Gisela K. Jooné
University of Pretoria
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Zeitschrift für Naturforschung C | 2003
Gisela K. Jooné; Johan Dekker; Constance Elizabeth Jansen van Rensburg
A unique process has been developed to convert bituminous coal by controlled wet oxidation followed by base treatment to a water-soluble humate called oxihumate. The effects of oxihumate on the proliferative response of lymphocytes has been studied in vitro and ex vivo. Oxihumate increased the proliferative response of phytohaemagglutinin-stimulated human lymphocytes, from a concentration of 20 μg/ml and upwards. This response was even more striking in the case of lymphocytes from HIV-infected patients and was not limited to the in vitro setting since similar effects were observed ex vivo following administration of a nontoxic dosage of 4 g oxihumate per day to HIV-positive individuals for two weeks. Mechanistic studies revealed that stimulation of the proliferative response of lymphocytes by oxihumate is associated with an increased production of IL-2, as well as expression of the IL-2 receptor in the setting of decreased production of IL-10. Oxihumate therefore holds promise for the treatment of immunocompromized patients.
Inflammation | 2004
Gisela K. Jooné; Constance Elizabeth Jansen van Rensburg
In this study the anti-inflammatory potential of potassium humate, derived from bituminous coal, has been investigated in vitro. Exposure of resting and phorbol-12-myristate-13-acetate (PMA) stimulated human neutrophils to potassium humate resulted in a decreased expression of CR3 by activated, but not resting cells, in a dose-related way. Humate also inhibited the adhesion of PMA-stimulated neutrophils to a baby hamster kidney cell line expressing ICAM1 (the CR3 ligand) (BHK331-7). Similar results were obtained using normal BHK cells indicating that this inhibition does not only target specific adhesion molecules on the neutrophil and eosinophil membrane by activated phagocytes, but also affects other mechanisms involved in cell adhesion. Opsonised Sephadex or FMLP/Cyto B-induced degranulation of neutrophils and eosinophils were also decreased by humate treatment. Inhibition of the adhesion of activated phagocytes, as well as inhibition of the release of granule polypeptides, both of which are responsible for tissue damage during inflammatory processes, are attractive targets for anti-inflammatory drugs. Because humate is well tolerated with an excellent safety profile it merits further evaluation in patients suffering from inflammatory conditions.
Dalton Transactions | 2011
Jacorien Coetzee; Stephanie Cronje; Liliana Dobrzańska; Helgard G. Raubenheimer; Gisela K. Jooné; Margo Nell; Heinrich C. Hoppe
Ylideneamine functionalised heterocyclic ligands, 1,3-dimethyl-1,3-dihydro-benzimidazol-2-ylideneamine (I), 3-methyl-3H-benzothiazol-2-ylideneamine (II) or 3,4-dimethyl-3H-thiazol-2-ylideneamine (III), were employed in the preparation of a series of both charged and neutral gold(I) complexes consisting either of a Au(C(6)F(5)) fragment (1-3), a [Au(PPh(3))](+) unit (4-6) or a [Au(NHC)](+) unit (7) coordinated to the imine nitrogen of the neutral ylideneamine ligand. These complexes were fully characterised by various techniques including X-ray diffraction. In addition, the antitumour and antimalarial potential of selected compounds were assessed in a preliminary study aimed at determining the medicinal value of such compounds. Complexation of the azol-2-ylideneamine ligands with [Au(PPh(3))](+) increases their antitumour as well as antimalarial activity.
Journal of Inorganic Biochemistry | 2012
Ulrike E. I. Horvath; Liliana Dobrzańska; Christoph E. Strasser; Wilna Bouwer; Gisela K. Jooné; Constance Elizabeth Jansen van Rensburg; Stephanie Cronje; Helgard G. Raubenheimer
A series of new neutral mononuclear or dinuclear gold(I) complexes and a cyclic cationic tetranuclear amidogold(I) complex comprising of the phosphines 1,2-bis(dimethylphosphino)ethane (dmpe), μ-1,2-bis(diphenylphosphino)ethane (dppe), μ-1,3-bis(diphenylphosphino)propane (dppp), μ-1,5-bis(diphenylphosphino)pentane (dpppe), μ-1,6-bis(diphenylphosphino)hexane (dpph) or trimethylphosphine, and several N-heterocyclic ring systems (imidazolate, pyrazolate, 1,2,3-triazolate, 1,2,4-triazolate, pyrrolate, 9H-purine-9-ate or 9H-purine-6-amine-9-ate) as ligands, reveal intermolecular aurophilic interactions and 2D channels available for solvent molecules in some of their crystal structures. The antitumour activity of the acyclic gold(I) compounds is highly dependent on the substituents on the phosphorus atoms being highest for phenyl groups and lower for methyl groups. The activity of these compounds against selected cell lines is linked to the length of the carbon bridge between the two phosphorus atoms being highest with a bridge consisting of 5 or 6 carbons. Two compounds with the highest tumour specifities that contain dpppe and pyrazolate (a lipophilic compound) or 1,2,4-triazolate (a hydrophilic compound) induce an apoptotic cell death pathway and a maximum dose to Balb/C mice is tolerated.
Cancer Letters | 1998
Constance Elizabeth Jansen van Rensburg; Gisela K. Jooné; Ronald Anderson
The effects of the membrane-stabilizing agent, alpha-tocopherol (25 microg/ml), on the chemosensitizing interactions of cyclosporin A (5 microg/ml), verapamil (2 microg/ml), clofazimine (1 microg/ml), B669 (0.5 microg/ml) and GF120918 (0.015 microg/ml) with a P-glycoprotein-expressing human lung cancer cell line (H69/LX4) have been investigated in vitro. In an assay of cell proliferation, all the chemosensitizing agents restored the sensitivity of H69/LX4 cells to doxorubicin and vinblastine. The inclusion of alpha-tocopherol (25 microg/ml) antagonized the multidrug-resistance (MDR)-modifying activity of all five chemosensitizing agents, effectively preventing restoration of sensitivity to both doxorubicin and vinblastine in H69/LX4 cells.
Chemotherapy | 1993
Ronald Anderson; Gisela K. Jooné
In this study the intraphagocytic bioactivities of the new fluoroquinolone antimicrobial agents clinafloxacin (CI-960) and PD 131628 (the active metabolite of CI-990) were investigated in vitro at final concentrations of 0.0005-0.5 microgram/ml using human neutrophils and the combination of a radiometric and a colony-counting method, which enabled us to distinguish between intracellular bacteriostatic and bactericidal mechanisms. Ciprofloxacin was included for comparison. Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) were used as the test intraphagocytic microbial pathogens. Clinafloxacin (> or = 0.05 microgram/ml) displayed potent intraphagocytic bactericidal activity against S. aureus, while PD 131628 was merely bacteriostatic. Ciprofloxacin displayed relatively unimpressive bacteriostatic rather than bactericidal activity for S. aureus. Against E. coli, the intraphagocytic activity of clinafloxacin (0.001-0.005 microgram/ml and above) was superior to that of PD 131628 or ciprofloxacin, which were approximately equipotent. Clinafloxacin is a potent intraphagocytic bactericidal agent for both gram-positive and gram-negative bacteria.
Chemotherapy | 1989
C.E.J. van Rensburg; Gisela K. Jooné; Ronald Anderson
In this study the intraphagocytic bioactivity of difloxacin, ciprofloxacin, pefloxacin and fleroxacin was investigated using human neutrophils and a combination of a radioassay, a colony-counting method and a fluorescence microassay which enables us to differentiate between intracellular bacteriostatic and bactericidal mechanisms. Staphylococcus aureus and Listeria monocytogenes were used as the test intraphagocytic microbial pathogens. It was found that difloxacin, ciprofloxacin and to a lesser extent pefloxacin and fleroxacin possess intracellular bacteriostatic activity for S. aureus and L. monocytogenes.
Chemotherapy | 1995
C.E.J. van Rensburg; Gisela K. Jooné; Ronald Anderson
In this study the intracellular bioactivity of ciprofloxacin and the new fluoroquinolone agents clinafloxacin (CI-960) and PD 131628 against Mycobacterium tuberculosis (H37Rv) was compared with rifampicin using human macrophages. Monocyte-derived macrophages were infected with M. tuberculosis in the presence of 10% autologous serum and treated with the antibiotics for 2 days, either immediately after infection or 3 days post-infection. The survival of the intracellular microorganisms was determined using the BACTEC tuberculosis system. Clinafloxacin, although not as active, compared favourably with rifampicin at concentrations ranging from 0.1 to 5 micrograms/ml in both systems, whereas PD 131628 performed reasonably well only when added directly after infection. However, ciprofloxacin was relatively unimpressive with intracellular bioactivity detected only with the highest concentration used (5 micrograms/ml). The ability of clinafloxacin, but not PD 131628, to inhibit mycobacteria after most of the organisms have escaped from the fused phagosomes emphasizes the importance of using a prolonged incubation time after infection when screening new antituberculosis drugs for intracellular bioactivity.
BMC Microbiology | 2014
Ian P Olwoch; Oppel B W Greeff; Gisela K. Jooné; Vanessa Steenkamp
BackgroundPectinex Ultra SP-L (Pectinex) is a microbial-derived enzyme that is used in the food industry and that has been shown to inhibit bacterial biofilms. It has been suggested that Pectinex may be useful in the management of biofilm-related bacterial infections and therefore warrants further investigation in this regard. The aim of this study was to investigate the cytotoxicity of Pectinex on cervical adenocarcinoma cells (HeLa), lymphocytes and neutrophils. Cell viability and morphology were assessed using an in vitro spectrophotometric MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay and polarization-optical transmitted light differential interference contrast microscopy. This study also investigated the antibacterial and antibiofilm actions of Pectinex, alone and in combination with antibiotics, on standard and clinical cultures of Staphylococcus aureus and Pseudomonas aeruginosa. Minimum inhibitory (MIC) and bactericidal (MBC) concentrations were determined using p-iodo-nitrotetrazolium violet staining of bacterial cultures and regrowth of subcultures. Biofilm biomass and cell viability were quantified spectrophotometrically after staining with crystal violet and MTT.ResultsThe IC50 (±SEM) of Pectinex was 193.9 (±22.2) PGU/ml for HeLa cells, 383.4 (±81.5) and 629.6 (±62.8) PGU/ml for fMLP-stimulated and non-stimulated lymphocytes respectively, and 245.9 (±9.4) and 529.7 (±40.7) PGU/ml for fMLP-stimulated and non-stimulated neutrophils, respectively. Induced morphological features characteristic of apoptosis and necrosis included cell membrane blebs and vacuolization in HeLa cells, clumping in lymphocytes, as well as shrunken rounded cells, apoptotic bodies and debris in all cultures. Pectinex (7.42 – 950 PGU/ml−1) was not bactericidal. In clinical cultures of Staphylococcus aureus, co-administration of Pectinex was associated with a 28.0% increase in both the MIC and MBC of amoxicillin-clavulanate. In clinical cultures of P. aeruginosa, there was an 89.0% and 92.8% increase in the MIC and MBC of ciprofloxacin, respectively. Pectinex≤118.75 PGU/ml−1 and incubation periods≤6 h were associated with increased biomass and cell viability in S. aureus or P. aeruginosa biofilms.ConclusionsPectinex appeared to antagonize the antibacterial effects of amoxicillin-clavulanate and ciprofloxacin and furthermore demonstrated significant cytotoxicity. It was therefore deemed unsuitable for the management of either planktonic or biofilm phenotypes of S. aureus or P. aeruginosa.
Journal of Antimicrobial Chemotherapy | 1988
Ronald Anderson; Gisela K. Jooné; Constance Elizabeth Jansen van Rensburg