Topical and Systemic Cannabidiol Improves Trinitrobenzene Sulfonic Acid Colitis in Mice

Background/Aims: Compounds of Cannabis sativa are known to exert anti-inflammatory properties, some of them without inducing psychotropic side effects. Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves chemically induced colitis in rodents when given intraperitoneally. Here, we tested the possibility whether rectal and oral application of CBD would also ameliorate colonic inflammation, as these routes of application may represent a more appropriate way for delivering drugs in human colitis. Methods: Colitis was induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring, histopathology and the myeloperoxidase (MPO) assay. Results: Intraperitoneal treatment of mice with CBD led to improvement of colonic inflammation. Intrarectal treatment with CBD also led to a significant improvement of disease parameters and to a decrease in MPO activity while oral treatment, using the same dose as per rectum, had no ameliorating effect on colitis. Conclusion: The data of this study indicate that in addition to intraperitoneal application, intrarectal delivery of cannabinoids may represent a useful therapeutic administration route for the treatment of colonic inflammation. Copyright (C) 2012 S. Karger AG, Base

Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase 2 (IKK2, IKK-beta, IKBKB) and TRAF2 indicating a dose dependent regulatory function of TRAF1 for NF-kappa B signaling

IKK2 is one of the most crucial signaling kinases for activation of the transcription factor NF-kappa B. Since many NF-kappa B activating pathways converge at the level of IKK2, we searched for interaction partners of this kinase using the C-terminal part (aa 466-756) as bait in a yeast two-hybrid system. We identified the N-terminal part (aa 1-228) of the TNF-receptor associated factor TRAF1 as putative interaction partner, which was subsequently confirmed in mammalian cells by coimmunoprecipitation experiments. However, this interaction seemed weaker than the interaction between TRAF1 and TRAF2, an important activating adapter molecule of NF-kappa B signaling indicating that relative levels of IKK2, TRAF1 and TRAF2 might be important for the final biological readout. Reporter gene and kinase assays using ectopic expression of TRAF1 indicated that it can have both activating and inhibiting functions for IKK2 and NF-kappa B. Co-expression of fluorescently tagged TRAF1 and TRAF2 at different ratios implied that TRAF1 can affect clustering and presumably the activating function of TRAF2 in a dose dependent manner

Fraksi Heksan Ekstrak Biji Pepaya Muda Dapat Menghambat Proses Spermatogenesis Mencit Jantan Lebih Besar Daripada Fraksi Metanol Ekstrak Biji Papaya Muda

Fraksi ekstrak heksan mengandung dua golongan zat aktif yang bersifat antifertilitas yaitu golongan steroid dan golongan triterpenoid yang diperkirakan bersifat antifertilitas, walupun mekanisme kerjanya belum jelas. Rancangan penelitian yang digunakan ialah ‘' Pre-test post-test control group design''. Penelitian ini memakai 30 ekor mencit jantan strain balb C , umur sekitar 12 minggu dengan berat 20-22 gram, kemudian dikelompokkan secara random menjadi 3 kelompok yang masing-masing terdiri dari 10 ekor. Satu kelompok kontrol (P0 = yang diberikan aquabides), dan dua kelompok perlakuan (P1 = kelompok perlakuan yang diberikan fraksi heksan ekstrak 20 mg/20 gram/hari, P2 = kelompok perlakuan yang diberikan fraksi ekstrak metanol 20 mg/20 gram/hari). Setelah 36 hari perlakuan lalu dilakukan pemeriksaan testis dan darah mencit. Data yang diperoleh dianalisis secara statistik dengan menggunakan uji normalitas Kolmogorov Smirnov Goodnees of Fit test, uji homogenitas, dan uji anova. Didapatkan hasil bahwa fraksi heksan ekstrak maupun metanol dapat menurunkan jumlah sel spermatogonia A, sel spermatosit primer pakhiten, sel spermatid, dan sel Sertoli secara sangat bermakna (p < 0,01), sedangkan jumlah sel Leydig dan kadar hormon testosteron menurun tidak bermakna (p > 0,05). Dari hasil penelitian ini dapat disimpulkan bahwa fraksi heksan ekstrak biji pepaya dapat menurunkan jumlah rata-rata sel spermatogonia A, spermatosit primer pakiten, spermatid, sel Sertoli, sel Leydig dan kadar hormon testosteron lebih besar dari pada fraksi metanol ekstrak biji pepaya muda

UMPAN BALIK PENERAPAN METODE CASE-BASED TEACHING PADA PERKULIAHAN FARMAKOLOGI BLOK KELAINAN SISTEM RESPIRASI MAHASISWA KEDOKTERAN UNIVERSITAS JAMBI

Background: In the medical program of Jambi University, Lectures on pharmacology use conventional methods. Teaching-learning with the case-method can improve critical reasoning and problem-solving analysis. Objective: to develop pharmacology lectures with the case-method and receive feedback from students and lecturer. Methods: The questionnaire contains several statements with answer choices using a 5-point Linkert scale, strongly agree-strongly disagree. The post-test assessment uses vignette questions, while the CBT test scores come from study program data. Results: Most of the students accepted the application of the case-method in pharmacology lectures. Some of the benefits that are felt by students include increasing understanding of pharmacology material, helping exam preparation, and the knowledges integration in learning. There is a significant relationship between post test scores and CBT test scores (p<0.05). Conclusion: There is good acceptance of students in pharmacology lectures using the case-method. Keywords: pharmacology, medical program student, block system curiculum, case-method, case-based teaching

National Institute for Clinical Excellence and its value judgments

The National Institute for Clinical Excellence (NICE) offers health professionals in England and Wales advice on providing NHS patients with the highest attainable standards of care. NICE gives guidance on individual health technologies, the management of specific conditions, and the safety and efficacy of interventional diagnostic and therapeutic procedures. Guidance is based on the best available evidence. The evidence may not, however, be very good and is rarely complete. Those responsible for formulating the NICE’s advice therefore have to make judgments both about what is good and bad in the available science (scientific value judgments) and about what is good for society (social value judgments). In this article we focus on the scientific and social judgments forming the crux of the institute’s assessment of cost effectiveness. Scientific value judgments and those relating to clinical effectiveness are considered elsewhere

POST-ISCHEMIC TREATMENT WITH CANDESARTAN PROTECTS FROM CEREBRAL ISCHEMIC REPERFUSION INJURY IN NORMOTENSIVE RAT

Large body of evidences has indicated that the renin – angiotensin system (RAS) and its effector peptide Angiotensin II may be involved in the pathophysiology of stroke. Previous studies showed that preischemic RAS inhibition reduced brain injury but effects of post-ischemic RAS inhibition on ischemic/reperfusion injuries have not completely been elucidated. Therefore, the present study has investigated the effects of post-ischemic AT1 receptor blocked with candesartan treatment on cerebral infarction and motor function following transient focal cerebral ischemia in normotensive rats. Male normotensive rats were studied in three groups as sham, ischemic control and ischemic group which received candesartan (0.3mg/kg) at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 90 min occlusion of the left middle cerebral artery, followed by 24h reperfusion. Neurological deficit score (NDS ) evaluated at the end of the reperfusion period. Total, cortical and striatal infarct volumes were determined using TTC staining technique. Animals in sham group had normal motor function and no ischemic lesions were observed in their cortical or striatal regions. MCAO in control ischemic group produced considerable infarctions in cortex and striatum in conjunction with severe impaired motor functions. AT1 receptor blocked with candesartan significantly reduced infarct volumes in the cortex and the striatum with improvement in NDS compared to control ischemic group. In conclusion, the results of the present study indicated that AT1 receptor blocked with candesartan can decrease ischemic brain injury and improve neurological outcome

Profiles of SUMO and ubiquitin conjugation in an Alzheimer's disease model

► Global levels of ubiquitinated proteins increased in the hippocampus of Tg2576 mice. ► No global changes in either SUMO-1 or SUMO-2/3 conjugation in any brain regions analysed. ► SUMO conjugating and deconjugating enzymes, UBC9 and SENP-1, unaltered in Tg2576 mice. ► Total levels of AMPA and kainate receptors were also unaffected in Tg2576 mice. ► Posttranslational modification by ubiquitin may play a role in Alzheimer's disease

To catch a comet 2: Technical update on CAN-DO

Since the presentation of, To Catch a Comet, was given at the last G.A.S. Symposium, many events have impacted the CAN-DO Comet Halley program. This paper summarizes the changes to the payload and its mission, including improvements in camera control and CAN-DO's participation in the Halley Armada