Cf van der Merwe

Some effects of the essential fatty acids linoleic acid and alpha-linolenic acid and of their metabolites gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and of prostaglandins A1 and E1 on the proliferation of human osteogenic sarcoma cells in culture.

Gamma-linolenic acid has been shown to suppress the rate of proliferation of a number of malignant cell lines in culture. To test the proposal that this was a specific prostaglandin 1- or 2-series effect, 379 batches of MG63 human osteogenic sarcoma cells were seeded in Greiner flasks and cultured in media supplemented with a range of unsaturated fatty acids and prostaglandins. The monounsaturated fatty acid oleic acid enhanced the rate of cancer cell proliferation. The polyunsaturated fatty acids linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as prostaglandins E1 and A1 suppressed the rate of cell proliferation. Total suppression of colony forming and cell proliferation occurred at high levels of polyunsaturated fatty acid supplementation. In addition gamma-linolenic in the form of evening primrose seed oil and vitamin C has been given to 6 patients with histologically diagnosed primary liver cell cancer. Some clinical improvement and reduction in tumor size occurred in 3 cases. One patient has shown remarkable improvement in reduction of liver and tumor size on the CAT scan and reduction of the serum alkaline phosphatase from 2830 to 295 units and gamma-glutamyl transaminase from 274 to 82 units. Thus preliminary clinical results suggest that gamma-linolenic acid may be effective in the management of human cancer patients and further trials should be conducted. However, the cell culture results suggest that although the essential fatty acids suppress proliferation, eicosanoids of all 3 series may be involved. The proliferation suppressive effect of docosahexaenoic acid suggests that other aspects than only eicosanoid activity may also be important in the suppression of cancer cell proliferation.

Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines.

A double-blind, placebo-controlled phase II trial (e-Track 444563-014/NCT00346892) was conducted in South Africa to evaluate the co-administration of RIX4414 (live-attenuated human G1P[8] rotavirus vaccine) and oral poliovirus vaccine (OPV) administered simultaneously. Healthy infants (n=450) were randomized into three groups (RIX4414+OPV, RIX4414+IPV or Placebo+OPV) to receive two oral doses of RIX4414/placebo with OPV or IPV using two vaccination schedules (6-10 weeks and 10-14 weeks). Serum anti-rotavirus IgA antibodies (ELISA) and neutralizing antibodies (micro-neutralization assay) to poliovirus serotypes 1, 2 and 3 were measured. Co-administration of RIX4414 with OPV did not result in a decrease in the high sero-protection rates against poliovirus serotypes 1, 2 and 3 detected after the third OPV dose (98-100%). The anti-rotavirus IgA antibody sero-conversion rates were higher for the 10-14 weeks schedule (55-61%) compared to the 6-10 weeks schedule (36-43%). Solicited symptoms were reported at similar rates between RIX4414 and placebo groups and no serious adverse events related to RIX4414 were reported. This study provided evidence that RIX4414 can be co-administered with routine EPI immunizations including OPV and that two doses of RIX4414 were well tolerated and immunogenic in South African infants.

The effect of gamma-linolenic acid, an in vitro cytostatic substance contained in evening primrose oil, on primary liver cancer. A double-blind placebo controlled trial

The cytostatic effects of essential fatty acid metabolic intermediates and of some prostaglandins and leukotrienes in vitro have been extensively documented. The essential fatty acids (EFAs) exhibit no side-effects when taken as a dietary supplement, even in large doses. Primary Liver Cancer (PLC) is a fatal disease in our area as it is always multifocal in nature. In vitro studies have shown a cytostatic effect of gamma-linolenic acid (GLA) on primary liver cancer cells. In a double-blind placebo controlled trial, using Evening Primrose Oil (as a source of GLA) as a dietary supplement in PLC patients, no statistically significant effect was observed on survival time or liver size. There was however a statistical significant beneficial effect on Gamma Glutamyl transferase values as a measure of liver function. No side-effects were observed. The large size of tumour and the low doses of GLA used in this trial probably explain the lack of significant effect on survival times.

Comparison of 2 Different Regimens for Reactogenicity, Safety, and Immunogenicity of the Live Attenuated Oral Rotavirus Vaccine RIX4414 Coadministered with Oral Polio Vaccine in South African Infants

BACKGROUND A phase II, randomized, double-blind, placebo-controlled study was conducted in South Africa during 2003-2004 to evaluate the safety, reactogenicity, and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Expanded Program on Immunization childhood vaccines, including oral polio vaccine. METHODS Healthy infants were randomized (2:2:1) to receive either 2 doses of RIX4414 (n = 190; at 10 and 14 weeks, with placebo at 6 weeks), 3 doses of RIX4414 (n = 189; at 6, 10, and 14 weeks), or 3 doses of placebo (n = 96), all with concomitant routine vaccinations. The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo. Antipolio types 1, 2, and 3 antibodies were measured using a virus neutralization assay. Solicited symptoms were recorded for 15 days after each dose. RESULTS The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups (44.3% and 44.4%, respectively; P = .544, by 1-sided Fisher exact test) and antirotavirus IgA geometric mean concentrations were also comparable. Seroprotection rates for antipolio types 1, 2, and 3 antibodies were high (93%-100%) and were not significantly different among groups. Solicited symptoms reported within 15 days after vaccination were similar in all groups. CONCLUSIONS The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen. There was no interference by either regimen with antibody response to oral polio vaccine, and RIX4414 was well tolerated when given with routine vaccinations.

Chronic arachidonic acid eicosanoid imbalance: A common feature in coronary artery disease, hypercholesterolemia, cancer and other important diseases. Significance of desaturase enzyme inhibition and of the arachidonic acid desaturase-independent pathway

A chronic imbalance between the essential fatty acid metabolites arachidonic acid, gamma-linolenic acid and eicosapentaenoic acid and of their respective eicosanoid derivatives appears to be implicated in the etiology of many intractable disease. Most notable among these are coronary artery disease, cancer and chronic inflammation. The factors leading to such an imbalance and their relatively simple prophylactic and therapeutic circumvention are discussed briefly.

Margarines and coronary artery disease

In a previous paper we predicted that health effects of dietary fats in humans would require half a century or more to be understood, instead of the decade or so predicted during 1956 by an Editorial in The Lancet. It would seem that our prediction may have been optimistic since it has now been reported that trans unsaturated fatty acids present in high concentrations in margarines promote hypercholesterolemia in humans. Consequently, there has been a call for the reclassification of dietary fats upon the basis of their hypercholesterolemic properties. Using the latter criterion, therefore, many margarine brands would be classified as coronary artery disease risk foods. The primary adverse metabolic action of trans unsaturated fatty acids is the competitive inhibition of delta-6-desaturase, the hepatic enzyme responsible for the initial metabolic desaturation of the essential fatty acids cis linoleic and cis alpha-linolenic acid. In addition to margarines, many other common foods such as deep-fried foods, many convenience foods and bakery products contain relatively high levels of trans fatty acids. Therefore, since it has become virtually impossible to avoid a consistent, daily dietary intake of trans fatty acids, it would appear that a precautionary, preventative supplementation of the diet with supplements containing the direct metabolic products of delta-6-desaturation of the essential fatty acids, would be prudent. Such supplements are readily available.

Mosquito Vectors of Human Disease in South Africa

Extracted from text ... Mosquito Vectors of Human Disease in South Africa To the Editor: With reference to the very informative article by PG Jupp on mosquitoes as vectors of human disease in South Africa1, I would like to comment as follows: I own a farm in the region concerned and found the article very informative. The author gave the vector and symptoms of each disease but failed to name the therapy or the drugs involved in treatment of these unknown diseases. I realise that he is not a doctor, but seeing the excellent way in which he listed all the symptoms he could ..

Use of iron pots in South Africa led to haemosiderosis

EDITOR—Minerva writes about the cheap remedy of using iron pots for anaemic children in Ethiopia.1 Her suggested solution is not as simple as it may seem. South African indigenous people have been using iron pots …

A conjugate counting method to determine [75Se]SeHCAT retention in the human body.

To evaluate the functional integrity of the distal part of the ileum the retention of a gamma-labelled bile acid (SeHCAT) in the human body can be measured with a detector. Due to the lack of a whole body counter at our institution a two detector system was designed to measure SeHCAT retention and an evaluation of such a system has been made. The detectors are positioned on either side of a patient lying supine on a hospital trolley. The trolley is stepped forward in 100 mm steps, to determine the SeHCAT activity in the patient. With these counts the location of the SeHCAT activity and total activity present in the body can be determined. A water filled phantom and a phantom consisting of nine 1-L saline bags with 75Se activity placed in them was used to determine system performance. Four patients with no history of bowel disease were compared with published data for normals. Results showed that the system performed satisfactorily, and accurate quantitative measurements could be made, showing that this inexpensive system could be used where a whole body counter is not available.