107 research outputs found
Hormonal effects of prohormones : novel approaches towards effect based screening in veterinary growth promoter control
No full textWithin the European Union the use of growth promoting agents in cattle fattening is prohibited according to Council Directive 96/22/EC. Interestingly, there is not a black list of substances, but 96/22/EC states that all substances having thyrostatic, estrogenic, androgenic or gestagenic activity are prohibited. Besides abuse of the “classical” synthetic steroids there is a tendency towards misuse of natural steroids and prohormones. Prohormones are compounds that exhibit limited or no hormonal activity but are direct precursors of bioactive hormones and are intended to be converted to full active hormones via enzymatic processes in the body. However, knowledge about metabolism, the mode of action and excretion profiles in cattle is often unclear, and methods to detect abuse of prohormones in livestock production are lacking. Therefore, the aim of this thesis was to get insight into the hormonal action of prohormones and to develop novel in vitro and in vivo screening methods allowing effective surveillance on the illegal use of prohormones in livestock production. Hereby the emphasis was on developing effect based approaches to better meet Council Directive 96/22/EC. The bioactivity of a wide variety of supplements which contained prohormones were tested using a yeast androgen bioassay. For supplements containing solely prohormones the value of this bioactivity based screening appeared to be limited as they require metabolism to become active. Therefore, screening methods for animal feed, supplements and preparations were set-up by using the same yeast androgen bioassay in combination with bovine liver models as well as enzymatic and chemical deconjugation procedures to mimic in vivo metabolic bioactivation. The use of either bovine liver S9, liver slices, pure enzymes or alkaline hydrolysis showed that prohormones could be activated, resulting in a significant increase in bioactivity as determined by the androgen yeast bioassay. For the detection of prohormone abuse at the farm and/or slaughterhouse the usefulness of ‘omics’ based profiling techniques was investigated. Within this scope a comprehensive metabolomics based screening strategy for steroid urine profiling was developed. Comparison of urinary profiles revealed large differences between the profiles of controls and dehydroepiandrosterone (DHEA) as well as pregnenolone treated animals. Moreover this steroid urine profiling approach allowed identification of biomarkers for treatment by specific prohormones. This resulted in respectively 7 and 12 specific mass peak loadings which could potentially be used as biomarkers for pregnenolone and DHEA treatment. In addition, the feasibility of a liver gene expression profiling approach was investigated to monitor the effects of DHEA treatment at the transciptome level. It was shown that identification and application of genomic biomarkers for screening of DHEA abuse in cattle is substantially hampered by biological variation. On the other hand, it was demonstrated that comparison of pre-defined gene sets versus the whole genome expression profile of an animal allows to distinguish DHEA treatment effects from variations in gene expression due to inherent biological variation. Altogether the results of this thesis increase the knowledge about the metabolism and bioactivation of prohormones in vitro as well as in vivo. Based on this knowledge, a panel of new effect based concepts and screening methods was developed that complement and improve the current testing programs. These new concepts will facilitate better implementation of the European ban on growth promoters in livestock production as described in Council Directive 96/22/EC. <br/
[[alternative]]In vitro Study on the Regulation og Human Immunoglobulin Production by Dehydroepiandrosterone(DHEA)
No full text[[abstract]]Dehydroepiandrosterone ( DHEA ) is a predominant androgen secreted by the adrenal cortex. Physiologically, DHEA appears as an intermediate of the androgen biosynthesis pathway. However, DHEA has been shown to play a multifunctional role in human and animal body. In addition, DHEA is a potential immunomodulator. DHEA regulates a variety of humoral and cellular immune response. Our previous report suggested that DHEA enhanced immunoglobulin secretion by murine B lymphocytes under in vitro condition. The same study also observed an antagonist effect of DHEA on the dexamethasone ( a glucocorticoid derivative )-mediated immunosuppression. The present study further extended the DHEA study from murine system to human immune cells. Data suggested that DHEA and DHEAS had no significant effect on the growth and viability of non-adherent peripheral blood mononuclear cells ( PMNC ). However, both drugs significantly augmented IgA and IgM secretion. Dexamethasone also enhanced IgA and IgM secretion by PMNC. Under our in vitro experimental condition, costimulating the cells with DHEA/DHEAS and dexmethasone shown a synergistic dffect on IgA and IgM secretion. To further investigate whether DHEA/DHEAS enhanced immunoglobulin secretion by direct stimulating the B lymphocytes, the growth and function of Dakiki ( an IgA secreting cells ) and SKW6.4 ( an IgM secreting cells ) in the presence of DHEA/DHEAS were studied. DHEA and DHEAS had no significant effect on the growth and viability of both Dakiki and SKW6.4. DHEA/DHEAS enhanced IgA and IgM secretion by Dakiki adb SKW6.4 cells, respectively dexamethasone suppressed the IgA secretion by IgA secretion by Dakiki. However, the dexamethasone- mediated suppressive effect could be overcome by both DHEA and DHEAS. In contrast, dexamethsaone enhanced IgM secretion by SKW6.4. Cosimulating the SKW6.4 with DHEA/DHEAS and dexamethasone has synergistic effect on IgM secretion. The IgM gene expression was studied by RT-PCR analysis. Result shown that the mRNA level of IgM in SKW6.4 cells were elevated after the cells were treated with DHEA, DHEAS or dexamethasone, suggesting that IgM production was stimulated at the transcription level.
High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS
No full textPolycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder with unclear etiology and unsatisfactory management. Effects of diets on the phenotype of PCOS were not fully understood. In the present study, we applied 45 and 60% high-fat diets (HFDs) on a rat model of PCOS induced by postnatal DHEA injection. We found that both DHEA and DHEA + HFDs rats exhibited reproductive abnormalities, including hyperandrogenism, irregular cycles and polycystic ovaries. The addition of HFDs, especially 60% HFDs, exaggerated morphological changes of ovaries and a number of metabolic changes, including increased body weight and body fat content, impaired glucose tolerance and increased serum insulin levels. Results from qPCR showed that DHEA-induced increased expression of hypothalamic androgen receptor and LH receptor were reversed by the addition of 60% HFDs. In contrast, the ovarian expression of LH receptor and insulin receptor mRNA was upregulated only with the addition of 60% HFDs. These findings indicated that DHEA and DHEA + HFDs might influence PCOS phenotypes through distinct mechanisms: DHEA affects the normal function of hypothalamus-pituitary-ovarian axis through LH, whereas the addition of HFDs exaggerated endocrine and metabolic dysfunction through ovarian responses to insulin-related mechanisms. We concluded that the addition of HFDs yielded distinct phenotypes of DHEA-induced PCOS and could be used for studies on both reproductive and metabolic features of the syndrome.National Natural Science Foundation of China [81170538, 81471427]; National Key Technology R&D Program in the Twelve Five-Year Plan [2012BAI32B01]; China Postdoctoral Foundation [2015M570905]SCI(E)[email protected]
Analisis Kebijakan Arab Saudi Dalam Normalisasi Hubungan Dengan Iran Tahun 2023
No full textArab Saudi dan Iran merupakan dua kekuatan regional di Timur Tengah yang terlibat dalam persaingan posisional untuk memperebutkan status sebagai hegemoni kawasan. Permusuhan kedua negara semakin meningkat ketika Arab Saudi melakukan pemutusan hubungan diplomatik dengan Iran tahun 2016. Penelitian ini bertujuan untuk menganalisis lebih lanjut terkait Kebijakan Arab Saudi dalam normalisasi hubungan dengan Iran tahun 2023. Dalam penelitian ini, penulis menggunakan teori Balance of Threat yang dikemukakan oleh Stephen M. Walt untuk menganalisis kebijakan normalisasi hubungan yang dilakukan oleh Arab Saudi. Kebijakan normalisasi merupakan perilaku bandwagoning oleh Arab Saudi untuk menghadapi ancaman yang ditimbulkan oleh Iran. Penelitian ini menggunakan metode kualitatif dengan pendekatan eksplanasi menggunakan data sekunder. Berdasarkan analisis menggunakan konsep Balance of Threat, penulis menemukan faktor yang mempengaruhi ancaman dari Iran kepada Arab Saudi seperti perbandingan kekuatan agregat Iran vs Arab Saudi, Arab Saudi dan Iran tetangga yang saling bermusuhan, kekuatan ofensif Iran mengungguli Arab Saudi, dan ambisi Ekspansionis Iran ‘Wilayah al-Faqih’ untuk mendominasi kawasan. Selanjutnya, penulis menemukan situasi yang mendorong Arab Saudi untuk melakukan normalisasi sebagai perilaku bandwagoning yaitu Iran sebagai negara dengan kekuatan ofensif yang kuat, tidak adanya aliansi yang potensial, dan kemenangan Iran pada perang proksi melawan Arab Saudi
The effect of dehydroepiandrosterone combined with a low-fat diet in spontaneously obese dogs: a clinical trial
No full textDehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a clinical trial. Spontaneously obese, euthyroid dogs, referred to the University of Wisconsin School of Veterinary Medicine for treatment of their obesity, were evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma lipoprotein and serum biochemistry profiles, complete blood count, and endocrine profiles (T4, T3, cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a significantly increased rate of actual and percent excess weight loss compared with placebo-treated dogs. Serum cholesterol decreased in both treatment groups; however, DHEA-treated dogs had a significantly greater reduction than placebo-treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma cholesterol, which was due to a 27% reduction in the lipoprotein fraction containing the high-density lipoprotein (HDL) and a 50% reduction in the lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo-treated dogs did not have a significant reduction in total plasma cholesterol or in the fraction containing LDL; however, they did have a significant 11% reduction in the fraction containing HDL. Significant decreases in serum T4 and T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA in combination with caloric restriction results in a faster rate of weight loss than does caloric restriction alone. In addition, DHEA has hypocholesterolemic activity, particularly affecting the lipoprotein fraction containing the LDL cholesterol.ID: 1593; LR: 20061115; JID: 9305691; 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Placebos); 50-23-7 (Hydrocortisone); 53-43-0 (Dehydroepiandrosterone); 57-88-5 (Cholesterol); 6893-02-3 (Triiodothyronine); 7488-70-2 (Thyroxine); ppublishSource type: Electronic(1
PENGARUH PENERAPAN GOOD CORPORATE GOVERNANCE TERHADAP KINERJA KEUANGAN PERUSAHAAN (Studi Pada Perusahaan BUMN yang Terdaftar di Bursa Efek Indonesia Tahun 2018-2022)
No full textThe company's financial performance is the result achieved by the company for various activities carried out in utilizing the resources it has. This research aims to prove the influence of good corporate governance on the financial performance
of state-owned companies listed on the IDX in 2018-2022. The dependent variable in this research is financial performance as measured by ROA. The independent variable in this research is good corporate governance (GCG) proxied by
institutional ownership, managerial ownership, independent commissioners, and audit committees. In this research, the type of data used is secondary data. This research is quantitative. The population in this research is state-owned companies registered on the IDX in 2018-2022, totaling 24 companies. The sampling method used a purposive sampling technique and 15 companies were obtained as samples
for this research. The analysis technique used is multiple linear regression analysis processed using SPSS 26. The results of this research show that institutional ownership, independent commissioners, and audit committees influence financial performance. Meanwhile, managerial ownership does not affect economic performance
Pengaruh Dispersi Perusahaan terhadap Penghindaran Pajak di Indonesia
No full textPenelitian ini bertujuan untuk mengetahui pengaruh dispersi perusahaan terhadap penghindaran pajak dari perspektif dispersi geografis. Untuk menguji hipotesis, digunakan data sekunder dalam bentuk cross section. Populasi dalam penelitian ini adalah semua perusahaan yang telah terdaftar di Bursa Efek Indonesia pada tahun 2018 terkecuali perusahaan pada sektor keuangan. Pengambilan sampel menggunakan metode purposive sampling sebanyak 212 perusahaan. Variabel yang digunakan adalah dispersi geografis sebagai variabel independen, sedangkan penghindaran pajak perusahaan sebagai variabel dependen. Dispersi geografis diukur dengan menggunakan standar deviasi jarak antara kantor pusat dan cabang. Penghindaran pajak diukur dengan proxy Effective Tax Rate (ETR). Metode analisis penelitian yang digunakan adalah regresi linear berganda dengan menggunakan software SPSS 22. Berdasarkan hasil analisis menunjukkan bahwa dispersi geografis berpengaruh negatif terhadap penghindaran pajak.The purpose of this study is to examine the influence of corporate dispersion on tax avoidance from geographical dispersion. To test the hypothesis, secondary data is used in the form of cross sections. The population in this research is all company that listing in Indonesia Stock Exchange (ISX) 2018 except a financial company. Sampling using purposive sampling method were 212 companies. The variable used was geographical dispersion as the independent variable, and tax avoidance as an dependent variable. Geographical dispersion measured by standard deviation of the distance between the head office and branches. Tax avoidance measured by proxy Effective Tax Rate (ETR). The method of analysis used was multiple linear regression with SPSS 22 software. Based on the result of the analysis it was indicated that geographical dispersion had negative impact to tax avoidance
[[alternative]]Study on the role of dehydroepiandrosterone in regulation of specific antibody response
No full text[[abstract]]Abstract
Dehydroepiandrosterone (DHEA) is one of the major androgens secreted by adrenal cortex and play a multifunctional role in regulating physiological system in mammals. DHEA is predominantly converted to DHEA-sulfate (DHEAS) in serum . Recent reports demonstrated that DHEA is a potent immunomodulator. In addition, recent data showed that DHEA might act as an effective vaccine adjuvant in aged human and mice. However, the immunostimulatory effect on the children and young animal upon immunization remain to be studied. Furthermore, the profile of cytokine associated with DHEA-mediated regulatory effect remained to be defined. The major purpose of this study is to investigate the possible immunostimulatory effect of DHEA on the young mice immunized with Escherichia coli (E.coli O78:H11), combined diphtheria, tetanus, acellular pertussis vaccine (DPT vaccine) or pertussis toxin (PT), and to investigate the profile of cytokine associated with DHEA administration. Results indicated that DHEA has an augmented effect on the young mice immunized with Escherichia coli (E.coli O78:H11) or pertussis toxin (PT). However, DHEA did not show adjuvant effect on DPT vaccine immunized mice. In the subsequent study, the mice were infected with E. coli or challenged with PT, followed by subcutaneous injection with DHEA. Result indicated that DHEA synergistically enhanced E. coli or PT induced IFN-g, IL-2 and IL-4, IL-10 cytokine productions. Therefore, the immunoregulatory effect of DHEA might closely relate with its ability to modulate cytokine production. This study not only confirmed the ability of DHEA to regulate specific antibody response, but also demonstrated the role of DHEA in regulation of cytokine production.
Nilai moral dalam film animasi Lorong Waktu di Youtube
No full textFilm Animasi “Lorong Waktu” di Youtube merupakan salah satu
film animasi buatan anak bangsa. Animasi ini menggambarkan cerita fiksi ilmiah menggunakan mesin waktu. Lorong Waktu memiliki durasi 7 menit dalam setiap episodenya. Program serial animasi banyak disukai kalangan masyarakat terutama anak-anak. Film animasi merupakan media hiburan sekaligus penyampaian pesan baik pesan edukasi maupun pesan moral.
Sayangnya tidak semua animasi mengandung pesan-pesan tersebut. Beberapa animasi terbukti tidak diperuntukkan untuk anak karena mengandung pornografi dan kekerasan seperti Naruto dan One Peace. Dari hal tersebut penulis ingin meneliti film animasi dengan mengambil subjek penelitian film aniamsi Lorong Waktu. Penulis mengambil rumusan masalah (1)Apa sajakah nilai moral dalam film animasi Lorong Waktu di Youtube? (2) Bagaimana teknik penyampaian pesan dari nilai moral yang terkandung dalam film animasi Lorong Waktu di Youtube? Tujuan yang ingin dicapai dalam penulisan penelitian ini adalah untuk mengetahui dan mendeskripsikan nilai moral serta teknik penyampaian pesan dalam film animasi Lorong Waktu
Jenis penelitian ini adalah penelitian kualitatif dengan
menggunakan dokumentasi sebagai metode pengumpulan data. Dokumentasi bertujuan untuk memperolah data langsung dari penelitian meliputi bukubuku, laporan kegiatan, foto-foto dan data yang relevan lainnya. Teknik analisis yang digunakan yaitu analisis isi Krippendoft yaitu teknik penelitian untuk membuat inferensi-inferensi yang dapat ditiru dan sahih data dengan memperhatikan konteksnya.
Hasil penelitian ini menunjukkan bahwa dalam Film Animasi
Lorong Waktu terdapat nilai moral diantaranya moral kepada Sang Pencipta yaitu berdo’a, bersyukur, berserah diri dan beramal shaleh. Nilai moral terhadap sesama manusia diantaranya tolong menolong, saling menyanyangi, saling memaafkan dan saling menasihati, Nilai moral terhadap diri sendiri yaitu jujur dan rajin. Serta teknik penyampaian pesan ditinjau dari segi audio yaitu musik ilustrasi, efek suara serta dialog dan visual yaitu teknik pengambilan gambar dan setting atau latar kemudian dilihat dari keefektifan komunikasi terdapat teknik komunikasi persuasif, informatif dan koersif
Pengaruh Profitabilitas, Likuiditas, Dan Leverage Terhadap Nilai Perusahaan Sub Sektor Farmasi di Bursa Efek Indonesia
No full textThis research aims to determine and analyze the effect of financial ratios on firm value in Pharmaceutical Sub Sector Companies on the Indonesia Stock Exchange. By using the independent variables Profitability, Liquidity, Leverage, and the dependent variable, namely Firm Value. The population in this study are all pharmaceutical companies listed on the Indonesian Stock Exchange on the web www.idx.co.id Samples that meet the criteria are (9) companies. This research method uses Method Purposive Sampling. The data analysis technique in this study uses Multiple Regression Analysis. The results of this study prove that profitability has a significant positive effect on firm value. Liquidity and leverage significant negative effect on company value in pharmaceutical companies listed on the Indonesia Stock Exchange
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