• Title/Summary/Keyword: drug-drug interactions

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Late avulsion of a free flap in a patient with severe psychiatric illness: Establishing a successful salvage strategy

  • Schaffer, Clara;Hart, Andrew;Watfa, William;Raffoul, Wassim;Summa, Pietro Giovanni di
    • Archives of Plastic Surgery
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    • v.46 no.6
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    • pp.589-593
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    • 2019
  • Post-traumatic defects of the distal third of the leg often require skipping a few steps of the well-established reconstructive ladder, due to the limited local reliable reconstructive options. In rare cases, the reconstructive plan and flap choice may encounter challenges when the patient has psychiatric illness affecting compliance with postoperative care. We describe a case of a patient with severe intellectual disability and an open fracture of the distal lower limb. After fracture management and debridement of devitalized tissues, the resultant soft tissue defect was covered with a free gracilis flap. On postoperative day 7, the patient ripped out the newly transplanted flap. The flap was too traumatized for salvage, so a contralateral free gracilis muscle flap was used. The patient showed good aesthetic and functional outcomes at a 1-year follow-up. When planning the postoperative management of patients with psychiatric illness, less complex and more robust procedures may be preferred over a long and complex surgical reconstruction requiring good compliance with postoperative care. The medical team should be aware of the risk of postoperative collapse, focus on the prevention of pain, and be wary of drug interactions. Whenever necessary, free tissue transfer should be performed despite potential compliance issues.

Interaction of Cu(II)-meso-tetrakis(n-N-methylpyridiniumyl)porphyrin (n = 2,3,4) with Native and Synthetic Polynucleotides Probed by Polarized Spectroscopy

  • Lee, Mi-Jin;Lee, Gil-Jun;Lee, Dong-Jin;Kim, Seog-K.;Kim, Jong-Moon
    • Bulletin of the Korean Chemical Society
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    • v.26 no.11
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    • pp.1728-1734
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    • 2005
  • The interactions of Cu(II)-meso-Tetrakis(n-N-methylpyridiniumyl)porphyrin (n = 2,3,4), respectively referred to as o-, m- and p-CuTMPyP, and DNA, poly$[d(A-T)_2]$ and poly$[d(G-C)_2]$ were investigated by circular and linear dichroism (CD and LD). In the o-CuTMPyP case, in which the rotation of the pyridinium ring is prevented, the shape of the CD spectrum when associated to DNA and poly$[d(A-T)_2]$ resembles and is characterized by a positive band at a low drug to DNA concentration ratio (R ratio) and is bisignate at a high R ratio. The former CD spectrum shape has been attributed to porphyrin that is bound monomerically outside of DNA while the latter can be attributed to those that are stacked. When o-CuTMPyP is bound to poly$[d(G-C)_2]$, the excitonic CD appeared at a relatively high R ratio. In contrast, a characteristic negative CD band in the Soret region was apparent for both m- and p-CuTMPyP when bound to DNA and poly$[d(G-C)_2]$ at the low R ratios, indicating that the porphyrin molecule intercalates. However, the DNA is bent near the intercalation site and the plane of the porphyrin molecule tilts relative to the DNA helix axis, as judged by the magnitude of the reduced LD. Various stacking patterns were identified by the shape of the CD spectrum for m- and p-CuTMPyP when bound to poly$[d(A-T)_2]$. Three species for the former complex and two for the latter complex were found which may reflect the extent of the stacking.

Recent Development of Protein Microarray and Proteogen Platform

  • Han, Moon-Hi;Kang, In-Cheol;Lee, Yoon-Suk;Cho, Yong-Wan;Lee, Eun-Kyoung
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.47-47
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    • 2005
  • There are many different surface technologies currently applied for preparation of protein chips. However, it requires innovative surface chemistry for capture proteins to be immobilized on chip surface keeping their conformation and activity intact and their orientation right, while they bind tightly and densely in a given array spot. Proteogen has developed 'ProteoChip BP' coated with novel proprietary linker molecules $(ProLinker^{TM})$ for efficient and robust immobilizations of capture proteins by improving surface properties of molecular captures. It was demonstrated that $ProLinker^{TM}$ gave the best surface performance in preparation of protein microarray chip base plates among others currently available on the market. In particular, the $ProLinker^{TM}-based$ surface chemistry has demonstrated to provide excellent performance in preparation of 'Antibody Chip' for analysis of biomarkers as well as proteome expression profiles. The linker molecule has also shown to be well applicable for development of biosensors and micro-beads as well as protein microarray and nano-array. ProteoChip BP can be used either for preparation of high-density array by using a microarrayer or for preparation of 'Well-on-a-Chip' with low density array, which is better applicable for quantitative analysis of biomarkers or protein-protein interactions. The biomarker assay can be performed either by direct or sandwich methods of fluorescence immunoassay. Application of ProteoChip BP has been well demonstrated by the extensive studies of 1) tumor-marker assays, 2) new drug screening by using 'Integrin Chip' and 3) protein expression profile analysis. Some of experimental results will be presented.

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The Application of Brain Stimulation in Psychiatric Disorders : An Overview (정신질환에서 뇌자극술의 적용)

  • Roh, Daeyoung;Kang, Lee Young;Kim, Do Hoon
    • Korean Journal of Biological Psychiatry
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    • v.24 no.4
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    • pp.167-174
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    • 2017
  • Based on advances in biotechnology and neuroscience, neuromodulation is poised to gain clinical importance as a treatment modality for psychiatric disorders. In addition to old-established electroconvulsive therapy (ECT), clinicians are expected to understand newer forms of neurostimulation, such as deep brain stimulation (DBS), vagus nerve stimulation (VNS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). Given the growing interest in non-invasive neuromodulation technologies, clinicians may seek sufficient information about neuromodulation to inform their clinical practice. A growing literature suggests that applications of non-invasive neuromodulation have evidence particularly for indications where treatments are currently insufficient, such as drug-resistant depression. However, positive neuromodulation studies require replication, and the precise interactions among stimulation, antidepressant medication, and psychotherapy are unknown. Further studies of long-term safety and the impact on the developing brain are needed. Non-invasive neuromodulatory devices could enable more individualized treatment. However, do-it-yourself (DIY) stimulation kits require a better understanding of the effects of more frequent patterns of stimulation and raise concerns about clinical supervision, regulation, and reimbursement. Wide spread enthusiasm for therapeutic potential of neuromodulation in clinical practice settings should be mitigated by the fact that there are still research gaps and challenges associated with non-invasive neuromodulatory devices.

Cosmetic Use of Botulinum Toxin Type A in the Face (A형 보튤리늄 톡신의 안면부 미용학적 적용)

  • Kang, Jae Goo
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.23 no.2
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    • pp.111-118
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    • 2012
  • Botulinum toxin is a potent neurotoxin that is produced by the bacterium Clostridium botulinum. The agent causes muscle paralysis by preventing the release of acetylcholine at the neuromuscular junction of striated muscle. Botulinum toxin A (Botox, AllerganInc., Irvine, California) is the most potent of seven distinct toxin subtypes that are produced by the bacterium. The toxin was initially used clinically in the treatment of strabismus caused by hypertonicity of the extraocular muscles and was sub-sequently described in the treatment of multiple disorders of muscular spasticity and dystonia. In treating patients with Botox for blepharospasm, Carruthers and Carruthers [5] noticed an improvement in glabellar rhytids. This ultimately led to the introduction and development of Botox as a mainstay in the treatment of hyperfunctional facial lines in the upper face. Since its approval by the U.S. Food and Drug Administration for the treatment of facial rhytids (2002), botulinum toxin A has expanded into wide-spread clinical use. Forehead, glabellar, and periocular rhytids are the most frequently treated facial regions. Indications for alternative uses for Botox in facial plastic and reconstructive surgery are expanding. These include a variety of well-established procedures that use Botox as an adjunctive agent to enhance results. In addition, Botox injection is finding increased usefulness as an independent modality for facial rejuvenation and rehabilitation. The agent is used beyond its role in facial rhytids as an effective agent in the management of dynamic disorders of the face and neck. Botox injection allows the physician to precisely manipulate the balance between complex and conflicting muscular interactions, thus resetting their equilibrium state and exerting a clinical effect. This article will address some of the new and unique indications on Botox injection in the face (the lower face and neck, combination with fillers). Important points in terms of its clinical relevance will be stressed, such as an understanding of functional facial anatomy, the importance of precise injections, and correct dosing all are critical to obtaining natural outcomes.

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Pairwise Neural Networks for Predicting Compound-Protein Interaction (약물-표적 단백질 연관관계 예측모델을 위한 쌍 기반 뉴럴네트워크)

  • Lee, Munhwan;Kim, Eunghee;Kim, Hong-Gee
    • Korean Journal of Cognitive Science
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    • v.28 no.4
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    • pp.299-314
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    • 2017
  • Predicting compound-protein interactions in-silico is significant for the drug discovery. In this paper, we propose an scalable machine learning model to predict compound-protein interaction. The key idea of this scalable machine learning model is the architecture of pairwise neural network model and feature embedding method from the raw data, especially for protein. This method automatically extracts the features without additional knowledge of compound and protein. Also, the pairwise architecture elevate the expressiveness and compact dimension of feature by preventing biased learning from occurring due to the dimension and type of features. Through the 5-fold cross validation results on large scale database show that pairwise neural network improves the performance of predicting compound-protein interaction compared to previous prediction models.

Selection of Potential Virulence Factors Contributing to Streptococcus suis Serotype 2 Penetration into the Blood-Brain Barrier in an In Vitro Co-Culture Model

  • Liu, Hongtao;Zhu, Seng;Sun, Yingying;Li, Na;Gu, Jingmin;Sun, Changjiang;Feng, Xin;Han, Wenyu;Jiang, Jianxia;Lei, Liancheng
    • Journal of Microbiology and Biotechnology
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    • v.27 no.1
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    • pp.161-170
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    • 2017
  • Meningitis caused by Streptococcus suis serotype 2 (S. suis 2) is a great threat to the pig industry and human health. Virulence factors associated with the pathogenesis of meningitis have yet to be clearly defined, even though many potential S. suis 2 virulence factors have been identified. This greatly hinders the progress of S. suis 2 meningitis pathogenesis research. In this study, a co-culture blood-brain barrier (BBB) model was established using primary porcine brain microvascular endothelial cells and astrocytes, and the whole genome library of S. suis 2 was constructed using phage display technology. Finally, a total of 14 potential virulence factors contributing to S. suis 2 adherence to and invasion of the BBB were selected by analyzing the interactions between the phage library and the co-culture model. Twelve of these factors have not been previously reported in meningitis-related research. The data provide valuable insight into the pathogenesis of S. suis 2 meningitis and potential targets for the development of drug therapies.

The Effect of Long-term Administration of Epigallocatechin on the Pharmacokinetics of Verapamil in Rats (흰쥐에서 에피게로카테친의 장기투여가 베라파밀의 약물동태에 미치는 영향)

  • Yun, Jae-Kyung;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.37 no.2
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    • pp.107-111
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    • 2007
  • Epigallocatechin gallate (EGCC), a flavonoid, is the main component of green tea extracts. EGCG has been reported to be an inhibitor of P-glycoprotein (P-gp) and cytochrom P450 3A(CYP3A4). This study investigated the effect of long-term administration of EGCG on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats pretreated with EGCG (7.5 mg/hg) for 3 and 9 days. Compared to oral control group, the presence of EGCG significantly (p<0.01) increased the area under the plasma concentration-time curve (AUC) of verapamil by 102% (coad), 83.2% (3 days) and 52.3% (9 days), and the peak concentration $(C_{max})$ by 134% (coad), 120% (3 days) and 66.1% (9 days). The absolute bioavailability (A.B.%) of verapamil was significantly (p<0.01) higher by 8.4% (coad), 7.7% (3 days), 6.4% (9 days) compared to control (4.2%), and presence of EGCG was no significant change in the terminal half-life $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of verapamil. Our results indicate that EGCG significantly enhanced oral bioavailability of verapamil in rats, implying that presence of EGCG could be effective to inhibit the CYP3A4-mediated metabolism and P-gp efflux of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with EGCG or EGCG-containing dietary.

Effect of Naringin on the Bioavailability of Losartan in Rats (흰쥐에서 나린진이 로살탄의 생체이용율에 미치는 영향)

  • Lee, Chong-Ki;Choi, Jun-Shik
    • YAKHAK HOEJI
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    • v.53 no.5
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    • pp.259-264
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    • 2009
  • The present study was to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of losartan in rats. Pharmacokinetic parameters of losartan in rats were determined after an oral administration of losartan (9 mg/kg) in the presence or absence of naringin (0.5, 2.5 and 10 mg/kg). The pharmacokinetic parameters of losartan were significantly altered by the presence of naringin compared with the control group (given losartan alone). Presence of naringin significantly (p<0.05, 2.5 mg/kg; p<0.01, 10 mg/kg) increased the area under the plasma concentration?time curve (AUC) of losartan by 43.7~63.0% and peak plasma concentration ($C_{max}$) of losartan by 31.7~45.5%. Consequently, the absolute bioavailability (AB) of losartan in the presence of naringin was 43.8~62.9%, which was enhanced significantly (p<0.05, p<0.01) compared to that in the oral control group (22.4%). The relative bioavailability (R.B.) of losartan increased by 1.44- to 1.63-fold in the presence of naringin. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($t_{1/2}$) of losartan in the presence of naringin. In conclusion, the presence of naringin significantly enhanced the oral bioavailability of losartan, implying that presence of naringin might be mainly effective to inhibit the cytochrome P450 (CYP)3A-mediated metabolism, resulting in reducing gastrointestinal and hepatic first-pass metabilism and Pglycoprotein (P-gp)-mediated efflux of losartan in small intestine. Concurrent use of naringin or naringin-containing dietary supplement with losartan should require close monitoring for potential drug interactions.

Effects of Thujae Orientalis Folium (TOF) on Gene Expression of Human melanoma cells (SK-MEL-2) (측백엽(側柏葉)이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향)

  • Jung, Min-Young;Kim, Jong-Han;Park, Su-Yeon;Choi, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.81-108
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    • 2010
  • Objective : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5, PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.