The DM9 domain is a protein unit of 60-75 amino acids that has been first detected in the fruit fly Drosophila as a repeated motif of unknown function. Recent research on proteins carrying DM9 domains in the mosquito Anopheles gambiae and the oyster Crassostrea gigas indicated an association with the uptake of microbial organisms. Likewise, in the trematode Fasciola gigantica DM9-1 showed intracellular relocalization following microbial, heat and drug stress. In the present research, we show that FgDM9-1 is a lectin with a novel mannose-binding site that has been recently described for the protein CGL1 of Crassostrea gigas. This property allowed FgDM9-1 to agglutinate gram-positive and -negative bacteria with appropriate cell surface glycosylation patterns. Furthermore, FgDM9-1 caused hemagglutination across all ABO blood group phenotypes. It is speculated that the parenchymal located FgDM9-1 has a role in cellular processes that involve the transport of mannose-carrying molecules in the parenchymal cells of the parasite.
The goals of the present study were to develop a simple method for obtain highly purified pig sperm hyaluronidase (pHyase) and to assess its activity, function, and safety. In mammals, sperm-specific glycophosphatidylinositol (GPI)-anchored Hyase assists sperm penetration through the cumulus mass surrounding the egg and aids in the dispersal of the cumulus-oocyte complex. Recently, Purified bovine sperm hyaluronidase (bHyase) has been shown to enhance therapeutic drug transport by breaking down the hyaluronan barrier to the lymphatic and capillary vessels, thereby facilitating tissue absorption. Commercially available Hyase is typically isolated from bovine or ovine; which have several disadvantages, including the risk of bovine spongiform encephalopathy, low homology with human Hyase, and the requirement for relatively complex isolation procedures. This study successfully isolated highly purified pHyase in only two steps, using ammonium sulfate precipitation and fast protein liquid chromatography. The isolated Hyase had activity equal to that of commercial bHyase, facilitated in vitro fertilization, and effectively dissolved high molecule hyaluronic acid. This simple, effective isolation method could improve the availability of pHyase for research and clinical applications.
Numerous investigators have conducted extensive investigation in the search for biological markers in psychiatric illness. There are, as a test of q biological approach to the diagnosis of the psychiatric illness, tests for the neurotransmitters, their metabolites, and related enzymes, the neurotransmitter receptors, the neuroendocrine output and response, the membrane transport, peptides and eletrolytes. They are called the biological markers, and they are helpful for the diagnosis or differential diagnosis, choice of treatment or drugs, symptom improvement, predictor of recurrence and anticipation of suicidal attempt. These studies are among the main purposes that are pursued in the neuroscience and based on the potential utility of the biological markers mentioned above. Since 1970's, lots 01 biological markers' studies for the diagnosis, differential diagnosis or subtypes differentiation have been done but varieties of different opinions have been drawn since then through they could explain the charaters of main psychiatric illness(especially schizophrenia and mood disorder). But, the search for biological markers, including displines of neuroendoclinology and neurochemistry(neurotransmitter and thair metabolite), has yielded a number of putative trait merkers and state markers for psychayric illness. This paper aims to anticipate or evaluate the good response to the therapy(Therpeutic response) with lots of markers. Acoording to the diagnosis of lots of diseases or subtypes, we are going to review the papers, mainly concern with 'Is there any Marker' or 'Is any test possible to detect the improvement clinically?' 'Is it possible to predict the recurrence or good prognsis?' or 'Is it possible to select any drug or therapy to bring the good response?' The biological tests to review are mainly the metabolites of catecholamine neurotransmitter, and especially neuroendocrine test based on the knowledge that hormons of the adenohypophysis are influenced by activity of the cerebral or limbic neurons as well as the hypothalamus ones. Among them, author introduced some clinically available tests that are DST, TRH stimulation test(TRHST), GH stimulation test, and the urine MHPG test that can give us the evaluation of the treatment response, the predictor for recurrence or choice of drug that can bring a good response. So author discussed thair potential utility in clarifying, therapeutic, and prognostic issues in psychatric illness. We hope they'll be used and look forward to more active study on the different opinion.
From the tuberous root of Aconitum carmichaeli Debx.(Ranunculaceae), the main root is called as common monkhood mother root and the later root is called as the prepared aconite root. From the prepared aconite root. Looking at the processing method of the prepared aconite root, it is divided into Yeombuja (prepared aconite root processed in salt) and heuksoonpyeon (baekbupyeon) following the processing method after removing the soil and this is a way of processing the prepared aconite root without damage it. The recently produced raw prepared aconite root is easily damaged, thus it shall be preserved in salt to have the crystal shape on the surface of the prepared aconite root and store and transport in firmly solidified yeombuja condition. Therefore, yeombuja shall remove the salt before use and requires processing for use but heuksoonpyeon or baekbupyeon may use immediately. For the succession of the unique processing techniques of our ancestors, there has to be studies on the techniques. Prepared aconite root is generally used as holy medicines to cure the yang depletion syndrome, kidney-yang deficiency syndrome, and obstruction of qi in the chest syndrome. However, they are the substances with toxicity. It is contemplated that the contents of processing are broadly understood through the document on the processing method, and based on such foundation, the systematic set and proof on the documents are made along with the addition of the contemporary scientific theory and technology to develop the traditional processing technology to maximize the treatment effect and safety of prepared aconite root. In this study, the historic data and records on the processing method of latteral root of aconitum carmichaeli Debx will be rearranged to contribute to the standardization of medicinal herbs, maximization of efficacy and minimization of the side effects.
Background: Honey bees play a crucial role in pollination and ecological balance. Apis mellifera L. colonies, especially those located in specific geographic regions, such as the palm garden in Eastern Thailand, are susceptible to potential threats from microbial contaminants. Understanding and detecting microbial organisms in these beehives is essential for the preservation of bee health, honey production, and the broader ecosystem. However, the problem of microbial infection and antibiotic-resistant bacteria is more severe and continuously increasing, resulting in a health, economic, and social crisis. The purpose of this study is to determine the prevalence of microorganisms in A. mellifera beehives in palm gardens in Rayong province, Eastern Thailand. Results: Ten swabs in transport media were swabbed and obtained from different parts of each beehive (1 swab per beehive), for a total of 10 hives. Traditional microbial culture-based methods, biochemical tests, and antimicrobial susceptibility (disc-diffusion) tests were used to detect microbial organisms and antibiotic resistance in bacteria. The swab tests from nine beehives resulted in the detection of Gram-positive bacteria (63.64%), Gram-negative bacteria (27.27%), and fungi/yeast (9.09%). These microorganisms are classified as a group of coagulase-negative Staphylococcus spp. and made up 40.91% of the bacteria discovered. Other bacteria found were Coryneform bacteria (13.64%), Pantoea spp. (13.64%), Bacillus spp. (9.09%), yeast (9.09%), glucose non-fermentative Gram-negative bacilli (9.09%), and Pseudomonas spp. (4.55%). However, due to the traditional culture-based and 0biochemical tests usually used to identify the microbial organisms in clinical specimens and the limitation of identifying some environmental microbial species, the results of the antimicrobial susceptibility test cannot reveal if the organism is resistant or susceptible to the drug. Nevertheless, drug-sensitive inhibition zones were formed with each antibiotic agent. Conclusions: Overall, the study supports prevention, healthcare, and public health systems. The contamination of microorganisms in the beehives may affect the quality of honey and other bee products or even the health of the beekeeper. To avoid this kind of contamination, it is therefore necessary to wear personal protective equipment while harvesting honey and other bee products.
To ensure the microbiological safety of food items prepared after cooking process, this study was aimed to identify the hazards related with cooked foods donated to foodbanks through quantitative microbial analysis. Five foodbanks located in Incheon and Gyeonggi area among government-dominant foodbanks were surveyed from February to June, 2007. Manager, recipient, donator, type and quantity of donated foot and facility and equipment were examined for the general characteristics of foodbank. The time and temperature of food md environment were measured at steps from after-production to before-distribution, and the microbial analysis was performed mainly with indicator organism and major pathogens. The amount of cooked foods donated to each foodbank was about 20 to 30 servings and consisted of 80% of total donated foods. Only three foodbanks had separate offices for foodbank operation and four institutions had at least one temperature-controlled vehicle. The flow of donated foods was gone through the steps; production, meal service and holding at donator, collection by foodbank, transport (or holding after transport) and distribution to recipients. It took about 3.8 to 6.5 hours at room temperature from after-production to before-distribution. Only aerobic plate counts (APC) and coliforms were found in microbial analysis. The APC after production were relatively high in $8.2{\times}10^5,\;7.4{\times}10^5,\;6.9{\times}10^5$ and $4.2{\times}10^5 CFU/g$ while $2.8{\times}10^6, \;9.4{\times}10^5,\;1.0{\times}10^6$ and $5.4{\times}10^5CFU/g$ before distribution in mixed Pimpinella brachycarpa, mixed chard mixed amaranth and mixed spinach, respectively. The levels of coliforms in mixed chard and mixed spinach were complied with the standards of the Ministry of Education and Human Resources Management The level of APC in boiled pork was increased from $< 1.0{\times}10 CFU/g$ to $4.0{\times}10^2 CFU/g$. One of delivery vessels was shown $6.2{\times}10^3 CFU/100 cm^2$ in APC, which was over the standards for environment. One of serving tables also showed the high level of $1.2{\times}10^3 CFU/100 cm^2$ in APC and $6.6{\times}10^2 CFU/100 cm^2$ in coliforms. These results suggest the sanitary management of holding at donator and the time-temperature control are key factors to ensure the safety of cooked foods donated to foodbank.
Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.
Lee, Sangbae;Lee, Yuno;Briggs, James M.;Lee, Keun Woo
Bulletin of the Korean Chemical Society
/
제34권7호
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pp.1972-1984
/
2013
Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol$^{TM}$) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two ${\beta}$-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.
The aim of this study was to investigate the absorption properties of ketoprofen. The in-situ perfusion model has advantages over in vitro models as it provides intact lymphatic and blood flow circulation. The absorption properties of six different concentrations of ketoprofen have been studied in single pass in-situ rat intestine model. $^{14}C-PEG$ 4000 was used as a permeability marker and the possibility of an energy dependent contribution to ketoprofen absorption was also Investigated using the metabolic inhibitor sodium azide. Three different concentrations of sodium azide were studied to examine its effect on absorption of ketoprofen from the rat intestine. The findings of this study suggest that mono-carboxylic type drugs like ketoprofen cause permeability changes in the intestine. This is shown by the increase in absorption of $^{14}C-PEG$ 4000 as the concentration of ketoprofen is increased. However, the trend for ketoprofen permeability is to decrease over the concentration ranges. It was observed that the Papp values for ketoprofen with sodium azide shows a trend towards reduction in the amount of ketoprofen absorbed from the rat intestine which was significantly different (p<0.05) from that of ketoprofen with sodium azide 3.0mM. This indicates that sodium azide has an affect on the absorption of ketoprofen. The pH of all the perfusion solutions was altered to ${\sim}pH\;6.7$ by the buffering capacity of the small intestine secretions. The results suggest that mechanisms other than passive diffusion may be involved in ketoprofen absorption. This would be consistent with the involvement of active transport or saturatable processes in the absorption of drugs containing monocarboxylic acid group, as has been previously suggested from in vitro data.
Hong, Sun-Mi;Jeon, Sang-Ok;Seo, Jo-Eun;Chun, Kyeung-Hwa;Oh, Dong-Ho;Choi, Young Wook;Lee, Do Ik;Jeong, Seong Hoon;Kang, Jae Seon;Lee, Sangkil
Bulletin of the Korean Chemical Society
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제35권11호
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pp.3188-3194
/
2014
Compound K (CK) was formulated as polymeric micelles (PM) using Pluronic$^{(R)}$ F-127 to enhance the oral absorption of CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin. The physicochemical properties of Ck-loaded PM were characterized and an in vitro transport study using the Caco-2 cell system as well as an in vivo pharmacokinetic study using SD rats was carried out. The hydrodynamic mean particle size of CK-loaded PM (CK-PM) was $254{\pm}23.45nm$ after rehydration and the drug loading efficiency was ca. 99.9%. The FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy data supported the presence of a new solid phase in the PM. The $P_{app}$ value of in vitro Caco-2 cell permeation of CK-PM and the oral absorption of CK was enhanced about 1.2-fold and 2.6-fold compared to CK suspension, respectively, showing that the present PM formulation enabled an enhancement of oral CK absorption.
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