based cellular therapies. To examine the role of the microRNA-103a-3p (miR-103a-3p) in hADSCs functions, miR-103a-3p mimics were transfected into hADSCs in order to overexpress miR-103a-3p. Osteogenic differentiation was induced for 14 days in an osetogenic differentiation medium and assessed by using an Alizarin Red S stain. The regulation of the expression of CDK6 (cyclin-dependent kinase 6), a predicted target of miR-103a-3p, was determined by western blot, real-time PCR and luciferase reporter assays. Overexpression of miR-103a-3p inhibited the proliferation and osteogenic differentiation of hADSCs. In addition, it downregulated protein and mRNA levels of predicted target of miR-103a-3p (CDK6 and DICER1). In contrast, inhibition of miR-103a-3p with 2'O methyl antisense RNA increased the proliferation and osteogenic differentiation of hADSCs. The luciferase reporter activity of the construct containing the miR-103a-3p target site within the CDK6 and DICER1 3'-untranslated regions was lower in miR-103a-3p-transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference-mediated downregulation of CDK6 and DICER1 in hADSCs inhibited their proliferation and osteogenic differentiation. The results of the current study indicate that miR-103a-3p regulates the osteogenic differentiation of hADSCs and proliferation of hADSCs by direct targeting of CDK6 and DICER1 partly. These findings further elucidate the molecular mechanisms governing the differentiation and proliferation of hADSCs.

Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

PURPOSE: Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. MATERIALS AND METHODS: ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBISPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. RESULTS: Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0+/-10.0 vs. -2.6+/-12.0, p=0.019; LVEF, -8.0+/-15.4 vs. -15.9+/-14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. CONCLUSION: Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model.

Effect of Phorbol 12-Myristate 13-Acetate on the Differentiation of Adipose-Derived Stromal Cells from Different Subcutaneous Adipose Tissue Depots

Human adipose-tissue-derived stromal cells (hADSCs) are abundant in adipose tissue and can differentiate into multi-lineage cell types, including adipocytes, osteoblasts, and chondrocytes. In order to define the optimal harvest site of adipose tissue harvest site, we solated hADSCs from different subcutaneous sites (upper abdomen, lower abdomen, and thigh) and compared their proliferation and potential to differentiate into adipocytes and osteoblasts. In addition, this study examined the effect of phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, on proliferation and differentiation of hADSCs to adipocytes or osteoblasts. hADSCs isolated from different subcutaneous depots have a similar growth rate. Fluorescence-activated cell sorting (FACS) analysis showed that the expression levels of CD73 and CD90 were similar between hADSCs from abdomen and thigh regions. However, the expression of CD105 was lower in hADSCs from the thigh than in those from the abdomen. Although the adipogenic differentiation potential of hADSCs from both tissue regions was similar, the osteogenic differentiation potential of hADSCs from the thigh was greater than that of hADSCs from the abdomen. Phorbol 12-myristate 13-acetate (PMA) treatment increased osteogenic differentiation and suppressed adipogenic differentiation of all hADSCs without affecting their growth rate and the treatment of Go6983, a general inhibitor of protein kinase C (PKC) blocked the PMA effect. These findings indicate that the thigh region might be a suitable source of hADSCs for bone regeneration and that the PKC signaling pathway may be involved in the adipogenic and osteogenic differentiation of hADSCs.

Adipose Tissue Derived Mesenchymal Stem Cells / 대한이식학회지

Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. Recent studies have shown that MSCs can be differentiated into nonmesordermal lineages. Although MSCs can be isolated from every type of connective tissues, the abundance, the easy and repeatable access to subcutaneous adipose tissue and the simple isolation procedures indicate that adipose tissue can be a preferable candidate in MSC isolation for clinical application. Therefore, in this review, the isolation, characterization, preclinical and clinical application, and the mechanisms and future roles of ADSC in cell therapy are discussed.

The effect of growth factors on osteogenic differentiation of adipose tissue-derived stromal cells

Future cell-based therapies such as tissue engineering will benefit from a source of autogenous pluripotent stem cells. There are embryonic stem cells (ESC) and autologous adult stem cells, two general types of stem cells potentilally useful for these applications. But practical use of ESC is limited due to potential problems of cell regulation and ethical considerations. To get bone marrow stem cells is relatively burden to patients because of pain, anesthesia requirement. The ideal stem cells are required of such as the following advantages: easy to obtain, minimal patient discomfort and a capability of yielding enough cell numbers. Adipose autologus tissue taken from intraoral fatty pad or abdomen may represent such a source. Our study designed to demonstrate the ability of human adipose tissue-derived stromal cells (hATSC) from human abdominal adipose tissue diffentiating into osteocyte and adipocyte under culture in vitro conditions. As a result of experiment, we identified stromal cell derived adipose tissue has the multilineage potentiality under appropriate culture conditions. And the adipose stromal cells expressed several mesenchymal stem cell related antigen (CD29, CD44) reactions. Secondary, we compared the culture results of a group of hATSC stimulated with TGF-beta1, bFGF with a hATSC group without growth factors to confirm whether cytokines have a important role of the proliferation in osteogenic differentiation. The role of cytokines such as TGF-beta1, bFGF increased hATSC's osteogenic differentiation especially when TGF-beta1 and bFGF were used together. These results suggest that adipose stromal cells with growth factors could be efficiently available for cell-based bone regeneration.

Study on the Culture and in vivo transplantation of Mesenchymal Stem Cells derived from Human Umbilical Cord Blood / 대한산부인과학회지

OBJECTIVE: Human MSCs (hMSCs) have the potential to differentiate along different lineages. Despite their potential clinical utilities for cellular and gene therapy, the fate of MSCs derived from human cord blood (UBMSCs) after systemic administration is mostly unknown. In this study we cultured UBMSCs and investigated distribution of them injected into the intravenous routes. METHODS: By flow cytometry, we investigated whether MSCs from human umbilical cord blood have similar characteristics of MSCs. In addition we induced those cells into the osteocyte and adipocyte to determine the characteristics of MSCs. UBMSCs were marked by transfection with LacZ-adeno virus and distribution of the injected cells were examined by x-gal staining in immuno-deficient mice. RESULTS: Umbilical cord blood-derived mononuclear cells, when set in culture, gave rise to adherent cells. Preterm, as compared with term pregnancy, cord blood is richer in MSCs. UBMSCs expressed several MSCs-related antigen (CD29 and CD44). Under appropriate culture conditions, UBMSCs were induced to differentiate to the osteocyte, and adipocyte lineages. UBMSCs were engrafted into various tissues after intravenous administration. When UBMSCs were transplanted into the distant site from cryogenic injury of mice brain, cells were preferentially migrated into the injured area. CONCLUSION: These results demonstrate that UBMSCs have the ability to proliferate extensively in culture, and they maintain their multi-lineage differentiation potential in vitro, and that they can integrate into various tissues after transplantation and migrate to injured area. Therefore, UBMSCs are promising candidates for developing cell-based therapeutic approaches for postnatal tissue repair.

Chondrogenesis of Mesenchymal Stem Cell Derived from Canine Adipose Tissue / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cartilage reconstruction is one of the important medical issues studied in otolaryngology today. Tissue engineering is presently being utilized in parts of cartilage repair. Sources of cells for tissue engineering are chondrocytes from mature cartilage and bone marrow mesenchymal stem cells that are able to differentiate into chondrocytes. Recent studies have shown that adipose tissue have mesenchymal stem cells which can differentiate into adipogenic, chondrogenic myogenic, osteogenic cells and neural cells in vitro. In this study, we have examined chondrogenic potential of the canine adipose tissue derived mesenchymal stem cell (ATSC). MATERIALS AND METHOD: We harvested canine adipose tissue from the inguinal area. ATSCs were enzymatically released from canine adipose tissue. Under appropriate culture conditions, ATSCs were induced to differentiate into chondrocyte lineages using micromass culture technique. We used immunostain to type II collagen and toluidine blue stain to confirm chondrogenic differentiation of ATSCs. RESULTS: We could isolate ATSCs from canine adipose tissue. ATSCs expressed CD29 and CD44 which are specific surface markers of mesenchymal stem cell. ATSCs differentiated into micromass that has positive response to immunostain of type II collagen and toluidine blue stain. CONCLUSION: In vitro, ATSCs differentiated into cells that have characteristic cartilage matrix molecules in the presence of lineage-specific induction factors. Adipose tissue may represent an alternative source to bone marrow-derived MSCs.

Apoptosis Induced by Single Cell Suspension Culture of Mouse Embryonic Stem Cells / 대한산부인과학회잡지

OBJECTIVE: Embryonic stem cells (ES cells) are pluripotential, and are therefore used to construct gene knock-out mice and to study cell differentiation and early developmental processes in mice. This study was designated to examine apoptotic processes in ES cells according to culture conditions and to study roles of extracellular matrix on the process. METHODS: Apoptosis was determined by DNA fragmentation and kinase activity during apoptotic process was measured. RESULTS: The apoptosis of mouse ES cells was induced when the cells were dispersed as single cells, whereas this process was suppressed when they proliferated in aggregates. Single cell suspension culture did not affect expression of bcl-2 and bax mRNA. Single cell suspension culture activated stress-activated protein kinase/c-jun-N-terminal kinase (SAPK/JNK), but not p38 kinase. The apoptosis of ES cells was repressed when the cells were cultured on feeders prepared from mouse embryonic fibroblasts (MEF), or on the petri dishes coated with fibronectin or laminin, but not with collagen or poly-L-lysine. Culture supernatants from MEF cells did not block the apoptosis of ES cells, which suggests that a direct interaction between ES cells and MEF cells is required for the suppression of apoptosis. Activation of SAPK/JNK by single cell suspension was protected by interaction of cells with laminin or fibronectin, but not with collagen or poly-L-lysine. CONCLUSION: The suspension of ES cells as single cells causes serious damage and induces apoptosis, and the apoptotic process is mediated by the activation of SAPK/JNK and is inhibited by the interaction of ES cells with extracellular matrix.

Extracellular ATP stimulates Na+ and Cl- transport through the activation of multiple purinergic receptors on the apical and basolateral membranes in M-1 mouse cortical collecting duct cells

The mammalian cortical collecting duct (CCD) plays a major role in regulating renal NaCl reabsorption, which is important in Na+ and Cl- homeostasis. The M-1 cell line, derived from the mouse cortical collecting duct, has been used as a mammalian model of the study on the electrolytes transport in CCD. M-1 cells were grown on collagen-coated permeable support and short circuit current (Isc) was measured. M-1 cells developed amiloride-sensitive current 5apprx7 days after seeding. Apical and basolateral addition of ATP induced increase in Isc in M-1 cells, which was partly retained in Na+/-free or Cl--free solution, indicating that ATP increased Na+ absorption and Cl- secretion in M-1 cells. Cl- secretion was mediated by the activation of apical cystic fibrosis transmembrane regulator (CFTR) chloride channels and Ca2+/-activated chloride channels, but Na+ absorption was not mediated by activation of epithelal sodium channel (ENaC). ATP increased cAMP content in M-1 cells. The RT-PCR analysis demonstrated that M-1 cells express P2Y2, P2X3 and P2Y4 receptors. These results showed that ATP regulates Na+ and Cl- transports via multiple P2 purinoceptors on the apical and basolateral membranes in M-1 cells.

Dexamethasone enhances phospholipase D activity in M-1 cells

Phospholipase D (PLD) is an enzyme involved in signal transduction and widely distributed in mammalian cells. The signal transduction pathways and role for phospholipid metabolism during hormonal response in cortical collecting duct remain partly undefined. It has been reported that dexamethasone increases transepithelial transport in M-1 cells that are derived from the mouse cortical collecting duct. We investigated the expression and activity of PLD in M-1 cells. Basal PLD activity of M-1 cells cultured in the presence of dexamethasone (5 microM) was higher than in the absence of dexamethasone. Dexamethasone and ATP activated PLD in M-1 cells but phorbol ester did not stimulate PLD activity. Vasopressin, bradykinin, dibutyryl cyclic AMP, and ionomycin were ineffective in activating PLD of the cells. The PLD2 isotype was detected by immunoprecipitation but PLD1 was not detected in M-1 cells. Addition of GTPgammaS and ADP-ribosylation factor or phosphatidylinositiol 4,5-bisphosphate to digitonin-permeabilized cells did not augment PLD activity. In intact cells PLD activity was increased by sodium oleate but there was no significant change between dexamethasone treated- and untreated cells by oleate. These results suggest that at least two types of PLD are present in M-1 cells and PLD plays a role in the corticosteroid-mediated response of cortical collecting duct cells.

Asymmetrical distribution of P2Y nucleotide receptors in rabbit inner medullary collecting duct cells

We cultured the rabbit inner medullary collecting duct (IMCD) cells as monolayers on collagen-coated membrane filters, and investigated distribution of the P2Y receptors by analyzing nucleotide-induced short circuit current (Isc) responses. Exposure to different nucleotides of either the apical or basolateral surface of cell monolayers stimulated Isc. Dose-response relationship and cross-desensitization studies suggested that at least 3 distinct P2Y receptors are expressed asymmetrically on the apical and basolateral membranes. A P2Y2-like receptor, which responds to UTP and ATP, is expressed on both the apical and basolateral membranes. In addition, a uracil nucleotide receptor, which responds to UDP and UTP, but not ATP, is expressed predominantly on the apical membrane. In contrast, a P2Y1-like receptor, which responds to ADP and 2-methylthio-ATP, is expressed predominantly on the basolateral membrane. These nucleotides stimulated intracellular cAMP production with an asymmetrical profile, which was comparable to that in the stimulation of Isc. Our results suggest that the adenine and uracil nucleotides can interact with different P2Y nucleotide receptors that are expressed asymmetrically on the apical and basolateral membranes of the rabbit IMCD cells, and that both cAMP- and Ca2+-dependent signaling mechanisms underlie the stimulation of Isc.

Molecular Identification and Distribution of Aquaporins in Human and Rat Testes / 대한불임학회지

OBJECTIVE: Several water channels (aquapoins; AQP) that belong to the MIP (major intrinsic protein) family have identified. In the selected tissues including red blood cells or renal tubules, water movements are abundant and/or physiologically important. Unexpectedly, a high water permeability of human and ram sperm has been reported. Recent studies showed that AQP7 and AQP8 are present in testes so that the high water permeability of human sperm suggested to be mediated by AQPs. METHOD: To identify the identity of aquaporins expressed in testes, RT-PCR was performed using degenerative primers, which were designed to correspond to highly conserved sequences surrounding the Asn-Pro-Ala (NPA) motifs in the aquaporins. New expressed AQP series were reconfirmed by immunohistochemical study using rabbit polyclonal antibodies. RESULTS: DNA sequencing of PCR products revealed that AQP2 and AQP3 mRNA as well as AQP7 and AQP8 are expressed in human and rat testes, AQP2 are expressed in spermatozoa, interstitial cells and myofibroblasts and AQP3 are expressed in myofibroblasts of semineferous tubules on immunocytochemical stain. CONCLUSION: These results indicate that multiple aquaporins are expressed in testes, and that they may have important roles in the spermatogenesis and the germ cell function of testis.

Activation of SAPK and increase in Bak levels during ceramide and indomethacin-induced apoptosis in HT29 cells

It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time-dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, Bcl-XL, Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

Role of phospholipase A2 in hypoxia-induced renal cell injury

The present study was designed to assess the roles of PLA2 activation and arachidonic acid (AA) metabolites in hypoxia-induced renal cell injury. Hypoxia increased LDH release in a dose-dependent manner in rabbit renal cortical slices, and this increase was significant after 20-min hypoxia. The hypoxia-induced LDH release was prevented by amino acids, glycine and alanine, and extracellular acidosis (pH 6.0). Buffering intracellular Ca2+ by a chelator, but not omission of Ca2+ in the medium produced a significant reduction in hypoxia-induced LDH release. The effect of hypoxia was blocked by PLA2 inhibitors, mepacrine, butacaine, and dibucaine. A similar effect was observed by a 85-kD cPLA2 inhibitor AACOCF3. AA increased hypoxia-induced LDH release, and albumin, a fatty acid absorbent, prevented the LDH release, suggesting that free fatty acids are involved in hypoxia-induced cell injury. These results suggest that PLA2 activation and its metabolic products play important roles in pathogenesis of hypoxia-induced cell injury in rabbit renal cortical slices.

Molecular analysis of AQP2 promoter. I. cAMP-dependent regulation of mouse AQP2 gene

To determine molecular mechanisms of Aquaporin-CD (AQP2) gene regulation, the promoter region of the AQP2 gene was examined by transiently transfecting a promoter-luciferase reporter fusion gene into mouse renal collecting duct cell lines such as mIMCD-3, mIMCD-K2, and M-1 cells, and NIH3T3 mouse embryo fibroblast cells. PCR-Southern analysis reveals that mIMCD-3 and mIMCD-K2 cells express AQP2, but M-1 and NIH3T3 cells do not, and that the treatment with cpt-cAMP (400 muM) or forskolin/isobutylmethylxanthine (IBMX) increased the AQP2 expression in IMCD cells. In both IMCD and NIH3T3 cells, the constructs containing the promoter of AQP2 gene showed promoter activities, indicating lack of tissue-specific element in the 1.4 kb 5'-flanking region of the mouse AQP2 gene. Luciferase activity in the IMCD cells transfected with the construct containing 5-flanking region showed responsiveness to cpt-cAMP, indicating that the 1.4 kb 5'-flanking region contains the element necessary for the regulatory mechanism by cAMP. The promoter-luciferase constructs which do not have a cAMP-responsible element (CRE) still showed the cAMP responsiveness in IMCD cells, but not in NIH3T3 cells. Increase in medium osmolarity did not affect AQP2 promoter activity in mIMCD-K2 cells. These results demonstrate that AQP2 gene transcription is increased with cAMP treatment through multiple motifs including CRE in the 5'-flanking region of the gene in vitro, and the regulatory mechanism may be important for in vivo regulation of AQP2 expression.

Effects of ethanol on Na+-dependent solute uptake in rabbit renal brush-border membrane vesicles

This study was undertaken to examine the effect of ethanol on Na+-dependent transport systems (glucose, phosphate, and dicarboxylate) in renal brush-border membrane vesicles (BBMV). Ethanol inhibited Na+-dependent uptakes of glucose, phosphate, and succinate in a dose-dependent manner, but not the uptakes of Na+-independent. The H+/TEA antiport was reduced by 8% ethanol. Kinetic analysis showed that ethanol caused a decrease in Vmax of three transport systems, leaving Km values unchanged. Ethanol decreased phlorizin binding, which was closely correlated with the decrease in Vmax of Na+-glucose uptake. These results indicate that ethanol inhibits Na+-dependent uptakes of glucose, phosphate, and dicaboxylate and that the reduction in Vmax of Na+-glucose uptake is caused by a decrease in the number of active carrier proteins in the membrane.

Effect of ethanol on Na+-Pi uptake in opossum kidney cells: Role of membrane fluidization and reactive oxygen species

This study was undertaken to examine the effect of ethanol on Na+-dependent phosphate (Na+-Pi) uptake in opossum kidney (OK) cells, an established renal proximal tubular cell line. Ethanol inhibited Na+-dependent component of phosphate uptake in a dose-dependent manner with I50 of 8.4%, but it did not affect Na+-independent component. Similarly, ethanol inhibited Na+-dependent uptakes of glucose and amino acids (AIB, glycine, alanine, and leucine). Microsomal Na+-K+-ATPase activity was not significantly altered when cells were treated with 8% ethanol. Kinetic analysis showed that ethanol increased Km without a change in Vmax of Na+-Pi uptake. Inhibitory effect of n-alcohols on Na+-Pi uptake was dependent on the length of the hydrocarbon chain, and it resulted from the binding of one molecule of alcohol, as indicated by the Hill coefficient (n) of 0.8-1.04. Catalase significantly prevented the inhibition, but superoxide dismutase and hydroxyl radical scavengers did not alter the ethanol effect. A potent antioxidant DPPD and iron chelators did not prevent the inhibition. Pyrazole, an inhibitor of alcohol dehydrogenase, did not attenuate ethanol-induced inhibition of Na+-Pi uptake, but it prevented ethanol-induced cell death. These results suggest that ethanol may inhibit Na+-Pi uptake through a direct action on the carrier protein, although the transport system is affected by alterations in the lipid environment of the membrane.

Principles for Creation of PBL problems / 한국의학교육

A key factor in successful application of PBL is creation of good problems. Unfortunately, published collections of problems do not exist for many subjects. Consequently, instructors usually write their own problems and case studies if they want to use problem-based instruction. In this study we proposed principles for creation of PBL problems and presented its example. If effective problems suitable to educational goals are engaged, PBL can be introduced to the first grade medical students who do not have any knowlege about medicine. However, additional factors such as number of faculties and students, budget, availability of learning materials also affect successful implementation of PBL.