• Title/Summary/Keyword: control drug

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Induction of Growth Inhibition and Apoptosis in Human Cancer Cells by a Brown Algae Extract (갈조류 추출물에 의한 인간 암세포 성장 억제 및 세포 사멸 유도)

  • Choo, Kang-Sik;Lee, Hae-Nim;Shin, Seong-Ah;Kim, Hyeong-Jin;Park, Young-Seok;Kim, Sang-Ki;Jung, Ji-Youn
    • Journal of Life Science
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    • v.26 no.5
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    • pp.555-562
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    • 2016
  • In this study, we investigated the effects of Undaria pinnatifida (UP), Petalonia binghamiae (PB) and Punctaria latifolia (PL) extracts on the inhibition of proliferation and apoptosis in human gastric and breast cancer cells. AGS, MDA-MB-231 and SK-BR-3 cells were treated with 0, 50, 100, and 200 μg/ml concentrations of the extracts to determine their anti-proliferative effects, using the MTT assay. The UP, PB and PL extracts inhibited proliferation of AGS, MDA-MB-231 and SK-BR-3 cells in a dose-dependent manner, and the PL extract was found to be the most effective. DAPI staining was also performed to determine changes in the cell nucleus. Further, the AGS, MDA-MB-231 and SK-BR-3 cells were treated with 0, 50, 100, and 200 μg/ml of only the PL extract. DAPI staining showed increased chromatin condensation, which is indicative of apoptosis, in the 200 μg/ml group. The expression of the Bax, Bcl-2, and PARP proteins in AGS, MDA-MB-231 and SK-BR-3 cells treated with the PL extract was also determined by western blot analysis. The expression of Bax (a pro-apoptotic protein) and cleaved-PARP was increased, whereas the expression of Bcl-2 (an anti-apoptotic protein) was decreased compared with the control. These findings indicate that the PL extract may have potential as an alternative anticancer drug and nutraceutical.

Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation (방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-Hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.571-578
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    • 2001
  • To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

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Production of Medium-chain Fatty Acids in Brassica napus by Biotechnology (유채에서의 중쇄지방산 생산)

  • Roh, Kyung-Hee;Lee, Ki-Jong;Park, Jong-Sug;Kim, Hyun-Uk;Lee, Kyeong-Ryeol;Kim, Jong-Bum
    • Journal of Applied Biological Chemistry
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    • v.53 no.2
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    • pp.65-70
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    • 2010
  • Medium-chain fatty acids (MCFA) are composed of 8-12 carbon atoms, and are found in coconut, cuphea, and palm kernel oil. MCFA were introduced into clinical nutrition in the 1950s for dietary treatment of malabsorption syndromes because of their rapid absorption and solubility. Recently, MCFA have been applied to Gastrointestinal Permeation Enhancement Technology (GIPET), which is one of the most important parts in drug delivery system in therapeutics. Therefore, to accumulate the MCFA in seed oil of rapeseed, much effort has been conducted by classical or molecular breeding. Laurate can be successfully accumulated up to 60 mol% in the seed oil of rapeseed by the expression of bay thioesterase (Uc FatB1) alone or crossed with a line over-expressing the coconut lysophosphatidic acid acyltransferase (LPAAT) under the control of a napin seed-storage protein promoter. Also, caprylate and caprate were obtained 7 mol% and 29 mol%, respectively, from plants over-expressing of the medium-chain specific thioesterase (Ch FatB2) alone or together with the chain-length-specific condensing enzyme (Ch KASIV). Despite the success of some research in utilizing parallel classical and molecular breeding to produce MCFA, commercially available seed oils have for the most part, not been realized. Recent research in the field of developing MCFA-enriched transgenic plants has established that there is no single rate-limiting step in the production of the target fatty acids. The purpose of this article is to review some of the recent progress in understanding the mechanism and regulation of MCFA production in seed oil of rapeseed.

Effect of Imipramine on the Contractility of Single Cells Isolated from Canine Detrusor (Imipramine이 배뇨근 세포의 수축성에 미치는 직접작용)

  • Huh, Chan-Wook;Lee, Kwang-Youn;Kim, Won-Joon
    • Journal of Yeungnam Medical Science
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    • v.11 no.2
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    • pp.293-302
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    • 1994
  • The objective of this study was to establish a good methodology to isolate single smooth muscle cells that are alive and respond properly to pharmacological agents. Canine urinary bladders were employed as the source of single cells, and acetylcholine, atropine and imipramine were used as indicators of pharmacological responsiveness. Imipramine, an antidepressant drug exhibited the anticholinergic and calcium antagonizing properties on rat detrusor muscle. To establish a control value for a further experiment to elucidate the mechanism of action of imipramine on detrusor muscle, we measured the concentration-response of single cells to acetylcholine in the presesnce of imipramine by length of the cells and compared the result with the response in the presence of atropine. Tiny chops of smooth muscle taken from anesthetized canine urinary bladder were incubated in collagenase solution at $36^{\circ}C$ for 17-20 minutes. The collagenase solution included collagenase 1.2 mg/ml, soybean tryspin inhibitor 0.08 mg/ml, bovine serum albumin 2% in 10 ml Krebs-Henseleit buffer solution aerated with a consistent breeze of 95/5% $O_2/CO_2$, to maintain the pH at 7.4. After washing with plain K-H solution on 450 mesh, cells were dissociated from the digested tissue for 12-15 minutes. Cell suspension was transfered in 5 ml test tubes and acetylcholine was added for the final concentration to be $10^{-14}M{\sim}10^{-9}M$. To find the optimal time to fix the cells to determine the contractile responses, 1% acrolein was added 5, 10, 20, 30, 60 and 120 seconds after the administration of ACh. The length of cells fixed by acrolein were measured by microscaler via CCTV camera on phaes-contrast microscope. The average length of 50 cells from a slide glass was taken as the value of a sample at the very concentration point. Single cells were isolated from canine detrusor. The length of untreated cells varied from 82 ${\mu}m$ to 94 ${\mu}m$. The maximal response to actylcholine $10^{-9}M$ was accomplished within 5 seconds of exposure, and the shortening was $19{\pm}3$%. Atropine reduced the contraction of the cells concentration-dependently. Imipramine which exerts a cholinergic blocking action on some smooth muscles also reduced the contraction concentration-dependently and by a similar pattern as atropine. These findings document that imipramine may exerts a cholinergic blocking activity in the single smooth muscle cells isolated from canine urinary bladder.

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Mucin2 is Required for Probiotic Agents-Mediated Blocking Effects on Meningitic E. coli-Induced PathogenicitiesS

  • Yu, Jing-Yi;He, Xiao-Long;Puthiyakunnon, Santhosh;Peng, Liang;Li, Yan;Wu, Li-Sha;Peng, Wen-Ling;Zhang, Ya;Gao, Jie;Zhang, Yao-Yuan;Boddu, Swapna;Long, Min;Cao, Hong;Huang, Sheng-He
    • Journal of Microbiology and Biotechnology
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    • v.25 no.10
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    • pp.1751-1760
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    • 2015
  • Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

Anti-Inflammatory Effect of Sargassum patens C. Agardh Ethanol Extract in LPS-induced RAW264.7 Cells and Mouse Ear Edema (LPS로 유도된 RAW 264.7 cell과 마우스 귀 부종 모델을 통한 쌍발이 모자반 에탄올 추출물의 항염증 효과)

  • Kim, Min-Ji;Kim, Min-Ju;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Choi, Hyeun-Deok;Park, So-Yeong;Kim, Ji-Hyun;Jang, Mi-Ran;Im, Moo-Hyeog;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.45 no.2
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    • pp.110-117
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    • 2017
  • The anti-inflammatory effect of Sargassum patens C. Agardh ethanol extract (SPEE) was examined based on the lipopolysaccharide (LPS)-induced inflammatory response in this study. SPEE treatment was not cytotoxic to macrophages compared to the control. The production of NO was suppressed by SPEE by approximately 28% at $100{\mu}g/ml$, and levels of interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ decreased in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ was suppressed by SPEE treatment. In vivo, croton oil-induced mouse ear edema was attenuated by SPEE and the infiltration of mast cells into the tissue decreased. Based on these results, SPEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SPEE is a potential agent for anti-inflammatory therapies.

1-β-D-Arabinofuranosyl-cytosine Induces Chromosomal Breaks in vitro (In vitro에서 1-β-D-arabinofuranosyl-cytosine의 염색체 파열 유도)

  • Jeon, In-sang
    • Clinical and Experimental Pediatrics
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    • v.46 no.12
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    • pp.1186-1193
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    • 2003
  • Purpose : Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-${\beta}$-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. Methods : T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. Results : Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. Conclusion : S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.

Clinical Characteristics and Prognosis of Neonatal Seizures (신생아 경련의 임상적 양상 및 예후에 관한 고찰)

  • Kim, Chang Wu;Jang, Chang Hwan;Kim, Heng Mi;Choe, Byung Ho;Kwon, Soon Hak
    • Clinical and Experimental Pediatrics
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    • v.46 no.12
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    • pp.1253-1259
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    • 2003
  • Backgroud : Seizures in the neonate are relatively common and their clinical features are different from those in children and adults. The study aimed to provide the clinical profiles of neonatal seizure in our hospital. Methods : A total of 41 newborns with seizures were enrolled in this study over a period of three years. They were evaluated with special reference to risk factors, neurologic examinations, laboratory data, neuroimaging studies, EEG findings, seizure types, response to treatment, and prognosis, etc. Results : The average age at onset of seizures was $6.1{\pm}4.6days$ and the majority of patients(42%) had multifocal clonic seizure and 24% had subtle seizure. Factors that are known to increase risk of neonatal seizures include abnormal delivery history, birth asphyxia, and electrolyte imbalance, etc. However, they remain obscure in about 20% of cases. More than 50 percent showed abnormal lesions on neuroimaging studies such as brain hemorrhage, periventricular leukomalacia, brain infarction, cortical dysplasia, hydrocephalus, etc. and 17 out of 32 patients showed abnormal electroencephalographic patterns. Phenobarbital was tried as a first line antiepileptic drug and phenytoin was added if it failed to control seizures. The treatments were terminated in the majority of patients during the hospital stay. The overall prognosis was relatively good except for those with abnormal EEG background or congenital central nervous system malformations. Conclusion : Neonatal seizures may permanently disrupt brain development. Better understanding of their clinical profiles and appropriate management may lead to a reduction in neurological disability in later childhood.

Functional and morphological changes of the livers by 5-fluorouracil treatment on diethylnitrosamine-treated rat (발암제 (DEN) 투여 rat의 간암 진행상태의 기능학적 및 형태학적 변화와 항암제(5-FU) 처리효과 시험)

  • Kim Cheol-Ho;Cheon Sung-Hwa;Bhak Jong-Sik;Kim Nam-Cheol;Kang Chung-Boo
    • Korean Journal of Veterinary Service
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    • v.29 no.3
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    • pp.347-364
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    • 2006
  • This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.

Clinical review of Typhoid Fever Patients (장티브스에 관한 임상적 관찰)

  • 최정신
    • Journal of Korean Academy of Nursing
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    • v.6 no.1
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    • pp.60-71
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    • 1976
  • The author reviewed the medical records of 96 typhoid fever patients who were diagnosed, admitted, and treated at Sea grave Memorial Hospital from January 1 , 1973 through August 31, 1975. Diagnosis was determined by clinical observation, aerology and bacteriology, eighty patients were treated medically, the remaining 16 patients required surgical intervention. The following results were obtained: 1) The age distribution of the patients revealed that 33.3% wert between 10 and 19 years old 21.9% were between 20 and 29, and 19.8% were between 30 and 39. The majority of patients were from these more active age groups. Male to female sex ratio was 1.3 : 1 2) Seasonal distribution was observed. Most illness occurred in the summer and autumn month 5. 3) 84. 3%of the patients came from farm families. 4) Duration between onset and admission averaged 16.0 days. The group without compilations was admitted after an average of 15. 1 days; The group with complications was ad-matted after an average of 19.4 days. 5) Methods of treatment before admission were as follows: 10.4% at medical clinics, 61, 5% at pharmacies (antibiotics 47.9%, other. drugs 13.5%), 7.3% by herb medications, 20.8% had no treatment. 6) Main clinical symptoms were as follows: fever 93.8%, headache 47.9%, abdominal pain 47.9%, chills 38.5%, cough 36.5%, general weakness 26.0%, nausea e vomiting 24.0% and generalized pain 21.9%. 7) Temperature of patients on admission: 22.9% were 39f or more, 67.6% were between 37℃ and 38℃, and 9.4% were 37℃ or less. 8) Occurrence of intensional bleeding after onset of disease averaged 9.3 days; perforation occurred at an average of 19. 1 days. 9) Interval between onset of major complication and surgical intervention averaged 2.8 days. 10) Among the 68 patients who underwent the bacteriological test the positive rate was 44.1% (30). The positive ,ales to, each separate culture method were as follows: 20.4% in the blood culture, 40.4% in the stool culture and 6.7% in the urine culture. Among these bacteriological positive patients 15 patients had a negative results or less than 160 titer of vidal reaction. 11) The initial vidal test of the total group showed a counts of 160 titer or more in 60.4% and less than 160 titer in 39.6%, 12) W. B. C. Counts in the uncomplicated group indicated that 32.5% were 6,000/㎣ or less, 47.5% were between 6,000 and 10,000, arid 20.0% were 10,000/㎣ or more. In the complicated group, 37.6% were 6,000/㎣ or less, 25,0% were 6,000-10,000/㎣ and 37.6% were 10,000/㎣ or more. 13) Duration of hospital stay of the patients averaged 6.4 days in the uncomplicated group and 12.7 days in the complicated group. 14) Subdiaphragmatic free air simple X-ray was found in 91.7% of the perforated cases. 15) Duration of antibiotic therapy until an febrile state was attained averaged 4.8 days in the uncomplicated group and 6.5 days in the complicated group. 16) Operative procedures were as follows: one layer simple closure of their perforation with or without debasement in 56.3%, drainage only in 6.3%, small bowel resection with primary anastomosis in 18.8% , externalization in 6.3%, cholecystectomy in 6.3%, The clinical findings of this study suggest the following recommendations. According to Top's report; 1% of typhoid fever patients treated with chlorarnphenicol and 2% of patients treated with other drugs become chronic carriers. Therefore, importance should be given to the strict control of these carriers. Immunization, improvement of sanitation and living standards are all needed for the prevention and treatment of disease, but a more serious problem is a lack of knowledge on the part of patients and their families. Thus it is most urgent to enlighten the citizens about the transmission and hygiene related to contagious disease. Legal restriction of sale of antibiotics at drug stores without a physician's prescription is an urgent matter for public health administrators. An even more important nursing responsibility is the reemphasis on health education both in the clinical setting and in the home.

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