Science Editor
Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
It's hard to avoid the pitch for Viagra on the television commercials and e-mail spam. Directed at the erectile-dysfunctional male, the usual disclaimer cautions that "Viagra may not be for you." Fine print at the bottom of the screen defines the Pfizer drug chemically as sildenafil citrate. By either name, it may have a future in the lung, treating an organ remote from Viagra's touted penile target.
A preliminary study in The Lancet, dated Sept. 21, 2002, carries the title: "Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomized controlled trial." Its co-authors are scientists at the Justus-Liebig University in Giessen, Germany.
Their paper suggests that Viagra may have a future role in the treatment of pulmonary hypertension (PH) - dangerously increased blood pressure in the pulmonary artery. PH is a potentially fatal condition causing respiratory impairment. Lung fibrosis - scarring of the lungs - is due to inflammation of the alveoli. These are the myriad small sacs where breathing swaps oxygen for carbon dioxide.
The controlled, randomized patient trial reported in Lancet compares the acute effects of oral sildenafil (Viagra) with intravenous prostacylin (conventional vasodilation treatment) after the 16 trial subjects inhaled nitric oxide (the treatment of choice, but with drawbacks).
The trial results reported reduction in the ratio of lung to systemic blood resistance - an indication of diminished pulmonary hypertension - but only in patients who received sildenafil. "Controlled randomized trials should be done to confirm our findings," the paper's senior author observed. "However, the unique profile of sildenafil - not previously shown for a systemically administered agent - suggests that the drug is a promising candidate for long-term treatment of secondary pulmonary hypertension in lung fibrosis."
A companion commentary, headed "Pulmonary hypertension and the search for the selective pulmonary vasodilator," states that the Lancet paper "adds to growing evidence for the use of sildenafil in patients with primary and secondary pulmonary hypertension." It says that sildenafil "is the best available orally administered selective pulmonary vasodilator."
Primary pulmonary hypertension is a progressive disease that mostly affects young people, is five times more common in women than in men, and has a mean survival of between two and three years from time of diagnosis. Discovery in the 1990s that endothelial-derived relaxing factor was the gas nitric oxide (NO) propelled that once obscure gas to vasodilator par excellence. However, cost and unresolved technical difficulties in delivering inhaled NO have prevented its widespread use and sharpened interest in Viagra, which achieves penile erection by pumping blood to dilate its vessels.
Sildenafil's shortcoming, the commentary noted, is that, unlike NO, it affects systemic blood pressure. In the trial, it dropped in patients receiving sildenafil and prostacyclin (another vasodilator of choice), but not in those who also inhaled NO.
Left-Right Mix-Up Of Internal Organs Starts Earlier Than Thought; Etiology Defined
"Your heart's in the right place" means - colloquially - that you are by nature compassionate or generous. But, of course, hearts belong on the left side of the body. Every year in the U.S., approximately one baby in 8,000 is born with misplaced, laterally defective internal organs. Normal organ sitting is called situs solitus; abnormal, situs inversus. Then there's total scrambling or jumbling of the internal pattern termed situs ambiguus, or heterotaxia. That's bad news.
Researchers at Harvard Medical School and its affiliated Forsyth Institute have discovered a novel molecular mechanism that determines right-left asymmetry in vertebrates. They have also determined that the process through which a fertilized egg begins left-right patterning starts much earlier in embryogenesis than was previously supposed. These findings, in the journal Cell, dated Oct. 4, 2002, have significance for dealing with right or left handedness, mirror-image twins, right vs. left brain dominance and birth defects that position developing organs on the wrong side of the body. Other implications include cancer (a condition in which cells are unable to assume their proper stance) and organ regeneration.
The paper in Cell is titled: "Asymmetries in H-K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning." Its co-authors show that a proton/potassium ATPase functions within hours of fertilization to generate left-right asymmetry in Xenopus (clawed-frog) embryos.
The report's senior author called the study "a major breakthrough tracing the origins of left-right organization to the very first stages of embryonic development and implicating a regulatory mechanism heretofore unrecognized for its significance in this context: the control of ions moving across cell membranes by the so-called H-K+-ATPase."
Salvaging Ovaries From Deceased Females May Perpetuate Their Viability In Surrogate Parents
When a female animal dies, her ovaries may live on, as it were, if they are grafted onto tissues in another animal. Australian physiologists transplanted ovarian tissue from mice onto the kidneys of live female and male rats. Later, they harvested eggs from the transplant, fertilized them in vitro, then implanted the potential embryos into foster mice. These surrogate mothers gave birth to pups that were fertile. This experiment provided some of the first evidence to date that eggs from xenografted tissue can grow. Unclear, however, was whether the embryos obtained specifically from the male rats were viable.
A one-page "Brevia" paper in Science dated Sept. 27, 2002, reports the feat under the title: "Generation of live young from xenografted mouse ovaries." Its authors point out, "Although this strategy could potentially be applied to humans, its use in human-assisted reproduction should be considered with caution."
On the other hand, they added, "It may be possible to collect ovarian tissue from other living animals, or salvage it from recently deceased animals to subsequently aid in the propagation of rare and endangered species."