• Journal of Ginseng Research
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• v.45 no.6
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• pp.726-733
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• 2021

Background: Panax notoginseng is a highly valued medicinal herb used widely in China and many Asian countries. Its root and rhizome have long been used for the treatment of cardiovascular and hematological diseases. Imaging the spatial distributions and dynamics of metabolites in heterogeneous plant tissues is significant for characterizing the metabolic networks of Panax notoginseng, and this will also provide a highly informative approach to understand the complex molecular changes in the processing of Panax notoginseng. Methods: Here, a high-sensitive MALDI-MS imaging method was developed and adopted to visualize the spatial distributions and spatiotemporal changes of metabolites in different botanical parts of Panax notoginseng. Results: A wide spectrum of metabolites including notoginsenosides, ginsenosides, amino acids, dencichine, gluconic acid, and low-molecular-weight organic acids were imaged in Panax notoginseng rhizome and root tissues for the first time. Moreover, the spatiotemporal alterations of metabolites during the steaming of Panax notoginseng root were also characterized in this study. And, a series of metabolites such as dencichine, arginine and glutamine that changed with the steaming of Panax notoginseng were successfully screened out and imaged. Conclusion: These spatially-resolved metabolite data not only enhance our understanding of the Panax notoginseng metabolic networks, but also provide direct evidence that a serious of metabolic alterations occurred during the steaming of Panax notoginseng.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.86-95
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• 2020

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 10⁹ CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA_A receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.92-98
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• 2014

The safety of fake anti-impotence drugs (fake Viagra : 26 samples, fake Cialis : 25 samples) distributed in Gyeonggi province was studied by monitoring the concentrations of anti-impotence pharmaceutical ingredient and their analogues. The concentrations of anti-impotence pharmaceutical ingredient 4 specis and their analogues 17 specis were estimated using by HPLC/PDA, LC-MS/MS. The range of concentration of sildenafil in fake viagra was 40~199 mg/tablet, among them the portion of the concentrations of sildenafil over 150 mg/tablet exceeded 65%. 3 cases in tested samples contained sildenafil and tadalafil. The range of concentration of sildenafil in fake cialis was 102~249 mg/tablet, among them the portion of the concentrations of sildenafil over 150 mg/tablet exceeded 88%. One case in tested samples contained demethylhongdenafil (90 mg/tablet). These results indicate that there were many fake anti-impotence drug contained high level of anti-impotence pharmaceutical ingredients, a sustainable monitoring and the blocked distribution of fake anti-impotence drugs recommended.

• The Korean Journal of Applied Statistics
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• v.35 no.2
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• pp.311-325
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• 2022

For count responses, the situation of excess zeros often occurs in various research fields. Zero-inflated model is a common choice for modeling such count data. Bayesian inference for the zero-inflated model has long been recognized as a hard problem because the form of conditional posterior distribution is not in closed form. Recently, however, Pillow and Scott (2012) and Polson et al. (2013) proposed a Pólya-Gamma data-augmentation strategy for logistic and negative binomial models, facilitating Bayesian inference for the zero-inflated model. We apply Bayesian zero-inflated negative binomial regression model to longitudinal pharmaceutical data which have been previously analyzed by Min and Agresti (2005). To facilitate posterior sampling for longitudinal zero-inflated model, we use the Pólya-Gamma data-augmentation strategy.

• Journal of Pharmaceutical Investigation
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• v.16 no.3
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• pp.110-117
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• 1986

Plasma disappearance of amaranth (AM), a model compound of organic anionic drugs, was retarded by intravenous infusion of taurodeoxycholate (TDC), a representative bile acid, in the rat. Biliary excretion accounted for 30-60% of the systemic excretion of AM. AM seemed to be metabolised in the hepatocyte to form a compound that is excreted more rapidly into the bile than AM itself, considering apparent biliary clearance, $CL_{bil}$, is much larger than systemic clearance, $CL_s$. Decrease in $CL_{bil}$ by TDC infusion might be due to elevated plasma level rather than decreased biliary excretion of AM. Decreased distribution or urinary excretion of AM by TDC was supposed to be one of the probable reasons of elevated plasma level. Competitive inhibition between AM and TDC on tissue distribution and urinary excretion might explain the mechanism. The effect of TDC on the $CL_{bil}$ of methylene blue, a cationic dye, was quite different from that of AM, as reported previously by us. More intensive study would be necessary to elucidate the difference of biliary excretion between organic anions and cations.

• Journal of Microbiology and Biotechnology
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• v.16 no.7
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• pp.1060-1067
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• 2006

This study was undertaken to determine the effect of reservoirs on water quality and the distribution of pathogenic and indicator bacteria in a drinking water distribution system (total length 14km). Raw water, disinfected water, and water samples from the distribution system were subjected to physicochemical and microbiological analyses. Most factors encountered at each season included residual chloride, nitrate, turbidity, and phosphorus for heterotrophic bacterial distribution, and hardness, heterotrophic bacteria, sampling site, and DOC (dissolved organic carbon) for bacteria on selective media. No Salmonella or Shigella spp. were detected, but many colonies of opportunistic pathogens were found. Comparing tap water samples taken at similar distances from the water treatment plant, samples that had passed through a reservoir had a higher concentration of heterotrophic bacteria, and a higher rate of colony formation with 10 times as many bacteria on selective media. Based on the results with m-Endo agar, the water in reservoirs appeared safe; however, coliforms and opportunistic pathogenic bacteria such as Pseudomonas aeruginosa were identified on other selective media. This study illustrates that storage reservoirs in the drinking water distribution system have low microbiological water quality by opportunistic pathogens, and therefore, water quality must be controlled.

• Journal of Food Hygiene and Safety
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• v.33 no.1
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• pp.83-88
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• 2018

The purpose of this study was to investigate and evaluate the safety of the wet tissues. In this study, we analyzed sterilizing preservatives and the presence of harmful substances in 62 wet tissue samples in the market. The contents of preservatives, formaldehyde and methanol were analyzed by HPLC and headspace-GC, respectively. Cetylpyridinium chloride was detected as 7-13 ppm in 5 samples. Sodium benzoate was detected in 46 samples ranging from 200 ppm to 3500 ppm, and 9 ppm of methylparahydroxy benzoate was detected in 1 sample. Propylparahydroxy benzoate was not detected in any samples. 5 ppm of methylchloroisothiazolinone and 140 ppm of methylisothiazolinone were detected in 1 sample. Formaldehyde was detected as $0.0069-1.796{\mu}g/g$ in 59 samples. Methanol was detected ranging from 2 ppm to 51 ppm in 22 samples, and 4 samples showed more than 20 ppm of the legal limit. The pH of the wet tissues was 4.0 to 8.2. Continuous investigation and monitoring are necessary to ensure safe distribution of products.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.249-264
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• 1995

Although liposome has many advantages as a pharmaceutical dosage form, its application in the industrial field has been limited because of some problems such as preparation method, reproducibility, scale-up, stability and sterilization etc. Liposomes prepared by microemulsification method had defined size, narrow size distribution, reproducibility and high entrapment efficiency. For enhancing the stability, the dry form of liposome was recommended. These types of liposome are proliposome and freeze-dried liposome. The liposome must have some properties for preparing of freeze-dried liposome; small size $(50{\sim}200\;nm)$, narrow size distribution and cryoprotectant. In this experiment, the liposomes containing 5-Fluorouracil(5-FU) and its prodrug(pentyl-5-FU-1-acetate; PFA, hexyl-5-FU-1-acetate; HFA) were made with soybean phosphatidylcholine, cholesterol, stearylamine(SA) and dicetyl phosphate(DCP) employing hydration method or microemulsification method using $Microfluidizer^{TM}$. Both or liposome types were MLV and MEL. After preparation, freeze drying and rehydration were performed. In the process of freezing, trehalose(Tr) was added as a cryoprotectant. Their evaluation methods were as follows; entrapment efficiency, mean particle size and size distribution, dissolution test, retain of entrapment efficiency and turbidity after freeze-drying. The results are summarized as belows. The entrapment efficiency of 5-FU was dependent on total lipid concentration and cholesterol content but that of PFA and HFA was decreased when cholesterol was added. When DCP and SA were added, entrapment efficiency was decreased. As the partition coefficient of drug was increased, entrapment efficiency was increased. Under the same condition, entrapment efficiency of MEL is similar to that of MLV. The mean particle size and size distribution of MEL were smaller than those of MLV. Dissolution rates of drug from both liposome types were comparatively similar. Dissolution rates of drugs with serum and liver homogenate were faster than without these material. After preparation of liposome, free drug was removed efficiency by Dowex 50W-X4. When liposome was freeze-dried and then rehydrated in the presence of Tr, characteristics of liposome were maintained well in MEL than MLV. Tr Was used successfully as a cryoprotectant in the process of freeze drying and the optimal ratio of Tr:Lipid was 4:1(g/g).

• Journal of Pharmaceutical Investigation
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• v.21 no.3
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• pp.155-160
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• 1991

Particulate is the foreign insoluble material in injectable solution inadvertently present in a given product. Considerable efforts have been made to avoid or minimize particulate contamination by pharmaceutical manufacturers during the production of parenteral products. Particulate contamination of the parenteral products can occur mainly during the opening (cutting) the container immediately before clinical use. In this study, particulate contamination generated during the opening process of ampoules (conventional type, 1-point and color-break ampoules) was compared with that of a prefilled injectable container (prefilled syringe). The particles were examined under a microscope after filtration of the total fluids in the containers. Particles having wide range of size distribution were found from all the ampoules tested. The contamination from the I-point ampoule and colorbreak ampoule was much less than from the conventional ampoule. Glass particles generated by cutting the glass-made ampoules seemed a principal source of the particulate contamination. The glass-partiaulte contamination could be improved substantially by replacing the ampoule containers with the prefilled syringe. Prefilled syringe, which can be used without any cutting process. did not generate particulates during the use. Therefore, it was concluded that prefilled syringe is most preferable container for the small volume parenteral (SVP) fluids in terms of particulate contamination.

• Mass Spectrometry Letters
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• v.9 no.2
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• pp.61-65
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• 2018

KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent $HIF-1{\alpha}$ inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells ($3.1{\times}10^{-6}cm/s$) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effective pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.