• Title/Summary/Keyword: Tolerance Intervals

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Single-Dose Oral Toxicity of Fermented Scutellariae Radix Extract in Rats and Dogs

  • Kim, Myoung-Seok;Ham, Seoung-Ho;Kim, Jun-Ho;Shin, Ji-Eun;Oh, Jin;Kim, Tae-Won;Yun, Hyo-In;Lim, Jong-Hwan;Jang, Beom-Su;Cho, Jung-Hee
    • Toxicological Research
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    • v.28 no.4
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    • pp.263-268
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    • 2012
  • The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu-100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.

Growing pigs developed different types of diabetes induced by streptozotocin depending on their transcription factor 7-like 2 gene polymorphisms

  • Tu, Ching-Fu;Hsu, Chi-Yun;Lee, Meng-Hwan;Jiang, Bo-Hui;Guo, Shyh-Forng;Lin, Chai-Ching;Yang, Tien-Shuh
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.185-194
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    • 2018
  • The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50-60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.

A Study of Six Sigma and Total Error Allowable in Chematology Laboratory (6 시그마와 총 오차 허용범위의 개발에 대한 연구)

  • Chang, Sang-Wu;Kim, Nam-Yong;Choi, Ho-Sung;Kim, Yong-Whan;Chu, Kyung-Bok;Jung, Hae-Jin;Park, Byong-Ok
    • Korean Journal of Clinical Laboratory Science
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    • v.37 no.2
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    • pp.65-70
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    • 2005
  • Those specifications of the CLIA analytical tolerance limits are consistent with the performance goals in Six Sigma Quality Management. Six sigma analysis determines performance quality from bias and precision statistics. It also shows if the method meets the criteria for the six sigma performance. Performance standards calculates allowable total error from several different criteria. Six sigma means six standard deviations from the target value or mean value and about 3.4 failures per million opportunities for failure. Sigma Quality Level is an indicator of process centering and process variation total error allowable. Tolerance specification is replaced by a Total Error specification, which is a common form of a quality specification for a laboratory test. The CLIA criteria for acceptable performance in proficiency testing events are given in the form of an allowable total error, TEa. Thus there is a published list of TEa specifications for regulated analytes. In terms of TEa, Six Sigma Quality Management sets a precision goal of TEa/6 and an accuracy goal of 1.5 (TEa/6). This concept is based on the proficiency testing specification of target value +/-3s, TEa from reference intervals, biological variation, and peer group median mean surveys. We have found rules to calculate as a fraction of a reference interval and peer group median mean surveys. We studied to develop total error allowable from peer group survey results and CLIA 88 rules in US on 19 items TP, ALB, T.B, ALP, AST, ALT, CL, LD, K, Na, CRE, BUN, T.C, GLU, GGT, CA, phosphorus, UA, TG tests in chematology were follows. Sigma level versus TEa from peer group median mean CV of each item by group mean were assessed by process performance, fitting within six sigma tolerance limits were TP ($6.1{\delta}$/9.3%), ALB ($6.9{\delta}$/11.3%), T.B ($3.4{\delta}$/25.6%), ALP ($6.8{\delta}$/31.5%), AST ($4.5{\delta}$/16.8%), ALT ($1.6{\delta}$/19.3%), CL ($4.6{\delta}$/8.4%), LD ($11.5{\delta}$/20.07%), K ($2.5{\delta}$/0.39mmol/L), Na ($3.6{\delta}$/6.87mmol/L), CRE ($9.9{\delta}$/21.8%), BUN ($4.3{\delta}$/13.3%), UA ($5.9{\delta}$/11.5%), T.C ($2.2{\delta}$/10.7%), GLU ($4.8{\delta}$/10.2%), GGT ($7.5{\delta}$/27.3%), CA ($5.5{\delta}$/0.87mmol/L), IP ($8.5{\delta}$/13.17%), TG ($9.6{\delta}$/17.7%). Peer group survey median CV in Korean External Assessment greater than CLIA criteria were CL (8.45%/5%), BUN (13.3%/9%), CRE (21.8%/15%), T.B (25.6%/20%), and Na (6.87mmol/L/4mmol/L). Peer group survey median CV less than it were as TP (9.3%/10%), AST (16.8%/20%), ALT (19.3%/20%), K (0.39mmol/L/0.5mmol/L), UA (11.5%/17%), Ca (0.87mg/dL1mg/L), TG (17.7%/25%). TEa in 17 items were same one in 14 items with 82.35%. We found out the truth on increasing sigma level due to increased total error allowable, and were sure that the goal of setting total error allowable would affect the evaluation of sigma metrics in the process, if sustaining the same process.

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A Phase I/II Trial of $DCVac/IR^{(R)}$ Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases (기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험)

  • Choi, Young-Min;Lee, Hyung-Sik;Kwon, Hyuk-Chan;Han, Sang-Young;Choi, Jong-Cheol;Chung, Ju-Seop;Kim, Chang-Won;Kim, Dong-Won;Kang, Chi-Duk
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.104-112
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    • 2008
  • Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

An Approximate Reconstruction of NPT for Synchronized Data Broadcasting (동기화된 데이터방송을 위한 근사적인 NPT 재구성 기법)

  • 정문열;김용한;백두원
    • Journal of Broadcast Engineering
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    • v.9 no.1
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    • pp.83-90
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    • 2004
  • DVB-MHP recommends that NPT(normal play time) be used as the times of stream events. NPT is the local time within an event(TV program). But we found that commercial transport stream (TS) generators and middlewares for DVB-MHP settop boxes are not ready to support the use of NPT by applications. In particular, TS generators do not create NPT reference descriptors needed to reconstruct NPT at the TV receiver. This situation is undesirable because program providers cannot experiment with the idea of synchronized applications. So we have implemented a TS generator that inserts NPT reference descriptors to TS and MyGetNPT API to approximately reconstruct NPT. STC (system time clock) is needed to reconstruct NPT, but Xlets are not allowed to read it. So, we approximate STC by using PCR (program clock reference) and the Java system tune. In this method, the stream generator extrats PCRs from an existing TS and inserts them into null TS packets in the form of MPEG sections, which can be read by Xlets. Because PCRs are displaced into new positions in TS, their values should be adjusted based on the time intervals between the original positions and the new positions. We implemented a synchronized application by using our TS generator and MyGetNPT API, where the task of stream events are to display graphic images. We found that graphic images are displayed where 240 ㎳ from their intended time, where 240ms is a human tolerance for the synchronization skew between graphic image and video.

Differential Expression of Th1- and Th2- Type Cytokines in Peripheral Blood Mononuclear Cells of Murrah Buffalo (Bubalus Bubalis) on TLR2 Induction by B. Subtilis Peptidoglycan

  • Shah, Syed M.;Ravi Kumar, G.V.P.P.S.;Brah, G.S.;Santra, Lakshman;Pawar, Hitesh
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.7
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    • pp.1021-1028
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    • 2012
  • Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and induce T-cell responses of appropriate effector phenotype accordingly. Toll-like receptors (TLRs), in part, mediate this microbial recognition and differentiation while the development of T-cell effector functions critically depends on the release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were stimulated under in vitro culture conditions by Bacillus subtilis cell wall petidoglycan, a TLR2 ligand, in a dose- and time- dependent manner. The expression of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type cytokines was measured. Stimulation was analyzed across five doses of peptidoglycan ($10{\mu}g/ml$, $20{\mu}g/ml$, $30{\mu}g/ml$, $40{\mu}g/ml$ and $50{\mu}g/ml$) for 3 h, 12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2 expression in a dose- and time-dependent manner and the peptidoglycan induced tolerance beyond $30{\mu}g/ml$ dose at all incubation periods. The correlation between peptidoglycan stimulation and TLR2 induction was found positive at all doses and for all incubation periods. Increased production of all the cytokines was observed at low doses for 3 h incubation, but the expression of IL-4 was relatively higher than IL-12 at the higher antigen doses, indicating tailoring towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4 and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating skewing to Th1 polarization. The expression of IL-12 was highest for all doses across all the incubation intervals at 24 h incubation, indicating Th1 polarization. The relative expression of TNF-${\alpha}$ and IFN-${\gamma}$ was also higher while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low doses, relative increase in the expression of IL-4 and IL-10 was observed which decreased at higher doses, as did the expression of all other cytokines. The exhaustion of cytokine production at 36 h indicated that PBMCs became refractory to further stimulation. It can be concluded from this study that the cytokine response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1 type with time till the cells become refractory to further stimulation.

Amelioration Effects of Irrigation-Aspiration on Renal Ischemia-Reperfusion Injury in Canine Model (개에서 신장의 허혈-재관류 손상에 대한관류-흡인의 감소효과)

  • Lee, Jae-Il;Son, Hwa-Young;Jeong, Seong-Mok;Kim, Myung-Cheol
    • Journal of Veterinary Clinics
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    • v.25 no.4
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    • pp.257-262
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    • 2008
  • Renal ischemia-reperfusion injury is great clinical important because viability of the transplanted organ depends on the tolerance of the graft to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of irrigation-aspiration in ischemia-reperfusion injury model induced by cross-clamping of renal vessels. Blood samples were collected from these dogs for measurement of kidney function and antioxidant enzyme activity, and RI at the intrarenal artery was measured at different time intervals. And the kidneys were taken for histopathologic evaluation at day 14. Kidney function (Cr and BUN) showed a significant increasing in untreated group compared to treated group. Resistive index of intrarenal artery was no significant difference among the groups. Activity of antioxidant enzymes in plasma was significant decrease in untreated group compare to control group while in treated group was no significant difference compared to control group. In histopathologic finding, treated group was showed less damage than that of untreated group. This result suggests that the processing of irrigation-aspiration is useful to reducing ischemia-reperfusion injury.

Effective Heat Treatment Techniques for Control of Mung Bean Sprout Rot, Incorporable into Commercial Mass Production

  • Lee, Jung-Han;Han, Ki-Soo;Kim, Tae-Hyoung;Bae, Dong-Won;Kim, Dong-Kil;Kang, Jin-Ho;Kim, Hee-Kyu
    • The Plant Pathology Journal
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    • v.23 no.3
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    • pp.174-179
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    • 2007
  • Seedlot disinfection techniques to control mung bean sprout rot caused by Colletoricum acutatum and C. gloeosporioides were evaluated for commercial production scheme. Soaking seedlots in propolis (100 X) and ethanol (20% for 30 min) appeared promising with control values of 85.5 and 80.8 respectively, but still resulted in up to 20% rot incidence. None of the C. acutatum conidia survived through hot water immersion treatment (HWT) for 10 min at temperatures of 55, 60 and $65^{\circ}C$, whereas the effective range of the dry heat treatment (DHT) was $60-65^{\circ}C$. Tolerance of mung bean seedlot, as estimated by hypocotyl elongation and root growth, was lower for HWT than for DHT. Germination and growth of sprouts were excellent over the range of $55-65^{\circ}C\;at\;5^{\circ}C$ intervals, except for HWT at $65^{\circ}C$ for 5 min. At this marginal condition, heat damage appeared so that approximately 2% of seeds failed to sprout to normal germling and retarded sprouts were less than 5% with coarse wrinkled hypocotyls. These results suggested that DHT would be more feasible to disinfect mung bean seedlots for commercial sprout production. Heat treatment at above ranges was highly effective in eliminating the epiphytic bacterial strains associated with marketed sprout rot samples. HWT of seedlot at 55 and $60^{\circ}C$ for 5 min resulted in successful control of mung bean sprout rot incidence with marketable sprout quality. DHT at 60 and $65^{\circ}C$ for 30 min also gave good results through the small-scale sprouting system. Therefore, we optimized DHT scheme at 60 and $65^{\circ}C$ for 30 min, considering the practical value of seedlot disinfection with high precision and accuracy. This was further proved to be a feasible and reliable method against anthracnose incidence and those bacterial strains associated with marketed sprout rot samples as well, through factory scale mung bean sprout production system.

Causes of Bacterial Growth in Gels and Gel Containers Used for Ultrasonography (초음파 검사용 젤과 젤 용기의 세균증식 원인)

  • Kim, A-Young;Cho, Pyoung-Kon;Song, Do-Young;Kim, Su-Jung
    • Journal of radiological science and technology
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    • v.43 no.5
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    • pp.359-365
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    • 2020
  • This study aimed to investigate the causes of bacterial growth to prevent infection caused by ultrasound gel and gel containers in contact with patients during ultrasonography. To investigate bacterial contamination during manufacturing or storage, we cultured ultrasound gels originally supplied from three manufacturers. To analyze bacterial growth according to the lapse of time and frequency of use of the ultrasound gel container, the gel and container were cultured at regular intervals every week for 4 weeks. In addition, to determine the source of infection, the examiner's hand was inspected with hand plate and the degree of bacterial contamination was measured before the test. As a result of the study, bacteria were not detected in the gel provided at the initial supply, and in the gel and gel container used repeatedly for 4 weeks, the same bacteria residing on the skin were identified in the examiner's hand, such as Staphylococcus epidermidis, Micrococcus luteus, Leuconostoc mesenteroid spp cremoris, Kocuria rhizophila, and etc. Separated strains were classified as those of the low- or non-pathogenicity; however, most of these strains may render fatal consequences to patients of lower level of immunity due to acquired tolerance to antibiotics. At week 1, when the number of tests was the highest, 44 colonies were identified, and at week 4, when the number of tests was the lowest, 4 colonies were identified. As r=0.994, it was found that the number of colonies increased as the number of tests increased. In conclusion, it was confirmed that the cause of the infection was not the ultrasound gel, but the examiner's hand. The ultrasound gel or gel container may be contaminated by skin flora of examiner's hands, which can cause opportunistic infection in patients with low immunity. The ultrasound gel or gel container may be contaminated by skin flora of examiner's hands, which can cause opportunistic infection in patients with low immunity. Therefore, it was confirmed that thorough hand disinfection was necessary to block healthcare-associated infections.

Optimal Enrichment Temperature, Time and Materials for L-type Rotifer (Brachionus plicatilis) Cultured at a Low Temperature (저온 배양한 L-type 로티퍼(Brachionus plicatilis)의 적정 영양강화 수온, 시간 및 영양강화제 종류)

  • Yoo, Hae-Kyun;Byun, Soon-Gyu;Choi, Jin;Nam, Myeong-Mo;Moon Lee, Haeyoung;Kang, Hee Wong;Lee, Chu
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.22 no.5
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    • pp.500-507
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    • 2016
  • This study was undertaken to improve the survival and early life growth rates of cold-water fish by culturing rotifer (Brachionus plicatilis) with low-temperature tolerance. The enrichment experiment was carried out at different temperatures and over different time intervals. Cultivation of the rotifer at low temperatures was repeated, with the selected and cultured as the water temperature was gradually lowered from $20^{\circ}C$ to $10^{\circ}C$. Enrichment of the rotifer was completed using A, S, SCV and SCP. Enrichment was carried out after 6, 12 and 24 hours at three different temperatures (10, 15 and $20^{\circ}C$). In the growth experiments, the rotifer increased to approximately triple their original size, from $350{\pm}7.9ind./ml$ to $1,064{\pm}5.7ind./ml$ at $10^{\circ}C$ over 50 days. The fatty acid composition of the four enrichment materials was species-specific, with the highest ratios belonging to eicosapentaenoic acid (EPA, C20:5n-3) and docosahezaenoic acid (DHA, C22:6n-3) in SCP. The fatty acid composition of the rotifers was affected by the enrichment materials. The EPA (% of total fatty acid) was more than 2 % in SCP, which showed a higher ratio than the other enrichment materials. DHA was higher in S reaching 12.40 % at $15^{\circ}C$ for 24 hours. The highest levels of EPA (3.09 %) and DHA (11.65 %) were obtained after the rotifers were enriched with S at $20^{\circ}C$ for 12hours.