Gummy Ulcers

Mastic vs. Helicobacter pylori

by David Bradley

mastic a plant to stomachMastic is usually used to seal gaps in door frames, because it is a tough sticky gum. But, according to microbiologist Dlawer Ala'Aldeen of Nottingham University, the gum from the leaves of the Middle Eastern mastic tree  - Pistacia lentiscus - can also kill the bugs that cause ulcers. It might one day lead to a new treatment for millions of sufferers without the expense and problems associated with conventional drugs.
   Ulcers are like open sores in the wall lining the stomach into which acid can eat. Peptic ulcers can be very painful and are a major risk factor for stomach cancer. Several years ago, Australian scientists demonstrated that a corkscrew-shaped bacteria known as Helicobacter pylori (subject of the 2005 Nobel Prize for Medicine) was the most important cause so antibiotics. Their findings overturned years of received wisdom regarding the nature of ulcers and for many cases meant that using antacids and acid suppressants, such as ranitidine and cimetidine, was not likely to cure an ulcer but merely suppress the symptoms. The obvious cure would be to use an antibiotic to kill the bug and so cut to the root of the ulcer.
   The trouble with antibiotics is that bacteria develop resistance to them quite quickly if they are not used properly and sometimes even if they are. So, while many sufferers have been cured with a complex course of strong antibiotics, an alternative is needed.
   This is where the mastic gum comes in. Ala'Aldeen's co-worker Debbie Thriwell, physician colleague Farhad Huwez and H pylori expert Alan Cockayne tested whether mastic might help ulcer patients. They found that d research assistant found that just 0.06 mg (0.00006 of a g/ml) was a high enough dose to kill the bacterium. Mastic, says Ala'Aldeen, killed H pylori far more effectively than any antibiotic and destroys even strains resistant to common antibiotics. The team is currently looking for the active components of the gum to try to work out why it is so potent.
   Mastic, it turns out, has been used as a traditional herbal remedy in Kurdistan for centuries to treat stomach complaints - especially those caused by the strong alcoholic drink arac, which is similar to Greek ouzo. Mastic, which tastes of eucalyptus is also used a lot in traditional baking and soups, says Ala'Aldeen. It seems that folklore could assist modern medicine once again.
   Ala'Aldeen et al., New Engl. J. Med., vol 339, p 1947.

Blocked up brains
 Edward NeuweltAMERICAN SCIENTISTS HAVE DISCOVERED that the brain is a lot cleverer than we thought at keeping out unwanted and potentially harmful chemicals. They have found that in addition to the well-known blood-brain barrier (the BBB) which blocks the path of many molecules into the brain, there is a second layer of protection that catches compounds that try to smuggle their way in. The discovery could have important implications for the development of therapies for many different brain diseases.
   Leslie Muldoon and Edward Neuwelt of the Oregon Health Sciences University and the Portland Veterans Affairs Medical Center in Portland know how to manipulate the blood-brain barrier so that they can deliver drugs into the brains of patients with brain tumours without having to use injections. They have spent several years developing techniques to lift this barrier by using osmosis to make the tight junctions between blood vessel cells - which form the barrier - open up and so allow patients to be treated without surgery.
   However, they also know that some medical agents simply cannot get through this border control. It would be useful if they could because it would mean potential drugs and gene therapy agents for diseases such as Parkinson's and Alzheimer's disease could be packaged up and delivered through the blood too.
Leslie Muldoon    Muldoon and her colleagues were looking into whether virus-sized particles might be able to get into the brain. Gene therapy carrier, vectors, would be this size so it is important to know whether it is possible or not. They were using different types of 'sugar'-coated iron oxide particles to model a gene vector.
   They found that the magnetic resonance images (MRI) they took showed a strange distribution of some of the particles. It seemed as if some could get right into the brain but others could not. This implied that there was a second barrier that was holding back some types of particle. It turned out that the particles completely coated with 'sugar' molecules could cross this second barrier but the incompletely covered particles get stuck in the protein layer surrounding capillaries, likes flies in a spider's web. Neuwelt believes the barrier is probably an electrically charged layer similar to that found in the kidney. It can select which particles pass through depending on their overall charge.
   The next step for the scientists is to work out how to disguise useful particles such as gene vectors so that they can get past the first and second barriers.
   Muldoon et al., Am. J. Neuroradiol., 20, 217

Attacking arthritis

AN X-RAY SNAPSHOT OF the enzymes involved in arthritis could lead to new drugs to treat the disorder, according to American scientists.
   Zinc-dependent matrix metalloproteinase (MMP) enzymes digest the connective tissues surrounding cells. This process helps keep the spaces between cells neat and tidy and allows cells to multiply. When things go wrong, however, the MMPs eat away at tissues surrounding joints causing inflammation and destroying the joints leading to the often-crippling pain of osteo- and rheumatoid-arthritis.
   Only a few of the fifteen known MMPs are involved in arthritis so finding a drug that blocks the damaging ones without interfering with the others is difficult. If the wrong MMP is blocked waste proteins can build up between cells causing their own problems.
Michelle Browner    Michelle Browner of Roche Bioscience in Palo Alto, California and her co-workers have recorded the X-ray crystal structures of two MMPs in which they had loaded inhibitor molecules - diphenylether sulfones - that stop them working. The X-ray structures, which reveal the positions of every atom in the molecule, can be used to produce an accurate computer model of the enzymes.
   According to Browner the models demonstrate that how well a molecule blocks the activity of the MMPs - human collagenase-1 and collagenase-3 - depends on the size and shape of the 'pocket' in which the molecules fit. This pocket is long and open in collagenase-3 so diphenylether sulfones, can fit. But, collagenase-1 has a smaller pocket and the bulky diphenylether group of the compound simply cannot squeeze inside properly. The researchers have developed inhibitor molecules that block different MMPs to different degrees, based on their results.

Such molecules would hopefully avoid potential side effects and might one day lead to new drugs for arthritis.
   Browner et al., Nature Struct. Biol., 1999, 217

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