Magister Pharmaceuticae - MPharm

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Investigation of the mechanism of fenfluramine-induced pulmonary phospholipidosis in the rat lung model
(University of the Western Cape, 1993) Hassan, Mogamat Shafick; Syce, J.A.
The aim of this study was to investigate the mechanism of fenfluramine-induced pulmonary phospholipidosis, by comparing the profile and levels of induced phospholipids in the rat and the mode of phospholipase inactivation, both relative to that produced by chlorphentermine. Wistar and BD9 rats were injected with fenfluramine (FF) and chlorphentermine (CP) intra-peritoneally daily over a six week period to induce phospholipidosis. The lungs isolated from such treated and untreated animals, were grouped into unlavaged lungs and lungs to be lavaged and from the latter group the alveolar macrophages were isolated. Small sections of the unlavaged lungs were microscopically examined to verify the induction of phospholipidosis. Further the levels of phosphatidyl choline (PC), spingomyelin (SPM), phosphatidyl ethanolamine (PE), phosphatidyl glycerol (PG), phosphatidyl inositol (PI), phosphatidyl serine (PS) and phosphatidic acid (PA) were determined in both groups of lungs using a TLC method. To assess whether the drug-mediated inactivation of the phospholipases (PL) occurred via direct inhibition of the enzymes or via the drug-phospholipid complex, the hydrolysis of the above phospholipids by PL-A or PL-C were monitored using colorimetric methods. The feasibility of the phospholipid-drug complex-mediated mechanism was further explored, by assessing the effect the two drugs had on the phase transition temperature of the phospholipids. Electron microscopy revealed the presence of hypertrophied and elevated counts of alveolar macrophages in the treated-Wistar and -BD9 rats. In the FF- and CP treated Wistar and BD9 rats there were, compared to the saline-treated rats, a 200 % and 235 % increase in macrophage counts, respectively, for the FF-treated rats and a 700 % and 965 % increase in macrophage counts, respectively, for the CP treated rats. The levels of all the phospholipids in the unlavaged lungs of both rat strains were elevated, except that for PG, PS and PA. In both rat strains following the treatment with both drugs the PG levels were not elevated and the PS levels were not elevated following CP treatment. Following the treatment for both drugs, the PA levels were also not elevated in the BD9 rats. Relative to the levels found in the unlavaged lungs of the control rats, the increases ranged from a minimum of 9 to a maximum of 216 %. In general, Wistar rats appeared to be more susceptible to both FF and CP treatment. In both rat strains, lavaging of the lungs considerably reduced the levels of phospholipids remaining in the lung and the differences between the treated and untreated animals became less striking. The addition of FF or CP, whether directly to the enzyme, or in the form of the drug phospholipid complex, resulted in significant decreases in the PL-A-mediated or PL-C-mediated hydrolysis of virtualy all the test phospholipids. The average decrease ranged from 0.811 to 4.04 ,.,.FFAbbb ,.,.1-1sample min-I, for the PL-A activity and 0.023 to 0.827 ,.,.gIp'CC100 ,.,.1-1 sample min-I, for the PL-C activity. In the case of FF, the inhibition of PL-A activity could not be ascribed exclusively to either direct inhibition of the enzyme or reduced susceptibility of the phospholipid substrate-drug complex. The PL-C activity appeared to be inhibited to a greater extent via the phospholipid substrate-drug complex rather than by direct inhibition. On the other hand, CP induced a small, but significantly greater degree of inhibition of PL-A activity, more via direct inhibition, rather than by the phospholipid substrate-drug complex. The PL-C activity appeared to be inhibited to a greater extent via phospholipid substrate-drug complexation than by direct inhibition. From the above data, considered collectively, it was not possible to declare either of the two possible mechanisms as the more likely one for FF or CP-induced inhibition of the phospholipases. The feasibility of the indirect mode was further explored, by determining the phase transition temperatures for the phospholipid-drug complexes of each drug. The addition of each drug caused a depression of the phase transition temperature of all the phospholipids with a .1T'dd ranging from 0.52 to 15.73 °C. This appears to support the notion that both drugs bind to the phospholipids and the differences in the extent of the phase transition temperature depression of the individual phospholipids may indicate differences in the binding capacities of these drugs. The following major conclusions may be drawn from the results of this investigation. Fenfluramine induces a phospholipidosis syndrome in the lungs of Wistar and BD9 rats that are histologically similar to that induced by CP. It induces the elevation of essentially the same phospholipids as CP, primarily in the alveolar spaces and macrophages, and by implication, most likely via similar mechanisms. For both FF and CP, both direct inhibition and phospholipid-drug complex-mediated inhibition of phospholipases were found to be a viable mechanism for this syndrome. The mechanism for FF-induced pulmonary phospholipidosis thus appears to be similar to that of CP; small quantitative differences in essentially similar mechanisms, may explain the differences in the levels of induced phospholipidosis found in this study.
The antimicrobial screening of four South African asteraceae species and the preliminary structural investigation of an antipseudomonal compound from Arctotts auriculata
(University of the Western Cape, 1998) Salie, Fuad; Eagles, P.F.K.
Infectious diseases represent one of the main causes of morbidity and mortality in developing countries, like South Africa. The indiscriminate use of antibiotics has also resulted in the emergence of a number of resistant bacterial strains. Four plants belonging to the Asteraceae (Daisy) Family, which forms part of the Fynbos Biome, were screened for their phytochemical composition and mantimicrobial activity. The plants investigated were: Helichrysum crispum, Felicia erigeroides, Eriocephalus africanzs and Arctotis auriculata. The plants were selected on the basis of their ethnobotanical use in various infectious diseases.
The antimicrobial screening of four South African Asteraceae species and the preliminary structural investigation of an antipseudomonal compound from Arctotis auriculata
(University of the Western Cape, 1998) Salie, Fuad; Eagles, Peter; Leng, H.M.J
Infectious diseases represent one of the main causes of morbidity and mortality in developing countries, like South Africa. The indiscriminate use of antibiotics has also resulted in the emergence of a number of resistant bacterial strains. Four plants belonging to the Asteraceae (Daisy) Family, which forms part of the Fynbos Biome, were screened for their phytochemical composition and antimicrobial activity. The plants investigated were: Helichrysum crispum, Felicia erigeroides, Eriocephalus africanzs and Arctotis auriculata. The plants were selected on the basis of their ethnobotanical use in various infectious diseases. The results from the phytochemical identification showed that all the plants tested positive for tannins. Flavonoids were detected in the leaves and stems of A. auriculata and F. erigeroides and the stems of E. africanus. Saponins were present in the leaves of H. crispum and the leaves and roots of F. erigeroides. Triterpene steroids were found in the stems of E. africanus and F. erigeroides. Akaloids were only detected in the leaves of A. auriculata and cyanogenic glucosides were in the stems of H. crispum and the leaves of A. auricula/a. None of the plants tested positive for quinones. The disc diffirsion method was used to determine the antimicrobial potential of the selected plant species. The results from this initial study showed that the organic extracts of A. auriculata and H. crispum inhibited the growth of Mycobacterium smegmatis. The same extracts, together with the organic extracts of F. erigeroides, were active against Pseudomonas aeruginosa. Antifungal activities against Candida albicans were exhibited by the organic extracts of E. africanus, F. erigeroide^s and H. crispum. Organic extracts of A. auriculata and E. africanus, as well as the aqueous extract of the latter plant, were active against Staphylococcus aureus. Hereafter, the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum fungicidal concentration (MFC) and minimum mycobactericidal concentration (MMC) of the most active solvent extracts of selected organs of the four plants were done.
Effect of inhaled cationic poly-peptides on respiratory mechanics in the isolated perfused rat lung
(University of the Western Cape, 1998) Wang, Weizhou; Syce, J. A
The inhalation route is increasingly being considered as a viable option to deliver protein drugs into the body, but there has been few studies dealing with the safety of this strategy. The results of in vitro studies have shown that proteins, especially cationic proteins, can interfere with pulmonary surfactant and affect its surface tension lowering activity. If such an interaction also occurs in vivo it may lead to the inactivation of endogenous pulmonary surfactant and have profound adverse effect on the respiratory mechanics of the lung. To investigate this contention a suitable model which allows the inhalation mode of administration of proteins and the continuous monitoring of lung compliance and other parameters is needed. The objectives of this study consequently were to (1) adapt the isolated perfused rat lung (IPL) to allow the administration of exogenous protein via the inhalation route into the alveoli, and (2) to use the adapted model to investigate the effect which inhaled cationic poly-peptides could have on lung function. It was hypothesised that such inhaled cationic peptides would interact with and inactivate the pulmonary surfactant leading to a decrease in lung compliance The lungs from adult Wistar rats were isolated and mounted in the IPL system. Three administration methods viz. aerosol administration, propellent driven administration and intra-tracheal instillation during positive pressure ventilation were considered.
Formulation and evaluation of tablets manufactured from Dodonaea Angustifolia plant material
(University of the Western Cape, 2001) Kayitare, Egide; Syce, James A.
The liquid dosage form is the most frequently used form for traditional plant medicines. However, this dosage form is associated with many problems, e.g. physicochemical instability, microbial contamination, etc. which may be solved using a solid dosage form. This study investigates the formulation and manufacture of tablets containing two types of material prepared from the leaves of Dodonaea angustifolia. The main goal of the present study was to formulate and produce tablets containing the same amount of plant material as found in the usual dose of D. angustifolia decoction. ln addition, the suitability of using directly dried leaf powder and dried aqueous extract of the leaves, as raw material for the tablets, was compared. lt was hypothesized that tablets with acceptable physical properties and containing 80% or more of plant material could be produced and that tablets containing dry leaf powder or dry plant extract would possess different properties. Raw plant material in the form of dried leaf powder and dried aqueous extracts (Dry Extract 1 from wide leaf plant and Dry Extract 2from narrow leaf plant) of D. angustifolr3 were prepared and their physical characteristics determined. Based on the latter, suitable excipients were selected and formulas containing the same amount of the plant material as found in a single decoction dose of D. angustifolia were elaborated. Thereafter, tablets containing these plant materials were manufactured using the direct compression method and the physical properties of the manufactured tablets were assessed. Results of the pre-formulation study indicated distinct differences in physical properties between the three plant materials. The dry leaf powder had a median particle size of 20prm compared to 200pm and 3441tm for Dry Extracts 1 and 2, respectively. The dry leaf powder was significantly more soluble in ethanol than water (55.7t0.g vs. 26.1+3o/o, t-test, p=0.05), while the extracts dissolved completely but required vigorous shaking. The compressibility of the dry powder was very good (11.910.5%), that of dry extract 2 good (15.9t2.8Yo) and that of Dry Extract 1 only passable (22.6tO.8%). All the powders showed poor flowability, but they had different potentials to pick up moisture. More importantly, the dry extracts became very cohesive and tended to dissolve in the absorbed moisture at relative humidity above 60%. The tablets containing the dry leaf powder and those containing Dry Extracts 1 and 2 required different formulas and different compression forces and displayed different physical properties. The final proportions of plant material per tablet were B5o/of or dry powder,650/o for dry extract 1 and 7Oo/of or dry extract 2. Finally, all the final tablets had acceptable physical properties. However, the tablets containing the dry extracts showed slow disintegration (27.6 and 29.6min for Dry Extracts 1 & 2, respectively, vs. 3.1min for dry powder) and low dissolution rate (38.60/o and 6o.20/o al 45min for Extracts 1 and 2 vs. 92.7o/o for the dry powder). We conclude that the different forms of raw material prepared from the leaves of D. angustifotia have different properties, but can be formulated and manufactured into directly compressed tablets. However, the form of raw material dictates whether the tablets can contain a high proportion (80% plus) of plant material and also influences the properties of the final tablets. Comparable results can be anticipated if materials from other parts of the plant and/or from other plants are to be used.
Syndromic treatment of sexually transmitted infections: a western cape community pharmacist study
(University of the Western Cape, 2001) Ward, Kim Lana; Butler, Nadine
This cross-sectional survey of 85 randomly selected community pharmacists in the Western Cape, South Africa. estimates that 200 000 sexually transmitted infections (STl) cases are seen in private community pharmacies throughout the Western Cape per annum, contirming anecdotal evidence that community pharmacies are a preferred source of STI care. This study also describes the views of pharmacists regarding their utilisation as STI care providers, and the treatment practices of those who currently provide this service to the community. The majority (74.1%) of pharmacists view their current role in STI treatment as under-utilised and 98oZ expressed a slight to strong willingness to play a role in the syndromic treatment of STIs. Pharmacists' knowledge of the link between HIV and STIs is associated with an increased willingness to provide STI syndromic treatment (RR: 3 03, 959/oCI 1.45- 6.31, p=0.0004). The quality of STI treatment among those pharmacists currently providing medication is poor, with only 13.6oh (n=44) of pharmacists prescribing the correct treatment for penile discharge, 6.37o(n:32) for genital ulcers and OYo (n:32) prescribing the correct treatment for vaginal discharge. The findings of this study underline the need for STI treatment services ln communlty pharmacies, and the need for a pharmacist training intervention in the syndromic treatment of STIs.
An assessment of three Carpobrotus species extracts as potential antimicrobial agents.
(University of the Western Cape, 2001) Springfield, Evan; Amabeoku, George J.
For centuries, indigenous people in South Africa have used a variety of medicinal herbs to treat chronic infections. This investigation focused on three Carpobrotus species, in an attempt to assess their potential antimicrobial activity. Extracts of varying polarities of the plants were prepared and tested against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Mycobacterium smegmatis. For the disc diffusion method Ciprofloxacin (4Opg/disc) served as positive control for ^S. aureus, P. aeruginosa and M. smegmatis, whereas amphotericin B (25 pg/disc) was the control for C. albicans. A sample concentration of 10mg/ml was used. Minimum inhibitory concentrations (MIC) were determined by two-fold serial dilution. Phytochemical analysis was completed to test for the presence of flavanoids, hydrolysable tannins, phytosterols and aromatic acids. The ethyl acetate extracts {2lpl of 95mg/ml) were used for bio-autography, together with TLC analyses and HPLC fingerprinting. Carpobrotus mellei, Carpobrotus muirrii and Carpobrotus quidrifidus showed antimicrobial activity against S. aureus and M. smegmatis in the disc diffusion method and inhibition against S. aureus and M.smegmatis was observed by clear zones on the TLC plate. HPLC fingerprinting of the three species showed similarities with common peaks detected at 366 nmi, and providing a phytochemical map of potentially important natural bioactives. This investigation confirms that extracts of the three Carpobrotus species that are used as indigenous medicines, exhibits anti-bacterial activity. This scientific information can serye as an important platform, for the development of inexpensive, safe and effective natural anti-infective therapeutics.
Pharmacological evaluation of the medicinal plants, pelargonium triste (l), elytropappus rhinocerotis (l.f), and olea europaea africana (mill.) for antidiarrhoeal activity in mice
(University of the Western Cape, 2001) Bamuamba, Kopinga; Amabeoku, George J
Three medicinal plant species, Pelargonium triste (L.), Elytropappus rhinocerof,s (L.F.), and Olea europaea africana (Mill.), commonly used in the Western Cape traditional medicine to treat various ailments were assessed for activity against castor oil-induced diarrhoea in mice. The chemical composition and the high performance liquid chromatographic (HPLC) analysis of the plant extracts were also investigated. At the doses of 25 mg/kg, 50 mg/kg, and 75 mg/kg all the plant extracts significantly (p< 0.05) reduced the number of diarrhoeal episodes in mice. At the doses of 50 mg/kg and 75 mg/kg the P. frisfe and E. rhinocerofis aqueous extracts significantly reduced the total diarrhoeal stool mass, and also significantly delayed the onset of diarrhoea in mice. The effect of P. fnsfe against castor oil-induced diarrhoea was dose dependent. Olea europaea africana did not significantly alter the onset of diarrhoea or the total diarrhoeal stool mass. The data obtained indicate that P. triste, E. rhinocerofis, and O. europaea africana possess anti-diarrhoeal properties, which justify their use in the Western Cape by traditional medicines practitioners to treat diarrhoea. The data also show that all three plant-species contain tannins and saponins. In addition, P. triste and O. europaea africana contain reducing sugars, where as E. rhinocerolzs contains cardiac glycosides.
An Evaluation of the Bronchodilator properties of Mentha longifolia and Artemisia afra, Traditional Medicinal Plants used in the Western Cape
(University of the Western Cape, 2002) Harris, Lynne; Syce, J.A.
The overall objective of this study was to investigate the claims that Mentha longifolia (ML) and Artemisia afra (AA) have anti-asthmatic properties. To realize this objective we were to determine the effects that the plants may have on contractions induced by agonists (e.g. methacholine, histamine, and leukotriene D+) and also to partially investigate the mechanism that may be involved' We hypothesized that extracts of Mentha longifolia and Artemisia afra would have respiratory airway smooth muscle relaxant properties and would be able to reverse methacholine and/or, histamine and/or leukotriene D+-induced contractions. plants were collected from Kirstenbosch National Botanical Institute and aqueous extracts prepared. Solutions of plant extracts were injected into an organ bath containing a zigzag cut guinea pig tracheal strip that had been pre-contracted with methacholine, histamine or leukotriene D+. The relaxant effects of the plants were expressed as a percentage of the maximal effect produced by isoprenaline (6.67}.10'sM). To determine the mechanism for the muscle relaxant effects of the plants, cumulative log dose-response curves (LDRC) for methacholine and histamine were obtained in the absence and presence of 2%o, l0%o and 20%o solutions of the plant extracts. In addition the possible involvement of a P2- adrenoreceptor-mediated mechanism was assessed by determining the effects of increasing concentrations of ML and AA on methacholine-induced contractions in the absence and the presence of propranolol. ML produced no direct contractile effect on the guinea pig tracheal muscle, but it relaxed methacholine (6.67X10-8M1-induced contractions in a dose dependent manner. ML was able to fully reverse the methacholine-induced contraction but the 2% and 10% solutions caused a non-parallel rightward shift in the LDR curves. In concentrations above 0.1% ML gave a lO0% relaxation of histamine-induced (6.67X104M) contractions. However, except for a slight leftward shift induced by 2yo ML, the plant extract had no significant effect on the histamine LDRC' Concentrations of ML > 5 o/o produced maximal relaxation of LTD+-induced (6.93X104M) contraction. Finally, in the presence of propranolol (6.67X10{M) the maximal relaxant effect of ML on methacholine (6.67x10'sM)-induced contractions was reduced by approximately 20%. AA produced no direct contractile effect on the guinea pig tracheal muscle, but on tracheal tissue not previously exposed to methacholine it produced a dose dependent relaxation. When the tissue had, however, been exposed to methacholine and thoroughly washed before being exposed to doses of plant extract, 1%o and 2 % AA solutions induced major contractile responses and displaced the LDRC upwards, while l0%o to 30% AA solutions induced relaxation. These contractile responses were inhibited by ipratropium (1.67X10rM) and mepyramine (4.13X104M). In the presence of 20% AA there was a pronounced non-parallel rightward shift of the LDRC of methacholine. AA, 10% to 30%o, also caused a dose-dependent relaxation of histamine (6.67X10{M)- and LTD+ (6.93x10'eM)-induced contractions. Finally, in the presence of propranolol (6.67X104M) the maximal relaxant effect of AA on methacholine (6.67X105IOinduced contractions was reduced by approximately 27%. Collectively these results indicate that aqueous extracts of Mentha longifolia and Artemisia afra have potent and qualitatively similar smooth muscle relaxant activity. These actions may be mediated via several receptor pathways and/or involve one or more common intermediate step (e.g. intracellular calcium flux) commonly involved in the mechanism of action of the agonists used. The results also very strongly suggest that the extracts may contain more than one active principle some of which may differ between the two plants. Overall the results confirm that aqueous solutions of Mentha longifolia and Artemisia afra, as used in local traditional practice, have potent bronchodilator activity that could be useful in the treatment of asthma.
The influence of the proposed professional fee for community pharmacists on prescription income
(University of the Western Cape, 2002) Terblanche, Sanri; Valodia, Praneet
prescription pricing in community pharmacies in South Africa involves a percentage mark-up on the cost of the product, followed by a varying discount to either the client or the medical scheme. The Pharmaceutical Society of South Africa (PSSA) has developed a new remuneration system for the community pharmacist whereby the price the client pays consists of the reimbursement cost of the product plus a professional fee. It was expected that the system would be implemented during 2002. An independent assessment of the development and validation of the professional fee was necessary. No standard operating procedure to apply the professional fee to a data set of prescriptions and comparing it to the current pricing method existed' There was uncertainty on how the prescription income of community pharmacies would be affected by the professional fee. The aim of the study was to explore the influence of the proposed professional fee for community pharmacists on prescription income.' The study was conducted to (l) assess the development and validation of the professional fee by PSSA and (2) develop a standard operating procedure to apply the proposed professional fee on a data set of prescriptions derived from community pharmacies. Three different sized pharmacies were conveniently selected. Claimed and private prescription information of six months was obtained. The data was used to determine the income using the mark-up pricing method. To determine the income using the professional fee pricing method, a formula was developed to calculate the cost price from the gross price of each item. The proposed professional fee of R28.39 (including VAT) was added to schedule 3-7 items and a 30% mark-up was added to schedule 0-2 items. The difference in income between the two pricing methods was calculated. The incidence of overpricing and a cost neutral professional fee was calculated. A cost neutral professional fee was the value of the fee when there was no difference in income between the two pricing methods.
The chemical stability of betamethasone valerate and fluocinolone acetonide cream and ointment in cetomacrogol and emulsifying cream and ointment bases
(University of the Western Cape, 2002) Titus, Michael John; Syce, James A.
The corticosteroids are powerful anti-inflammatory molecules but their usage is hampered by adverse effects. To minimise their adverse reactions, proprietary brands of topical corticosteroids are commonly diluted with a variety of bases. Dilution may affect the stability of the corticosteroid molecule and may result in accelerated degradation. This degradation may vary depending on the diluent base used. Such dilutions are also made in the Western Cape Department of Health public health system where unique formulations of cetomacrogol and emulsifying preparations are used as diluents. Because of the uncertainty of how these diluents would affect the steroid molecules, no accurate expiry dates could be allocated to the diluted preparations. This study set out to determine the chemical stability of betamethasone valerate and fluocinolone acetonide creams and ointments when diluted with the bases used in the public hospital system and to assign shelf lives to them. Samples of the branded topical corticosteroid products used by the Western Cape Department of Health were diluted 1 :10 and 50:50 with cetomacrogol and emulsifying cream and ointment bases. The diluted preparations were stored protected from light, moisture and air at 25'C. Samples of the preparations were assayed at intervals for their corticosteroid content using reverse phase High Performance Liquid Chromatography. These concentrations of corticosteroid provided a degradation profile of each preparation from which degradation rate constants were determined and shelf lives calculated. The HPLC method used was sensitive, accurate and specific for the active ingredients studied. The retention times of betamethasone valerate and fluocinolone acetonide were 4,00 and 5,15 minutes respectively. Betamethasone valerate was significantly more stable in the cream dilutions than in the ointment dilutions (e g. 1 .10 dilution in cetomacrogol cream t* = 5,46 +- months vs 1 :10 dilution in cetomacrogol ointment tgo = 1 ,62 +- months P = 0,0181 ). Conversely, fluocinolone acetonide was more stable in the ointment dilutions than in the cream dilutions but not significantly so (e.9. 1:10 dilution in cetomacrogol ointment tgo = 12,69 +- months vs 1 :10 dilution in cetomacrogol cream tro = l,$! +- months P = 0,1938). ln general, both corticosteroids degraded more slowly when diluted with cetomacrogol cream (e.9. 1 :10 dilutions of betamethasone valerate cream tro = 5,46 +- months and fluocinolone acetonide cream teo= 2,63 +- months) than with emulsifying cream (e.g. 1 :10 dilutions of betamethasone valerate cream tno = 3,05 +- months but not significantly so P = 0,8280 and fluocinolone acetonide cream tro= 0,0111 +- months extremely significantly so P<0,0001) and more slowly when diluted with cetomacrogol ointment (e g. 1 :10 dilutions of betamethasone valerate ointment tso = 1 ,62 +- months and fluocinolone acetonide ointment tso = 12,69 +- months) than with emulsifying ointment (e.g. 1 :10 dilutions of betamethasone valerate ointment t* = 0,18 +- months and fluocinolone acetonide ointment 1 .10 t* = 9,81 +- months although not significantly so P = 0,6590). Also, generally, the more concentrated dilutions were more stable than the more dilute ones (e.g 50:50 dilution of betamethasone valerate in cetomacrogol ointment tro = 4,33 +- months vs 1:10 dilution tgo = 1,62 months significantly so P = 0,0140 and 50:50 dilution of fluocinolone acetonide in cetomacrogol ointment t* = 46,90 +- months vs 1:10 dilution tro = 12,69 +- months although not significantly so P = 0,6005). Due to the rapid breakdown of the molecules it is therefore recommended that 1 :10 dilutions of betamethasone valerate ointment not be made using emulsifying ointment nor should branded products of fluocinolone acetonide be diluted with emulsifying cream at all. The calculated shelf lives should be used as a guide when the various combinations of steroids and diluents are to be used.
Evaluation of satherlandia frutescens for anti.cancer activity
(University of the Western Cape, 2002) Ghogomu, T; Amabeoku, G
The claim for anti-cancer activity of the plant Sutherlandiafrutescens was investigated against some cancer cell lines in-vitro and against a dichlorvos induced chemical carcinogenesis in-vivo. A preliminary phytochemical analysis of the plant extract was also done.
An evaluation of the Bronchodilator properties of Mentha longifolia and Artemisia afra, traditional medicinal plants used in the Western Cape.
(University of the Western Cape, 2002) Harris, Lynne; Syce, James
The overall objective of this study was to investigate the claims that Mentha longifulia (ML) and Artemisia afra (AA) have anti-asthmatic properties. To realize this objective we were to determine the effects that the plants may have on contractions induced by agonists (e.g. methacholine, histamine, and leukotriene D+) and also to partially investigate the mechanism that may be involved' We hypothesized that extracts of Mentha longifotia arrd Artemisia afra would have respiratory airway smooth muscle relaxant properties and would be able to reverse methacholine and/or,histamine and/or leukotriene D+-induced contractions. plants were collected from Kirstenbosch National Botanical Institute and aqueous extracts prepared. Solutions of plant extracts were injected into an organ bath containing a zigzagcut guinea pig tracheal strip that had been pre-contracted with methacholine, histamine or leukotriene D+.
Effects of the alkaloid present in the ethyl acetate: hexane (1 :4) fraction of Crinum macowanii on the isolated perfused rat heart
(University of the Western Cape, 2004) Njagi, Angela Gakii; Mugabo, Pierre
Crinum macowanii (CM) is used in traditional medicine in the treatment of various diseases including ischemic heart disease, rheumatic fever, cancer and skin diseases. The aqueous extract of CM bulbs was found have a positive inotropic effect similar to the one of adrenaline in normotensive rats. After the extraction of CM bulbs four fractions were collected, (1:4), (2:3), (3:2) and (4:1), from ethyl actetate: hexane as an eluent. The (1:4) further using PLC and the major band used for the experiments. Structure elucidation was further carried out on the major band isolated and a new alkaloid was identified from the bulbs of CM. The major aim of the study was to test the alkaloid isolated on the "double sided" working heart system. The parameters to be assessed were coronary flow (Qe), aortic output (Qa), cardiac output (CO), systolic and diastolic pressure (SP/DP), pulse pressure and heart rate (Hr). Wistar rats weighing between 250-350g were used. The hearts were isolated and perfused using Krebs Henseleit solution on the "double sided" working heart system. The parameters were monitored through a pressure transducer connected to a power lab and a computer. The Qe, Qa, CO, SP/DP, Pulse pressure and Hr reduced significantly when lycorinone (the proposed name given to the new alkaloid extracted from Crinium macowanii) was used at the concentrations of 0.005μg and 0.05μg. Further studies are recommended for the verification of the mechanism of action of lycorinone (negative chronotropic and negative inotropic effects).
Cardiovascular effects of Leonotis leonurus extracts in normotensive rats and in isolated perfused rat heart
(University of the Western Cape, 2004) Obikeze, Kenechukwu; Dietrich, Danielle; Green, Ivan; Burger, Andreas; School of Pharmacy; Faculty of Science
This thesis discussed the cardiovascular effects of the aqueous leaf extract and a fraction of the methanol extract of Leonotis leonurus, a plant commonly used in traditional medicine in South Africa for the treatment of hypertension and other cardiac problems. The cardiovascular effects was tested on anaesthetized normotensive male Wistar rats and isolated perfused rat hearts.
The formulation and evaluation of rapid release tablets manufactured from Artemisia Afra plant material
(University of the Western Cape, 2004) Komperlla, Mahesh Kumar; Syce, James A.; Bapoo, Rafik A.; School of Pharmacy; Faculty of Science
Infusions, decoctions, alcoholic preparations and other dosage forms of Artemisia afra are frequently used in South African traditional medicine. Generally when these preparations are made without applying good manufacturing practices they do not meet microbial quality control standards, safety and toxicity criteria and encourage poor patients compliance. To overcome the aforementioned disadvantages of traditional dosage forms a sold dosage form, i.e. a table might be recommended. The first objective of this study was to formulate and manufacture a rapid release tablet dosage of Artemisia afra that would contain an amount of plant material equivalent to that found in its traditional liquid dosage forms and that would meet conventional pharmaceutical standards. The second objective was to conduct a pilot study to obtain a preliminary profile of the bioavailability of select flavonoids presents in both the tablet and traditional liquid preparation of Artemisia afra in humans.
The development and evaluation of the Objective Structured Dispensing Examination (OSDE) for use in an undergraduate pharmacy training programme
(University of the Western Cape, 2004) Frieslaar, Denise Eleanor; Syce, James A.; Bheekie, Angeni; Faculty of Science
Neuropharmacological profile of Mentha longifolia: Effects on convulsion, nociception and pentobarbitone-induced sleep in mice
(University of the Western Cape, 2004) Erasmus, Shaun; Amabeoku, G
Mentha longifolia Huds., subspecies, capensis Briq, a plant species used for the treatment of epilepsy, painful conditions such as headache and toothache, and insomnia amongst other ailments, was investigated for anticonvulsant, analgesic and central nervous system depressant activities using chemically-induced seizures, acetic acid-induced writhing and hot-plate thermal stimulation, and pentobarbitone sleeping tests respectively in mice. The parameters used for the measurement of the anticonwlsant activity included the onset of seizures and/or the incidence of the seizures. For the analgesic activities, the parameters of measurement were, the number of writhes for the acetic acid test and reaction time of animals to thermal stimulation for the hot-plate test. For the central nervous system depressant activity, akin to the anti-insomniac activity, the parameter of measurement was the duration of sleep elicited by pentobarbitone. All the data obtained were analysed using the paired Student's t-test with the exception of that on the incidence of seizures, which was analysed using Chi-squared test. Aqueous extract of M. longifolia significantly delayed the onset of pentylenetetrazoleinduced seizures, profoundly antagonised the seizures elicited by picrotoxin and had no effects against seizures induced by either bicuculline or N-methyl-Dl-aspartic acid. M. longifulia completely antagonised acetic acid-induced writhing and profoundly delayed the reaction times of the animals to hot-plate thermal stimulations in similar manner to the standard drugs, paracetamol and morphine respectively. Like the standard drug, diazeparn, M. longifolia significantly prolonged the duration of sleep induced by pentobarbitone. The phytochemical analysis carried out on the leaves of M. longifolia showed the presence ofsaponins, tannins, reducing sugars, cardiac glycosides, flavonoids and triterpene steroids. The HPLC spectrum of M. longifolia showed major peaks at the following retention times (minutes) : 20.52, 22.37, 23.1 5, 24.87 and 26.93. The data obtained show that M. longifoliahas anticonvulsant, analgesic and anti insomniac activities, thus justifying the claim by traditional health practitioners of its use in epilepsy, painful conditions and insomnia.
Evaluation of guidelines for clinical trials of traditional plant medicines
(University of the Western Cape, 2005) Van Wyk, Anthea; Syce, James A.; School of Pharmacy; Faculty of Community and Health Sciences
The World Health Organization estimates that 4 billion people use herbal medicine for some aspect of primary health care. These herbal products are however mostly used without the necessary clinical trial done to prove their pharmacological activities and, therefore, their quality, efficacy and safety. It was the objective of this study to review the current international guidelines for the evaluation of herbal medicine; to gain a perspective on the number, type and quality of clinical trials that have been done on herbal medicine and to adopt a set of guidelines that could be used to conduct trial on a traditional herbal medicine used in South Africa. To verify these guidelines, a protocol for a clinical trial was drafted and submitted for approval to the regulatory and ethical authorities in South Africa.
Acute and chronic toxicity of the flavonoid-containing plant, Artemisia afra in rodents
(University of the Western Cape, 2005) Mukinda, James Tshikosa; Syce, James A.; School of Pharmacy; Faculty of Community and Health Sciences
The aim of this study was to investigate the possible toxicity of the flavonoid-containing plant, Artemisia afra and especially establish the safety of the aqueous extract of this plant after acute and chronic administration to mice and rats respectively.

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