Posts tagged pharmacology
Articles and news from the latest research reports.
Building a human on a chip, organ by organ
Human “organs on chips” could be linked to make the ideal guinea pig, revolutionising the way drugs are tested and cancer is treated
Such organs on chips can be used to model how human organs function and respond to drugs, says Ingber. He thinks that they even have the potential to eliminate the use of animals in drug testing. “Animal testing is expensive and time-consuming, and animals are not always representative of humans.”
Still, Ingber points out that the chips can perform some roles that animal studies cannot. For instance, they could be personalised by building them from an individual’s own cells. In theory, a doctor could send tissue samples to a lab to test a potentially harmful therapy on such a chip before handing out a prescription. This would be especially useful for people with cancer, as the various therapies available can have very different effects on different people, Ingber says. “You could get a quick yes-or-no answer to whether a drug would work or not,” he says.
Personalised chips might also speed up clinical trials. “Someday it might be possible to shortcut clinical trials by using chips containing cells from different human populations that are known to respond differently to specific drug classes,” Ingber says.
Long-term ADHD drug use appears safe, brain development not affected
July 18, 2012
Drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) do not appear to have long-term effects on the brain, according to new animal research from Wake Forest Baptist Medical Center.
As many as five to seven percent of elementary school children are diagnosed with ADHD, a behavioral disorder that causes problems with inattentiveness, over-activity, impulsivity, or a combination of these traits. Many of these children are treated with psychostimulant drugs, and while doctors and scientists know a lot about how these drugs work and their effectiveness, little is known about their long-term effects.
Linda Porrino, Ph.D., professor and chair of the Department of Physiology and Pharmacology, along with fellow professor Michael A. Nader, Ph.D., both of Wake Forest Baptist, and colleagues conducted an animal study to determine what the long-lasting effects may be. Their findings were surprising, said Porrino. “We know that the drugs used to treat ADHD are very effective, but there have always been concerns about the long-lasting effects of these drugs,” Porrino said.
"We didn’t know whether taking these drugs over a long period could harm brain development in some way or possibly lead to abuse of drugs later in adolescence."
Findings from the Wake Forest Baptist research are published online this month in the journal Neuropsychopharmacology.
The researchers studied 16 juvenile non-human primates, whose ages were equivalent to 6-to 10-year-old humans. Eight animals were in the control group that did not receive any drug treatment and the other eight were treated with a therapeutic-level dose of an extended-release form of Ritalin, or methylphenidate (MPH), for over a year, which is equivalent to about four years in children. Imaging of the animals’ brains, both before and after the study, was conducted on both groups to measure brain chemistry and structure. The researchers also looked at developmental milestones to address concerns that ADHD drugs adversely affect physical growth.
Once the MPH treatment and imaging studies were concluded, the animals were given the opportunity to self administer cocaine over several months. Nader measured their propensity to acquire the drug and looked at how rapidly and in what amounts, to provide an index of vulnerability to substance abuse in adolescence. As reported in the research paper, they found no differences between groups – monkeys treated with Ritalin during adolescence were not more vulnerable to later drug use than the control animals.
"After one year of drug therapy, we found no long-lasting effects on the neurochemistry of the brain, no changes in the structure of the developing brain. There was also no increase in the susceptibility for drug abuse later in adolescence," Porrino said. "We were very careful to give the drugs in the same doses that would be given to children. That’s one of the great advantages of our study is that it’s directly translatable to children."
Porrino said non-human primates provide exceptional models for developmental research because they undergo relatively long childhood and adolescent periods marked by hormonal and physiological maturation much like humans.
"Our study showed that long-term therapeutic use of drugs to treat ADHD does not cause long-term negative effects on the developing brain, and importantly, it doesn’t put children at risk for substance abuse later in adolescence," she said.
One of the exciting things about this research, Porrino said, is that a “sister” study was conducted simultaneously at John Hopkins with slightly older aged animals and different drugs and their findings were similar. “We feel very confident of the results because we have replicated each other’s studies within the same time frame and gotten similar results,” she said. “We think that’s pretty powerful and reassuring.”
Provided by Wake Forest University Baptist Medical Center
Source: medicalxpress.com
Your brain on ‘shrooms: fMRI elucidates neural correlates of psilocybin psychedelic state
Decreased cerebral blood flow (CBF) after psilocybin imaged by fMRI. Regions where there was significantly decreased CBF after psilocybin versus after placebo are shown in blue. No CBF increases in any region were observed. Image Copyright © PNAS, doi:10.1073/pnas.1119598109
(Medical Xpress) — Psychedelic substances have long been used for healing, ceremonial, or mind-altering subjective experiences due to compounds that, when ingested or inhaled, generate hallucinations, perceptual distortions, or altered states of awareness. Of these, the psychedelic substance psilocybin, the prodrug (a precursor of a drug that must in vivo chemical conversion by metabolic processes before becoming an active pharmacological agent) of psilocin (4-hydroxy-dimethyltryptamine) and the key hallucinogen found in so-called magic mushrooms, is widely used not only in healing ceremonies, but, more recently, in psychotherapy as well – but little has been known about its specific activity in the brain.
Recently, however, scientists in the Neuropsychopharmacology Unit at Imperial College London used complementary blood-oxygen level dependent (BOLD) functional MRI, or fMRI, in conjunction with a technique for imaging the transition from normal waking consciousness to the psychedelic state. The study found decreased blood flow and BOLD in the thalamus, anterior and posterior cingulate cortex, and medial prefrontal cortex. The researchers concluded that the surprising results strongly suggest that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.
Lead researcher Dr. Robin L. Carhart-Harris, working in the Neuropsychopharmacology Unit created by Prof. David J. Nutt, recounts the team’s main challenges in establishing an fMRI methodology that would be specific enough to highly correlate neurophysiological activity with the neuronal presence or absence of psilocybin. “There were a number of considerations,” Carhart-Harris tells Medical Xpress. “In terms of experimental design, we had to determine the precise dose and delivery protocol that would be appropriate for obtaining clear fMRI results. “For example,” he explains, “we had to consider temporal dynamics: If the drug was administered orally, the protracted period of time between ingestion, metabolism, and crossing of the blood-brain barrier would fall outside of the short scanning window needed to capture induced brain activity.” They therefore had to rely on intravenous administration.
New drug offers bigger window to treat stroke
A DRUG which minimises brain damage when given three hours after stroke has proved successful in monkeys and humans.
A lack of oxygen in the brain during a stroke can cause fatal brain damage. There is only one approved treatment - tissue plasminogen activator - but it is most effective when administered within 90 minutes after the onset of stroke. Immediate treatment isn’t always available, however, so drugs that can be given at a later time have been sought.
In a series of experiments, Michael Tymianski and colleagues at Toronto Western Hospital in Ontario, Canada, replicated the effects of stroke in macaques before intravenously administering a PSD-95 inhibitor, or a placebo. PSD-95 inhibitors interfere with the process that triggers cell death when the brain is deprived of oxygen.
To test its effectiveness the team used MRI to measure the volume of damaged brain for 30 days following the treatment, and conducted behavioural tests at various intervals within this time.
Monkeys treated with the PSD-95 inhibitor one hour after stroke had 55 per cent less damaged tissue in the brain after 24 hours and 70 per cent less after 30 days, compared with those that took a placebo. These animals also did better in behavioural tests. Importantly, the drug was also effective three hours after stroke (Nature, DOI: 10.1038/nature10841).
An early stage clinical trial in humans, run by firm NoNO in Ontario has also seen positive results.
Source: New Scientist