• 제목/요약/키워드: Synthetic drugs

검색결과 124건 처리시간 0.028초

Bovine Lactoferricin Induces Intestinal Epithelial Cell Activation through Phosphorylation of FAK and Paxillin and Prevents Rotavirus Infection

  • Jeong, Ye Young;Lee, Ga Young;Yoo, Yung Choon
    • Journal of Microbiology and Biotechnology
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    • 제31권8호
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    • pp.1175-1182
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    • 2021
  • We investigated the effect of bovine lactoferricin (Lfcin-B), a peptide derived from bovine lactoferrin, on activation of intestinal epithelial cells in IEC-6 intestinal cell, and protection against in vivo rotavirus (RV) infection. Treatment with Lfcin-B significantly enhanced the growth of IEC-6 cells and increased their capacity for attachment and spreading in culture plates. Also, Lfcin-B synergistically augmented the binding of IEC-6 cells to laminin, a component of the extracellular matrix (ECM). In the analysis of the intracellular mechanism related to Lfcin-B-induced activation of IEC-6 cells, this peptide upregulated tyrosine-dependent phosphorylation of focal adhesion kinase (FAK) and paxillin, which are intracellular proteins associated with cell adhesion, spreading, and signal transduction during cell activation. An experiment using synthetic peptides with various sequences of amino acids revealed that a sequence of 9 amino acids (FKCRRWQWR) corresponding to 17-25 of the N-terminus of Lfcin-B is responsible for the epithelial cell activation. In an in vivo experiment, treatment with Lfcin-B one day before RV infection effectively prevented RV-induced diarrhea and significantly reduced RV titers in the bowels of infected mice. These results suggest that Lfcin-B plays meaningful roles in the maintenance and repair of intestinal mucosal tissues, as well as in protecting against intestinal infection by RV. Collectively, Lfcin-B is a promising candidate with potential applications in drugs or functional foods beneficial for intestinal health and mucosal immunity.

Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria

  • Oehadian, Amaylia;Santoso, Prayudi;Menzies, Dick;Ruslami, Rovina
    • Tuberculosis and Respiratory Diseases
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    • 제85권2호
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    • pp.111-121
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    • 2022
  • Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

가축의 설사변에서 분리한 대장균과 살모넬라균의 항균물질 감수성과 마우스에서의 치료효과 (Antimicrobial drug susceptibility and treatment efficacy in mice against Escherichia coli and Salmonella spp isolated from feces of diarrheal animals)

  • 김종만;진남섭;김종완;진영화;이희수;권창희;우승룡;이해천;박종명;김재학;이재진
    • 대한수의학회지
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    • 제37권2호
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    • pp.389-403
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    • 1997
  • Survey on MIC of antimicrobial drugs and its treatment efficacy in mice were conducted for the strains of Escherichia coli and Salmonella spp isolated from feces of young domestic animals with diarrhea in 1996. A total of 338 strains of E coli and 61 strains of Salmonella spp were examined for the susceptibility to 20 antibiotics and 7 synthetic antimicrobial drugs. The results indicated that the majority of strains were susceptible to amikacin(93.5%), cefoperazone/sulbactam(93.5%), cefotaxim(93.3%), cefomandole(92.8%), cefoperazone(91.6%) and ciprofloxacin(85.1%), in order. Although gentamicin, ciprofloxacin and norfloxacin showed the relatively low MIC distributions, erythromycin, doxycycline, sulfamethoxazole and oxytetracycline revealed the high MIC distributions to most of isolates. The $MIC_{90}$ of antimicrobials for E coli were > $62.5{\mu}g/ml$ in gentamicin, $2.0{\mu}g/ml$ in ciprofloxacin, $1.0{\mu}g/ml$ in norfloxacin, > $500{\mu}g/ml$ in erythromycin, $125{\mu}g/ml$ in doxycycline, > $1000{\mu}g/ml$ in sulfamethoxazole and > $250{\mu}/ml$ in oxytetracycline. In general, the MIC of E coli isolates was higher than that of Salmonella spp isolates. Although variation in synergism or additivity of antibiotic combinations were demonstrated, ampicillin-gentamicin was the most efficacious combination both against E coli and Salmonella spp with the fluctuation of 7.7-77.5%. In the experiment of treatment efficacy in mice, the highest survival ratio(83.3%) after challenge with pathogenic E coli and Salmonella typhimurium was detected in the group treated with gentamicin.

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임상에서 분리한 메치실린 내성 황색포도상구균에 대한 녹나무잎 추출물의 항균활성 (Synergistic Effects of Cinnamomum camphora Leaves Extract against Clinical Isolated Methicillin-resistant Staphylococcus aureus)

  • 차정단;최미래;고은실;황승미;강제란;오좌섭;박영진;정용환;전아림;최경민
    • 한국자원식물학회지
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    • 제28권1호
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    • pp.9-15
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    • 2015
  • 메치실린내성 황색포도상구균(MRSA)은 가장 중요한 지역 사회 병원성 균주의 하나로서 항생제 내성 문제가 세계적으로 대두되고 있다. 감염 치료에 대한 부작용과 내성이 적은 새로운 항생제의 개발에 많은 관심과 연구가 필요하다. Cinnamomum camphora는 제주도에서 자생하는 녹나무과의 식물이다. 민간에서는 신경 쇠약, 간질, 방광염, 신우 신염, 당뇨, 암과 당뇨병 치료제로 이용되고 있다. 본 연구에서는 80% 에탄올을 이용하여 녹나무잎을 추출물하여 임상에서 분리한 메치실린 내성 균주에 대한 항균활성을 연구하였다. 그 결과 녹나무잎 추출물에서 높은 항균활성을 관찰 할 수 있었고, 항생제와의 병용처리 녹나무잎 추출물의 MIC와 MBC의 범위는 $156-313{\mu}g/ml$$313-625{\mu}g/ml$로 판독되었고, oxacillin의 병용처리의 범위는 $1288-256{\mu}g/ml$$128-512{\mu}g/ml$, 그리고 ampicillin의 병용처리 범위는 ${\mu}g/ml$$8-128{\mu}g/ml$로 판독되었다. 녹나무잎 추출물과 항생제의 병용처리는 MRSA 항균활성에 대한 상승효과가 높게 나타났다.

Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice

  • Nagwa S. M. Aly;Hiroaki Matsumori;Thi Quyen Dinh;Akira Sato;Shin-Ichi Miyoshi;Kyung-Soo Chang;Hak Sun Yu;Fumie Kobayashi;Hye-Sook Kim
    • Parasites, Hosts and Diseases
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    • 제61권1호
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    • pp.33-41
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    • 2023
  • The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

Differential Expression of Kidney Proteins in Streptozotocin-induced Diabetic Rats in Response to Hypoglycemic Fungal Polysaccharides

  • Hwang, Hye-Jin;Baek, Yu-Mi;Kim, Sang-Woo;Kumar, G. Suresh;Cho, Eun-Jae;Oh, Jung-Young;Yun, Jong-Won
    • Journal of Microbiology and Biotechnology
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    • 제17권12호
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    • pp.2005-2017
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    • 2007
  • Diabetic nephropathy remains a major cause of morbidity and mortality in the diabetic population and is the leading cause of end-stage renal failure. Despite current therapeutics including intensified glycemic control and blood pressure lowering agents, renal disease continues to progress relentlessly in diabetic patients, albeit at a lower rate. Since synthetic drugs for diabetes are known to have side effects, fungal mushrooms as a natural product come into preventing the development of diabetes. Our previous report showed the hypoglycemic effect of extracellular fungal polysaccharides (EPS) in streptozotocin (STZ)-induced diabetic rats. In this study, we analyzed the differential expression patterns of rat kidney proteins from normal, STZ-induced diabetic, and EPS-treated diabetic rats, to discover diabetes-associated proteins in rat kidney. The results of proteomic analysis revealed that up to 500 protein spots were visualized, of which 291 spots were differentially expressed in the three experimental groups. Eventually, 51 spots were statistically significant and were identified by peptide mass fingerprinting. Among the differentially expressed renal proteins, 10 were increased and 16 were decreased significantly in diabetic rat kidney. The levels of different proteins, altered after diabetes induction, were returned to approximately those of the healthy rats by EPS treatment. A histopathological examination showed that EPS administration restored the impaired kidney to almost normal architecture. The study of protein expression in the normal and diabetic kidney tissues enabled us to find several diabetic nephropathy-specific proteins, such as phospholipids scramblase 3 and tropomyosin 3, which have not been mentioned yet in connection with diabetes.

Etomidoline이 각종 평활근에 미치는 영향 (Effect of Etomidoline on the Isolated smooth Muscle of Rabbit)

  • 김원준;김정희;신윤용
    • 대한약리학회지
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    • 제16권2호
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    • pp.25-29
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    • 1980
  • Etomidoline ($Nonspa^{\circledR}$), which is chemically related to tertiary amine, is new synthetic antispasmodic agent with analgesic action. Antispasmodic effect of this agent is stronger than hyoscine butylbromide ($Buscopan^{\circledR}$), quaternary amine, and the absorption from intestine is also much higher. This study was undertaken to determine the effect of etomidoline on duodenal motility and other smooth muscles of rabbit. Strips of various isolated smooth muscle, 2 cm long from adult rabbits weighting about 2 kg, were suspended in a muscle chamber containing Tyrode's solution, which was bubbled with oxygen gas, and the temperature of the solution was kept constant at $38^{\circ}C$. After being washed with fresh solution several times the strips of smooth muscle attained constant motility and tonus. Etomidoline and other drugs were added in various concentrations to the chamber. Contractility of the strips was measured by using polygraph (Grass, model 7). The results are as follows: 1) In isolated rabbit atrium etomidoline produces a slight depression of contractility and the rate is also decreased. 2) On the other hand, etomidoline relaxed isolated strips of stomach, duodenal, and detrusor of rabbit. This relaxing effect of etomidoline on isolated duodenal strip of rabbit was not blocked by ${\alpha}$-adrenergic blocking agent, phenoxybenzamine, but by ${\beta}$-adrenergic blocking agent, propranolol. 3) Etomidoline did not exert any effect on isolated aorta, gall bladder, and trigone of rabbit. From the above results, it may be concluded that the relaxing effect of etomidoline on duodenal strip is related ${\beta}$-adrenergic receptor.

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해조류 유래 호흡기 질환 천식 치료제 연구 동향 (A Review of Marine Algae-derived Therapeutic Agents for Respiratory Disease Asthma)

  • 김태희;허성영;오건우;김민성;최일환;정원교
    • 한국해양바이오학회지
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    • 제12권1호
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    • pp.1-10
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    • 2020
  • Asthma is a complex inflammatory disease of the lung characterized by variable airflow obstruction, airway hyperresponsiveness, airway inflammation, and reduction of respiratory function. Its prevalence and incidence are increasing because of the effect of various environmental and lifestyle risk factors. Steroid inhalation, long-acting agonists, and other synthetic drugs are used for the treatment of this disease. However, they have some side effects and show unsatisfied result and response after treatment. Therefore, many researchers have focused on the development of natural product-related treatment for asthma to suppress the side effects and unsatisfied results. Seaweeds contain various bioactive compounds with anti-inflammatory, antibacterial, and anti-oxidant activities. Thus, we investigated the asthma treatment-related literature using marine algae via the Google scholar search engine. Consequently, the literature is rarely investigated, but is increasing steadily. The literature was performed as a comparison study with an ovalbumin-induced group or drug-treated group, and investigated the antiasthma activity of algae ethanol extract. Although many researchers have studied marine algae-derived therapeutic agents for asthma, the amount of literature is rare compared with those of herbal medicine-derived therapeutic agents. Conclusively, we suggest that many researchers should investigate and develop algae-derived therapeutic agents for asthma treatment.

General Pharmacology of Artesunate, a Commonly used Antimalarial Drug: Effects on Central Nervous, Cardiovascular, and Respiratory System

  • Lee, Hyang-Ae;Kim, Ki-Suk;Kim, Eun-Joo
    • Toxicological Research
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    • 제26권3호
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    • pp.223-232
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    • 2010
  • Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

고속액체크로마토그라피에 의한 계란중의 합성항균제 잔류량 (Residue of Synthetic Antimicrobial Agent in Eggs by High Performance Liquid Chromatography)

  • 김종배;이성국;김두희
    • 농촌의학ㆍ지역보건
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    • 제18권1호
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    • pp.55-63
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    • 1993
  • 고속액체크로마토그라피를 이용하여 계란 중의 합성항균제 설파메라진, 설파메타진, 설파디메톡신, 후라졸리돈, 죠렌 등의 잔류량에 관한 신속하고 간편한 동시분서법을 검토하였는데, 각 합성항균제 표준용액을 첨가하여 나타난 회수율은 설파메라진 81.2%, 설파메타진 87.6%, 설파디메톡신 92.5%, 후라졸리돈 86.1%, 죠렌 73.9%로 나타났으며, 검출한계는 설파메라진, 설파메타진, 설파디메톡신이 0.2ppb 수준으로 나타났고, 후라졸리돈과 죠렌 0.5ppb 수준으로 나타났다. 본 분석방법으로 대구지역 시판계란 84개에 대한 잔류량을 조사한 결과, 설파메타진 3개 계란, 설파디메톡신이 4개 계란에서 각각 0.005-0.008ppm과 0.012-0.019ppm 정도 검출되었으며, 설파메라진, 후라졸리돈, 죠렌은 모든 시료에서 검출되지 않았다. 이상의 결과로 추정해 볼 때 설파메라진, 설파메타진, 설파디메톡신, 후라졸리돈, 죠렌의 계란내 잔류정도는 비교적 안전한 수준으로 나타났다.

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