• Title/Summary/Keyword: Drug-associated

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Highly Active Antiretroviral Therapy Alters Sperm Parameters and Testicular Antioxidant Status in Diet-Induced Obese Rats

  • Oyeyipo, Ibukun P.;Skosana, Bongekile T.;Everson, Frans P.;Strijdom, Hans;du Plessis, Stefan S.
    • Toxicological Research
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    • v.34 no.1
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    • pp.41-48
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    • 2018
  • The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the in vivo effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART. An antiretroviral drug combination of Tenofovir, Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered for the latter 6 weeks via jelly cube feeding. At the end of the experimental period, sperm analysis was performed on sperm collected from the caudal epididymis, while the testis was homogenized for antioxidant enzyme and lipid peroxidation assays. Results showed that HAART significantly decreased sperm motility (p < 0.05) in both lean and obese animals, and viability (p < 0.05) in the DIO group. Testicular glutathione, catalase and superoxide dismutase were significantly decreased (p < 0.05), while Thiobarbituric acid reactive substances (TBARS) levels were significantly increased (p < 0.05) when the DIO+ART group was compared to Control group. Thus, the decreased sperm qualities associated with HAART might be as a result of increased testicular oxidative stress prominent in obese animals.

Screening on Allogeneic Mixed Lymphocyte Culture Inhibitory Activity for the Extracts of Marine-Derived Microorganisms (해양미생물 추출물의 동종세포반응 (Allogeneic Mixed Lymphocyte Culture) 억제효능 검색)

  • Yun, Keum-Ja;Oh, Keun-Hee;Lee, Dong-Sup;Choi, Hong-Dae;Kang, Jung-Sook;Son, Byeng-Wha
    • Korean Journal of Pharmacognosy
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    • v.42 no.4
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    • pp.354-360
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    • 2011
  • In order to screen new allogeneic mixed lymphocyte culture (allo-MLR) inhibitor which is expected to be immunomodulating drug lead, we have investigated allo-MLR inhibitory activity on the marine-derived symbiotic microorganisms (1,895 strains) from the marine algae. The potent inhibitory activities (over 45% inhibition of proliferation at 10 and 2 ${\mu}g/ml$) without cytotoxicity were observed in the extracts of 46 strains. While, the significant stimulating activities (over 100% proliferation at 10 and 2 ${\mu}g/ml$) without cytotoxicity were observed in the extracts of 5 strains. In the second assay using 46 bioactive strains, 14 strains exhibited again significant allo-MLR inhibitory activity. Finally, 11 strains among the 14 strains inhibited proliferation and IFN-${\gamma}$ production of CD4+ T cells during the stimulation with specific antigen in the third assay. On the basis of above results, the marine algae is nice source for isolation of immunomodulating microorganism, and the marine algae-associated microorganism is also nice target for development of the new immunomodulating drug lead.

Radiographic Estimation of Experimentally Induced Splenomegaly in Dogs (개에서 실험적으로 유발한 비장종대의 방사선학적 평가)

  • Jung, In-Jo;Wang, Ji-Hwan;Yun, Je-Woong;Lee, Kyung-Woo;Yeon, Seong-Chan;Lee, Hyo-Jong;Lee, Hee-Chun
    • Journal of Veterinary Clinics
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    • v.23 no.3
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    • pp.263-266
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    • 2006
  • The purpose of this study was to assess the usefulness of radiographic examination of the splenomegaly associated with drug-induced splenic congestion and to establish the standard goal of the splenomegaly in dogs. Radiographic images of spleen in normal dogs were collected to determine the maximum diameter prior to, and 15 minutes after, administration of acepromazine, ketamine/diazepam combination, or propofol. Significant splenic enlargement was seen after administration of acepromazine, but statistical signalficant was found in a ventrodorsal view only. Splenic size tended to decrease after administration of ketamine/diazepam combination. Significant splenic enlargement was not found after administration of propofol. These results suggest that measurable splenomegaly can be detected by radiographic examination after some kind of drug administration and the evaluation of splenomegaly is more useful at ventrodorsal view than lateral view.

Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and syste­mic symptoms syndrome with coincident post­infectious glomerulonephritis

  • Kim, Kyung Min;Sung, Kyoung;Yang, Hea Koung;Kim, Seong Heon;Kim, Hye Young;Ban, Gil Ho;Park, Su Eun;Lee, Hyoung Doo;Kim, Su Young
    • Clinical and Experimental Pediatrics
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    • v.59 no.3
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    • pp.145-148
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    • 2016
  • Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature.

HMGB1 regulates autophagy through increasing transcriptional activities of JNK and ERK in human myeloid leukemia cells

  • Zhao, Mingyi;Yang, Minghua;Yang, Liangchun;Yu, Yan;Xie, Min;Zhu, Shan;Kang, Rui;Tang, Daolin;Jiang, Zhigang;Yuan, Wuzhou;Wu, Xiushan;Cao, Lizhi
    • BMB Reports
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    • v.44 no.9
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    • pp.601-606
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    • 2011
  • HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML.

Prevalence and Associated Factors of Alcohol and Cigarette Use among Peruvian Adolescents

  • Chavez, Rosemary Cosme;Nam, Eun Woo
    • Journal of the Korean Society of School Health
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    • v.33 no.1
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    • pp.28-38
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    • 2020
  • Purpose: This study aimed to identify the prevalence of alcohol and cigarette use and assess its relationship with socio-environmental, psychological, violent and behavioral factors among a sample of high school students from Lima and Callao, Peru. Methods: We utilized the data from a cross-sectional study conducted by the Yonsei Global Health Center in collaboration with the Korea International Cooperation Agency (KOICA) Peru office in November 2016. The total sample size of this study was 1,477 students. For analysis, we used bivariate and multivariate logistic regression to calculate the unadjusted and adjusted odds ratios and their respective 95% confidence intervals. Results: The current prevalence of alcohol and cigarette use among adolescents was found to be 24.2% and 12.1%, respectively. Alcohol use was affected by age, friends' alcohol use, experience of physical fighting, and involvement in other risk behaviors (smoking, drug use, and sexual intercourse). Cigarette use was affected by perceived academic performance, friends' cigarette use, and involvement in other risk behaviors (drinking, drug use, and sexual intercourse). Furthermore, students who received affection from their parents and whose parents monitored their activities were less likely to report using both alcohol and cigarettes. Conclusion: Alcohol and cigarette use among Lima and Callao adolescents is affected by socio-environmental, violent and behavioral factors. Alcohol and cigarette use prevention initiatives should promote positive parenting practices, family togetherness, and a supportive school climate. In addition, it is needed to establish peer-led programs that promote behavioral changes in students and strengthen social relations without the presence of alcohol, cigarettes, and other harmful substances.

Detection and Identification of Vibrio Species Using Whole-Cell Protein Pattern Analysis

  • Lee, Chae-Yoon;Hong, Yeun;Ryu, Jio;Kim, Young-Rok;Oh, Sang-Suk;Lee, Soon-Ho;Hwang, In-Gyun;Kim, Hae-Yeong
    • Journal of Microbiology and Biotechnology
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    • v.22 no.8
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    • pp.1107-1112
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    • 2012
  • Outbreaks of foodborne diseases associated with Vibrio species such as V. parahaemolyticus, V. vulnificus, and V. cholerae frequently occur in countries having a dietary habit of raw seafood consumption. For rapid identification of different Vibrio species involved in foodborne diseases, whole-cell protein pattern analysis for 13 type strains of 12 Vibrio species was performed using SDS-PAGE analysis. Pathogenic Vibrio species such as V. parahaemolyticus, V. vulnificus, V. cholerae, V. alginolyticus, V. fluvialis, and V. mimicus were included in the 12 Vibrio species used in this study. Each of the 12 Vibrio species showed clearly specific band patterns of its own. Two different strains of V. parahaemolyticus showed two different SDS-PAGE whole-cell protein patterns, giving the possibility of categorizing isolated strains in the same V. parahaemolyticus species into two subgroups. The 36 Vibrio isolates collected from sushi restaurants in Busan were all identified as V. parahaemolyticus by comparing their protein patterns with those of Vibrio type strains. The identified isolates were categorized into two different subgroups of V. parahaemolyticus. The whole-cell protein pattern analysis by SDS-PAGE can be used as a specific, rapid, and simple identification method for Vibrio spp. involved in foodborne diseases at the subspecies level.

Nasal Administration of Granisetron to Rats (흰쥐를 이용한 Granisetron함유 경비 투여제제의 평가 및 그 적용)

  • Woo, Jong-Soo
    • Journal of Pharmaceutical Investigation
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    • v.36 no.6
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    • pp.363-369
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    • 2006
  • Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

Marine Algicolous Endophytic Fungi - A Promising Drug Resource of the Era

  • Sarasan, Manomi;Puthumana, Jayesh;Job, Neema;Han, Jeonghoon;Lee, Jae-Seong;Philip, Rosamma
    • Journal of Microbiology and Biotechnology
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    • v.27 no.6
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    • pp.1039-1052
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    • 2017
  • Endophytic fungi have currently been acknowledged as the most promising source of bioactive compounds for drug discovery, and considerable progress has been made in exploring their diversity, species richness, and bioprospecting. Fungal endophytes from unique environmental settings offer a pool of potentially useful medicinal entities. Owing to the constant stresses imposed on macroalgae by marine environments, it is believed that algae and their associated endophytic symbionts represent a good source of structurally diverse bioactive secondary metabolites. Despite the proven significance of active metabolites of algal endophytes, little have been exploited. This review highlights the latest discoveries in algicolous endophytic research, with particular focus on the bioactive metabolites from algal endophytes. Compounds are classified according to their reported biological activities, like anticancer, antibacterial, antifungal, and antioxidant properties. Present experimental evidence suggests that a majority of the bioactive metabolites were reported from Phaeophyceae followed by Rhodophyceae and Chlorophyceae. An intensive search for newer and more effective bioactive metabolites has generated a treasure trove of publications, and this review partially covers the literature published up to 2016.

Combination of Doxorubicin with Gemcitabine-Incorporated G-Quadruplex Aptamer Showed Synergistic and Selective Anticancer Effect in Breast Cancer Cells

  • Joshi, Mili;Choi, Jong-Soo;Park, Jae-Won;Doh, Kyung-Oh
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1799-1805
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    • 2019
  • Doxorubicin (DOX) is one of the most effective anticancer agents used for the treatment of multiple cancers; however, its use is limited by its short half-life and adverse drug reactions, especially cardiotoxicity. In this study, we found that the conjugate of DOX with APTA12 (Gemcitabine incorporated G-quadruplex aptamer) was significantly more cancer selective and cytotoxic than DOX. The conjugate had an affinity for nucleolin, with higher uptake and retention into the cancer cells than those of DOX. Further, it was localized to the nucleus, which is the target site of DOX. Owing to its mechanism of action, DOX has the ability to intercalate into the nucleotides thus making it a suitable drug to form a conjugate with cancer selective aptamers such as APTA12. The conjugation can lead to selectively accumulate in the cancer cells thus decreasing its potential nonspecific as well as cardiotoxic side effects. The aim of this study was to prepare a conjugate of DOX with APTA12 and assess the chemotherapeutic properties of the conjugate specific to cancer cells. The DOX-APTA12 conjugate was prepared by incubation and its cytotoxicity in MCF-10A (non-cancerous mammary cells) and MDA-MB-231 (breast cancer cells) was assessed. The results indicate that DOX-APTA12 conjugate is a potential option for chemotherapy especially for nucleolin expressing breast cancer with reduced doxorubicin associated side effects.