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Chai Young Lee,1,&ast; Sun Hye Shin,1,&ast; Hye Sook Choi,2 Yunjoo Im,1 Bo-Guen Kim,1 Ju Yeun Song,1 Daegeun Lee,1 Hye Yun Park,1 Jun Hyeok Lim3 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hye Yun Park, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Tel +82-2-3410-3429, Fax +82-2-3410-3849, Email hyeyunpark@skku.edu Jun Hyeok Lim, Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea, Tel +82-32-890-1038, Fax +82-32-890-3099, Email jhl@Inha.ac.krPurpose: Vitamin D insufficiency or deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD). However, the association between vitamin D levels and respiratory symptoms in patients with stable COPD has not been fully investigated. This study evaluated the association between vitamin D levels and respiratory symptoms in patients with stable COPD.Patients and Methods: Patients with COPD who had their serum 25-hydroxyvitamin D (25-OH vitamin D) level measured within 6 months of spirometry between January 2016 and April 2020 were retrospectively included. Respiratory symptoms were assessed using the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT) score.Results: Of the 329 included patients, 193, 88, and 48 were categorized as having vitamin D deficiency (< 20 ng/mL), insufficiency (20– 29 ng/mL), and sufficiency (≥ 30 ng/mL), respectively. The mean serum 25-OH vitamin D level of each group was 13.45 ng/mL, 24.61 ng/mL, and 38.90 ng/mL, respectively. Patients with vitamin D insufficiency/deficiency showed higher CAT scores than those with vitamin D sufficiency (p = 0.004). In multivariable adjusted models, vitamin D insufficiency/deficiency was significantly associated with a CAT score of 10 or more (adjusted odds ratio [aOR] = 2.41, 95% confidence interval [CI] = 1.20– 4.82, p = 0.013) and mMRC ≥ 2 (aOR = 2.39, 95% CI = 1.08– 5.32, p = 0.032). Among CAT items, the amount of phlegm (p = 0.008), chest tightness (p = 0.030), breathlessness walking upstairs (p < 0.001), home activity limitations (p = 0.002), and lack of energy (p = 0.003) were significantly associated with vitamin D insufficiency/deficiency after adjustment for age, sex, body mass index, smoking history, Charlson comorbidity index, post-bronchodilator forced expiratory volume in 1 second, and season of blood draw.Conclusion: Vitamin D insufficiency/deficiency were associated with worse respiratory symptoms in patients with stable COPD.Keywords: chronic obstructive pulmonary disease, vitamin D, respiratory symptoms, COPD assessment test, modified Medical Research Council

Ina Jeong,1,* Jae-Hyun Lim,2,* Dong Kyu Oh,3 Woo Jin Kim,4 Yeon-Mok Oh3 1Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea; 2Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea *These authors contributed equally to this work Purpose: As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues. Patients and methods: First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers. COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity

Joel Hua-Liang Lim,1 Hong Liang Tey,1,2 Wei-Sheng Chong,11Department of Dermatology, National Skin Centre, 2Lee Kong Chian School of Medicine, Nanyang Technologicial University, SingaporeAbstract: Confluent and reticulated papillomatosis (CRP) of Gougerot and Carteaud was first typified in 1927. With the help of electron microscopy, it has been elucidated that CRP arises due to aberrant keratinization. However, till date, there is no clear consensus on the etiologic trigger for CRP. Prevailing postulates include a bacterial trigger by Dietzia papillomatosis (type strain N 1280T), an exaggerated cutaneous response to Malassezia furfur, an endocrine basis stemming from insulin resistance, ultraviolet light-induced epidermal change, amyloid deposition, and a loss-of-function mutation in keratin 16. CRP typically presents as asymptomatic hyperpigmented papules and plaques with peripheral reticulation over the nape, axillae, upper chest, and upper back, occasionally with extension superior to the forehead and inferior to the pubic region. Dermoscopy may be used in the evaluation of CRP, but its diagnosis is made on clinical grounds given its nonspecific histopathological findings. Although successful treatment with topical keratolytics, retinoids, or antifungals has been reported, antibiotics, such as minocycline, at anti-inflammatory doses have emerged as a preferred therapeutic option. In this article, we review the diagnostic considerations in CRP and its therapeutic options. Keywords: Gougerot, Carteaud, reticulate, papillomatous, diagnosis, treatment

Seung-Jun Seo,1,* Chung Wung Bark,2,* Jae-Hong Lim,1 Yong-Gun Kim3 1Industrial Technology Convergence Center, Pohang Accelerator Laboratory, POSTECH, Pohang, Gyeongbuk, 2Department of Electrical Engineering, Gachon University, Seongnam, 3Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea *These authors contributed equally to this work Objective: Maxillary sinus floor augmentation has been shown to be the most predictable surgical technique for enhancing the bone volume in the posterior area of the maxilla. The purpose of this study was to analyze the serial slice image segmentation of newly formed bone and bone substitutes after sinus floor elevation using synchrotron radiation X-ray micro-computed tomography (SR-µCT).Materials and methods: Bone biopsy specimens were collected after 6 months of sinus floor augmentation. From the six bone biopsy specimens, the cross-sectional images at every 8 µm along the apical direction from the inferior border using serial segmentation from three-dimensional reconstructed X-ray images were analyzed. The amount of new bone and bone substitutes were measured at each slicing image (300–430 images per specimen).Results: The bone dynamics between the new bone and bone substitutes along the inferior–superior direction in humans after maxillary sinus floor elevation (MSFE) were analyzed using the whole sample region. Although these observations suggest that the specimens are structurally inhomogeneous, sinus floor elevation was confirmed to be a reliable surgical procedure for increasing the amount of bone.Conclusion: SR-µCT is highly effective for obtaining high-resolution images. An analysis of biological specimens using SR-µCT is quite reliable and this technique will be an important tool in the wide field of tissue engineering. Keywords: maxillary sinus floor elevation, synchrotron radiation, micro-computed tomography, serial segmentation, new bone formation

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

Ji-Ho Lim1,*, Sung-Kyun You1,*, Jong-Suep Baek1, Chan-Ju Hwang1, Young-Guk Na1, Sang-Chul Shin2, Cheong-Weon Cho11College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea, 2College of Pharmacy, Chonnam National University, Buggu, Gwangju, South Korea *These authors contributed equally to this workBackground: Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects.Methods: In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated.Results: There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone.Conclusion: Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.Keywords: gemcitabine, polymeric microparticulates, mucoadhesive, enteric coating, cellular uptake, oral absorption

Chang-Gu Keum1*, Young-Wook Noh1*, Jong-Suep Baek1, Ji-Ho Lim1, Chan-Ju Hwang1, Young-Guk Na1, Sang-Chul Shin2, Cheong-Weon Cho11College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea; 2College of Pharmacy, Chonnam National University, Yongbongdong, Buggu, Gwangju, South Korea *These authors contributed equally to this work Background: Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. Methods: Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2–5 minutes of sonication time, 70–130 W sonication power, and 5–25 mg drug loading. Results: A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. Conclusion: Our research shows that the choice of surfactant is important for controlled release of docetaxel. Keywords: docetaxel, nanoparticles, poly (lactic-co-glycolic acid), formulation variables, sonication, encapsulation efficiency

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

Objective: This study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor-beta1 (TGF-beta1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia. Method: We estimated the levels of sEng and TGF-beta1 in plasma collected in the second trimester at the time of genetic amniocentesis from 60 women who subsequently developed preeclampsia and 124 contemporaneous normotensive women. Results: sEng levels were higher in cases than in controls, whereas TGF-beta1 levels were lower (P < 0.001). sEng levels, but not TGF-beta1 levels, were higher in cases with severe or preterm delivery than in cases with mild preeclampsia or term delivery (P < 0.001) and were increased in cases destined to deliver a small gestational age neonate (P < 0.001). Moreover, sEng levels, but not TGF-beta1 levels, showed a positive correlation with maximum diastolic and systolic blood pressure (r = 0.57, P < 0.001; and r = 0.33, P < 0.001, respectively) and proteinuria (r = 0.42, P < 0.001). Conclusion: Early midtrimester plasma levels of sEng are predictive of subsequence occurrence and severity of preeclampsia, in terms of severity of hypertension and proteinuria, prematurity, and association with small for gestational age neonates. [ABSTRACT FROM AUTHOR]

Patients undergoing treatment for cancer have reported a variety of work-related problems. The aim of this study was to investigate the impact of a cancer diagnosis on employment status, and to identify relevant associated factors. This prospective cohort study was conducted at the National Cancer Center in Korea. Male patients newly diagnosed with stomach, liver, or colorectal cancers were recruited. Patients were interviewed and asked to complete an employment questionnaire every 3 months for 24 months. Clinical, sociodemographic and work-related factors were assessed. There were 305 male patients who had a primary diagnosis of cancer and underwent appropriate treatment. Of the 305 male patients who were employed at the time of diagnosis, 53% lost their job, and of these 23% later reemployed. In a multivariate Cox regression analysis, job loss was significantly associated with years of education, job characteristics and disease stage. Reemployment was significantly associated with disease stage and cancer site. Change of employment was common among cancer patients in Korea. With an understanding of the factors involved, it should be possible to reduce unnecessary work cessation, and increase the rate of employment of cancer survivors. Copyright (c) 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the provision of acupuncture services in the general practice setting.

Background: Nontypeable Haemophilus influenzae (NTHi) is an important respiratory pathogen implicated as an infectious trigger in chronic obstructive pulmonary disease, but its molecular interaction with human lung epithelial cells remains unclear. Herein, we tested that the hypothesis that NTHi induces the expression of cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) via activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B in pulmonary alveolar epithelial cells.Methods: Human alveolar epithelial A549 cells were infected with different concentrations of NTHi. The phosphorylation of p38 MAPK was detected by Western blot analysis, the DNA binding activity of NF-kappa B was assessed by electrophoretic mobility shift assay (EMSA), and the expressions of COX-1 and 2 mRNA and PGE2 protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. The roles of Toll-like receptor (TLR) 2 and TLR4, well known NTHi recognizing receptor in lung epithelial cell and gram-negative bacteria receptor, respectively, on the NTHi-induced COX-2 expression were investigated in the HEK293 cells overexpressing TLR2 and TLR4 in vitro and in the mouse model of NTHi-induced pneumonia by using TLR2 and TLR4 knock-out mice in vivo. In addition, the role of p38 MAPK and NF-kappa B on the NTHi-induced COX-2 and PGE2 expression was investigated by using their specific chemical inhibitors.Results: NTHi induced COX-2 mRNA expression in a dose-dependent manner, but not COX-1 mRNA expression in A549 cells. The enhanced expression of PGE2 by NTHi infection was significantly decreased by pre-treatment of COX-2 specific inhibitor, but not by COX-1 inhibitor. NTHi induced COX-2 expression was mediated by TLR2 in the epithelial cell in vitro and in the lungs of mice in vivo. NTHi induced phosphorylation of p38 MAPK and up-regulated DNA binding activity of NF-kappa B. Moreover, the expressions of COX-2 and PGE2 were significantly inhibited by specific inhibitors of p38 MAPK and NF-kappa B. However, NTHi-induced DNA binding activity of NF-kappa B was not affected by the inhibition of p38 MAPK.Conclusion: NTHi induces COX-2 and PGE2 expression in a p38 MAPK and NF-kappa B-dependent manner through TLR2 in lung epithelial cells in vitro and lung tissues in vivo. The full understanding of the role of endogenous anti-inflammatory PGE2 and its regulation will bring new insight to the resolution of inflammation in pulmonary bacterial infections. [ABSTRACT FROM AUTHOR]