Current
Pharmaceutical Biotechnology
ISSN: 1389-2010
Current Pharmaceutical Biotechnology
Volume 7, Number 1, February 2006
Contents
Identification of Genes for a Complex Trait: Examples from
Hypertension Pp. 1-13
A. Binder
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Nutraceuticals - An Emerging Era in the Treatment
and Prevention of Cardiovascular Diseases Pp. 15-23
C.S. Ramaa, A.R. Shirode, A.S. Mundada and V.J. Kadam
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ADAMTS Proteinases: Potential Therapeutic Targets?
Pp. 25-31
G.C. Jones
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Micropropagation: A Tool for the Production of
High Quality Plant-Based Medicines Pp. 33-49
M. Debnath, C.P. Malik and P.S. Bisen
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Fluorescence Fluctuation Spectroscopy in Reduced Detection
Volumes Pp. 51-66
H. Blom, L. Kastrup and C. Eggeling
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Abstracts
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Identification of Genes for a Complex
Trait: Examples from Hypertension
A. Binder
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.
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Nutraceuticals - An Emerging Era in the Treatment
and Prevention of Cardiovascular Diseases
C.S. Ramaa, A.R. Shirode, A.S. Mundada and V.J. Kadam
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.
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ADAMTS Proteinases: Potential Therapeutic Targets?
G.C. Jones
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.
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Micropropagation: A Tool for the Production of High
Quality Plant-Based Medicines
M. Debnath, C.P. Malik and P.S. Bisen
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 high-quality products for consumers.
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Fluorescence Fluctuation Spectroscopy in Reduced Detection
Volumes
H. Blom, L. Kastrup and C. Eggeling
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.
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