Investigation of the pharmacokinetics of paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments by the skin-blood synchronous microdialysis coupled with LC/MS is reported in this study. The microdialysis systems were established by linear probes and concentric circles probes. In vivo recovery of paeonol in skin is (69.7 +/- 4.8) % and in blood is (51.6 +/- 7.2)%. The paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments were administered to rats. PBS (pH 7.4) served as perfused solution. The perfusion rate was 5 microL x mL(-1) and the microdialysis samples were collected every 20 min intervals. The paeonol concentration in perfused solution was determined by LC/MS. The results showed that paeonol microemulsion and microemulsion-based gels significantly raised the drug concentrations in skin more than that of paeonol ointments. The paeonol microemulsion-based gels has similar bioavailability as the paeonol ointments in blood, but its blood drug concentrations were steadier. The paeonol microemulsion-based gels may be developed into a new preparation for dermis eczema. The skin-blood synchronous microdialysis technique proved to be a new method for the pharmacokinetics study of transdermal delivery systems.

Aim To explore the possible anti-inflammation mechanism of paeonol by investigating its effects on the MMP-9 mRNA expression and cytokines production in human dermal fibroblasts induced by TNF-?.Methods The effect of paneonol on the expression of MMP-9 mRNA was detected by semi-quantitative RT-PCR.The modulation of paneonol on the production of IL-1?,IL-6 and IL-8 in fibroblasts was measured by ELISA.Results MMP-9 hardly expressed in human dermal fibroblast.The results also showed that TNF-? significantly induced the expression of MMP-9 in fibroblasts and at the same time paeonol inhibited the expression of MMP-9.TNF-? stimulated the production of IL-1? and IL-8 in fibroblasts,while 10~100 mg?L-1 paeonol inhibited TNF-?-induced IL-1? and IL-8 production in fibroblasts but had nothing to do with the production of IL-6.Conclusions Paeonol can inhibit the expression of MMP-9 mRNA,IL-1? and IL-8 induced by TNF-?.

BACKGROUND: Some studies have showed that after indirect co-culture, bone marrow mesenchymal stem cells can differentiate into myocardial cells and hepatocypte-like cells. OBJECTIVE: To investigate the possibility of human umbilical cord blood mesenchymal stem cells (UCB-MSCs) to differentiate into hepatocytes by co-culture with human hepatocyte line LO2 in vitro.METHODS: Full-term umbilical cord blood samples were obtained sterilely. The UCB-MSCs were isolated by density gradient centrifugation and directly adherence growth, then passaged with trypsin digestion at 80% cell fusion. By utilizing cell culture plate insets with microporous membrane combined with 6-well plate, the LO2-/UCB-MSCs co-culture system was established. UCB-MSCs were plated into the wells of 6-well plate at a density of 1×10~7/L. LO2 cells were plated into the cell culture plate insert at a density of 1×10~5/L. UCB-MSCs were plated in both layers in the control group. Surface markers of adhered cells were detected by flow cytometry. Morphological changes of UCB-MSCs were observed by inverted phase contrast microscopy. mRNA expression was detected by reverse transcriptase PCR. RESULTS AND CONCLUSION: HUCB MSCs expressed CD44 and CD29 strongly, but CD34 and CD45 were expressed negatively. After 5 days, fusiform-shaped cells were reduced in the co-culture group; while, the time passing by, cells shaped irregular round or polygonal were increased, which were similar to hepatocytes. At 4 weeks after culture, UCB-MSCs were still fusiform-shaped in the control group. At day 5 after culture, alpha fetoprotein mRNA expressed positively, but other expressed negatively in the co-culture group; at day 14 after culture, cytokeratin-19 mRNA and albumin mRNA expressions were observed; moreover, with the time passing by, the expression of albumin mRNA was increased, but the expression of alpha fetoprotein-19 mRNA was decreased. Antigenic expressions in the control group were negative. This suggested that UCB-MSCs could differentiate into hepatocypte-like cells by co-culture with human hepatocyte line LO2 in vitro.

OBJECTIVETo prepare paeonol microemulsion and microemulsion gel, and investigate its content, physical and chemical properties. Their transdermal properties in vitro were studied as well.

METHODIPM acted as oil phase, lecithin/APG as surfactant, 1,2-propanediol as cosurfactant, water was added dropwise to the oil phase to prepare paeonol microemulsion at room temperature using magnetic stirring. HPLC method were used to determine the content of paeonol in paeonol microemulsion. Transmission electron microscopy and laser particle size analyzer were used to determine the shape and size of the microemulsion. Carbopol 940 was uesd as substrate to prepare paeonol microemulsion gel. Franz diffusion cell was used for characterizing the microemulsion and gel transdermal properties in vitro.

RESULTThe paeonol microemulsion was O/W microemulsion. Its uniform particle size was 32 nm and was with roundness appearance and stable content. The steady-state permeation rates of paeonol saturated aqueous solution, microemulsion, and microemulsion gel were 47.846, 103.760, 70.401 microg x cm(-2) x h(-1), and their 12 h cumulative amount of infiltration were 657.179, 1 266.484, 881.217 microg x cm(-2), respectively.

CONCLUSIONThe 12 h cumulative infiltration and infiltration rate of paeonol microemulsion and microemulsion gel are better than the saturated aqueous solution. Paeonol microemulsion gel is a new dosage form for transdermal drug delivery.

Acetophenones ; pharmacokinetics ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; pharmacokinetics ; Emulsions ; chemistry ; Gels ; chemistry ; Models, Biological ; Skin Absorption

Objective To investigate image quality and clinical value of dual-source dual energy virtual non-contrast (VNC) CT of the head. MethodsSixty-two patients suspected of cerebrovascular diseases underwent conventional non-contrast (CNC) CT and dual energy CTA examination of the head with dual-source CT. Virtual non-contrast images were reconstructed using dual energy software. The CT values of gray matter, white matter, cerebrospinal fluid, hyperdense hemorrhagic lesion and hypodense ischemic lesion were compared between CNC and VNC images. A four-score scale was used to assess image quality subjectively. Image noise, radiation dosage and detection rate were compared between CNC and VNC images. Paired t test, Wilcoxon signed ranks test and Chi-square test (McNemar test and Kappa test) were used. Results The CT value on CNC and VNC images, were (43. 3 ± 1.5) and (33. 2 ± 1.3) HU for gray matter (t = 46.98, P ＜ 0. 01), (32. 9 ± 1.3) and (28.8 ± 1.6) HU for white matter(t = 16. 28, P ＜0.01), (9.0 ± 1.4) and (5.3 ± 1.9) HU for cerebrospinal fluid (t=12.41, P＜0.01),(62.8 ±10.0) and (51.3 ± 11.5) HU for hyperdense lesion (Z = -4.37, P ＜ 0.01), (20.7 ±4.7) and (18.0 ±6. 9) HU for hypodense lesion (t = 3. 84, P ＜ 0. 01), respectively. VNC images[(1.63 ±0.34) HU]had more noise than CNC images[(0.99±0.18) HU](Z= -6.41, P＜0.01). VNC [(0. 53 ± 0. 08) mSv]had less effective dose than CNC[(1.37 ± 0. 23) mSy](Z= - 6. 45, P ＜ 0. 01).In subjective assessment, VNC images had more noise (2. 7 ± 0. 5 for VNC and 3.9 ± 0. 3 for CNC,Z = -6. 84, P ＜ 0. 01) and skull base-related artifacts (2. 4 ± 0. 9 for VNC and 3.7 ± 0. 5 for CNC,Z = -6. 15, P ＜0. 01) than CNC images. The gray/white matter contrast (1.3 ± 0. 5 for VNC and 3.3 ±0. 6 for CNC, Z = - 7. 01, P ＜ 0. 01), hyperdense lesion display (3.0 ± 0. 4 for VNC and 4. 0 ± 0. 0 for CNC,Z = -4. 52, P ＜ 0. 01) and hypodense lesion display (3.2 ± 0. 8 for VNC and 3.9 ± 0. 3 for CNC,Z= -3. 12, P ＜0. 01) on VNC images were lower than those on CNC images. In per-patient analysis,29 cases of hyperdense lesion (hemorrhage) were found on VNC images without misdiagnosis. The sensitivity, specificity, positive predictive value and negative predictive value were all 100. 0% (29/29,33/33, 29/29, 33/33). VNC images had the same detection rate of hyperdense lesions as CNC images (P ＞0. 05, Kappa = 1. 000) at per-patient level. Twenty-two patients with hypodense ischemic lesions were found on VNC images with one false positive case and two false negative cases. The sensitivity,specificity, positive predictive value and negative predictive value were 91.3% (21/23), 97.4%(38/39), 95.5% (21/22) and 95.0% (38/40) respectively. No statistical difference was found in detecting hypodense lesions between VNC and CNC images (χ2 = 0. 00, P ＞ 0. 05, Kappa = 0. 895). In per-lesion analysis, 53 hemorrhage lesions were found on VNC images with false negative results of four lesions and no false positive result. The sensitivity, specificity, positive predictive value and negative predictive value were 93.0% (53/57), 100. 0% (38/38), 100. 0% (53/53) and 90. 5% (38/42)respectively. There was no significant difference in detection rate of hyperdense lesion between VNC and CNC images (χ2 =2. 25, P ＞0. 05, Kappa =0. 914). Thirty-eight hypodense lesions were found on VNC images with 2 false positive lesions and 13 false negative lesions. The sensitivity, specificity, positive predictive value and negative predictive value were 73.5% (36/49), 96.4% (53/55), 94. 7% (36/38)and 80. 3% (53/66) respectively. The detection rate of hypodense lesion on VNC images was lower than that on CNC images (χ2 = 6. 67 ,P ＜ 0.01, Kappa = 0. 707). Conclusion Compared with CNC images,head VNC images have reduced image quality and radiation dosage. VNC images can replace CNC images potentially in detecting intracranial hemorrhage and provide information for ischemic cerebrovascular diseases to some extent.

OBJECTIVE: To evaluate the clinical usefulness of the Korean Developmental Screening Test (K-DST) via comparison with Korean Ages and Stages Questionnaire (K-ASQ) for the diagnosis of developmental delay in pediatric patients. METHODS: The K-DST and K-ASQ were used to screen pediatric patients who visited the hospital for evaluation and diagnosis of delayed development. Korean Bayley Scales of Infant Development-II (K-BSID-II) or Korean Wechsler Preschool and Primary Scale of Intelligence III (K-WPPSI-III) were used for the standardized assessment. Moreover, the final clinical diagnosis was confirmed by three expert physicians (rehabilitation doctor, psychiatrist, and neurologist). The sensitivity and specificity of each screening tool for the final diagnosis were investigated and correlated with standardized assessments. RESULTS: A total of 145 pediatric consultations were conducted, which included 123 developmental disorders (40 autism spectrum disorders, 46 global developmental delay/intellectual disability, and 37 developmental language disorders) and another 22 that were not associated with any such disorders. The sensitivity and specificity of K-DST based on the final clinical diagnosis were 82.9% and 90.9%, respectively, which were not significantly different from that of K-ASQ (83.7% and 77.3%). Both K-DST and K-ASQ showed good correlation with K-BSID-II and K-WPPSI-III. No significant difference was found between the K-DST and K-ASQ measures. CONCLUSION: K-DST is an excellent screening tool and is expected to replace K-ASQ with high validity.
Autism Spectrum Disorder ; Communication Disorders ; Developmental Disabilities ; Diagnosis ; Humans ; Infant ; Intellectual Disability ; Intelligence ; Mass Screening ; Motor Skills Disorders ; Psychiatry ; Referral and Consultation ; Sensitivity and Specificity ; Weights and Measures

PURPOSE: South Korea has a high prevalence of gallstones, the type of which could be influenced by changes in diet and socioeconomic status. Here we aimed to investigate the epidemiological characteristics and changing patterns of gallstones over the past 20 years in Korea. METHODS: A total of 5,808 patients who underwent cholecystectomy due to gallstones at Seoul National University Hospital between 1996 and 2015 were analyzed. Patients were divided into 4 subgroups: period 1 (1996–2000, n = 792), period 2 (2001–2005, n = 1,215), period 3 (2006–2010, n = 1,525), period 4 (2011–2015, n = 2,276). Gallstones were classified by type: pure cholesterol (PC), mixed cholesterol (MC), calcium bilirubinate (CB), black pigment (BP), and combination (COM). RESULTS: The female to male ratio was 1.16 with mean ages of 53.6 and 55.3 years old, respectively. The ratio of cholesterol stones to pigment stones was 0.96:1. The mean age and male to female ratio of the patients increased over time. The proportion of cholesterol vs pigment stone did not differ significantly. Proportions of PC and MC stone subtypes did not change notably, whereas proportion of BP stones increased (34.0% to 45.5%), and CB stones decreased (20.7% to 5.3%). CONCLUSION: Gallstone types and occurrences were affected by environmental changes, and pigment stones remained common in Korea. Although no distinct increase in cholesterol stones was noted, the proportion of CB stones decreased. As the mean age at gallstone presentation increases, BP stones could become more prevalent.
Bilirubin ; Cholecystectomy ; Cholecystolithiasis ; Cholelithiasis ; Cholesterol ; Classification ; Diet ; Female ; Gallstones ; Humans ; Korea ; Male ; Prevalence ; Seoul ; Social Class

BACKGROUND: Sugammadex is a novel neuromuscular reversal agent, but its associated hypersensitivity reaction and high cost have been obstacles to its widespread use. In the interest of reducing the necessary dosage of sugammadex, the reversal time of the combined use of sugammadex and neostigmine from moderate neuromuscular blockade were investigated. METHODS: The patients enrolled ranged in age from 18 to 65 years old with American Society of Anesthesiologists class 1 or 2. The subjects were randomly assigned into one of the four groups (Group S2, S1, SN, and N; n = 30 per group). The reversal agents of each groups were as follows: S2 - sugammadex 2 mg/kg, S1 - sugammadex 1 mg/kg, SN - sugammadex 1 mg/kg + neostigmine 50 microg/kg + glycopyrrolate 10 microg/kg, N - neostigmine 50 microg/kg + glycopyrrolate 10 microg/kg. The time to recovery of the train-of-four (TOF) ratio was checked in each group. RESULTS: The time to 90% recovery of TOF ratio was 182.6 +/- 88.9, 371.1 +/- 210.4, 204.3 +/- 103.2, 953.2 +/- 379.7 sec in group S2, S1, SN and N, respectively. Group SN showed a significantly shorter recovery time than did group S1 and N (P < 0.001). However, statistically significant differences between the S2 and SN groups were not be observed (P = 0.291). No hypersensitivity reactions occurred in all groups. CONCLUSIONS: For the reversal from rocuronium-induced moderate neuromuscular blockade, the combined use of sugammadex and neostigmine may be helpful to decrease the recovery time and can also reduce the required dosage of sugammadex. However, the increased incidence of systemic muscarinic side effects must be considered.
Glycopyrrolate ; Humans ; Hypersensitivity ; Incidence ; Neostigmine* ; Neuromuscular Blockade*

Purpose: The objective of this study was to propose a deep-learning model for the detection of the mandibular canal on dental panoramic radiographs. Materials and Methods: A total of 2,100 panoramic radiographs (PANs) were collected from 3 different machines: RAYSCAN Alpha (n=700, PAN A), OP-100 (n=700, PAN B), and CS8100 (n=700, PAN C). Initially, an oral and maxillofacial radiologist coarsely annotated the mandibular canals. For deep learning analysis, convolutional neural networks (CNNs) utilizing U-Net architecture were employed for automated canal segmentation. Seven independent networks were trained using training sets representing all possible combinations of the 3 groups. These networks were then assessed using a hold-out test dataset. Results: Among the 7 networks evaluated, the network trained with all 3 available groups achieved an average precision of 90.6%, a recall of 87.4%, and a Dice similarity coefficient (DSC) of 88.9%. The 3 networks trained using each of the 3 possible 2-group combinations also demonstrated reliable performance for mandibular canal segmentation, as follows: 1) PAN A and B exhibited a mean DSC of 87.9%, 2) PAN A and C displayed a mean DSC of 87.8%, and 3) PAN B and C demonstrated a mean DSC of 88.4%. Conclusion This multi-device study indicated that the examined CNN-based deep learning approach can achieve excellent canal segmentation performance, with a DSC exceeding 88%. Furthermore, the study highlighted the importance of considering the characteristics of panoramic radiographs when developing a robust deep-learning network, rather than depending solely on the size of the dataset.

Sucrose is a natural product occurs widely in nature. In living organisms such as plants, sucrose phosphate synthase (SPS) is the key rate-limiting enzyme for sucrose synthesis. SPS catalyzes the synthesis of sucrose-6-phosphate, which is further hydrolyzed by sucrose phosphatase to form sucrose. Researches on SPS in recent decades have been focused on the determination of enzymatic activity of SPS, the identification of the inhibitors and activators of SPS, the covalent modification of SPS, the carbohydrate distribution in plants regulated by SPS, the mechanism for promoting plant growth by SPS, the sweetness of fruit controlled by SPS, and many others. A systematic review of these aspects as well as the crystal structure and catalytic mechanism of SPS are presented.
Carbohydrate Metabolism ; Glucosyltransferases/metabolism* ; Plants/metabolism* ; Sucrose