PERANG SALIB III (Faktor Penyebab, Peran dan Perjuangan Shalahuddin Al Ayyubi)

M. Iqbal Hasby A. 1411315000. PERANG SALIB III (FAKTOR PENYEBAB, PERAN DAN PERJUANGAN SHALAHUDDIN AL AYYUBI). Skripsi. Jurusan Sejarah Kebudayaan Islam. Fakultas Adab Dakwah. IAIN Syekh Nurjati Cirebon. 2016. Perang Salib merupakan sebuah peristiwa peperangan yang terjadi dalam kurun waktu kurang lebih dua ratus tahun (1096-1292 M), yang mempertemukan Umat Islam dan Kristen Eropa demi mendapatkan kekuasaan atas wilayah Baitul Maqdis (Yerusalem). Dalam serangkaian Perang Salib ini telah memunculkan peran seorang tokoh yang cukup berjasa besar peranannya dalam mempertahankan Baitul Maqdis (Yerusalem), dia adalah seorang raja dan pahlawan umat Islam yaitu Shalahuddin Al Ayyubi. Sesuai dengan latar belakang yang telah di ungkapkan di atas, di sini penulis mencoba menguraikan rumusan masalah mengenai latar belakang perang salib dan sejauh mana peran dan perjuangan Shalahuddin Al Ayyubi dalam peristiwa Perang Salib, yang dirumuskan ke dalam pembahasan terkait latar belakang terjadinya perang salib serta peran dan perjuangan yang dimunculkan oleh Shalahuddin Al Ayyubi dalam peristiwa Perang Salib tersebut. Peristiwa ini memfokuskan pembahasannya pada peran penting seorang Shalahuddin dalam mempertahankan Baitul Maqdis (Yerusalem) saat Perang Salib III (1096 s/d 1198 M) sehingga tetap di dalam kekuasaan Umat Muslim. Untuk metode penelitian ini penulis menggunakan pendekatan Library Research dengan menggunakan metode heuristik, di mana setelah sumber-sumber informasi terkait diperoleh, berikutnya dilakukan kritik dan verivikasi kemudian dibuat alur yang logis dengan penafsiran-penafsiran agar apa yang penulis tulis memiliki alur cerita sejarah yang runtut dengan metode historiografi. Dari hasil penelitian tersebut dapat ditarik sebuah kesimpulan bahwa Perang Salib terjadi kurang lebih selama 200 tahun yang memperebutkan wilayah (Baitul Maqdis/Yerusalem) yang diangap suci oleh 3 agama besar (Yahudi, Kristen dan Islam) karena faktor Agama, faktor Politik (Kekuasaan), dan faktor Ekonomi. Shalahuddin Al Ayyubi menjadi tokoh yang paling dikenal dalam peristiwa Perang Salib ini, peran dan perjuangannya yang cukup berarti demi mempertahankan Baitul Maqdis (Yerusalem) dari serangan Pasukan Salib Eropa. Kata Kunci : Perang Salib, Shalahuddin Al Ayyubi, Peran dan perjuanga

Mycophenolate pharmacokinetics and pharmacodynamics in belatacept treated renal allograft recipients – a pilot study

<p>Abstract</p> <p>Background</p> <p>Mycophenolic acid (MPA) is widely used as part of immunosuppressive regimens following allograft transplantation. The large pharmacokinetic (PK) and pharmacodynamic (PD) variability and narrow therapeutic range of MPA provide a potential for therapeutic drug monitoring. The objective of this pilot study was to investigate the MPA PK and PD relation in combination with belatacept (2^ndgeneration CTLA4-Ig) or cyclosporine (CsA).</p> <p>Methods</p> <p>Seven renal allograft recipients were randomized to either belatacept (n = 4) or cyclosporine (n = 3) based immunosuppression. Samples for MPA PK and PD evaluations were collected predose and at 1, 2 and 13 weeks posttransplant. Plasma concentrations of MPA were determined by HPLC-UV. Activity of inosine monophosphate dehydrogenase (IMPDH) and the expressions of two <it>IMPDH </it>isoforms were measured in CD4+ cells by HPLC-UV and real-time reverse-transcription PCR, respectively. Subsets of T cells were characterized by flow cytometry.</p> <p>Results</p> <p>The MPA exposure tended to be higher among belatacept patients than in CsA patients at week 1 (P = 0.057). Further, MPA concentrations (AUC_{0–9 h}and C₀) increased with time in both groups and were higher at week 13 than at week 2 (P = 0.031, n = 6). In contrast to the postdose reductions of IMPDH activity observed early posttransplant, IMPDH activity within both treatment groups was elevated throughout the dosing interval at week 13. Transient postdose increments were also observed for <it>IMPDH1 </it>expression, starting at week 1. Higher MPA exposure was associated with larger elevations of <it>IMPDH1 </it>(r = 0.81, P = 0.023, n = 7 for MPA and <it>IMPDH1 </it>AUC_{0–9 h}at week 1). The maximum <it>IMPDH1 </it>expression was 52 (13–177)% higher at week 13 compared to week 1 (P = 0.031, n = 6). One patient showed lower MPA exposure with time and did neither display elevations of IMPDH activity nor <it>IMPDH1 </it>expression. No difference was observed in T cell subsets between treatment groups.</p> <p>Conclusion</p> <p>The significant influence of MPA on <it>IMPDH1 </it>expression, possibly mediated through reduced guanine nucleotide levels, could explain the elevations of IMPDH activity within dosing intervals at week 13. The present regulation of IMPDH in CD4+ cells should be considered when interpreting measurements of IMPDH inhibition.</p

Intracellular interferons in fish : a unique means to combat viral infection

Peer reviewedPublisher PD

Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer

Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. But it is unclear whether microRNAs play a role in regulating oncogene expression in fulvestrant-treated prostate cancer. Here, this study reports hsa-miR-765 as the first fulvestrant-driven, ERβ-regulated miRNA exhibiting significant tumor suppressor activities like fulvestrant, against prostate cancer cell growth via blockage of cell-cycle progression at the G2/M transition, and cell migration and invasion possibly via reduction of filopodia/intense stress-fiber formation. Fulvestrant was shown to upregulate hsa-miR-765 expression through recruitment of ERβ to the 5′-regulatory-region of hsa-miR-765. HMGA1, an oncogenic protein in prostate cancer, was identified as a downstream target of hsa-miR-765 and fulvestrant in cell-based experiments and a clinical study. Both the antiestrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression. In a neo-adjuvant study, levels of hsa-miR-765 were increased and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose (250 mg) of fulvestrant 28 days before prostatectomy. These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer. © 2014 Leung et al

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference