This was a comparative study to determine if FIV infected SPF cats in a barrier unit is a superior model to FIV infected non SPF cats in a random access facility. A group of 8 SPF cats and a group of 16 non SPF cats were infected with blood from the same donor cat. Routine clinical examination and blood investigations were done at regular intervals for 200 weeks. Mean trend lines for all parameters and changes within groups and differences between groups were analyzed. Large individual and group variations were found, as well as many differences between groups. Most of these were clinically irrelevant. Possibly relevant differences included eosinophil count, C133 and CD8 percentages, CD4 absolute counts and CD4/CD8 ratio. The most significant difference was the death of several cats in the non SPF group and none in the SPF group. The conclusion of this study is that the SPF model is not superior to the non SPF model when routine clinical and laboratory parameters are studied.

Apoptosis, or programmed cell death, plays a significant role in the loss of CD4 lymphocytes, as well as the control of virus production in HIV and FIV infected humans and cats.' Many factors play a role in the enhancement or reduction of spontaneous CD4 apoptosis, including infective agents and environmental influences. This study looked at three groups of Specified Pathogen Free cats in a barrier unit, whereby these two influences are excluded. Spontaneous CD4 apoptosis and various other white blood cell parameters were compared between FIV infected SPF cats treated with the immune modulator BSS/BSSG and an untreated group. A FIV negative group of SPF cats served as a control. There were statistically significant differences between the treated and untreated groups, while the treated group's results tended more towards the FIV negative group. The conclusion is that the survival benefit provided by the compound(2) is at least partially due to an influence on spontaneous CD4 apoptosis.

CITATION: Bouic, P. J. D. et al. 2001. Plant sterol/sterolin supplement use in a cohort of South African HIV-infected patients : effects on immunological and virological surrogate markers. South African Medical Journal, 91(10):848-850.

A pilot study was undertaken to investigate the effects of the intake of capsules containing the plant sterols and sterolins (BSS:BSSG mixture) on selected immune parameters of volunteers participating in an ultra-marathon in Cape Town, South Africa. Those runners having received active capsules (n=9) showed less neutrophilia, lymphopenia and leukocytosis when compared to their counterparts having received placebo capsules (n=8): the placebo treated individuals showed significant increases in their total white blood cell numbers as well as in their neutrophils (p=0.03 and 0.03 respectively). Furthermore, statistically significant increases within lymphocyte subsets were observed in the runners having received the active capsules: CD3+ cells increased (p=0.02) as did CD4+ cells (p=0.03). In parallel, the BSS:BSSG capsules decreased the plasma level of IL6 in the runners using the active capsules (p=0.08) and significantly decreased the cortisol: DHEAs ratio (p=0.03), suggesting that these volunteers had less of an inflammatory response and were less immune suppressed during the post-marathon recovery period. These findings justify further investigations into the use of the phytosterols to prevent the subtle immunosuppression associated with excessive physical stress.

OBJECTIVE:To evaluate the adjuvant effect of beta-sitosterol and its glucoside in the treatment of culture proven pulmonary tuberculosis (PTB).DESIGN:A blinded randomised placebo-controlled trial in culture proven drug sensitive PTB. Patients were hospitalised for the duration of treatment and evaluated at monthly intervals with regard to sputum culture positivity, chest radiography, weight gain, Mantoux test response, routine haematology and liver functions. STATISTICAL EVALUATION: General linear models for repeated measures (SAS GLM package) compared the interaction effects, group effects and time effects of findings in 19 patients receiving sitosterols with those in 18 patients receiving a placebo (talcum powder). Absolute values and change from baseline values were evaluated, although only the latter are reported.RESULTS:Weight gain was significantly greater in the sitosterol group (mean weight gain 8.9 kg) than the placebo group (mean gain 6.1 kg) (P = 0.0023 group effects; P = 0.0001 for time effects). Speed of achieving culture negativity, radiological improvement and induration on Mantoux testing was similar in the two groups. Change in lymphocyte counts from baseline was significantly higher in the sitosterol group (P = 0.0001 and P = 0.0001 for group and time effects) as was the increase in eosinophil counts (P = 0.0001 and P = 0.0137 for group and time effects).CONCLUSION:The study has shown significantly improved weight gain and higher lymphocyte and eosinophil counts in PTB patients receiving sitosterols in addition to an efficacious antituberculosis regimen. Sitosterols and their possible mode of action should now be evaluated in larger numbers of tuberculosis patients and in diseases with a similar immunopathogenesis.

Two sisters living in Holland, with a niece now living in South Africa, were reported in 1958 to have inherited intermittent acute porphyria (IAP). In 1994 both sisters died from primary liver cancer. Other reports have also noted an increased mortality from carcinoma of the liver in porphyrics. Porphyria variegata has a high prevalence in white and coloured South Africans, and it would be relatively easy to ascertain whether those who have inherited the gene for this disorder, in South Africa, have a higher than reported mortality from liver cancer. If they do, consideration should be given to ways to reduce their risk of developing and dying from this cancer.

Objective. To study the pharmacokinetic behaviour of hypoxoside taken orally by 24 patients with lung cancer.Design. Randomised open study with three single doses of 1 600, 2 400 and 3 200 mg standardised Hypoxis plant extract (200 mg capsules) and a multiple-dose study on the first 6 patients taking 4 capsules 3 times daily for 11 days,Participants and setting. Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised at the Radiation Oncology Ward, Karl Bremer Hospital, Bellville, W. Cape.Methods. Blood was drawn at regular intervals up to 75 hours after single doses and the concentrations of metabolites of the aglucone of hypoxoside, rooperol, were measured with a high-performance liquid chromatography method, For the multiple-dose study blood was drawn before the first dose each day, Concentration-time relationships were analysed according to a conventional single open-compartment model and also by using the NONMEM digital computer programme,Results. Neither hypoxoside nor rooperol appear in circulation, This is due to complete phase II biotransformation to diglucuronide, disulphate and mixed glucuronide-sulphate metabolites, of which the latter is the major component, Considerable interpatient variation in concentration-time relationships was found in the single-dose studies, It was due to an active enterohepatic recirculation in some patients and a distinct lag phase in others together with zero-order rate of formation of rooperol in the colon, Computer modelling indicated a single open-compartment model in which the mass of the patient did not influence volume of distribution and clearance because formation of the metabolites is dependent on the metabolising capacity of the patient, However, the elimination of the metabolites follows first-order kinetics with half-lives ranging from 50 hours for the major metabolite to 20 hours for-the two minor metabolites, Multiple-dose studies also showed large interpatient variation.Conclusion. In order to reach metabolite levels near 100 mu g/ml, which have been shown to be tumouricidal after enzymatic deconjugation to rooperol, maintenance doses need to be individualised for each patient, For most patients, however, a daily dose of 2 400 mg was sufficient.

OBJECTIVE:To assess the toxicity of hypoxoside taken orally by 24 patients with lung cancer.DESIGN:Open study with patients taking 1,200-3,200 mg standardised Hypoxis plant extract (200 mg capsules) per day divided in 3 doses in order to maintain metabolite blood levels near 100 micrograms/ml.PARTICIPANTS AND SETTING:Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised initially at the radiation oncology ward, Karl Bremer Hospital, Bellville, W. Cape. Thereafter they returned every 2 weeks for full clinical examinations.METHODS:Routine biochemical and haematological measurements were done. Patients underwent regular full clinical examinations including radiographs and computed tomography scanning according to the discretion of the principal investigator.RESULTS:Nineteen patients on hypoxoside therapy survived for an average of 4 months with progression of their primary tumours and metastases, while 5 survived for more than a year. One of them survived for 5 years and histological examination of the primary lesion showed absence of cancer. No toxic effects, in clinical examinations or biochemical or haematological measurements, were found that could be ascribed to the ingestion of hypoxoside. Only one occasion of possible drug intolerance, with anxiety, nausea, vomiting and diarrhoea, was noted.CONCLUSION:The absence of toxicity warrants further investigation of hypoxoside as an oral prodrug, especially in patients with slow-growing necrotising tumours that are inoperable and have high concentrations of beta-glucuronidase and sulphatase as well as a high sensitivity for rooperol.