Effect of Annona muricata aqueous leaf extract on reactive oxygen and nitrogen species.

OBJECTIVE: Annona muricata extracts are used in traditional medicine due to their significant biological effects. Verification and elucidation of their mechanisms is beneficial in terms of the usefulness of these extracts in everyday life or in the context of disease treatment or prevention. MATERIALS AND METHODS: The effectiveness of the extract was assessed from dried A. muricata leaves available for direct consumption. It is targeted against reactive oxygen and nitrogen species such as superoxide (O2•-), hydroxyl (•OH), nitric oxide (NO) radicals, and peroxynitrite anion (ONO2-) at concentrations of 5, 10, 25, 50, 100 µg.ml-1. RESULTS: No significant inhibitory activity was measured against O2·- at the assessed concentrations of the extract. Conversely, substantial antioxidant properties were found towards ·OH. Moreover, very efficient uptake was recorded at low concentrations of the extract, 5 µg.ml-1 (53.91%) and 10 µg.ml-1 (45.3%). The antioxidant effect decreased with increasing concentration. By indirect determination of NO oxidation derivatives it was found that, as the extract concentration increased, the nitrite concentration decreased. In contrast, even at low concentrations, the extract causes an increase in the peroxynitrite concentration. CONCLUSIONS: The results themselves show that the effects of A. muricata leaf extract are mainly mediated by the activity against •OH, as well as the consequences of increased ONO2- formation.

CEPHEUS SA: a South African survey on the undertreatment of hypercholesterolaemia.

AIM: The aim of the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) was to evaluate the current use and efficacy of lipidlowering drugs (LLDs), and to identify possible patient and physician characteristics associated with failure, if any, to achieve low-density lipoprotein cholesterol (LDL-C) targets. METHODS: The survey was conducted in 69 study centres in South Africa and recruited consecutive consenting patients who had been prescribed LLDs for at least three months. One visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Physicians and patients completed questionnaires regarding their knowledge, awareness and perceptions of hypercholesterolaemia and the treatment thereof. RESULTS: Of the 3 001 patients recruited, 2 996 were included in the final analyses. The mean age was 59.4 years, and 47.5% were female. Only 60.5 and 52.3% of patients on LLDs for at least three months achieved the LDL-C target recommended by the NCEP ATP III/2004 updated NCEP ATP III and the Fourth JETF/South African guidelines, respectively. Being male, older than 40 years, falling into the lower-risk categories, compliance with the medication regimen, and patient knowledge that the LDL-C goal had been reached, were associated with the highest probability of attaining LDL-C goals. CONCLUSION: The results of this survey highlight the sub-optimal lipid control achieved in many South African patients taking lipid-lowering therapy.

PBMCs from both atopic asthmatic and nonatopic children show a TH2 cytokine response to house dust mite allergen.

BACKGROUND: The hypothesis that in atopic diseases the T-helper response is skewed toward a T(H)2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. OBJECTIVE: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T(H)2 response and nonatopic subjects have a T(H)1 response to allergen and (2) whether atopic patients have a decreased ability to mount T(H)1 immune responses to mycobacterial antigens. METHODS: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. RESULTS: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-gamma ratio were significantly increased in subjects with atopic asthma, whereas IFN-gamma release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-gamma release, and the IL-5/IFN-gamma ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-gamma ratio in response to HDM than to PPD (a T(H)1 stimulus). CONCLUSION: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T(H)1 response to allergens, indicates that HDM stimulates a T(H)2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T(H)1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T(H)2 response.

Reduced interferon-gamma but normal IL-4 and IL-5 release by peripheral blood mononuclear cells from Xhosa children with atopic asthma.

BACKGROUND: Allergic asthma is increasing in black South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-gamma (IFN-gamma); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-gamma release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. OBJECTIVES: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-gamma release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. METHODS: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris-specific IgE was measured. RESULTS: Proliferation did not differ between the groups. The release of IFN-gamma was progressively decreased (and the IL-4/IFN-gamma ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-alpha release was reduced, but IL-4, IL-5, and granulocyte-macrophage-colony stimulating factor release was unchanged. The presence of Ascaris-specific IgE did not influence the cytokine profiles. CONCLUSION: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-gamma release is a generalized feature of atopic diseases. This study-the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles-indicates that the extent of the defect in IFN-gamma release might be related to asthma severity.

Chronic beta-blockade does not influence muscle power output during high-intensity exercise of short-duration.

Patients receiving beta-receptor antagonists for the treatment of hypertension frequently complain of impaired exercise tolerance. To determine whether these medications impair skeletal muscle contractile function, we measured isokinetic muscle function in ten healthy male cyclists receiving nebivolol (N), atenolol (A), propranolol (P) and the calcium channel antagonist diltiazem (D). The subjects performed standardized tests of muscle power on an isokinetic cycle ergometer following subacute ingestion of N, A, P, D and placebo (PL) in a double blind crossover trial. Subjects exercised maximally for 10 s at 90, 110, 120, 130 and 150 rpm with 2-min rest between sessions. Thereafter, they performed a 30-s fatigue test at 120 rpm. Resting heart rate was decreased 13.4%, 21.9% and 14.6% by N, A and P, respectively (P < 0.05 vs PL). Resting systolic blood pressure was decreased 6.7% by A only (P < 0.05 vs PL). Peak power, average power and work done was not different among treatment groups at any crank velocity, nor was there any difference in total work done or rate of work decline in the 30-s test. We concluded from our study that peak isokinetic muscle power during maximal exercise of short duration is not affected by beta-blockade or the calcium antagonist diltiazem. Fatigue during beta-receptor antagonism would not appear therefore to be due to changes in the ability of skeletal muscle to produce peak power output during exercise of short duration.

Genetic and environmental influences on cord blood serum IgE and on atopic sensitisation in infancy.

It has recently been reported that cord blood serum IgE (CBsIgE) concentrations in a black Third-World cohort were significantly higher than those in a similar cohort of white and coloured newborns, and were not influenced by an atopic family history (aFH). This study reports on the 1-year follow-up of these newborns carried out to determine whether statistical differences in median CBsIgE values at birth could be found between infants in each ethnic group who subsequently developed clinical atopy in the first year of life and those who remained healthy. The infants were seen at 3, 7 and 12 months of age. At each visit a detailed history was taken from the mothers, the infants were examined clinically for the presence of atopic disease and blood was taken for immunological assay (total serum IgE by paper-disc radio-immunosorbent testing, and radio-allergosorbent testing for egg-white, cow's milk and Dermatophygoides pteronyssinus). A combination of clinical and immunological variables was assessed in order to categorise the infants into 'atopic' or 'not atopic' groups at the end of the 1-year follow-up period. The black infants who completed the study had the lowest incidence of aFH (16%), but 64% of them developed atopic disease during infancy. The median CBsIgE values for the black infants who became atopic were lower than, but not statistically different from, those for the group who remained non-atopic (P = 0.57). The white and coloured infants who completed the study had 81.6% and 30.4% incidences of aFH respectively, with 47.4% and 58.7% respectively developing atopic disease during infancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug regulation in South Africa.

South Africa has a population of approximately 30 million people. The country has a mixture of advanced industrial and rural economies, but the medicine control system is consistent with similar systems established in the major industrial countries of Western Europe and North America. Because most of South Africa's population lives in conditions more closely akin to the developing world than to the Western nations, it is important to examine whether the country is optimally served by this drug regulation model and to define critically the strengths and limitations of the established system. The conclusions might be relevant for other countries at a comparable stage of development.

The influence of ethnicity, an atopic family history, and maternal ascariasis on cord blood serum IgE concentrations.

Raised concentrations of cord blood serum (CBs) IgE have previously been demonstrated to reflect a hereditary predisposition for atopy in First World, predominantly white populations. A cross-sectional study of 53 black, 52 white, and 58 mixed race newborn infants and maternal pairs was performed in a multiethnic, mixed First and Third World society. The CBs IgE concentrations were measured with a modification of the standard IgE PRIST, which could reliably determine IgE concentrations to an accuracy of 0.01 kU/L. The black group had the highest geometric mean and median CBs IgE concentrations (0.21; 0.16 kU/L), followed by the white group (0.12; 0.12 kU/L) and the mixed group (0.10; 0.08 kU/L). If those newborn infants with an atopic family history and maternal ascariasis were excluded, the remainder had geometric mean and median CBs IgE concentrations of 0.20; 0.16 kU/L in the black subgroup, followed by values of 0.06; 0.05 kU/L in the mixed subgroup, and 0.05; 0.07 kU/L in the white subgroup. Statistically significant ethnic differences in the median CBs IgE concentrations of these subgroups were demonstrated between the black-white (p less than 0.05) and the black-mixed (p less than 0.005) ethnic groups. A positive family history of atopy influenced the CBs IgE concentrations in the white and mixed groups but not in the black group. Of those newborn infants with a CBs IgE concentration greater than 0.5 kU/L, a family history of atopy was found in 100% of the white newborn infants, in 58.3% of the mixed newborn infants, and only in 14.3% of the black newborn infants. Many of the black newborn infants without a family history of atopy had extremely high CBs IgE concentrations. The influence of maternal ascariasis was equivocal in the mixed group but of no significance in the black group. The high CBs IgE concentrations in the black newborn infants, independent of an atopic family history and maternal ascariasis, suggest that this atopic marker may therefore be of limited use in identifying the "high allergic-risk" newborn infant in black Third World populations who appear to represent a pool of genetic high IgE-responder phenotypes.

The role of acute and latent virus infections in the pathogenesis of inner ear disturbances.

The possible role of herpesviral infections of the inner ear in suddenly appearing inner ear disturbances was investigated. Experimental pseudorabies virus (PRV, Herpes sui 1) infection of mice and swine was used as a model system. Infected mice represented the productive cycle of PRV infection (acute phase), whereas the latent phase of infection could be tested in swine. From the acutely infected mice the virus could be reisolated from perilymphatic fluid and various parts of the brain. Massive histopathologic alterations and signs of total cell damage to the organ of Corti and the vestibular organ were found. Accordingly, in all of the cells of the inner ear multiple copies of the PRV genome could be demonstrated. We therefore suggest that the disturbances of the inner ear were induced by the acute virus infection. In two latently infected swine (sixty weeks after infection), PRV could not be recovered either from the perilymphatic fluid or from a variety of different neural and extraneural tissues. However, histopathologic changes similar to those found in the acutely infected mice were observed. The presence of viral DNA could be demonstrated by in situ cytohybridization in both sensory and supportive cells of the inner ear and vestibular organ, but not in the corresponding nerve fibers, which is in contrast to the acutely infected mice. The distribution of the viral genome was further analyzed in adjacent areas of the central nervous system. An involvement of acute and latent herpes virus infection in inner ear dysfunction including sudden deafness and vestibular neuronitis in man, might be suggested from the results described. The presented animal model system, PRV-infected swine, should permit further studies on a possible role of herpetic recurrences, particularly with regard to inner ear disturbances.