OpenUCT :: Browsing by Author "Folb, Peter I"

Browsing by Author "Folb, Peter I"

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Open Access
The antimalarial activity of Dicoma anomala and the chloroquine resistance reversing effects of Sclerocarya birrea on Plasmodium falciparum in vitro
(2001) Matsabisa, Motlalepula Gilbert; Folb, Peter I; Smith, Peter J; Campbell, William E
Two plants, Dicoma anomala [Sond.]; a member of the Asteraceae and Sclerocarya birrea [(A. Rich) Hoechst. subspecies caffra (Sond.) Kokwaro], a member of the Anarcadiaceae families, are used widely in Africa for a variety of traditional treatments. In this thesis it has been shown that these plants possess in vitro pharmacological activities against the malaria parasite. The extracts of D. anomala are active in vitro against Plasmodium falciparum and those of S. birrea selectively enhance the in vitro accumulation of chloroquine in resistant strains of Plasmodium falciparum.
Open Access
The antimalarial potential of Ugandan traditional medicines : a study of six plants used to treat malaria symptoms
(2003) Waako, Paul; Folb, Peter I; Smith, Peter
The study investigates the antimalarial potential of six Ugandan traditional medicinal plants Senecfo discifolius oliv, Senecio stuhlmannii, Indigofera emarginella steud. Ex A. Rich, Aspifia africana (Pers) C.D. Adams, Cardiospermum halicacabum L. and Momordica foetida Schumch. Et Thonn. Selection of the plants was based on ethnobotanical surveys of traditional treatment of malaria symptoms and reports from traditional healers practising in three different communities.
Open Access
Antimycobacterial activity of the red algae gelidium pristoides, plocamium corallorhiza and polysiphonia virgata
(2006) Saravanakumar, Denise; Folb, Peter I; Smith, Peter J; Campbell, William E
In 1993, the World Health Organisation declared tuberculosis a global health emergency. Currently, efforts are underway to improve the way the disease is managed and to find more effective treatments that would combat the problem of long treatment periods, toxicity, drug-resistance and HIV-coinfection. In the process, natural product chemistry continues to play an important role in the search for new compounds to treat tuberculosis. Terrestrial plants have been investigated for antimycobacterial activity, while marine plants are yet to receive as much attention. In this project, three South African marine plants were drawn into the search for novel anti-tuberculosis compounds. One of the seaweeds is already part of the local seaweed industry, namely Gelidium pristoides, while Plocamium corallorhiza and Polysiphonia virgata have economic potential. These three red algae were extracted extensively and fractionated using preparative layer chromatography and preparative centrifugally accelerated radial thin-layer chromatography (Chromatotron). The crude extracts of the algae showed no inhibitory activity to growth of the causative agent of human tuberculosis, Mycobacterium tuberculosis. However, when the purified fractions were tested against M. tuberculosis in the BACTEC-460 radiometric method at a concentration of 125 μg/mL, fractions 322, 323 and 333 of P. virgata showed 100% inhibition, while two fractions of G. pristoides showed 91.7% and 79.2% inhibition, respectively. Two fractions of P. corallorhiza demonstrated 41.2% and 73.5% inhibition. The bioactive fractions of P. virgata were further purified and resulted in the isolation of a known compound namely, 2-methoxyethyl-2-methacrylate (MEMA). When MEMA was tested by radiometric assay against M. tuberculosis, it showed anti-tuberculosis activity at a MIC-value of 100 μg/mL and no cytotoxicity against Chinese hamster ovarian cells. However, in a re-investigation into the bioactive compounds of P. virgata it was established that MEMA was not the major bioactive compound. Long chain fatty acids were responsible for the antimycobacterial activity of the algal extract particularly oleic acid, linoleic acid, dodecanoic acid, and myristic acid. Oleic acid inhibited the growth of M. tuberculosis at and MIC-value of 25 11 g/rnL, while dodecanoic acid, myristic acid and linoleic acid all had MIC-values of 50 μg/mL. Stearic acid and palmitic acid was also isolated from the seaweed, but only moderate inhibition of M. tuberculosis was observed for at MIC-values of 50 μg/mL. Oleic acid showed moderate inhibition at 50 μg/mL against the multi-drug resistant isolate of M. tuberculosis, while myristic acid and dodecanoic acid showed significant inhibition against the same at 50 μg/mL and moderate inhibition at 25 μg/mL. Linoleic acid also inhibited the growth of the multi-drug resistant strain at 50 μg/mL. Oleic acid showed the most inhibition of the growth of M. smegmatis in direct bioautography with an MIC-value of 0.8 μg/mL, while linoleic acid and dodecanoic acid had MIC-values of 1.56 μg/mL and 3.125 μg/mL., respectively. Stearic acid, palmitic acid, and myristic acid did not inhibit the growth of M. smegmatis.
Open Access
Bioassay-guided fractionation of Artemisia afra for in vitro antimalarial activity against Plasmodium falciparum
(1997) Abrahams, Meryl Arlene; Folb, Peter I; Gammon, David W
With the increase in recent years in the prevalence of malaria, and in drug resistance of Plasmodium falciparum, there has been much interest in natural plant products for new antimalarials with novel modes of action against Plasmodium. Artemisinin or Qinghaosu is one such antimalarial isolated from a Chinese herb, Anemisia annua (Asteraceae) and it is currently undergoing phase I and II clinical trials. The Southern African species, Artemisia afra (African wormwood, wildeals, lengana) is commonly used by local traditional healers for symptoms of malaria, in particular fever. Thus it seemed appropriate to investigate this species for antimalarial activity. Crude petroleum ether soxhlet extracts of Anemisia afra had demonstrated antimalarial activity against Plasmodium falciparum, FCR-3, cultured in vitro. The IC₅₀ values ranged from 5-13μg/ml. The extract from leaves and flowers was then screened against D10 (chloroquine-sensitive) and FAC8 (chloroquineresistant) P. falciparum, in vitro, with IC₅₀ values of 1.03μg/ml and l.5μg/ml respectively. This extract was fractionated by column chromatography using silica gel-60 and the fractions obtained were screened for antimalarial activity. The most active fraction had an IC₅₀ of 0.5μg/ml against D10 and FAC8. Using TLC and HPLC-UV analysis with pure artemisinin as a standard, no artemisinin could be detected in this fraction. This result was confirmed by thermospray LC-MS analyses. Purification of this fraction yielded ultimately a single pure compound; a clear colourless oil identified by MS and NMR analyses as hydroxydavanone. The compound was screened against a variety of P. falciparum strains with varying degrees of sensitivity and resistance to both chloroquine and mefloquine. Their sensitivity against artemisinin was also established. IC₅₀ values obtained for the isolated pure compound against P. falciparum ranged from 0.87 to 2.54μg/ml. The IC₅₀ values obtained for general cytotoxicity of the crude extract and isolated pure compound against RAT-I fibroblast cells were 34.78 ± 8.23 and 6.29 ± 0.95 μg/ml (n=4) respectively. Thus the crude extract and isolated pure compound exhibited a greater antimalarial than cytotoxic effect. Hence, there are implications for A. afra to be used as a phytomedicine for the treatment of malaria. In vivo studies are recommended for hydroxydavanone in order to fully assess its potential for clinical use.
Open Access
The biogenesis of erythropoietin during inflammation
(1995) Leng, Henry Martin John; Folb, Peter I; Keraan, M E; Kidson, Sue H
Anaemia frequently accompanies chronic inflammatory diseases like rheumatoid arthritis and cancer. It is postulated to result primarily from the suppression of erythropoiesis by inflammatory cytokines. A contributing factor could be the inhibition of erythropoietin synthesis which may also be mediated by cytokines. Erythropoietin is the hormone which regulates erythropoiesis. The aims of this project were to investigate whether cytokines can indeed suppress erythropoietin production, and to determine whether the erythropoietin response in experimental models of acute and chronic inflammation was appropriate for the associated anaemia. Macrophage-conditioned medium, interleukin-1β, interleukin-6, tumour necrosis factor-α, and neopterin were assayed for inhibition of erythropoietin synthesis by HepG2 cells in culture. All, except neopterin, effected dose-dependent reductions in the secretion of the hormone. Interleukin-1β and tumour necrosis factor-α down-regulated erythropoietin gene transcription, whereas interleukin-6 inhibited a post-transcriptional process. Rats with acute inflammation developed a mild anaemia which evoked an increase in their serum levels of erythropoietin. The serum erythropoietin levels were optimal, since rats with acute inflammation and severe phenylhydrazine-induced anaemia did not have lower levels of the hormone than controls with a similar degree of anaemia, but without acute inflammation. Erythropoietin is, therefore, not an acute phase reactant. Mice with cancer developed a progressive anaemia which was not due to bone marrow invasion by tumour cells. During the first fourteen days after inoculating them with cancer cells, the mice responded by increasing their serum levels of erythropoietin as the anaemia worsened. The erythropoietin response was appropriate when compared to mice with the same degree of phenylhydrazine-induced anaemia. Erythropoietin levels measured in mice with tumours older than fourteen days were significantly lower than those of control mice with the same degree of experimental anaemia. These animals were very cachectic, suggesting that a blunted erythropoietin response may depend on disease activity.
Open Access
Characterisation of Mefloquine accumulation in Plasmodium falciparum
(2003) Walden, Jason C; Smith, Peter; Folb, Peter I
Meﬂoquine has been in use for over twenty years and still very little is known about its interaction with Plasmodium falciparum. In 1979, Fitch er al carried out the only other published extensive investigation of meﬂoquine accumulation, but were not able to demonstrate energy dependent uptake. They later indicated that an energy requirement may be being masked by meﬂoquine’s ability to bind membrane phospholipids to a large extent (Chevli & Fitch, 1982).Until now no energy requirement for meﬂoquine accumulation has been uncovered. This thesis investigates the relationship between chloroquine and meﬂoquine resistance, and characterizes the mechanism of meﬂoquine accumulation in Plasmodium falciparum. Conditions were established that enabled the ampliﬁcation of the parasites' contribution to overall meﬂoquine accumulation in the parasitised erythrocyte. It was found that meﬂoquine accumulation is stimulated by glucose and is inhibited by the glycolysis inhibitor, iodoacetate, and also by incubation at low temperature. Meﬂoquine accumulation was also found to be partly dependent on the pH gradient between the acidic food vacuole and the external medium. It has also been determined that meﬂoquine-resistant Plasmodium falciparum accumulate approximately half the amount of meﬂoquine than do meﬂoquine-sensitive parasites. It has been shown that the accumulation of both chloroquine and meﬂoquine have two components, a high affinity saturable component and a low affinity non-saturable component (Fitch et aI., 1979; Fitch et al., 1974; Bray et al., 1998). The saturable component has been well characterized, but until now the non-saturable component has not been identiﬁed. This thesis shows that chloroquine and meﬂoquine adsorption to synthetic β-haematin and pure isolated haemozoin is non-saturable. It is proposed that the malaria pigment is responsible for the low afﬁnity, non-saturable component of chloroquine and meﬂoquine accumulation. The effect of chloroquine, meﬂoquine and artemisinin on haemoglobin levels in parasitised erythrocytes was also measured. Chloroquine caused a buildup in haemoglobin and meﬂoquine caused a decrease in haemoglobin levels. This adds weight to previously published work (Famin & Ginsburg, 2002) suggesting that chloroquine prevents the degradation of haemoglobin, while meﬂoquine inhibits the endocytosis of haemoglobin.
Open Access
Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells
(2007-04-18) Hiss, Donavon C; Gabriels, Gary A; Folb, Peter I
Abstract Background The pharmacologic modulatory effects of the antibiotic, tunicamycin (TM), on multidrug-resistant human UWOV2 ovarian cancer cells are reported. The UWOV2 cell line was derived from a cystadenocarcinoma in a patient refractory to combination chemotherapy with actinomycin D, vincristine (VCR), cis-diaminedichloroplatinum (II) (CDDP) and doxorubicin (DXR). In an attempt to explain drug resistance in this cell line, we examined the effects of TM on their sensitivity to various anticancer drugs, the uptake, efflux and retention of [3H]VCR, and their ability to bind [14C]DXR and [3H]azidopine (AZD), a photoaffinity label of the multidrug transporter, P-glycoprotein (Pgp). Results TM effectively decreased the EC50 for DXR, EXR, VCR and CDDP, thus enhancing their cytotoxicity. The antibiotic also prolonged the intracellular retention time of [3H]VCR and increased the binding of both [14C]DXR and [3H]AZD to the cells. Conclusion It is concluded that the pharmacomodulatory effects of TM in these cells are mediated by global inhibition of protein and glycoprotein synthesis and synergistic interaction with antineoplastic drugs. The ability of TM to enhance the sensitivity of drug resistant tumour cells may have impact on the design and optimization of novel resistance modifiers to improve the efficacy of combination treatment of intractable neoplasms.
Open Access
A cost analysis of the treatment of first-line uncomplicated malaria in the Tonga district of Mpumalanga
(1999) Wilkins, Justin; Barnes, Karen I; Folb, Peter I
Following the completion of a detailed baseline study of malaria in the region, a model was developed to assess the cost-effectiveness of switching from chloroquine to sulfadoxine-pyrimetharnine as first line treatment in the Tonga district of Mpumalanga, South Africa, where malaria is seasonal and the population is non-immune. In vivo drug resistance was used to create a resistance variable, which was used to assess the 1997 relative costs to the health care system of employing the two drugs, analysing factors such as drug costs, staff time, transport costs, maintenance costs, utility costs, training costs and consumables costs to generate an average cost-effectiveness ratio. The model was subsequently used to estimate the average cost-effectiveness ratios of nine other potential agents for the treatment of first line malaria, including artesunate monotherapy, artesunate combinations, pyronaridine, atovaquone-proguanil, co-artemether, halofantrine, amodiaquine, and mefloquine. It was found that sulfadoxinepyrimethamine was 5 times more cost-effective as first line therapy than chloroquine. Of the other modelled drugs, it was recommended that an artesunate combination should be implemented when it becomes necessary to replace sulfadoxine-pyrimethamine; artesunate-mefloquine and artesunate-SP were estimated to be 6 times and 9 times as cost-effective as chloroquine, respectively.
Open Access
Design and construction of a laboratory system for neuromuscular stimulation of the lower extremities during cycling
(1986) Popp, Matthias H; Folb, Peter I
Functional Neuromuscular Stimulation (FNS) is a method by which paralyzed muscles are stimulated electrically in order to produce a useful movement. The design and testing of a laboratory system for the modulated control of the lower extremities during FNS-induced cycling on an exercising device (Paracycle) is described. The system hardware, which is designed around a standard IBM compatible Personal Computer, features six independent stimulation channels. Waveform characteristics such as pulse frequency, width and amplitude are defined as a function of the crank position of the Paracycle for each channel. An extensive software package allows programmability of the waveform parameters and supports the user in the definition of stimulation sequences. The effective performance of the complete FNS-controller/ Paracycle system has been demonstrated during a controlled case study with two paraplegic subjects.
Open Access
Determinants and consequences of the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol in a cohort of tuberculosis patients
(2004) McIlleron, Helen; Folb, Peter I; Little, Francesca; Smith, Pete
A prospectlve pharmacokinetic study was conducted amongst a cohort of 142 patients with tuberculosis (TB) susceptible to rifampicin and isoniazid at Brewelsleloof Hospital, Worcester, in the Western Cape.
Open Access
The determination and validation of population pharmacokinetic parameters of phenytoin in adult epileptic patients in the Western Cape using nonlinear mixed-effects modelling
(1995) Valodia, Praneet; Folb, Peter I; Seymour, M A
The pharmacokinetics of phenytoin is complicated by the nonlinearity of the dose-concentration relationship which is a consequence of capacity-limited metabolism. Individualized therapy with phenytoin is therefore optimally required. As no data are available on the population pharmacokinetics of phenytoin in the Western Cape, this study was undertaken to address this issue. This study was conducted prospectively primarily to: (1) investigate the influence of various patient variables on the population pharmacokinetic parameters of phenytoin, (2) assess whether the parallel Michaelis-Menten and first-order elimination model provides a better fit to the data than the Michaelis-Menten model, (3) determine population pharmacokinetic parameter estimates of phenytoin representative of the patient population, and (4) validate and compare the clinical applicability of the parameter estimates and the models. The study population comprised 332 black and coloured, adult, male and female epileptic patients residing in the Western Cape, South Africa. All patients were on phenytoin monotherapy for the management of their epilepsy and no drugs known to interfere with phenytoin pharmacokinetics were taken concurrently. Clinical pharmacokinetic dosing services were initiated at 9 clinics from which patients were selected for this study. The service entailed a patient interview, a chart review, drug analysis and provision of either a written or verbal consultation report. The data were analyzed using NONMEM (nonlinear mixed-effects modelling), a computer programme designed for population pharmacokinetic analysis that allows pooling of data from many individuals. The Michaelis-Menten and the parallel Michaelis-Menten and first-order elimination models were fitted to 853 steady-state dose: serum concentration pairs.
Open Access
Determination of the effect of blood testing intervals on bioavailability and bioequivalence assessment of fixed-dose drug combination anti-tuberculosis drugs
(2003) Gabriels, Gary Anthony; Folb, Peter I; Smith, Peter
Open Access
The development, initial implementation and support of a primary health care training programme in rational drug use
(1998) Orrell, Catherine Jane; Folb, Peter I; Woods, David R
The Rational Drug Use Training Project is a district-oriented programme designed to improve rational drug use among primary health care prescribers in the South African public sector. This thesis describes the development of the project and details the initial implementation study in 3 facilities in Region B of KwaZulu-Natal. This was a small before-after study, with no control. There were three components: 1. A series of easily collectable drug use indicators, adapted from those developed by WHO/INRUD. These allow primary health care staff to monitor their prescribing patterns in a district or facility. Ninety sets of prescribing indicators were collected as a baseline at 3 facilities in KwaZulu-Natal in December 1996, by the district trainers and the Rational Drug Use Training Project staff. The process was repeated in March 1997, after the training intervention, by the district trainers alone. 2. The intervention was a 2-day training workshop in rational drug use. This is problem-based and trained on-site in primary health facilities. Training was done by 8 district trainers from Region B who were taught to present the workshop by the Rational Drug Use Training Project staff. The workshop covers principles of prescribing, use of standard treatment guidelines, principles of clinic stock management and principles of good dispensing. Staff are encouraged to develop their self-learning skills through questioning, and seeking answers to clinical and drug related queries. 3. A set of resources, including texts, treatment guidelines and information centres, to provide quality, safe and unbiased drug information, are made accessible to staff at primary care level. These are available by post, telephone or e-mail. The Primary Care Medicines Resource Centre at the University of Durban-Westville was developed as a result of this study. Significant improvements in prescribing habits were noticed after the study. There was an increase in the percentage of drugs prescribed by their generic names (p=0.000); an increase in the number of medications adequately labelled (p=0.0132); a decrease in the cost of prescriptions (p=0.0134); and a decrease in the number of prescriptions that did not follow standard treatment guidelines at all for that diagnosis (p=0.0109). The Mann-Whitney U- test was used for statistical analysis. There were no significant changes in the average number of drugs per prescription; the percentage of drugs from the Essential Drugs List; and the number of prescriptions that completely followed standard treatment guidelines. Qualitative feedback was favourable too. This was a difficult study to undertake. The staff and funding organisation, Health Systems Trust, fell outside of the provincial health structure and met resistance at that level. Regional politics shaped the programme's design. District trainers needed for the cascade approach were not available. District staff remained entrenched in a traditional health hierarchy and found it difficult to function as a team. The will of district prescribing staff to learn was low. Rational drug use training is only one of a number of essential elements of in-service training urgently needed by these staff. Despite these problems, quantitative and qualitative success was shown. The Training Manual, developed in support of the training, has been in demand. The Primary Care Medicines Resource Centre is growing. Primary care prescribers have been motivated to monitor their own practices and manage their own clinic stock. The project is a successful example of multi-disciplinary and institutional collaboration. The Rational Drug Use Training Project has expanded to eight other health districts in 1997. A list of criteria, such as the need for a district trainer, have been set. These must be met by the district before training will commence. The project is a resource for Initiative for Sub-District Support, a joint district development programme of Health System Trust and the Department of Health. Most expansion in 1998 will be through this initiative. The difficulties encountered and achievements made during this small study will be used to support, and hopefully strengthen, the development of the primary health care oriented district health system, so urgently needed by the South African population.
Open Access
Disseminated candida infection in man, with particular reference to the disease as a complication of steroid and immunosuppressive therapy
(1970) Folb, Peter I
Open Access
The effect of diphenylhydantoin upon the stem cells of the murine teratocarcinoma cell line PC 13
(1984) Wojtowicz, Wendy Anne; Folb, Peter I
Open Access
An electrophoretic study of fetal mouse brain proteins after in vivo exposure to phenytoin and disulfiram
(1990) Heiberg, Ludvig; Folb, Peter I
Although there have been two-dimensional electrophoretic studies on fetal brain tissue (for instance, Yoshida and Takahashi, 1980), the emphasis in most of this work has been on developmental changes in protein expression, and not on the effects that drugs have on fetal brain protein complement. Klose and co-workers (1977) did an early study using two-dimensional gel electrophoresis to determine the effects of various teratogens on whole embryos. No protein changes were found and that line of research was not continued. In this study two-dimensional gel electrophoresis is extensively used, in the belief that the usefulness of this technique to experimental teratology has not been fully evaluated. It is reasonable to suppose that a central nervous system teratogen administered during critical periods of susceptibility will led to perturbations of orderly brain development, and that these perturbations will be reflected as changes to the protein complement. The total brain protein complement of mice that have been exposed to drugs in utero will therefore be analysed, in the hope that any inductions or deletions of proteins as a result of drug exposure may provide a clue to the molecular events underlying drug injury to the fetus.
Open Access
Expression of the P-glycoprotein Homologue1 on food vacuoles isolated from Chloroquine-sensitive and resistant Plasmodium falciparum strains
(1999) Lindt, Meinrad; Smith, Peter J; Folb, Peter I
Worldwide occurrence of chloroquine resistance is an expanding problem in prophylaxis and treatment of malaria. Similarities between the drug resistance phenotype in certain cancers and in malaria suggest that homologue multidrug resistance proteins might be involved in the mechanism of resistance. In this thesis, the expression of a putative multidrug resistance protein of the malaria parasite Plasmodium falciparum, the P-glycoprotein homologue1 (Pgh1), was quantified on food vacuoles, the site of action of chloroquine. Chloroquine susceptibility was determined in 8 different P. falciparum strains. Food vacuoles were isolated from trophozoites of two chloroquine-sensitive (307 and D10) and three chloroquine-resistant (FAC8, K1 and RSA 11) strains. Antibodies against an 18 amino acid long peptide of Pgh1 were raised, as well as two other antibodies against the N-terminal ATP-binding site and the C-terminus of Pgh1. With these antibodies, Pgh1 was detected on isolated food vac.uoles and on trophozoites by immunoblotting. The exact Pgh1 expression levels on food vacuoles were measured with digital image analysis. The chloroquine-sensitive strains 307 and D10 and the chloroquine-resistant strains K1 and RSA 11 expressed equal amounts of Pgh1. The chloroquine-resistant FAC8 strain expressed at least three times more vacuolar Pgh1. No correlation was found between chloroquine IC₅₀ and vacuolar Pgh1 expression levels. Phosphorylation studies on intact food vacuoles indicated that Pgh1 is not a major kinase substrate.
Open Access
The first-pass extraction of pindolol in comparison with propranolol in rat liver
(1979) Basset, Helen Margaret; Folb, Peter I
Reports in the literature have shown that in man propranolol has a larger first-pass effect (70%) than pindolol (13%). The aim of this research was to make a direct comparison of first-pass extraction and other pharmacokinetic parameters of these drugs under identical experimental conditions by means of an isolated rat liver perfusion model.
Open Access
The identification, purification and characterization of the fetal rat liver glutathione S-transferase isoenzyme YcYfetus
(1988) Scott, Trevor Robert; Kirsch, Ralph E; Folb, Peter I
This study has examined the expression of the glutathione S-transferases (GSH S-T) in fetal rat livers in order to provide more information about the role played by this important group of enzymes in the fetus. The study commenced with an examination of the subunit composition of adult and fetal rat liver GSH S-T using affinity chromatography followed by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. Adult livers contained four major GSH S-T subunits. An additional and previously unidentified subunit was detected in fetal livers. This subunit, which differed from that found in rat placenta, had a Mᵣ of approximately 25 500. Densitometric measurements suggest that the newly detected subunit accounts for as much as 26% of the GSH S-T in fetal livers. The novel fetal isoenzyme comprising this subunit was purified using a combination of affinity chromatography, carboxymethyl-cellulose column chromatography and chromatofocusing. The six major basic rat liver GSH S-T were purified for reference and comparative purposes. The fetal isoenzyme is composed of two non-identical subunits, namely, subunit Yc (Mᵣ 28 000) and the fetal subunit referred to as 'Yfetus'· The enzyme which I have termed GSH S-transferase Yc Y fetus has an isoelectric point of approximately 8.65 and has GSH S-T activity towards a number of substrates. Significantly, the fetal isoenzyme has one of the highest glutathione peroxidase activities yet described for the purified rat liver GSH S-T towards the model substrate, cumene hydroperoxide. Kinetic studies reveal that the fetal isoenzyme has a catalytic efficiency for the peroxide substrate which is four fold higher than that of the adult rat liver isoenzyme, GSH S-T YcYc. The in vitro effect of the GSH S-T substrate and teratogen, acrolein, on this fetal isoenzyme was investigated and compared with acrolein's effect on some of the adult rat liver GSH S-T isoenzymes in the standard 1-chloro-2,4-dinitrobenzene assay. Surprisingly, acrolein was identified as a non-competitive inhibitor of the GSH S-T. Exposure to acrolein in various guises could therefore result in inhibition of the fetal isoenzyme and its subsequent failure in inhibiting lipid peroxidation. Inhibitor studies were performed to look at the effect of acrolein, as well as other substrate and non-substrate ligands, on the glutathione peroxidase activity of GSH S-T YcY fetus and YcYc. The glutathione peroxidase activity of the fetal isoenzyme was far less susceptible to acrolein inhibition than the YcYc isoenzyme and the fetal isoenzyme was found to retain significant glutathione peroxidase activity despite saturating concentrations of non-substrate ligand. This study suggests that the fetal isoenzyme serves a specific function in protecting fetuses against the possible teratogenic effects of organic peroxides.
Open Access
In vitro efficacy tests against Mycobacterium species of South African traditional medicinal plants
(2002) Ntutela, Siyabulela Calvin Sibusiso; Folb, Peter I; Smith, Peter J; Steyn, Lafras
Tuberculosis is the leading cause of death due to a single organism; with a mortality of more than 3million people each year, worldwide. The emergence of multi-drug resistance and HIV/AIDS are the major causes of this problem. New therapeutic agents with a different mode of action, and thereby of resistance to Mycobacterium tuberculosis, the causative agent, are needed urgently. Amongst the methods used, the area of ethnopharmacology is explored in this study. Visits were performed to collect the plants used by traditional healers in 7 provinces of South Africa for the treatment of tuberculosis.