Current Pharmaceutical Biotechnology - Volume 7, Issue 1, 2006

Essential hypertension (EH) affects ≈20% of the adult population, and has a multifactorial origin arising from an interaction between susceptibility genes and environmental factors. Several strategies and methods have been used to identify hypertension susceptibility genes. This review is thought to highlight current strategies for a better understanding of their limitations and strengths in a complex trait like EH. Linkage analysis is less effective at identifying common variants with modest effects typical for complex traits, and has therefore proved to be largely unsuccessful in EH. No candidate gene was assessed by a human linkage study so far. Possible redesigns of the linkage approach for complex diseases may include larger sample sizes and dense marker maps. Genetic association studies may be an effective approach to the problems posed by complex traits. With the explosion of genotyping technologies, genome-wide association studies have become feasible, and small-scale association studies have become plentiful. The different types of association studies are reviewed and issues that are important to consider when interpreting association studies of complex traits are discussed. Properly defined phenotypes, large enough sample cohorts to achieve sufficient statistical power, carefully matched samples to avoid population stratification are all integral parts of a high-quality association study. Multiple testing often results in false-positive results by chance, and inconclusive results may arise from ignoring linkage disequilibrium of the tested polymorphism, an effect avoidable by haplotype analysis. A new evolutionary development of the candidate gene approach is introduced which will extent traditional association study settings gaining better understanding of complex diseases like hypertension and might give better chances to evaluate association studies for their functional relevance.

Foods and nutrients play a vital role in normal functioning of the body. They are helpful in maintaining the health of the individual and in reducing the risk of various diseases. Worldwide acceptance of this fact formed a recognition link between "nutrition" and "health" and the concept of "nutraceuticals" was evolved. Nutraceuticals are medicinal foods that play a role in maintaining well being, enhancing health, modulating immunity and thereby preventing as well as treating specific diseases. Thus the field of nutraceuticals can be envisioned as one of the missing blocks in the health benefit of an individual. More than any other disease, the etiology of cardiovascular disease reveals many risk factors that are amenable to nutraceutical intervention. The scientific literature shows that several ingredients marketed for use in dietary supplements address each of these. The ability of nutraceuticals to positively influence cardiovascular risk factors should be recognized as an enormous opportunity in the treatment of a highly prevalent disease. Nutraceuticals hold promise in clinical therapy as they have the potential to significantly reduce the risk of side effects associated with chemotherapy along with reducing the global health care cost. In this review, an attempt has been made to summarize some of the recent research findings on garlic, omega-3-fatty acids, soy products, dietary fibres, vitamins, antioxidants, plant sterols, flavonoids, prebiotics and probiotics that have beneficial effects on the heart, in order to update the practising clinician on the benefit of using nutraceuticals for the management of cardiovascular diseases.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases have been implicated in a number of connective tissue pathologies including Ehlers-Danlos syndrome type VII C, Weill-Marchesani syndrome, encephalomyelitis, and arthritis. These proteinases therefore represent potential therapeutic targets for the treatment of such conditions. The synthesis and activity of ADAMTS proteinases is regulated at multiple levels: transcription, RNA splicing, translation, proteolytic processing, cofactor stimulation and inhibition, each of which represents a possible point of therapeutic intervention. Recent research suggests that, in addition to the direct inhibition of ADAMTS proteinases with low molecular weight non-peptidic inhibitors, targeting the transcription and protein processing of these enzymes could be effective therapeutic approaches.

Medicinal plants are the most important source of life saving drugs for the majority of the world's population. The biotechnological tools are important to select, multiply and conserve the critical genotypes of medicinal plants. Plant tissue culture techniques offer an integrated approach for the production of standardized quality phytopharmaceutical through mass-production of consistent plant material for physiological characterization and analysis of active ingredients. Micropropagation protocols for cloning of some medicinal plants such as Catharanthus roseus (Apocynaceae), Chlorophytum borivilianum (Liliaceae), Datura metel (Solanaceae), and Bacopa monnieri (Scrophulariaceae) have been developed. Regeneration occurred via organogenesis and embryogenesis in response to auxins and cytokinins. The integrated approaches of our culture systems will provide the basis for the future development of novel, safe, effective, and highquality products for consumers.

Fluorescence fluctuation spectroscopy is a versatile technique applied to in vitro and in vivo investigations of biochemical processes such as interactions, mobilities or densities with high specifity and sensitivity. The prerequisite of this dynamical fluorescence technique is to have, at a time, only few fluorescent molecules in the detection volume in order to generate significant fluorescence fluctuations. For usual confocal fluorescence microscopy this amounts to a useful concentration in the nanomolar range. The concentration of many biomolecules in living cell or on cell membranes is, however, often quite high, usually in the micro- to the millimolar range. To allow fluctuation spectroscopy and track intracellular interaction or localization of single fluorescently labeled biomolecules in such crowded environments, development of detection volumes with nanoscale resolution is necessary. As diffraction prevents this in the case of light microscopy, new (non-invasive) optical concepts have been developed. In this mini-review article we present recent advancements, implemented to decrease the detection volume below that of normal fluorescence microscopy. Especially, their combination with fluorescence fluctuation spectroscopy is emphasized.