EFFECTS OF ‘OTHER’ DEVICES ON CARDIAC PACEMAKERS
Mr. V.P. Shrivastava
The cardiac rhythm under normal circumstances is maintained due to the function of specific heart cells. These types of cells produce small current at the heart site less than one hundredth of a volt, and maintain the congestive heart function. More specifically, each heart beat is starting from a certain point of the heart, which is called sinus node. The sinus node exists in the right atrium and is supposed to be the natural pacemaker of the heart. Thus, the cardiac heart rate is dependent on the produced rate from sinus node. The electrical pulse is transferred very slowly to both artias. After this, the atrium chambers collect the blood from the body and the ventricle chambers push it out again.
The normal heart rate changes with age. A normal cardiac rate for an adult man is 70 beats per minute, but it is always determined by the body needs. And the blood which is pumped is approximately 4 litres.
It is important to mention that heart rhythm has to be maintained in specific limits. If the heart beats too slow, then blood supply to the brain is not sufficient. In this case the patient may become unconscious. Besides, a faster heart rate will cause other problems. Therefore it is essential that the cardiac rate remain between 50 beats per minute to 150. However, in some cases the natural pacemaker may fail to produce electrical pulse. Other cardiac cells near to the sinus node take on the responsibility to maintain the congestive cardiac function, but then the heart rate becomes slower.
Other factors may influence the cardiac function, such as infections, and various cardiac diseases.
In that case when a drug therapy fails, implantation of a cardiac pacemaker is inevitable. The first implantable cardiac pacemaker (ICP) was implanted to a 77-year-old patient in 1960 in Buffalo U.S.A. This first approach was successful, because the patient continued his life without specific limitations on his lifestyle for a significant period of time. (1)
INDICATIONS FOR PACING
In 1984 for the first time, a joint commission of the American college of Cardiology and the American Heart Association determined specific indications for pacing. However, new indications after 1984 were added.
More specifically, the indications are classified as below:
All these indications are related with common heart diseases, such as:
In all of these cases a pacemaker can provide an appropriate treatment, and prevent heart failure.
Types of pacemaker
There are two major types of cardiac pacemakers: The first one is called temporary pacemaker, and is mainly used for patients with temporary heart problems. The other type is permanent pacemaker and is helpful for permanent heart diseases. Permanent pacemakers can be:
(1) Fixed ventricular rate pacemaker, in which the cardiac rate is predetermined regardless of the heart function. In this case the heart function is based on pacemaker’s function.
(2) Demand pacemaker. It is the most frequently used, and it has a sensing system that detects abnormal heart rhythm. If the heart rate is unusually, then the pacemaker provides cardiac pacing, and
(3) Synchronous pacemaker, which has many advantages for young people.
Pacemaker components and function
Pacemaker is composed of a pulse generator and some leads. Besides this, they use CMOS circuit technology and ROM memory, which includes all their programmed functions. RAM (Random Access Memory) is also used to store adverse events related to the heart function for diagnostic reasons.
The pulse generator with its entire component is housed in a hermetically sealed case, mostly made of titanium. It has also a connector block for the leads, which are placed on the heart site.
It is not the intention of this article to detail the design of a pacemaker, but to show the various effects of different devices found around us in a routine basis, on pacemakers, so that people are aware of the inverse effects and avoid themselves from such environment.
PICTURE 1: On the left top of the picture, there is the first pacemaker which was used in1960.On the right bottom, a new model with decreased size, is demonstrated.
Risks associated with the device
Extensive research has been conducted to ascertain possible health effects of exposure to many parts of the frequency spectrum. All reviews conducted so far have indicated that exposures below the limits recommended in the ICNIRP (1998) EMF guidelines, covering the full frequency range from 0-300 GHz, do not produce any known adverse health effect. However, there are gaps in knowledge still needing to be filled before better health risk assessments can be made. Some of the risks associated with ICP are listed below:
· Airport Metal Detectors Interfere With Cardiac-Pacemakers
It is reported that metal detectors with a strong magnetic field cause several adverse effects to those who have an implantable cardiac pacemaker (ICP). There are three important factors which may lead to this interference.
There are also several adverse events; some of them causing cardiac failure. More specifically when the magnetic field interrupts the congestive function of the ICP an internal shock with potential symptoms such as dizziness and syncope might occur (3).
· Industrial environment influence people with an ICP
It is a fact that a certain group of patients, who come back to work after an implantation face problems as machines and especially motor’s magnetic field causes adverse effects and so there are limitations to their work. These systems may provide low or high frequencies magnetic fields, which can interfere with the leads causing inappropriate shocks at the site of the heart (4).
· Mobile phones interactions
The interaction between mobile phones and ICP had been reported several times, but manufacturers have reported, that their studies do not show any relation. It is shown from in vitro experiments that there is some influence of mobile phones magnetic field of the pacemaker due to different frequencies and the peak sources supplies (5). Some studies show that mobile phones could interfere with implanted cardiac pacemakers if the phone is placed within eight inches of the pacemaker during use. To avoid this potential problem, pacemaker patients may want to avoid placing a phone in a pocket close to the location of their pacemaker.
A new study in the journal Physics in Medicine and Biology, published by Institute of Physics claims that the new generation of digital mobile phones can interfere with many types of heart pacemakers. Pacemakers are able to confuse mobile-phone signals with the electrical signals of the heart itself, causing misinterpretation and malfunction.
"This phenomenon could pose a critical problem for people wearing pacemakers because digital mobile phones use extremely low-frequency signals, which can be mistaken for a normal heartbeat," according to biomedical engineer and lead investigator Giovanni Calcagnini of the Italian Institute of Health in Rome. "If a pacemaker detects a normal heartbeat, it will not function properly and could be very dangerous for the wearer."
New pacemakers fitted with a ceramic filter seem to be immune from the problem, Hence it is recommended that all manufacturers use these filters and surgeons use such pacemakers in this modern world of mobile phones.
Medical devices interactions
A MRI system also influences the ICP performance by the shimming and the gradients coils. The gradient coils produce high frequencies in order to change the angle orientation of the protons that are going to be detected by the receive coil through RF communication. Both magnetic fields are very strong (e.g. 1.5 TESLA) and affect the function of the ICP.
FIGURE 4: The pulse generator is placed in the pectoral area of the chest, and the leads on the heart trough the subclavian vein.
The fast developing technology of pacemakers has improved the quality of life of patients, and provides significant advantages in the field of diagnosis and treatment for patients with heart diseases. New algorithms discriminate the cardiac signals and minimize the possibilities for inappropriate treatments. The pacemaker average life time is increased because of new types of batteries, and related complications have been limited. Despite all these, sufficient care has to be taken by patients with ICP and surgeons should wisely advise the patients to avoid being in places with such hazards. Newer pacemakers with ceramic filters should be used as far as practicable.
1. Kirk Jeffrey, Victor Parsonnet, “Cardiac pacing, 1960-1985, A quarter century of Medical and Industrial innovation” American Heart Association bulletin, 1998.
2. John Wallwork, Rob Stepney,’ Heart disease what it is and how it is treated’, 1987,p. 8-12, 27, 96-98,138-139
3. Christof Kolb, MD, Sebastian Schmieder, MD, Gunter Lehmann, MD, Bernhard Zrenner, MD,Martin R. Karch, MD, Andreas Plewan, MD, Claus Schmitt, MD,
Do Airport Metal Detectors Interfere With Implantable Pacemakers or Cardioverter-Defibrillators? Journal of the American College of Cardiology Vol. 41, No. 11, 2003, 0735-1097.
4. JOSEPH G. FETTER, RPEE, DAVID G. BENDITT, MD, FACC,MARSHALL S. STANTON, MD, FACC’ Electromagnetic Interference From Welding and Motors on Implantable Cardioverter-Defibrillators As Tested in the Electrically Hostile Work Site’ Published by Elsevier Science, by the American College of Cardiology Inc, 1996 0735-1097.
5. J. A. Chiladakis, P. Davlouros, G. Agelopoulos and A. S. Manolis,’ In-vivo testing of digital cellular telephones in patients with implantable cardioverter-defibrillators’ European Heart Journal 22 ,2001, 1337–1342.
A Glimpse At The Status of Medical Equipment in Nepal
- Bhesh R Kanel, Head of the Department and,
- Murari B Pokhrel, Chief Admin. Officer
Sarawoti Maya, a resident of Swoyambhu, fell down from the top of her house and became unconscious. She was rushed to a central hospital in Kathmadu, where she was x-rayed and diagnosed to have a fracture of the skull on the right side. The attending doctor suggested an urgent CT scan of her head, but the hospital CT machine was not operable as it was broken for few weeks and was waiting repair. She had to be taken to a private diagnostic center for the CT.
She expired the same day while returning to the hospital. CT scan report showed a massive epidural hemorrhage. She could not make to the emergency Operation Theatre in time as there was quite a delay in arranging her CT scan.
Mangal Prasad, a resident of Gulmi, had asthma. He fell severely sick one day and was rushed to the district hospital in Tamghas. But the Oxygen Concentrator at the hospital was broken and he could not be given oxygen. He died the same night.
Fortunately the stories are not real. Unfortunately, there are many instances when many real ‘Saraswotis’ and ‘Mangals’, although manage to reach hospitals in time, can not receive due treatment and risk their lives because of failure of machinery. Everyone knows that machineries do fail. Equally, everyone also knows that they can be repaired and brought into good condition.
A study of the regional/zonal and district hospitals conducted by the Department of Health Services (DOHS) with the assistance of GTZ reveals a very sorry sate of medical equipment at the hospitals. According to the information available in the document “Health Care Technology Policy, Ministry of Health & Population Nepal, 2006”, the status of the equipment is depicted in the following figures.
The graphs show that only 30 % of the equipment, in average, is in operation. Over 50 % of the equipment requires urgent maintenance, 10 % needs repairs and 10 % needs to be scrapped. Such a situation is indeed a matter of serious concern to all. Lack of spare parts and qualified maintenance personnel has plagued many equipment pieces in many hospitals. Maintenance resources are centralized and any breakdown of equipment at districts has to wait a long time for repair pending dispatch of personnel and spares.
Besides, many essential and expensive pieces of equipment like mobile x-ray machines and audiometers were not installed and commissioned in some hospitals even after 2 years of their receipt.
In various interviews with the director and other responsible persons of Tribhuwan University Teaching Hospital (TUTH), the authors came to know that TUTH has a lot of equipment donated by various agencies as well as ones bought by the Hospital itself. Although the technicians at hospitals or the agencies who supply them do provide the maintenance service, many pieces of equipment were lying broken. There is neither the proper expertise nor enough funds to repair and maintain them. The types and the technology of equipment normally donated by various agencies are so much varied that maintenance is becoming quite difficult. The situation is further aggravated by the lengthy and complicated auctioning procedures in the public sector. The problem is so much severe that there is not even enough space to keep the broken equipment. It was revealed that they are laying in corridors and under the staircases.
Some two years ago an American Bio-medical Engineer had volunteered to prepare an inventory of the TUTH hospital equipment and their status. It took him almost a year to do the work. Few corrective actions could be taken to address the situation. Things have changed much after that, and updates of the database have not been made successful.
Our attempts to enquire about the status of hospital equipment at Bir Hospital could not succeed due to the reasons of well known long bureaucratic procedures in government agencies. The authors are of the opinion that the situation there is hardly any better than at the TUTH.
These examples typically represent the status of the equipment in majority of the Public Sector Hospitals
The problem of perennial shortage of qualified and skilled manpower, inadequate resources for maintenance and the lack of a clear policy regarding the health care technology utilization are responsible for the sorry state of affairs in many hospitals
The authors could not conduct studies of the status of the Private Hospitals. Naturally, their status, in terms of the operability of the equipment, and the efficiency of use are expected to be better. At this stage we can only hope that their status in terms of their effectiveness and risk management are equally good.
With a view to improve such a sorry state of affairs of the Health Care Technology in Nepal, the Government of Nepal has conducted a policy study with the assistance of donor agencies, particularly of GTZ and has come up with the “Health Care Technology Policy (HCTP), 2006”.
The Policy aims to meet the following objectives:
o Promote appropriate Health Care Technology
o Improve policy planning and procurement procedures of medical devices, and facilities
o Utilize HCT effectively and efficiently
o Promote good clinical practices including safety aspects and risk management
o Ensure conditions of appropriate Human Resource Development.
The strategies to attain the objectives also include, among others, Government Commitment to foster Public-Private Partnership (PPP) in the areas of HCT in the following domains of services
o Human Resource Development in the equipment management
o Sharing of knowledge
o Outsourcing of services, acquisition and management of equipment
o Leasing and Renting of equipment with an option to own.
It is a great pride for us that College of Biomedical Engineering and Applied Sciences (CBEAS) was a precursor to the HCTP with the twin objectives of Human Resource Development and Biomedical Research in Nepal. In a meeting at the Department of Health, the Director General and the GTZ functionaries have expressed great satisfaction at the establishment of CBEAS at private sector. They opined that all possible cooperation should be extended to this college.
We, at CBEAS, are more than prepared for any meaningful Public-Private Partnership in the health care technology.
WHEN DOES LIFE BEGIN AND WHEN DOES IT END?
Dr. Uma Shrivastava
It always fascinated me from the time, and I was very much concerned about the origin of life. I tried several times to co-relate things from scrape. According to Veda and Purana, Bramha, Vishnu and Shiva, also known in the form of OM, were self-born and represent the commencement of the universe. These three are supposed to function as God of creation, God of protection and God of destruction respectively. If something is created regardless of living or non-living, it has some time till it is destroyed or dead. Its life depends on the quality of the matter it is made up of.
Veda confirms that human body is made up of Panchatatwa, the non-living matter that consists of water, air, heat, earth and sky. The modern science and the law of physics also confirm that these are the basis of our life. Scientific explanation by Aristotle in the 4th century BC formulated that living cells are developed from non-living matters. The living cells utilize non-living biomolecules for their development and stability. It is not yet clear how these simple organic molecules could form a living cell. The evolution theory of Panspermia explains that there were seeds of life delivered to earth. Miller-Urey in 1953 experimented and concluded that simple organic molecules could be building blocks of life. These biomolecules also control and regulate cellular function.They also noted that DNA and RNA bases could be formed through simulated chemical reaction.
The unit structure of our body is a Cell. Human body possesses more than 200 different types of cells and there are about 5 trillion cells in our body. These are somatic or body building cells. These cells contain entire human genome to build a human being.
In addition to them, man and woman possess special types of cells, the gamet cells. In man, it is the sperm cell and in a woman it is the egg cell. In vivo, the life of the sperm and egg cell is usually 1-2 days. But in in-vitro conditions, only cryo- preservation in liquid nitrogen can stretch their life. When these two precious cells are left to unite either in vivo or in vitro conditions, another single celled structure is formed called the zygote. From this zygote cell structure, man or woman will be developed and born in this world as individuals with the life expectancy of more than 100 years. Is not that interesting?
The zygote seems to have some tricks of programming the developmental process and, may be, life expectancy too. How, when and at what level does it program life expectancy of an individual cell? The zygotes undergo phases of cell cleavage and continuously divide into different cell types. During differentiation process, they form different organs and systems of human body.
I have closely watched these cells during In-Vitro Fertilization treatment process, their cleaving process in cultured environment, the two-celled stage, four-celled stage, till blastocyst stage and the pre-embryo. They then start differentiating into several cell types. There are specialized and unspecialized cells, of which the specialized are responsible for the development of special organs, while the unspecialized cells are popular as stem cells now-a-days as they can be used to repair abnormal tissues of the body. These cells are extracted from a pre-embryo, cultured after their nucleus is removed with another cell without removing nucleus and allowed to fuse and grow. Thus these fused growing cells carry the property of the nucleus carrying cell. This is now a cloned cell prepared for particular purpose.
These days, not only cells and tissues, but a whole human can be cloned like an identical twin but clones differ in age. After the advent of cloning, it is clear that the genetic material determines traits. Among all other cells, the embryonic tissue seems best for tissue cloning. It is not easy, but possible to clone any type of body cell or tissue. Its role is great in different diseased state like Alzheimer's disease, Genetic disorders where there is irreversible tissue damage. As such, the damaged tissue can be replaced by cloned tissue so that the organ can function well. This is therapeutic cloning. Modification and insertion of new type of genes delays the disease process. In addition, cloned embryos are supposed to produce smarter children. On the other hand, cloning technique has some answers to the origin of life given in the Purana. In that era, the devil, Rakta-biz was created by drops of blood and today fetal cord blood is used as one of the sources of stem cells for cloning which may further be useful to create the whole human if not the similar Devil.
Overall, these techniques have opened a new era in the line of tissue engineering and medicine apart from different types of grafts of different origin for replacement therapy.
The successful application of implants, organ transplant and separation of conjoint twins assures a lot to develop in this area. On the other hand, there is also a great danger of such knowledge being misused. Unethical insertion of genes apart from for therapeutic purposes may even cause disasters. There may be cross breeding of human embryos with animal cells and some day pure human being with 46 chromosomes may be rare to identify. This part of science may develop newer creatures which may neither look like a human nor like an animal. With this technology, it looks possible to have ten headed Ravana, elephant-headed Ganesha and goat- headed Dakchhaprajapati around us in the years to come. Such knowledge of creation and development has led to much confusion in this era. What is the eventual destiny of all these creatures? How do they vanish? Do they really vanish? What is death and when does a man die? Is it supposed to be the end of life?
There is also a great concern about the death of an individual which is the death of a million celled human. Does a human die when the heart stops working, the ECG goes flat and there is no consciousness? It is just the death of those functional units, but all the cells and organs have not died. What about the organs transplantation (like eyes, kidney etc.) after death? If these organs can be functional in another living individual, how can we call it a dead? It is very important to note the death of different organs. Do we really know when all these organs die?
It is a well known fact that in human context, a clinical death is declared after failure to regularize the functions of heart and lungs by all resuscitation measures. When there is loss of consciousness with cessation of all activities of the brain, brain death is declared and the individual is biologically dead. Brain death can be compared to the death of central processing unit (CPU) of computer which loses the command to particular activities of body. This causes loss of command to pump blood by the heart; death of heart leads to the loss of ventilation to lungs, death of lungs stops the blood flow into blood vessels and eventually there will be loss of response to all stimuli. The loss of blood circulation decreases the body temperature, gradually down below 37 degree which stops cellular metabolism and production of energy. When the source of free energy production in the body necessary for the living cell function is stopped, the cells turn harder, change in color from pink to pallor to bluish to black.
If a young man's heart fails, transplantation of heart itself or an artificial circulation system to other organs along with the application of an artificial heart pump in place of the heart may well revive the individual for quite some time though there may not be total consciousness. We can also switch on a ventilator and check all his survival possibilities. These are all trials to buy the time lag which has something to do with revitalization.
In Hindu ritual a dead body should be cremated before it gets damaged. How long does the body take to be damaged? None of the religious books properly define death in relation to individual cell life.
In conclusion, every cell has definite life but who programs its life is yet not clear.
Human life begins from zygote stage.
Hundred years of Human life is not true, it is much more than that.
All human body cells do not die when a man dies.
There must be proper scientific and religious outlines to declare when a man really dies. Perhaps there is no Life of human being but rather, it is the lives of all cells in toto, yet to be identified.
AN INTRODUCTION TO BIOINFORMATICS
The Mendelian work on classical genetics gave birth to new field of science called bioinformatics. In general, bioinformatics is defined as the intersection of biological sciences with information technology however; no strict limitations have been introduced. Researches performed during last decades created huge collection of data pressurizing the need of databases like GenBank, EMBL (European Molecular Biology Laboratory) and DDBJ (DNA Databank of Japan). The information related to DNA/RNA and protein helped the scientists, researchers and pharmaceutical companies in drug designing processes. Since bioinformatics tools have been applied in different fields like molecular medicine, personalized medicine, biotechnology, drug design, gene therapy etc., bioinformatics has been a field of great interest and need to all researchers and scientists. In context of Nepal, bioinformatics seems very useful since researches with bioinformatics cost less. Being a very rich source in flora and fauna, Nepal needs to create a database including all necessary informations regarding these flora and fauna.
KEYWORDS: Genetics, Bioinformatics, Personalized medicine, Biotechnology, Drug design, Gene Therapy, Flora, Fauna, EMBL, DDBJ
History and Definition of Bioinformatics:
Understanding of Bioinformatics started almost a century ago when an Austrian Monk, Gregor Mendel cross-fertilized the different colors of the same species of flowers. Gregor Mendel explained that the inheritance of traits shown during his experiment could be illustrated more easily if the factors passed down from generation to generation were controlled. Since Gregor Mendel, genetic record keeping and bioinformatics have come a long way.
The Human Genome Organization (HUGO) was founded in 1988. The first complete genome map was published that of bacteria Haemophilus Influenza. In 1990, the Human Genome Project was started. By 1991, a total of 1879 human genes had been mapped. In France, in 1993, Genethon, a human genome research center produced a physical map of the human genome. Three years later, Genethon published the final version of the human genetic map. This concluded the end of the first phase of the Human Genome Project (1).
The need of bioinformatics was felt after the continuous discovery of new genomes and genome sequences. Piles of data coming out of the Researches and discoveries in the field of molecular biology finally led to the creation of huge databases like GenBank, EMBL and DDBJ (2). Through these databases, researchers were enabled to store and compare the DNA sequence data from the human genome project and other genome sequencing projects. Thus, bioinformatics can be thought to be a central hub that combines several disciplines and methodologies such as molecular biology, information technology, databases, computational resources, CADD (Computer Aided Drug Design) and Genomics/Proteomics/n-omics.
Gene sequence databases and related sequence analysis tools all help scientists to determine whether and how a particular molecule is directly involved in a disease process; these days they call it as Drug Design. Computer-Aided Drug Design (CADD) is a specialized discipline that uses computational methods to simulate drug-receptor interactions (3). CADD methods are heavily dependent on bioinformatics tools, applications and databases. As such, there is considerable overlap in CADD research and bioinformatics.
Bioinformatics brings together these disciplines and this may explain why we get so many definitions for bioinformatics. Bioinformatics is the collective name for a set of skills that has now become arguably one of the most important information-gathering and knowledge-building tools in current science research (4). The increase in the reliance upon bioinformatics in current research has made it essential for training in these skills to become an integral part of current science education. The definition of bioinformatics is not universally agreed upon. Generally speaking, it is defined as the creation and development of advanced information and computational technologies for problems in biology, most commonly molecular biology (but increasingly in other areas of biology). As such, it deals with methods for storing, retrieving and analyzing biological data, such as nucleic acid (DNA/ RNA) and protein, genomic, and chemical data to support the drug discovery process (5). Some people define bioinformatics more narrowly, and include only those issues dealing with the management of genome project sequencing data. Others define bioinformatics more broadly and include all areas of computational biology, including population modeling and numerical simulations.
It is interesting to note that there is no one single definition of bioinformatics. Different organizations define it in their own way. A simpler definition of bioinformatics is that it is the application of computer technology to the management and analysis of biological data. It is an interdisciplinary research area that is the interface between the biological and computational sciences, its ultimate goal being to uncover the wealth of biological information hidden in the mass of data and to obtain a clearer insight into the fundamental biology of organisms. Simply put, it is the marriage between biology and information technology. Bioinformatics concerns the development of new tools for the analysis of genomic and molecular biological data including sequence analysis ,genetic algorithms, phylogenetic inference, database organization and mining, optical computation and holographic memory, pattern recognition and image analysis, biologically inspired computational models.
According to National Institute of Mental Health on June 7, 2000, bioinformatics is research, development, or application of computational tools and approaches for expanding the use of biological, medical, behavioral or health data including those to acquire, store, organize, archive, analyze, or visualize such data. National Center for Biotechnology Information, 2001 defines bioinformatics as the field of science in which biology, computer science, and information technology merge into a single discipline. However, I would like to define bioinformatics in simple mathematics which is as follow:
“Bioinformatics (BI) = Biotechnology (BT) + Information Technology (IT)”
Application of Bioinformatics:
Advances in molecular biology and information technology have fuelled the need of bioinformatics in several areas such as molecular medicines, personalized medicine, drug design, preventive medicine, biotechnology, gene therapy, and waste clean up, Evolutionary Studies etc.
Since every disease has a genetic component, it’s possible that this genetic component is inherited as in case of Cystic fibrosis or can be the result of the alteration of genome due to environmental stresses as in case of cancer, heart diseases etc. Understanding of human genome project helps medical practitioners and researchers to search the genes directly related to the disease which deals more clearly the molecular nature of disease. Completion of human genome project helps the medical doctors and scientists to understand the molecular mechanisms of diseases clearly leading to the treatment of the diseases more efficiently.
Clinical medicine has made it more perfect by the introduction of the term `Pharmacogenomics` which focuses on the understanding of the correlation between an individual patient’s genotype (genetic make-up) and their response to the drug treatment (6). A 1998 study of hospitalized patients published in the Journal of the American Medical Association reported that in 1994, adverse drug reactions accounted for more than 2.2 million serious cases and over 100,000 deaths, making adverse drug reactions (ADRs) one of the leading causes of hospitalization and death in the United States (7). Due to the adverse drug reactions, certain drugs cannot affect the patients in the way they are expected. To solve this problem, medical practitioners and researchers have started classic method called `Hit and Trial method` which helps to find the best drug to treat a particular patient as those with the same clinical symptoms can show a wide range of responses to the same treatment. The understanding of individual’s genetic profile will help the doctors to prescribe the right drug for right disease.
The role of bioinformatics in drug discovery deals with the management of the databases of small molecules that are potential lead compounds, to search databases of protein structures for structure-based drug design methods, and to model the docking of compounds and their target proteins. At this moment, only 500 proteins are targeted by the drugs available in the market. A lead compound is a small molecule that serves as the starting point for an optimization involving many small molecules that are closely related in structure to the lead compound. Structure-based drug design involves the modeling 3-dimensional structure of protein that can be the drug target for the lead compound. Potential compounds are modeled computationally to estimate their "fit" to the target by computing a scoring function or an energy function (8). With an improved understanding of disease mechanisms and using computational tools to identify and validate new drug targets, more specific medicines that act on the cause, not merely the symptoms could be discovered.
With detailed understanding of the genetic profile of individuals and the genetic mechanisms of the diseases, preventive processes can be adapted which include change of life styles, earliest treatment of the diseases.
“If biotechnology is hot, bioinformatics is its hottest arm” (9). The term bioinformatics evolved in the same way (biological informatics) as biotechnology evolved (biological technology). Lots of archea and bacteria have been used in biotechnological processes. The complete knowledge of genetic make-up of these archea and bacteria has boosted biotechnological researchers and scientists to find the most efficient way out. Corynebacterium glutamicum has been used by chemical industries for biotechnological production of lysine (Lysine is rich source in animal nutrition). Xanthomonas campestris is used to produce exopolysacharide xanthan gums which are used as a viscosifying and stabilizing agent in many industries. Furthermore, Lactococcuss lactis is used in most of the dairy industries. The understanding of the genome and the physiology of these microorganisms will prove invaluable for the pharmaceutical industries and the food researchers.
Gene therapy is the approach used to treat, cure or even prevent disease by changing the expression of a person’s genes. In western world, gene therapy has already been introduced to some extent but it’s not too far from the entire world to adopt this method to cure the diseases.
Microbial genome applications
Microorganisms are everywhere; they are present in our body, in our food, in our environment etc. Some of these microorganisms can survive in very high temperature whereas some can even survive at very low temperature. Due to this peculiarity, some of these microorganisms have been very beneficial. Therefore, United States Department of Energy initiated the Microbial Genome Project to sequence the genomes of bacteria useful in energy production, waste clean up, biotechnology, industrial processing etc. Sequencing the complete genomes of these bacteria, scientists have begun to understand these organisms at very fundamental levels.
Waste Clean up
Certain microorganisms like Deinococcus radiodurans have high capacity to resist the radiation. So, scientists have started to study the genome of these bacteria so that they could use it for cleaning up the waste sites with more radioactive waste products.
The complete sequencing of the three domains of life like archea, eukaryota and bacteria helps scientists to predict that all of these three domains of life have common ancestors (7).
The Scope of Bioinformatics in Nepal
Although the term `bioinformatics` seems a buzzword in current times, Nepal is still a lot behind than the rest of the world. Despite of the satisfactory development in the field of molecular biology, biotechnology and information technology, biological informatics has not yet been introduced.
In context of Nepal, there is a lot to do with the bioinformatics. Nepal is very rich in flora and fauna; the world is not aware of all the species including the medicinal plants present in Nepal. It’s our responsibility to publicize our resources that have high economic values. Bioinformatics can be fuelled by the need of the development of a database that includes all the details of flora and fauna available in Nepal.
Since Nepal can not afford expensive equipment needed for research in molecular biology and biotechnology, bioinformatics seems very useful in the sense that, performing researches with bioinformatics does not need physical or wet laboratory. With the help of bioinformatics and bioinformatics tools, the information regarding the molecular biology and biotechnology provided on the web can be used as the resource for the researches. The research activities can be performed only with a computer with the internet connection to it.
Pharmaceutical companies in Nepal are growing like mushrooms. As already mentioned, bioinformatics provides invaluable effort in drug design which is a key work in pharmaceutical companies. Pharmaceutical companies can boost their market using bioinformatics and bioinformatics tools which help them to find new drugs.
Even in medical and biomedical field, bioinformatics seems very useful. The sequencing of individual genetic profile, the understanding of genetic mechanisms of diseases and the sequencing the microbial genomes that are responsible for the diseases help the doctors to prescribe the correct drug for the patient.
Concluding, bioinformatics is the field of science that is emerging very fast in the modern world. Nepal, being an underdeveloped country, also has to move a step towards the fast moving biotechnological world.
1. Bioinformatics Web- Comprehensive Educational resource in bioinformatics (www.geocities.com/bioinformaticsweb)
2. Bioinformatics Methods and Applications; Genomics, Proteomics and Drug Discovery, S.C. Rastogi, N. Meddiratta, P. Rastogi
3. Bioinformatics, D.R. Westhead, J.H. Parish and R.M. Twyman
4. Fundamental concepts of Bioinformatics, Dan E. Krans, Michael L. Raymer
5. Introduction to Bioinformatics, T K Attwood and D J Parry-Smith
6. Genomics, Transcriptomics and Proteomics: Glossary of Terms
7. Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources (http://www.ncbi.nlm.nih.gov/About/primer/pharm.html)
8. Drug Design, Susan Cates http://cnx.rice.edu/content/m11113/latest/
9. Bioinformatics in Biotechnological Education, C Kameswara Rao (http://www.fbae.org/Channels/bioinformatics/BIOINFORMATICS%20IN.htm)