Browsing by Author "Van Zyl, A."

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    The control of peroxidase-catalysed iodination and de-iodination
    (Health & Medical Publishing Group, 1981) Van Zyl, A.; Burger, B.; Rossouw, P.; Wilson, B.
    It has been demonstrated that the H2O2/l- ratio is a critical factor in the control of iodination and deiodination of covalently bound tyrosyl residues in proteins and free iodotyrosines by peroxidase enzymes. This has been shown for myeloperoxidase (MPO) isolated from normal human polymorphonuclear lymphocytes in particular, and also for peroxidases of animal origin such as thyroid peroxidase (TPO) and lactoperoxidase (LPO). It has also been shown that the H2O2/l ratio exerts a controlling influence on MPO-catalysed reactions of fully iodinated tyrosines, e.g. di-iodotyrosine, and of partially and completely iodinated thyronines such as thyroxine and tri-iodothyronine. Using an in vivo model system it has been shown that MPO catalyses the sequential events of iodination, iodine exchange and de-iodination of tyrosines and, furthermore, that all three reactions are influenced by the rate of H2O2 generation and the iodide concentration of the reaction medium. The action of MPO on iodothyronine substrates only affects de-iodination irrespective of whether the iodothyronine is partially iodinated, as in triiodothyronine, or completely iodinated, as in thyroxine. This MPO-catalysed de-iodination of thyroxine and tri-iodothyronine can also be regulated by the H2O2/l- ratio. Moreover, the results show that MPO-catalysed iodine exchange can only occur in completely iodinated tyrosines such as diiodotyrosine (DIT). Iodine exchange in partially iodinated tyrosines such as mono-iodotyrosine (MIT) or in iodothyronines (T3 and T4) cannot be catalysed by MPO irrespective of the H2O2/l- ratio. These results introduce a new concept which may be important in understanding the control of thyroid activity in thyroid disease and the control of MPO activity in biological defence mechanisms in man.
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    The cost of nephroblastoma treatment in South Africa : a very cost-effective investment with guidelines for the rest of Africa
    (Health & Medical Publishing Group, 2014-11-13) Stefan, Daniela Cristina; Stones, D. K.; Van Zyl, A.; Uys, R.
    Background. Nephroblastoma is one of the most common childhood malignancies in Africa, but with a survival rate significantly lower than in developed countries. In African countries with a small gross domestic product (GDP) per capita, the cost of treating nephroblastoma may be prohibitive. Objectives. To determine the direct costs of treatment of nephroblastoma in South Africa (SA) and to propose a more cost-effective approach to investigations and treatment for the disease in Africa. Methods. Data from 2000 - 2010 from two SA paediatric oncology units were retrospectively analysed. The costs included investigations, chemotherapy and radiotherapy, comparing early-v. advanced-stage disease. In both units, the nephroblastoma International Society of Paediatric Oncology (SIOP) protocol was used. Results. Stage I disease was the most common, followed by stage IV. The total cost of diagnosis, staging and treatment of stage I disease was ZAR9 304.97 (EUR882.80 or USD1 093.40), compared with a five-times higher cost for stage IV (ZAR48 293.62 (EUR4 581.9 or USD5 674.9)). Treating one patient averted more than 32 disability adjusted life years. The investigation and treatment of early- and advanced-stage disease is very cost-effective when compared with the local GDP per capita. Conclusion. The cost of investigation and treatment of nephroblastoma remains a challenge everywhere, but especially in Africa. However, it is a very cost-effective disease to treat and children in Africa should not be denied treatment.
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    Cystic partially differentiated nephroblastoma-like lesion following neoadjuvant chemotherapy for nephroblastoma : a case report and review of the literature
    (Elsevier, 2020) Bruce-Brand, C.; Reyes-Mugica, M.; Van Zyl, A.; Schubert, P. T.
    Cystic partially differentiated nephroblastoma (CPDN) and cystic nephroblastoma are paediatric renal tumours characterised by the presence of a variable combination of primitive epithelium, immature stroma and blastema. Cystic nephroblastoma can be identified by the presence of solid expansile areas of tumour which are absent in CPDN. The distinction can pose diagnostic difficulty pre-operatively and is of paramount importance as their metastatic potential, prognosis and hence therapeutic strategies differ. We present a 2 year old girl, with two right renal masses, diagnosed pre-operatively as synchronous nephroblastoma based on clinical, radiological and cytologic findings. Neo-adjuvant chemotherapy was administered followed by nephrectomy. Two discrete tumours were present, one being an epithelial predominant nephroblastoma and the other a CPDN. The CPDN showed an unusual spectrum of epithelial cells lining the cysts including intestinal type epithelium with goblet cells. This case represents one of three cases described thus far in the literature of concomitant nephroblastoma and CPDN or cystic nephroma (CN) and is the only case in which nephroblastoma occurred synchronously with CPDN. Due to neo-adjuvant therapy being instituted for the nephroblastoma, this case provides unique insights into possible chemotherapy induced changes in a CPDN (usually treated by surgical excision alone). This case highlights several important issues in paediatric cystic renal neoplasms, particularly the distinction between cystic nephroma, CPDN and cystic nephroblastoma. The differential diagnosis of cystic paediatric renal neoplasms is broad and requires appropriate clinical, radiological and histological assessment, often with ancillary immunohistochemical and molecular studies to arrive at a correct diagnosis. Histologic features of chemotherapy effect, although well-described in nephroblastoma, are not well-described in CPDN. Based on our knowledge of possible chemotherapy induced changes in nephroblastoma, such as maturation of epithelial and stromal elements that may be so marked as to mimic mature teratoma, we hypothesize that this case demonstrates such changes within a CPDN.
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    The evaluation of the applicability of Fourier Transform Near-Infrared (FT-NIR) spectroscopy in the measurement of analytical parameters in must and wine
    (South African Society for Enology and Viticulture, 2001) Manley, M.; Van Zyl, A.; Wolf, E. E. H.
    Fourier transform near-infrared (FT-NIR) spectroscopy can be used as a rapid method to measure the percentage of sugar and to discriminate between different must samples in terms of their free amino nitrogen (FAN) values. It can also be used as a rapid method to discriminate between Chardonnay wine samples in terms of their malolactic fermentation (MLF) status. By monitoring the conversion of malic to lactic acid, the samples could be classified on the basis of whether MLF has started, is in progress or has been completed. Furthermore, FT-NIR spectroscopy can be used as a rapid method to discriminate between table wine samples in terms of their ethyl carbamate (EC) content. It is claimed that high concentrations of ethyl carbamate in wine can pose a health threat and has to be monitored by determining the EC content in relation to the regulatory limits set by authorities. For each of the above-mentioned parameters QUANT+™ methods were built and calibrations were derived and it was found that a very strong correlation existed in the sample set for the FT-NIR spectroscopic predictions of the percentage of sugar (r = 0.99, SEP= 0.31 °Brix). However, the correlation for the FAN predictions (r = 0.602, SEP= 272.1 g.L-1), malic acid (r = 0.64, SEP= 1.02 g.L-1), lactic acid (r = 0.61, SEP= 1.35 g.L-1) and EC predictions (r = 0.47, SEP = 3.6 μg.kg·1) were not good. The must samples could be classified in terms of their FAN values when Soft Independent Modelling by Class Analogy (SIMCA) diagnostics and validation were applied as a discriminative method, with recognition rates exceeding 80% in all cases. When SIMCA diagnostics and validation were applied to the Chardonnay and EC wine samples, recognition rates exceeding 88% and 80% respectively were obtained. These results therefore confirm that this method is successful in discriminating between samples.
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    Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase
    (Health & Medical Publishing Group, 1979) Theron, C. N.; Lubbe, S.; Van Zyl, A.
    Myeloperoxidase with an A420!280 ratio of 0,48 was prepared from normal human leucocytes. This partially purified preparation catalysed guaiacol oxidation, iodination of bovine serum albumin and de-iodination of 1251-thyroxine. Non-steroidal anti-inflammatory drugs (naproxen, indomethacin and f1ufenamic acid) showed a significant inhibitory effect on myeloperoxidase-catalysed iodination at concentrations of 10"4M and higher. Guaiacol also inhibited myeloperoxidase-catalysed iodination, and its iodination inhibition curve was nearly identical to that obtained with the anti-inflammatory drugs. At concentrations between 10"'M and 10"M the antiinflammatory drugs had very little or no effect on thyroxine de-iodination. Flufenamic acid and indomethacin, however, inhibited de-iodination significantly at a concentration of 10'M. It is postulated that non-steroidal anti-inflammatory drugs may inhibit myeloperoxidase-catalysed protein iodination by acting as oxidizable cofactors which compete with other oxidiza'ble substrates for oxidants formed by the peroxidase-hydrogen peroxide complex. In view of this and because the myeloperoxidase-hydrogen peroxide system may be involved in inflammatory tissue damage, the possibility should be considered that the action of non-steroidal anti-inflammatory drugs is at least partly attributable to a radical scavenging effect or to sequestration of oxidants.