HIV and Drugs: Interface

By: Azilleo Kristo Mozihim

Human Immunodefiency Virus, most commonly abbreviated in daily conversations as HIV, is a phrase that strikes fear into the hearts of many. The Malaysian community is of no exception. The issue of HIV is still considered a taboo topic to be discussed but this is not the case during a HIV talk presented by Professor Altice on the 18^th of January at Baylis Theatre at 5 pm.

Professor Frederick Lewis Altice is a professor from Yale University whose main research interest lies in the interface between infectious disease and substance abuse. He started the talk quite casually and did not consider it as a formal event which can be obviously seen from the way he casually dressed. He stated that HIV is a widespread infectious disease not only in Malaysia but also globally. He showed a series of graphs illustrating the prevalence of HIV based on sexual activities and demographical parameters such as race and age. He emphasised that the treatment for HIV is not reaching those who needed them the most which are the intravenous drug abusers. Also, the stigmatisation of HIV-infected people should be dispelled because it deters them from going to healthcare professional to seek prompt treatment.

          

         He paid a great deal of time talking about the treatment of drug addiction particularly relating to prisoners. He stated that prisoners who were drug abusers are treated with, ironically, drugs such as naltrexone to assist in curbing their drug addiction. Based on his research, those who were part of the drug therapy had significantly less chance of relapsing into drug addiction than those who did not undergo the treatment once released from incarceration. He also stated that prisoners are significantly more likely than the general community to contract tuberculosis and fifteen times more likely to be HIV-infected. He suggested that prisoners who are infected with tuberculosis should not be placed in closed and tight spaces with other prisoners to reduce the risk of transmission to uninfected prisoners.

        

        In a nutshell, the talk given by Professor Altice emphasised the need to dispel the stigmatisation and negative attitude surrounding HIV and substance abuse so as to not deter those involved from seeking proper medical treatment. He suggested that the healthcare system should be restructured in such a way that it prevents those needing the treatment from being unfairly judged and from being stigmatised. The talk ended around 6.30 pm with the Academic Medicine Society (AMS) committee presenting to him a souvenir of appreciation. 

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Bioartificials

By: Muzhaffar Abdullah

The nation was saddened over the news of the death of Tee Hui Yi, 19, who made headlines in 2007 following her double heart transplant surgery. Hui Yi from Batu Pahat, Johor had a second heart transplant within 24 hours after her body rejected the first heart that was transplanted into her. It was merely a miracle that a second heart became available and the heart that previously belonged to a 15 year old stranger, became hers. The success story of the cardiothoracic team from National Heart Institute (IJN) captured the heart of millions of people around the country who had followed Hui Yi’s health progress since she was 13. 

Tee Hui Yi passed away at the Batu Pahat Hospital on 18^th September 2012, the day she was to have started work as a kindergarten teacher.

On October this year, Jakub Halik from Czech Republic died from liver failure at the age of 37. He died after surviving more than six months without a real heart. He had his heart replaced with two mechanical pumps after an aggressive cancerous tumour was found. He was awaiting a suitable donor when he died.

Both Hui Yi and Jakub, albeit from continent afar and a huge age gap between them had their life depended on man-made mechanical structure for a considerable period of time. Hui Yi had it earlier when she was 13. She was like Jakub, waiting for a heart donor. She had underwent a five-hour operation at the IJN to implant an external mechanical heart made of a 9.8kg device. The device was placed outside her abdomen and connected to the left side of her heart. 

For Jakub, despite being pulseless and unable to feel his own heartbeat (as he had no heart), he described his post-surgical experience as normal. He felt that his body was functioning normally. Although he had to always carry a battery pack to power the mechanical heart, he was able to walk around and use the hospital gym. He felt much like a healthy man.

Although these stories ended sadly, they told us how much potential artificial organs have in the future of medicine. With ingenious understanding of how the body functions, researchers have been able to design and produce devices that could be implanted or integrated to replace a natural organ.

These devices serve the purpose of restoring the normal function of our body. The uses of current state of the art artificial hearts devices for instance is hoped to be able to sustain life for up to 18 months for patients awaiting transplants whose death is imminent, such as in the case of Hui Yi and Jakub.

Artificial organs are also helpful in improving the patient's ability for self care as in the use of artificial limb. The use of cochlear implantation has become among standard proposed management to improve patient’s ability to interact socially among hearing impaired individuals.

Current progress brings even more exciting promises. In the near future, we might expect to see the use of bioartificial; part artificial and part our own body. This will potentially provide us with abundant supply of ready-made replacement livers, kidneys and hearts, by being partly built in the lab and partly built inside the body.

There has been ongoing research using tissue engineering technique to build organs using patient’s own cells. Success had been reported in the Unites States after the researchers in Wake Forest University, North Carolina has successfully transplanted laboratory grown bladder into a patient in 2006.

Tissue engineers used a different approach in developing these bioartificial organs as compared to the more old-fashioned artificial hearts used by Hui Yi. They are trying to develop something which is considered more human. The ultimate aim is to make organs with cells, blood vessels and nerves to become a living and functioning part of the body.

They are trying to execute this by manipulating the body’s own natural repair mechanism. The two body’s own cells that are being used are the stem cells and organ scaffolding. Stem cells has the potential to develop into any tissue in the body while organ scaffolding gives organs their shape and in which cells embed themselves to form organs. This stem cells-seeded fibrous web (scaffolding) will keep the stem cells in the right place and this hopefully will allow the new organ to grow.

The prospect with this proposition has been bright; a plastic form of artificial scaffold has been used in a pioneering windpipe replacement surgery for a man with cancer. The patient is currently doing well 15 months after the procedure.

The bioartificials are also hoped to eliminate the usual risks associated with current standard organ transplant such as immune rejection as it will not be using foreign cells. This also means the use of drugs which suppress the immune system will not be needed and patient will be less prone to infection.

Further expansion of the potential therapeutic uses of artificial organs has also been suggested in other areas such as vision, memory and information processing and the research is proceeding. There has even been speculation that we might be able to enhance our memory through implantation of related cells to the brain.

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Heroes of Stem Cell Research

By Azilleo Kristo Mohinim

The Nobel Prize is considered globally to be the most prestigious accolade that can be awarded to a person or an institution for contributing to specific fields of human endeavour. One of these fields is Medicine or Physiology. The Nobel Prize for Physiology or Medicine is annually awarded to people who have immensely contributed to the advancement of Physiology or Medicine. It represents the zenith of intellectual originality and creativity in the field of Physiology or Medicine. For the year 2012, the Nobel Prize of Medicine or Physiology was awarded to and shared by two distinguished scientists who are Shinya Yamanaka and Sir John Gurdon for their peerless contribution in stem cell research.

Shinya Yamanaka (right) and John B Gurdon (left), the winners of the 2012 Nobel prize in Physiology or Medicine. Photograph: The Guardian

Shinya Yamanaka

Shinya Yamanaka was born on the 4^th of September 1962 in Osaka, Japan. He obtained his MD from Kobe University in 1987 and his PhD from Osaka City University in 1993. From 1993 to 1996 he was a postdoctoral fellow in the Gladstone Institute of Cardiovascular Disease in San Francisco. After that he went back to Osaka City University Medical School to assume the position of an assistant professor and became an associate professor at Nara Institute of Science and Technology in 1999 which led to a full professorship in 2003. In 2008, he became the Director of Centre for Induced Pluripotent Stem Cell Research and Application (CiRA). He is also the member of the International Society of Stem Cell Research (ISSCR) Board of Directors.

Sir John B. Gurdon

Sir John B. Gurdon was born at Dippenhall, United Kingdom on 2^nd October 1933. He attended Eton College before undertaking Classics at Christ Church, Oxford. During his course of studying Classics, he decided to switch to Zoology. He obtained his doctorate from the University of Oxford in 1960. He did his postdoctoral research at California Institute of Technology and in 1962 he returned to England and was given a teaching post at the Department of Zoology of the University of Oxford. He is currently at the Gurdon Institute in Cambridge.

Removal of a cell from a dividing fertilised animal egg.
Photograph: The Telegraph

The Nobel Prize for Physiology or Medicine was awarded for reprogramming mature differentiated cells into pluripotent stem cells. In 2007, Yamanaka managed to induce mature human skin cells to become stem cells. These stem cells which are were artificially derived from mature cells are called induced pluripotent stem (iPS) cells. He managed to accomplish such a feat by introducing four pieces of genetic material which are now called Yamanaka factors into the genome of the cell. The Yamanaka factors in actuality are four distinct transcription factors called Oct 3/4, Sox2, Klf 4 and c-Myc. These transcriptions factors regulate cellular gene expressions and are highly expressed in embryonic stem cells.

For John B. Gurdon, his main concern was regarding the genes which were present in the nucleus of specialised cells. He was wondering whether cellular specialisation involved the loss of unwanted genes from the genome of cell or merely the inactivation of the unneeded genes. In 1962, he did an experiment which involved the removal of the nucleus of an egg of a frog and transferring the nucleus of a tadpole’s intestinal cells into the enucleated frog egg. Instead of differentiating into intestinal cells, the egg developed into a normal tadpole. The result gave concrete evidence that the nucleus of mature differentiated cells still contain the genes required to develop into a fully functional organism.

Our understanding of cell biology and the discovery of new experimental techniques to form iPS have opened many to avenues to improve the quality of life of mankind as well as give us a glimmer of hope in curing previously incurable disease. An example of the incurable disease is cardiovascular disease. It is the main killer disease in the world currently with, according to the World Health Organisation (WHO), an estimated 7.3 million people died of ischemic heart disease in 2008 alone. Heart cells cannot regenerate and once they are dead due to restricted supply of blood, they are replaced with fibrous tissues which cannot function as heart muscle. With iPS, it is possible to replace these dead heart cells by substituting with heart cells differentiated from iPS. In the near future, it is possible that stem cell therapy for many currently incurable diseases will become routine clinical practice.

One of the main concerns when it comes to stem cell research is the usage of embryos in order to obtain the stem cells. Many religious bodies are fervently against the usage of embryos in stem cell research since it violates the concept of sanctity of life espoused by them. Religious opposition to stem cell research significantly impeded the advancements in stem cell research. However, with the new technique discovered by Yamanaka, the ethical controversy shrouding stem cell research can be circumvented considering the fact that the stem cells obtained are derived from mature cells instead of from embryos. With the absence of religious opposition, stem cell research can be elevated to greater heights more quickly.

We are a species of curiosity. We strive to understand the world as well as ourselves. The achievements of the two great men mentioned in this article and their benefits are just a few out of many that exist. As humans accumulate more knowledge, we are able to manipulate nature in accordance of our will in order to improve our quality of life. However, bear in mind that we should do so within ethically acceptable boundaries. 

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Unravelling the mysteries of unpleasant scrapping sounds

Unravelling the mysteries of unpleasant scrapping sounds.

A team of researchers led by Professor Tim Griffiths from Newcastle University have found out that higher activation in the brain regions which processed emotion and sound, and the correlation between these two are the main reason why the sound of knife on the bottle or nails on the blackboard are so unpleasant.

In their recent study published in the Journal of Neuroscience October 2012, the scientists at Institute of Neuroscience, Newcastle and Wellcome Trust Centre, London explained the model of interaction between the auditory cortex, the part of the brain that processes sound, and the amygdala which processes negative emotions. 

When we hear a nasty noise, the sound is first processed to a high level in the auditory cortex. The information is then relayed to the amygdala where not only it determines the acoustic features of the stimulus, it will also decide how unpleasant the noise is. If the unpleasantness of the sound is perceived as higher, the amygdala will then return the information to the auditory cortex causing a heightened activity in the auditory cortex in response to this sound compared to a less unpleasant sound.

A total of sixteen volunteers participated in the study where functional magnetic resonance imaging (fMRI) was used to examine their brain activity in response to unpleasant sounds played in the MRI scanner. The choices of sounds were based on the scientists’ previous work in 2008 in which 50 volunteers were recruited to rank a set of 74 sounds according to their unpleasantness. These included the most unpleasant knife on a bottle, chalk scratched on blackboard, and bubbling water which was deemed least unpleasant.

The MRI data collected was then analysed and a connectivity analysis was conducted to determine the interactions between different brain regions, how a brain area may respond to a change in activity another area. For the purpose of this research, four brain regions were specifically studied which were the right and left auditory cortex and right and left amygdala.

Image 1: MRI image showing the response in amygdala which correlates with acoustic features and rating of unpleasantness. The red areas indicate where the acoustic features are processed while blue areas indicate the valence (or degree of unpleasantness). 

 The study found that sounds in the frequency range of 2000 to 5000 Hz were found to be unpleasant. Based on the relationship models tested in this research, it was also found that the brain parts did not work independently from one another, but in a very integrated manner. Stimulus received by the auditory cortex was processed and forwarded to the amygdala. A backward connection from amygdala to the auditory cortex subsequently takes place in accordance to the interpretation of the amygdala of the characteristic of the stimulus.

 Although the study is rather limited in the sense that there is very small sample size, such findings is significant to pave our ways to a better understanding of certain medical conditions in which there is lack of tolerance to sound. This includes hyperacusis (decreased sound tolerance), misophonia (“hatred” of sound) and phonophobia (fear of sound).

"This work sheds new light on the interaction of the amygdala and the auditory cortex. This might be a new inroad into emotional disorders and disorders like tinnitus and migraine in which there seems to be heightened perception of the unpleasant aspects of sounds," says Professor Tom Griffiths in a press release in last October.

Future studies are necessary to gain more understanding regarding the subject and to investigate further on the effect of different sounds, both pleasant and unpleasant and to answer whether similar pathway plays the role in processing nice sounds compared to these nasty scraping noises that makes us grind our teeth.

(This article is adapted from The Institute of Neuroscience press release, Nasty noises: Why do we recoil at unpleasant sounds?, published on 10^th October 2012, accessible at http://www.ncl.ac.uk/ion/news/news/item/nasty-noises-why-do-we-recoil-at-unpleasant-sounds-copy)

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