Multi-targeted action of rooibos may protect against ischaemic stroke-induced neurological deficit and endothelial dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigenous use communities in the Western Cape (South Africa) where Aspalathus linearis (Brum.f) R.Dahlgren - or rooibos - grows naturally, has a long history of using rooibos for medicinal purposes. Apart from its well-known antioxidant effect, the Cederberg community in particular has been using rooibos as a treatment for high blood pressure. Given the detrimental effects of high blood pressure on endothelial cells, rooibos may either directly or indirectly affect vascular health. This, together with more recent reports of neuroprotective effects, may position rooibos as complementary medicine in related vascular conditions such as ischaemic stroke. AIMS OF THE STUDY: The study aimed to evaluate the potential benefit of acute administration of unfermented rooibos, on vascular health in a larval zebrafish model of stroke. MATERIALS AND METHODS: Stroke was induced via 24-h ponatinib exposure, in the presence or absence of an aqueous solution of an ethanolic extract of unfermented Rooibos (GreenOxithin™). The magnitude of stroke was assessed by monitoring larval locomotion and thrombus formation. In terms of specific mechanisms probed, changes in redox status (MDA and TEAC), neurological markers (TH and NeuroD1) and endothelial health (tight/adhesion junction protein expression) were assessed. RESULTS: Rooibos treatment limited thrombus formation and prevented stroke-induced deficits on larval motility. In terms of redox status, rooibos treatment prevented lipid peroxidation 3 days after initial stroke induction, reducing the need for significant upregulation of endogenous antioxidant mechanisms. Stroke-induced changes in neuronal (NeuroD1 and TH) protein expression were normalized in the presence of rooibos, suggesting a neuroprotective role. In terms of tight junction proteins, stroke-related decreases in ZO-1 expression were again prevented by rooibos treatment. In addition, rooibos treatment may beneficially modulate levels of claudin-5 and VE-cadherin, to indirectly limit stroke-associated vascular dysfunction. CONCLUSIONS: Taken together, activity data and physiological assessments suggest that unfermented rooibos may indeed have benefit in the context of stroke, via action at multiple targets. Thus, current data further our understanding of the mechanisms of actions of rooibos and warrant future research to confirm sufficient bioavailability of rooibos in target tissues, in mammalian systems.

Accelerated ageing profile in inflammatory arthritis is unique and tissue compartment specific.

Rheumatoid arthritis is prevalent in more than 1% of the global population, with the highest occurrence between ages 35 and 50, which places a huge burden on the economy. Drug discovery for the prevention of this chronic disease is; therefore, a priority. It is known that subclinical progression of many chronic non-communicable diseases is exacerbated via accelerated ageing, a pro-inflammatory phenotype shift. However, rheumatoid arthritis additionally has significant humoral immune activation, inflammatory signalling-and thus the accelerated ageing profile-may differ from other chronic inflammatory diseases. The current study simulated inflammatory arthritis onset in a collagen-induced arthritis (CIA) rodent model, to characterise the redox and inflammatory profile at the onset of clinical symptoms, in different tissues, in the presence and absence of preventative antioxidant treatment. The data illustrate that an increased free radical level are evident already very early on in RA disease progression. Furthermore, oxidative stress seems to somewhat precede a significant pro-inflammatory state, perhaps due to humoral immune activation. Our data across different compartments further suggest that the compensatory increase in endogenous antioxidant activity is gradually exhausted at a different pace, with the liver showing the first signs of oxidant damage, even before significant evidence exist in circulation. The current data further suggest that preventative antioxidant intervention may have a sparing effect on endogenous antioxidant mechanisms and preserve telomere length to delay disease progression-or at least the accelerated ageing known to exacerbate RA symptoms-although it did not seem to have a significant direct effect on the autoimmune activity.

Comparative efficiency of prostate-specific antigen screening strategies for prostate cancer detection.

CONTEXT: Despite widespread use of serum prostate-specific antigen (PSA) testing to detect prostate cancer, the relative effectiveness of different PSA screening strategies is unknown. OBJECTIVE: To compare prostate cancer mortality, PSA testing rates, and biopsy rates using various PSA screening strategies, including the standard strategy of annually testing men aged 50 through 75 years. DESIGN AND SETTING: A Monte-Carlo simulation based on a Markov model was used to simulate the natural history of prostate cancer using different starting ages, testing intervals, and PSA thresholds for prostate biopsy. Age-specific PSA levels and prostate biopsy detection probabilities were determined from population data and surgical series. MAIN OUTCOME MEASURES: Numbers of prevented prostate cancer deaths, PSA tests, and prostate biopsies per 1000 men aged 40 through 80 years, compared among 7 different strategies vs no screening. RESULTS: Compared with annual PSA testing beginning at age 50 years, the strategy of PSA testing at ages 40 and 45 years followed by biennial testing beginning at age 50 years was estimated to simultaneously reduce prostate cancer mortality and number of PSA tests and biopsies performed per 1000 men. Specifically, compared with no screening, the standard strategy prevents 3.2 deaths, with an additional 10,500 PSA tests and 600 prostate biopsies, while the earlier but less frequent strategy prevents 3.3 deaths, with an additional 7500 PSA tests and 450 prostate biopsies. Strategies that lowered the PSA threshold for prostate biopsy to below 4.0 ng/mL or strategies that used age-specific PSA levels were not more efficient than use of a PSA threshold of 4.0 ng/mL. These 2 findings remained true under all sensitivity analyses performed to test assumptions of the model. CONCLUSION: Recognizing that the efficacy of PSA screening is unproved, the standard strategy of annual PSA screening beginning at age 50 years appears to be less effective and more resource intensive compared with a strategy that begins earlier but screens biennially instead of annually. JAMA. 2000;284:1399-1405.

In vivo and in vitro maturation of human oocytes: effects on embryo development and polyspermic fertilization.

OBJECTIVE: To compare the effects of in vivo and in vitro maturation of human oocytes. DESIGN: Women (n = 60) undergoing follicular stimulation for in vitro fertilization, using long-course analog therapy to suppress endogenous luteinizing hormone (LH), were randomly allocated to a short (34 hour) or long (39 hour) delay between human chorionic gonadotropin (hCG) administration and oocyte retrieval. Each patient's oocytes were divided into two groups that were either inseminated immediately or after 5 hours. RESULTS: The incidence of polyspermic fertilization was highest in oocytes inseminated immediately after a short hCG/oocyte retrieval interval (17/100) and was significantly (P less than 0.05) reduced by preincubation and/or a long hGG/oocyte retrieval interval. Fertilization rates were higher with 39 hours than with 34 hours in vivo maturation (84.2% versus 76.8%; P less than 0.05). The incidence of delayed fertilization was reduced by extending the hCG/oocyte retrieval interval (short, 12.9%; long, 3.9%; P less than 0.001). CONCLUSIONS: Extension of the in vivo maturation time increased fertilization rates and eliminated the requirement for preinsemination incubation, allowing simplification of laboratory procedures.

Repeated freezing and thawing of peripheral blood and DNA in suspension: effects on DNA yield and integrity.

The possibility of DNA degradation is of concern to all involved in the storage of DNA, whether for diagnostic or research purposes. Many DNA banks are at present maintained at low temperatures, but optimum conditions for storage and handling have yet to be fully assessed. Both DNA and fresh blood have been subjected to repeated cycles of freezing and thawing and DNA extracted from the blood. DNA yield has been established and integrity examined by digestion, electrophoresis, and Southern blot analysis using DNA fingerprinting techniques. No degradation of DNA could be detected using these techniques; however, DNA yield was shown to be adversely affected by freezing, with yield reduced by more than 25% in blood samples frozen only once.

The concentration of ascorbic acid in the posterior and anterior chambers of the rhesus monkey (Macaca mulatta).

The ascorbic acid concentration in the posterior and anterior chambers of the rhesus monkey (Macaca mulatta) eye was determined, and found to be significantly higher in the posterior chamber. Monkeys anesthetized with pentobarbital sodium had a higher posterior chamber ascorbic acid concentration than monkeys sedated with phencyclidine. The ascorbic acid diffusion coefficient, calculated from the posterior and anterior chamber data, was 0.0012 min.-1 for monkeys given phencyclidine and 0.0010 min.-1 for pentobarbital-anesthetized monkeys.