Scientists at The Scripps Research Institute (TSRI) have solved the mystery of why a specific signaling pathway can be associated with alcohol dependence.
This signaling pathway is regulated by a gene, called neurofibromatosis type 1 (Nf1), which TSRI scientists found is linked with excessive drinking in mice. The new research shows Nf1 regulates gamma-aminobutyric acid (GABA), a neurotransmitter that lowers anxiety and increases feelings of relaxation.
“This novel and seminal study provides insights into the cellular mechanisms of alcohol dependence,” said TSRI Associate Professor Marisa Roberto, a co-author of the paper. “Importantly, the study also offers a correlation between rodent and human data.”
In addition to showing that Nf1 is key to the regulation of the GABA, the research, which was published recently in the journal Biological Psychiatry, shows that variations in the human version of the Nf1 gene are linked to alcohol-dependence risk and severity in patients.
Pietro Paolo Sanna, associate professor at TSRI and the study’s corresponding author, was optimistic about the long-term clinical implications of the work. “A better understanding of the molecular processes involved in the transition to alcohol dependence will foster novel strategies for prevention and therapy,” he said.
A Genetic Culprit
Researchers have long sought a gene or genes that might be responsible for risk and severity of alcohol dependence. “Despite a significant genetic contribution to alcohol dependence, few risk genes have been identified to date, and their mechanisms of action are generally poorly understood,” said TSRI Staff Scientist Vez Repunte-Canonigo, co-first author of the paper with TSRI Research Associate Melissa Herman.
This research showed that Nf1 is one of those rare risk genes, but the TSRI researchers weren’t sure exactly how Nf1 affected the brain. The TSRI research team suspected that Nf1 might be relevant to alcohol-related GABA activity in an area of the brain called the central amygdala, which is important in decision-making and stress- and addiction-related processes.
“As GABA release in the central amygdala has been shown to be critical in the transition from recreational drinking to alcohol dependence, we thought that Nf1 regulation of GABA release might be relevant to alcohol consumption,” said Herman.
The team tested several behavioral models, including a model in which mice escalate alcohol drinking after repeated withdrawal periods, to study the effects of partially deleting Nf1. In this experiment, which simulated the transition to excessive drinking that is associated with alcohol dependence in humans, they found that mice with functional Nf1 genes steadily increased their ethanol intake starting after just one episode of withdrawal. Conversely, mice with a partially deleted Nf1 gene showed no increase in alcohol consumption.
Investigating further, the researchers found that in mice with partially deleted Nf1 genes, alcohol consumption did not further increase GABA release in the central amygdala. In contrast, in mice with functional Nf1 genes, alcohol consumption resulted in an increase in central amygdala GABA.
In the second part of the study, a collaboration with a distinguished group of geneticists at various U.S. institutions, the team analyzed data on human variations of the Nf1 gene from about 9,000 people. The results showed an association between the gene and alcohol-dependence risk and severity.
The team sees the new findings as “pieces to the puzzle.” Sanna believes future research should focus on exactly how Nf1 regulates the GABA system and how gene expression may be altered during early development.
Respiratory tree anatomy and histology
28 June 2014
Take One Onion…
For patients with multiple drug prescriptions, remembering what to take and when can be tricky – giving out the right drugs daily on hospital wards is a time-consuming task. Researchers have found a new way to deliver drugs in ‘slow-release’ packages that could make this easier. They created microscopic drug delivery molecules with multiple layers, like an onion, inspired by the natural outer layers of some bacterial cells. The molecules were made simply by mixing particles called dendrimers – which have similar properties to the components of our cell membranes – with water, which made stable layers form spontaneously. Drugs could be packaged and released slowly from these molecules, layer by layer, so that they don’t have to be taken repeatedly – or different drugs could be contained in different layers so they could be released in sequence, simplifying the drug administration process.
Written by Emma Saxon
Antibiotic Resistance Is Now Rife across the Globe
Dangerous antibiotic-resistant bacteria and other pathogens have now emerged in every part of the world and threaten to roll back a century of medical advances. That’s the message from the World Health Organization in its first global report on this growing problem, which draws on drug-resistance data in 114 countries.
“A post antibiotic-era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century,” wrote Keiji Fukuda, WHO’s assistant director general for Health Security, in an introduction to the report. The crisis is the fruit of several decades of overreliance on the drugs and careless prescribing practices as well as routine use of the medicines in the rearing of livestock, the report noted.
Antibiotic resistance is putting patients in peril in both developing and developed countries, as bacteria responsible for an array of dangerous infections evolve resistance to the drugs that once vanquished them.
Gonorrhea, once well treated by antibiotics, is once again a major public health threat due to the emergence of new, resistant strains. Drugs that were once a last resort treatment for the sexually transmitted disease—which can lead to infertility, blindness and increased odds of HIV transmission if left untreated—are now the first-line treatment and are sometimes ineffective among patients in countries such as the U.K., Canada, Australia, France, Japan, Norway, South Africa, Slovenia and Sweden.
Drugs to treat Klebsiella pneumoniae—a common intestinal bacteria that can cause life-threatening infections in intensive care unit patients and newborns—no longer work in more than half of patients in some countries. And fluoroquinolones, drugs used to treat urinary tract infections, are also ineffective in more than half of sufferers in many parts of the world. Efforts to limit the spread of multidrug-resistant tuberculosis, malaria and HIV are also all under threat due to increasing bacterial resistance.
Although the development of resistance is to be expected over time, overuse of the drugs has accelerated the process by supplying additional selective pressure, noted the report, which was authored by an extensive team of researchers with WHO. And there are few drugs to replace the ones that are now ineffective: The last entirely new class of antibacterial drugs was discovered 27 years ago, according to the report.
Read more via scientificamerican.com
Infographic by who.int
Important stuff, and accompanied by a nicely done graphic.
Also, a graphic on the different major types of antibiotics would definitely be an interesting one - one for my to-do list!
Sirenomelia, aka Mermaid Syndrome.
Cross-section of human heart, displaying heart valves, chordae tendineae, and papillary muscles
Have you ever heard the expression “Tugging on your heart-strings”? Well, it’s not completely metaphorical, at least in terminology. There are literally parts of your heart known colloquially as “heart strings”, which have been described in an anatomical sense as far back as Vesalius.
These “heart strings” are more properly called chordae tendineae. You can see them in the illustration, looking like thin wires or netting within the ventricles. They start at the atrioventricular heart valves (the bicuspid or mitral and the tricuspid), and connect to the papillary muscles near the apex of the heart. The collagenous structure of these strings imparts to them a high level of strength, and the papillary muscles combined with some elastin give a high level of flexibility. they’re what keep your heart valves from everting (prolapsing) when the blood moves from the atria to the ventricles.
See, the valves have no muscular structure of their own, but work because the pressure of the blood pushing against them makes them open and close taut. But if the chordae tendineae weren’t there, that same pressure that makes sure they shut well also means that their fibrous structure would end up simply turning inside-out, and the blood would flow back into the atria, instead of to the lungs or the rest of the body. Insufficiency of the heart strings is one of many possible causes of mitral prolapse and valve insufficiency (leaky valves).
Anatomy: Descriptive and Surgical. Henry Gray, 1900.
An H&E stained section of epididymis, showing the basement membrane connective tissue and pseudostratified epithelium. You can see stereocilia protruding into the lumen where the sperm are.
Thrombocytopaenia with Absent Radius (TAR) Syndrome
- genetic disorder characterised by severely low platelet count and absent radius bone
Compartment syndrome after foot was run over by a mining drill. Compartment syndrome is a serious condition that involves increased pressure in a muscle compartment. It can lead to muscle and nerve damage and problems with blood flow.Swelling that leads to compartment syndrome occurs from trauma such as a car accident or crush injury, or surgery. Swelling can also be caused by complex fractures or soft tissue injuries due to trauma. Compartment syndrome is most common in the lower leg and forearm, although it can also occur in the hand, foot, thigh, and upper arm.
I have seen a couple cases in the hand after meth injections gone wrong. Bad news bears. Again, don’t do drugs kids.
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