Singapore scientists unravel cancers linked to herbal remedies

A team of scientists from the National Cancer Centre Singapore, Duke-NUS Graduate Medical School Singapore, and Taiwan's Chang Gung Memorial Hospital, LinKou, have made a breakthrough in understanding the cancer-promoting action of Aristolochic Acid (AA), a natural product of Aristolochia plants traditionally used in some Asian herbal remedies for weight loss and slimming. Using advanced DNA sequencing technologies, the team, led by Professors Teh Bin Tean, See-Tong Pang, Patrick Tan and Steve Rozen discovered that AA is the most potent carcinogen identified to date, causing more DNA mutations than cigarette smoke or ultraviolent light. The team also discovered that besides its previously known contribution to kidney failure and a form of kidney cancer, AA may also contribute to liver cancer. The team identified a "genetic fingerprint" of AA exposure that may pave the way to new approaches to detect AA presence in humans and the environment. The group is also affiliated with the Cancer Science Institute in Singapore, and the Genome Institute of Singapore.
AA is a natural compound found in Aristolochia plants commonly used in traditional herbal preparations for various health problems such as weight-loss, menstrual symptoms and rheumatism. It was officially banned in Europe and North America since 2001 and in Asia since 2003. However, its long-term impact is still being felt as patients with associated kidney failure and cancer are still being diagnosed, especially in Taiwan. In addition, certain AA-containing products are still permitted under supervision and products containing AA are still easily available worldwide, including over the internet.
The potent cancer-promoting activity of AA strongly warrants efforts to restrict the use of AA containing products, including health supplements. "We would like to call for greater public awareness on the adverse health effects of AA. It is therefore important to know the contents of herbal products before one consumes them." said Prof Pang. Reassuringly, in Singapore there is no cause for worry as under the Poisons Act since 1 January 2004, products and herbs sold and supplied in Singapore are not allowed to contain AA and the toxic constituents of Aristolochia herbs.
The Singapore-Taiwan study also reports that carcinogens can leave tell-tale "genetic fingerprints" of their exposure in the DNA of cancer cells, and provides a valuable demonstration of how such fingerprints can be used to identify other cancers not previously associated with that carcinogen. Dr Poon Song Ling, the lead author of the study, said: "AA's contributions to kidney failure and cancer have been documented, but AA's possible role in other cancer types was unknown. In this study, we found that the AA-related DNA fingerprint could be used to screen for the potential involvement of AA in other cancers, such as liver cancer." Such findings could lead to a new wave of DNA-based detection systems for monitoring carcinogen exposures in humans and the environment.
This breakthrough came after 1.5 years of intensive research and was published online on 7 August 2013, 2.00pm, U.S. Eastern Time in Science Translational Medicine, a publication that focuses on practical medical advances that result from all stages of translational medicine. The research was supported by grants from the Singapore National Medical Research Council, the Singapore Millennium Foundation, the Lee Foundation, the National Cancer Centre Research Fund, The Verdant Foundation, the Duke-NUS Graduate Medical School Singapore, the Cancer Science Institute of Singapore, the Chang Gung Memorial Hospital, LinKou, the Taiwan National Science Council, and the Wellcome Trust.
Source:Science Translational Medicine

How DNA Repair Helps Prevent Cancer

Chemical engineers find that arrays of carbon nanotubes can detect flaws in drugs and help improve production.

 MIT chemical engineers have discovered that arrays of billions of nanoscale sensors have unique properties that could help pharmaceutical companies produce drugs — especially those based on antibodies — more safely and efficiently. Using these sensors, the researchers were able to characterize variations in the binding strength of antibody drugs, which hold promise for treating cancer and other diseases. They also used the sensors to monitor the structure of antibody molecules, including whether they contain a chain of sugars that interferes with proper function.
“This could help pharmaceutical companies figure out why certain drug formulations work better than others, and may help improve their effectiveness,” says Michael Strano, an MIT professor of chemical engineering and senior author of a recent paper describing the sensors in the journal ACS Nano.
The team also demonstrated how nanosensor arrays could be used to determine which cells in a population of genetically engineered, drug-producing cells are the most productive or desirable, Strano says.
Lead author of the paper is Nigel Reuel, a graduate student in Strano’s lab. The labs of MIT faculty members Krystyn Van Vliet, Christopher Love and Dane Wittrup also contributed, along with scientists from Novartis. 

Testing drug strength
Strano and other scientists have previously shown that tiny, nanometer-sized sensors, such as carbon nanotubes, offer a powerful way to detect minute quantities of a substance. Carbon nanotubes are 50,000 times thinner than a human hair, and they can bind to proteins that recognize a specific target molecule. When the target is present, it alters the fluorescent signal produced by the nanotube in a way that scientists can detect.Some researchers are trying to exploit large arrays of nanosensors, such as carbon nanotubes or semiconducting nanowires, each customized for a different target molecule, to detect many different targets at once. In the new study, Strano and his colleagues wanted to explore unique properties that emerge from large arrays of sensors that all detect the same thing.
The first feature they discovered, through mathematical modeling and experimentation, is that uniform arrays can measure the distribution in binding strength of complex proteins such as antibodies. Antibodies are naturally occurring molecules that play a key role in the body’s ability to recognize and defend against foreign invaders. In recent years, scientists have been developing antibodies to treat disease, particularly cancer. When those antibodies bind to proteins found on cancer cells, they stimulate the body’s own immune system to attack the tumor. 
For antibody drugs to be effective, they must strongly bind their target. However, the manufacturing process, which relies on nonhuman, engineered cells, does not always generate consistent, uniformly binding batches of antibodies. 
Currently, drug companies use time-consuming and expensive analytical processes to test each batch and make sure it meets the regulatory standards for effectiveness. However, the new MIT sensor could make this process much faster, allowing researchers to not only better monitor and control production, but also to fine-tune the manufacturing process to generate a more consistent product.
“You could use the technology to reject batches, but ideally you’d want to use it in your upstream process development to better define culture conditions, so then you wouldn’t produce spurious lots,” Reuel says.

Measuring weak interactions
Another useful trait of such sensors is their ability to measure very weak binding interactions, which could also help with antibody drug manufacturing.Antibodies are usually coated with long sugar chains through a process called glycosylation. These sugar chains are necessary for the drugs to be effective, but they are extremely hard to detect because they interact so weakly with other molecules. Drug-manufacturing organisms that synthesize antibodies are also programmed to add sugar chains, but the process is difficult to control and is strongly influenced by the cells’ environmental conditions, including temperature and acidity. 
Without the appropriate glycosylation, antibodies delivered to a patient may elicit an unwanted immune response or be destroyed by the body’s cells, making them useless. 
“This has been a problem for pharmaceutical companies and researchers alike, trying to measure glycosylated proteins by recognizing the carbohydrate chain,” Strano says. “What a nanosensor array can do is greatly expand the number of opportunities to detect rare binding events. You can measure what you would otherwise not be able to quantify with a single, larger sensor with the same sensitivity.”
This tool could help researchers determine the optimal conditions for the correct degree of glycosylation to occur, making it easier to consistently produce effective drugs. 

Mapping production
The third property the researchers discovered is the ability to map the production of a molecule of interest. “One of the things you would like to do is find strains of particular organisms that produce the therapeutic that you want,” Strano says. “There are lots of ways of doing this, but none of them are easy.”The MIT team found that by growing the cells on a surface coated with an array of nanometer-sized sensors, they could detect the location of the most productive cells. In this study, they looked for an antibody produced by engineered human embryonic kidney cells, but the system could also be tailored to other proteins and organisms.
Once the most productive cells are identified, scientists look for genes that distinguish those cells from the less productive ones and engineer a new strain that is highly productive, Strano says.
The researchers have built a briefcase-sized prototype of their sensor that they plan to test with Novartis, which funded the research along with the National Science Foundation. 
“Carbon nanotubes coupled to protein-binding entities are interesting for several areas of bio-manufacturing as they offer great potential for online monitoring of product levels and quality. Our collaboration has shown that carbon nanotube-based fluorescent sensors are applicable for such purposes, and I am eager to follow the maturation of this technology,” says Ramon Wahl, an author of the paper and a principal scientist at Novartis.
Source:Journal of Physical Chemistry B

Effects of Parkinson's-disease mutation reversed in cells

UCSF study shows potential for new treatment strategy

UC San Francisco scientists working in the lab used a chemical found in an anti-wrinkle cream to prevent the death of nerve cells damaged by mutations that cause an inherited form of Parkinson’s disease. A similar approach might ward off cell death in the brains of people afflicted with Parkinson’s disease, the team suggested in a study reported online in the journal Cell on August 15.
The achievement marks a pharmacologic milestone as the first highly specific targeting of a member of an important class of enzymes called kinases to increase rather than to inhibit their activity, according to UCSF chemistKevan Shokat, PhD, the senior scientist on the study. The research raises hope that similar pharmaceutical strategies might be used for combatting other diseases, including diabetes and cancer, he said.
Mutations that cause malfunction of the targeted enzyme, PINK1, are directly responsible for some cases of early-onset Parkinson’s disease. Loss of PINK1 activity is harmful to the cell’s power plants, called mitochondria, best known for converting food energy into another form of chemical energy used by cells, the molecule ATP.
In Parkinson’s disease, poorly performing mitochondria have been associated with the death of dopamine-producing nerve cells in a region of the brain called the substantia nigra, which plays a major role in control of movement. Loss of these cells is a hallmark of Parkinson’s disease and the cause of prominent symptoms including rigidity and tremor.
A UCSF team led by Shokat, a Howard Hughes Medical Institute Investigator, used the chemical, called kinetin, to increase mutant PINK1 enzyme activity in nerve cells to near normal levels.
“In light of the fact that mutations in PINK1 produce Parkinson’s disease in humans, the finding that kinetin can speed mutated PINK1 activity to near normal levels raises the possibility that kinetin may be used to treat these patients,” Shokat said.
The researchers also found that, in nerve cells with normal PINK1, kinetin boosted enzyme activity beyond typical levels. This finding may be relevant for the most common forms of Parkinson’s disease, in which PINK1 is not mutated, because a previous study showed that similar overactivity of PINK1 can slow the development of abnormal movement in a fruit-fly modelof Parkinson’s disease caused by another defect. This defect is elevated production of the protein alpha-synuclein, also a cause of some inherited cases of Parkinson’s disease.
The demonstration in the new study that PINK1 can be boosted in human nerve cells that lack PINK1 mutations therefore suggests that kinetin might also have therapeutic potential in common cases of Parkinson’s disease in which PINK1 is not mutated, Shokat said.
Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease, and the 14th leading cause of death in the United States, according to the U.S Centers for Disease Control and Prevention. Current treatments primarily aim to boost availability of dopamine to brain regions where dopamine-producing nerve cells have been lost.
Although many drugs that inhibit the activity of kinases have been developed over the past decade, including 15 currently approved to treat cancer, Shokat said none has yet been marketed to directly boost activity of a kinase.
The breakthrough in revving up PINK1 activity pharmacologically stemmed from Shokat’s unconventional approach. He targeted the enzyme’s “substrate,” a molecule that binds to an enzyme and undergoes a quick chemical transformation as a result. PINK1 uses ATP as a substrate, and the chemical reaction helps PINK1 in turn drive the activation of another enzyme, called Parkin.
Both of these enzymes are among a small number that previously have been strongly linked to Parkinson’s disease. PINK1 and Parkin act together to monitor the health of mitochondria, and help trigger repair or disposal of damaged mitochondria within the cells, thereby promoting cell survival.
“Therapeutic approaches for enhancing the activity of PINK1 had not been considered, because scientists had not conceived of the idea of developing a new substrate for the enzyme,” Shokat said.
“We found that a small molecule, called KTP, speeds chemical reactions catalyzed by PINK1 better than ATP, the natural substrate. That kind of better-than-natural response is essentially unheard of.”
KTP is too big to fit into other kinases, Shokat said, but PINK1 has a larger ATP “pocket” to hold KTP.
After discovering the potential of KTP, the researchers then determined that kinetin is converted to KTP within cells. Experimentally, kinetin, which can cross blood vessels to get into the brain, has been given by mouth to treat a rare, genetic, neurological disease called familial dysautonomia.
Source:ACS Nano

AHMA in Kerala to start diploma course in Ayurveda nursing to beat shortage of paramedical staff

As a solution for the burning issue of shortage of paramedical staff in ayurvedic hospitals in Kerala, the Ayurveda Hospital Management Association (AHMA) has designed an academic programme to mould skilled staff to fill up the lacunae in the traditional health sector.As part of the programme, the association, with the support of speciality hospitals in Kerala is starting a diploma course approved by National Council for Vocational Training (NCVT). The course will be known as Diploma in Ayurveda Nursing and Punchakarma Therapy (ANPT). The duration of the course is one year.
Sources in the association said classes for the first batch of the course will be started on September 2 in five Ayurveda Hospitals in Kerala. AHMA has formed an academic council under the leadership of Prof Dr K G Vidyasagar, retired professor, Ayurveda College Thiruvananthapuram. Kottakkal Arya Vaidyasala, Sreedhareeyam Ayurvedic Eye Hospital, Kootthattukulam, Punarnava Ayurveda Hospital, Ernakulam, Dhathri Ayurveda Hospital, Kayamkulam and Moulana Abdul Rasak Moulavi Hospital, Kozhikodu are the selected hospitals for the academic purpose, said Dr Baby Krishnan, secretary of AHMA.
The syllabus of the course was prepared by an academic sub committee consisting eminent doctors and academicians and got the approval of NCVT. The course will equip the students to manage services of hospital nurses, masseurs and therapists, the secretary told Pharmabiz.
The basic qualification to join the ANPT is a pass in matriculation and the fee is Rs.25,000. For students belonging to SC-ST are eligible to get fee concession. On completion of the course they will be absorbed by the hospitals for the vacancies of nurses and therapists. But, they will not be posted in the vacancies of pharmacists, he added.

Source: Pharmabiz

Researchers Explain How Neurons Get Wired

An unknown mechanism that establishes polarity in developing nerve cells was discovered by the University of Arizona scientists. Understanding how nerve cells make connections is an important step in developing cures for nerve damage resulting from spinal cord injuries or neurodegenerative diseases such as Alzheimer's.In a study published on Aug. 12 in the journal Proceedings of the National Academy of Sciences, UA doctoral student Sara Parker and her adviser, assistant professor of cellular and molecular medicine Sourav Ghosh, report that the decision which will be the "plus" and the "minus" end in a newborn nerve cell is made by a long and a short version of the same signaling molecule. 
Nerve cells - or neurons - differ from many other cells by their highly asymmetric shape: Vaguely resembling a tree, a neuron has one long, trunk-like extension ending in a tuft of root-like bristles. This is called the axon. From the opposite end of the cell body sprout branch-like structures known as dendrites. By connecting the "branches" of their dendrites to the "root tips" of other neurons' axons, nerve cells form networks, which can be as simple as the few connections involved in the knee-jerk reflex or as complex as those in the human brain.
Source:journal Proceedings of the National Academy of Sciences
 

Unique Virus-Derived Particles can Kill Blood Cancer Cells

Unique virus-derived particles developed by researchers led by Dr David Conrad and Dr John Bell of the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa (uOttawa) can kill human blood cancer cells in the laboratory and eradicate the disease in mice with few side effects, a new study published in the Blood Cancer Journal reveals.While Dr. Bell and his colleagues have been investigating replicating viruses for the treatment of solid cancers for many years, with very promising results, this is the first major success they have had treating blood cancer (leukemia). It is also the first success they have had using a non-replicating virus-derived particle as opposed to a replicating virus. 
"Our research indicated that a replicating virus might not be the safest or most effective approach for treating leukemia, so we decided to investigate whether we could make virus-derived particles that no longer replicate but still kill cancer," said Dr. Conrad, a hematologist conducting research in the Blood and Marrow Transplant Program at The Ottawa Hospital, and currently completing his PhD at OHRI and uOttawa in the Department of Cellular and Molecular Medicine. "We were delighted to see that this novel therapy was very safe at high doses, and worked extremely well in our laboratory leukemia models. We hope to test this in patients in the near future." 
The researchers used a specific method and dose of UV light to transform regular replicating viruses into unique particles that could no longer replicate and spread, but could still enter cancer cells efficiently, kill them and stimulate a strong immune response against the cancer. These particles were able to kill multiple forms of leukemia in the laboratory, including samples taken from local patients who had failed all other therapies. Normal blood cells were not affected. This novel treatment was also successful in mouse models of leukemia. In fact, 80 per cent of the mice that received the therapy had markedly prolonged survival and 60 per cent were eventually cured, while all of the untreated mice died of their leukemia within 20 days. 
"Leukemia is a devastating disease that can be very difficult to treat, and new therapies are urgently needed," said Dr. Conrad. "While we're still at the early stages of this research, I think this therapy holds a lot of promise because it appears to have a potent, long-lasting effect on leukemia without the debilitating side effects of many cancer therapies used in the clinic right now. We will likely see even better results once we optimize the dose in our preparations to advance this research into human clinical trials." 
Source: Blood Cancer Journal 

 

 

Imaging in mental health and improving the diagnostic process

What are some of the most troubling numbers in mental health? Six to 10 -- the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a 'biomarker' in the brain that will help diagnose and treat two commonly misdiagnosed disorders.
Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.
Dr. Osuch looked to identify a 'biomarker' in the brain which could help optimize the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.
What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. "The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder," states Dr. Osuch.
In order to reach this conclusion, the study approached mental health research from a different angle. "The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses." Dr. Osuch explains, "This approach can help to uncover a 'biomarker' for bipolarity, independent of the current mood symptoms or mood state of the patient."
Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients. The hope is that one day there could be a definitive biological marker which could help differentiate the two disorders, leading to a faster diagnosis and optimal care.
In using a co-relative approach, a novel method in the field, Dr. Osuch uncovered results in patients that extend beyond verbal history and observation. These results may go on to change the way mental health is diagnosed, and subsequently treated, worldwide.
Source:Journal of Affective Disorders

News Video:Busting medical myths about childhood diseases

Courtesy:Fox News

Placebo effects of different therapies not identical

Conditioning, association affect people's responses to placebos

Not all placebos are equal, and patients who respond to one placebo don't always respond to others, according to research published July 31 in the open access journal PLOS ONE by Jian Kong from Massachusetts General Hospital, Harvard Medical School and colleagues from other institutions.
The researchers tested the analgesic effects of genuine acupuncture, sham acupuncture and a placebo pill on healthy participants' pain sensitivity. Participants were not told what treatment they were receiving, but were informed that the pill was Tylenol, a well-known painkiller and different schools of acupuncture: electroacupuncture and manual acupuncture (sham acupuncture). A control group received no treatment at all. Shortly before and after each treatment, a warm electrode was placed on participants' forearms and the temperature gradually increased. They were asked to indicate when the heat first became painful and when it became too hot to tolerate to identify pain thresholds and tolerance.
No significant associations were found between participants' responses to the different treatments, suggesting that none of these individuals could be identified as placebo 'responders' or 'non-responders'. However, participants' expectations that the treatment would help relieve pain correlated with their pain thresholds and tolerance.
According to the authors, these and other parameters in their study suggest that responses to a placebo depend on diverse factors including the route of administration (pills or acupuncture), environmental cues, and learning based on verbal suggestions or conditioning. Kong adds, "It implies that placebo responses may not be dependent on stable individual traits but rather are more a characteristic of the circumstances of individuals or a combination of both trait and state."
In addition, they also found subjects' responses to sham acupuncture correlated significantly with their response to genuine acupuncture. This suggest that people who responded to genuine acupuncture were significantly more likely to experience pain relief from sham acupuncture, but the authors clarify that this does not indicate the two are the same. Instead, they suggest that acupuncture may have non-specific pain-relieving effects that may contribute to this observation.
Source:journal PLOS ONE

Scientists Identify Origins of Cancer

Genetic imprints and signatures left by DNA-damaging processes that lead to cancer have been discovered by researchers. 
They have provided the first comprehensive compendium of mutational processes that drive tumour development.By studying 7,042 genomes of people with the most common forms of cancer, the team uncovered more than 20 signatures of processes that mutate DNA. 
For many of the signatures, they also identified the underlying biological process responsible. 
All cancers are caused by mutations in DNA occurring in cells of the body during a person's lifetime. 
Although we know that chemicals in tobacco smoke cause mutations in lung cells that lead to lung cancers and ultraviolet light causes mutations in skin cells that lead to skin cancers, we have remarkably little understanding of the biological processes that cause the mutations which are responsible for the development of most cancers. 
"We have identified the majority of the mutational signatures that explain the genetic development and history of cancers in patients," Ludmil Alexandrov first author from the Wellcome Trust Sanger Institute, said. 
"We are now beginning to understand the complicated biological processes that occur over time and leave these residual mutational signatures on cancer genomes," the researcher said. 
The team found that a family of enzymes, which is known to "edit" (ie mutate) DNA, was linked to more than half of the cancer types. 
These enzymes, known as APOBECs, can be activated in response to viral infections. 
It may be that the resulting signatures are collateral damage on the human genome caused by the enzymes' actions to protect cells from viruses.
Source-ANI
 

Red Blood Cell Flow Predicted By Computer Model

A peculiar thin layer of clear plasma, devoid of red blood cells exists adjacent to the walls of our arterioles, capillaries, and venules -- the blood vessels that make up our microcirculation. Although it is just a few millionths of a meter thick, that layer is vital. It controls, for example, the speed with which platelets can reach the site of a cut and start the clotting process."If you destroy this layer, your bleeding time can go way up, by 60 percent or more, which is a real issue in trauma," said Eric Shaqfeh, the Lester Levi Carter Professor and a professor of chemical engineering and mechanical engineering at Stanford University. Along with his colleagues, Shaqfeh has now created the first simplified computer model of the process that forms that layer -- a model that could help to improve the design of artificial platelets and medical treatments for trauma injuries and for blood disorders such as sickle cell anemia and malaria. 
The model is described in a paper appearing in the journal Physics of Fluids. 
The thin plasma layer, known as the Fåhræus-Lindqvist layer, is created naturally when blood flows through small vessels. In the microcirculation, the layer forms because red blood cells tend to naturally deform and lift away from the vessel walls. "The reason they don't just continually move away from the wall and go far away is because, as they move away, then also collide with other red blood cells, which force them back," Shaqfeh explained. "So the Fåhræus-Lindqvist layer represents a balance between this lift force and collisional forces that exist in the blood." 
Because the deformation of red blood cells is a key factor in the Fåhræus-Lindqvist layer, its properties are altered in diseases, such as sickle cell anemia, that affect the shape and rigidity of those cells. The new model, which is a scaled-down version of an earlier numerical model by Shaqfeh and colleagues that provided the first large-scale, quantitative explanation of the formation of the layer, can predict how blood cells with varying shapes, sizes, and properties -- including the crescent-shaped cells that are the hallmark of sickle cell anemia -- will influence blood flow. 
The model can also help predict the outcome of -- and perfect -- treatments for trauma-related injuries. One common thing to do during treatment for trauma injuries is to inject saline, which among other things reduces the hematocrit, the blood fraction of red blood cells. With our model, Shaqfeh said, "we can predict how thick the Fåhræus-Lindqvist layer will be with a given hematocrit, and therefore how close the platelets will be to the periphery of the blood vessels -- and how quickly clotting will occur." 

Courtesy: journal Physics of Fluids
 

 

News Video:The plant behind heart treatments

The Medicine Hunter, Chris Kilham, travels to the New York Botanical Garden for a look at a plant called foxglove that helps heart failure patients
Source:Fox News

Scientists Use Stem Cells to Grow Human Heart Tissue

Scientists have been able to grow human heart tissue that contracts spontaneously in a petri dish. 
A team from the University of Pittsburgh, Pennsylvania, used induced pluripotent stem (iPS) cells generated from human skin cells to create precursor heart cells called MCPs.iPS cells are mature human cells "reprogrammed" into a versatile, primitive state from which they can be prompted to develop into any kind of cell of the body. The primitive heart cells created in this way were attached to a mouse heart "scaffold" from which the researchers had removed all mouse heart cells, they wrote in the journal Nature Communications. 
The scaffold is a network of non-living tissue composed of proteins and carbohydrates to which cells adhere and grow on. 
Placed on the 3D scaffold, the precursor cells grew and developed into heart muscle, and after 20 days of blood supply the reconstructed mouse organ "began contracting again at the rate of 40 to 50 beats per minute," said a University of Pittsburgh statement. 
"It is still far from making a whole human heart," added senior researcher Lei Yang. 
Ways have to be found to make the heart contract strongly enough to pump blood effectively and to rebuild the heart's electrical conduction system. 
"However, we provide a novel resource of cells -- iPS cell-derived MCPs -- for future heart tissue engineering," Yang told AFP by email. 
"We hope our study would be used in the future to replace a piece of tissue damaged by a heart attack, or perhaps an entire organ, in patients with heart disease." 
According to the World Health Organisation, an estimated 17 million people die of cardiovascular ailments every year, most of them from heart disease. 
Due to a shortage of donor organs, "end-stage heart failure is irreversible," said the study. 
More than half of patients with heart disease do not benefit from drugs. 
"Heart tissue engineering holds a great promise... based on the reconstruction of patient-specific cardiac muscle," the researchers wrote. 
Last month, scientists in Japan said they had grown functional human liver tissue from stem cells in a similar process. 
Creating lab-grown tissue to replenish organs damaged by accident or disease is a Holy Grail for the pioneering field of stem cell research. 
Until a few years ago, when iPS cells were created, the only way to obtain stem cells was to harvest them from human embryos. This was controversial because it required the destruction of the embryo, a process to which religious conservatives and others object.
Source-AFP
 
 

Grapefruit may Help Prevent Cardiovascular Diseases

Grapefruit contains health-promoting biomolecules could be the key to beating heart disease, say researchers.
 The study, which was carried out by the researchers from Glasgow University, has found out that biomolecules could be used to reduce the inflammation that is the main cause of various heart problems, the Daily Express reported. 
This research may give rise to a new generation of anti-inflammatory drugs that are cheaper and less lethal than some existing therapies.
Source-ANI

 

Researchers: Estrogen Enhancers Tied to Aggressive Breast Cancer

"Distant estrogen response elements" (DEREs) can act independently of oncogenes to spur tumor development, report researchers from the Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center, while adding to the picture of what prompts breast cancers to form.DEREs appear to be depots or hubs that remotely and simultaneously control multiple target genes in response to estrogen stimulation, said Pei-Yin Hsu, Ph.D., lead author of the paper in Cancer Cell. As such, they are prime targets for the study of novel therapies for breast cancer and could also be useful in diagnosis. 
Copy numbers 
Where DEREs are multiplied or present in abnormal numbers, this contributes to tumor development, especially in estrogen receptor-positive breast cancers, said study senior author Tim Hui-Ming Huang, Ph.D., deputy director of the CTRC. 
Decreasing the number of DERE copies could have therapeutic potential to treat women with this aggressive form of cancer, Dr. Huang said. 
DEREs at 2 sites 
The researchers analyzed two DERE clusters on human chromosomes 17 and 23. They found that the DEREs induce pro-growth factors and inhibit growth-suppressing genes. "It is worthwhile to note that DERE-DERE interactions, instead of DERE interactions with genes, may also contribute to tumor development," Dr. Hsu said. 
The team found a correlation between a subset of DERE-regulated genes and tamoxifen resistance. Tamoxifen is a widely prescribed hormone therapy for breast cancer. It may be possible to evaluate how a woman will respond to tamoxifen by measuring DERE activity, Dr. Hsu said. 
Potential biomarkers 
In addition, the two DEREs that were studied could turn out to be good biomarkers for whether a woman will develop estrogen receptor-positive breast cancer. "Perhaps we could prevent some cases of this cancer," Dr. Huang said. 
Several units of the UT Health Science Center joined in the work, including the Greehey Children's Cancer Research Institute, the Institute of Biotechnology, and the Department of Molecular Medicine and Department of Epidemiology and Biostatistics in the School of Medicine. 
Source: University of Texas Health Science Center
 

Men Think About Sex More Often Than Women: Study

Thought of sex occurs to men at least 34 times in a day, as compared to their female counterparts, who think about it around 18 times a day, shows new study. 
The new research shows that men think about sex twice as much as women, the Daily Star reported.The new figures are being associated with the success of E.L. James's erotic novel 'Fifty Shades of Grey'. 
For the research, students at the Ohio State University were asked to record every time they thought about sex, food and sleep each day. 
It found that men do indeed think most about sex, but women have sex on their mind far more than what was previously believed. 
The poll concluded that ladies think about sex on average 18.6 times a day, which works out at once every 51 minutes when allowing for eight hours' sleep. 
The study also revealed that men thought about sex 34.2 times a day, coming down to once every 28 minutes. 
During the survey, psychologists recorded the behaviour of 283 college students, aged 18-25, over the course of a week using hand-held counters.
Source-ANI

 
 

Virus-derived particles target blood cancer

Ottawa researchers have developed an experimental therapy that can kill human blood cancer cells in the laboratory and eradicate the disease in mice

Ottawa researchers have developed unique virus-derived particles that can kill human blood cancer cells in the laboratory and eradicate the disease in mice with few side effects. The study is published in Blood Cancer Journal by co-senior authors Drs. David Conrad and John Bell of the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa (uOttawa).
While Dr. Bell and his colleagues have been investigating replicating viruses for the treatment of solid cancers for many years, with very promising results, this is the first major success they have had treating blood cancer (leukemia). It is also the first success they have had using a non-replicating virus-derived particle as opposed to a replicating virus.
"Our research indicated that a replicating virus might not be the safest or most effective approach for treating leukemia, so we decided to investigate whether we could make virus-derived particles that no longer replicate but still kill cancer," said Dr. Conrad, a hematologist conducting research in the Blood and Marrow Transplant Program at The Ottawa Hospital, and currently completing his PhD at OHRI and uOttawa in the Department of Cellular and Molecular Medicine. "We were delighted to see that this novel therapy was very safe at high doses, and worked extremely well in our laboratory leukemia models. We hope to test this in patients in the near future."
The researchers used a specific method and dose of UV light to transform regular replicating viruses into unique particles that could no longer replicate and spread, but could still enter cancer cells efficiently, kill them and stimulate a strong immune response against the cancer. These particles were able to kill multiple forms of leukemia in the laboratory, including samples taken from local patients who had failed all other therapies. Normal blood cells were not affected. This novel treatment was also successful in mouse models of leukemia. In fact, 80 per cent of the mice that received the therapy had markedly prolonged survival and 60 per cent were eventually cured, while all of the untreated mice died of their leukemia within 20 days.
"Leukemia is a devastating disease that can be very difficult to treat, and new therapies are urgently needed," said Dr. Conrad. "While we're still at the early stages of this research, I think this therapy holds a lot of promise because it appears to have a potent, long-lasting effect on leukemia without the debilitating side effects of many cancer therapies used in the clinic right now. We will likely see even better results once we optimize the dose in our preparations to advance this research into human clinical trials."
Source:Blood Cancer Journal 

Who benefits from vitamin D?

Studying the expression of genes that are dependent on vitamin D makes it possible to identify individuals who will benefit from vitamin D supplementation, shows a University of Eastern Finland study published recently in PLoS One.
Population-based studies have shown that vitamin D deficiency may increase the risk for chronic diseases and weaken the body's immune system. In the present study carried out at the University of Eastern Finland, Kuopio, the study participants were given a daily dose of either 40 or 80 micrograms of vitamin D, or a placebo, over a course of 5 months during Finnish winter. The results showed that the expression of vitamin D dependent genes in adipose tissue and monocytes, i.e. white blood cells, correlated only in half of the study participants with their vitamin D concentrations in the blood.
The researchers concluded that persons whose expression of the CD14 and thrombomodulin genes was not altered as a result of vitamin D supplementation already had a sufficiently high serum vitamin D concentration or their utilization of vitamin D was disturbed, which calls for further study. The researchers believe that studying the expression of vitamin D dependent genes in tissues is a novel way to identify individuals who might benefit from long-term vitamin D supplementation. This observation is further supported by the fact that studying alterations in the expression of genes also made it possible to identify persons whose levels of interleukin 6, an inflammation marker, were reduced as their serum vitamin D levels increased.

Source:PLOS ONE

US Public Health Service Issues New Federal Guidelines for Managing Occupational Exposures to HIV

The recommendations for the management of healthcare personnel (HCP) with occupational exposure to HIV and use of postexposure prophylaxis (PEP) were updated by new guidelines from the United States Public Health Service. The guidelines, published online today in Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America (SHEA), emphasize the immediate use of a PEP regimen containing three or more antiretroviral drugs after any occupational exposure to HIV.The PEP regimens recommended in the guidelines encourage the consistent use of a combination of three or more drugs, that are better tolerated than those recommended in the previously published guidelines from 2005, for all occupational exposures to HIV. The guidance eliminates the previous recommendation to assess the level of risk associated with individual exposures to help determine the appropriate number of drugs recommended for PEP. 
"Preventing exposures should be the leading strategy to prevent occupational HIV infections," said David Kuhar, MD, an author of the guidelines and medical epidemiologist with the Centers for Disease Control and Prevention's (CDC) Division of Healthcare Quality Promotion. "However, when an exposure occurs, it should be considered an urgent medical concern and a PEP regimen should be started right away, ideally within hours of the potential exposure." 
Expert consultation should be sought, but not at the expense of delaying treatment. Exposed HCP taking HIV PEP should complete a full four-week regimen and undergo follow-up HIV testing, monitoring for drug toxicity and counseling, beginning with follow-up appointments within 72 hours of the exposure. If a newer 4th generation HIV antigen/antibody combination test is used for follow-up testing, an option to conclude HIV testing at 4 months, rather than the recommended 6 months after exposure, is provided. Many of the revised recommendations are intended to make the PEP regimen better tolerated, increasing the possibility that HCP complete the full regimen. 
The guidelines were developed by an interagency Public Health Service working group comprised of representatives from the CDC, National Institutes of Health, Food and Drug Administration and the Health Resources and Services Administration, in consultation with an external expert panel. The updated revisions were based upon expert opinion. 
HCP might include emergency medical service personnel, dental personnel, laboratory personnel, autopsy personnel, environmental maintenance personnel, nurses, nursing assistants, physicians, technicians, therapists, pharmacists, students and trainees. Many HCP exposures to HIV occur outside of health clinic hours of operation and initial exposure management is often overseen by emergency physicians or other providers who are not experts in the treatment of HIV infection or the use of antiretroviral medications. As such, the updated guidelines should be distributed and made readily available to emergency physicians and other providers as needed.
Source:Infection Control and Hospital Epidemiology online journal

Garlic Oil May Reduce Adverse Effects of Chemotherapy and Radiotherapy

Garlic oil could be used as complementary medicine for cancer patients receiving Chemotherapy / Radiotherapy, to ease the adverse effects of these treatments, reveals a study published in the Journal of Food Science.Chemo and radiation therapy are effective against the cancer, but they also have many side effects that adversely affect the patient's body. Side effects such as anemia (causing fatigue, paleness, shortness of breath, and a fast heartbeat) and blood clotting problems (causing small red spots on the skin, bloody or black bowel movements or vomit, or bleeding from the nose or gums) are often seen with chemotherapy because these drugs and radiation adversely affect the body's production of healthy blood cells including RBC, WBC, and platelets. With the incidence of cancer cases rising globally, it has become imperative to find natural ways to reduce the adverse effects of the two major methods for cancer treatment, chemotherapy and radiation therapy. 
Anticancer effects of garlic and its products have already been demonstrated by various studies but not much information is available on whether garlic benefits people undergoing chemo/ radiotherapy. 
So, researchers at School of Public Health, Shandong University, China, set out to investigate the effects of garlic oil on the adverse effects of chemo/radiotherapy in mice with cancerous tumors.
In the chemotherapy test, the tumor-bearing mice were treated with cyclophosphamide (CTX) or CTX plus garlic oil for 14 days, while the mice received a single 5 Gy radiation or radiation plus garlic oil in radiotherapy test. 
The findings showed that garlic oil did not enhance the sensitivity of cancer cells to chemotherapy or radiotherapy, but they did have the following positive results with garlic oil co-treatment - 
• CTX / radiation plus garlic oil suppressed the decrease of the peripheral total white blood cells (WBCs) count induced by chemo / radiation. 
• Added garlic oil treatment significantly inhibited the decrease of the DNA contents and the micronuclei ratio of the bone marrow. Micronuclei are small nuclei in the DNA that are essential for reproduction. 
• The garlic oil treatment also suppressed the reduction of the endogenous spleen colonies induced by CTX/radiation. Spleen colonies are stem cells located in the bone marrow that is responsible for the formation of RBC, WBC, and platelets and have the capability of self-renewal. 
The findings thus support the idea that garlic oil does help reduce the adverse effects of chemotherapy and radiotherapy. 
However, further research is needed to find out if garlic oil could reduce the adverse effects induced by other chemotherapeutic drugs. 

Reference: http://www.ncbi.nlm.nih.gov/pubmed/23772706 
 

 

Oily Fish Consumption Cuts Rheumatoid Arthritis Risk

The research conducted on more than 32,000 Swedish women found that a fish diet is beneficial because it is rich in omega-3- a good anti-inflammatory agent, the BBC reported.The researchers found that women who consistently ate any type of fish at least once a week cut their risk of developing rheumatoid arthritis by nearly a third, while those who ate at least one portion of oily fish or four servings of other fish each week halved their risk. 
Talking about fish oil supplements, Prof Alan Silman, medical director of Arthritis Research UK, said that taking high levels of fish oils can prevent inflammation from starting in the joint. 
The study is published in journal Annals of the Rheumatic Diseases.
Source-ANI
 

News Video:What do you need to know about drug interactions?

Times when drugs can cause unwanted reactions.
Source:Fox News

Why You Should Eat Breakfast Like a King ?

A recent research found that the timing of your meals is crucial to maintain weight as well as offset many lifestyle diseases like hypertension, diabetes and cardiovascular disease.Researchers said that a good breakfast helped in giving the body the right amount of nutrients, improving mood and keeping disease at bay. Since metabolism is influenced by the circadian rhythm, it is important to follow meal timings strictly. So, it is not just what we eat that matters but also when we eat food that matters in aiding a healthy metabolism. 
In a recent study, researchers found that those who consume their hugest daily meal during breakfast have a greater chance of losing weight and having a healthy waistline as compared to those who consume a huge dinner. 
Such people also had markedly reduced levels of insulin, glucose, and triglycerides throughout the day, translating into reduced risk of hypertension, diabetes and cardiovascular disease. 
So, "eat breakfast like a king, lunch like a prince, and dinner like a pauper", to live a healthy life. 

 

 

Low Childhood Conscientiousness Predicts Adult Obesity

Results from a longitudinal study show that children who exhibit lower conscientiousness (e.g., irresponsible, careless, not persevering) could experience worse overall health, including greater obesity, as adults. The Oregon Research Institute (ORI) study examines the relationship between childhood personality and adult health and shows a strong association between childhood conscientiousness (organized, dependable, self-disciplined) and health status in adulthood. ORI scientist Sarah Hampson, Ph.D., and colleagues at the Kaiser Permanente Center for Health, Hawaii report these findings in the August issue of Health Psychology. Hampson was recently the discussant for a panel on personality and health at the national American Psychological Association meeting in Honolulu, HI.“These results are significant and unique because they show the far-reaching effects of childhood conscientiousness on adult health. Others have shown that more conscientious children live longer. Now we have shown that these conscientious children are also healthier at midlife” noted Dr. Hampson.Hawaii school-children rated by their teachers in the 1960’s as less conscientious had worse global health status as adults and had significantly greater obesity, high cholesterol, and increased risk for cardiovascular disease. Childhood conscientiousness was significantly associated with decreased function of the cardiovascular and metabolic systems. This association was independent of the other Big Five personality childhood traits, adult conscientiousness, childhood socioeconomic status, ethnicity, and gender. This is the first study in which all the Big Five personality traits (extraversion, agreeableness, conscientiousness, emotional stability, and intellect/imagination) assessed in childhood have been used to predict objective health status assessed by multiple biomarkers over 40 years later in older adulthood.In the 1960’s, over 2,000 children from entire classrooms in elementary schools on two Hawaiian Islands were comprehensively assessed on their personality characteristics. ORI researchers were funded in 1998 by the National Institute of Mental Health to locate and examine the health-related behaviors and mental and physical health status of these individuals. Almost 75% of those in the original group who could be located (mean age 51 years) have agreed to participate, and over 800 individuals completed a medical and psychological examination supported by subsequent grants from the National Institute on Aging.The physical examinations took place at the Kaiser Permanente Center for Health Research, Hawaii in Honolulu and at medical clinics on the islands of Kauai, Hawaii, and Maui and included biomarkers of cardiovascular and metabolic systems such as height, weight, waist and hip circumference, blood pressure, cholesterol and fasting blood glucose.“These findings suggest avenues for further research that may lead to interventions. People who are more conscientious tend to have better health habits and less stress, which protects them from disease. Self-control is a key part of being conscientious, so our findings confirm the importance of teaching children self-control to enable then to grow up to be healthy adults,” said Hampson.Founded in 1960, Oregon Research Institute is a non-profit behavioral research center with offices in Eugene & Portland, Oregon, Seattle, Washington, and in Albuquerque, New Mexico. This research was supported by grant AG020048 from the National Institute on Aging, National Institutes of Health.

Source:Oregon Research Institute

Macrophage proliferation appears to drive progression of atherosclerosis

Proliferation of immune cells within plaques is key mechanism, potential treatment target

New insights into the development of vulnerable atherosclerotic plaques could lead to better treatment or prevention of heart attacks and strokes. In a report being published online in Nature Medicine, researchers at the Massachusetts General Hospital (MGH) Center for Systems Biology re-evaluated previous assumptions regarding the role of inflammatory cells in atherosclerosis and found that the process relies on proliferation of certain immune cells within plaques and not exclusively on the uptake of cells from the blood.
The prevailing theory of atherosclerosis has been that plaques grow by drawing white blood cells called monocytes in from the circulation. These monocytes then mature into macrophages, cells that ingest lipid and cholesterol molecules but remain within the plaques, leading to the buildup of a fatty core that contributes to the risk of plaque rupture. While it had been believed that each macrophage descended from a single monocyte that had entered a plaque, the MGH team found that proliferation of new macrophages within plaques is a major driver of their growth.
"Currently, there is quite a bit of interest in targeting inflammation as a way to treat vascular disease, and one of the ways to do so is by targeting the cells responsible, says Filip Swirski, PhD, of the MGH Center for Systems Biology, senior author of the Nature Medicine report. "We discovered that the atherosclerotic lesion is a very dynamic environment, and even though the macrophages within a lesion are fundamentally derived from monocytes, they do not require constant monocyte input to sustain their numbers."
In a series of experiments in mice, the MGH-CSB team first found that existing plaques within the aortas of animals fed a high-cholesterol diet showed evidence of a rapid and constant proliferation of macrophages that did not require the presence of monocytes in the blood. Although monocytes were needed for the initiation of atherosclerosis, once plaques had formed, macrophage proliferation became the primary mechanism for the further growth of plaques. The investigators also identified a receptor protein on macrophages that appears to contribute to their proliferation within plaques without the involvement of monocytes. While further study is required to determine whether the same processes occur in humans, the MGH team did find evidence of macrophage proliferation in plaques from human carotid arteries.
 "I think this work will force some major re-evaluations," says Swirski, an assistant professor of Radiology at Harvard Medical School. "People have been thinking of targeting monocyte influx to treat atherosclerosis, but they need to consider macrophage proliferation as an additional or alternative approach, especially in established disease. That might actually be better than targeting circulating monocytes, since interrupting pathological processes within the plaques themselves could spare the beneficial immune responses mediated by monocytes."
Source:Nature Medicine

New study redefines how plaques grow in heart disease

The growth of deadly plaque inside the walls of arteries may not happen as scientists believed, research from the University of Toronto and Massachusetts General Hospital has found.
The research also suggests a new potential target in the treatment of atherosclerosis, a leading cause of cardiovascular disease and death globally.
The research team found that macrophages, white blood cells that drive atherosclerosis, replicate inside plaques. Moreover, this growth is not reliant on cells outside the plaques called monocytes, as scientists had assumed.
"Until now, the thinking was that inflammatory macrophages arise mainly from the recruitment of their precursors — monocytes — from the bloodstream," said Clint Robbins, lead author on the study and an Assistant Professor in U of T's Departments of Laboratory Medicine and Pathobiology, and Immunology. "Our study shows that the accumulation of macrophages also depends on their proliferation locally within the developing plaque."
The journal Nature Medicine published the study results today.
The impact of the research on clinical treatments could be large. Many pharmaceutical companies are pouring resources into potential therapies that can block the recruitment of white blood cells into plaques. But if macrophages self-sustain through local cell division, blocking recruitment may not be the best strategy.
"I think this work will force some major re-evaluations," said Filip Swirski, the study's principal investigator who is a scientist in the Center for Systems Biology at Massachusetts General Hospital and an Assistant Professor at Harvard Medical School. "People have been thinking of targeting monocyte influx to treat atherosclerosis, but they need to consider macrophage proliferation as an additional or alternative approach, especially in established disease."
That approach might be better than targeting circulating monocytes, since interrupting disease-causing processes within plaques could spare other beneficial immune responses that monocytes control, said Swirski.
As well, it could help improve the current standard of care in treating atherosclerosis: statin therapy. Statins, in addition to lowering blood lipids that contribute to plaque, have anti-inflammatory properties. The researchers are now looking at whether statins might limit the spread of macrophages within plaques.
"Additional targeting of macrophage proliferation may further decrease inflammation in atherosclerosis and prove clinically advantageous," said Robbins, who is also a scientist in the Toronto General Research Institute at University Health Network.
The researchers conducted their study in mice, and they caution that much more research is needed to see how the work will translate to humans. But encouragingly, they found evidence of macrophage growth in plaques from human carotid arteries.
Next, the team will compare macrophage proliferation to monocyte recruitment during different stages of atherosclerosis, and look at whether all macrophages, or only subsets, replicate.
Source:Nature Medicine