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BioJournal -
Jain PharmaBiotech Reports
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This report reviews the current state-of-art of antiviral approaches
including vaccines, pharmaceuticals and innovative technologies for delivery
of therapeutics. The introduction starts with a practical classification of
viral diseases according to their commercial importance. Various antiviral
approaches are described including pharmaceuticals and molecular biological
therapies such as gene therapy and RNA interference (RNAi) as well as
vaccines for virus infections. Expert opinion is given about the current
problems and needs in antiviral therapy. SWOT (strengths, weaknesses,
opportunities and threats) analysis of antiviral approaches is presented
against the background of concept of an ideal antiviral agent. |
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This report deals with cytogenetics in a broader sense rather than
the classical use mainly to describe the chromosome structure and
identify abnormalities related to disease. In the age of molecular
biology, it is also referred to as molecular cytogenetics. Historical
landmarks in the evolution of cytogenetics are reviewed since the first
images of chromosomes were made in 1879. The scope of cytogenetics
includes several technologies besides fluorescence in situ hybridization
(FISH), comparative genomic hybridization (CGH), and multicolor FISH.
Molecular cytogenetics includes application of nanobiotechnology,
microarrays, real-time polymerase chain reaction (PCR), in vivo imaging,
and single molecule detection. Bioinformatics is described briefly as it
plays an important role in analyzing data from many of these
technologies. |
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This report follows the broad definition of a biomarker as a
characteristic that can be objectively measured and evaluated as an
indicator of normal biological or pathogenic processes as well as
pharmacological responses to a therapeutic intervention. Tests based on
biomarkers have been around for more than half a century, but interest
in their application for diagnostics and drug discovery as well as
development has increased remarkably since the beginning of the 21st
century. This report describes different types of biomarkers and their
discovery using various “-omics” technologies such as proteomics and
metabolomics. Molecular diagnostics technologies are used for the
discovery of biomarkers and new tests are also based on biomarker. |
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Drug delivery to the cardiovascular system is different from
delivery to other systems because of the anatomy and physiology of the
vascular system; it supplies blood and nutrients to all organs of the
body. Drugs can be introduced into the vascular system for systemic
effects or targeted to an organ via the regional blood supply. In
addition to the usual formulations of drugs such as controlled release,
devices are used as well. This report starts with an introduction to
molecular cardiology and discusses its relationship to biotechnology and
drug delivery systems. |
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This report describes and evaluates the molecular diagnostics
technologies that will play an important role in practice of medicine,
public health, pharmaceutical industry, forensics and biological warfare
in the 21st century. This includes several polymerase chain reaction (PCR)-based
technologies, fluorescent in situ hybridization (FISH), peptide nucleic
acids (PNA), electrochemical detection of DNA, biochips, nanotechnology
and proteomic technologies. |
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This report describes and evaluates cell therapy technologies and
methods, which have already started to play an important role in the
practice of medicine. Hematopoietic stem cell transplantation is
replacing the old fashioned bone marrow transplants. Cell therapy is
bound to become a part of medical practice.
Stem cells are discussed in detail in one chapter. Some light is thrown
on the current controversy of embryonic sources of stem cells and
comparison with adult sources. Other sources of stem cells such as the
placenta, cord blood and fat removed by liposuction are also discussed.
Stem cells can also be genetically modified prior to transplantation. |
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This report describes and evaluates the proteomic technologies that
will play an important role in drug discovery, molecular diagnostics and
practice of medicine in the post-genomic era - the first decade of the
21st century. Most commonly used technologies are 2-D gel
electrophoresis for protein separation and analysis of proteins by mass
spectrometry. Microanalytical protein characterization with
multidimentional liquid chromatography/mass spectrometry improves the
throughput and reliability of peptide mapping. Matrix-Assisted Laser
Desorption Mass Spectrometry (MALDI-MS) has become a widely used method
for determination of biomolecules including peptides, proteins.
Functional proteomics technologies include yeast two-hybrid system for
studying protein- protein interactions. Establishing a proteomics
platform in the industrial setting initially requires implementation of
a series of robotic systems to allow a high-throughput approach for
analysis and identification of differences observed on 2-D
electrophoresis gels. Protein chips are also proving to be useful.
Proteomic technologies are now being integrated into the drug discovery
process as complimentary to genomic approaches.
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This report describes the role of neuroprotection in acute disorders
such as stroke and injuries of the nervous system as well as in chronic
diseases such as neurodegenerative disorders because many of the
underlying mechanisms of damage to neural tissues are similar in all
these conditions and several products are used in more than one
disorder. Over 500 products have been investigated for neuroprotective
effects including those from the categories of free radical scavengers,
anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors,
anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion
channel modulators and gene therapy. Some of the agents are old
established pharmaceuticals whereas others are new biotechnology
products. |
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This report deals with transdermal drug delivery - an approach used
to deliver drugs through the skin for therapeutic use as an alternative
to oral,intravascular, subcutaneous and transmucosal routes. Various
transdermal drug delivery technologies are described including the use
of suitable formulations, carriers and penetration enhancers. The most
commonly used transdermal system is the skin patch using various types
of technologies. Transdermal technologies may be applied for several
categories of pharmaceuticals used for the treatment of disorders of the
skin or for systemic effect to treat diseases of other organs. Several
transdermal products and applications include hormone replacement
therapy, management of pain, angina pectoris, smoking cessation and
neurological disorders such as Parkinson's disease. The value of the
global market for transdermal delivery was $12.7 billion in the year
2005 and is expected to increase to $21.5 billion in the year 2010 and
$31.5 billion in the year 2015.This market is analyzed according to
geographical regions as well. |
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This report describes and evaluates animal biotechnology and its
application in veterinary medicine and pharmaceuticals as well as
improvement in food production. Knowledge of animal genetics is
important in the application of biotechnology to manage genetic
disorders and improve animal breeding. Genomics, proteomics and
bioinformatics are also being applied to animal biotechnology.
Transgenic technologies are used for improving milk production and the
meat in farm animals as well as for creating models of human diseases.
Transgenic animals are used for the production of proteins for human
medical use. Biotechnology is applied to facilitate xenotransplantation
from animals to humans. Genetic engineering is done in farm animals and
nuclear transfer technology has become an important and preferred method
for cloning animals. |
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This report describes the latest concepts of pathomechanisms of pain
as a basis for management and development of new pharmacotherapies for
pain. Major segments of the pain market are arthritis, neuropathic pain
and cancer pain. Because pain is a subjective sensation, it is difficult
to evaluate objectively in clinical trials. Various tools for pain
measurement are described, including brain imaging.
Most of the currently used analgesic drugs fall into the categories of
opioids and nonsteroidal antiinflammatory drugs such as COX-2
inhibitors. Non-opioid analgesics include ketamine, a
N-methyl-D-aspartate receptor antagonist. Adjuvant analgesics include
antidepressants and antiepileptic drugs used for the treatment of
neuropathic pain. Management of pain is multidisciplinary and includes
both pharmacological and non-pharmacological methods such as
acupuncture, transcutaneous electrical nerve stimulation and surgery.
Various pain syndromes require different approaches in management, for
example, the main category of drugs for migraine are triptans such as
sumatriptan. |
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The aim of personalized medicine or individualized treatment is to
match the right drug to the right patient and, in some cases, even to
design the appropriate treatment for a patient according to his/her
genotype. This report describes the latest concepts of development of
personalized medicine based on pharmacogenomics,
pharmacogenetics,pharmacoproteomics, and metabolomics. Basic
technologies of molecular diagnostics play an important role,
particularly those for single nucleotide polymorphism (SNP) genotyping.
Diagnosis is integrated with therapy for selection of the treatment as
well for monitoring the results. Biochip/microarray technologies are
also important and finally bioinformatics is needed to analyze the
immense amount of data generated by various technologies. |
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This report describes the latest concepts of the role of nitric
oxide (NO) in health and disease as a basis for therapeutics and
development of new drugs. Major segments of the market for nitric
oxide-based drugs are described as well as the companies involved in
developing them.
Nitric oxide (NO) can generate free radicals as well as scavenge them.
It also functions as a signaling molecule and has an important role in
the pathogenesis of several diseases. A major focus is delivery of NO by
various technologies. Another approach is modulation of nitric oxide
synthase (NOS), which converts L-arginine to NO. NOS can be stimulated
as well as inhibited by pharmacological and gene therapy approaches.
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Alzheimer's disease remains a challenge in management. With nearly 8
million sufferers from this condition in the seven major markets of the
world and anticipated increases in the future. Considerable research is
in progress to understand the pathomechanism of the disease and find a
cure. The only drugs approved currently are acetylcholinesterase
inhibitors but they do not correct the basic pathology of the disease,
beta amyloid deposits and neurofibrillary tangles. Several new
approaches emphasize neuroprotection as well. |
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Drug delivery remains a challenge in management of cancer.
Approximately 12.5 million new cases of cancer are being diagnosed
worldwide each year and considerable research is in progress for drug
discovery for cancer. Cancer drug delivery is no longer simply wrapping
up cancer drugs in a new formulations for different routes of delivery.
The focus is on targeted cancer therapy. The newer approaches to cancer
treatment not only supplement the conventional chemotherapy and
radiotherapy but also prevent damage to normal tissues and prevent drug
resistance. |
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RNA interference (RNAi) or gene silencing involves the use of double
stranded RNA (dsRNA). Once inside the cell, this material is processed
into short 21-23 nucleotide RNAs termed siRNAs that are used in a
sequence-specific manner to recognize and destroy complementary RNA. The
report compares RNAi with other antisense approaches using
oligonucleotides, aptamers, ribozymes, peptide nucleic acid and locked
nucleic acid.
Various RNAi technologies are described, along with design and methods
of manufacture of siRNA reagents. These include chemical synthesis by in
vitro transcription and use of plasmid or viral vectors. Other
approaches to RNAi include DNA-directed RNAi (ddRNAi) that is used to
produce dsRNA inside the cell, which is cleaved into siRNA by the action
of Dicer, a specific type of RNAse III. MicroRNAs are derived by
processing of short hairpins that can inhibit the mRNAs. Expressed
interfering RNA (eiRNA) is used to express dsRNA intracellularly from
DNA plasmids. |
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Gene therapy can be broadly defined as the transfer of defined
genetic material to specific target cells of a patient for the ultimate
purpose of preventing or altering a particular disease state. Genes and
DNA are now being introduced without the use of vectors and various
techniques are being used to modify the function of genes in vivo
without gene transfer. If one adds to this the cell therapy particularly
with use of genetically modified cells, the scope of gene therapy
becomes much broader. Gene therapy can now combined with antisense
techniques such as RNA interference (RNAi), further increasing the
therapeutic applications. |
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Nanotechnology is the creation and utilization of materials,
devices, and systems through the control of matter on the
nanometer-length scale (a nanometer is one billionth of a meter.
Nanobiotechnology, an integration of physical sciences, molecular
engineering, biology, chemistry and biotechnology holds considerable
promise of advances in pharmaceuticals and healthcare. The report starts
with an introduction to various techniques and materials that are
relevant to nanobiotechnology. It includes some of the physical forms of
energy such as nanolasers. Some of the technologies are scaling down
such as microfluidics to nanofluidic biochips and others are
constructions from bottom up. Application in life sciences research,
particularly at the cell level sets the stage for role of
nanobiotechnology in healthcare in subsequent chapters. |
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The delivery of drugs to central nervous system (CNS) is a challenge
in the treatment of neurological disorders. Drugs may be administered
directly into the CNS or administered systematically (e.g., by
intravenous injection) for targeted action in the CNS. The major
challenge to CNS drug delivery is the blood-brain barrier (BBB), which
limits the access of drugs to the brain substance.
Advances in understanding of the cell biology of the BBB have opened new
avenues and possibilities for improved drug delivery to the CNS. Several
carrier or transport systems, enzymes, and receptors that control the
penetration of molecules have been identified in the BBB endothelium.
Receptor-mediated transcytosis can transport peptides and proteins
across the BBB. Methods are available to assess the BBB permeability of
drugs at the discovery stage to avoid development of drugs that fail to
reach their target site of action in the CNS. |
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