A COMPREHENSIVE REVIEW ON COMPARISON OF GDOCP IN PHARMACEUTICAL MANUFACTURING UNIT AS PER EUROPEAN AND WHO GUIDELINES

To review the good documentation practices in the pharmaceutical industry as per the guidelines provided in the European Commission and WHO (World Health Organisation). GDocP is a systematic method of planning, evaluating, approving, issuing, documenting, preserving, and archiving records. GDocP is a must when operating in an atmosphere of existing GMP. To provide an overview of good documentation practices for those employed in the pharmaceutical and healthcare sectors. The GDocP stands for good documentation practice which can be described as an integral part of quality assurance (QA) and thus related to all aspects of GMP. There are very few articles related to the comparison of GDocP in the pharmaceutical manufacturing unit as per European and WHO guidelines hence we are trying to develop a study on the comparison of GDocP guidelines. Public and private organizations, institutions, and regulatory authorities working and cooperating and with the pharmaceutical industry are involved at the international and national level to reach a consensus on the guidelines and laws for the production of medicinal products for human. This article explains how these participants work and cooperate and set out current regulations along the lines of the European community and WHO referencing, where appropriate, the practiced guidelines, outside space regulatory action referred to above. In this way, the goal is to achieve exceptional standards of quality, protection, and efficacy in the manufacture of health products

Ekstrak Enzim Protease dari Daun Palado (Agave Angustifolia) dan Pemanfaatannya dalam Proses Pembuatan Virgin Coconut Oil

Virgin coconut oil (VCO) can be made in several ways, namely through a heating process at low temperature, freeze-drying, fermentation, enzymatic, mechanical pressure or centrifugation. VCO with an enzymatic method is the making of VCO fromcoconut milk by using enzyme. The protein-oil bonds in the emulsions in coconut milk can be broken down into protease enzyme. The purpose of this research is to extract the protease enzyme in palado leaves and utilize the enzymes in the manufacturing process as well as determining the quality of VCO. This research method passed through some processes. Firstly enzyme extracts from palado leaves are prepared and coconut milk from coconut cream is made, then it is tested qualitatively the presence of protease enzyme with ninhydrin color reagent. Furthermore, the making of VCO enzymatically is undertaken by varying the ratio of the volume of coconut cream and enzyme extracts of 24 hours. VCO quality is analysis by using the parameters of smell, flavor, color, moisture content, levels of FFA (free fatty acid) and peroxide. The testing result with ninhydrin reagent gave a positive reaction (blue-purple) showing that there is enzymes alleged a class of protease in the palado leaf. The result of VCO made with the comparison of coconut cream and enzyme extracts from palado (10 : 1) has generate a VCO with a yield of 25.4%. However, from the analysis of VCO quality test results, it is obtained the smell of distinctive flavor oils, fragrance, the clean color, water content of 0.5% , FFA content of 0.25% and the peroxide number of 0 meq/kg

The Matrix: Reviewing, Re-ordering and Regenerating Undergraduate Provision for post-2012.

The University of Hull’s Faculty of Education has provision split across two campuses: Teacher Education and Education Studies. With the approach of 2012 funding process the Head of Education Studies requested a review of undergraduate degrees in Education Studies (non QTS) with the overall aim of providing a more efficient, effective and integrated undergraduate provision. Specific objectives were to develop UG provision to ensure that we: Strengthened cross campus working; Minimised competition between campuses ; Maximised good practice; Shared expertise (administrative as well as academic); Supported strategies for internationalisation and the development of Technology Enhanced Learning. This paper reports on the process of review and specifically on the work undertaken by the Chair of the Review Panel, Dr. Ken Spencer, in developing a matrix of modules that allowed for a comparison of provision. The instrument he developed not only catalogued the 140+ modules that were in existence for UG degree programmes (and provided direct access to module specifications via URL links), but also entered module provision into a matrix through use of a spreadsheet that allowed the provision to be sorted and compared through use of many variables. As a consequence the review team were not only able to analyse the viability of the provision, but were also in a position to advise the development team of priorities. This paper will allow BESA delegates to see the matrix in action and evaluate the applicability of such an approach for their own use

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

Expression of chemokines and their receptors by human brain endothelium: Implications for multiple sclerosis

Leukocyte migration into the CNS is mediated by chemokines, expressed on the surface of brain endothelium. This study investigated the production of chemokines and expression of chemokine receptors by human brain endothelial cells (HBEC), in vitro and in situ in multiple sclerosis tissue. Four chemokines (CCL2, CCL5, CXCL8 and CXCL10), were demonstrated in endothelial cells in situ, which was reflected in the chemokine production by primary HBEC and a brain endothelial cell line, hCEMC/D3. CXCL8 and CCL2 were constitutively released and increased in response to TNF and/or IFN . CXCL10 and CCL5 were undetectable in resting cells but were secreted in response to these cytokines. TNF strongly increased the production of CCL2, CCL5 and CXCL8, while IFN up-regulated CXCL10 exclusively. CCL3 was not secreted by HBECs and appeared to be confined to astrocytes in situ. The chemokine receptors CXCR1 and CXCR3 were expressed by HBEC both in vitro and in situ, and CXCR3 was up-regulated in response to cytokine stimulation in vitro. By contrast, CXCR3 expression was reduced in silent MS lesions. Brain endothelium expresses particularly high levels of CXCL10 and CXCL8, which may account for the predominant TH1-type inflammatory reaction seen in chronic conditions such as multiple sclerosis

Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood–Brain Barrier Both in Vitro and in Vivo

Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood–brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with nonpsychotropic cannabinoids as pioneering nonimmunogenic brain-targeting molecules and to the evaluation of their brain-targeting ability both in vitro and in vivo. Noticeably, both the permeability experiments across the hCMEC/D3 cell-based in vitro BBB model and the biodistribution experiments in mice consistently demonstrated that the highest brain-targeting ability was achieved with the smallest-sized cannabinoid-decorated LNCs. Importantly, the enhancement in brain targeting achieved with the conjugation of cannabidiol to LNCs outperformed by 6-fold the enhancement observed for the G-Technology (the main brain active strategy that has already entered clinical trials for the treatment of CNS diseases). As the transport efficiency across the BBB certainly determines the efficacy of the treatments for brain disorders, small cannabinoid-decorated LNCs represent auspicious platforms for the design and development of novel therapies for CNS diseases

Structural Properties, Cytotoxicity, and Anti-Inflammatory Activity of Silver(I) Complexes with tris(p-tolyl)Phosphine and 5-Chloro-2-Mercaptobenzothiazole

The synthesis and characterization of the silver(I) chloride complex of formula {[AgCI(CMBZT)(TPTP)2] · (MeOH)} (1) (CMBZT = 5-chloro-2-mercaptobenzothiazole, TPTP = tris(p-tolyl)phosphine) is described. Also the structure of the hydrate derivative {[AgCI(TPTP)3] · (0.5 · H2O)} (2) of the corresponding known anhydrous silver complex (Zartilas et al., 2009), and the polymorph 3 of the known [AgI(TPTP)3] complex (Zartilas et al., 2009) were determined and compared with the known ones. In addition, the structure of the known one silver(I) cluster {[AgI(TPTP)]4} (4) (Meijboom et al., 2009) was re-determined at 120(2) K and possible Ag-Ag interactions were analyzed. The compounds 1–4 were characterized by X-ray crystallography at r.t (1) and 120 K (2–4). All these complexes and {[(Et3NH)+]2 · [Ag6(μ3-Hmna)4(μ3-mna)2]2− · (DMSO)2 · (H2O)} (5) (Hmna = 2-mercaptonicotinic acid) were evaluated for cytotoxic and anti-inflammatory activity. The in vitro testing of cytotoxic activity of 1–5 against leiomyosarcoma cancer cells (LMS), were evaluated with Trypan Blue and Thiazolyl Blue Tetrazolium Bromide or 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assays. The flow cytometry assay for complex 1 and showed that at 15 μM of 1, 62.38% of LMS cells undergo apoptosis, while 7% of LMS cells undergo cell necrosis. The antitumor activity of 3 is comparable with that of its reported polymorph (Zartilas et al., 2009). The anti-inflammatory, activity of complexes 1–3 and 5 was also studied. The activity towards cell viability was 2 > 3 > 5 > 1 > 4, while the order of the inhibitory activity in cell growth proliferation follows the order, 2 > 3 > 1 > 4 > 5. The anti-inflammatory activity on the other hand is 1 > 2 > 5 > ⋯ >3

Chemokine transport across human vascular endothelial cells

Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP]-1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface