Jacques Snyman - Academia.edu (original) (raw)

Papers by Jacques Snyman

Clinical and Experimental Gastroenterology, 2014

The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D), is a synthetically enhance... more The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D), is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1) endoscopically negative gastroesophageal reflux disease (ENGORD) and 2) nonsteroidal anti-inflammatory drug (NSAID) medication. Two randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0-3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary. In the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05) in severity of symptoms including reduction in heartburn (44%), discomfort (54%), and pain (56%). Symptom-free days improved by 41% compared to the group who received placebo (not significant). This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated clinoptilolite. Treatment with the potentiated clinoptilolite resulted in significant prevention (P≤0.05) of mucosal erosion severity as graded by the gastroenterologist. Absorbatox is a nonabsorbable aluminosilicate with potential gastroprotective benefits as it protected against ENGORD symptoms and NSAID-induced gastric events. The exact mechanism of action is not clear but may be due to its binding to hydrogen ions and biologically active amines and nitrates.

World Allergy Organization Journal, 2007

World Allergy Organization Journal, 2007

Journal of Clinical Nursing, 2007

To investigate the hypothetical benefits of the IV 2TM flow medical device.

Clinical, Cosmetic and Investigational Dermatology, 2011

The purpose of this study was to evaluate the efficacy and safety of carbohydratederived fulvic a... more The purpose of this study was to evaluate the efficacy and safety of carbohydratederived fulvic acid (CHD-FA) in the treatment of eczema in patients two years and older. In this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks. All safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results. CHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.

Clinical Chemistry and Laboratory Medicine, 2000

The co-ordinate expression and regulation of the drug metabolising enzymes, cytochrome P4501A1 (C... more The co-ordinate expression and regulation of the drug metabolising enzymes, cytochrome P4501A1 (CYPlAl) and glutathione transferases (GSTM1, GSTT1 and GSTP1), and their metabolic balance in the cells of target organs may determine whether exposure to carcinogens results in cancer. Besides showing variability in activity due to induction and inhibition, these enzymes also exhibit genetic polymorphism that alter enzyme levels and activity. We determined frequencies of common allelic variants of CYP1A1 and glutathione (M1, T1 and P1) among Tanzanians, South African Venda and Zimbabweans using PCR/restriction fragment length polymorphism techniques. The CYP1A1 Val462 mutant variant was found at a frequency of 1.3% among 114 subjects. The GSTM1*0 genotype was found at a frequency of 29% and 33% among Tanzanian psychiatric patients and healthy volunteers, respectively. Similarly, the GSTT1*0 polymorphism was present with a frequency of 25% in both the psychiatric patients and healthy controls. The frequency of GSTP1 Val105 variant was 16%, 12% and 21% among Tanzanians, South African Venda and Zimbabweans, respectively. We conclude here that CYP1A1 Val462 polymorphism is very rare among Africans. This is the first report of the GSTP1 Val105 variant frequency in African populations. We show here that there are no differences in frequencies of the variant alleles for CYP1A1, GSTM1, GSTT1 and GSTP1 in the three African populations.

European Journal of Clinical Pharmacology, 1994

Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramin... more Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine.

The Open Conference Proceedings Journal, 2010

A pilot study was done to determine if potassium humate, a natural substance derived from brown c... more A pilot study was done to determine if potassium humate, a natural substance derived from brown coal, with known anti-inflammatory properties, is safe and effective in reducing pain and inflammation in osteoarthritis of the knee. This was conducted as a randomized, double-blind, placebo-controlled, single centre, cross-over. Participants were enrolled for a total of 14 weeks, starting with an initial 1-week washout period, after which they were randomly assigned to either potassium humate or lactose, administered orally for 6 weeks at a dosage of 600mg three times daily. Following another 1-week washout period, participants were crossed over to the other treatment for another 6 weeks. Participants were not permitted the use of anti-inflammatory medications. Paracetamol was allowed as rescue medication for the duration of the trial. The primary efficacy variable were the WOMAC™ scores (visual analogue version) for pain, stiffness, physical function and total score and health related issues using the RAND 36 levels, rescue medication use, adverse effects and tolerability. 28 participants were enrolled and 21 participants successfully completed the protocol. A carry-over effect in the stiffness subscale was observed. There was a significantly greater clinical benefit with potassium humate over placebo with reduction in all the WOMAC subscale scores for pain. After adjusting for baseline, potassium humate showed a greater reduction in hs-CRP levels when compared to placebo. Tolerability was good for all groups. Safety parameters remained unchanged, except for an increase in the GGT-levels (n=4 in potassium humate group, n=2 in the placebo group). Levels of GGT returned to baseline within 2 weeks of discontinuation of therapy. In conclusion, potassium humate showed benefit over placebo in patients with OA of the knee, with a statistically significant reduction in hs-CRP levels. The patient reported outcomes proved a clinically significant benefit of potassium humate over placebo. The small sample size and the carry-over effect limited further interpretation of data.

The Open Conference Proceedings Journal, 2010

A pilot study was done to determine if potassium humate, a natural substance derived from brown c... more A pilot study was done to determine if potassium humate, a natural substance derived from brown coal, with known anti-inflammatory properties, is safe and effective in reducing pain and inflammation in osteoarthritis of the knee. This was conducted as a randomized, double-blind, placebo-controlled, single centre, cross-over. Participants were enrolled for a total of 14 weeks, starting with an initial 1-week washout period, after which they were randomly assigned to either potassium humate or lactose, administered orally for 6 weeks at a dosage of 600mg three times daily. Following another 1-week washout period, participants were crossed over to the other treatment for another 6 weeks. Participants were not permitted the use of anti-inflammatory medications. Paracetamol was allowed as rescue medication for the duration of the trial. The primary efficacy variable were the WOMAC™ scores (visual analogue version) for pain, stiffness, physical function and total score and health related issues using the RAND 36 levels, rescue medication use, adverse effects and tolerability. 28 participants were enrolled and 21 participants successfully completed the protocol. A carry-over effect in the stiffness subscale was observed. There was a significantly greater clinical benefit with potassium humate over placebo with reduction in all the WOMAC subscale scores for pain. After adjusting for baseline, potassium humate showed a greater reduction in hs-CRP levels when compared to placebo. Tolerability was good for all groups. Safety parameters remained unchanged, except for an increase in the GGT-levels (n=4 in potassium humate group, n=2 in the placebo group). Levels of GGT returned to baseline within 2 weeks of discontinuation of therapy. In conclusion, potassium humate showed benefit over placebo in patients with OA of the knee, with a statistically significant reduction in hs-CRP levels. The patient reported outcomes proved a clinically significant benefit of potassium humate over placebo. The small sample size and the carry-over effect limited further interpretation of data.

Current Therapeutic Research-clinical and Experimental, 1995

The present study, carried out in nine healthy male volunteers, investigated the effects of metoc... more The present study, carried out in nine healthy male volunteers, investigated the effects of metoclopramide, ondansetron, and granisetron on gastric emptying of liquids, as assessed by the percentage cumulative fraction absorbed-time profiles of paracetamol. A single-blind, crossover, randomized design was followed that allowed at least a 2-week interval between study sessions. On each occasion, 1.5 g paracetamol was taken at

Pharmacogenetics, 1998

The expression and regulation of the xenobiotic metabolizing enzymes, cytochrome P4501A1 (CYP1A1)... more The expression and regulation of the xenobiotic metabolizing enzymes, cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTM1 and GSTT1), and their metabolic balance in the cells of target organs may determine whether exposure to carcinogens results in cancer (Daly et al, 1994). The genes for these enzymes exist as various mutant variants resulting in metabolic polymorphisms where a proportion of the population exhibits deficient, reduced or enhanced activity of a ...

Waste Management & Research, 2011

Excessive MSW production is a growing management problem for cities in developing countries, such... more Excessive MSW production is a growing management problem for cities in developing countries, such as South Africa. This study addresses these challenges with particular focus on the City of Tshwane. A major problem in Tshwane is that all the MSW generated in the city, including garden waste, is currently being landfilled. A waste stream analysis of Tshwane reveals the largest fraction of MSW is organic and biodegradable, and therefore suitable for compost production. The study proposes that Tshwane will have to address composting the biodegradable fraction of the MSW stream. This study attempts to understand the economics of composting practices in Tshwane, whether composting in Tshwane is financially viable. A comparative study, applying the dome aeration technology on a conventional static windrow, was conducted with the objective of investigating and proposing alternative improved composting technologies for green waste. Although the study focused on Tshwane, it can be argued that the findings could be implemented in any other South African municipality, and even implemented in other emerging countries.

Waste Management & Research, 2011

Tshwane is presently landfilling all of its municipal solid waste (MSW) with no pre-processing or... more Tshwane is presently landfilling all of its municipal solid waste (MSW) with no pre-processing or minimization efforts. This is a result of the available capacity of its existing landfills, thought to be able to satisfy the city's needs for, at most, the next 10 years. It is possible that the authorities will not wake up to the problem before it is too late. This study addresses these challenges. This study first identified and evaluated technologies available in developed countries for processing the various components of the MSW stream, appropriate to local conditions, as an alternative to landfilling, to ensure that these components will be either reused, recycled or rendered harmless to the environment before disposal. Then most appropriate technologies for Tshwane were selected and assembled into an optimal configuration to achieve a zero waste situation in Tshwane within a decade or two. This represents a significant change in MSW management in Tshwane, from total landfill to zero waste to landfill. Although the study focused on Tshwane, it can be argued that the findings can be implemented in any other South African municipality, and even implemented in other emerging countries.

Pharmacogenetics, 2003

This study was carried out to characterize the distribution of NAT2 allelic variants among a samp... more This study was carried out to characterize the distribution of NAT2 allelic variants among a sample of three African populations. We determined the frequencies of major NAT2 allele clusters (NAT2 à 5, à 6, à 7 and à 14) using PCR/ restriction fragment length polymorphism and sequencing techniques. The genotypes predict slow acetylator phenotypes of 49, 38 and 52% among Tanzanians, Venda and Zimbabweans, respectively. The most common genotype was NAT2 à 4/ à 5. NAT2 à 5 was the most common allele while NAT2 à 7 was the least common. A new allele with two base changes occurring together, 481C>T and 590G>A, is reported. The frequency of the occurrence of the combination 481C>T and 590G>A, was found to be 9% (30/326), 7% (14/192) and 8% (18/234) among Zimbabweans, Venda and Tanzanians, respectively. The allele has been named NAT2 à 6E. Among Africans, the change 481C>T is not only associated with 341C>T (i.e. the NAT2 à 5 allele cluster) as in other populations, but also with 590G>A on the same allele. Pharmacogenetics

European Journal of Clinical Pharmacology, 2001

The study was carried out to investigate the distribution of cytochrome P450 2D6 (CYP2D6) and CYP... more The study was carried out to investigate the distribution of cytochrome P450 2D6 (CYP2D6) and CYP2C19 genotype frequencies in three African populations and to compare these frequencies between healthy individuals and psychiatric patients. Three hundred and eighty-four subjects from South Africa (Venda), Tanzania, and Zimbabwe who consented to the study were genotyped for CYP2D6 (CYP2D6*1, *2, *3, *4, *5, and *17) and CYP2C19 (CYP2C19*1, *2, and *3) by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) techniques. The genotypes for CYP2D6 predicted a poor metabolizer frequency of 2.3% (2/88) in Tanzanian psychiatric patients, 1.9% (2/106) in Tanzanian healthy controls and 2.6% (2/76) in the South African Venda. The low-activity CYP2D6*17 allele frequency was higher in psychiatric patients (30%, 53/176) than in healthy individuals (20%, 43/212) in Tanzanians. The frequencies for CYP2C19*2 genotypes were predictive of a low prevalence of poor metabolizers (PMs). The CYP2C19*3 allele was absent in the three populations studied. There was no difference in CYP2D6 or CYP2C19 PM genotype frequencies between psychiatric patients and healthy subjects. The genotype results predict a low prevalence of people with deficient CYP2D6 and CYP2C19 activity among linguistically (Bantu) related populations of East and Southern Africa. The high frequency of the low-activity CYP2D6*17 allele predicts that the Bantu people have a reduced capacity to metabolise drugs that are CYP2D6 substrates.

Drug Development Research, 2010

ABSTRACT The anti-inflammatory properties of products that contain high levels of humic acid, suc... more ABSTRACT The anti-inflammatory properties of products that contain high levels of humic acid, such as peat, sapropeles, and mumie, are well described. The aim of this study was to establish the clinical efficacy of brown coal-derived potassium humate, as in vivo animal models had suggested similar efficacy of humate to prednisolone. In this double-blind, placebo-controlled study, atopic volunteers were recruited and randomized to placebo or 1.8 g potassium humate/day (three divided dosages) when they presented with hay fever. The efficacy parameters used were skin-prick tests for wheal and flare reactions, nasal smears for inflammatory cell accumulation, and cytokine levels. Patients also filled out daily symptom score cards to determine efficacy against symptoms of hay fever. Potassium humate resulted in a significant decrease in wheal and flare reactions as well as nasal eosinophil counts. These findings were supported by similar changes (not significant) in cytokine levels. Changes in symptom scores did not reach significance. This proof of concept study clearly demonstrated the potential of potassium humate in the treatment of inflammatory conditions such as hay fever. Drug Dev Res 71:358–363, 2010. © 2010 Wiley-Liss, Inc.

Current Therapeutic Research, 1993

Current Therapeutic Research, 1997

Serotonin (5-hydroxytryptamine [5-HT]) has been shown to act as a modulator of the cough reflex i... more Serotonin (5-hydroxytryptamine [5-HT]) has been shown to act as a modulator of the cough reflex in some species; however, the subtype of the 5-HT receptor influencing the cough reflex remains to be clarified. In this study, we compared the influence of prolonged treatment with buspirone (a 5-HT~A dualist), alone or combined with metergoline (a 5-HT 1 antagonist), pisotifen (a 5-HT 2 antagonist), or placebo, on capsaicin-induced cough. Fourteen normal volunteers with no history of respiratory infection within the preceding 6 weeks were involved in the study. For the construction of capsaicin cough dose-response curves the subjects took single breaths at 30-second intervals of either sodium chloride or a range of doses of capsaicin (0.4-50 nmol) in random order from a nebulizer controlled by a breath-activated dosimeter. The number of coughs occurring in the 30 seconds following each inhalation was noted and the results were expressed as the total cough count, the concentration of capsaicin causing two coughs (D2), and the concentration causing five or more coughs (D5). There were no statistically significant differences in D2, D5, or the total cough count with any of the treatment regimens when compared with the baseline capsaicin response obtained on the first study day. This study, therefore, shows that bnspirone does not significantly influence capsaicin-induced cough in humans, either alone or in the presence of various 5-HT antagonists. However, the bnspironeJpisotifen combination tended to be more cough-suppressing.

Clinical Drug Investigation, 1998

The present placebo-controlled study was designed to compare the effect of acute pretreatment wit... more The present placebo-controlled study was designed to compare the effect of acute pretreatment with dexfenfluramine and fluoxetine on the plasma aldosterone response to metoclopramide. Study Participants and Design: Ten healthy ambulatory male volunteers participated. Following a single-blind, randomised design, each volunteer received metoclopramide as an intravenous bolus of 10mg at 0700 hours on each experimental day. Participants were pretreated at 2200 hours the previous evening and 0500 hours in the morning with one of the following: fluoxetine 20mg, dexfenfluramine 30mg, or placebo. Results: In response to metoclopramide administration, the maximum concentration was significantly higher (p = 0.004) than baseline with placebo, fluoxetine and dexfenfluramine. The area under the curve of dexfenfluramine was significantly larger than that with both placebo (p = 0.007) and fluoxetine (p = 0.004), while that of fluoxetine was significantly larger than that of placebo (p = 0.01). Conclusion: Acute pretreatment with both dexfenfluramine and fluoxetine caused an enhancement of metoclopramide-induced aldosterone secretion, probably by augmenting serotonergic neurotransmission via serotonin (5-HT)4 receptors. The plasma aldosterone levels were significantly higher with dexfenfluramine compared with fluoxetine, probably as a result of larger 5-HT concentrations being available for stimulation of glomerulosa cell activity.

Clinical Drug Investigation, 1997

The lowering of the mean blood pressure (MBP) by a combination of losartan 50mg/captopril 50mg an... more The lowering of the mean blood pressure (MBP) by a combination of losartan 50mg/captopril 50mg and by, respectively, losartan 50mg and 100mg and captopril 50mg and 100mg was studied in 10 sodium-depleted normal subjects. A double-blind, randomised, 5-way crossover study design was followed. To induce the mild sodium depletion, each subject took 40mg furosemide orally 12 hours preceding each study session. On each study day the subjects were placed in a semirecumbent position and the MBP and heart rate were monitored at defined intervals over the 8 hours following the administration of the antihypertensive drug. The difference between captopril IOOmg and the combination regimens did not reach statistical significance. The combination of losartan 50mg/captopril 50mg caused a significantly greater maximum baselinesubtracted fall in MBP at 2 hours than did the 50 or 100mg losartan at 6 hours (p < 0.05). In addition, the area under the concentration-time curve from I to 8 hours (AUC 1-8) for the fall in MBP with the combination was significantly larger than that with the losartan-only regimens.

Clinical and Experimental Gastroenterology, 2014

The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D), is a synthetically enhance... more The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D), is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1) endoscopically negative gastroesophageal reflux disease (ENGORD) and 2) nonsteroidal anti-inflammatory drug (NSAID) medication. Two randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0-3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary. In the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05) in severity of symptoms including reduction in heartburn (44%), discomfort (54%), and pain (56%). Symptom-free days improved by 41% compared to the group who received placebo (not significant). This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated clinoptilolite. Treatment with the potentiated clinoptilolite resulted in significant prevention (P≤0.05) of mucosal erosion severity as graded by the gastroenterologist. Absorbatox is a nonabsorbable aluminosilicate with potential gastroprotective benefits as it protected against ENGORD symptoms and NSAID-induced gastric events. The exact mechanism of action is not clear but may be due to its binding to hydrogen ions and biologically active amines and nitrates.

World Allergy Organization Journal, 2007

World Allergy Organization Journal, 2007

Journal of Clinical Nursing, 2007

To investigate the hypothetical benefits of the IV 2TM flow medical device.

Clinical, Cosmetic and Investigational Dermatology, 2011

The purpose of this study was to evaluate the efficacy and safety of carbohydratederived fulvic a... more The purpose of this study was to evaluate the efficacy and safety of carbohydratederived fulvic acid (CHD-FA) in the treatment of eczema in patients two years and older. In this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks. All safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results. CHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.

Clinical Chemistry and Laboratory Medicine, 2000

The co-ordinate expression and regulation of the drug metabolising enzymes, cytochrome P4501A1 (C... more The co-ordinate expression and regulation of the drug metabolising enzymes, cytochrome P4501A1 (CYPlAl) and glutathione transferases (GSTM1, GSTT1 and GSTP1), and their metabolic balance in the cells of target organs may determine whether exposure to carcinogens results in cancer. Besides showing variability in activity due to induction and inhibition, these enzymes also exhibit genetic polymorphism that alter enzyme levels and activity. We determined frequencies of common allelic variants of CYP1A1 and glutathione (M1, T1 and P1) among Tanzanians, South African Venda and Zimbabweans using PCR/restriction fragment length polymorphism techniques. The CYP1A1 Val462 mutant variant was found at a frequency of 1.3% among 114 subjects. The GSTM1*0 genotype was found at a frequency of 29% and 33% among Tanzanian psychiatric patients and healthy volunteers, respectively. Similarly, the GSTT1*0 polymorphism was present with a frequency of 25% in both the psychiatric patients and healthy controls. The frequency of GSTP1 Val105 variant was 16%, 12% and 21% among Tanzanians, South African Venda and Zimbabweans, respectively. We conclude here that CYP1A1 Val462 polymorphism is very rare among Africans. This is the first report of the GSTP1 Val105 variant frequency in African populations. We show here that there are no differences in frequencies of the variant alleles for CYP1A1, GSTM1, GSTT1 and GSTP1 in the three African populations.

European Journal of Clinical Pharmacology, 1994

Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramin... more Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine.

The Open Conference Proceedings Journal, 2010

A pilot study was done to determine if potassium humate, a natural substance derived from brown c... more A pilot study was done to determine if potassium humate, a natural substance derived from brown coal, with known anti-inflammatory properties, is safe and effective in reducing pain and inflammation in osteoarthritis of the knee. This was conducted as a randomized, double-blind, placebo-controlled, single centre, cross-over. Participants were enrolled for a total of 14 weeks, starting with an initial 1-week washout period, after which they were randomly assigned to either potassium humate or lactose, administered orally for 6 weeks at a dosage of 600mg three times daily. Following another 1-week washout period, participants were crossed over to the other treatment for another 6 weeks. Participants were not permitted the use of anti-inflammatory medications. Paracetamol was allowed as rescue medication for the duration of the trial. The primary efficacy variable were the WOMAC™ scores (visual analogue version) for pain, stiffness, physical function and total score and health related issues using the RAND 36 levels, rescue medication use, adverse effects and tolerability. 28 participants were enrolled and 21 participants successfully completed the protocol. A carry-over effect in the stiffness subscale was observed. There was a significantly greater clinical benefit with potassium humate over placebo with reduction in all the WOMAC subscale scores for pain. After adjusting for baseline, potassium humate showed a greater reduction in hs-CRP levels when compared to placebo. Tolerability was good for all groups. Safety parameters remained unchanged, except for an increase in the GGT-levels (n=4 in potassium humate group, n=2 in the placebo group). Levels of GGT returned to baseline within 2 weeks of discontinuation of therapy. In conclusion, potassium humate showed benefit over placebo in patients with OA of the knee, with a statistically significant reduction in hs-CRP levels. The patient reported outcomes proved a clinically significant benefit of potassium humate over placebo. The small sample size and the carry-over effect limited further interpretation of data.

The Open Conference Proceedings Journal, 2010

A pilot study was done to determine if potassium humate, a natural substance derived from brown c... more A pilot study was done to determine if potassium humate, a natural substance derived from brown coal, with known anti-inflammatory properties, is safe and effective in reducing pain and inflammation in osteoarthritis of the knee. This was conducted as a randomized, double-blind, placebo-controlled, single centre, cross-over. Participants were enrolled for a total of 14 weeks, starting with an initial 1-week washout period, after which they were randomly assigned to either potassium humate or lactose, administered orally for 6 weeks at a dosage of 600mg three times daily. Following another 1-week washout period, participants were crossed over to the other treatment for another 6 weeks. Participants were not permitted the use of anti-inflammatory medications. Paracetamol was allowed as rescue medication for the duration of the trial. The primary efficacy variable were the WOMAC™ scores (visual analogue version) for pain, stiffness, physical function and total score and health related issues using the RAND 36 levels, rescue medication use, adverse effects and tolerability. 28 participants were enrolled and 21 participants successfully completed the protocol. A carry-over effect in the stiffness subscale was observed. There was a significantly greater clinical benefit with potassium humate over placebo with reduction in all the WOMAC subscale scores for pain. After adjusting for baseline, potassium humate showed a greater reduction in hs-CRP levels when compared to placebo. Tolerability was good for all groups. Safety parameters remained unchanged, except for an increase in the GGT-levels (n=4 in potassium humate group, n=2 in the placebo group). Levels of GGT returned to baseline within 2 weeks of discontinuation of therapy. In conclusion, potassium humate showed benefit over placebo in patients with OA of the knee, with a statistically significant reduction in hs-CRP levels. The patient reported outcomes proved a clinically significant benefit of potassium humate over placebo. The small sample size and the carry-over effect limited further interpretation of data.

Current Therapeutic Research-clinical and Experimental, 1995

The present study, carried out in nine healthy male volunteers, investigated the effects of metoc... more The present study, carried out in nine healthy male volunteers, investigated the effects of metoclopramide, ondansetron, and granisetron on gastric emptying of liquids, as assessed by the percentage cumulative fraction absorbed-time profiles of paracetamol. A single-blind, crossover, randomized design was followed that allowed at least a 2-week interval between study sessions. On each occasion, 1.5 g paracetamol was taken at

Pharmacogenetics, 1998

The expression and regulation of the xenobiotic metabolizing enzymes, cytochrome P4501A1 (CYP1A1)... more The expression and regulation of the xenobiotic metabolizing enzymes, cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTM1 and GSTT1), and their metabolic balance in the cells of target organs may determine whether exposure to carcinogens results in cancer (Daly et al, 1994). The genes for these enzymes exist as various mutant variants resulting in metabolic polymorphisms where a proportion of the population exhibits deficient, reduced or enhanced activity of a ...

Waste Management & Research, 2011

Excessive MSW production is a growing management problem for cities in developing countries, such... more Excessive MSW production is a growing management problem for cities in developing countries, such as South Africa. This study addresses these challenges with particular focus on the City of Tshwane. A major problem in Tshwane is that all the MSW generated in the city, including garden waste, is currently being landfilled. A waste stream analysis of Tshwane reveals the largest fraction of MSW is organic and biodegradable, and therefore suitable for compost production. The study proposes that Tshwane will have to address composting the biodegradable fraction of the MSW stream. This study attempts to understand the economics of composting practices in Tshwane, whether composting in Tshwane is financially viable. A comparative study, applying the dome aeration technology on a conventional static windrow, was conducted with the objective of investigating and proposing alternative improved composting technologies for green waste. Although the study focused on Tshwane, it can be argued that the findings could be implemented in any other South African municipality, and even implemented in other emerging countries.

Waste Management & Research, 2011

Tshwane is presently landfilling all of its municipal solid waste (MSW) with no pre-processing or... more Tshwane is presently landfilling all of its municipal solid waste (MSW) with no pre-processing or minimization efforts. This is a result of the available capacity of its existing landfills, thought to be able to satisfy the city&amp;amp;#39;s needs for, at most, the next 10 years. It is possible that the authorities will not wake up to the problem before it is too late. This study addresses these challenges. This study first identified and evaluated technologies available in developed countries for processing the various components of the MSW stream, appropriate to local conditions, as an alternative to landfilling, to ensure that these components will be either reused, recycled or rendered harmless to the environment before disposal. Then most appropriate technologies for Tshwane were selected and assembled into an optimal configuration to achieve a zero waste situation in Tshwane within a decade or two. This represents a significant change in MSW management in Tshwane, from total landfill to zero waste to landfill. Although the study focused on Tshwane, it can be argued that the findings can be implemented in any other South African municipality, and even implemented in other emerging countries.

Pharmacogenetics, 2003

This study was carried out to characterize the distribution of NAT2 allelic variants among a samp... more This study was carried out to characterize the distribution of NAT2 allelic variants among a sample of three African populations. We determined the frequencies of major NAT2 allele clusters (NAT2 à 5, à 6, à 7 and à 14) using PCR/ restriction fragment length polymorphism and sequencing techniques. The genotypes predict slow acetylator phenotypes of 49, 38 and 52% among Tanzanians, Venda and Zimbabweans, respectively. The most common genotype was NAT2 à 4/ à 5. NAT2 à 5 was the most common allele while NAT2 à 7 was the least common. A new allele with two base changes occurring together, 481C>T and 590G>A, is reported. The frequency of the occurrence of the combination 481C>T and 590G>A, was found to be 9% (30/326), 7% (14/192) and 8% (18/234) among Zimbabweans, Venda and Tanzanians, respectively. The allele has been named NAT2 à 6E. Among Africans, the change 481C>T is not only associated with 341C>T (i.e. the NAT2 à 5 allele cluster) as in other populations, but also with 590G>A on the same allele. Pharmacogenetics

European Journal of Clinical Pharmacology, 2001

The study was carried out to investigate the distribution of cytochrome P450 2D6 (CYP2D6) and CYP... more The study was carried out to investigate the distribution of cytochrome P450 2D6 (CYP2D6) and CYP2C19 genotype frequencies in three African populations and to compare these frequencies between healthy individuals and psychiatric patients. Three hundred and eighty-four subjects from South Africa (Venda), Tanzania, and Zimbabwe who consented to the study were genotyped for CYP2D6 (CYP2D6*1, *2, *3, *4, *5, and *17) and CYP2C19 (CYP2C19*1, *2, and *3) by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) techniques. The genotypes for CYP2D6 predicted a poor metabolizer frequency of 2.3% (2/88) in Tanzanian psychiatric patients, 1.9% (2/106) in Tanzanian healthy controls and 2.6% (2/76) in the South African Venda. The low-activity CYP2D6*17 allele frequency was higher in psychiatric patients (30%, 53/176) than in healthy individuals (20%, 43/212) in Tanzanians. The frequencies for CYP2C19*2 genotypes were predictive of a low prevalence of poor metabolizers (PMs). The CYP2C19*3 allele was absent in the three populations studied. There was no difference in CYP2D6 or CYP2C19 PM genotype frequencies between psychiatric patients and healthy subjects. The genotype results predict a low prevalence of people with deficient CYP2D6 and CYP2C19 activity among linguistically (Bantu) related populations of East and Southern Africa. The high frequency of the low-activity CYP2D6*17 allele predicts that the Bantu people have a reduced capacity to metabolise drugs that are CYP2D6 substrates.

Drug Development Research, 2010

ABSTRACT The anti-inflammatory properties of products that contain high levels of humic acid, suc... more ABSTRACT The anti-inflammatory properties of products that contain high levels of humic acid, such as peat, sapropeles, and mumie, are well described. The aim of this study was to establish the clinical efficacy of brown coal-derived potassium humate, as in vivo animal models had suggested similar efficacy of humate to prednisolone. In this double-blind, placebo-controlled study, atopic volunteers were recruited and randomized to placebo or 1.8 g potassium humate/day (three divided dosages) when they presented with hay fever. The efficacy parameters used were skin-prick tests for wheal and flare reactions, nasal smears for inflammatory cell accumulation, and cytokine levels. Patients also filled out daily symptom score cards to determine efficacy against symptoms of hay fever. Potassium humate resulted in a significant decrease in wheal and flare reactions as well as nasal eosinophil counts. These findings were supported by similar changes (not significant) in cytokine levels. Changes in symptom scores did not reach significance. This proof of concept study clearly demonstrated the potential of potassium humate in the treatment of inflammatory conditions such as hay fever. Drug Dev Res 71:358–363, 2010. © 2010 Wiley-Liss, Inc.

Current Therapeutic Research, 1993

Current Therapeutic Research, 1997

Serotonin (5-hydroxytryptamine [5-HT]) has been shown to act as a modulator of the cough reflex i... more Serotonin (5-hydroxytryptamine [5-HT]) has been shown to act as a modulator of the cough reflex in some species; however, the subtype of the 5-HT receptor influencing the cough reflex remains to be clarified. In this study, we compared the influence of prolonged treatment with buspirone (a 5-HT~A dualist), alone or combined with metergoline (a 5-HT 1 antagonist), pisotifen (a 5-HT 2 antagonist), or placebo, on capsaicin-induced cough. Fourteen normal volunteers with no history of respiratory infection within the preceding 6 weeks were involved in the study. For the construction of capsaicin cough dose-response curves the subjects took single breaths at 30-second intervals of either sodium chloride or a range of doses of capsaicin (0.4-50 nmol) in random order from a nebulizer controlled by a breath-activated dosimeter. The number of coughs occurring in the 30 seconds following each inhalation was noted and the results were expressed as the total cough count, the concentration of capsaicin causing two coughs (D2), and the concentration causing five or more coughs (D5). There were no statistically significant differences in D2, D5, or the total cough count with any of the treatment regimens when compared with the baseline capsaicin response obtained on the first study day. This study, therefore, shows that bnspirone does not significantly influence capsaicin-induced cough in humans, either alone or in the presence of various 5-HT antagonists. However, the bnspironeJpisotifen combination tended to be more cough-suppressing.

Clinical Drug Investigation, 1998

The present placebo-controlled study was designed to compare the effect of acute pretreatment wit... more The present placebo-controlled study was designed to compare the effect of acute pretreatment with dexfenfluramine and fluoxetine on the plasma aldosterone response to metoclopramide. Study Participants and Design: Ten healthy ambulatory male volunteers participated. Following a single-blind, randomised design, each volunteer received metoclopramide as an intravenous bolus of 10mg at 0700 hours on each experimental day. Participants were pretreated at 2200 hours the previous evening and 0500 hours in the morning with one of the following: fluoxetine 20mg, dexfenfluramine 30mg, or placebo. Results: In response to metoclopramide administration, the maximum concentration was significantly higher (p = 0.004) than baseline with placebo, fluoxetine and dexfenfluramine. The area under the curve of dexfenfluramine was significantly larger than that with both placebo (p = 0.007) and fluoxetine (p = 0.004), while that of fluoxetine was significantly larger than that of placebo (p = 0.01). Conclusion: Acute pretreatment with both dexfenfluramine and fluoxetine caused an enhancement of metoclopramide-induced aldosterone secretion, probably by augmenting serotonergic neurotransmission via serotonin (5-HT)4 receptors. The plasma aldosterone levels were significantly higher with dexfenfluramine compared with fluoxetine, probably as a result of larger 5-HT concentrations being available for stimulation of glomerulosa cell activity.

Clinical Drug Investigation, 1997

The lowering of the mean blood pressure (MBP) by a combination of losartan 50mg/captopril 50mg an... more The lowering of the mean blood pressure (MBP) by a combination of losartan 50mg/captopril 50mg and by, respectively, losartan 50mg and 100mg and captopril 50mg and 100mg was studied in 10 sodium-depleted normal subjects. A double-blind, randomised, 5-way crossover study design was followed. To induce the mild sodium depletion, each subject took 40mg furosemide orally 12 hours preceding each study session. On each study day the subjects were placed in a semirecumbent position and the MBP and heart rate were monitored at defined intervals over the 8 hours following the administration of the antihypertensive drug. The difference between captopril IOOmg and the combination regimens did not reach statistical significance. The combination of losartan 50mg/captopril 50mg caused a significantly greater maximum baselinesubtracted fall in MBP at 2 hours than did the 50 or 100mg losartan at 6 hours (p < 0.05). In addition, the area under the concentration-time curve from I to 8 hours (AUC 1-8) for the fall in MBP with the combination was significantly larger than that with the losartan-only regimens.