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Current Pharmaceutical
Analysis
ISSN: 1573-4129
Current Pharmaceutical
Analysis
Volume 3, Number 1, February 2007
Contents
Activity of the TNF-α
System in Patients with Brain Disorders and During Psychopharmacological
Treatment Pp. 1-5
Hubertus Himmerich
[Abstract] [Full
text article]
Therapeutic Opportunities for Trophic Factors
in Brain Inflammation Pp. 7-15
Beatriz Moreno and Pablo Villoslada
[Abstract] [Full
text article]
Lipid Disorders in Diabetes Mellitus and Current Management
Pp. 17-24
Garry X. Shen
[Abstract] [Full
text article]
Immunochemical Analysis of Endogenous and Exogenous
Estrogens Pp. 25-38
Meiping Zhao, Shuang Zhou, Jin Yan and Lin Li
[Abstract] [Full
text article]
Mass Spectrometric Analysis of F2-Isoprostanes:
Markers and Mediators in Human Disease Pp. 39-51
Edzard Schwedhelm, Ralf A. Benndorf, Rainer H. Böger
and Dimitrios Tsikas
[Abstract] [Full
text article]
An Orthogonal Approach to Chiral Method Development
Screening Pp. 53-70
Anne Akin, Frederick J. Antosz, Jenny L. Ausec, Kimberly
F. Greve, Rebecca L. Johnson, Lars-Erik Magnusson, Tore Ramstad,
Stephen L. Secreast, Donna S. Seibert and Gregory K. Webster
[Abstract] [Full
text article]
Immobilized Polysaccharide CSPs: An Advancement in
Enantiomeric Separations Pp. 71-82
Imran Ali and Hassan Y. Aboul-Enein
[Abstract] [Full
text article]
Abstracts
[Back to top]
Activity of the TNF-α
System in Patients with Brain Disorders and During Psychopharmacological
Treatment
Hubertus Himmerich
[Full
text article]
The tumor necrosis factor-α
(TNF-α)
system is involved in several regulatory processes within
the body. The action of TNF-α
is mediated by the two cell surface receptors TNF-R p55 and
TNF-R p75. Soluble TNF receptors (sTNF-Rs) are soluble variants
of the extracellular domains of their membrane-bound form.
To assess the activity of the TNF-α
system in patients suffering from disorders of the central
nervous system - such as depression, narcolepsy, multiple
sclerosis, Alzheimer’s and Parkinson’s disease
- and during psychopharmacological therapy, several studies
investigated plasma levels of TNF-α,
TNF-R p55 and TNF-R p75 and the local concentration of TNF-α
in the brain. It could be shown that an activation of the
TNF-α
system might promote the development of psychiatric or neurological
symptoms or disorders. Additionally, endocrine changes associated
with brain disorders may lead to alterations of the TNF-α
system.
Psychotropic drugs influence the TNF-α
system by normalizing the HPA axis changes associated with
psychiatric diseases, and inducing weight gain and liver damage.
Several side effects of psychotropic drugs resemble brain
disorders in which the TNF-α
system plays an important pathogenetic role. One could wonder
whether these side effects may at least in part be mediated
by an activation of the TNF-α
system.
[Back to top]
Therapeutic Opportunities for Trophic Factors
in Brain Inflammation
Beatriz Moreno and Pablo Villoslada
[Full
text article]
Inflammation is a key element in the pathophysiology of Central
Nervous System (CNS) diseases, irrespective of the etiology
of such diseases. From inflammatory or infectious diseases
to neurodegenerative, ischemic or traumatic diseases, inflammation
plays a fundamental role both in controlling the ongoing pathological
processes and in promoting neuroprotection or regeneration.
Indeed, due to the complex architecture and activities in
the brain, the side effects of brain inflammation are fundamental
to the outcome of neurological diseases (for example bystander
neuronal damage). The CNS differs from the other organs as
it is partially isolated from the immune system by the restrictive
blood-brain barrier and the presence of an immunosuppressive
environment (brain immune privilege). Inappropriate immune
responses are responsible for diseases such as Multiple Sclerosis
(MS) or for the increased disability after brain trauma or
stroke. Inflammation also plays an important role in neurodegenerative
diseases such as Alzheimer (AD) or Parkinson diseases (PD).
However, in certain circumstances immune responses in the
brain might have a neuroprotective effect, possibly mediating
the release of trophic factors by inflammatory or glial cells.
Neurotrophic factors protect axons and myelin from inflammatory
damage, and they have immunosuppressive properties that contribute
to the maintenance of brain immune privilege. Thus, in addition
to their neuroprotective activities, neurotrophic factors
may offer new therapeutic perspectives by targeting inflammatory
processes in brain disorders.
[Back to top]
Lipid Disorders in Diabetes Mellitus and Current Management
Garry X. Shen
[Full
text article]
Lipid disorders are common in diabetes mellitus (DM), and
play crucial roles in the development of diabetic cardiovascular
complications. Diabetic dyslipidemia is characterized by hypertriglyceridemia,
increased levels of very low density lipoproteins (VLDL),
small dense low density lipoprotein (LDL), and decreased levels
of high density lipoprotein (HDL)-cholesterol. The activity
of lipoprotein lipase is reduced in diabetic patients, which
attenuates the lipolysis of triglyceride-rich lipoproteins
and the uptake of free fatty acids. The increased uptake of
triglycerides in liver promotes the production of VLDL. Hypertriglyceridemia
promotes the exchange of cholesteryl ester from HDL to VLDL
or LDL for triglycerides. Obesity or nephropathy deteriorates
the dyslipidemia in DM patients. The initial management of
lipid disorders in diabetic patients without cardiovascular
disease is lifestyle intervention and glucose control. The
abnormalities in the metabolism of LDL or HDL in diabetic
patients often require pharmacological intervention. Target
of LDL-cholesterol (LDL-c) is more restrict in diabetic patients
than in non-diabetic subjects. Treatment with HMG-CoA reductase
inhibitors (statins) effectively reduces LDL-c and cardiac
events, and that was associated with moderately increases
in HDL-c. The combination of ezetimibe with a statin helps
to achieve LDL-c target in patients with unsatisfactory cholesterol
lowering by statin alone. Fibrates (PPAR-α
agonists) or PPAR-γ
agonists reduce the levels of triglycerides and moderately
elevate HDL-c. PPAR-γ
agonists also improve insulin sensitivity. Cholesteryl ester
transfer protein inhibitors may dramatically increase HDL-c.
Lipid management has been considered as an effective approach
to reduce cardiovascular risk in diabetes.
[Back to top]
Immunochemical Analysis of Endogenous and Exogenous
Estrogens
Meiping Zhao, Shuang Zhou, Jin Yan and Lin Li
[Full
text article]
Endogenous estrogens, namely estradiol, estriol and estrone
are essential substances for the sexual determination, growth
and reproduction of human beings. Their levels in the human
sera are important index in monitoring pregnancy, evaluating
menstrual dysfunctions and diagnosing many other diseases.
On the other hand, many exoestrogens, including the phytoestrogen
such as isoflavones, the synthetic estrogens such as diethylstilbestrol
and chemicals of industry origin with suspected estrogenic
activity such as bisphenol A and 4-nonylphenol, are drawing
increasing attention in recent years. This paper reviews the
main immunochemical analytical methods for these important
estrogenic substances. The immunizing hapten design and its
influence on the specificity of produced antibody were discussed.
The typical available immunoassays including enzyme immunoassay
(EIA), fluoroimmunoassay (FIA) and chemiluminescence immunoassay
(CLIA) for the detection of estrogens were compared with respect
to their features (especially dynamic range and limit of detection).
The performance of different types of immunosensors with respect
to their advantages and disadvantages were evaluated. The
future developing trend in this field was also briefly discussed.
[Back to top]
Mass Spectrometric Analysis of F2-Isoprostanes:
Markers and Mediators in Human Disease
Edzard Schwedhelm, Ralf A. Benndorf, Rainer H. Böger
and Dimitrios Tsikas
[Full
text article]
Free radical-induced peroxidation of arachidonic acid and
other polyunsaturated fatty acids esterified to lipids and
subsequent hydrolysis generates prostaglandin-like compounds
including the isoprostanes and neuroprostanes. These compounds
are endogenously formed, characteristic in structure, stable,
and accessible to quantitative determination in tissue, plasma
and urine. Isoprostanes have emerged as reliable markers of
lipid peroxidation in vivo in humans. Among them
8-iso-prostaglandin (PG) F2α
(8-iso-PGF2α,
8-epi-PGF2α,
15-F2t-IsoP,
iPF2α-III)
and its major urinary metabolites, i.e. 2,3-dinor-4,5-dihydro-8-iso-PGF2α
and 2,3-dinor-8-iso-PGF2α,
are subject of extensive investigation. Different analytical
approaches are currently used to isolate, identify and quantify
various members of the isoprostane and neuroprostane families.
They include chromatographic approaches such as thin-layer
chromatography (TLC), high-performance liquid chromatography
(HPLC), and gas chromatography (GC), and in particular mass
spectrometry (MS)-based techniques. Gas chromatography-mass
spectrometry (i.e. GC-MS and GC-tandem MS), previously proved
as the most reliable quantitative technique in the field of
prostanoid research, was the first method which was applied
to measure isoprostanes. In recent years, liquid chromatography-tandem
mass spectrometry (i.e. LC-tandem MS) has also been introduced
and established in the analysis of isoprostanes and related
compounds. The present paper gives an overview of analytical
methods currently applied to analyze isoprostanes in various
biological matrices. Special emphasis is given to the quantitative
determination in human urine which is a non-invasive method.
In this context, the impact of solid-phase extraction (SPE),
immunoaffinity column chromatography (IAC), HPLC, and TLC
in sample preparation/purification is discussed. Differences
in sample preparation depending on the biological matrix,
i.e. tissue, blood plasma, and urine, are outlined. Furthermore,
to meet increasing interest in isoprostanes as valid and stable
markers of oxidative stress in human disease, results from
various clinical trials in the cardiovascular field are discussed
and relevant experimental findings as well as potential direct
effects of isoprostanes in these pathophysiological settings
are reviewed. Moreover, relevant clinical data from other
disease entities is summarized in a schematic fashion.
[Back to top]
An Orthogonal Approach to Chiral Method Development
Screening
Anne Akin, Frederick J. Antosz, Jenny L. Ausec, Kimberly
F. Greve, Rebecca L. Johnson, Lars-Erik Magnusson, Tore Ramstad,
Stephen L. Secreast, Donna S. Seibert and Gregory K. Webster
[Full
text article]
Many of the new chemical entities under development in the
pharmaceutical industry are chiral. The specific stereochemistry
of these substances affects both the biological activity and
commercial viability of the potential new drug. Thus, enantioselective
separation techniques play a vital role in the development
of these entities into commercial products.
In an attempt to improve upon the efficiency of chiral method
development, column manufacturers and industry scientists
have developed screening procedures to efficiently evaluate
various chiral separation conditions in an unattended mode.
While these systems have been shown to be successful in their
initial and literature studies, it is important to evaluate
these systems for the molecules of interest to each particular
business concern. After optimizing the analysis conditions
of several literature chiral screening procedures, the individual
screens were challenged by novel chemical entities developed
for commercial use. The entities were randomly selected based
on availability and how well they represent molecules of interest
to common pharmaceutical portfolios.
Our chiral screening program is currently focusing on four
separation technologies: a) Liquid Chromatography (LC), b)
Supercritical Fluid Chromatography (SFC), c) Capillary Electrophoresis
(CE), and Gas Chromatography (GC). An overview of the results
from each of these screens, future directions and a final
unified strategy for chiral method development screening are
presented.
[Back to top]
Immobilized Polysaccharide CSPs: An Advancement in
Enantiomeric Separations
Imran Ali and Hassan Y. Aboul-Enein
[Full
text article]
With the advancement of science and technology chiral chromatography
has achieved an important place in analytical science. Coated
polysaccharide chiral stationary phases (CSPs) are most popular
due to their high chiral recognition power. But during last
few years, immobilization of polysaccharide derivatives with
silica gel has opened new realms in this area as these CSPs
can be used with normal and prohibited solvents (tetrahydrofuran,
chloroform, dichloromethane, acetone, 1,4-dioxane, ethylacetate,
and certain other ethers). The present article describes status
and method protocol of immobilized polysaccharides CSPs for
the chiral resolution of different racemates using liquid
chromatography. The contents of this article include methods
of immobilization, their applications under optimized conditions,
enantioselectivities, efficiencies and a comparison of the
chiral recognition capabilities of coated vs immobilized
CSPs.
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