The organ distribution and pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), were compared after single and repeated subcutaneous administration ( 50${\mu}$/kg, 10${\mu}g$Ci/kg of $^{125}I$-DWP401, twice a day for 7 consecutive days) to rats. The pharmacokinetic parameters such as AUC and terminal half-life were similar between two different administration. During repeated administration, the plasma concentration of DWP401 seemed to be constant when the plasma was collected at 15 min after each dosing. The TCA-precipitated radioactivities in thyroid, liver, kidney, and stomach were higher than those of other organs studied after both single and repeated administration. The TCA-precipitated radioactivities after repeated administration in several organs, such as thyroid, stomach, prostate, adrenal, eye ball, and testis were higher than those after single administration. But, according to the observations using gel filtration chromatography and antibody binding assay, the radioactivities in thyroid and stomach were not primarily due to the intact DWP401 or its metabolites but due to the $^{125}I$-thyroxine binding protein. In conclusion, it can be suggested that DWP401 is metabolized to each amino acid or small polypeptides, and there was no significant changes in pharmacokinetics or any indications for accumulation of DWP401 in rat plasma and organs after repeated treatment.
Lee, Soo Ok;Cheong, Hyun Sub;Park, Byung Lae;Bae, Joon Seol;Sim, Won Chul;Chun, Ji-Yong;Isbat, Mohammad;Uh, Soo-Taek;Kim, Yong Hooun;Jang, An-Soo;Park, Choon-Sik;Shin, Hyoung Doo
Molecules and Cells
/
v.27
no.2
/
pp.175-181
/
2009
The myosin light chain kinase (MYLK) gene encodes both smooth muscle and nonmuscle cell isoforms. Recently, polymorphisms in MYLK have been reported to be associated with several diseases. To examine the genetic effects of polymorphisms on the risk of asthma and related phenotypes, we scrutinized MYLK by re-sequencing/genotyping and statistical analysis in Korean population (n = 1,015). Seventeen common polymorphisms located in or near exons, having pairwise $r^2$ values less than 0.25, were genotyped. Our statistical analysis did not replicate the associations with the risk of asthma and log-transformed total IgE levels observed among African descendant populations. However, two SNPs in intron 16 (+89872C> G and +92263T> C), which were in tight LD (|D'| = 0.99), revealed significant association with log-transformed blood eosinophil level even after correction multiple testing ($P=0.002/P^{corr}=0.01$ and $P=0.002/P^{corr}=0.01$, respectively). The log-transformed blood eosinophil levels were higher in individuals bearing the minor alleles for +89872C> G and +92263T> C than in those bearing other allele. In additional subgroup analysis, the genetic effects of both SNPs were much more apparent among asthmatic patients and atopic asthma patients. Among atopic asthma patients, the log-transformed blood eosinophil levels were proportionally increased by gene-dose dependent manner of in both +89872C> G and +92263T> C(P = 0.0002 and P = 0.00007, respectively). These findings suggest that MYLK polymorphisms might be among the genetic factors underlying differential increases of blood eosinophil levels among asthmatic patients. Further biological and/or functional studies are needed to confirm our results.
There are several remediation technologies for heavy metal contaminated soils but increasing cost limits the application of the technology if the contaminated area is large. Therefore, stabilization, which blocks the release of heavy metals or makes slow the release, is one of the applicable technology for the heavy metal contaminated soil. Current study is an applicability test for a smelter area with various stabilizer such as magnetite, hematite, zeolite-A, zeolite-X, zeolite-Y, zinc oxide, calcium oxide, carbon trioxide, manganese oxide, manganese dioxide, fish bone, sodium phosphate. The soil contaminated with arsenic, lead, copper, nickel, and zinc could not be stabilized only one stabilizer which is known to have stability for certain metal. Many of the stabilizer works for a few metal but not all of the heavy metal. In several cases, stabilizers increase the release of the other metals while they stabilize some metals. In general, the stabilizing efficiency was increased with time. For Ni, Pb, calcium oxide, carbon trioxide, manganese oxide had good stabilizing effect in water extractable portion. For Cu, manganese oxide, zeolite showed good results especially in the exchangeable portion of the sequential extraction. For As, magnetite had good ability but most of the metal oxide which showed good result for other heavy metals increased with the release of As. Current study suggest that multiple stabilizers are needed for the contaminated soil and dose of the stabilizer and stabilizing time should be carefully considered for the soil contaminated with various metals.
The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.
The Plastic material had been developed in the middle of the 19th century as an alternative material. Along with the development of the electrical engineering industry, it cropped up into center stage as an effective material and has increasingly expanded its use. As such, the plastic material has bound deep-seated ties with the design activities of industrial products, coming into the main material for a variety of industrial designs. Despite its dose affinity to design function in terms of its materialistic property, we have rarely seen examples of intensive study on the realtionship between plastics and designs. This study aims to find the importance that the substance affects industrial products in designs along with the development of plastic materials. With the objective in mind, we made a review of the streamline stylishness that had flourished in the twenties and thirties of the 19th century. Through this study, we understand that the plastic material has a close realtionshop with design activities in three different aspects. First, its amorphous state of nature makes it possible to change into any shape one desires in plastic surgery, which feature in turn influences the moulding of any design forms. Second, the plastic material is best suited to mass-manufacture, which induces to reduce the cost of production. Hence, the expansion of design industry. Third, the plastic material allows the multiple variety of colors, sensitivity, gloss and patterns and infinitely large possibility ranging from natural senses to human senses with the result that numberless diversity of designs cdould come into being.
Purpose: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. Methods: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) signaling was examined by nuclear translocation of $NF-{\kappa}B$ p65 subunit and phosphorylation of $I{\kappa}B$. Results: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced $NF-{\kappa}B$ p65 nuclear translocation and phosphorylation of $I{\kappa}B$. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an $NF-{\kappa}B$ inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. Conclusion: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of $NF-{\kappa}B$ signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.
We investigated the improvement of surface roughness and states after high temperature annealing using reduced-graphene oxide (r-GO) capping layer on ion-implanted 4H-SiC epitaxial layer. The specification of the 4H-SiC wafer grown on n-type $4^{\circ}$ off-axis 4H-SiC was $10{\mu}m$-thick and n-type epitaxial layer with a dose of $1.73{\times}10^{15}cm^{-2}$. The $n^+$ region were formed by multiple nitrogen ion-implantations and r-GO capping layer was produced by spray coating method. AFM measurements revealed that RMS value of the sample capped with r-GO was tenfold decrease compared to the sample without r-GO capping. The improvement of surface states was also verified by the improvement of leakage current level.
Soil-transmitted helminth (STH) infections are still a considerable challenge in Myanmar. We undertook a control program for STH infections (especially Trichuris trichiura) among schoolchildren in Myanmar using mass drug administration (MDA) and health education. Around 1,700 schoolchildren from 15 primary schools in 3 suburban districts (Shwe Pyi Thar, Twantay, and Kyauktan) of the Yangon Region were subjected in this study during 2017-2019. All of the schoolchildren in each school were orally administered albendazole (400 mg in a single dose) 2, 3, and 4 times a year in 2017, 2018, and 2019, respectively. The results revealed that the egg positive rate of any intestinal helminths (including STH) was reduced from 37.6% (649/1,724) in 2017 to 22.8% (352/1,542) in 2019. The egg positive rate of Ascaris lumbricoides was decreased remarkably from 23.3% (402/1,724) in 2017 to 3.6% (56/1,542) in 2019. However, that of T. trichiura was only slightly reduced from 26.9% (464/1,724) in 2017 to 20.2% (312/1,542) in 2019. The intensity of infection with A. lumbricoides and T. trichiura was both more or less reduced, and the proportion of light infection cases with A. lumbricoides and T. trichiura increased from 35.6% in 2017 to 64.3% in 2019 and from 70.3% in 2017 to 81.7% in 2019, respectively. The results indicated that repeated MDAs (2-4 times a year for 3 years) using albendazole on schoolchildren in Myanmar failed to control T. trichiura infection. For a successful control of trichuriasis in Myanmar, new MDA strategies, using a modified albendazole regimen (multiple daily doses for 2 or 3 days) or an alternative anthelmintic drug, such as oxantel pamoate, is strongly recommended.
Gi-Seok Kwon;Dong-ha Kim;Hyun-Ju Seo;Young-Eun Cho;Jung-Bok Lee
Journal of Life Science
/
v.33
no.2
/
pp.183-190
/
2023
Red yeast rice, also known as Hong Qu and red Koji, has been used for a long time in Asian functional food and traditional medicine. It consists of multiple bioactive substances, which can potentially be used as nutraceuticals. Alcoholic liver disease (ALD) can range from simple steatosis or inflammation to fibrosis and cirrhosis, possibly through leaky gut and systemic endotoxemia. This study examined the liver and gut effects of red yeast rice (RYR) (Monascus purpureus) ethanol extract against binge ethanol-induced liver injury in mice. RYR extract was orally administered to C57BL/6N mice at a concentration of 200 mg/kg body weight per day for 10 days. Then, mice were administered binge alcohol (5 g/kg/dose) three times at 12 hr intervals. Binge alcohol exposure significantly elevated the endotoxin, aspartate aminotransferase (AST), and alanine transaminase (ALT) activity of plasma, as well as hepatic triglyceride levels; however, RYR treatments reduced these levels. In addition, RYR pretreatment significantly reduced the alcohol-induced oxidative maker protein and apoptosis maker in binge alcohol-induced gut and liver injuries. These results suggest that RYR may prevent alcohol-induced acute leaky gut and liver damage.
Objective: 68Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68Ga-NGUL in healthy volunteers and the lesion detection rate of 68Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68Ga-NGUL PET/CT or conventional imaging. Among them, 68Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: 68Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68Ga-NGUL is a valuable option for prostate cancer imaging.
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