Stents relieve post-infection problem
Placing stents in blood vessels damaged by complications of previous fungal lung infection can provide long-term relief, Erin Albers, M.D., and colleagues report in the April 5 issue of Circulation.
Decades after infection with the soil-dwelling fungus Histoplasma capsulatum, patients can develop a rare complication – called fibrosing mediastinitis – that compresses airways and blood vessels in the chest, causing symptoms like cough, chest pain and labored breathing. There have been no treatments shown to provide long-term benefit.
In 2001, Thomas Doyle, M.D., and colleagues reported that placing stents in the affected vessels provided immediate clinical improvement in four patients. The investigators have now analyzed data from more than 40 patients who had this procedure between 1996 and 2008. They found that 87 percent of patients reported substantial improvement in their symptoms following stent placement.
The results suggest that stents can provide not only short-term symptom relief, but also sustained clinical improvement for patients with this rare condition.
— Melissa Marino
Gene variants impact blood pressure
The transporter protein NET actively removes the neurotransmitter norepinephrine – a mediator of the sympathetic (fight-or-flight) nervous system – from synapses. Genetic variants in NET have been associated with neuropsychiatric disorders, but their effects on cardiovascular regulation have not been explored.
The teams of Randy Blakely, Ph.D., Michael Stein, M.D., and Daniel Kurnik, M.D., genotyped the NET gene and studied cardiovascular responses at rest and during exercise in 145 healthy subjects. They found that 44 percent and 59 percent of participants had at least one of two common variants in the NET gene (T-182C and A-3081T, respectively). Participants with NET variants had higher systolic blood pressures during exercise and higher diastolic blood pressures at low levels of exercise, but no differences in heart rate or norepinephrine concentrations.
The findings, reported in the April issue of Pharmacogenetics and Genomics, may have clinical relevance since exaggerated blood pressure response during exercise is associated with future adverse cardiovascular outcomes, including hypertension.
— Leigh MacMillan
Host cell factors keep toxin at bay
Clostridium perfringens – a relative of the bacteria that cause botulism and tetanus – produces a potent toxin (epsilon-toxin) that can be fatal to livestock and is considered a “select agent” by the U.S. government due to its potential danger to humans. There are no therapies to counteract the toxin in humans, and the host mechanisms that allow the toxin to damage and kill cells remain unclear.
Mark McClain, Ph.D., and colleagues identified cells resistant to the toxin and investigated the differences in gene expression between resistant and sensitive cells. They identified several genes, including HAVCR1 (hepatitis A virus cellular receptor 1), which may account for the difference in toxin sensitivity. Further experiments showed that HAVCR1 binds epsilon-toxin and is more abundant in human kidney cells than in human cells that are resistant to the toxin. The findings, reported in PLoS One, suggest that HAVCR1 and the other genes may contribute to epsilon-toxin-induced cell death and represent new targets for therapies against this potential bioweapon.
— Melissa Marino
Fishing for a new model of TSC
Tuberous sclerosis complex (TSC) is a genetic disease caused by mutations in either the TSC1 or TSC2 genes. Patients with TSC have hamartomas – benign collections of abnormally differentiated cells – in organs throughout the body. In the brain, hamartomas are associated with intractable epilepsy, autism, behavioral problems and mental retardation.
Seok-Hyung Kim, Ph.D., Kevin Ess, M.D., Ph.D., and colleagues have now generated a zebrafish model of TSC, with a mutation in the tsc2 gene. They reported in the March issue of Disease Models & Mechanisms that zebrafish with two mutant copies of tsc2 died during early larval development with enlarged cells in the brain and liver. Their forebrains were poorly organized and had higher levels of TORC1, a protein whose action is normally blocked by tsc2. Transplanted mutant cells were able to mislocalize normal cells in the forebrain, which may help explain the formation of brain hamartomas in patients with TSC. A zebrafish model will greatly facilitate new approaches to study TSC and hopefully result in the identification of new therapies.
— Leigh MacMillan
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