2458 Despite dramatic improvements in treatment over the past 40 years, acute lymphoblastic leukemia (ALL) remains one of the most common causes of death from disease in childhood. Glucocorticoids are among the most effective agents used in the treatment of lymphoid malignancies, and patient response to treatment is an important determinant of long-term outcome in childhood ALL. In spite of its clinical significance, the molecular basis of glucocorticoid resistance is still poorly understood. The aim of this study was to develop an experimental model system to define clinically relevant mechanisms of glucocorticoid resistance in childhood ALL. An in vivo model of childhood ALL has been developed in our laboratory, using patient biopsies established as xenografts in immune-deficient nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice. This model is highly representative of the human disease (Lock et al., Blood, 99: 4100-4108, 2002). The in vivo responses of these xenografts to the glucocorticoid dexamethasone (DEX) correlated significantly with patient outcome (p 1 μM) in xenografts from six patients, five of whom died of their disease. In contrast, four DEX-sensitive xenografts (IC50 values 2-fold in sensitive xenografts within 8 hours of treatment. In contrast, Bim induction was dramatically attenuated in DEX-resistant xenografts. These results have identified a clinically significant and novel mechanism of glucocorticoid resistance in childhood ALL, which occurs downstream of receptor-ligand interactions, but upstream of the signalling pathway resulting in Bim induction and apoptosis.

Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.

The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

Biochemistry of oxidative stress

Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa) that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6,000 citations. In addition, over one hundred clinical studies have been carried out with curcumin. One of the major problems with curcumin is perceived to be the bioavailability. How curcumin should be delivered in vivo, how bioavailable is it, how well curcumin is absorbed and how it is metabolized, is the focus of this review. Various formulations of curcumin that are currently available are also discussed.

http://www.e-crt.org/upload/pdf/crt-46-2.pdf

Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: The golden pigment from golden spice

We investigated the effects of inhibitors of clathrin-mediated endocytosis (chlorpromazine and K(+) depletion) and of caveolae-mediated uptake (filipin and genistein) on internalization of FITC-poly-l-lysine-labeled DOTAP/DNA lipoplexes and PEI/DNA polyplexes by A549 pneumocytes and HeLa cells and on the transfection efficiencies of these complexes with the luciferase gene. Uptake of the complexes was assayed by fluorescence-activated cell sorting. Lipoplex internalization was inhibited by chlorpromazine and K(+) depletion but unaffected by filipin and genistein. In contrast, polyplex internalization was inhibited by all four inhibitors. We conclude that lipoplex uptake proceeds only by clathrin-mediated endocytosis, while polyplexes are taken up by two mechanisms, one involving caveolae and the other clathrin-coated pits. Transfection by lipoplexes was entirely abolished by blocking clathrin-mediated endocytosis, whereas inhibition of the caveolae pathway had no effect. By contrast, transfection mediated by polyplexes was completely blocked by genistein and filipin but was unaffected by inhibitors of clathrin-mediated endocytosis. Fluorescence colocalization studies with a lysosomal marker, AlexaFluor-dextran, revealed that polyplexes taken up by clathrin-mediated endocytosis are targeted to the lysosomal compartment for degradation, while the polyplexes internalized via caveolae escape this compartment, permitting efficient transfection.

Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes

Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.

https://northumbria-test.eprints-hosting.org/id/document/268389

A comprehensive review on tyrosinase inhibitors.

Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. Previously, we have successfully developed recombinant human interferon alpha 2b (rhIFNα2b) by using a synthetic gene. In addition, two mutein forms of rhIFNα2b were generated to improve the characteristics of this protein. Two point mutations showed better pharmacokinetic profiles than one point mutation as well as the native form. In the present study, this mutein form was studied for ist antitumor effect in vitro using HepG2 cells. As a comparison, the native form as well as a commercial rIFNα2b were used. Several parameters were investigated including the MTT assay, cell viability test, cell cycle using flow cytometric analysis, and the genes and protein expressions involved in cell growth. The latest was observed to study the mechanism of rhIFNα2b. There was no significant difference in the MTT assay and cell viability after cells were treated with both forms of rhIFNα2b. However, the mutein rhIFNα2b tended to show better proapoptotic activity reflected by flow cytometric data, protein expression of pSTAT1, and DNA expression of caspase 3.

/pdf/removing-a-cystein-group-on-interferon-alpha-2b-at-position-5e2h1ujmxa.pdf

Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the Protein, Even Better.

Diabetic disease is one of top ten threathening diseases requires effective therapy with high effectivenes and safety. As a chronic disease, diabetes may need long term treatment. Metformin is one of standard therapies for diabetic patients. It has serious pharmacokinetic problems: incomplete and slow absorption as well as plasma concentration fluctuation as a consequence of its narrow absorption window. The aim of this study was to develop a multiple-unit gastro retentive sustained release system of metformin hydrochloride to improve its efficacy. This system consisted of a drug core pellet prepared by extrusion-spheronization method, coated subsequently with release controller polymer (Eudragit RS PO), gas generating substance (sodium bicarbonate), and gas entrapping matrix (Eudragit RS PO and Eudragit RL PO). Coating process was performed with fluidization method. A complex combination of formula resulted in product with long resident time in the gastric via buoyancy mechanism. This formula contained 18.68 mg metformin HCl per 100 mg coated pellet, with a desirable floating lag time (<30 s), and 81.10% pellet remained floating until 8 hs. The in vitro drug release study also revealed that this formula showed the best sustained release system, with 68.16% of metformin HCl released in the gastric compartment after 8 hs.

/pdf/development-of-a-buoyancy-based-multiple-unit-gastro-17lmbcq9v2.pdf

Development of a buoyancy-based multiple-unit gastro retentive system containing metformin hydrochloride to improve antidiabetic activity

Cytokines and other biological compounds are considered as future drugs and they are of particular interest for the treatment of chronic diseases. These endogenous compounds, that normally mediate local cellular communications, are very promising candidates to generate new drugs because of their high potency (pM-nM concentrations) and their fundamental roles in pathological processes. However, the therapeutic application of cytokines is limited, because several problems are encountered with their application in vivo (Schooltink and Rose-John 2002; Standiford 2000; Vilcek and Feldmann 2004). For instance, some cytokines are efficiently degraded in plasma by various enzymes and cytokines are rapidly excreted by the kidneys. Consequently their residence time in the body and thus the exposure to the diseased cells is short (plasma half life is often minutes), which does not favour an optimal biological efficacy. Another major problem is the occurrence of side effects. Because cytokine receptors are ubiquitously expressed in all organs, unusual high plasma concentrations of the cytokine can lead to (unwanted) effects in various organs.

/pdf/modification-of-interleukin-10-with-mannose-6-phosphate-7h2dn16hp7.pdf

Modification of Interleukin-10 with Mannose-6-Phosphate Groups Yields a Liver-Specific Cytokine with Antifibrotic Activity in Rats

Perkembangan teknologi web dewasa ini sudah sangat berkembang dengan berbagai variasi bahasa pemrograman seperti PHP, Javascript, Ruby, dan lain-lain. ASP.NET adalah salah satu bahasa pemrograman web sebagai platform pengembangan web yang memiliki infrastruktur perangkat lunak yang komprehensif, serta menyediakan model dan layanan yang dapat dijalankan pada perangkat PC maupun seluler. Dalam memperkenalkan pemrograman web menggunakan ASP.NET, maka kegiatan ini memberikan pelatihan berupa dasar-dasar pemrograman untuk siswa/siswi SMAN 1 Pekanbaru. ASP.NET ini lebih mudah difahami dan dipelajari, dengan materi berupa pembuatan form, otentikasi client, validasi data, konfigurasi situs dan deployment. Kegiatan ini diawali dengan penyusunan materi berupa modul oleh dosen yang memiliki kompetensi di bidang pemrograman terutama pemrograman web, lalu penyampaian materi oleh mahasiswa dengan didampingi oleh dosen, kemudian melakukan praktik langsung dengan perintah koding yang terdapat di dalam modul. Dengan adanya pelatihan ini, siswa/siswi SMAN 1 Pekanbaru telah mengetahui konsep dasar pemrograman web dengan materi yang diberikan serta mempraktikan program web dengan keluaran output yang sesuai.

/pdf/workshop-pengenalan-pemrograman-asp-net-di-sman-3-pekanbaru-2lfwjnw2.pdf

Workshop Pengenalan Pemrograman “ASP.NET” Di SMAN 3 Pekanbaru

Curcumin, a naturally occuring polyphenolic phytoconstituent, is isolated from the rhizomes of Curcuma longa Linn (Zingiberaceae) It is water insoluble under acidic or neutral conditions but dissolves in alkaline environment In neutral or alkaline conditions, curcumin is highly unstable undergoing rapid hydrolytic degradation to feruloyl methane and ferulic acid Thus, the use of curcumin is limited by its poor aqueous solubility in acidic or neutral conditions and instability in alkaline pH In the present study, curcumin nanocrystals were prepared using high-pressure homogenization, to improve its solubility Five different stabilizers (polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), D-"-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium dodecyl sulfate (SDS), carboxymethylcellulose sodium salt) possessing different stabilization mechanism were investigated The nanoparticles were characterized with regard to size, surface charge, shape and morphology, thermal property, and crystallinity A short-term stability study was performed storing the differently stabilized nanoparticles at 4 ◦ C and room temperature PVA, PVP, TPGS, and SDS successfully produced curcumin nanoparticle with the particle size in the range of 500-700 nm PVA, PVP, and TPGS showed similar performance in preserving the curcumin nanosuspension stability However, PVP is the most efficient polymer to stabilize curcumin nanoparticle This study illustrates that the developed curcumin nanoparticle held great potential as a possible approach to improve the curcumin solubility then enhancing bioavailability © 2012 Wiley Periodicals, Inc and the American Pharmacists Association J Pharm Sci 102:204-214, 2013

Heni Rachmawati

Papers

Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the Protein, Even Better.

Development of a buoyancy-based multiple-unit gastro retentive system containing metformin hydrochloride to improve antidiabetic activity

Modification of Interleukin-10 with Mannose-6-Phosphate Groups Yields a Liver-Specific Cytokine with Antifibrotic Activity in Rats

Workshop Pengenalan Pemrograman “ASP.NET” Di SMAN 3 Pekanbaru

Pharmaceutical Nanotechnology Development of Curcumin Nanocrystal: Physical Aspects