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Biomarkers can help guide immune-suppressing treatment after organ transplantation

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Recently discovered biomarkers may provide valuable new approaches to monitoring immunosuppressive drug therapy in organ transplant recipients–with the potential for individualized therapy to reduce organ rejection and minimize side effects, according to a special article in the April issue of Therapeutic Drug Monitoring, official journal of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. The journal is published by Wolters Kluwer.

“Biomarkers should help to tailor immunosuppressive therapy to the needs of the individual patient,” according to the review by an international Expert Committee. The initial “Barcelona Consensus Statement” includes a preliminary set of recommended tests for use in biomarker-based immunosuppressive drug management after organ transplantation. The lead author is Mercè Brunet, PhD, of Hospital Clinico de Barcelona.

 

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Computer model predicts how our livers will store fat

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Computer model developed to predict how ‘T09’ causes the liver to store fat could be used to predict liver fat storage for other drugs and conditions

As part of an effort to understand how an experimental drug for atherosclerosis causes the build-up of fat in the liver, scientists have developed a computer model that can predict how the rate at which liver stores fat in response to various situations. Being able to model liver fat storage gives researchers a way to predict the side effects of drugs and environmental factors at much earlier stages in the research and drug development process, possibly reducing the number of experiments involving animal models. Additionally, this computer simulation helps describe all of the possible ways in which the liver stores fat, including how the liver takes up or creates fats and how it disposes of fat. This knowledge could lay the foundation for future research regarding the liver and its functions. This was published in the April 2015 issue of The FASEB Journal.

 

 

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Researchers use the latest in nanotechnology and transdermal drug delivery to take on an old problem: Acne

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Acne, a scourge of adolescence, may be about to meet its ultra high-tech match. By using a combination of ultrasound, gold-covered particles and lasers, researchers from UC Santa Barbara and the private medical device company Sebacia have developed a targeted therapy that could potentially lessen the frequency and intensity of breakouts, relieving acne sufferers the discomfort and stress of dealing with severe and recurring pimples.

Acne Nanoparticle
The particles are delivered into the sebaceous gland by the ultrasound, and are heated by the laser. The heat deactivates the gland.
Credit: Peter Allen Illustration

“Through this unique collaboration, we have essentially established the foundation of a novel therapy,” said Samir Mitragotri, professor of chemical engineering at UCSB.

Pimples form when follicles get blocked by sebum, an oily, waxy substance secreted by sebaceous glands located adjacent to the follicle. Excretion of sebum is a natural process and functions to lubricate and waterproof the skin. Occasionally, however, the openings of the follicles (pores) get blocked, typically by bits of hair, skin, dirt or other debris mixed in with the sebum. Overproduction of sebum is also a problem, which can be caused by hormones or medications. Changes in the skin, such as its thickening during puberty, can also contribute to follicle blockage. Whatever the cause, the accumulating sebum harbors bacteria, which results in the inflammation and local infection that we call acne

 

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Catalyst-where-you-want-it method expands the possibilities for new drug development

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Chemists at The Scripps Research Institute (TSRI) and the Shanghai Institute of Organic Chemistry have described a method for creating and modifying organic compounds that overcomes a major limitation of previous methods. The advance opens up a large number of novel chemical structures for synthesis and evaluation, for example, as candidate pharmaceuticals.

The new method was designed to avoid an unwanted side effect – a diversion of a catalyst molecule to the wrong location – that prevents chemists from manipulating many organic compounds in the class known as heterocycles, which are commonly used as drugs.

The newly described technique gets around this obstacle by generating a reactive catalyst at precisely the desired site on a molecule to be modified.

“We have already applied this technology to enable the modification of a wide range of chemical structures, including a complex drug candidate being developed by a major pharmaceutical company,” said Jin-Quan Yu, professor of chemistry at TSRI.

Yu and his colleagues describe the new method in a paper published by the journal Nature.

 

Full story at MNT

Type 2 diabetes drug switched on and off by blue light

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Diabetes drugs encourage the pancreas to release insulin to control blood sugar levels, but many of them cause side effects, affecting other organs such as the brain and heart. Some drugs, meanwhile, encourage too much insulin release, causing blood sugar levels to drop too much. Now, scientists have created a type 2 diabetes drug that can be switched on and off by blue light, potentially improving treatment.
human body with pancreas and diabetes
In type 2 diabetes, the body builds resistance to insulin, requiring more insulin to bring down blood glucose levels. As such, the pancreas needs to produce more insulin than it normally would.

The researchers – from the Department of Medicine at Imperial College London in the UK and LMU Munich in Germany – publish their findings in the journal Nature Communications.

They note that type 2 diabetes, which impairs an individual’s control over their blood sugar levels, affects about 350 million people around the world. The disease can lead to a higher risk of heart disease and stroke, causing potential damage to the kidneys, nerves and retinas.

According to the Centers for Disease Control and Prevention (CDC), in 2012, 29.1 million people in the US – 9.3% of the population – had diabetes.

The disease involves a disturbance of normal glucose homeostasis caused by a failure of the pancreas’ beta cell mass to compensate for increased insulin resistance. However, in their new study, the researchers show that their prototype drug – called JB253 – stimulates insulin release from pancreatic cells when exposed to blue light.

 

Full story at MNT

 

What is a cohort study in medical research?

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Cohort studies are a type of medical research used to investigate the causes of disease, establishing links between risk factors and health outcomes.

Cohort studies are usually forward-looking – that is, they are ‘prospective’ studies, or planned in advance and carried out over a future period of time.

A research question is raised – a hypothesis is formed about the potential causes of a disease – and the researchers then observe a group of people, the cohort, over a period, often a very long one, to detect any changes in health in relation to predetermined risk factors.

For example, the scientists may ask participants to record their lifestyle factors over the course of time, and then analyze the way these correlate with disease.

  • Cohort studies are used by epidemiologists looking into the factors that affect the health and illness of populations.
  • Other terms for cohort studies include: incidence, longitudinal, forward-looking, follow-up, concurrent, and prospective.

‘Etiology’ is the term doctors use for studying the causes of disease. When doctors talk about the etiology of a condition they mean the cause, and they may describe the mechanism by which a cause leads to a disease effect.

 

Full Article on MNT

A protein may be linked to heart attacks

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A protein may be linked to heart attacks

A team of researchers at the University of Ottawa Heart Institute, led by Dr. Alexandre Stewart, have uncovered an intriguing link between heart attacks and a protein that is of great interest to drug companies for its impact on cholesterol.

The team found that levels of the protein PCSK9 were elevated in the blood of patients having an acute heart attack, but not in those who never had a heart attack or who had recovered from one previously. The results were replicated in two separate groups of patients, all of whom have coronary artery disease but were not taking a cholesterol-lowering statin drug.

Published in the journal PLOS One, the findings point to an important question: “Are PCSK9 levels elevated shortly before you get a heart attack?” asks Dr. Stewart, principal investigator in the Ruddy Canadian Cardiovascular Genetics Centre at the Ottawa Heart Institute. “If levels only go up after, that would suggest a side effect of the heart attack. But if they go up before, that suggests it might trigger the event, or make it worse.”

The Heart Institute researchers first identified the PCSK9 link to heart attacks using blood samples from patients enrolled in the Ottawa Heart Genomics Study. They then confirmed these results in a group of patients from Emory University in Atlanta, Georgia. Again, they found elevated PCSK9 levels in samples taken from patients at the time of acute heart attack, but not in samples taken from patients with a history of heart attack or from those with coronary artery disease who never had a heart attack.

 

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Polypill helps heart attack survivors take their meds, potentially saving lives

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king a polypill instead of a cocktail of tablets increases the chances that heart attack survivors will keep to their medication regime, which may prevent more patients having further heart attacks. This was the conclusion of a US-led international study presented at a meeting this week.
Pills
A clinical trial reveals that patients are more likely to take their heart attack prevention medication as a polypill than as three separate pills.

Lead investigator Dr. Valentin Fuster, director of Mount Sinai Heart Hospital, New York, NY, presented the findings of the FOCUS study at the European Society of Cardiology (ESC) 2014 Congress in Barcelona, Spain, on Tuesday.

Read full story at MNT

He notes that despite medical advances in tackling cardiovascular disease, rates in the population have steadily increased, to the point where it is the number one killer worldwide.

 

Novel approach mimicks natural evolution with ‘promiscuous reactions’ to improve the diversity of drugs

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A revolutionary new scientific method developed at the University of Leeds will improve the diversity of ‘biologically active molecules’, such as antibiotics and anti-cancer agents.

The researchers, who report their findings online in the journal Nature Chemistry, took their inspiration from evolution in nature. The research may uncover new pharmaceutical drugs that traditional methods would never have found.

“Nature produces some amazing structures with really interesting biological activity, but the plant or animal did not design them. Instead the organisms gradually evolved both the chemical structures and the methods to produce them over millennia because they were of benefit. We wanted to capture the essence of this in our approach to discovering new drugs,” said George Karageorgis, a PhD student from the School of Chemistry and the Astbury Centre for Structural Molecular Biology at the University of Leeds, and first author of the study.

The traditional method for discovering new drugs involves preparing new biologically active molecules by adjusting the chemical structure of an existing one slightly and analysing the results. This trial and error method is both time consuming and limits the variety of new types of drugs that are developed.

“There is a known problem with limited diversity in drug discovery. It’s like a baker always going to the same storage cupboard and using the same ingredients, yet hoping to create something that tastes different,” said Dr Stuart Warriner from the School of Chemistry and the Astbury Centre for Structural Molecular Biology at the University of Leeds, a co-author of the research paper.

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Night light exposure could make breast cancer tumors tamoxifen resistant

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Tamoxifen is an estrogen-blocking medication typically used to treat breast cancer that has spread to other parts of the body. But new research conducted in rats suggests exposure to dim light at night – as little as that coming in a window from a street light – suppresses melatonin production, making tumors resistant to the drug.
dim indoor lamp
Researchers found that exposure to dim light at night results in breast cancer tumors becoming resistant to tamoxifen.

The study, led by Prof. Steven M. Hill of Tulane University School of Medicine in New Orleans, LA, is published in Cancer Research, a journal of the American Association for Cancer Research.

“Our levels of melatonin are not determined by sleep, as many people think,” explains Prof. Hill. “It is actually the darkness that is important. During the night, if you sleep in a brightly lit room, your melatonin levels may be inhibited; however, if you are in the dark but cannot sleep, your melatonin levels will rise normally.”

He and his team note that disruption of circadian rhythms by night shift work or disturbed sleep could result in an increased risk of breast cancer and other diseases. For patients with hormone receptor-positive breast cancer, Prof. Hill adds that tamoxifen resistance “is a growing problem.”

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