Lighting Up the Tangles
Several contrast agents are in development for imaging beta-amyloid plaques in patients with incipient Alzheimer's disease, but what about the disorder's other major pathology, neurofibrillary tangles? Nothing suitable has yet come along for measuring these abnormalities in live patients.
That may now be changing, thanks to efforts by Masahiro Ono, PhD, and colleagues at Japan's Kyoto University. In ACS Medicinal Chemistry Letters, they say they have identified a new agent that binds both to beta-amyloid plaques and to neurofibrillary tangles made of rogue tau proteins.
Studies in mice showed that the compound, based on fluorine-18, is stable enough in vivo to serve as a useful contrast agent. And, when applied to brain sections from deceased Alzheimer's disease patients, tangles as well as plaques lit up brightly in PET and SPECT scans.
Telomeres Foretell Death Almost from Birth
The length of telomere segments at the end of one's chromosomes may foretell lifespan early in life, British researchers found in a study of zebra finches.
Telomeres form a protective cap for the end of the chromosome, shrinking with each round of normal cell replication until they reach a critical length that signals the cell to stop dividing, a process thought to account in part for aging.
In zebra finches, how fast telomeres wore away didn't predict longevity, though longer telomeres were linked to longer natural lives at every age.
The best predictor of lifespan was telomere length in 25-day-old chicks at the end of their main growth spurt, the investigators reported in Proceedings of the National Academy of Sciences.
Understanding what determines telomere length so early in life – genetics, maternal factors, or conditions during growth – may help in finding the key to longevity, they suggested.
Slowing Parasitic Diseases
A protein that allows certain parasites to invade host cells and release their progeny may represent a therapeutic target to prevent parasite-borne diseases, such as malaria and toxoplasmosis.
Reporting in Science, Marc-Jan Gubbels, PhD, of Boston College, and colleagues found that the inability of a mutant form of Toxoplasma gondii – which causes toxoplasmosis -- to invade cells and release its progeny was the result of a mutation in the DOC2.1 protein. That protein is necessary for the secretion of microneme organelles.
By sequencing the parasite's genome, the researchers identified the gene responsible for coding DOC2.1 and engineered it into another parasite, Plasmodium falciparum, which causes malaria. It similarly affected the ability of the parasite to invade host cells.
"Since neither microneme secretion nor invasion itself are currently targeted by any anti-malaria drugs, a potentially new class of anti-malaria reagents can be developed," Gubbels said in a statement. "The high incidence of drug resistance against malaria is a big problem, so new drugs are urgently needed."
A Lung Cancer Future for Endocrine Therapy?
Significantly fewer lung tumors formed in mice treated with an endocrine combination versus placebo or an anti-estrogen alone, investigators reported this week at the AACR-IASLC Joint Conference on the Molecular Origins of Lung Cancer in San Diego.
An average of 0.5 tumors developed in mice that received fulvestrant (Faslodex) and anastrozole (Arimidex) during exposure to the NNK tobacco carcinogen. Animals treated with fulvestrant alone or placebo averaged 3.4 and 4.6 tumors, respectively (P<0.001 for both comparisons versus dual therapy).
In a second lung cancer model, mice previously exposed to NNK developed fewer tumors when treated with the endocrine combination as compared with fulvestrant alone or placebo.
Several lines of evidence support a therapeutic potential for hormonal therapy in lung cancer, according to Jill Siegfried, PhD, of the University of Pittsburgh. Estrogens have been implicated in lung cancer proliferation and progression. Moreover, human lung tumors express estrogen receptor beta and aromatase.
Just One Hit Takes Away the Pain
Packing a powerful punch of opioids in a single high dose may permanently reverse chronic pain, researchers found.
Pain patients currently take continuous, low doses of opioids that temporarily relieve synaptic potentiation -- a tightening of connections between neurons that is responsible for their hurt.
But rats given a bigger hit of the ultra-short-acting mu-opioid agonist remifentanil (450 mcg/kg) had significantly diminished potentiation that lasted long after the infusion was over, Jurgen Sandkuhler, PhD, of the Medical University of Vienna, and colleagues reported in Science.
Potentiation was permanently reversed by a second dose of remifentanil given an hour later, they reported.
Sandkuhler said he and colleagues are currently exploring whether the concept can be applied in human pain patients, adding that they're sure to have on their team an anesthesiologist experienced in opioid overdose and mechanical ventilation.
Platelet Gel Heals Infarcted Hearts
Regenerative platelet gel, which has shown promise in repairing cartilage, bone, and spinal cords, may also help heal the damage from an acute myocardial infarction, researchers found.
An autologous platelet gel minimized immunological responses in rats and released various growth factors, such as vascular endothelial growth factor, which is known for its pro-angiogenic effects, according to Ke Cheng, PhD, of Cedars-Sinai Heart Institute in Los Angeles, and colleagues in the Journal of the American College of Cardiology.
Compared with control rats, those injected with the platelet gel had enhanced tissue protection of their infarcted hearts. The gel elicited greater endogenous regeneration, resulted in higher capillary density, and blunted left ventricular remodeling.
Advantages of platelet gel include its ability to be autologous, biocompatible, biodegradable, and provide both mechanical and function support to the heart, researchers said.