The synthesis and study of multimetallic Platinum Group Metal complexes as in vitro phamacological agents

Includes bibliographical references.The success of cisplatin and its analogues for the treatment of different cancers has had a profound effect on establishing the application of metal complexes in medicine. Lately, increasing drug resistance and the emergence of unwanted side effects to currently available therapies have bred a need for novel pharmacological agents. Thus, the design and study of organometallic complexes as potential chemotherapeutics may potentially identify new drug candidates. Apart from platinum based compounds, platinum-like metals such as ruthenium(II), rhodium(III) and iridium(III), have been identified as biologically relevant metals. The purpose of this study is to synthesize three classes of polynuclear complexes containing metals from the Platinum Group Metal (PGM) series and evaluate each class for pharmacological activity in vitro. Each complex class is based on a different ligand type. New mono- and polynuclear organometallic Platinum Group Metal (PGM) complexes based on three ligand classes have been synthesised and characterised using several analytical and spectroscopic techniques including 1H, 13C and 31P NMR, infrared and UV-vis spectroscopy. The first complex series is based on the thiourea containing ligand, 3,4-dichloroacetophenonethiosemicarbazone, which has demonstrated in vitro pharmacological activity. This ligand was reacted with K2[PtCl4] to afford a tetranuclear cycloplatinated thiosemicarbazone complex (2.2). Reaction of 2.2 with different mono- and diphosphanes yielded two mono- and three dinuclear Pt(II) thiosemicarbazone ligands (2.3-2.7). In all of the complexes (2.2-2.7), the thiosemicarbazone ligands act as a dinegative tridentate [C,N,S] donor to each metal centre. Single crystal X-ray analyses of three of the complexes in this series, including the tetraplatinum derivative, confirmed the structural integrity of these complexes. Reactivity studies of the mononuclear platinum(II) complexes revealed that one complex is able to undergo oxidative addition reactions with different aryl iodide substrates. In vitro pharmacological studies of a selection of these complexes as antiparasitic agents have been carried out against the P. falciparum strains, D10 (cisplatin sensitive) and Dd2 (cisplatin resistant)) and Trichomonas vaginalis T1. Their cytotoxic effects on the A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian carcinoma cell line has also been determined. All of the complexes demonstrated moderate cytotoxic effects as antiparasitics and antitumor agents. No correlation between the number of platinumthiosemicarbazone moieties and pharmacological activity could be discerned. Instead, the type of ancillary ligand used to prepare each complex may influence the lipophilic nature of each complex thus explaining the trend observed

The elements of life and medicines

Which elements are essential for human life? Here we make an element-by-element journey through the periodic table and attempt to assess whether elements are essential or not, and if they are, whether there is a relevant code for them in the human genome. There are many difficulties such as the human biochemistry of several so-called essential elements is not well understood, and it is not clear how we should classify elements that are involved in the destruction of invading microorganisms, or elements which are essential for microorganisms with which we live in symbiosis. In general, genes do not code for the elements themselves, but for specific chemical species, i.e. for the element, its oxidation state, type and number of coordinated ligands, and the coordination geometry. Today, the biological periodic table is in a position somewhat similar to Mendeleev's chemical periodic table of 1869: there are gaps and we need to do more research to fill them. The periodic table also offers potential for novel therapeutic and diagnostic agents, based on not only essential elements, but also non-essential elements, and on radionuclides. Although the potential for inorganic chemistry in medicine was realized more than 2000 years ago, this area of research is still in its infancy. Future advances in the design of inorganic drugs require more knowledge of their mechanism of action, including target sites and metabolism. Temporal speciation of elements in their biological environments at the atomic level is a major challenge, for which new methods are urgently needed

Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice

<p>Abstract</p> <p>Background</p> <p>Short half-life and low levels of growth factors in the niche of injured microenvironment necessitates the exogenous and sustainable delivery of growth factors along with stem cells to augment the regeneration of injured tissues.</p> <p>Methods</p> <p>Here, recombinant human hepatocyte growth factor (HGF) was incorporated into chitosan nanoparticles (CNP) by ionic gelation method and studied for its morphological and physiological characteristics. Cirrhotic mice received either hematopoietic stem cells (HSC) or mesenchymal stemcells (MSC) with or without HGF incorporated chitosan nanoparticles (HGF-CNP) and saline as control. Biochemical, histological, immunostaining and gene expression assays were carried out using serum and liver tissue samples. One way analysis of variance was used for statics application</p> <p>Results</p> <p>Serum levels of selected liver protein and enzymes were significantly increased in the combination of MSC and HGF-CNP (MSC+HGF-CNP) treated group. Immunopositive staining for albumin (Alb) and cytokeratin 18 (CK18), and reverse transcription-polymerase chain reaction (RT-PCR) for Alb, alpha fetoprotein (AFP), CK18, cytokeratin 19 (CK19) ascertained that MSC-HGF-CNP treatment could be an effective combination to repopulate liver parenchymal cells in the liver cirrhosis. Zymogram and western blotting for matrix metalloproteinases 2 and 9 (MMP2 and MMP9) revealed that MMP2 actively involved in the fibrolysis of cirrhotic tissue. Immunostaining for alpha smooth muscle actin (αSMA) and type I collagen showed decreased expression in the MSC+HGF-CNP treatment. These results indicated that HGF-CNP enhanced the differentiation of stem cells into hepatocytes and supported the reversal of fibrolysis of extracellular matrix (ECM).</p> <p>Conclusion</p> <p>Bone marrow stem cells were isolated, characterized and transplanted in mice model. Biodegradable biopolymeric nanoparticles were prepared with the pleotrophic protein molecule and it worked well for the differentiation of stem cells, especially mesenchymal phenotypic cells. Transplantation of bone marrow MSC in combination with HGF-CNP could be an ideal approach for the treatment of liver cirrhosis.</p

Masālik al-ʿillah in the convention of qiyās: An investigation of its foundations and contemporary Application

Magister Artium - MAThis study examines the foundations of the various methods of identifying legal cause (masālik al-ʿillah). It studies its various theories, spanning the classical and premodern period and investigates its application in contemporary times. The investigation analyses the theories of masālik al-ʿillah while placing the legal cause (ʿillah) contextually within the convention of analogical reasoning (qiyās). The findings of this investigation are then used to study practical applications of identifying legal cause, in a selection of three case constructions of qiyas, under the topic of suicide attacks

Synthesis, characterization, biological and catalytic studies of tridentate monothiosemicarbazone palladium (II) complexes

Includes abstract.Includes bibliographical references.Nine monothiosemicarbazone ligands were prepared by Schiff-base condensation reactions of thiosemicarbazide and the appropriate aryl aldehyde or ketone. These compounds were isolated as air- and moisture- stable solids and were characterized using NMR and IR spectroscopies, as well as mass spectrometry and elemental analysis in the case of ligand 3-terl.-butyl-2-hydroxy-benzaldehyde thiosemicarbazone, which is a new compound. Four of these ligands were reacted with precursors of type Pd(L)2CI2 yielding eight tridentate thiosemicarbazone Pd(II) complexes with general formula [Pd( 3-0,N,Sthiosemicarbazone)(L)] (L = PPh3 or 4-picoline). Six of these complexes are new compounds and were fully characterized using NMR and IR spectroscopies, mass spectrometry and elemental analysis. In addition, the solid state structures of three complexes were elucidated using single crystal X-ray diffraction methods

Implications of antimicrobial combinations in complex wound biofilms containing fungi

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while mono-treatment approaches influenced biofilm composition it had no discernible effect on overall quantity. Only by combining bacterial and fungal specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition

An investigation into a lower temperature and low cost direct reduction process for iron-making.

Thesis (M.Sc.Eng.)-University of Natal, Durban, 2003.The blast furnace process for the reduction of iron ore to pig iron faces problems such as emission of air pollutants, high investment cost and the current major problem of decreasing supplies of coke. Coke is used in large quantities to promote a combination of direct and indirect reduction within the furnace. Due to the lack of good coking coal within South Africa, and dwindling supplies worldwide, new iron-making processes, are being developed using coal and/or natural gas to replace coke as the reductant. The new processes allow efficient use of carbon, fed in the form of coal pellets (coalbased processes) or natural gas (gas-based processes), as the reducing agent. Presently, most coal-based processes Use an excess of coal, up to 500% stoichoimetric addition, and are run at temperatures up to ±1200°C, although reduction tends to proceed at ±850°C. This project developed a low temperature process using mixed pellets of fine waste iron oxide and fine domestic coal with a natural carbonaceous binder (a by-product from local pulping industry). Reduction tests performed on composite pellets in a tube furnace and thermobalance indicated, upon analysis by X-Ray Diffraction and Scanning Electron Microscope, that reduction occurred gradually at 900°C. Implementing induction heating of bulk pellets reduced heating times substantially. Induction heating also resulted in direct reduced iron [DRI] containing 75 - 80% metallic iron. Energy consumption based on coal usage amounted to 23.71 GJ/ton DRI, which compares with the calorific consumption of most coal-based processes, i.e. coal consumption range between 15 and 25 GJ/ton DRI. Energy consumed during induction heating amounted to 9.94 GJ/ton DRI, as electricity. This energy consumption value does not take into account the efficiency of the primary energy required to generate electricity

EXTRACELLULAR BIOFABRICATION OF SILVER AND GOLD NANOPARTICLES: TREASURES FROM THE ABYSSAL ZONE

The synthesis of nanoparticles can be accomplished by physical, chemical and biological strategies. Since this has become an expanding area of research in the field of medical sciences and Technology, owing to its potential applications, the need for eco-friendly, non-toxic and economical methods of synthesis have arisen. Biosynthesis of nanoparticles have become the main field of research as it is time efficient, cost effective, less toxic and has abundant resource. This review emphasizes on the biosynthesis of gold (Au) and silver nanoparticles (AgNPs) using marine sources with special reference to algae, their characterisation and its applications. The characterisation of metal nanoparticles is an essential step and can be carried out by various instruments. The various pharmacological, electrical, pest management, parasitology and medical applications of these marine source induced synthesis of nanoparticles have also been portrayed in this review.Â

An audit tool for relicensing inspection for private hospitals in eThekwini district, South Africa

Background: South Africa is moving towards National Health Insurance (NHI), which aims to provide access to universal health coverage for all South Africans. The NHI will only accredit and contract eligible health facilities that meet nationally approved quality standards in the public and private sector. Detailed tools for measuring compliance with the National Core Standards (NCS) and Batho Pele principles have been developed and implemented in the public sector. To date and since its implementation in the public sector, very little is known about the national audit tool and the method used to evaluate quality and patient safety standards in private hospitals in eThekwini district. Objective: The aim of the study was to develop an audit tool for relicensing inspection of private hospitals in eThekwini district based on the clinical domains of the NCS and Batho Pele principles. Methodology: An exploratory sequential mixed method research design was used with a qualitative first phase involving 24 nurse managers through purposive sampling. This was followed by a quantitative phase in which a structured questionnaire was administered to 270 nurses who were randomly sampled for the study from 4 hospitals. Results: The results revealed that the NCS and the Batho Pele principles are not fully implemented or evaluated in the selected hospitals in eThekwini district. Conclusion: These findings were significant and denoted the need for a standardised clinical audit tool for private hospitals in eThekwini district