Table of contents :
)),
to counteract the late decelerations
caused by cord compression, or to dilute thick meconium to prevent meconium
aspiration syndrome (MAS)
extracted from the bacterium Magnetospirillum magnetotacticum (just
30-50 nm across, small enough to pass through a hypodermic needle) could
be used to guide expensive or poisonous drug molecules to where they are
needed in the body. Besides targeting tumours, the technique could potentially
also be used to treat site-specific ailments such as arthritis. Doctors
could then direct the drugs to a certain area of the body using magnets,
then patients could wear an electromagnetic device to keep the drug in
its place. When moving freely in the blood, instead of confined inside
a cell, their natural magnetism might cause them to aggregate. In a worst-case
scenario, this could block blood vessels and cause an embolism. Particles
of magnetite or pure iron created by purely chemical means, rather than
harvesting them from bacteria, would not have any intrinsic magnetism themselves
but could be moved around by a magnet, like a microscopic version of iron
filings. The main advantage of using bacteria, however, is that they have
the potential to produce particles in huge numbers. One drawback is that
M.
magnetotacticum is difficult to grow, and yields of magnetite particles
are not reliably high : but genetic modification could be used to create
a more robust strain (geneticists already have identified the suite of
genes responsible for producing the particles, which could potentially
be transferred to another bacterial species).
(AmBisome©), doxorubicin
(Doxil©, Evacet©),
daunorubicin
(DaunoXome©), annamycin(Aronex©),
nystatin
(Nyotran©), and cytarabine
(DepoCyt©).
)).
Thus, molecules that are otherwise non-permeant can gain direct access
to the cytosol of cells in the treated area. A highly toxic molecule that
does not usually pass the membrane barrier is the hydrophilic drug bleomycin
occurs occasionally)
and nephrotic
syndrome)),
Pb
and Ra
(the latter damages bone vessels resulting in a vicious cycle that slows
its rate of elimination)
(amines)
(phenols, amines, catecholamines)
and fluoxetine
!)
and benzodiazepines
(synergy while the alcoholic is drinking !))
forced Abbott Laboratories to withdraw the capsule form of this drug from
the market. Pharmaceutical companies would like nothing more than
to be able to predict all of the obtainable polymorphs of a compound so
they could patent them. They had trouble working out what had gone wrong
and getting their original polymorph back. In the end, they had to gain
approval for the new polymorph, which was less soluble in the bloodstream
and, as a gel capsule, had to be refrigerated. This is estimated to have
cost them hundreds of millions of dollars. To anticipate such potential
problems, researchers attempt to find out about the polymorphs of drugs
using lab techniques such as crystallography. But this takes an enormous
amount of time and leaves a considerable amount to chance. Price's software
aims to cut short this process and predict the shapes a drug might take.
The test for Price's team came when Colin Pulham, a chemist at the University
of Edinburgh, UK, challenged it to predict a new polymorph of piracetam,
a drug used to treat Alzheimer's disease. Pulham had just discovered a
new conformation of this drug in his lab, and wanted to see if Price's
team could guess its shape. Price's team, which was already looking at
piracetam as a test case for their software, fed all the information about
the bonds between atoms of piracetam into their program. Using the processing
power of 30 computers, the program considered some 50,000 possible crystal
structures of the compound, with each structure taking 1-2 hours to generate
and analyse. After a few months, Price handed Pulham a list of possible
polymorphs, ranked in descending order of probability. The conformation
at the top of the list exactly matched the shape that he and his colleagues
had found. The team members, who present their work this week at the e-Science
All Hands Meeting in Nottingham, UK, says the test proves the efficacy
of their computerized method. Being able to meet this blind challenge adds
a lot of credibility. It will be a while yet before companies can put their
faith into Price's program. It's not going to be superseding the experimental
approaches any time soon. But after further testing, it could cut down
the work needed to isolate the best conformation for market, or to anticipate
potential problems in production. Pharmaceutical companies would like nothing
more than to be able to predict all the obtainable polymorphs of a compound
so they could patent them
-using
pregnants having 20% malformated newborns vs. 1.5% controls, and expecially
phocomelia
and meloxicam
in general practice in England using prescription-event monitoring dataref.
associated with cisapride:
limitations of the pharmacoepidemiological studies conducted and proposals
for the futureref
in Englandref;
Esophagitis
associated with the use of alendronateref
and other non-steroidal anti-inflammatory drugsref
and rhabdomyolysis.
Pharmacogenomics explains idiosyncratic
reactions on the basis of genetic polymorphisms. Geographic patterns
of genetic variation, including variation at drug metabolizing enzyme (DME)
loci and drug targets, indicate that geographic structuring of inter-individual
variation in drug response may occur frequently. This raises 2 questions:
)
:
Copyright © 2001-2014 Daniele Focosi.
All rights reserved
| Terms of use | Legal
notices
Cite
this page!
|
|
|
|
|
