Model building and quantitative analysis of a tandem immuno-capturing assay as a screening tool for breast cancer.

The onset of breast cancer appears to occur, on average, a decade earlier in Mexican women in comparison to American or European women. Early detection and prevention of breast cancer are of crucial importance to increase survival and improve quality of life. Based on the molecular elucidation of critical events leading to breast carcinogenesis, a tandem immuno-capturing blood test was developed as a quantitative population screening assay in view of providing a cost-effective and non-invasive alternative to population screening. Clinical analysis of 63 Mexican women within an age group of 35-70, revealed that Interstron activity increases from 800+/-65 IUJPA (Interstron Units) in the asymptomatic normal women to 994+/-100 IUJPA in the symptomatic/benign group, reaching 1289+/-81 IUJPA in the cancerous group. Accordingly, activity thresholds were established at 800 and 1200 IUJPA respectively, encompassing three risk groups: (i) Healthy Otherwise Normal (<800 IUJPA); (ii) Grey Risk Area (>800 and <1200 IUJPA), and (iii) At Risk group (>1200 IUJPA). Taking into account both baseline and clinical case reports, the Healthy Otherwise Normal group and the At Risk group were mostly homogeneous in nature, comprising a population of normal and cancer patients respectively. The Grey Risk group is heterogeneous, likely reflecting a transitional nature towards a potential early stage of breast disease development. Based on these results, a screening algorithm was developed as the underlining principle for population surveillance encompassing over 30,000 Mexican women. The current screening results have enabled us to objectively prioritize medical attention to approximately 1 in 8 women out of the general population mapped within the At Risk group. Overall, our findings suggest that monitoring Interstron activity units provides a valuable quantitative screening analysis as to selectively streamline the population of women in need of early medical counseling and/or mammography, thereby enhancing both the quality and cost-effectiveness of preventative population surveillance programs targeting breast cancer.

Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species and upon nitrergic neurotransmission.

The major phenolics from the polar fraction of virgin olive oil (caffeic acid, oleuropein, tyrosol and hydroxytyrosol) have well-established antioxidant activities but their effects on reactive nitrogen species and nitrergic neurotransmission have not been fully investigated. The three catechol compounds were active as scavengers of nitric oxide generated spontaneously from the decomposition of sodium nitroprusside (approximately 50% inhibition achieved at 75 microM), and had similar ability to scavenge chemically generated peroxynitrite, as determined by an alpha1-antiproteinase inactivation assay (67.2%-92.4% reduction when added at 1 mM). Tyrosol was less active in these tests, but does not possess the catechol functionality. Despite their ability to interact with chemically prepared nitric oxide, neither oleuropein nor hydroxytyrosol at 5 microM altered NO*-mediated relaxations of the nerve-stimulated rat anococcygeus preparation, but this may be because the nitrergic transmitter is protected from the effects of externally applied scavengers. In conclusion, the phenolics found in virgin olive oil possess ability to scavenge reactive oxygen and nitrogen species that are implicated in human pathologies, but their impact may be restricted to those species present in the extracellular environment.

Anti-inflammatory activity of Agave intermixta Trel. and Cissus sicyoides L., species used in the Caribbean traditional medicine.

Agave intermixta Trel. and Cissus sicyoides L. are two tropical plants originating from the Dominican Republic. Aqueous extracts from these species are used in traditional medicine. In contrast, biological activity and toxicity of these plants are not yet evaluated systematically. The aim of the present work is to investigate a potential anti-inflammatory activity, and to elucidate the toxicity of the extracts. No lethal effects were produced after oral administration of the extracts. The values of the medium lethal doses after intraperitoneal administration were quite high for both species, although A. intermixta seems to be rather more toxic than C. sicyoides. The anti-inflammatory effects have been investigated in two experimental in vivo models. The carrageenan-induced rat paw oedema was chosen as a model for general inflammation, and the mice ear oedema test using tetradecanoylphorbol acetate as inflammatory agent as a model of topical inflammation. Dry extracts from decoctions of A. intermixta leaves and C. sicyoides stems were administered in doses of 300 and 500 mg/kg (p.o.) in the general model, and in doses of 3 and 5 mg/mouse ear for both plants in the topical model. In the general anti-inflammation assay, the oral administration of both extracts produced a significant anti-inflammatory effect, most pronounced for A. intermixta than for C. sicyoides. In the topical model, the administration of both extracts produced similar inhibitions of the oedema, with a reduction of approximately 50% in comparison with the control group. In homogenated tissue samples from the inflamed areas, a distinct decrease in the level of myeloperoxidase enzyme was noted.