Saturday, February 24, 2007

A glass a day won't keep illness at bay

If you think a glass of wine in the evening is good for your heart, think again. The long held belief that moderate drinking reduces risk of a heart attack is based on flawed data and is most likely wrong, according to a new study released on Thursday.

A couple of glasses of wine aren't going to hurt, the study found, but they aren't going to help much either. Heavy drinking, of course, is unquestionably bad.

"Our results suggest that light drinking is a sign of good health, and not necessarily its cause," said epidemiologist Kaye M. Fillmore of the University of California, San Francisco School of Nursing.

"No one should recommend drinking," said Dr Michael Criqui of UC San Diego, who was not involved in the study.

Although he thinks Fillmore underestimates the potential benefits of alcohol, he cautions that many people use such a recommendation as "an excuse to drink to excess. It's a very dangerous recommendation."

The new findings, published online in the journal Addiction Research and Theory, are an outgrowth of ideas first proposed 15 years ago by Dr A.G. Shaper of the Royal Free Hospital School of Medicine in London.

In his studies on heart disease and death, Shaper observed that many people who abstained from alcohol did so because of advancing age, serious illness or the use of drugs whose effects were altered by alcohol.

He has warned since then that counting such people as abstainers in alcohol studies would bias the results because their increased likelihood of disease and death was unrelated to the fact that they didn't drink.

But his has been a voice in the wilderness.

The idea that a couple of drinks are beneficial "Is such an appealing hypothesis" that few have taken him seriously, he said. "It's a lovely story, an appealing story. Doctors like it, patients like it everybody likes it."

The paper by Fillmore and an international team of colleagues "is the first time anybody has had a good, critical look at all the evidence",he added.

Fillmore's team identified 54 papers in the literature that examined the health effects of drinking. They found that the vast majority of the papers included significant numbers of people who had recently quit drinking- for whatever reason-among the group who abstained from alcohol.

Only seven of the studies had long-term abstainers in that group-people who had never consumed alcohol or who had stopped drinking years earlier for reasons unrelated to their current health.

All seven of those studies showed no benefit from moderate drinking.

Fillmore cautioned that the study had not totally disproved the notion that light drinking was good for health, but "it reopens the debate about this matter".

Criqui agreed that more studies were needed, but argued that the gold standard for reaching a decision-a blinded, randomised clinical trial-was out of the question. it would be difficult or impossible ethically to randomise patients for alcohol use, he said, and the study would not be blind because participants would readily recognise the booze.

So physicians have to deduce the answers from epidemiological studies, "which are fraught with errors", Criqui said.

He noted there was some biological evidence to support a beneficial effect from light drinking.

His own studies and those of others show that light drinking raises levels of high- density lipoprotein, the so-called good cholesterol.

There may be some value to the evening glass of wine, he said, "but it is less than previously believed", and he doesn't recommend it.

Friday, February 23, 2007

How do antibiotics kill bacterial cells but not human cells?

Harry Mobley, chair of the department of microbiology and immunology at the University of michigan Medical school, provides this answer.

IN order to be useful in treating human infections, antibiotics must selectively target bacteria for eradication and not the cells of its human host.

Indeed, modern antibiotics act either on processes that are unique to bacteria-such as the synthesis of cell walls or folic acid- or on bacterium-specific targets within processes that are common to both bacterium and human cells, including protein or DNA replication.

The following are some examples:
Most bacteria produce a cell wall that is composed partly of a macromolecule called peptidoglycan, which is itself made up of amino sugars and short peptides. Human cells do not make or need peptidoglycan.

Penicillin, one of the first antibiotics to be used widely, prevents the final cross-linking step, or transpeptidation, in assembly of this macromolecule. The result is a very fragile cell wall that bursts, killing the bacterium. No harm comes to the human host because penicillin does not inhibit any biochemical process that goes on within us.

Bacteria can also be selectively eradicated by targeting their metabolic pathways. Sulfonamides, such as sulfamethoxazole, are similar in structure to para-aminobenzoic acid, a compound critical for synthesis of folic acid. All cells require folic acid and it can diffuse easily into human cells. But the vitamin canot enter bacterial cells and thus bacteria must make their own.

The sulfa drugs such as sulfonamides inhibit a critical enzyme- dihydropteroate synthase-in this process. Once the process is stopped, the bacteria can no longer grow.

Another kind of antibiotic-tetracycline-also inhitits bacterial growth by stopping protein synthesis. Both bacteria and humans carry out protein synthesis on structures called ribosomes.
Tetracycline can cross the membranes of bacteria and accumulate in high concentrations in the cytoplasm. Tetracycline then binds to a single site on the ribosome-the 30S (smaller) ribosomal subunit-and blocks a key RNA interaction, which shuts off the lengthening protein chain.
In human cells, however, tetracycline does not accumulate in sufficient concentrations to stop protein synthesis.

Similarly, DNA replication must occur in both bacteria and human cells. The process is sufficiently different in each that antibiotics such as ciprofloxacin-a fluoroquinolone notable for its activity against the anthrax bacillus-can specifically target an enzyme called DNA gyrase in bacteria.

This enzyme relaxes tightly wound chromosomal DNA, thereby allowing DNA replication to proceed. But this antibiotic does not affect the DNA gyrases of humans and thus, again, bacteria die while the host remains unharmed.

Many other compounds can kill both bacterial and human cells. It is the selective action of antibiotics against bacteria that make them useful in the treatment of infections while at the same time allowing the host to live another day.-c.2006 Scientific American

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