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Current
Medicinal Chemistry
ISSN: 0929-8673
Current Medicinal Chemistry
Volume 13, Number 21, 2006
Contents
Determination of Bioactive Constituents in Traditional Chinese
Medicines by CE with Electrochemical Detection Pp.
2467-2485
Gang Chen, Yizhun Zhu, Yufeng Wang, Xuejiao Xu and Tao Lu
[Abstract]
Toll-Like Receptor (TLR) Response Tolerance: A
Key Physiological “Damage Limitation” Effect and
an Important Potential Opportunity for Therapy Pp.
2487-2502
Andrea Broad, David E.J. Jones and John A. Kirby
[Abstract]
The Emergence of Multiplexed Technologies as Diagnostic
Platforms in Systemic Autoimmune Diseases Pp. 2503-2512
Marvin J. Fritzler and Mark L. Fritzler
[Abstract]
Comprehensive Comparison of Trace Metal Concentrations
in Cancerous and Non-Cancerous Human Tissues Pp.
2513-2525
Mehmet Yaman
[Abstract]
In Utero Exposure to Phthalates and Fetal
Development Pp. 2527-2534
Giuseppe Latini, Antonio Del Vecchio, Marika Massaro,
Alberto Verrotti and Claudio DE Felice
[Abstract]
Drug Excipients Pp. 2535-2563
Huba Kalász and István Antal
[Abstract]
N-Acetylcysteine and Other Preventive Measures
for Contrast Induced Nephropathy in the Intensive Care Unit
Pp. 2565-2570
Marcus J. Schultz, Marije C. Baas, Hans P. van der Sluijs,
G. André Stamkot and Watske Smit
[Abstract]
Natural Products from Plants as Drug Candidates
and Lead Compounds Against Leishmaniasis and Trypanosomiasis
Pp. 2571-2598
Manar M. Salem and Karl A. Werbovetz
[Abstract]
Abstracts
[Back to top]
Determination of Bioactive Constituents in Traditional
Chinese Medicines by CE with Electrochemical Detection
Gang Chen, Yizhun Zhu, Yufeng Wang, Xuejiao Xu and Tao Lu
This paper reviews the recent advances and the key strategies
in capillary electrophoresis (CE) with electrochemical detection
(ECD) for separating and detecting a variety of bioactive
constituents in traditional Chinese medicines (TCMs). The
subjects covered include the separation modes for the CE analysis
of the constituents in TCMs, the CE-ECD system, the sample
preparations of TCMs, the ECD of TCMs, the applications of
CE-ECD in the determination of various bioactive constituents
in Chinese medicinal materials and their preparations, the
identification and differentiation of TCMs by CE-ECD, and
future prospects. It is expected that CE-ECD will become a
powerful tool in the herbal medicinal fields and will lead
to the creation of truly routine devices for TCM analysis.
[Back to top]
Toll-Like Receptor (TLR) Response Tolerance:
A Key Physiological “Damage Limitation” Effect
and an Important Potential Opportunity for Therapy
Andrea Broad, David E.J. Jones and John A. Kirby
Endotoxin tolerance is a well known phenomenon, described
both in vivo and in vitro, in which repeated
exposure to endotoxin results in a diminished response, usually
characterised as a reduction in pro-inflammatory cytokine
release. The mechanisms responsible for endotoxin tolerance
have become clear in recent years as our understanding of
the pathways through which endotoxin mediates its effects
has increased. The principal cell surface receptor for the
lipopolysaccharide (LPS) component of endotoxin is Toll-Like
Receptor 4 (TLR-4), a member of a highly conserved family
of receptors specific for highly conserved bacterial and viral
components which play key roles in the early inflammatory
response to pathogens. As our understanding of the part played
by TLR-4 signalling in endotoxin has increased, so it has
become clear that response tolerance occurs to other TLR ligands
in addition to LPS/endotoxin. Clinically, endotoxin/TLR response
tolerance is thought to play an important part in susceptibility
to reinfection in patients treated for severe sepsis. Whilst
this may have developed as a protective evolutionary mechanism
to prevent death caused by overwhelming cytokine release in
sepsis, in the modern era of antibiotics, vasopressors and
organ support, undoing this downregulation or “re-booting”
the immune system may be a useful therapeutic target in the
post-septic patient. This should, however, be approached with
caution as it is possible that endotoxin/TLR response tolerance
is also a physiological regulatory mechanism in areas normally
exposed to bacterial-derived TLR-ligands such as the gut and
liver.
[Back to top]
The Emergence of Multiplexed Technologies as
Diagnostic Platforms in Systemic Autoimmune Diseases
Marvin J. Fritzler and Mark L. Fritzler
In the last decade, there has been a rapid proliferation
of new technologies that are capable of identifying an increasing
spectrum of autoantibodies and other biomarkers in autoimmune
diseases. These newer diagnostic technologies include line
immunoassays, addressable laser bead immunoassays, microarrays
in microfluidics platforms and nanobarcode particles. Multiplexed
bead assays are a particularly robust platform because they
are adaptable to the detection of a variety of disease specific
biomarkers, such as autoantibodies, cytokines, adipokines,
drugs, oligonucleotides and single nucleotide polymorphisms,
Although many laboratories have adopted a variety of these
diagnostic platforms to improve turn around times and meet
budget constraints, there is an urgent need to ensure that
the rapid adoption of new technologies is attended by an appropriate
balance of assay sensitivity and specificity.
[Back to top]
Comprehensive Comparison of Trace Metal Concentrations
in Cancerous and Non-Cancerous Human Tissues
Mehmet Yaman
The roles of metals in the development and inhibition
of cancer have a complex character and have risen many questions
because of their essential and toxic effects on human health.
Question of whether trace metal concentrations in tissues
are increased or decreased in cancerous patients in comparison
with non-cancerous patients has not been answered yet, due
to the fact that the data known in this field is rare and
have contradictory results. Although Zn and Cu concentrations
in serum and tissues of cancerous patients have been extensively
studied, the precise role of these metals in carcinogenesis
is not clearly understood. On the other hand, the comprehensive
review on trace metal concentrations in cancerous and non-cancerous
tissues is uncommon. The differences in literature on the
increases or decreases in trace metal concentrations of cancerous
tissues in comparison with non-cancerous tissues may be attributed
to a few reasons such as the tissue basis-dry or wet weight,
different sensitivities and basis of analysis methods that
affect the accuracy, and the difficulties in taking of the
sample representing the cancerous or non-cancerous area.
In this study, the data published up to now have been reviewed.
Comparison of results was done according to tissue and cancer
types and trace metal species. The probable causes of differences
in literature data were discussed. Especially, the published
studies in recent years needed such a review.
[Back to top]
In Utero Exposure to Phthalates and
Fetal Development
Giuseppe Latini, Antonio Del Vecchio, Marika Massaro,
Alberto Verrotti and Claudio DE Felice
The diesters of benzene-1,2-dicarboxylic (phthalic) acid,
commonly known as phthalates, are a family of industrial compounds,
primarily used as plasticizers in enormous quantities for
a variety of industrial uses in the formulation of plastics.
Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used
plasticizer. These plasticizers are not covalently bound to
the polymer and leach out into the environment, thus becoming
ubiquitous environmental contaminants. Cumulating evidence
points out on the adverse effects of phthalate exposure during
intrauterine life. Recently, it has been documented that in
utero phthalate exposure is associated with a shorter duration
of pregnancy. Phthalates induce and activate a subset of peroxisome
proliferator-activated receptors (PPARs) and have an intrinsic
pro-inflammatory activity, while some natural PPAR agonists
induce cyclooxygenase (COX)-2 expression. To this regard,
COX-2 is thought to be overexpressed in chorioamnionitis (CA),
a fetal systemic inflammatory response syndrome and a leading
cause of preterm birth. An adequate maternal dietary intake
of essential fatty acids, well known anti-inflammatory agents,
is indispensable to fetal development. Recently, it has been
shown that phthalates alter the placental essential fatty
acids (EFAs) homeostasis so potentially leading to abnormal
fetal development. Likewise, a possible down-regulation of
COX-2 by omega-3 fatty acids has been suggested. As a consequence,
maternal supplementation with omega 3 during pregnancy could
counteract the adverse effects of phthalates exposure in the
human fetus. Here, we analyze the existing evidence on the
link between antenatal phthalate exposure and abnormal fetal
development, as well as on possible therapeutic tools to fight
the adverse effect of this exposure.
[Back to top]
Drug Excipients
Huba Kalász and István Antal
The therapeutical use of drugs involves the application
of dosage forms, serving as carrier systems together with
several excipients to deliver the active ingredient to the
site of action. Drug delivery technology combines an understanding
of medicinal chemistry and pharmacology with the skill of
formulation, aiming the preparation of improved pharmaceuticals.
The recently introduced Biopharmaceutical Classification System
provides guidance for dosage form design, taking the molecular
and physico-chemical properties of drugs into consideration
through their solubility and permeability characteristics.
Pharmaceutical excipients used for oral dosage form have been
traditionally assumed as being inert. However, recent experience
and new results have shown that they can interact with the
active drug ingredient, affecting its dissolution, absorption
and bioavailability.
Classification of the excipients is based on their role in
the pharmaceutical formulation and on their interactions influencing
drug delivery, based on their chemical and physico-chemical
properties. The main classes are the antioxidants, coating
materials, emulgents, taste- and smell-improvers, ointment
bases, conserving agents, consistency-improvers and disintegrating
materials. Some of the excipients may serve multiple purposes;
for example, methylcellulose is a coating material, is applied
in the preparation of suspensions, to increase viscosity,
as a disintegrating agent or binder in tablets.
The aim of this paper is to review the drug-excipients with
respect to their chemistry, importance and interactions altering
the pharmacokinetics of the drug substances. Emphasis will
be given to two major classes of excipients: the antioxidants
and disintegrants (substances facilitating disintegration
of the drug tablets in the gastro-intestinal tract). Details
will be given on the mechanisms through which they can alter
drug effectiveness and tolerance, and control their application.
Examples and references will be given for their analysis.
[Back to top]
N-Acetylcysteine and Other Preventive Measures
for Contrast Induced Nephropathy in the Intensive Care Unit
Marcus J. Schultz, Marije C. Baas, Hans P. van der Sluijs,
G. André Stamkot and Watske Smit
The increase in diagnostic imaging procedures that require
infusion of intravenous radiographic contrast has led to a
parallel increase in the incidence of contrast-induced nephropathy
(CIN). Since CIN accounts for a significant increase of hospital-acquired
renal failure, length of stay and mortality, several additive
strategies to prevent CIN are presently advocated, including
N-acetylcysteine (NAC), sodium bicarbonate, theophylline or
fenoldopam, and peri-procedural hemofiltration/hemodialysis.
As only one (non-randomized) study has been performed in the
intensive care setting, at present it is hard to give firm
recommendations on preventive measures for CIN in intensive
care patients. Indeed, future studies are needed to determine
the true role of the above-mentioned preventive measures in
critically ill patients at risk for CIN. Since NAC has only
few side-effects, we presently advise NAC as an additive preventive
measure in the intensive care setting. Theophylline or sodium
bicarbonate hydration are viable options, either in conjunction
NAC or as alternatives.
[Back to top]
Natural Products from Plants as Drug Candidates
and Lead Compounds Against Leishmaniasis and Trypanosomiasis
Manar M. Salem and Karl A. Werbovetz
Millions of people in the developing world are affected
by diseases caused by the kinetoplastid parasites: the leishmaniases,
African trypanosomiasis, and Chagas disease. In many cases
the drugs employed for treatment are toxic, marginally effective,
given by injection, and/or compromised by the development
of resistance. Since safe, effective, and affordable chemotherapeutic
agents for leishmaniasis and trypanosomiasis are clearly needed,
the identification of new antikinetoplastid drug candidates
should be an urgent priority. Numerous plant-derived natural
products from different structural classes have been investigated
as antileishmanial and antitrypanosomal candidates, including
various alkaloids, terpenoids, flavonoids, and quinonoids.
This review outlines the antikinetoplastid activities of plant-derived
natural products reported in the literature and also provides
an overview of mechanistic studies that have been conducted
with these compounds. Given the activities of these agents
and their diverse range of effects on parasite biology, natural
products are a potentially rich source of drug candidates
and leads against leishmaniasis and trypanosomiasis.
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