Treating Cancer

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Treating Cancer

There are only subtle differences between healthy and cancerous cells in the body.

Because of these differences, it is difficult to attack cancerous cells without harming healthy body cells. However, depending on the stage of cancer and what type it is, there are several possible treatments.

Surgery is used commonly to remove the area ‘infected’ with cancer cells. But if surgery will not remove all of the cancer, options such as radiation and chemotherapy are used.

Radiation therapy.
Source: Creative Commons (Stevenfruitsmaak)

Radiation therapy involves applying high energy radiation to the problem area.

The radiation will kill off cancer cells by damaging their DNA.

But it will also kill normal cells: it is indiscriminate. Because of this, many side effects can result but used carefully, this technique is very effective.

For more information about radiation therapy, refer to the New Zealand Cancer Society’s website, http://www.cancernz.org.nz/assets/files/docs/info/Informationsheets/8636_CSNAT_IS_Rad%20Therapy_v2_for%20web.pdf or the US National Cancer Institute website at http://www.cancer.gov/cancertopics/factsheet/Therapy/radiation

Chemotherapy involves the use of drugs that target rapidly dividing cells. However, cancer cells are not the only ones in the body that divide quickly. Blood cells, cells in the mouth and intestines as well as hair cells all divide quickly, which is why people undergoing chemotherapy often lose their hair and experience other side effects. For more information on chemotherapy, the New Zealand Cancer Society has put together an e-book which can be accessed at: http://epublishbyus.com/ebook/ebook?id=10024090#/2

A newer way of targeting cancer cells in the body is Photodynamic Therapy (PDT). There are several steps involved in this therapy:

  1. The patient is given a drug which is sensitive to a certain wavelength of light, for example red light. This drug will accumulate within all cells, with more of it in cancer cells.
  2. A red light laser is pointed at the precise place where a tumour has been identified. The drug in the cells that this light touches is then activated. The light activates the drug to react with molecular oxygen, forming highly toxic hydroxyl radical molecules.
  3. These produced radicals will interfere with the cell DNA and cause cell death.

A surgeon points a red laser at a tumour site in photodynamic therapy.
Source: National Cancer Institute, John Crawford.

However, there are problems with this therapy as well. One disadvantage of PDT is photosensitivity. Once the drug has been activated and killed the cancer cell it was in, it is free to circulate around the body and accumulate in eyes and skin. This causes the patient to become very sensitive to light and so it is necessary to avoid sunshine for some time after this therapy.

A further disadvantage is that the light needed to activate most of these photosensitive drugs cannot pass through much more than 1 cm of skin so the targeted tumour must be fairly close to the skin surface.

Cancer in the world

According to the World Health Organisation, cancer is a leading cause of death worldwide. In 2008, cancer killed 7.6 million people worldwide. That’s 13% of all deaths in 2008. The WHO also say that 30% of cancer deaths are due to the five leading behavioral and dietary risks:

  • Tobacco use (causes 22% of global cancer deaths and 71% of global lung cancer deaths)
  • Alcohol use 
  • High body mass index (large amount of body fat, can be calculated using your height and weight)
  • Low fruit and vegetable intake
  • Lack of physical activity

So it would be worth starting to make some life-style changes. Cancer is an incredibly hard disease to treat successfully. However, new and improved drugs and technologies are being introduced all the time to fight cancer. 

Resources:

New Zealand Cancer Society, http://www.cancernz.org.nz/information/

World Health Organisation, http://www.who.int/mediacentre/factsheets/fs297/en/

US National Library of Medicine, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002267/

MediLexicon International, UK, http://www.medicalnewstoday.com/info/cancer-oncology/

Cancer: An Overview

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Cancer: the problem

Cancer is really hard to target.

Cancer cells are normal human body cells that are growing abnormally fast. Normal healthy body cells follow a carefully timed process of growth and division, followed by death. Cancer cells don’t follow this pattern: they don’t die.

The division of cancer cells can cause formation of lumps or masses of tissue called tumours.

Cancer cells photographed by a camera under a microscope using time-lapse photography. Source: Creative Commons (Asd.and.Rizzo)

A tumour is a collection of cancer cells, which are human body cells that are growing abnormally fast and dividing constantly.

Tumours can grow and interfere with the body working normally. They can cause problems in the circulatory, digestive and nervous systems and the uncontrolled release of hormones. In the case of leukaemia, cancer causes abnormal cell division in the blood stream that prevents normal blood function.

Benign tumours are ones that stay in one spot and do not show much growth. More dangerous tumours form when a cancer cell spreads through the body using the blood or lymph system and new tumours grow in a different place.

There are over 100 different types of cancer.

 

A Cancer Animation

This Youtube clip was originally created by BioDigital Systems. It is a good animation that explains the basics of cancer.

 

Cancer: limited solutions

Causes of cancer are thought to include:

  • Genetic problems
  • Excessive sunlight exposure
  • Drinking too much alcohol
  • Tobacco smoking or exposure to it
  • Exposure to chemicals
  • Obesity

The huge variation in causes of cancer complicates any effort to cure the condition. It is worth noting that several of the above contributing factors are lifestyle choices.

 

Diagnosing Cancer

Medical imaging techniques such as MRI scans, X-rays, CT scans and ultrasounds are used to help to diagnose cancer.

These techniques show pictures of the inside of the body and allow experienced doctors to spot tumours. Endoscopies (inserting a thin tube with a camera and light into the body) are also used to spot signs of cancer.

The only certain way to diagnose cancer is by biopsy, where cells are removed from the body and examined under microscope.

Close Up New Zealand: Scientist focuses on malaria

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Close up, one of the NZ news shows, had a segment on the 16th April about a New Zealand scientist who is investigating a new compound to fight malaria.

Norrie Pearce is a a scientist investigating natural product drug discovery. She has discovered a promising anti-malarial, based on a compound found in a sea squirt. Unfortunately, funding for her research has dried up.

Have a look at the story at the Television New Zealand website: http://tvnz.co.nz/national-news/kiwi-scientists-taking-drastic-action-fund-research-4835971

Iron in Biology: Part III

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Iron levels in Health

Low levels of Fe in the body can cause fatigue and anaemia.

The reason you can bleed to death is that loss of blood means loss of haemoglobin in your blood. This prevents cells from getting oxygen to produce energy and so they starve to death in your body.

The flip side to this is that too much iron in the body can cause Fe to form iron solids in body tissues, which is not healthy either. Too much iron has been implicated in causing cardiovascular disease.

It is important to have a balanced level of Fe in your body.

Food is the usual source of iron in the body, although dietary supplements are available. These foods are high in iron:

  • Red meat
  • Liver
  • Dark leafy greens
  • Dried fruit
  •  Egg yolks

Eating foods high in Vitamin C at the same time as eating iron-rich foods will help iron be absorbed into the body. (Most fruits are high in Vitamin C, particularly oranges, kiwifruit, and also red peppers).

 

Iron Reactions

However, Fe can be very dangerous in the body if it is released from haemoglobin. As already discussed in the post regarding malaria, free iron will react with hydrogen peroxide to create free radicals that attack DNA, killing cells and making you sick.

Fenton Reaction produces dangerous radical molecules in the body

The only place haeme (an iron centre with the immediate surrounding protein) from haemoglobin can be safely disposed of is in the liver, where a chemical pathway is available to recycle red blood cells. Haemoglobin is broken down into Bilirubin.

Bilirubin can then be broken down by certain wavelengths of light as well as enzymes in the body.

Neonatal hyperbilirubinaemia is a condition where newborn babies turn yellow because they cannot break down this yellow bilirubin.

This condition can be fixed by putting the baby under special blue lights. This light causes the bilirubin to break down. 

 Phototherapy used to treat a baby with jaundice.
 Photo: Wikipedia Commons, Rjmunro 
An interesting website to explore for more information is:

http://www.chemistry.wustl.edu/~edudev/LabTutorials/Ferritin/Ferritin.html

 

The Iron War

Iron is used for more than just oxygen transport in the body. Bacteria, yeast and fungi also need iron to live.

Interestingly, the first layer of protection against bacterial infection is at the entry points to the body: mouth, nose etc. Lactoferrin is an antibiotic produced in saliva and snot, which strips Fe from bacteria.

The idea is that if bacteria need Fe to reproduce and infect you, take their Fe off them and they will die.

However, bacteria have chemicals of their own. Siderophores, another chemical that binds strongly to iron helps bacteria to capture iron from their environments.

Siderophores are used to remove iron from transferrin iron transfer and storage proteins in the body. The siderophore is then absorbed by bacteria that breaks down the siderophore and stashes a source of iron for themselves.

Electron Micrograph of a colony of E. Coli bacteria.
Photo: Eric Erbe, US Department of Agriculture

Enterobactin (excreted by E. coli) is an extremely efficient siderophore. It is so strong, it can remove iron from glass.

Once the first-line defences have failed, the body’s next response to a bacterial invasion is the production of a molecule called siderocalin. Siderocalin binds enterobactin and so prevents bacteria getting any iron, killing them. 

However, bacteria are developing resistance to siderocalin and so the battle for iron- and life- continues.

To find out further information, have a look at the Public Library of Science article ‘The Battle for Iron between Bacterial pathogens and their Vertebrate Hosts’, available at:

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000949

This article about the bacterial gene that allows bacteria to steal iron from humans is also an interesting read:

http://www.sciencedaily.com/releases/2008/07/080731140223.htm

Iron is an essential mineral for humans and other life forms to function properly. It has an essential role in transporting oxygen around the human body and also in battling infection.

Like all minerals, it is important to have a safe level of it in the blood to prevent either anaemia (low iron) or cardiovascular disease (high iron).

Iron in Biology: Part II

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Iron as an Oxygen Transporter

Iron, chemical symbol Fe, is the 26th element of the periodic table and has a molecular mass of 55.85 g/mol. Picture: Wikipedia Commons, Albedo-ukr

Fe is used for possibly the most important job in the human body: oxygen transport. All of the cells in our body need oxygen in order to do cellular respiration, changing glucose into energy.

Because the body is made up of so many trillions of cells, getting oxygen to every one of them is difficult. Oxygen in the air can’t simply touch the skin and reach all the cells in the body.

A brilliant system has been designed to transport oxygen to all of the cells in the body.

  • Oxygen is breathed into the lungs.
  • Thin-walled alveoli sacs in the lungs allow oxygen to pass through into the bloodstream.
  • Oxygen forms a chemical bond to haemoglobin proteins (part of red blood cells).
  • These blood cells transport oxygen around all parts of the body using the blood system.

Haemoglobin is a type of protein. It is made up of four different parts. Each of these parts has a haem ring with a Fe atom in its centre. This is chemically attached to the protein by four strong bonds.

Note: a ‘chemical bond’ means that the two atoms involved share electrons.

Iron is capable of forming 6 bonds. In haemoglobin it sits within a haem ring, binding to four amino acids. A molecule of oxygen will attach at one of the remaining empty sites.

Haemoglobin: A ribbon representation of the protein. The 4 green areas show the Fe haem centres where oxygen will bind.
Diagram: Wikipedia Commons, first uploaded by Zephyris and adapted by Richard Wheeler

An intricate balancing system is required so that oxygen will bind to Fe in haemoglobin (to be transported) but when cells around the blood system need it, the oxygen will be released.

Basically, the strength of the Fe-O bond has to change based on how much oxygen is around. Scientists have tried to understand how this works by using a ‘spring-tension’ model.

The reason that inhaling CO (carbon monoxide) is fatal, is because CO will bind to haemoglobin molecules. This prevents the transport of oxygen to cells which in turn prevents cell respiration and effectively starves cells to death.

 

The Spring-Tension Model

This model says that a haemoglobin molecule changes its shape depending on the concentration of oxygen around it.

It’s sort of like a crab claw.

Diagram of the Spring Tension Model, used to understand haemoglobin and oxygen binding in high and low oxygen concentrations. Source: Lecture notes from University College Dublin course: ‘Metals in Biology’

In the lungs and other areas where there is lots of oxygen, each Fe centre in the haemoglobin forms a strong bond to an oxygen molecule. This can be compared to a crab closing its pincher around a piece of food.

The formation of a Fe-O bond (an oxygen molecule attaches to the haemoglobin molecule) causes the protein to change shape, becoming more compact. This signals the other three Fe centres in the protein to bind oxygen quickly.

This is like signalling the other pincher of the crab to close, getting a better grip on the crab food.

In areas where there is not much oxygen, the presence of carbon dioxide gas signals the haemoglobin to release oxygen. The Fe-O chemical bonds between the haemoglobin iron centre and the oxygen become much weaker.

Once one Fe-O bond has broken, the protein gets bigger and this triggers the other Fe centres again to release their oxygen.

In our crab analogy, the crab looks at what is in its pinchers and decides it would prefer to eat something else. The crab releases its pinchers, one at a time.

Iron in Biology: Part I

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To really understand why iron is important in the human body, we have to review several scientific concepts. 

Atom Theory

We learn at secondary school that everything is made up of atoms too small to see.

Scientists believe for example that when we look at a tree, if we have a strong enough microscope, we would see lots of tiny atoms all joined together making up the tree.

Each atom has a nucleus and electrons that orbit around this nucleus.

An atom: electrons orbiting a central nucleus.
Diagrm based on work by Ahnode (Wikipedia Commons)

The human body is made up of lots of these atoms, working together as cells.

 

Cells in the body

Scientists generally think of the smallest building block of the human body as a cell. Organs and body tissues are made up of lots of cells.

A cell is an intricate living system, made up of lots of atoms.
Diagram: Mariana Ruiz

For the body to work properly, each of these cells has a specific job to do- individually, as part of a body organ and as part of the whole body.

Cells use nutrients such as glucose (a sugar from food that we eat) to create energy for our lungs to breathe in and out, our heart to pump blood around the body and for growth.

The process cells use to make this energy is called cell respiration.

 

Cell Respiration

Cell respiration is a series of complex reactions and processes that result in the production of cell energy (2880 kJ of energy per mole of glucose).

Oxidation and reduction reactions are part of this reaction series, meaning that electrons are moved between reactants.

Molecular oxygen (O2) is used as an oxidant (meaning that it will remove electrons from glucose) to start these reactions.

Cell respiration: a chemical equation

The waste products of cell respiration are gaseous carbon dioxide (CO2) and water.

 

Atoms in the body

The human body is made up of several different types of atoms. The main atoms are Oxygen (65%), Carbon (18%), Hydrogen (10%) and Nitrogen (3%).

These make up the cells in the body. You may notice that this only adds up to 96%. Minerals such as calcium, phosphorus, iron and copper make up the remaining 4% of the body.

These minerals have key roles to play in helping cells to function properly.

An average 75kg adult may only have 6g of Iron (chemical symbol Fe) in the body. Is something we have so little of in our body really important for it to function correctly?

 

Iron Uses

Iron (Fe) is an important part of our world.

Fe is essential for life and plays critical roles in several cellular processes, including DNA replication and oxygen transport.

Fe is also a crucial player in infection.

Without iron, cells would not be able to replicate, meaning that we couldn’t grow. Nor would cells be able to produce energy for the body.

The War on Malaria

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Malaria: What is it?

Malaria is a debilitating disease. It triggers periodic flu-like attacks with headaches, chills and severe fevers that can last for 48 to 72 hours.

It is caused by Plasmodium parasites that are spread from human to human through bites from infected mosquitoes.

If not treated with anti-malarial drugs, the disease is often fatal. Today in Africa, malaria is responsible for one in every five childhood deaths.

Areas where malaria is endemic (there is some level of malarial infection maintained within the population) are coloured yellow. Diagram: CDC Division of Parasitic Diseases.

 

Plasmodium parasites use human red blood cells, which contain large quantities of haemoglobin, as food sources.

Haemoglobin is a protein used in the body for oxygen transport. If there is not enough haemoglobin (which contains iron), parts of the body will not receive adequate oxygen to keep the cells in the body producing energy.

This results in anaemia (low iron levels), causing fatigue and other symptoms.

Diagram: Based on work by National Human Genome Research Institute (US)

Interestingly, many people who live in areas where malaria is prevalent have developed resistance to the Plasmodium parasite. This appears to be linked to the genetically shaped-altered haemoglobin (sickle-like shapes, as opposed to the usual spheres).

 

How was malaria originally treated?

The first significant drug for malaria was quinine, a bitter-tasting white powder that comes from the bark of the cinchona tree. This tree is found in the Andes mountain ranges of Ecuador and Peru.

Quinine was introduced to Europe in the mid-seventeenth century and demand for quinine resulted in most cinchona trees being cut down.

A steady supply of quinine was re-established in the 20th century, when a chemical method of making quinine from coal tar was introduced.

For more information, refer to:

Centres for Disease Control and Prevention website: http://www.cdc.gov/malaria/about/history/

World Health Organisation website: http://www.who.int/features/factfiles/malaria/malaria_facts/en/index.html

Magdalen College School, Oxford website: http://www.chem.ox.ac.uk/mom/quinine/quinine.htm

Doctors Without Borders website: http://www.msf.org/msf/articles/2011/04/frontline-a-better-way-to-beat-malaria.cfm

 

The Global Malaria Eradication Program

Chloroquine is a chlorine and quinine-based drug that shows improved anti-malarial properties. Its development was a significant part of the Global Malaria Eradication Program.

A Mosquito biting a human. Picture: Centres for Disease Control and Prevention

This program began in the 1950’s, when the World Health Organisation attempted to eliminate malaria by spraying Chloroquine and DDT (potent anti-malarial drugs) over malaria-infected countries.

The idea was to kill off both the Plasmodium bacteria and the mosquitoes transmitting them.

There was some success seen from this program, with malaria being eradicated from 37 of the 143 countries where the disease had been a constant problem.

Over the duration of the program, a sharp drop in numbers of malaria cases from 110 million in 1955 to less than one million in 1968 was seen in India.

In Sri Lanka a decrease from 2.8 million cases of  malaria in 1946 to just 18 cases in 1966 was seen.

Once the program stopped, there was huge resurgence of malaria in these regions.

Fallout from the failed eradication program included the Plasmodium parasite developing resistance to both chloroquine and DDT insecticides.

This prompted a call for scientists to design other anti-malarial drugs, resulting in development of Ferroquine and the artemisinin family of drugs.

Ferroquine, an iron-quinine derivative, is one of the most recent quinine-based drugs with potential to wipe out Plasmodium parasites resistant to chloroquine.    

There is a very good journal article (Tropical Medicine and International Health (2009) 14 (7) : 1-7) that describes the 1950’s initiative and the current WHO perspective on malaria. Available at: https://docs.google.com/viewer?a=v&q=cache:jrCMllzfXAoJ:www.afro.who.int/index.php?option%3Dcom_docman%26task%3Ddoc_download%26gid%3D4133+malaria+eradication+WHO+1950&hl=en&gl=nz&pid=bl&srcid=ADGEESga30czeJunyLiQ9xD8ZSpKczIgwN_uNXhMhK5RWFz1sKS6oEDVvgUJNZCZFvGVvunCHLtCqS4kOs1Y3MOPU2gwzNj4ZY0EVXD7jQHt4TFkFC2tlwPEGvusWmme6ZN9S8vLI3Zx&sig=AHIEtbTJGjUuaMty5rwNHMV-MiXAglZ8fw

 

How Chloroquine and Ferroquine work

The Cl (Chlorine) and Fe (Iron) parts of chloroquine and ferroquine are thought to be used to get the active quinine part of the drug close enough to kill Plasmodium parasites; they are important for drug delivery.

Plasmodium parasites affect humans by destroying haemoglobin molecules in food vacuoles of red blood cells.

This destruction causes a build-up of free iron in the cell, which would normally poison the parasite.

Spontaneous oxidation-reduction reactions use free iron to generate dangerous hydroxyl radicals, which damage DNA, proteins and other important parts of the infected cell, killing the parasites.

Iron is oxidised by hydrogen peroxide, which is produced by the liver in small quantities.

However, Plasmodium has a system to deal with the free iron by chemically binding it into ‘dimers’ (double iron molecules Fe2) to prevent it being poisonous.

There are two ways these drugs are thought to hinder Plasmodium:

Once the drugs are delivered into the food vacuoles of red blood cells they increase the pH (make the food vacuole more basic). This helps to prevent the parasites from reproducing.

The second way is by ‘capping’ the free iron in the vacuole to prevent the parasites from making the harmless Fe2 molecule. This causes a build-up of free iron in the cell that poisons the parasite.  

Refer to these online journal articles for more information:

J. Antimicrob. Chemother.(2001) 48 (2): 179-184. Available at http://jac.oxfordjournals.org/content/48/2/179.full#ref-19

 Journal of Cell Biology (1985) 101 (6): 2302-2309. Available at http://jcb.rupress.org/content/101/6/2302.abstract?ijkey=2108a9235d03fda791e32a1d31ff8a4b8384b4c7&keytype2=tf_ipsecsha

 

Current Anti-Malarial Drugs: Artemisinins

The World Health Organisation guidelines now call for artesunate, an artemisinin drug, as the treatment of choice for children with severe malaria.

Quinine and quinine-based drugs are now being phased out as they are considered to have more side effects and be less effective than the artemisinin drugs.

Artemisia Annua. Photo: Kristian Peters

Artemisinin drugs have been developed from the Chinese herb qinghao, also known as Artemisia annua that has been used in China for over 1000 years to treat malaria.

They are believed to work by using lots of different free radicals to intensifying the attack on Plasmodium parasites. As of 2010, the exact way they work has not been discovered.

For more information, see the journal article: Jerapan Krungkrai et al. /Asian Pacific Journal of Tropical Medicine (2010)748-753.

Drug Development: The Process

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Before discussing any one disease or family of drugs in much depth, it’s worth having a look at the method used by pharmaceutical companies to develop drugs.

Mankind has been using plants extracts as medicine for a long time.

During the mid 19th century, people started trying to isolate the active compounds within these plants- the molecules responsible for the medicinal qualities.

This was the beginning of the pharmaceutical industry.

Picture: Clip Art

Drug Companies work on the basis of expected return for their investment. So, sadly, when they identify a disease to try to cure, it is not usually going to be a disease attacking the developing world where people do not have much money.

 When you have a look at the rate of success in drug development, the reasons behind this mercenary attitude become a little clearer: 

  • For every 10 000 molecules investigated for possible medicinal qualities, only 10 reach clinical trials and only 1 of those may be made available for patients.
  • The average overall development cost for a new drug is estimated to be over NZ$800 million at current exchange rates (GBP £444 million).
  • Average time to develop a drug is 10-15 years

Once a disease has been chosen, the next step is to identify a suitable drug target. This is where it is very important to understand how the disease works and what is going on in the body.

Typically, a drug target is one of the following three parts of the body that is involved in the disease.

  • Receptor (a protein on a cell surface, allows chemical messengers into the cell)
  • Enzyme (act as catalysts to make biological reactions happen easier)
  • Nucleic acid (part of DNA)

Thousands of molecules are then screened to choose a lead compound. This is a molecule that interacts with the drug target in a therapeutic way to help control the disease.

Chemistry comes to the fore now as lots of variations of this lead compound are made. These different compounds are then analysed to discover which will control the target disease safely.

Having discovered the best compound to act as your drug, the next step is to make sure the drug will reach its target in the body.

Drugs need to be absorbed into the blood, to reach their target efficiently, to be stable enough to survive the journey, and to be excreted within a reasonable length of time.

Again, chemistry is used to manipulate the properties of the chosen compound to get this to happen.

Before this drug hits the market, there are still many different issues to deal with:

  • patents,
  • pre-clinical trials,
  • three stages of clinical trials
  • on-going studies to monitor the long-term effects of this drug
  • registration and approval from the Food and Drug Administation in the United States.

  

Drug Development: An Example

Identified disease: Asthma.

Disease background: Asthma is when lung bronchi (airways) become narrower. When faced with certain triggers, these airways may partially close up, swell or make more mucous and become clogged up.

This can cause difficulty in breathing, a feeling of tightness in the chest, coughing and wheezing. Severe asthma can cause death.

Diagram: United States Federal Government (Wikipedia Commons)
 

Chosen drug target: Beta-2 Adrenoreceptor.

There are several different types of receptors in the body that are activated or ‘turned on’ by a molecule of adrenaline reaching them.

Adrenaline activates Beta-2 receptors. This causes smooth muscles to relax. Relaxing the smooth muscles in the bronchi will widen the airways, which helps a person suffering from asthma to breathe easier.

Lead compound: Adrenaline.

Adrenaline itself was one of the first compounds used to help in asthma attacks.

It produces short-term relaxation of the airways but it also stimulates a lot of other types of adrenergic receptors, leading to many side-effects including heart problems.

Developed drug compound: Salbutamol (trade name Ventolin).

Salbutamol is over 2000 times less active on the heart than adrenaline, meaning it produces fewer side effects.

The relaxing effect of Salbutamol on the smooth muscle of the bronchi lasts for 4 hours.

Interestingly, Salbutamol is a chiral compound, meaning that it is two non-superimposable mirror images.

For a simple example of chiral objects hold your hands out, palms facing away from you. Your hands are mirror images of each other. Try to get your hands to look exactly the same, top and bottom of the hands facing the same way and thumbs on the same side. It’s not possible: your hands are non-superimposable mirror images.

Both of these mirror image compounds (called R and S to distinguish them) were produced in the Salbutamol drug until it was recognised that the R-compound is 68 times more active than the S-compound.

The less-active S-compound is also the one held responsible for side effects. This resulted in production of pure R-salbutamol, called Levalbutarol (trade name Xopenex).

To summarise, the process of drug development process requires investment of a phenomenal sum of time and money. Return on investment currently holds great influence over which disease is chosen to design drugs for. The desperate need seen in developing countries for drugs to tackle tuberculosis (TB), malaria, sleeping sickness and other tropical diseases is largely ignored.

For more information, refer to:

Patrick, G. (2009) An Introduction to Medicinal Chemistry, 4th Ed., New York: Oxford University Press. Chapters 12-16, pages 595, 602, 603.

Asthma Foundation New Zealand’s webpage: http://www.asthmafoundation.org.nz/_6.php

UK Parliament web document on disease in developing countries and the need for new drugs: http://www.parliament.uk/documents/post/postpn241.pdf

The Eye: A Chemical Perspective, Part III

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So, we now have some idea of how the eye works and the role of Vitamin A in sight. Colour blindness is only one of the problems that may occur in the eye, one that has no real solution. So what are some of the solvable eye problems?  

Conjuctivitis (cornea)

Picture: Ansevilu

This is also known as ‘pink eye’ and is the result of irritation of the clear membrane covering the white part of the eye and interior of the eyelid. There are three general causes:

  • Allergies
  • Bacterial Infection
  • Viral Infection

Viral conjunctivitis usually clears up within a few weeks, while anti-biotic eye drops are used to kill off bacterial infections in the eye. Artificial tears are often used to help prevent the symptoms of allergic conjunctivitis, as they help to dilute any dust or foreign allergy-causing substance in your eye. Anti-histamine pills can also help to control conjunctivitis.

 

Short- or Long-Sightedness

 

Myopia, or short-sightedness, is an eye condition where distant objects appear blurry because light rays are focused to a point in front of the retina.

Hyperopia, or long-sightedness, is the corresponding eye condition that makes close objects appear blurry because light rays are focused behind the retina.  

These conditions are caused either because the cornea is too curved or flat, respectively, or by an unusually shaped eyeball.

Traditional methods of dealing with short- and long-sightedness include glasses and contact lenses.

In the case of short-sightedness, a concave lens in the glasses is used to move the point where the light converges from the middle of the eye to the retina.

In long-sightedness, a convex lens is used to move the focus point of light forward onto the retina rather than behind the eye.

Specially trained eye surgeons are now able to use laser technology to re-shape the cornea of the eye. This removes the need for corrective glasses or contact lenses.

For further information about correcting short- or long-sightedness, see

http://www.allaboutvision.com/visionsurgery/other.htm

http://www.medicinenet.com/lasik_eye_surgery/article.htm

 

Cataract

A cataract is when the lens of the eye becomes cloudy. A cloudy lens prevents light from going through the lens to the retina and so blindness ultimately results.

According to the World Health Organisation cataracts are the leading cause of blindness, being responsible for 48% of blindness in the world.

Most cataracts are caused by aging. Because the lens in the eye is made up of mainly protein and water, as it ages the carefully-arranged proteins can clump together, clouding the lens.  

Occasionally children are born with a cataract or one may develop after eye injury, inflammation or some other eye disease.

Cataracts are treated by surgery to remove the clouded lens and replace it with a synthetic one. This synthetic lens can be concave or convex in order to fix short- or long-sightedness at the same time as restoring sight.

For more information, refer to:

http://www.vision2020.org/main.cfm?type=WIBCATARACT

http://www.who.int/blindness/Vision2020_report.pdf

Understanding better how the eye works, from both a biological and chemical perspective, has led to important discoveries about how to improve night vision and prevent blindness.

Eye conditions such as conjunctivitis, short-and long-sightednesss and cataracts can be successfully treated using a variety of methods. Vitamin A is now deliberately added to food while lens and laser surgery are restoring sight.

The Eye: A Chemical Perspective, Part II

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Vitamin A in Sight

Source: Creative Commons, Kander

Retinal, one of the parts of rhodopsin, is a special form of Vitamin A. One of the sources of Vitamin A in our diet is carrots so there is a strong belief that eating carrots will help you see better in the dark.

Retinal is essential for the functioning of the eye, in particular the rods in the eye. Rods provide black and white vision and respond in dim light, while cones provide colour vision and respond to bright light.

During the day, the incoming light is strong enough that what little retinal is around will be activated to start the process of vision. At night, when there is a lack of retinal, it becomes difficult for the rods to sense the small amount of light around and this results in poor night vision.

Geneticist Phillip Simon and horticulturalist Clinton Peters at the University of Wisconsin have developed a new variety of carrot called the Beta III. This ‘supercarrot’ contains three to five times the concentration of Vitamin A in normal carrots. This Beta III carrot is designed to combat the blindness caused in developing countries by a lack of Vitamin A.

“Worldwide each year Vitamin A deficiency causes 10 million cases of night blindness and one million cases of cloudy vision.” Dr Phillip Simon. 

However, lack of Vitamin A in your diet not only affects night vision, but can cause poor immune responses and has been linked to anaemia.

Good sources of Vitamin A include green leafy plants, yellow fruits such as golden mangoes, palm oils and of course carrots. Other foods that have been artificially fortified with Vitamin A include margarine, wheat, rice, edible oils, and sugar.

Interestingly, eating large amounts of carrots will only improve your eyesight if you don’t already have enough Vitamin A in your diet. A professor at Melbourne University in Australia has this to say about the carrot myth:

“No amount of carrots will improve your eyesight if you already have a well-balanced diet.” Professor Algis Vingrys of Melbourne University

If you are interested in learning more about Vitamin A and its role in sight, refer to the World Health Organisation’s Sight and Light Manual on Vitamin A, available at: http://www.who.int/ncd/vision2020_actionplan/documents/00allman.pdf

Other interesting articles are available from ABC news’ and Hubnews’ websites: http://www.abc.net.au/health/talkinghealth/factbuster/stories/2008/03/19/2176569.htm  http://aufait.hubpages.com/hub/What-Do-Carrots-and-Chocolate-Have-In-Common

Historical Aside

The idea that carrots help you to see in the dark was promoted by Britain’s Air Ministry during World War II. This tale served a two-fold purpose.

Firstly, it prompted people to eat more home-grown vegetables when few other food supplies were available.

But the main purpose was to disguise Britain’s new and secret Airborne Interception Radar technology, used to target enemy bombers before they reached the English Channel.

Britain’s increased success was attributed by both the public and the enemy to increased carrot consumption by British pilots, rather than new technology developments.

 

What is colour blindness?

Remember how cones in the eye are responsible for colour vision?

Colour blindness is caused by a problem with blue, red or green light-receptive cone cells in the eye. The spectrum of colours that we see is made up of different amounts of blue, red and green light.

If for example the green light-sensitive cones in the eye do not work properly, it is difficult to tell the difference between colours such as oranges, greens, browns and pale reds.

A Red-Green colour blind person would not be able to see the number 6 in this picture.

Some people suffer from a rare eye condition called monochromatism, where a person only sees in black, white and grey.

There are thought to be a number of causes of colour blindness:

  • Genetic problems
  • Trauma that causes retina and brain damage 
  • Long term alcoholism and diabetes 
  • Side effect or taking some drugs or medication.

Colour blindness is usually untreatable.