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Добірка наукової літератури з теми "Liver cells Effect of drugs on"

Автор: Grafiati
Опубліковано: 4 червня 2021
Оновлено: 29 січня 2023

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Статті в журналах з теми "Liver cells Effect of drugs on"

1

HATANO, MOTOHISA. "Studies on free liver cells of rats. Effect of various drugs." Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics 18, no. 1 (1987): 87–88. http://dx.doi.org/10.3999/jscpt.18.87.

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Rashid, M. S., Faheem Hadi, Zoya Muzaffar, H. M. Asif, Naveed Akhtar, Memoona Zahra, Maqbool, L. Sumreen, T. Shamim, and A. Malik. "Cytotoxic Effect of Kigelia Africana Plant Extracts on Liver Cancer Cells." Pakistan Journal of Medical and Health Sciences 16, no. 10 (October 30, 2022): 68–71. http://dx.doi.org/10.53350/pjmhs22161068.

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Background: Various medicinal plants have much efficacious value as treatment of many fatal conditions including cancer. Kigelia africana has known therapeutic efficacy in different ailments and has been used as traditional medicine since ages. Aim: To evaluate anticancer property of any drug or plant extract including HepG2 cell line. Methodology: Anticancer activity of n-hexane and ethanolic extracts of Kigelia africana was checked. IC50 was evaluated via MTT assay, crystal violet assay was performed to check the viability of cells and trypan blue assay to count dead cells. Furthermore, muse analysis was performed using count and viability kit to count total living as well non-living cells. Results: Cancer cells of HepG2 cell line showed reduced viability and proliferation with increased apoptosis when treated with Kigelia extracts. Conclusion: Many drugs have been proved as anticancer but with severe side effects. Thus, phytoextracts have been tested in this study to evaluate their anti-cancer activity so minimize the side effect. Kigelia africana extracts were found to be effective against liver cancer cells. Keyword: Kigelia africana, HepG2, MTT, liver cancer, anticancer drug, plant based drugs.
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3

Ting, Liu, Liu Juan, and Yang Jian Qiong. "Effective Components of Hepatoprotective Drugs." Applied Mechanics and Materials 633-634 (September 2014): 533–36. http://dx.doi.org/10.4028/www.scientific.net/amm.633-634.533.

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Pathological changes in animal models of autoimmune hepatitis and liver cells were similar to the mechanism of injury and viral hepatitis, the thesis of the active component of several common liver substances studied, wild chrysanthemum extract has anti-bacterial, anti-viral, pharmacological effects such as anti-inflammatory and immune liver and nerve protection, Dicliptera polysaccharide with excellent hepatoprotective activity of the liver that can be used as an adjunct to clinical medicine. Introduction
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4

Li, Rui, Chengyong Dong, Keqiu Jiang, Rui Sun, Yang Zhou, Zeli Yin, Jiaxin Lv, Junlin Zhang, Qi Wang, and Liming Wang. "Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux." Carcinogenesis 41, no. 11 (May 11, 2020): 1583–91. http://dx.doi.org/10.1093/carcin/bgaa029.

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Abstract Liver cancer is a major threat to human life and health, and chemotherapy has been the standard non-surgical treatment for liver cancer. However, the emergence of drug resistance of liver cancer cells has hindered the therapeutic effect of chemical drugs. The discovery of exosomes has provided new insights into the mechanisms underlying tumour cell resistance. In this study, we aimed to determine the proteins associated with drug resistance in tumour cells and to elucidate the underlying mechanisms. We found that Rab27B expression in drug (5-fluorouracil, 5Fu)-resistant Bel7402 (Bel/5Fu) cells increased significantly compared with that in drug-sensitive Bel7402 cells. In addition, Bel/5Fu cells secreted more exosomes under 5Fu stimulation. The number of exosomes secreted by Bel/5Fu cells significantly reduced after knocking down Rab27B, and the cellular concentration of 5Fu increased, enhancing its therapeutic effect. We also found that the administration of classical drug efflux pump (P-glycoprotein, P-gp) inhibitors together with knockdown of Rab27B further improved the therapeutic effects of chemotherapy drugs. In conclusion, our findings suggest that Rab27B could be a new therapeutic target in liver cancer.
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Renovaldi, Dede, and Abdul Khalik Adam. "Potential of Sweet Basil (Ocimum basilicum) as a Hepatoprotector Agent for Liver Injury Related to Drugs." Muhammadiyah Medical Journal 1, no. 2 (November 16, 2020): 63. http://dx.doi.org/10.24853/mmj.1.2.63-68.

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The use of drugs is one of the most common causes of liver injury, because the liver is the main organ that metabolizes drugs. Little is currently done if there is a liver injury due to the hepatotoxic side effects of a drug. Herbal plants have active natural compounds that have pharmacological effects so they are widely used as alternative treatments. Sweet basil (Ocimum basilicum) is one of the most cultivated plants in Asia. Studies on the use of Ocimum basilicum in medicine have been carried out, one of which is the hepatoprotector effect. Studies indicate that Ocimum basilicum is rich in high antioxidant content (flavonoids, saponins, tannins, sterols, triterpenes, and rosmaniric acid) capable of providing hepatoprotector effects by helping the regeneration process of hepatocyte cells that are damaged by hepatotoxic agents and significantly decreasing liver damage biomarkers. The purpose of this review is to explain the potential of Ocimum basilicum as a hepatoprotective agent for liver injury associated with drugs. The conclusion of this review is Ocimum basilicum has high potential in its utilization as a hepatoprotector against liver injury mainly related to the consumption of drugs that have hepatotoxic effects.
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Renovaldi, Dede, and Abdul Khalik Adam. "Potential of Sweet Basil (Ocimum basilicum) as a Hepatoprotector Agent for Liver Injury Related to Drugs." Muhammadiyah Medical Journal 1, no. 2 (November 16, 2020): 21. http://dx.doi.org/10.24853/mmj.1.2.21-26.

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Анотація:
The use of drugs is one of the most common causes of liver injury, because the liver is the main organ that metabolizes drugs. Little is currently done if there is a liver injury due to the hepatotoxic side effects of a drug. Herbal plants have active natural compounds that have pharmacological effects so they are widely used as alternative treatments. Sweet basil (Ocimum basilicum) is one of the most cultivated plants in Asia. Studies on the use of Ocimum basilicum in medicine have been carried out, one of which is the hepatoprotector effect. Studies indicate that Ocimum basilicum is rich in high antioxidant content (flavonoids, saponins, tannins, sterols, triterpenes, and rosmaniric acid) capable of providing hepatoprotector effects by helping the regeneration process of hepatocyte cells that are damaged by hepatotoxic agents and significantly decreasing liver damage biomarkers. The purpose of this review is to explain the potential of Ocimum basilicum as a hepatoprotective agent for liver injury associated with drugs. The conclusion of this review is Ocimum basilicum has high potential in its utilization as a hepatoprotector against liver injury mainly related to the consumption of drugs that have hepatotoxic effects.
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7

Liao, Wei, Yan Tang, Zhengcui Hu, Chunyan Wang, Yi Chen, Yi Zhang, and Wenhan Fan. "Preparation of Galactosyl Nanoparticles and Their Targeting Efficiency to Hepatocellular Carcinoma." Journal of Nanoscience and Nanotechnology 21, no. 2 (February 1, 2021): 987–94. http://dx.doi.org/10.1166/jnn.2021.18666.

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Liver diseases seriously endanger people’s physical health, especially liver cancer, and its morbidity and mortality have increased year by year. The reason why liver cancer is difficult to cure is that in addition to the low lethality of cancer drugs to cancer cells, another important factor is that the drugs do not have liver targeting, and there is no way to efficiently deliver anti-cancer drugs to the liver lesions. Hepatocytes can specifically recognize galactose, therefore the galactosyl liver-targeted drug carrier can deliver the drug to the liver in a targeted manner, so that the drug can be directed to the liver, reduce the dose and times of drug administration, reduce toxic side effects, and reduce the adverse reactions of patients, which is of great significance for the treatment of liver cancer. In this thesis, paclitaxel long-circulating nano-liposomes targeting liver cancer constructed with galactose as raw materials can improve the pharmacokinetics and tissue distribution of traditional formulations of paclitaxel, and enhance the safety and tumor suppressive effect of paclitaxel in vivo.
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8

ÖNAL, Müge Gülcihan. "A New Approach: Treatment with Sodium Vanadate and Cisplatin Combination for Human Hepatocellular Carcinoma." Proceedings 40, no. 1 (December 25, 2019): 14. http://dx.doi.org/10.3390/proceedings2019040014.

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The most common primary liver malignancy is hepatocellular carcinoma. Various chemotherapy drugs are used for treatment. These drugs have high toxicity to liver tissue. More effective, less toxic options should be preferred for treatment. The aim of this study is to investigate the cytotoxic effect of cisplatin and sodium vanadate combination (NaV) in hepatocellular carcinoma. The hepatocellular cancer cell line (HepG2) was used in this study. Increased concentration of cisplatin and a selected concentration of sodium vanadate were treated to HepG2 cells for 24- and 72-hours incubation times. The proliferation of HepG2 cells decreased with the combination of NaV and cisplatin. While cisplatin was effective in 10–4 M concentration in the proliferation of HepG2 cells, 10–4 M cisplatin with 10–3 M NaV in combination was less effective in the proliferation of HepG2 cells. According to these results, NaV and cisplatin show toxic effects on hepatocellular carcinoma cells. However, the combination of cisplatin and NaV has a less toxic effect than cisplatin and NaV on hepatocellular carcinoma cells.
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9

Tian, Shiliu, Rui Su, Ke Wu, Xuhan Zhou, Jaydutt V. Vadgama, and Yong Wu. "Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells." Journal of Personalized Medicine 12, no. 8 (August 16, 2022): 1318. http://dx.doi.org/10.3390/jpm12081318.

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Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer.
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Hatta, Fazleen Haslinda Mohd, Ruhil Nadirah Che Omar, Mohd Ikhwan Ismail, Rosmadi Mohd Yusoff, and Mohd Shihabuddin Ahmad Noorden. "Determining the Population Doubling Time of HepG2 and Huh-7 Cells and the Toxic Effect of Dimethyl Sulfoxide (DMSO)." ASM Science Journal 17 (November 7, 2022): 1–5. http://dx.doi.org/10.32802/asmscj.2022.1238.

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Developing cell lines that carry promising qualities closest to human hepatocytes in drug studies is a dream of many research laboratories. About 90% of drugs are metabolised by the liver. Therefore, most drug discovery studies utilise hepatocytes to understand the basic mechanism of the drug’s breakdown. To assure hepatocytes survival, various solvents were tested for their cytotoxicity on the cell line. Since most drugs are weakly soluble in water, they can be dissolved in an aprotic solvent. To obtain accurate results, the requirements of these solvents are biocompatible and non-toxic to the cells. One of the most commonly used solvents is dimethyl sulfoxide (DMSO). This study aims to understand the cell characteristic of cells doubling time and investigate the toxic effect of DMSO using the cell proliferation measurement technique. The toxicity was measured on liver-derived cell lines HepG2 and Huh-7. Cell growth and morphology were observed with an inverted phase microscope while cell viability was counted using Vi-Call XR 2.03. Results showed that a doubling time of 32 hours would be best for treatments on both cells. A concentration of more than 0.40% DMSO has significant toxicity and caused inhibition of proliferation on both cell lines, resulting in low cell count and higher cell death. Ethanol and methanol were observed as good solvents since they have low toxicity. However, drugs that were only dissolved in a low concentration of DMSO (0.05-0.2%) gave the best result without any harmful effect on cell proliferation.
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Дисертації з теми "Liver cells Effect of drugs on"

1

Nicholls-Grzemski, Felicity April. "The effect of short-term pretreatment with peroxisome proliferators on the acute toxicity of various toxicants, including paracetamol /." Title page, table of contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phn6158.pdf.

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2

Weng, Yu-I. "Acute and chronic ethanol effects on liver p42/44 mitogen activated protein kinase." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3036867.

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Gronert, Álvarez Anna Christina [Verfasser], and Hans-Heinrich [Akademischer Betreuer] Wedemeyer. "Regulatory T cells in liver transplantation : phenotypical characterisation and effects of immunosuppressive drugs / Anna Christina Gronert Álvarez. Klinik für Gastroenterologie, Hepatologie und Endokrinologie der Medizinischen Hochschule Hannover. Betreuer: Hans-Heinrich Wedemeyer." Hannover : Bibliothek der Medizinischen Hochschule Hannover, 2014. http://d-nb.info/1050008200/34.

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Eng, Heather Sui-Fong. "Evaluating the use of cryopreserved hepatocytes for the prediction of in vivo hepatic clearance /." See Full Text at OhioLINK ETD Center (Requires Adobe Acrobat Reader for viewing), 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=toledo1091638312.

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Thesis (M.S.P.)--University of Toledo, 2004.
Typescript. "A thesis [submitted] as partial fulfillment of the requirements of the Master of Science degree in Pharmaceutical Sciences." Bibliography: leaves 64-68.
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5

Silberstein, D. J. "The effect of renal failure on the elimination of drugs by the liver." Thesis, University of Leeds, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379649.

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6

Ngamratanapaiboon, Surachai. "Metabolomics investigations of the effect of drugs on mammalian cells." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/41178/.

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Cell-based metabolomics using LC-MS systemizes the study of the uniqueness of small-molecule metabolite (metabolomes) profiles in cellular processes. Cell-based metabolomics can potentially be used in many applications for the study of biological perturbation from stimulants in cellular pathways. The advantages of cell-based metabolomics include ease of control and interpretation when compared to the study of human subjects and animal models. Furthermore, this method can decrease some highly challenging problems that occur in genomics, transcriptomics and proteomics. Nowadays, cell culture in metabolomics studies has been used in many applications. These include cell culture and bioreactor optimisation, phenotype classification, stimulant testing effect, target and toxicity analysis, metabolic networks determination and modelling, and biomarker and drug target discovery. In this study, the reverse phase-liquid chromatography-mass spectrometry and hydrophilic interaction chromatography-mass spectrometry for comprehensive metabolic profiling well suited to the untargeted analysis of non-polar and polar metabolites in mammalian cells were developed, optimized and validated. These methods can separate and detect most of hydrophobic and polar metabolites that are normally found in mammalian cell lines. After that the LC-MS methods were applied to assess the effects of drugs with known and unknown cellular metabolic effects on three mammalian cell lines, namely HMVECs for antipsychotics experiment, MCF-7 cells for cordycepin experiment and MIN6 cells for fluoxetine experiment by using untargeted metabolic profiling. The global effects of antipsychotics at high therapeutic dosage in HMVECs were investigated. The results support for the toxicity hypothesis with measurements that confirm previous findings and reveal the exact biological pathways of antipsychotic-altered BBB functions. It was found that antipsychotics may affect the bioenergetics pathway due to mitochondrial dysfunction resulted in ketoacidosis and inducing oxide stress by reactive oxygen species generation. In the MCF- cell experiment, the results of the untargeted metabolite profiling demonstrated the clear anti-breast cancer effects of cordycepin and pentostatin. By investigating the metabolite profiles, clear synergistic effects of cordycepin and pentostatin combined in comparison to cordycepin activity alone in MCF-7 cells was observed. Furthermore, the pathway analysis indicated that anti-breast cancer activity was mainly responsible for alterations in purine and pyrimidine metabolism and bioenergetics. Additionally, cordycepin may be involved in the inhibition of cell proliferation and differentiation, and the activation of cell apoptosis. The last experiment on MIN6 cells, the developed and optimized HILIC-MS approach in order to determine the biological pathways which are impaired by fluoxetine on glucose-stimulated insulin secretion on MIN6 cell lines was performed. It is found that fluoxetine may impair glycolysis, TCA and fatty acid metabolism on MIN6 cell lines. Moreover, it is also reveal that the alteration of biological pathways on MIN6 cells by known ETC inhibitors (rotenone (Complex I inhibitor) antimycin (Complex III inhibitor)) and azide (a complex IV inhibitor). From comparison with these ETC inhibitors, it is found that fluoxetine may have the same effect pattern with azide.
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Abumansour, Hamza M. A. "Quantitative pharmacoproteomics investigation of anti-cancer drugs in mouse : development and optimisation of proteomics workflows for evaluating the effect of anti-cancer drugs on mouse liver." Thesis, University of Bradford, 2016. http://hdl.handle.net/10454/15724.

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Minimizing anti-cancer drug toxicity is a major challenge for the pharmaceutical industry. Toxicity is most frequently due to either the direct interaction of the drug on previously unidentified targets or its conversion to metabolites by drug metabolizing enzymes (e.g. CYP450 enzymes) that cause cellular, tissue or organ damage. Pharmacoproteomics is beginning to take a central role in studying changes in protein expression corresponding to drug administration, the results of which, inform about the mode of action, toxicity, and resistance in pre-clinical and clinical stages of drug development. The main aim of this research is to apply comparative proteomics studies on livers from male and female mice xenograft models treated with major anti-cancer drugs (5-flourouracil, paclitaxel, cisplatin, and doxorubicin) and CYP inducer, TCPOBOP, to investigate their effect on protein expression profiles (proteome). Within this thesis, an attention is paid to optimise a highly validated proteomics workflow for biomarker identification. Proteins were extracted from liver microsomes of mice treated in two separate sets; Set A – male (5-fluoruracil, doxorubicin, cisplatin and untreated) or Set B – female (5-fluoruracil, paclitaxel, TCPOBOP and untreated) using cryo-pulverization and sonication method. The extracts were digested with trypsin ii and the resulting peptides labelled with 4-plex iTRAQ reagents. The labelled peptides were subjected for separation in two-dimensions by iso-electric focusing (IEF) and RP-HPLC techniques before analysis by mass spectrometry and database searching for protein identification. Set A and Set B resulted in identification and quantification of 1146 and 1743 proteins, respectively. Moreover, Set A and Set B recovered 26 and 34 cytochrome P450 isoforms, respectively. The microsomal changes after drug treatments were quite similar. However, more changes were observed in the male set. Up-regulation of MUPs showed the greatest distinction in the protein expression patterns in the treated samples comparing to the untreated controls. In Set A, 5-fluoruracil and cisplatin increased the expression of three isoforms (MUP1, 2, and 6), whereas doxorubicin has increased the expression of four isoforms (MUP1, 2, 3, and 6). On the other side, only TCPOBOP in Set B has increased the expression of two isoforms (MUP1 and 6). Our findings showed that the expression of MUP, normally involved in binding and excretion of pheromones, have drug- and sex-specific differences. The mechanism and significance of MUP up-regulation are ambiguous. Therefore, the impact of each therapeutic agent on MUP and xenobiotic enzymes will be discussed.
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Teng, Shuzhi, and 滕曙智. "Hepatocellular injury induced by endotoxin and galactosamine." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241037.

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Kassahun, Kelem. "Mechanistic studies of valproic acid hepatotoxicity : identification and characterization of thiol conjugates." Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/30831.

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The severe hepatotoxicity of the antiepileptic drug valproic acid (VPA) is believed to be mediated through chemically reactive metabolites. The monounsaturated metabolite 4-ene VPA is steatogenic in the rat, and in a similar fashion to the hepatotoxin 4-pentenoic acid, is thought to be oxidized by mitochondria to a highly reactive α,β-unsaturated ketone, 3-keto-4-ene VPA. The tripeptide thiol, glutathione (GSH), is known to react with a variety of electrophilic compounds that have the potential to interact with cellular macromolecules. The identification and structural characterization of GSH conjugates provides a means of identifying short-lived unstable electrophiles and thus an insight into the mechanisms of toxicity. This thesis describes the synthesis and characterization of thiol conjugates of reactive metabolites derived from the in vivo metabolism of VPA, 4-ene VPA, (E)-2,4-diene VPA, and 4-pentenoic acid. A negative ion chemical ionization gas chromatographic/mass spectrometric (NICI/GC/MS) method for the determination of VPA and 14 of its metabolites in a single chromatographic run was developed. A combination of pentafluorobenzyl and trimethylsilyl derivatization resulted in the [M-181]̄̄̄ ̄anion as the base peak for all the metabolites measured. When these ions were monitored sensitivities in the low picogram range were achieved. The VPA metabolite profile was determined in pediatric patients on VPA monotherapy and on combined therapy with either carbamazepine or clobazam. 4-Ene- and (E)-2,4-diene-VPA were found to be minor metabolites with serum levels below 1% that of VPA. In patients on combined therapy with carbamazepine, the ω and ω-l pathways of VPA metabolism were induced, while products of β-oxidation were significantly decreased. Polytherapy had no significant effect on the serum levels of 4-ene- or (E)-2,4-diene-VPA. Rats were dosed intraperitoneally with 100 mg/kg of the sodium salts of VPA, 4-ene-, (E)-2,4-diene-VPA, 4-pentenoic or (E)-2,4-pentadienoic acids. Methylated bile extracts were analyzed by high pressure liquid chromatography and liquid chromatography/tandem mass spectrometry (LC/MS/MS) for GSH conjugates while urine samples were analyzed by GC/MS and LC/MS for N-acetylcysteine (NAC) conjugates and other metabolites. The GSH conjugate of (E)-2,4-diene VPA was detected in the bile of rats treated with 4-ene- and (E)-2,4-diene-VPA. The NAC conjugate was a major urinary metabolite of rats given (E)-2,4-diene VPA and was a prominent urinary metabolite of those animals given 4-ene VPA. The structures of these metabolites were confirmed by comparing GC/MS or LC/MS properties of the isolated metabolites to those of synthetic standards. The GSH and NAC conjugates of (E)-2,4-diene VPA were chemically synthesized and their structures established to be (E)-5-(glutathion-S-yl)-3-ene VPA and (E)-5-(N-acetylcystein-S-yl)-3-ene VPA by nuclear magnetic resonance spectroscopy and mass spectrometry. In contrast to the very slow reaction of the free acid of (E)-2,4-diene VPA with GSH, the methyl ester reacted rapidly with GSH to yield the adduct. In vivo it appears the diene forms an intermediate with enhanced electrophilic reactivity to GSH as indicated by the facile reaction of the diene with GSH in vivo (about 40% of the (E)-2,4-diene VPA administered to rats was excreted as the NAC conjugate in 24 hr). In rats treated with 4-pentenoic and/or (E)-2,4-pentadienoic acids the following conjugates were identified and characterized by synthesis: GSH and cysteine conjugates of 3-oxo-4-pentenoic acid, GSH and NAC conjugates of (E)-2,4-pentadienoic acid, and the NAC conjugate of acrylic acid. The results thus provided the first direct biochemical evidence for the in vivo formation of the metabolite of 4-pentenoic acid considered responsible for the irreversible inhibition of fatty acid metabolism. The results also revealed basic differences between the mitochondrial metabolism of 4-ene VPA and 4-pentenoic acid. The 3-keto-4-ene VPA and its GSH and NAC conjugates were synthesized in order to facilitate the in vivo identification of these compounds following the administration of VPA, 4-ene-, or (E)-2,4-diene-VPA to rats. However, neither the 3-keto-4-ene VPA nor its thiol derivatives were evident in any of the treatments. The NAC conjugate of (E)-2,4-diene VPA was also found to be a metabolite of VPA in patients. The level of the conjugate appeared to be higher in two patients who recovered from VPA-induced liver toxicity. The characterization of GSH and NAC (in humans and rats) conjugates of (E)-2,4-diene VPA suggests that VPA is metabolized to a chemically reactive intermediate that may contribute to the hepatotoxicity of the drug.
Pharmaceutical Sciences, Faculty of
Graduate
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10

Jansen, Robert Walter. "Modified human serum albumins as carriers for the specific delivery of antiviral drugs to liver- and blood cells." [S.l. : [Groningen : s.n.] ; University of Groningen] [Host], 2008. http://irs.ub.rug.nl/ppn/.

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Книги з теми "Liver cells Effect of drugs on"

1

International Symposium on "Liver Cells and Drugs" (1987 Rennes, France). Liver cells and drugs: Proceedings of the International Symposium on Liver Cells and Drugs, held in Rennes on July 7-10, 1987. Paris: Editions INSERM, 1988.

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2

International Symposium on Liver Cells and Drugs (1987 Rennes, France). Liver cells and drugs =: Cellules hépatiques et médicaments : proceedings of the International Symposium on "Liver cells and drugs" held in Rennes on July 7-10, 1987. London: Libbey, 1988.

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3

Kenʼichi, Kitani, ed. Liver and aging, 1986: Liver and brain : proceedings of the Third Symposium on Liver and Aging--Liver and Brain, held in Tokyo, Japan on August 20-22, 1986. Amsterdam: Elsevier Science Publishers, 1986.

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Neil, Kaplowitz, and DeLeve Laurie D. 1955-, eds. Drug-induced liver disease. New York: Marcel Dekker, 2003.

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International, Symposium on Hepatology and Clinical Pharmacology "Liver and Drugs" (1st 1994 Bratislava Slovakia). Liver and drugs '94: Proceedings of the 1st International Symposium on Hepatology and Clinical Pharmacology "Liver and Drugs", Bratislava, Slovakia, November 24-26, 1994. Bratislava, Slovak Republic: Liver and Drug Foundation, 1995.

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Convegno medico di informazione epatologica (4th 1986 Cormons, Italy). Fegato e farmaci: Atti del IV Convegno annuale di informazione epatologica, Cormons, 28 giugno 1986. [Padova]: Istituto di medicina interna dell'Università di Padova, Cattedra di patologia medica I, 1986.

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7

D, T͡Syrenzhapova O., Shantanova L. N, and Nikolaev S. M, eds. Optimizat͡sii͡a adaptivnykh prot͡sessov organizma. Moskva: "Nauka", 1990.

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Ballachey, Brenda Elizabeth. Comparison of Cytochrome P450 1A induction in blood and liver cells of sea otters. Anchorage, Alaska: Exxon Valdez Oil Spill Trustee Council, 2003.

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9

Advances in mitochondrial medicine. Dordrecht: Springer Verlag, 2012.

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W, Wang Kevin K., and Yuen Po-Wai, eds. Calpain: Pharmacology and toxicology of calcium-dependent protease. Philadelphia, PA: Taylor & Francis, 1999.

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Частини книг з теми "Liver cells Effect of drugs on"

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Van Bezooijen, C. F. A., G. J. M. J. Horbach, and C. F. Hollander. "The Effect of Age on Rat Liver Drug Metabolism." In Drugs and Aging, 45–55. Berlin, Heidelberg: Springer Berlin Heidelberg, 1986. http://dx.doi.org/10.1007/978-3-642-70788-9_4.

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Neuman, M., R. Cameron, and N. Shear. "Drug-Induced Apoptosis of Skin Cells and Liver." In Apoptosis and Its Modulation by Drugs, 343–55. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-642-57075-9_13.

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Kostner, G. M. "The Interaction of Lp(A) with Liver Cells: Implications for Lipid Lowering Therapy." In Drugs Affecting Lipid Metabolism, 151–59. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1703-6_21.

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Geerts, Albert, Luc Bouwens, Ronald De Zanger, Hans Van Bossuyt, and Eddie Wisse. "The Structure of Different Types of Liver Cells in Relation to Uptake and Exchange Processes." In Targeting of Drugs, 1–14. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4684-5574-8_1.

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Lindner, J., R. Eurich, K. Grasedyck, P. Schmiegelow, and A. Nüssgen. "Age-Dependent Differences of the Therapeutic Effect on Experimental Liver Fibrosis and Cirrhosis (Morphology and Biochemistry)." In Drugs and Aging, 80–103. Berlin, Heidelberg: Springer Berlin Heidelberg, 1986. http://dx.doi.org/10.1007/978-3-642-70788-9_7.

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Lirussi, F., and L. Okolicsanyi. "The Effect of Drugs on Liver Function and Biliary Secretion." In Biochemical Pharmacology as an Approach to Gastrointestinal Disorders, 239–47. Dordrecht: Springer Netherlands, 1997. http://dx.doi.org/10.1007/978-94-011-5390-4_19.

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Scherphof, Gerrit L., Toss Daemen, Hans Derksen, George Lázár, Halbe H. Spanjer, and Frits H. Roerdink. "In Vivo Uptake and Processing of Liposomes by Parenchymal and Non-Parenchymal Liver Cells; Application to Immunotherapeutic Treatment of Hepatic Metastases." In Targeting of Drugs, 109–20. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4684-5574-8_10.

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Dini, L. "Clearance of Apoptotic Lymphocytes by Human Kupffer Cells. Phagocytosis of Apoptotic Cells in the Liver: Role of Lectin Receptors and Therapeutic Advantages." In Apoptosis and Its Modulation by Drugs, 319–41. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-642-57075-9_12.

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Rossaro, L., S. R. Dowd, V. Simplaceanu, R. Naccarato, D. H. Van Thiel, and C. Ho. "Effect of FK 506 and Cyclosporins on Model Membranes Studied by Nuclear Magnetic Resonance Spectroscopy." In Drugs and the Liver: High Risk Patients and Transplantation, 177–84. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1994-8_29.

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Ansari, Nariman, Stefanie Hardung, Katharina Hötte, Stefanie Rakel, Patrick Antonietti, Donat Kögel, Ernst H. K. Stelzer, and Francesco Pampaloni. "Quantifying the Autophagy-Triggering Effects of Drugs in Cell Spheroids with Live Fluorescence Microscopy." In Methods in Molecular Biology, 19–29. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0856-1_3.

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Тези доповідей конференцій з теми "Liver cells Effect of drugs on"

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Ma, Liang, Jeremy Barker, Changchun Zhou, Biaoyang Lin, and Wei Li. "A Perfused Two-Chamber System for Anticancer Drug Screening." In ASME 2010 International Manufacturing Science and Engineering Conference. ASMEDC, 2010. http://dx.doi.org/10.1115/msec2010-34326.

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A cell culture microfluidic device has been developed to test the cytotoxicity of anticancer drugs while reproducing multi-organ interactions in vitro. Cells were cultured in separate chambers representing the liver and tumor. The two chambers were connected through a channel to mimick the blood flow. Glioblastoma (GBM) cancer cells (M059K) and hepatoma cells (HepG2) were cultured in the tumor and the liver chambers, respectively. The cytotoxic effect of cancer treatment drug Temolozomide (TMZ) was tested using this two chamber system. The experimental results showed that with the liver cells, the cancer cells showed much higher viability than those without the liver cells. This indicates that the liver metabolism has strong effect on the toxicity of the anticancer drug. The results demonstrated that the perfused two chamber cell culture system has the potential to be used as a platform for drug screening in a more physiologically realistic environment.
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Tourlomousis, Filippos, and Robert C. Chang. "Computational Modeling of 3D Printed Tissue-on-a-Chip Microfluidic Devices as Drug Screening Platforms." In ASME 2014 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/imece2014-38454.

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Physiological tissue-on-a-chip technology is enabled by adapting microfluidics to create micro scale drug screening platforms that replicate the complex drug transport and reaction processes in the human liver. The ability to incorporate three-dimensional (3d) tissue models using layered fabrication approaches into devices that can be perfused with drugs offer an optimal analog of the in vivo scenario. The dynamic nature of such in vitro metabolism models demands reliable numerical tools to determine the optimum tissue fabrication process, flow, material, and geometric parameters for the most effective metabolic conversion of the perfused drug into the liver microenvironment. Thus, in this modeling-based study, the authors focus on modeling of in vitro 3d microfluidic microanalytical microorgan devices (3MD), where the human liver analog is replicated by 3d cell encapsulated alginate hydrogel based tissue-engineered constructs. These biopolymer constructs are hosted in the chamber of the 3MD device serving as walls of the microfluidic array of channels through which a fluorescent drug substrate is perfused into the microfluidic printed channel walls at a specified volumetric flow rate assuring Stokes flow conditions (Re<<1). Due to the porous nature of the hydrogel walls, a metabolized drug product is collected as an effluent stream at the outlet port. A rigorous modeling approached aimed to capture both the macro and micro scale transport phenomena is presented. Initially, the Stokes Flow Equations (free flow regime) are solved in combination with the Brinkman Equations (porous flow regime) for the laminar velocity profile and wall shear stresses in the whole shear mediated flow regime. These equations are then coupled with the Convection-Diffusion Equation to yield the drug concentration profile by incorporating a reaction term described by the Michael-Menten Kinetics model. This effectively yields a convection-diffusion–cell kinetics model (steady state and transient), where for the prescribed process and material parameters, the drug concentration profile throughout the flow channels can be predicted. A key consideration that is addressed in this paper is the effect of cell mechanotransduction, where shear stresses imposed on the encapsulated cells alter the functional ability of the liver cell enzymes to metabolize the drug. Different cases are presented, where cells are incorporated into the geometric model either as voids that experience wall shear stress (WSS) around their membrane boundaries or as solid materials, with linear elastic properties. As a last step, transient simulations are implemented showing that there exists a tradeoff with respect the drug metabolized effluent product between the shear stresses required and the residence time needed for drug diffusion.
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Tourlomousis, Filippos, and Robert C. Chang. "2D and 3D Multiscale Computational Modeling of Dynamic Microorgan Devices as Drug Screening Platforms." In ASME 2015 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/imece2015-52734.

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The ability to incorporate three-dimensional (3D) hepatocyte-laden hydrogel constructs using layered fabrication approaches into devices that can be perfused with drugs enables the creation of dynamic microorgan devices (DMDs) that offer an optimal analog of the in vivo liver metabolism scenario. The dynamic nature of such in vitro metabolism models demands reliable numerical tools to determine the optimum process, material, and geometric parameters for the most effective metabolic conversion of the perfused drug into the liver microenvironment. However, there is a current lack of literature that integrates computational approaches to guide the optimum design of such devices. The groundwork of the present numerical study has been laid by our previous study [1], where the authors modeled in 2D an in vitro DMD of arbitrary dimensions and identified the modeling challenges towards meaningful results. These constructs are hosted in the chamber of the microfluidic device serving as walls of the microfluidic array of channels through which a fluorescent drug substrate is perfused into the microfluidic printed channel walls at a specified volumetric flow rate assuring Stokes flow conditions (Re<<1). Due to the porous nature of the hydrogel walls, a metabolized drug product is collected at the outlet port. A rigorous FEM based modeling approach is presented for a single channel parallel model geometry (1 free flow channel with 2 porous walls), where the hydrodynamics, mass transfer and pharmacokinetics equations are solved numerically in order to yield the drug metabolite concentration profile at the DMD outlet. The fluid induces shear stresses are assessed both in 3D, with only 27 cells modeled as single compartment voids, where all of the enzymatic reactions are assumed to take place. In this way, the mechanotransduction effect that alters the hepatocyte metabolic activity is assessed for a small scale model. This approach overcomes the numerical limitations imposed by the cell density (∼1012 cells/m3) of the large scale DMD device. In addition, a compartmentalization technique is proposed in order to assess the metabolism process at the subcellular level. The numerical results are validated with experiments to reveal the robustness of the proposed modeling approach and the necessity of scaling the numerical results by preserving dynamic and biochemical similarity between the small and large scale model.
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Lin, Mei, Ziyu Wang, and Dongsheng Zhang. "Cytotoxic Effect of As2S3 Nanoparticles on Liver Cancer Cells." In 2006 1st IEEE International Conference on Nano/Micro Engineered and Molecular Systems. IEEE, 2006. http://dx.doi.org/10.1109/nems.2006.334566.

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Помыткина, Татьяна Евгеньевна, Анастасия Андреевна Холзенева, and Екатерина Владимировна Копытова. "TREATMENT OF LIVER CIRRHOSIS IN OUTPATIENT CONDITIONS." In Psychology, Sports science and Medicine (Психология. Спорт. Здравоохранение): сборник статей международной научной конференции (Санкт-Петербург, Октябрь 2022). Crossref, 2022. http://dx.doi.org/10.37539/221030.2022.81.26.005.

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В статье исследуется применение максимальных доз препаратов, после отсутствия эффекта от минимальных и средних дозировок лекарственных препаратов у пациента с идиопатическим циррозом печени. The article examines the use of maximum doses of drugs, after the absence of the effect of minimum and average dosages of drugs in a patient with idiopathic cirrhosis of the liver.
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Tryndyak, Volodymyr, Iryna Kindrat, Brigit McDannell, Frederick A. Beland, and Igor P. Pogribny. "Abstract 5887: A microRNA signature panel predicts differential sensitivity of liver cancer cells to chemotherapeutic drugs." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-5887.

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Alexopoulos, L. G., I. N. Melas, A. D. Chairakaki, J. Saez-Rodriguez, and A. Mitsos. "Construction of signaling pathways and identification of drug effects on the liver cancer cell HepG2." In 2010 32nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2010). IEEE, 2010. http://dx.doi.org/10.1109/iembs.2010.5626246.

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Tamiya, Nobuyo, Shigekuni Hosogi, Takashi Nakahari, Yoshinori Marunaka, and Koichi Takayama. "The effect of anticancer drugs on mucociliary clearance of bronchial ciliary cells in mice." In ERS International Congress 2018 abstracts. European Respiratory Society, 2018. http://dx.doi.org/10.1183/13993003.congress-2018.pa4261.

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Hansen, J. B., J. O. Olsen, L. Wilagård, and B. Østerud. "THE EFFECT OF COD LIVER OIL INTAKE ON THE STIMULATION OF BLOOD CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643406.

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In an in vitro model, stimulation of blood cells with a low concentration of lipopolysaccharides (LPS) revealed differences between women and men that possibly could be an explanation to why young women have less coronary heart disease than men (see abstract Hansen et al. “A model to--”).This model was also used to study the effect of intake of cod liver oil (CLO). 40 students (20 men and 20 women) were tested followed by an intake of 25 ml CLO daily for 2 months by 20 of the students.Heparinized blood samples were incubated with 2 ng LPS/ ml for 2 hours followed by isolation of plasma for thromboxane B2 and 6-keto-PG 1α quantitation.After the first 2 months period of CLO drinking we have the following results:The two months of CLO intake had no significant effect pn the thromboplastin induced synthesis in monocytes. In addition platelet aggregation was tested in a whole blood aggregometer using ADP addition to heparinized blood or collagen induced platelet aggregation in citrated whole blood. ADP aggregation was reduced from 75.9 ± 16.8% to 55.4 ± 19% in the CLO group of women, whereas the reduction in the CLO group of men was 70.1 ± 17.1% to 60.9±18.6%. Similar result were found with collagen aggregation (57% to 33% for women and 48% to 30% for men).It is concluded that CLO intake reduces TxA2 production and plateletaggregation without having reduced effect on PGI2 production in whole blood.
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Valle, Blanca L., Theresa D'Souza, Kevin G. Becker, William H. Wood, Robert P. Wersto, and Patrice J. Morin. "Abstract C96: The effect of non‐steroidal anti‐inflammatory drugs (NSAIDs) in ovarian cancer cells." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-c96.

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Звіти організацій з теми "Liver cells Effect of drugs on"

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He, zhe, liwei Xing, ming He, yuhuan Sun, jinlong Xu, and rong Zhao. Effect of Acupuncture on Mammary Gland Hyperplasia (MGH): a Bayesian network meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, September 2022. http://dx.doi.org/10.37766/inplasy2022.9.0058.

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Review question / Objective: This review aims at conducting a network meta-analysis to assess the potential therapeutic effectiveness and safety of acupuncture therapy for the treatment of MGH. Condition being studied: MGH is a benign breast disease caused by excessive growth of mammary duct epithelial cells and interstitial fibers. Its prevalence rate among women of childbearing age is about 13.5-42%, accounting for 99.3% of the total number of patients with breast related diseases, and its possibility of developing breast cancer can reach 5-10%. Breast hyperplasia can cause clinical symptoms such as breast pain, breast lump, nipple pigmentation and mood fluctuation, which brings severe physical and mental burden to patients. Modern medicine believes that the pathogenesis of MGH is related to sexual hormone disorder secondary to hypothalamus pituitary ovary axis dysfunction.At present, the treatment options of MGH are limited and not completely effective. The commonly used drugs in clinical practice, such as tamoxifen, danazol and goserelin, are expensive, which may lead to breast pain, swelling and increase of interstitial fibrous nodules, and the long-term use of MGH has huge side effects. The clinical guidelines recommend that the use time should be 2 to 6 months. Therefore, it is necessary to seek a treatment method of MGH that is effective, stable and safe.
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Elmann, Anat, Orly Lazarov, Joel Kashman, and Rivka Ofir. therapeutic potential of a desert plant and its active compounds for Alzheimer's Disease. United States Department of Agriculture, March 2015. http://dx.doi.org/10.32747/2015.7597913.bard.

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We chose to focus our investigations on the effect of the active forms, TTF and AcA, rather than the whole (crude) extract. 1. To establish cultivation program designed to develop lead cultivar/s (which will be selected from the different Af accessions) with the highest yield of the active compounds TTF and/or achillolide A (AcA). These cultivar/s will be the source for the purification of large amounts of the active compounds when needed in the future for functional foods/drug development. This task was completed. 2. To determine the effect of the Af extract, TTF and AcA on neuronal vulnerability to oxidative stress in cultured neurons expressing FAD-linked mutants.Compounds were tested in N2a neuroblastoma cell line. In addition, we have tested the effects of TTF and AcA on signaling events promoted by H₂O₂ in astrocytes and by β-amyloid in neuronal N2a cells. 3. To determine the effect of the Af extract, TTF and AcA on neuropathology (amyloidosis and tau phosphorylation) in cultured neurons expressing FAD-linked mutants. 4. To determine the effect of A¦ extract, AcA and TTF on FAD-linked neuropathology (amyloidosis, tau phosphorylation and inflammation) in transgenic mice. 5. To examine whether A¦ extract, TTF and AcA can reverse behavioral deficits in APPswe/PS1DE9 mice, and affect learning and memory and cognitive performance in these FAD-linked transgenic mice. Background to the topic.Neuroinflammation, oxidative stress, glutamate toxicity and amyloid beta (Ab) toxicity are involved in the pathogenesis of Alzheimer's diseases. We have previously purified from Achilleafragrantissimatwo active compounds: a protective flavonoid named 3,5,4’-trihydroxy-6,7,3’-trimethoxyflavone (TTF, Fl-72/2) and an anti-inflammatory sesquiterpenelactone named achillolide A (AcA). Major conclusions, solutions, achievements. In this study we could show that TTF and AcA protected cultured astrocytes from H₂O₂ –induced cell death via interference with cell signaling events. TTF inhibited SAPK/JNK, ERK1/2, MEK1 and CREBphosphorylation, while AcA inhibited only ERK1/2 and MEK1 phosphorylation. In addition to its protective activities, TTF had also anti-inflammatory activities, and inhibited the LPS-elicited secretion of the proinflammatorycytokinesInterleukin 6 (IL-6) and IL-1b from cultured microglial cells. Moreover, TTF and AcA protected neuronal cells from glutamate and Abcytotoxicity by reducing the glutamate and amyloid beta induced levels of intracellular reactive oxygen species (ROS) and via interference with cell signaling events induced by Ab. These compounds also reduced amyloid precursor protein net processing in vitro and in vivo in a mouse model for Alzheimer’s disease and improvedperformance in the novel object recognition learning and memory task. Conclusion: TTF and AcA are potential candidates to be developed as drugs or food additives to prevent, postpone or ameliorate Alzheimer’s disease. Implications, both scientific and agricultural.The synthesis ofAcA and TTF is very complicated. Thus, the plant itself will be the source for the isolation of these compounds or their precursors for synthesis. Therefore, Achilleafragrantissima could be developed into a new crop with industrial potential for the Arava-Negev area in Israel, and will generate more working places in this region.
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Funkenstein, Bruria, and Cunming Duan. GH-IGF Axis in Sparus aurata: Possible Applications to Genetic Selection. United States Department of Agriculture, November 2000. http://dx.doi.org/10.32747/2000.7580665.bard.

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Анотація:
Many factors affect growth rate in fish: environmental, nutritional, genetics and endogenous (physiological) factors. Endogenous control of growth is very complex and many hormone systems are involved. Nevertheless, it is well accepted that growth hormone (GH) plays a major role in stimulating somatic growth. Although it is now clear that most, if not all, components of the GH-IGF axis exist in fish, we are still far from understanding how fish grow. In our project we used as the experimental system a marine fish, the gilthead sea bream (Sparus aurata), which inhabits lagoons along the Mediterranean and Atlantic coasts of Europe, and represents one of the most important fish species used in the mariculture industry in the Mediterranean region, including Israel. Production of Sparus is rapidly growing, however, in order for this production to stay competitive, the farming of this fish species has to intensify and become more efficient. One drawback, still, in Sparus extensive culture is that it grows relatively slow. In addition, it is now clear that growth and reproduction are physiological interrelated processes that affect each other. In particular sexual maturation (puberty) is known to be closely related to growth rate in fish as it is in mammals, indicating interactions between the somatotropic and gonadotropic axes. The goal of our project was to try to identify the rate-limiting components(s) in Sparus aurata GH-IGF system which might explain its slow growth by studying the ontogeny of growth-related genes: GH, GH receptor, IGF-I, IGF-II, IGF receptor, IGF-binding proteins (IGFBPs) and Pit-1 during early stages of development of Sparus aurata larvae from slow and fast growing lines. Our project was a continuation of a previous BARD project and could be divided into five major parts: i) obtaining additional tools to those obtained in the previous project that are necessary to carry out the developmental study; ii) the developmental expression of growth-related genes and their cellular localization; iii) tissue-specific expression and effect of GH on expression of growth-related genes; iv) possible relationship between GH gene structure, growth rate and genetic selection; v) the possible role of the IGF system in gonadal development. The major findings of our research can be summarized as follows: 1) The cDNAs (complete or partial) coding for Sparus IGFBP-2, GH receptor and Pit-1 were cloned. Sequence comparison reveals that the primary structure of IGFBP-2 protein is 43-49% identical to that of zebrafish and other vertebrates. Intensive efforts resulted in cloning a fragment of 138 nucleotides, coding for 46 amino acids in the proximal end of the intracellular domain of GH receptor. This is the first fish GH receptor cDNA that had been cloned to date. The cloned fragment will enable us to complete the GH - receptor cloning. 2) IGF-I, IGF-II, IGFBP-2, and IGF receptor transcripts were detected by RT-PCR method throughout development in unfertilized eggs, embryos, and larvae suggesting that these mRNAs are products of both the maternal and the embryonic genomes. Preliminary RT-PCR analysis suggest that GH receptor transcript is present in post-hatching larvae already on day 1. 3) IGF-1R transcripts were detected in all tissues tested by RT-PCR with highest levels in gill cartilage, skin, kidney, heart, pyloric caeca, and brain. Northern blot analysis detected IGF receptor only in gonads, brain and gill cartilage but not in muscle; GH increased slightly brain and gill cartilage IGF-1R mRNA levels. 4) IGFBP-2 transcript were detected only in liver and gonads, when analyzed by Northern blots; RT-PCR analysis revealed expression in all tissues studied, with the highest levels found in liver, skin, gonad and pyloric caeca. 5) Expression of IGF-I, IGF-II, IGF-1R and IGFBP-2 was analyzed during gonadal development. High levels of IGF-I and IGFBP-2 expression were found in bisexual young gonads, which decreased during gonadal development. Regardless of maturational stage, IGF-II levels were higher than those of IGF-L 6) The GH gene was cloned and its structure was characterized. It contains minisatellites of tandem repeats in the first and third introns that result in high level of genetic polymorphism. 7) Analysis of the presence of IGF-I and two types of IGF receptor by immunohistochemistry revealed tissue- and stage-specific expression during larval development. Immunohistochemistry also showed that IGF-I and its receptors are present in both testicular and ovarian cells. Although at this stage we are not able to pinpoint which is the rate-limiting step causing the slow growth of Sparus aurata, our project (together with the previous BARD) yielded a great number of experimental tools both DNA probes and antibodies that will enable further studies on the factors regulating growth in Sparus aurata. Our expression studies and cellular localization shed new light on the tissue and developmental expression of growth-related genes in fish.
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Hajarizadeh, Behzad, Jennifer MacLachlan, Benjamin Cowie, and Gregory J. Dore. Population-level interventions to improve the health outcomes of people living with hepatitis B: an Evidence Check brokered by the Sax Institute for the NSW Ministry of Health, 2022. The Sax Institute, August 2022. http://dx.doi.org/10.57022/pxwj3682.

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Анотація:
Background An estimated 292 million people are living with chronic hepatitis B virus (HBV) infection globally, including 223,000 people in Australia. HBV diagnosis and linkage of people living with HBV to clinical care is suboptimal in Australia, with 27% of people living with HBV undiagnosed and 77% not receiving regular HBV clinical care. This systematic review aimed to characterize population-level interventions implemented to enhance all components of HBV care cascade and analyse the effectiveness of interventions. Review questions Question 1: What population-level interventions, programs or policy approaches have been shown to be effective in reducing the incidence of hepatitis B; and that may not yet be fully rolled out or evaluated in Australia demonstrate early effectiveness, or promise, in reducing the incidence of hepatitis B? Question 2: What population-level interventions and/or programs are effective at reducing disease burden for people in the community with hepatitis B? Methods Four bibliographic databases and 21 grey literature sources were searched. Studies were eligible for inclusion if the study population included people with or at risk of chronic HBV, and the study conducted a population-level interventions to decrease HBV incidence or disease burden or to enhance any components of HBV care cascade (i.e., diagnosis, linkage to care, treatment initiation, adherence to clinical care), or HBV vaccination coverage. Studies published in the past 10 years (since January 2012), with or without comparison groups were eligible for inclusion. Studies conducting an HBV screening intervention were eligible if they reported proportion of people participating in screening, proportion of newly diagnosed HBV (participant was unaware of their HBV status), proportion of people received HBV vaccination following screening, or proportion of participants diagnosed with chronic HBV infection who were linked to HBV clinical care. Studies were excluded if study population was less than 20 participants, intervention included a pharmaceutical intervention or a hospital-based intervention, or study was implemented in limited clinical services. The records were initially screened by title and abstract. The full texts of potentially eligible records were reviewed, and eligible studies were selected for inclusion. For each study included in analysis, the study outcome and corresponding 95% confidence intervals (95%CIs) were calculated. For studies including a comparison group, odds ratio (OR) and corresponding 95%CIs were calculated. Random effect meta-analysis models were used to calculate the pooled study outcome estimates. Stratified analyses were conducted by study setting, study population, and intervention-specific characteristics. Key findings A total of 61 studies were included in the analysis. A large majority of studies (study n=48, 79%) included single-arm studies with no concurrent control, with seven (12%) randomised controlled trials, and six (10%) non-randomised controlled studies. A total of 109 interventions were evaluated in 61 included studies. On-site or outreach HBV screening and linkage to HBV clinical care coordination were the most frequent interventions, conducted in 27 and 26 studies, respectively. Question 1 We found no studies reporting HBV incidence as the study outcome. One study conducted in remote area demonstrated that an intervention including education of pregnant women and training village health volunteers enhanced coverage of HBV birth dose vaccination (93% post-intervention, vs. 81% pre-intervention), but no data of HBV incidence among infants were reported. Question 2 Study outcomes most relevant to the HBV burden for people in the community with HBV included, HBV diagnosis, linkage to HBV care, and HBV vaccination coverage. Among randomised controlled trials aimed at enhancing HBV screening, a meta-analysis was conducted including three studies which implemented an intervention including community face-to-face education focused on HBV and/or liver cancer among migrants from high HBV prevalence areas. This analysis demonstrated a significantly higher HBV testing uptake in intervention groups with the likelihood of HBV testing 3.6 times higher among those participating in education programs compared to the control groups (OR: 3.62, 95% CI 2.72, 4.88). In another analysis, including 25 studies evaluating an intervention to enhance HBV screening, a pooled estimate of 66% of participants received HBV testing following the study intervention (95%CI: 58-75%), with high heterogeneity across studies (range: 17-98%; I-square: 99.9%). A stratified analysis by HBV screening strategy demonstrated that in the studies providing participants with on-site HBV testing, the proportion receiving HBV testing (80%, 95%CI: 72-87%) was significantly higher compared to the studies referring participants to an external site for HBV testing (54%, 95%CI: 37-71%). In the studies implementing an intervention to enhance linkage of people diagnosed with HBV infection to clinical care, the interventions included different components and varied across studies. The most common component was post-test counselling followed by assistance with scheduling clinical appointments, conducted in 52% and 38% of the studies, respectively. In meta-analysis, a pooled estimate of 73% of people with HBV infection were linked to HBV clinical care (95%CI: 64-81%), with high heterogeneity across studies (range: 28-100%; I-square: 99.2%). A stratified analysis by study population demonstrated that in the studies among general population in high prevalence countries, 94% of people (95%CI: 88-100%) who received the study intervention were linked to care, significantly higher than 72% (95%CI: 61-83%) in studies among migrants from high prevalence area living in a country with low prevalence. In 19 studies, HBV vaccination uptake was assessed after an intervention, among which one study assessed birth dose vaccination among infants, one study assessed vaccination in elementary school children and 17 studies assessed vaccination in adults. Among studies assessing adult vaccination, a pooled estimate of 38% (95%CI: 21-56%) of people initiated vaccination, with high heterogeneity across studies (range: 0.5-93%; I square: 99.9%). A stratified analysis by HBV vaccination strategy demonstrated that in the studies providing on-site vaccination, the uptake was 78% (95%CI: 62-94%), significantly higher compared to 27% (95%CI: 13-42%) in studies referring participants to an external site for vaccination. Conclusion This systematic review identified a wide variety of interventions, mostly multi-component interventions, to enhance HBV screening, linkage to HBV clinical care, and HBV vaccination coverage. High heterogeneity was observed in effectiveness of interventions in all three domains of screening, linkage to care, and vaccination. Strategies identified to boost the effectiveness of interventions included providing on-site HBV testing and vaccination (versus referral for testing and vaccination) and including community education focussed on HBV or liver cancer in an HBV screening program. Further studies are needed to evaluate the effectiveness of more novel interventions (e.g., point of care testing) and interventions specifically including Indigenous populations, people who inject drugs, men who have sex with men, and people incarcerated.
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