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If we review the story of the H Pylori so far we come to realise that
the organism poses a couple of mysteries to the scientific community. This
Gram-negative microaerophilic and acid-resistant organism, with a size of
0.5 mu by 1.5 mu, is dependant on the availability of carbon di-oxide for
its existance. The Carbon di-oxide is derived from the splitting up of
urea by the cytoplasmic urease. The amount of urease present in the
cytoplasm is over 100 times that present in the Proteus, and it is a rapid
test for the presence of the organism in the gastric antrum. Scientists
now tell us that the survival of the organism in the acid medium of the
stomach is because of an acid-gated membrane channel which effectively
controls the amount of alkali produced by the organism to combat the
gastric acid (1). The organism apparently activates its own urease,
thereby converting urea into carbon di-oxide and ammonia. In the acid
medium the entry of urea is increased 300-fold.
Benzimidazole derivatives such as omeprazole, lansoprazole and
pantoprazole are weak bases that concentrate under the acid conditions of
the secretory canaliculi of the parietal cells, where they undergo a
rearrangement of the active sulfonamide form which reacts with the
H+/K+/ATPase. As proton pump inhibitors they are also efective as first
line drugs in the management of H. pylori infections.
The inhibition of the proton pump decreases the H+ ion concentration
( and increases the pH) of the gastric juice, which in turn decreases the
amount of urease formed, which then makes the availability of substances
like carbon di-oxide and ammonia (which are essential for the survival of
the microaerophilic organism) deficient. As a result the organism fails to
thrive. In that sense the proton pump inhibitors are bacteristatic in
therapeutic concentrations, a fact which is also evidenced by the
observation that on stopping the treatment for a few weeks the clinical
condition recurs. It would therefore be more appropriate to call the
channel 'proton-gated' rather than 'acid-gated'. It is just a variant of
an ion-gated membrane channel.
But this does not minimise the superb contribution that the
researchers have made in identifying the amidoporein protein UreI.
Though some of the investigators of the study on Roxithromycin in
acute coronary events were convinced that infection with H Pylori is not a
causal factor for atherosclerosis (2) Tanne (3) was of the opinion that
antibiotics could prevent heart attacks. The next step in research would
need to be to examine how this organism, with its rather peculiar
biochemistry, can be found in the alkaline medium of the blood and how it
can (if at all) predispose to coronary artery disease.
References:
1. Berger A. Scientists discover hoe H pylori survic\ves in gastric acid.
BMJ 2000; 320:268
2. Beck E. ATB or not ATB. eBMJ Feb 13, 1999, in response to Tanne
JH. Antibiotics may prevent heart attackes. BMJ 1999; 318: 417
Acid-gated or proton-gated channels?
If we review the story of the H Pylori so far we come to realise that
the organism poses a couple of mysteries to the scientific community. This
Gram-negative microaerophilic and acid-resistant organism, with a size of
0.5 mu by 1.5 mu, is dependant on the availability of carbon di-oxide for
its existance. The Carbon di-oxide is derived from the splitting up of
urea by the cytoplasmic urease. The amount of urease present in the
cytoplasm is over 100 times that present in the Proteus, and it is a rapid
test for the presence of the organism in the gastric antrum. Scientists
now tell us that the survival of the organism in the acid medium of the
stomach is because of an acid-gated membrane channel which effectively
controls the amount of alkali produced by the organism to combat the
gastric acid (1). The organism apparently activates its own urease,
thereby converting urea into carbon di-oxide and ammonia. In the acid
medium the entry of urea is increased 300-fold.
Benzimidazole derivatives such as omeprazole, lansoprazole and
pantoprazole are weak bases that concentrate under the acid conditions of
the secretory canaliculi of the parietal cells, where they undergo a
rearrangement of the active sulfonamide form which reacts with the
H+/K+/ATPase. As proton pump inhibitors they are also efective as first
line drugs in the management of H. pylori infections.
The inhibition of the proton pump decreases the H+ ion concentration
( and increases the pH) of the gastric juice, which in turn decreases the
amount of urease formed, which then makes the availability of substances
like carbon di-oxide and ammonia (which are essential for the survival of
the microaerophilic organism) deficient. As a result the organism fails to
thrive. In that sense the proton pump inhibitors are bacteristatic in
therapeutic concentrations, a fact which is also evidenced by the
observation that on stopping the treatment for a few weeks the clinical
condition recurs. It would therefore be more appropriate to call the
channel 'proton-gated' rather than 'acid-gated'. It is just a variant of
an ion-gated membrane channel.
But this does not minimise the superb contribution that the
researchers have made in identifying the amidoporein protein UreI.
Though some of the investigators of the study on Roxithromycin in
acute coronary events were convinced that infection with H Pylori is not a
causal factor for atherosclerosis (2) Tanne (3) was of the opinion that
antibiotics could prevent heart attacks. The next step in research would
need to be to examine how this organism, with its rather peculiar
biochemistry, can be found in the alkaline medium of the blood and how it
can (if at all) predispose to coronary artery disease.
References:
1. Berger A. Scientists discover hoe H pylori survic\ves in gastric acid.
BMJ 2000; 320:268
2. Beck E. ATB or not ATB. eBMJ Feb 13, 1999, in response to Tanne
JH. Antibiotics may prevent heart attackes. BMJ 1999; 318: 417
3. Tanne JH. Antibiotics may prevent heart attacks. BMJ 1999; 318:
417
Competing interests: No competing interests