118 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.
Analysis of the COVID-19 Severity Based on NLR and the Mortality Rate of Pregnant Women with COVID-19 at Dr. Moewardi General Hospital, Surakarta, Central Java, Indonesia
No full textBackground: Coronavirus Disease 2019 (COVID-19) is a disease of the human respiratory system. Pregnant women are more susceptible to respiratory infections due to physiological changes in the immune and cardiopulmonary systems. Routine laboratory biomarkers such as lymphocytes, neutrophils, and NLR are considered prognostic in COVID-19. This study aimed to analyzed the severity of COVID-19 based on NLR on the mortality of pregnant women with COVID-19 at Dr. Moewardi, Surakarta.Subjects and Method: This study used analytic observational with a cross-sectional. The study subjects were 82 pregnant women with confirmed COVID-19, aged over 18 years, and being treated at RSUD Dr. Moewardi Surakarta between March 2020 to January 2022. The samples were taken using the consecutive sampling technique. The independent variable is the severity of COVID-19 based on clinical presentation. The dependent variable is the laboratory results in lymphocytes, neutrophils, and NLR. Data were collected from medical records and anlayzed using SPSS software.Results: There was correlation between NLR on the severity of pregnant women with COVID-19 (Mean= 10.11; SD= 4.10; p= 0.026) and there was a significant correlation between NLR on the mortality rate of pregnant women with COVID-19 (Mean= 9.92; SD= 3.94; p<0.001).Conclusion: NLR affected the severity and the mortality rate among pregnant women with COVID-19.Keywords: COVID-19, pregnancy, lymphocytes, neutrophils, NLR, mortalityCorrespondence: Dhea Fitria Rachma. Faculty of Medicine Universitas Sebelas Maret Surakarta. Jl. Ir. Sutami 36A, Surakarta 57126, Indonesia. Email: [email protected]. Mobile: 085702594898.Indonesian Journal of Medicine (2022), 07(04): 401-410https://doi.org/10.26911/theijmed.2022.07.04.05
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]
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
[[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.
[[alternative]]Regulatory role of dehydroepiandrosterone on B cell immuno-
No full text[[abstract]]Dehydroepiandrosterone (DHEA) 是腎上腺皮質分泌雄性激素時之前
驅物。前人報告提出DHEA對Ｔ淋巴球、巨噬細胞之功能及白血球新生具有
顯著之調節功能。本實驗證明 DHEA 對Ｂ淋巴球分泌Ig之功能也有影響。
DHEA與脂多醣體同時刺激Ｂ淋巴球時，對IgA有促進的作用，IgG及IgM 的
分泌則無影響。DHEA在Ｂ淋巴球受脂多醣體活化24小時後加入，則對 IgA
及IgG 的分泌有促進作用，對IgM分泌卻有明顯的抑制情形。DHEA 對Ｂ淋
巴球功能的調節不受 Anti IL-2 之影響，但受 Anti TGF-.beta.影響。
顯示 TGF-.beta. 參與DHEA對Ｂ淋巴球功能之調節作用。當DHEA與脂多醣
體同時加入時，Anti TGF-.beta. 抑制了DHEA所誘導之IgA分泌 ，但反而
促進IgG與IgM之分泌，顯示DHEA在Ｂ淋巴球活化初期可促進 IgG與 IgM分
泌，但是受TGF-.beta.所抑制，不過DHEA間接利用TGF-.beta.促進了IgA
之分泌。當 DHEA 在Ｂ淋巴球以脂多醣體活化24小時之後加入，則 Anti
TGF-.beta.抑制了DHEA對三種 Ig分泌的調節效應，顯示DHEA對活化後之
Ｂ細胞只藉TGF-.beta.之協助，才能調節Ｂ細胞之功能。 DHEAS為DHEA在
血清中存在的主要形式，但是DHEAS 對Ｂ淋巴球的功能無顯著影響。Dexa
-methasone為 glucocorticoid 之衍生物，對Ｂ淋巴球的增生、存活率及
IgA 分泌皆有顯著抑制作用，而DHEA可以拮抗Dexamethasone 的抑制作用
。DHEA直接或間接對免疫球蛋白分泌之調節作用，為內分泌與免疫系統之
關係提供了重要佐證，而 DHEA 與 glucocorticoid 之間之拮抗作用也顯
示體內，這兩種類固醇荷爾蒙平衡的重要性。
Dehydroepiandrostone(DHEA), a precusor androgen biosynthesis
in adrenal cortex, has been show to regulate the functions of T
lymphocytes and macrophages,and to suppress the lymphopoisis and
myelopoisis. Theresults of this study indicate that DHEA also
has ability to modulateB cell immunoglobulin secretion. DHEA did
enchance IgA secretion buthad no effect on IgG and IgM secretion
when B cells were stimulated by DHEA and lipopolysaccharide(LPS)
at the same time. However, if DHEA was added 24 hours after LPS
induced B cell activation, both the IgA and IgG secretion were
enhanced but IgM secration was suppressed by DHEA.The modulatory
function of DHEA on B cells was not affected by anti-inteleukin2
(IL-2) antibodies but it was significant affected by anti trans-
forming growth factor .beta.( TGF-.beta. ), suggesting that TGF-
.beta.was involved in DHEA-mediated immunoregulation. Anti TGF-
.beta. inhibited DHEA induced IgA secretion but significantly
enhanced IgG and IgMsecretion when B cells were stimulated by
DHEA and LPS at the same time. It implied that DHEA could enhance
IgG and IgM secreation during theearly stage of B cell activation
.However, both IgG and IgM secretionwere suppressed by TGF-.beta.
. On the contrary, TGF-.beta. together with DHEA induced IgA
secretion. Anti-TGF-.beta. completely abrogated the immunoregu-
latory function of DHEA when B cells were stimulated by DHEA 24
hoursafter LPS-induced activiation, suggesting that the presence
of TGF-.beta. is essential for DHEA to regulate the function of
activated B cells, DHEAS , the specific form of DHEA in serum,
showed no effect on immunogloublin secretion. Dexamethasone, a
derivative of glucocorticoid, suppressed B cell growth, reduced
B cell viability and IgA secretion. Results in this study showed
that DHEA significantly antagonized immunosuppresive effect of
dexamethasone. The observation that DHEA directlyor indirectly
regulated immunoglobulin secretion provided an additional evi-
dence to demonstrate the close relationship between endocrine
andimmune system. Furthermere, the counter reaction between DHEA
and glucocorticoid suggested that it is essential to maintance
the properratio between these two important steroid hormone in
body fluid.
Dehydroepiandrostone(DHEA), a precusor androgen biosynthesis
Subcellular redistribution of NHERF1 in response to dehydroepiandrosterone (DHEA) administration in endometrial glands of Wistar rats
No full textTo understand the regulation of Na(+)/H(+) exchanger regulatory factor (NHERF1) in polycystic ovarian syndrome, we studied the expression of NHERF1 in uterus of Wistar rats injected with (6 mg/kg) of dehydroepiandrosterone (DHEA) for 7 and 20 days. Immunohistochemistry analysis of NHERF1 showed a substantial shift in the intracellular localization of NHERF1 in endometrial glands and areas of luminal epithelium as early as 7 days of DHEA administration. The NHERF1 accumulated in the "Golgi apparatus area" virtually in all the glands in the 7-day protocol, and in the majority of the glands of 20-day protocol. In contrast, NHERF1 is expressed in the apical membrane and slightly in the cytoplasm of the control epithelium. The subcellular redistribution of NHERF1 could affect the sorting of proteins to the apical membrane and the organization of the apical compartment. © 2013 The Author(s).Fil: Kreimann, Erica Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad Presidencia; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Cabrini, Rómulo L.. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentin
ANALISIS KUALITATIF ADMINISTRATIF DOKUMEN REKAM MEDIS RAWAT INAP PADA KASUS ULKUS DIABETIK DI RS LUDIRA HUSADA TAMA
No full textLatar Belakang: Rekam medis yang diisi secara lengkap dapat menggambarkan mutu pelayanan rumah sakit yang baik. Mengingat pentingnya rekam medis untuk peningkatan mutu pelayanan rumah sakit, diperlukan audit pendokumentasian
rekam medis salah satunya dengan cara analisis kualitatif administratif. Analisis kualitatif administratif sangat diperlukan untuk mengetahui persentase dokumen rekam medis yang lengkap dan konsisten.
Tujuan penelitian: Untuk mengetahui hasil kelengkapan analisis kualitatif administratif dokumen rekam medis rawat inap pada kasus ulkus diabetik di RS Ludira Husada Tama.
Metode Penelitian: Jenis penelitian ini adalah penelitian deskriptif kuantitatif dengan metode observasi dan desain penelitian retrospektif. Populasi pada penelitian ini adalah semua dokumen rekam medis sebanyak 47 dokumen rekam medis.
Hasil Penelitian: Berdasarkan hasil penelitian terhadap 47 dokumen rekam medis diperoleh review kelengkapan dan kekonsistenan diagnosa sebanyak 20 (41%) dokumen rekam medis lengkap, review kekonsistenan pencatatan sebanyak 7 (15%) dokumen rekam medis lengkap. review pencatatan hal-hal yang dilakukan saat perawatan dan pengobatan sebanyak 26 (56%) dokumen rekam medis lengkap, review adanya informed consent sebanyak 45 (96%) dokumen rekam medis lengkap, review cara atau praktik pencatatan sebanyak 26 (54%) dokumen rekam medis lengkap, review hal-hal yang berpotensi menyebabkan tuntutan ganti rugi sebanyak 0 (0%) tidak terdapat item yang menyebabkan RS mengalami kerugian.
Kesimpulan: Melihat hasil penelitian terhadap 47 dokumen rekam medis diperoleh rata-rata kelengkapan analisis administratif sebanyak 21 dokumen rekam medis dengan persentase 44%.
Kata Kunci: Analisis Kualitatif Administratif, Rekam Medis, Ulkus Diabetik
Tinjauan hukum Islam terhadap sanksi denda pada nasabah murâbahah : studi putusan Pengadilan Agama Demak Nomor 04/Pdt.G.S/2021/PA. Dmk
No full textPerkara ekonomi syariah Nomor 04/Pdt.G.S/2021/PA.Dmk yang didaftarkan di Pengadilan Agama Demak pada tanggal 30 Juni 2021 diselesaikan dengan cara gugatan sederhana. Perkara ini merupakan perkara akad Murābaḥah yang terjadi antara Koperasi Simpan Pinjam Pembiayaan Syariah (KSPPS) Dana Li Mardhatillah sebagai Penggugat dan Sutiyo (bukan nama sebenarnya) sebagai Tergugat I serta Susi (bukan nama sebenarnya) Tergugat II dengan gugatan materiil sebesar Rp. 13.735.000,00. Dalam putusannya, Majelis Hakim menyatakan Para Tergugat melakukan perbuatan wanprestasi, mengabulkan gugatan Penggugat sebagian dengan verstek dan menyatakan tidak dapat diterima selain dan selebihnya, serta menghukum Para Tergugat untuk membayar kerugian materiil sebesar Rp. 8.735.000,00.
Rumusan masalah dalam penelitian ini yaitu bagaimana dasar pertimbangan Hakim dalam mengabulkan dan menolak denda dalam perkara nomor 04/Pdt.G.S/2021/PA.Dmk, serta bagaimana analisis hukum Islam terhadap denda pembiayaan Murābaḥah. Metode yang digunakan dalam penelitian ini adalah penelitian hukum normatif, dengan menggunakan Peraturan Mahkamah Agung Nomor 4 Tahun 2019 tentang Tatacara Penyelesaian Gugatan Sederhana. Penelitian ini menggunakan pendekatan yuridis yaitu putusan gugatan ekonomi syariah di Pengadilan Agama Demak. Sumber data yang diperoleh dalam penelitian ini adalah metode wawancara dengan hakim Pengadilan Agama Demak selaku hakim pemeriksa perkara gugatan tersebut. Setelah data terkumpul, kemudian dilakukan analisis terhadap data tersebut menggunakan pola pikir induktif.
Hasil penelitian dari perkara ini yaitu Hakim dalam memutus perkara ini terlebih dahulu mengolah data-data yang diperoleh dari bukti surat, saksi, persangkaan, pengakuan maupun sumpah yang terungkap dalam persidangan, sehingga putusan yang ditetapkan Hakim dapat didasari oleh rasa tanggungjawab, keadilan, kebijaksanaan, profesionalisme dan bersifat objektif. Bahwa denda dalam pembiayaan Murābaḥah boleh dilakukan pada nasabah yang melakukan ingkarjanji/wanprestasi dan dalam keadaan mampu membayar tetapi menunda – nunda pembayaran serta tidak mempunyai itikad baik untuk membayar. Denda Murābaḥah adalah sah menurut syari’ah berdasarkan fatwa DSN MUI No. 17 tahun 2000. Alasan Majelis Hakim dalam menolak mengenai biaya penagihan dan penyelesaian perkara yaitu karena biaya tersebut tidak diperjanjikan di awal perjanjian maka bisa disebut ini klaim sepihak dan hal ini sejalan dengan Fatwa DSN MUI No. 17 Tahun 2000
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