• 제목/요약/키워드: single crossover

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Rapid Diagnosis of CMT1A Duplications and HNPP Deletions by Multiplex Microsatellite PCR

  • Choi, Byung-Ok;Kim, Joonki;Lee, Kyung Lyong;Yu, Jin Seok;Hwang, Jung Hee;Chung, Ki Wha
    • Molecules and Cells
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    • 제23권1호
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    • pp.39-48
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    • 2007
  • Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are frequent forms of genetically heterogeneous peripheral neuropathies. Reciprocal unequal crossover between flanking CMT1A-REPs on chromosome 17p11.2-p12 is a major cause of CMT type 1A (CMT1A) and HNPP. The importance of a sensitive and rapid method for identifying the CMT1A duplication and HNPP deletion is being emphasized. In the present study, we established a molecular diagnostic method for the CMT1A duplication and HNPP deletion based on hexaplex PCR of 6 microsatellite markers (D17S921, D17S9B, D17S9A, D17S918, D17S4A and D17S2230). The method is highly time-, cost- and sample-saving because the six markers are amplified by a single PCR reaction and resolved with a single capillary in 3 h. Several statistical and forensic estimates indicated that most of these markers are likely to be useful for diagnosing the peripheral neuropathies. Reproducibility, as determined by concordance between independent tests, was estimated to be 100%. The likelihood that genotypes of all six markers are homozygous in randomly selected individuals was calculated to be $1.6{\times}10^{-4}$, which indicates that the statistical error rate for this diagnosis of HNPP deletion is only 0.016%.

세파클러 캅셀제에 대한 생물학적 동등성 평가 (Bioequivalence of Cefaclor Capsules Following Single Dose Administration to Healthy Male Volunteers)

  • 복혜숙;김명민;권이오;최경업
    • 한국임상약학회지
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    • 제7권1호
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    • pp.17-21
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    • 1997
  • Cefaclor is a second generation cephalosporin antibiotic that shows a potent antibacterial activity against both Gram-positive and Gram-negative bacteria, when it is orally administered. Due to its patent expiration, a number of generic drugs have been marketed, but not yet elucidated to ensure therapeutic equivalence. In this study, cefaclor capsules manufactured by Chong Kun Dang were bioequivallently assessed by comparing with $Ceclor^{TM}$ introduced originally by Daewoong Lilly. A total of 16 healthy male volunteers were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of cefaclor in plasma were measured upto 6 hours following a single oral administration of two capsules (500 mg of cefaclor) by high-performance liquid chromatography with UV detection. Although the plasma concentration at 6 hours was not detected, the computed half-life of cefaclor was approximately 0.5 hours. The area under the concentration-vs-time curve from 0 to 4 hours $(AUC_{0-4h})$ was calculated by the trapezoidal summation method. The differences in mean values of $AUC_{0-4h}$, peak plasma concentration $(C_{max})$, and time to peak concentration $(T_{max})$ between the two products were $4.63\%,\;1.84\%,\;and\3.28\%$, respectively. The least significant differences at $\alpha4= 0.05 for $AUC_{0-4h},\;C_{max},\;and\;T_{max}\;were\;6,53\%,\;4.05\%,\;and\;6.47\%$, respectively. In conclusion, the test drug was bioequivalent with the reference drug.

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카베딜롤(25mg)정제의 생물학적 동등성 및 약물동태연구 (Bioequivalence and Pharmacokinetics of Carvedilol (25mg) Tablets in Volunteers)

  • 우수경;김호순;강종성;권광일
    • 약학회지
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    • 제45권6호
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    • pp.650-655
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    • 2001
  • Carvedilol is a nonselective $\beta$-blocking agent with vasodilating properties that are attributed mainly to its blocking activity at $\alpha$$^{1}$-receptors. Carvedilol is used in the treatment of mild to moderate hypertention and angina pectoris and is often used in combination with other drugs. This study was carried out to evaluate the bioequivalence and pharmacokinetics of two carvedilol 25mg tablet formulations according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty healthy volunteers are enrolled and received a single dose (25mg as carvedilol) of each drug in the fasting state, in a randomized 2-way crossover design. After oral administration, blond samples were collected for a period of 30 hours. Plasma concentrations of carvedilol were determined by a rapid and sensitive HPLC method with spectrofluorometric detection. The major pharmacokinetic parameters such as AU $C_{0-}$30hr/, AU $C_{inf}$ , $C_{max}$, $T_{max}$, $t_{1}$2 / Cl/F and V $_{\beta}$//F were calculated. ANOVA test and t-test were utilized for the statistical analysis of each parameter. The results showed that the differences in AU $C_{0-}$30hr/, $C_{max}$ and $T_{max}$ between two were ~5.66, 1.74 and 0.00%, respectively. Minimum detectable differences ($\Delta$) at $\alpha$=0.05 were less than$\pm$ 20% except $T_{max}$ (8.44, 18.36, and 33.86%, respectively). The 90% confidence intervals of all parameters were within $\pm$20% (-10.60~ -0.72, -9.00~12.49 and -19.81~19.81%, respectively). Therefore, it is concluded that the two formulations are bioequivalent for both the extent and the rate of absorption after single dose administration.ation.ion.ion.ation.ion.n.

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시각적 전이에 기초한 1인 경험 내러티브에 관한 연구: COVID-19의 고립 요인을 중심으로 (A Study on the Narratives of Single Person Experience based on Visual Transference: Focusing on the Isolated Factors of COVID-19)

  • 이유진
    • 디지털융복합연구
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    • 제20권4호
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    • pp.519-528
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    • 2022
  • 연구 목적은 COVID-19 사태 이후 1인이 경험한 고립 요인을 시각적 전이에 기초한 내러티브 방법으로 살펴, 1인 경험의 디자인 방향을 탐구하는 데 있다. 연구 범위는 비대면 디지털 플랫폼을 통해 참여한 20대 여성 8명의 COVID-19 경험이다. 연구 방법은 참여자가 COVID-19 상황과 유사한 디지털 이미지를 선택하여 이에 근거한 경험 사실을 기술하면, 이를 연구자가 미시적으로 분석한 것으로 한정한다. 분석 결과, 고립 요인은 대면 소통의 부족, SNS 의존, OTT 서비스 중독, 외부 장소 이용 및 활동 한정, 비대면 기술의 한계, 비대면 교육 효과의 한계, 감염병 우려 등으로 요약되었다. 그러므로 고립 극복 요소에 근거한 1인 경험 디자인 방향은 관계 회복을 위한 커뮤니케이션, 온·오프라인 통합의 비 경계 장소, 현존감 구현을 위한 디지털 융·복합 콘텐츠 등이 전제되어야 할 것으로 예측된다.

Loperamide로 억제된 위장관 운동에 대한 사관혈의 자침효과: 무작위배정, 단일눈가림, 교차설계, 대조 임상시험 (A Crossover Clinical Trial to Determine the Effect of Siguan(Four Gates) Points on Gastrointestinal Motility Suppressed by Loperamide Administration)

  • 오달석;정소영;김애란;강위창;박지은;구창모;최준용;정희정;최선미;손창규
    • 대한한의학회지
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    • 제29권1호
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    • pp.1-6
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    • 2008
  • Objective : To investigate the therapeutic effect of manual acupuncture at Siguan (four gates, bilateral LI4 and LR3) on suppression of gastrointestinal motility. Methods : A single blind, randomized, sham-acupuncture controlled, crossover study was conducted. Twenty healthy male subjects were admitted at hospital, and gastrointestinal motility suppression was induced by loperamide administration. Just after intake of 20 radio-markers, four gates or sham acupoint treatments were administered every 12 hours, 4 times over 48 hours. Gastrointestinal motility was evaluated by radiographic distribution of the radiomarkers at stomach or ileum, ascending, transverse, descending colon, sigmoid/rectum, and outside body at serial time points (0, 6, 12, 24, and 48 h). Results : Four gates acupuncture activated gastrointestinal movement as evidenced by significantly changed distributionof radio-makers at 6, 12, and 48 hours (P < 0.0001, P = 0.001, and P = 0.03, respectively) in Cochran-Mantel-Haenszel statistics. No serious adverse events occurred in either group. Conclusions : This study showed a scientific clinical relevance of four gates acupuncture to gastrointestinal disorders.

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디푸루칸 캡슐 50 mg (3 캡슐, 플루코나졸 150mg)에 대한 푸루나졸 정 150mg의 생물학적 동등성 (The Bioequivalence of Plunazol Tablet (Fluconazole 150 mg) to Three capsules of Diflucan 50 mg)

  • 장희철;이민석;유정현;류승효;조상헌;최연진;황애경;김윤아;박시현;윤지원;배균섭
    • Journal of Pharmaceutical Investigation
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    • 제39권3호
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    • pp.207-216
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    • 2009
  • Fluconazole is used as an orally administrated antifungal drug for the treatment of tinea corporis, candidiasis including skin mycotic pneumonia infections. The dosage of fluconazole varies with indication ranging from 50 mg/day to 400 mg/day. The fluconazole capsule 50 mg (3 capsules daily) is already available in Korean market. To improve the patient compliance, a fluconazole tablet 150 mg (once a day administration) was developed recently. The purpose of this study was to evaluate the bioequivalence of three doses of fluconazole capsule 50 mg (Diflucan 50 mg, Pfizer Korea Inc., as a reference drug) and a single dose of fluconazole tablet 150 mg (Plunazol 150 mg, Daewoong Pharm. Co., Korea) according to the guidelines of the Korea Food and Drug Administration (KFDA). The bioequivalence for three capsules of Diflucan 50 mg and a single tablet of Plunazol 150 mg was investigated in twenty-four healthy male volunteers under a randomized 2${\times}$2 crossover trial design. The average age of twenty-four volunteers was 24.78${\pm}$3.27 year-old, average height was 175.56${\pm}$5.45 cm and average weight was 67.24${\pm}$6.86 kg. After three capsules of Diflucan 50 mg or a single tablet of Plunazol 150 mg were orally administered, blood was taken at predetermined time intervals and the plasma concentrations of fluconazole in plasma were determined using LC-MS-MS. The 90% confidence intervals for the main parameters of statistical results after logarithmic transformation were AUCt 0.9272-1.0084 and Cmax 0.8423-0.9544 respectively, which are in the range of log 0.8 to log 1.25 and the statistical results of additional parameters (AUClast, t1/2 and MRT) were also in the 90% confidence interval that is in the range of log 0.8 to log 1.25. Therefore, the results of this study confirm the bioequivalence of three capsules of Diflucan 50 mg to one tablet of Plunazol 150 mg.

수동급기 직접 메탄올 연료전지의 동적 모델 (Dynamic Model of a Passive Air-Breathing Direct Methanol Fuel Cell)

  • 하승범;장익황;차석원
    • 한국신재생에너지학회:학술대회논문집
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    • 한국신재생에너지학회 2008년도 춘계학술대회 논문집
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    • pp.33-36
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    • 2008
  • The transient behavior of a passive air breathing direct methanol fuel cell (DMFC) operated on vapor-feeding mode is studied in this paper. It generally takes 30 minutes after starting for the cell response to come to its steady-state and the response is sometimes unstable. A mathematical dynamic one-dimensional model for simulating transient response of the DMFC is presented. In this model a DMFC is decomposed into its subsystems using lumped model and divided into five layers, namely the anodic diffusion layer, the anodic catalyst layer, the proton exchange membrane (PEM), the cathodic catalyst layer and the cathodic diffusion layer. All layers are considered to have finite thickness, and within every one of them a set of differential-algebraic governing equations are given to represent multi-components mass balance, such as methanol, water, oxygen and carbon dioxide, charge balance, the electrochemical reaction and mass transport phenomena. A one-dimensional, isothermal and mass transport model is developed that captures the coupling between water generation and transport, oxygen consumption and natural convection. The single cell is supplied by pure methanol vapor from a methanol reservoir at the anode, and the oxygen is supplied via natural air-breathing at the cathode. The water is not supplied from external source because the cell uses the water created at the cathode using water back diffusion through nafion membrane. As a result of simulation strong effects of water transport were found out. The model analysis provides several conclusions. The performance drop after peak point is caused by insufficiency of water at the anode. The excess water at the cathode makes performance recovery impossible. The undesired crossover of the reactant methanol through the PEM causes overpotential at the cathode and limits the feeding methanol concentration.

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테놀민 정(아테놀올 50 mg)에 대한 신일아테놀올 정의 생물학적 동등성 (Bioequivalence of Sinil Atenolol Tablets to Tenormin Tablets (Atenolol 50 mg))

  • 곽혜선;강성하;전인구
    • Journal of Pharmaceutical Investigation
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    • 제33권1호
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    • pp.51-53
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    • 2003
  • This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, $Tenormin^{\circledR}$ Tablets in 20 healthy Korean volunteers. The volunteers received a single 50 mg dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration $(C_{max})$, time to reach peak plasma concentration $(T_{max})$, and terminal first order elimination half-life $(t_{1/2})$. No statistically significant difference was obtained between the $T_{max}$ values, and the logarithmic transformed AUC and $C_{max}$ values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and $C_{max}$ values of Sinil Atenolol Tablets over those of $Tenormin^{\circledR}$ Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of $T_{max}$ in $Tenormin^{\circledR}$ Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of $t_{1/2}$ between the two products were found comparable, and the mean $t_{1/2}$ values of $Tenormin^{\circledR}$ Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to $Tenormin^{\circledR}$ Tablets in both the rate and extent of absorption, indicating that Sinil Atenolol Tablets were bioequivalent to the reference product, $Tenormin^{\circledR}$ Tablets

Efficient and Precise Construction of Markerless Manipulations in the Bacillus subtilis Genome

  • Yu, Haojie;Yan, Xin;Shen, Weiliang;Shen, Yujia;Zhang, Ji;Li, Shunpeng
    • Journal of Microbiology and Biotechnology
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    • 제20권1호
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    • pp.45-53
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    • 2010
  • We have developed an efficient and precise method for genome manipulations in Bacillus subtilis that allows rapid alteration of a gene sequence or multiple gene sequences without altering the chromosome in any other way. In our approach, the Escherichia coli toxin gene mazF, which was used as a counter-selectable marker, was placed under the control of a xylose-inducible expression system and associated with an antibiotic resistance gene to create a "mazF-cassette". A polymerase chain reaction (PCR)-generated fragment, consisting of two homology regions joined to the mazF-cassette, was integrated into the chromosome at the target locus by homologous recombination, using positive selection for antibiotic resistance. Then, the excision of the mazF-cassette from the chromosome by a single-crossover event between two short directly repeated (DR) sequences, included in the design of the PCR products, was achieved by counter-selection of mazF. We used this method efficiently and precisely to deliver a point mutation, to inactivate a specific gene, to delete a large genomic region, and to generate the in-frame deletion with minimal polar effects in the same background.

Effects of Plantain (Plantago lanceolata L.) Herb and Heat Exposure on Plasma Glucose Metabolism in Sheep

  • Al-Mamun, M.;Tanaka, C.;Hanai, Y.;Tamura, Y.;Sano, H.
    • Asian-Australasian Journal of Animal Sciences
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    • 제20권6호
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    • pp.894-899
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    • 2007
  • An experiment was conducted using a [6, 6-$^2H$]glucose isotope dilution method to determine the effects of plantain (Plantago lanceolata L.) on plasma glucose metabolism in sheep taken from a thermoneutral environment and exposed to a hot environment. The sheep were fed either mixed hay (MH) of orchardgrass (Dactylis glomerata L.) and reed canarygrass (Phalaris arundinacea L.) at a 60:40 ratio or MH and plantain (PL) at a 9:1 ratio in a crossover design for each 23-day period. In both dietary treatments the metabolizable energy (ME) and crude protein intake were designed to be isoenergetic and isoproteinous at around maintenance level. The sheep were taken from a thermoneutral environment ($20^{\circ}C$, 70% RH) and exposed to a hot environment ($28-30^{\circ}C$, 70% RH) for 5 days. The isotope dilution method using a single injection of [6, 6-$^2H$]glucose was performed on the $18^{th}$ day of the thermoneutral environment and on the $5^{th}$ day of heat exposure. Plasma glucose pool size was numerically lower (p = 0.26) during heat exposure on both dietary treatments, and numerically higher (p = 0.13) on the MH diet irrespective of environmental temperature. Plasma NEFA concentration (p = 0.01) and glucose turnover rate (p = 0.03) were decreased during heat exposure, but remained similar between diets. It could be concluded that, although no positive impact of plantain on glucose metabolism was found under the present experimental conditions (plantain constituted only 10% of basal diet), plantain herb is an alternative to MH for rearing sheep in both thermoneutral and hot environments.