• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.2
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• pp.37-43
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• 2020

Phenylketonuria is the most prevalent disorder caused by an inborn error in aminoacid metabolism. It results from mutations in the phenylalanine hydroxylase (PAH) gene. If untreated or late treated, results in profound and irreversible mental disability. Newborn screening test identify patients with phenylketouria. The early initiation of a phenylalanine restricted diet very soon prevents most of the neuropsychiatric complications. However, the diet therapy is difficult to maintain and compliance is poor, especially in adolescents and adulthood. Since 2015, American Medical College of Medical Genetics and Genomics (ACMG) recommended more strong restrictive diet therapy for target blood level of phenylalanine (<360 umol/L). For over four decades the only treatment was a very restrictive low phenylalanine diet. This changed in 2007 with the approval of cofactor therapy (Tetrahydrobiopterin, BH4) which is effective in up to 30% of patients. Data from controlled clinical trials with sapropterin dihydrochloride indicate a similar occurrence of all-cause adverse events with this treatment and placebo. Large neutral aminoacids (LNAA) competes with phenylalanine for transport across the blood-brain-barrier and have a beneficial effect on executive functioning. A new therapy has just been approved that can be effective in most patients with PAH deficiency regardless of their degree of enzyme deficiency or the severity of their phenotype. Phenylalanine ammonia lyase (PAL-PEG) was approved in the USA by FDA in May of 2018 for adult patients with uncontrolled blood phenylalanine concentrations on current treatment. Nucleic acid therapy (therapeutic mRNA or gene therapy) is likely to provide longer term solutions with few side effects.

• Journal of Navigation and Port Research
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• v.27 no.3
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• pp.283-288
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• 2003

Recently, the growth of applications and services over high-speed Internet increases, ATM networks as wide area back-bone has been a major solution. As the conventional TCP/IP suite is still the standard protocol used to support upper application on current. Internet, the issues regarding whether TCP/IP will operate efficiently on top of an ATM infrastructure and how to control its QoS still remain for studies. TCP uses a window-based protocol for flow control in the transport layer. When TCP uses the UBR service in ATM layer, the control method is only buffer management. If a cell is discarded in ATM layer, one whole packet of TCP will be lost; this fact occur the most TCP performance degradation. Several dropping strategies, such as Tail Drop, EPD, PPD, SPD, FBA, have been proposed to improve the TCP performance over ATM. In this paper, to improve the TCP performance, we propose a packet dropping scheme that is based on comparison with EPD, SPD and FBA. Our proposed scheme is applied to schemes discussed in the previous technology. Our proposed scheme does not need to know each connection's mean packet size. When the buffer exceeds the given threshold, it is based on comparison between the number of dropped packet and the approved packet. Our results are reported and discussed for comparing these discarding schemes under similar conditions. Although the number of virtual channel (VC) is increased, the simulation results showed that the proposed scheme can allocate more fairly each VC than other scheme.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.7-13
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• 2001

Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

• Journal of Biomedical Engineering Research
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• v.37 no.4
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• pp.134-139
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• 2016

US Food and Drug Administration (FDA) approved as a innovative cure for cancer, 1996. The effect is death of cancer cells through necrosis, apoptosis. Mainly the Continuous Wave mode (CW) use for PDT Laser. It sting, the question including itch, and etc. Reportedly, the increase of temperature with the perforated edema, ulcer, necrosis. The Thermal relaxation time and Oxygen recovery time is necessary. To give a normal oxygen recovery time of the cell, used Pulse mode. Progress, it was Burst Pulse mode when easing the thermal wake, the simplicity was secured, the PDT effect is good. Excepted in control group CW, Pulse, Burst pulse mode were incubated with various concentrations of 5-aminolevulinic acid hydrochloride (ALA-5). The tumor size reduction CW mode (44%), Pulse mode (48%), Burst pulse mode (53%) at 4 week after PDT with 0.3, 0.3, 0.3 mg/ml of ALA-5. After 4 hours, investigation of 100, 100, $100J/cm^2$ laser irradiation. The pulse mode was superior in expirimental data analysis. And it was the Burst pulse mode edge head of a family effect.

• Journal of Microbiology and Biotechnology
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• v.28 no.2
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• pp.275-283
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• 2018

Ischemic stroke can result from blockage of blood vessels, forming fibrin clots in the body and causing irreparable brain damage. Remedial thrombolytic agents or anticoagulants have been studied; however, because the FDA-approved tissue plasminogen activator has low efficacy and side effects, it is necessary to develop safer and more effective treatment candidates. This study aimed at assessing the fibrinolytic and anticoagulation features of a novel serine protease extracted and purified from Diopatra sugokai, a polychaeta that inhabits tidal flats. The purified serine protease was obtained through ammonium sulfate precipitation, affinity chromatography, and ion-exchange chromatography. Its molecular size was identified via SDS-PAGE. To characterize its enzymatic activities, the protease activity at various pH and temperatures, and in the presence of various inhibitors, was measured via azocasein assay. Its fibrinolytic activity and anticoagulant effect were assessed by fibrin zymography, fibrin plate assay, and fibrinogenolytic activity assays. The novel 38 kDa serine protease had strong indirect thrombolytic activity rather than direct activity over broad pH (4-10) and temperature ($37^{\circ}C-70^{\circ}C$) ranges. In addition, the novel serine protease exhibited anticoagulant activity by degrading the ${\alpha}$-, ${\beta}$-, and ${\gamma}$-chains of fibrinogen. In addition, it did not produce cytotoxicity in endothelial cells. Therefore, this newly isolated serine protease is worthy of further investigation as a novel alkaline serine protease for thrombolytic therapy against brain ischemia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7981-7984
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• 2014

Purpose: Colorectal cancer (CRC) screening with fecal occult blood testing (FOBT) has been associated with a reduction in CRC incidence and CRC-related mortality. However, a conventional FOBT requires stool collection and handling, which may be inconvenient for participants. The EZ-Detect$^{TM}$ (Siam Pharmaceutical Thailand) is a FDA-approved chromogen-substrate based FOBT which is basically a self-checked FOBT (no stool handling required). This study aimed to evaluate the accuracy of EZ-Detect for CRC detection. Methods: This prospective study was conducted in the Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand between November 2013 and May 2014. Some 96 patients with histologically-proven CRC and 101 patients with normal colonoscopic findings were invited to perform self-checked FOBT according to the manufacturer's instructions. Results were compared with endoscopic and pathologic findings. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CRC detection were calculated. Results: The present study revealed the sensitivity, specificity, PPV and NPV of this self-checked FOBT for CRC detection to be 41% (95% CI: 31-51), 97% (95% CI: 92-99), 93% (95% CI: 81-98) and 63% (95% CI: 55-70), respectively. The overall accuracy of the self-checked FOBT for identifying CRC was 70%. The sensitivity for CRC detection based on 7th AJCC staging was 29% for stage I, 32% for stage II and 50% for stage III/IV (P=0.19). The sensitivity was 33% for proximal colon and 42% for distal colon and rectal cancer (P=0.76). Notably, none of nine infiltrative lesions gave a positive FOBT. Conclusions: The self-checked FOBT had an acceptable accuracy of CRC detection except for infiltrative tumors. This home-administrated or 'DIY' do-it-yourself FOBT could be considered as one non-invasive and convenient tool for CRC screening.

• Archives of Plastic Surgery
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• v.35 no.6
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• pp.653-658
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• 2008

Purpose: Skin and soft tissue defect is one of the major challenges faced by plastic surgeons. Adipose derived stromal cells, which can be harvested in large quantities with low morbidity, display multilineage mesodermal potential. Therefore, adipose derived stromal cells have been met with a great deal of excitement by the field of tissue engineering. Recently, Adipose derived stromal cells have been isolated and cultured to use soft tissue restoration. In order to apply cultured cells for clinical purpose, however, FDA approved facilities and techniques are required, which may be difficult for a clinician who cultures cells in a laboratory dedicated to research to utilize this treatment for patients. In addition, long culture period is needed. Fortunately, adipose derived stromal cells are easy to obtain in large quantities without cell culture. The purpose of this study is to present a possibility of using uncultured adipose derived stromal cells for wound coverage. Methods: Seven patients who needed skin and soft tissue restoration were included. Five patients had diabetic foot ulcers, 1 patient got thumb amputation, and 1 patient had tissue defect caused by resection of squamous cell carcinoma. The patients' abdominal adipose tissues were obtained by liposuction. The samples were digested with type I collagenase and centrifuged to obtain adipose derived stromal cells. The isolated adipose derived stromal cells were applied over the wounds immediately after the wound debridement. Fibrin was used as adipose derived stromal cells carrier. Occlusive dressing was applied with films and foams and the wounds were kept moist until complete healing. Results: One hundred to one hundred sixty thousand adipose derived stromal cells were isolated per ml aspirated adipose tissue. All patients' wounds were successfully covered with the grafted adipose derived stromal cells in a 17 to 27 day period. No adverse events related to this treatment occurred. Conclusion: The use of uncultured adipose derived stromal cells was found to be safe and effective treatment for wound coverage without donor site morbidity.

• Food Science of Animal Resources
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• v.37 no.6
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• pp.931-939
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• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.517-535
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• 2014

Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained-release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.

• The Journal of Korean Medicine
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• v.25 no.1
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• pp.152-160
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• 2004

Backgrounds : Androgenetic alopecia is a relatively common disorder, but its precise mechanism is not elucidated. There are two commercial drugs approved by FDA. One(finasteride) has an inhibition activity of 5$\alpha$-reductase(type 2) and the other(minoxidil) has a vasodilation activity. Objectives : A verified herbal remedy for baldness is needed for medicinal treatment or preventing alopecia, which could be demonstrated by alopecia-related in vitro & in vivo tests Methods : On the basis of oriental pharmacognosy, we classified many herbal medicines into four groups (malnutrition, aging, alopecia and gray hair) according to its effect. The mitosis induction of hairy dermal papillae cell and the metabolic inhibition for type 2 $5{\alpha}-reductase$ were tested with five herbal extracts. Also, five herbal extracts were added to the normal essence formulation (HHRHG0202-80) in ranges of 0.1~0.3%, which was applied two-mouse models to validate each hair growing activity in vivo. Results : Stimulation of follicular papillae cell proliferation was observed in treatment of three herbal extracts (Glycyrrhizae radix:159.7%, Corni fructus : 144.7%, and Coicis semen : 136.6%) at a dose of $10\mu\textrm{g}/ml$. Three herbal extracts (Biotae semen. Glycyrrhizae radix and Coicis semen) showed inhibitory activity for $5{\alpha}-reductase$(type 2) at 93.18%, 73.36% and 47.6%, respectively at the same dose. We observed the enhancement of hair growth activity in C57b1/6 mouse and the inhibition of alopecia in AGA mouse after topical administration of the hair essence. Conclusions : Hair essence product, which contains five medicinal plants, would be used for the remedy for male pattern baldness (MPB) and the other alopecia diseases.