Fragile X Syndrome

Fragile X syndrome is an inherited condition that can cause learning disabilities in sufferers. The condition is cause by a mutation to the FMR1 gene on the X chromosome. Because of this it is more prevalent in males (who only inherit one X chromosome, from their mother, so if it is faulty, will have the condition) however, it can also be inherited by females. Fragile X is also the largest genetic cause of autism accounting for 5% of cases. Around 1 in 4000 males and less than 1 in 6000 females are estimated to suffer from fragile X.

The mutation of the FMR1 gene is due to the number of repeats of the gene, which has the sequence CGG (the triplet: cytosine, guanine, guanine nitogenous bases that codes for the amino acid arginine in the proteins created by translation of the sequence). People with less than 45 repeats do not suffer from fragile X. Those with between 55 and 200 repeats are said to have a permutation, as their gene is unstable, and could cause the syndrome in their descendants, these people can also suffer from fragile X associated disorders. In female carriers, during the division to form egg cells, extra repeats of CGG can be added, and a child that develops from that egg is likely to be a sufferer. Around 1 in 250 women may be carriers and around 1 in 800 men. In people with over 200 copies of the CGG sequence, the gene is methylated, this means that a methyl group (1 carbon and 3 hydrogen atoms) is added to either C or A nucleotides, this process ‘silences’ the gene so that it is no longer expressed.

The FMR1 gene codes for a protein known as FMRP (fragile X mental retardation protein). This protein is involved in the formation of dendritic spines. Dendritic spines are developed by neurons (nerve cells) and are used to help transmit electrical signals and to increase the number of connections between neurons. Without this protein, people can have severe intellectual impairment, including a decline in memory with age, and children often learn 55% slower than their unaffected peers; however, some people with fragile X have a normal IQ.

Fragile X sufferers often have a characteristic phenotype, including large protruding ears, a long face, hyperextensible fingers and thumbs, flat feet, low muscle tone (hypertonia), macroorchidism (large testes in post-pubescent men) and a single palm crease. Fragile X also has an effect on vision and common problem include strabismus (lazy eye) or refractive errors. Sufferers are also at risk of suffering from seizures, but these can be treated with medication.

Fragile X syndrome can also affect emotions and behaviour in addition to IQ, sufferers can also have social anxieties such as poor eye contact and difficulties forming per relationships. Up to 75% of male sufferers where categorised as having excessive shyness, and many suffered from panic attacks. This is thought to be due to challenges that sufferers have with recognising faces of people they have met and also due to hypersensitivity to noise (so a dislike of crowds). Obsessive or anxiety based behaviours are also common such as hand flapping or biting(self-injury), perseveration (repeating an action even when a stimulus has been removed), self-talk and aggression. Most males and around 30% of females with the full mutation for fragile X have ADHD so display symptoms such as hyperactivity and inattentiveness.

Associated disorders of fragile X syndrome include autism, FXTAS and FXPOI. FXTAS is fragile X associated tremor/ataxia syndrome, which is an adult onset disorder which can lead to dementia, mood instability, cognitive decline and memory loss, tremors, ataxia (loss of balance) and symptoms of Parkinson’s disease such as shuffling movement. FXPOI is fragile X associated primary ovarian insufficiency, and includes symptoms similar to menopause such as hot flushes, unusual menstruation, FXPOI can lead to decreased fertility or infertility, and occurs in around 20% of women with fragile X or carriers of fragile X.

We can screen for fragile X in pregnancy by testing the amniotic fluid or CVS (chorionic villus sampling), however this cannot accurately determine whether a child will develop any of the associated disorders.

There is no cure for fragile X at the moment, however, with educational and emotional support, many affected people are able to cope with related disorders, and some medications or therapies can help alleviate certain symptoms. Other options could include gene therapy to demethylate genes using drugs or blocking receptors for mGluR5 a protein which, when FMRP is missing, causes over-activity of the brain, and by inhibition can reduce seizures and learning delays.

Base pairs, are found as part of the nucleotides in DNA, A-adenine which pairs with T-thymine and C-cytosine with G-guanine.

Nucleotides, the molecules which make up DNA and are made from a phosphate group, 5-carbon sugar and an organic base (see base pairs)

Phenotype, is the observable, physical and behavioural characteristics of an organism.

http://www.bbc.co.uk/health/physical_health/conditions/fragilex1.shtml#what_causes_it_

http://www.nhs.uk/news/2010/02February/Pages/Fragile-X-syndrome-studied.aspx

http://www.sciencedaily.com/search/?keyword=fragile+x

http://www.fragilex.org/

HIV/AIDS the disease of our time

HIV/AIDS is a pandemic which over the last 30 years has infected 60 million people and killed around 30 million. At the moment there is no cure for HIV.

HIV or human immunodeficiency virus is a virus that attacks your immune system, using white blood cells to reproduce itself, leaving sufferers vulnerable to infections. AIDS or acquired immunodeficiency syndrome is the illness that occurs when you contract a secondary infection or HIV has destroyed most of your disease fighting cells. HIV is an infectious disease and is transmitted via sexual contact, directly into the blood stream (i.e. by the sharing of unsterilized needles for intravenous drug use) or from mother to baby across the placenta or in breast milk, but not by saliva.

HIV replicates itself within the human body by binding to cells with CD4 (cluster of differentiation 4) receptors, these include T helper cells and macrophages; this replication permanently damages the cells. These are white blood cells which are involved in stimulating the immune response to infections. An important role of CD4+ T helper cells (i.e. those with CD4 receptors) is initiating the action of CD8 cells which are known as killer T cells, these cells bind to infected, damaged or cancerous host cells and destroy them. Normally, people have 1600 CD4+ cells per cubic mm of blood. If HIV is untreated, the CD4 count drops very low (to around 350 cells/mm³), and the body cannot respond as effectively to infection (and so diagnosis of AIDS).

The gp120 proteins on the surface of the virus bind to the CD4 receptor, with the help of a co receptor called CCR5 or CXCR4; it fuses with the host cell and releases its genetic information in the form of RNA, and some enzymes into the host cell. The virus an enzyme called reverse transcriptase turns the RNA into double stranded DNA using the RNA of the host cell. Another enzyme called integrase allows the viral DNA to then integrate with that of the host cell, where it can remain undetected and inactive for many years. The host cell is then used produce the proteins that make up the HIV virus, the virus matures and then can go on to infect more cells of the body.

HIV symptoms and diagnosis

Several weeks after HIV infection, most people experience seroconversion illness, which lasts up to a month, where the immune system attempts to protect the body from the virus. During this time, sufferers may experience fever, fatigue, swollen glands, muscle or joint pain or an unexplained body rash (the latter being particularly helpful in identifying HIV infection). Unfortunately most of these symptoms are indicative of other illnesses such as flu. After the initial symptoms, whilst HIV spreads throughout the body, there are often no further symptoms for about ten years, this is known as asymptomatic HIV infection. As the person often feels healthy, they are able to transmit their infection to others.

Once the virus has destroyed a significant number of CD4 cells, symptomatic HIV develops, along with a range of symptoms such as persistent tiredness, night sweats, weight loss, persistent diarrhoea, blurred vision, white spots on the tongue or mouth, fever, swollen glands, depression and shortness of breath. These symptoms can last for several months. At this point, sufferers are very vulnerable to opportunistic infections and AIDS. Common opportunistic infections include Candidiasis (thrush is a fungal infection of the mouth throat or vagina), Pneumocystis pneumonia (PCP is a fungal infection leading to fatal pneumonia that can occur when CD4+ count is below 200), Cytomegalovirus (CMV is an infection which causes a disease of the retina of the eye and blindness and can occur when CD4+ count is below 50); some cancers (such as Kaposi sarcoma where tumours commonly grow in the skin, mouth or throat and often grow simultaneously in more than one site), herpes, TB and malaria.

Because its early symptoms mimic other illnesses, and it can lie dormant for many years, HIV is difficult to diagnose. Blood spot tests and saliva tests can be used to confirm if someone is HIV positive(i.e. is infected with HIV) though it make take up to three months for the virus to show up as present in the body. It is estimated that currently 24% of HIV sufferers in the UK are unaware of their condition.

HIV treatment

There is no cure for HIV. Recent studies have shown that the average life expectancy for a patient who is receiving treatment that maintains a CD4+ cell count of over 500cells/mm³ is equivalent to someone who does not have the disease. Worldwide, it is estimated that only 28% of HIV sufferers receive the full course of treatment, and often in developing countries (where the disease is more prevalent) there is less protection against opportunistic infections.

Preventing the spread of HIV is important in reducing the deaths due to HIV/AIDS. Although more people have unprotected sex than inject drugs, the risk of contracting H.I.V. is 1 in 125 from an unsterilized syringe, about 1 in 1,200 from unprotected anal sex and 1 in 2,000 from unprotected vaginal sex. In the UK knowingly transmitting HIV to another person is a criminal offence.

Education about the risks of unprotected sex is essential in reducing transmission of HIV. Sex with multiple partners is a large risk factor for contracting HIV, especially with those in the sex industry, encouraging monogamy could help reduce the spread of HIV. Anal, vaginal and oral sex can all transmit HIV, abstinence from these activities provides 100% protection, and male and female condoms can both significantly reduce the risk of transmission. Improving availability of condoms (and lubricants to prevent condoms breaking), encouraging HIV tests and encouraging sexual partners to be honest with one another.

Intravenous drug users should not share syringes or preparation equipment with others, and use sterile syringes and water. Governments and charities have created needle-exchange programs a reliable source of sterilised syringes, and recommend users to be screened for HIV each year. Though obviously the ideal solution would be to stop the use of drugs, as they can affect judgement (i.e. more likely to forget to take medication, engage in unprotected sex or offer paid sex in exchange for drugs), and 50-90% of HIV positive drug users also have Hepatitis C, but due to the nature of addiction this is usually not possible. Heroin users at risk of HIV are offered methadone treatment as the drug can be taken orally; users of other drugs such as methamphetamine are encouraged not to inject.

People living with HIV are encouraged to be routinely vaccinated against opportunistic infections such as flu, to prevent AIDS. They are encouraged to engage in safe sex, not only to prevent the spread of HIV, but to protect themselves against sexually transmitted infections. Maintaining a healthy lifestyle and good hygiene are also important to eliminate infection. These precautions have been successful, as in the UK, death rates due to AIDS are falling. However, this means there are more healthy HIV carriers to spread the disease.

A huge problem with HIV treatment is that most HIV sufferers do not stay on their course of treatment. There are a few side effects of HIV drugs such as nausea, fatigue and diarrhoea and they can worsen mental health conditions such as depression. Recreational drugs such as cocaine also react unpredictably with HIV medication. However, due to improvements in HIV pharmaceuticals, most HIV treatment consists of just one or two pills a day each providing drug combinations, making it easier to remember to take all of the medication required. We need to improve education to ensure that everyone who is able to receive treatment is able to stick with the course.

Anti-retroviral therapy is the current treatment for HIV. It is very effective as not only can it significantly Improve well-being of people with HIV, it can reduce the risk of transmission by 96%. A combination of ARV drugs is used because HIV can quickly adapt and become resistant to one single ARV. If treatment involves three or more different drugs it is known as HAART (highly active anti-retroviral therapy). For the treatment to be effective, it will need to be taken on time, every time. The drugs keep the virus at a low level in the body which allows the person to recover from damage caused by the virus. This treatment must be continued throughout the life of an HIV positive individual, as even if they feel healthy, the virus can be latent within CD4 cells (i.e. has integrated its genetic information with that if its host but has not made new copies).

At the moment, 20 ARV drugs have been approved by the FDA (though not all are available in every country) and these can be classed into 5 groups. NRTIs are nucleotide/nucleoside reverse transcriptase inhibitors, they prevent the action of the reverse transcriptase enzyme, by binding with the enzyme instead of the host nucleotide (the molecules used to make chains of DNA and RNA), so the virus create DNA, so cannot make new copies of itself. NNRTIs have a similar effect, but permanently change the shape of the enzyme, so it can no longer bind to nucleotides. Integrase inhibitors prevent the virus inserting its genetic material into that of the host cell. Protease inhibitors, prevent the virus from making its protein coat or enzymes (which are proteins). Fusion or entry inhibitors prevent the virus binding to a host cell. The latter three ARV drugs are less widely available in developing countries, as they are expensive, particularly protease inhibitors, where a large number of pills need to be taken. Usually treatment includes two NRTIS and an NNRTI or protease inhibitor.

PrEP or Pre-exposure prophylaxis is the use of anti-HIV drugs to reduce the risk of contracting HIV. The first PrEP drug Truvada a daily oral combination tablet has recently been approved by the FDA to help prevent HIV as it reduced infection risk by 73% in a study of heterosexual couples in Africa and 42% amongst homosexual couples. Vaginal gels containing similar drugs have also been trialed in the hope of empowering women whose partners will not wear condoms so that they may be protected. The drugs were found to be effective, yet trials of African females were not particularly successful, mostly due to the lack of adherence to the treatment (with only 21% of under 25s with good adherence to the treatment), so alternatives are being developed that may be more appealing/easier for the use of at risk groups. Drugs are also being trialed amongst injecting drug users. 

PEP, post-exposure prophylaxis, is a month long treatment program with a fairly high success rate that can be administered within the first 72 hours of HIV exposure to prevent infection. The earlier the treatment is started, the more effective it is, but the entire course must be completed and there are some serious side effects of the drugs used.

HIV can be transmitted vertically from mother to baby during pregnancy, during childbirth or by breast feeding. If a HIV positive mother receives no treatment, her baby has a 25% of developing HIV. Mothers can reduce transmission by taking ARV drugs during pregnancy, having caesarean sections, avoiding breastfeeding and ensuring the child receives HIV treatment as a newborn, doing all of these things reduces the risk of transmission to only 2%. In developing countries it is particularly important to provide alternative nourishment for babies born to HIV positive mothers, to prevent transmission via breast milk. Usually babies are treated with a preliminary ARV at birth and tested for HIV from 3 months (so as to be able to differentiate between antibodies produced by the mother and the baby), after which stronger ARVs may be prescribed.

HIV, will there ever be a cure?

So far there has been no luck in finding a permanent cure for HIV sufferers. However, vaccines for the similar virus in chimpanzees, SIV (simian immunodeficiency virus) were successful in that 80% of the rhesus monkeys vaccinated did not contract SIV upon exposure, and those already with SIV were in control of the virus, which over time was no longer found in their bodies. Scientists have had less success in translating these ideas to the human virus, as HIV is very variable, and even weakened forms are dangerous due to the virus’s ability to lie undetected within the body for many years.

Vorinostat is a drug currently used in the treatment of T-cell lymphoma (cancer of the white blood cells). It has been found to have the ability to induce the expression of latent integrated HIV genes (i.e. forcing any cells that are hiding the virus’s genes to produce the virus) This could help in diagnosing patients and in potentially finding a way to ‘flush out’ the virus. There are dangers however, that ‘awakening’ the virus could cause harm to the patient.

In the human body, HIV could produce 100 billion new viruses each day, with each reproduction there are many errors, so great variation between particles, so vaccines are impossible to develop. However, there are several sectors where mutations are very rare so are similar in all forms of the virus. The HIV virus packages its RNA in a specific shape and uses a type of protein called a Gag protein to identify the viral genetic information amongst that of the host. The genetic information for this protein lacks variation, so a potential route for stopping the spread of the virus within the body is to target the RNA that codes for the Gag proteins.

Functionally cured

A baby born in America is thought to have been functionally cured of HIV. The girl who is two-and-a-half years old was born to an HIV positive mother and immediately from birth was treated to a combination of 3 ARVs; she stopped treatment after 18 months, and now appears functionally cured. However, it is unknown whether in this case the baby was born HIV positive.Functionally cured means that a previously HIV positive person no longer needs to take ARV treatment in order to have a healthy immune system, no risk of transmitting the virus and a normal life expectancy (though they may still have traces of the virus in their body). This news, if valid, could be helpful in developing treatments for babies born HIV positive as in Sub-Saharan Africa, 300,000 infants were born HIV positive in 2011. There have also been a group of patients called the Visconti patients, all with HIV infection caught at an early stage (10 weeks), 10% of whom, after 3 years of ARV therapy, have been able to control the virus within their bodies for a decade and appear functionally cured. With both of these cases however, the infection was caught very early, on average people in the UK are diagnosed 5 years after infection.

There has been another high profile case of a cure for HIV, and a potential explanation for the functionally cured baby. In 2007 news broke of an HIV positive man received a bone marrow transplant, and after several months tests no longer showed the presence of the virus. His donor was an ‘super controller’ of the virus, and individual who has a natural resistance to HIV due to a faulty gene for CCR5 co receptors (which allow HIV to bind to CD4+ cells). It is though that 1% of Europeans are super controllers, perhaps due to its ability also to protect from small pox. Tests to disable CCR5 co receptors have so far not had any success, with people treated returning to ARV treatment within 3 months.

Enzymes, proteins which speed up particular metabolic reactions

FDA, the American Food and Drugs Administration are responsible for the approval of new drugs

Macrophages, white blood cells that engulf invading micro-organisms and display the foreign cell markers so that our bodies know which antibodies (which inhibit the micro-organism) to produce.

RNA, a single stranded molecule containing genetic information, unlike double-helical DNA

T helper cells, white blood cells which send out chemical signals to other cells stimulating the production of antibodies and the engulfing of foreign micro-organisms.

http://aids.gov/

http://www.nhs.uk/Conditions/HIV/Pages/Introduction.aspx

http://www.who.int/hiv/en/

http://www.sciencedaily.com/news/health_medicine/hiv_and_aids/

http://www.med.cam.ac.uk/blog/offensive-manoeuvres-in-the-war-against-hiv/

http://www.avert.org/treatment.htm

Antibiotic resistance and the rise of superbugs

Antibiotics have been crucial in the fight against infectious diseases, specifically those caused by bacteria, over the last century. The first antibiotic, penicillin was discovered in 1929, and protected against staphylococcal and streptococcal infections. These are the bacteria which cause diseases such as septicaemia, abscesses and impetigo (Staphylococcus) or scarlet fever and tonsilitis (Streptococcus). However, since the 1940s, cases of resistance to these drugs have begun to appear in pathogens (disease causing microorganisms), leading to complications in treatment of the diseases that they cause, and  around 25,000 deaths a year in the EU.

Antibiotics usually work by inhibiting enzyme action in the bacterium pathogen, which means that the bacteria cannot survive or reproduce. The penicillin family and cephalosporin antibiotics inhibit the enzyme for the production of peptidoglycan, which is used to make bacterial cell walls, without which, the bacteria would burst. The antibiotics aminoglycoside, tetracycline and erythromycin (a penicillin substitute which can treat Legionnaires’ disease) inhibit protein synthesis, preventing the bacteria from making any more enzymes and growing. Some others like sulfamethoxazole work by inhibiting enzymes responsible for metabolic reactions. Because of the way in which antibiotics work (by preventing the formation different aspects of bacterial structure), they cannot treat viral infections, as bacteria are cellular organisms and viruses are not.

  

If one bacterium has an inherent antibiotic resistance or develops a resistance to antibiotics due to a genetic mutation or change in environment, it is then able to pass on its resistance in several ways, creating colonies of resistant bacteria. An example of resistance is the gene for the production of the enzyme penicillinase, which turns penicillin into penicilloic acid, preventing the action of penicillin.

Vertical gene transfer: If a course of antibiotics is prescribed, all non-resistant bacteria will be killed, but the resistant bacteria will thrive. The antibiotics act as a selective pressure, as only the resistant bacteria will reproduce, so the resistance will be passed on to all its offspring.  Because bacterial cells can, in optimum conditions, divide every 20 minutes, in less than 7 hours hours you would have a colony of 1 million bacteria all with antibiotic resistance.

Horizontal gene transfer: Plasmids are rings of DNA present in bacteria. Segments of these plasmids can be exchanged between different species of bacteria, for example Staphylococcus bacteria can share genetic information with Bacillus, Streptococcus and Enterococcus bacteria. This means that bacteria with antibiotic resistance which do not cause disease could pass on their resistance to pathogens. Genes can also be accumulated from dead bacteria in the environment being broken down, and their genetic information taken up by others or by viruses transferring genetic information between cells.

Recent studies have shown that bacteria under stress (in this case growth at high temperatures) can spontaneously develop resistance to unseen antibiotics (in this case the E. coli bacteria developed resistance to rifampicin). Rifampicin is an antibiotic used in the treatment of TB, leprosy and meningococcal meningitis.

 

The overuse or unnecessary use of antibiotics has played the most significant role in allowing resistant strains of bacteria to reproduce and spread. Also by not finishing a course of antibiotics or having too mild a dose, could lead the bacteria to develop a resistance. We would assume, therefore, that when reintroduced with other bacteria, without antibiotic presence, the resistant strain may die out, because it no longer has an advantage over other strains. Unfortunately the same studies as mentioned previously have shown that this is not always the case rifampicin resistant E. coli reproduced at a 20% faster rate, the first time this has ever been seen in resistant bacteria.

Staphylococcus aureus is a bacterium which is carried on the skin, and in the nostrils and throat. The bacteria is mostly harmless but can cause boils (pus filled lumps) or impetigo (fluid-filled blisters or sores that leave a yellow-brown crust) if it gets inside hair follicles. Staphylococcus aureus could enter the bloodstream through a break in the skin such as a wound, burn, due to the insertion of an IV (intravenous) drip or catheter, or due to invasive surgery. Inside the body it could lead to blood poisoning/sepsis (overreaction of the immune system leading to high temperature, dizziness, nausea, inflammation and blood clots), urinary tract infection or endocarditis (infection of the lining of the heart which could damage the heart valves and lead to heart failure).

MRSA is methicillin-resistant staphylococcus aureus, a strain of the bacteria resistant to many classes of antibiotics (including penicillin and cephalosporin families). The first case in the UK was in1961, two years after the introduction of the antibiotic methicillin, but over the past decade MRSA has been a severe problem. Within hospitals and nursing homes, it is known as Hospital-Associated or HA-MRSA, the main route of transmission being the presence of the bacteria on the skin of patients and healthcare workers. Deaths due to MRSA rose to a peak in 2007 and in the USA deaths due to MRSA overtook those due to AIDS, but in 2011 were reduced to only 364 deaths in England and Wales where MRSA was cited as the direct cause. This was due to the isolation of infected patients, the introduction of more rigorous hygiene enforcement for staff and visitors and a swab test and antibacterial wash for patients undergoing surgical procedures. MRSA also spread in homeless shelters and army camps due to close contact and poor hygiene, known as Community-Associated or CA-MRSA. The more serious infections due to Staphylococcus aureus are usually treated with antibiotics, though this would be dependent on the strain of the bacteria, and combination treatments may be necessary.

Clostridium difficile is a bacterium that is present in the human bowel (because it prefers the anaerobic conditions) and does not normally pose any threat. However, after antibiotic treatment, the other bacteria present in the bowel are killed, creating an imbalance leading to the multiplication of the bacteria and the production of harmful toxins. The disease can also be spread as C. difficile spores are present in faeces and can remain on surfaces for months.  C. difficile infections can cause diarrhoea, dehydration, nausea, fevers and abdominal cramps. Occasionally infections can lead to kidney failure due to dehydration, the swelling of the bowel or perforated colon, which can be treated by a colectomy. Similarly, Escherichia coli which naturally occur in the gut of all humans, but can cause urinary tract infections which cause pain when urinating but could also lead to kidney failure or blood poisoning. UTIs are usually treatable by a course of antibiotics, but resistant strains are becoming a big problem, and are thought to be due to the antibiotic resistant strains of the bacteria due to the overuse of antibiotics to prevent disease in agriculture, which accounts for 60% of antibiotic use.

Due to the development of resistant strains of C. difficile, it is important not to continue with an antibiotic treatment which is not working, so as not to put excessive selective pressure on the bacteria. The antibiotics currently used are metronidazole and vancomycin. We can prevent C. difficile by hand washing (though not alcohol hand rubs), disinfection of surfaces around the patient and in hospitals, staff are encouraged to wear gloves when treating patients with the infection In 2011 there were 2,053 deaths due to C. difficile infection, though like MRSA due to the improvement of hygiene, these rates are falling. Unfortunately deaths due to E.coli are rising.

Mycobacterium tuberculosis is the bacterium which causes tuberculosis (TB), one of the oldest infectious diseases which has been in human populations for 40,000 years, a slowly developing condition spread by droplets through the air (i.e. sneezing). Often infections occur in the lungs, known as pulmonary TB, which causes breathlessness, coughing up blood, high temperature, fatigue, severe weight loss. TB can also affect the digestive, lymphatic (glands), skeletal and nervous system as well as the bladder, with various symptoms such as pain, swelling or bleeding of the infected area. TB is not very contagious compared with colds or flu, but in conditions of poverty such as overcrowded housing and poor diet, it can spread quickly with one infected person infecting 15 others each year. Until 2005, all children in the UK were given the BCG vaccine which protects against TB, especially TB meningitis which is common in children, though it does not provide absolute protection against TB in adults. Currently several antibiotics and anti-TB drugs are available to effectively treat tuberculosis, rifampin and isoniazid (the first line treatment) and streptomycins, para-aminosalicylic acid and ethambutol. However, these second line drugs are very expensive can have side effects such as depression, hepatitis and hallucinations.

Since 1990 global cases of TB have decreased by 41%, but misuse of antibiotics has created strains which are resistant and once again TB is on the rise in the UK with 8,963 cases, and is a huge problem in the developing world in countries such as India. It is also thought that over 30% of the World’s population is infected with latent TB, which will only develop once the immune system is weakened. It is becoming even harder to treat. This is because of the development of MDR (multi drug resistant) strains of the virus, which is resistant to first line treatment which is treated in poverty stricken countries by different drug combinations in an attempt to find one that will work, potentially driving further resistance. It is thought that the first case of TDR (totally drug resistant) TB was recorded in India in 2011 (although we cannot be 100% certain that it would have been resistant to all the antibiotics available to us at the moment, though the case was certainly extensively drug resistant). Unfortunately, though trials for new vaccines and drugs are being developed it is likely that we will only extend the antibiotic fuelling bacterial resistance cycle, creating as much harm as good, creating the incurable diseases of future.

http://www.dh.gov.uk/health/tag/antibiotic-resistance/
http://www.nhs.uk/Conditions/MRSA/Pages/Introduction.aspx

http://www.nhs.uk/Conditions/Clostridium-difficile/Pages/Introduction.aspx
http://www.cdc.gov/HAI/organisms/cdiff/Cdiff-current-strain.html

TIME magazine March 4th 2013

New Scientist March 2nd 2013

Telomeres- aglets for your genes

Telomeres are repetitive sequences of base pairs of our DNA at the end of each of our chromosomes, in humans the telomere sequence is TTAGGG, and this is the same for most animals.

Our telomeres are important because when our DNA is copied (this happens every time a cell divides) the polymerases which copy DNA do not start from the very tip, so if we did not have telomeres, we would loose a little bit of genetic material every time we needed to make a new cell, leaving raggedy gene ends which could lead to mutations (which could cause cells to form tumors). Telomeres also stop the ends of different chromosomes sticking together and altering our genetic makeup. In a way telomeres act like an aglet to our chromosome shoelaces, by protecting the ends from wear and tear.

When we are born, our telomeres are up to 15000 base pairs long (though each individual has a genetically determined number). Each time our cells divide by mitosis, we lose around 30-200 base pairs from our telomeres. This gives most of the cells in our body a lifespan of 50-70 divisions, after which they usually 'die' in a way that does not affect the working of neighbouring cells known as cell senescence. However sometimes can continue to divide causing mutations as less genetic material is copied in successive cell divisions. Notably, artery wall cells have far shorter telomeres than those in veins due to stress, damadge and therefore the need for the replication of cells.

Our bodies also produce an enzyme called telomerase reverse transcriptase which adds base pairs to the end of our telomeres, preventing them from shortening too quickly, however this process appears to stop in adult cells. This enzyme is also responsible for the 'immortality' of cancerous cells which divide rapidly. There is hope amongst scientists to prevent the development of tumours by inhibiting telomerase, however this can have significant side effects such as problems with fertility, wound healing and blood cell production.

Studies on mice in November 2012 have shown that their rate of telomere shortening is 100 faster than in humans and perhaps accountable for the difference in lifespan between our species. The studies also have shown that exending telomeres can increase life expectancy in mice by up to 24% and postpone the advance of age related diseases such as osteoporosis and insulin-resistance. 20 year studies on birds (without natural predators) in the Seychelles, found links between longer telomeres and longer life as well as rapidly shortening telomeres as a sign of a bird within the last year of its life.

Links between telomere length and shortening have been linked to aging and many human diseases, people with shorter telomeres are apparently 3 times more likely to suffer from cardiovascular diseases; 8 times more likely to suffer form infectious diseases; there have beeen links to Alzheimers disease as well as bone, prostate, bladder and kidney cancers to name a few. Telomere length also has direct links to Werner's syndrome (where oxidative stress cannot be repaired) and Dyskeratosis congenita (where telomeres shorten rapidly), diseases both with symptoms of premature aging.

Links have been found between the age of a child's father and telomere length as unlike body cells, the sex cells increase telomere length with age, so the father will pass on these longer telomeres to his offspring.

Some laboratories are offering blood tests to determine telomere length, the '£400 blood test to tell you when you will die'. However this advertisment was misleading and was exaggerated by the media, as longevity cannot be predicted through one blood test, due to the huge varaition between people's original telomere length. Though discovering a fast rate of telomere shortening could be an incentive to improve liefstyle (for example telomeres are shortened by oxidative stress, a process which is prevented by eating antioxidants)

An issue however is that if further studies were to confirm that telomeres played a significant role in causing aging and age-related diseases, that insurance companies or employers could use the imformation about an individual's telomere length to discriminate against that individual.

There is hope that by studying the action of telomerase in cancer cells and its apparent ability to provide cell immortality that we could potentially postpone the aging process. Natural selection only prepared us to outlive our offsping, but now with an aging population due to the irradication of many diseases which have blighted our species in the past, are telomeres the final barrier to immortality?

Definitions:

Base pairs, our DNA is made of pairs of complementary molecules, one on each strand, bonded together

Enzymes, proteins in the body which speed up metabolic reactions

Mitosis, cell division where by cells make an identical copy of their genetic material 

Polymerases, a type of enzyme that copies DNA

Oxidative stress, is an imbalance between the production of reactive oxygen and the body's abillity to restore the balance of oxidants

Sources:

 http://www.guardian.co.uk/science/2011/oct/11/blood-test-predict-when-you-die

www.sciencedaily.com/releases/2012/05/120514204050.htm

http://www.nature.com/nature/journal/v413/n6854/fig_tab/413370a0_F1.html

http://news.bbc.co.uk/1/hi/health/8359735.stm

Genome by Matt Ridley

Starting my blog

So this is me starting a blog, writing things that other people can actually see on the internet!

First of all, I'm Ellie, currently studying for my AS levels and aspiring to be a doctor. For the last couple of months I've been scribbling down on various notepads anything that I hear about regarding medicine or health, and wondered if I should be sharing the things that I've found interesting with others. 

Just to add, any information that I post up here can probably be found elsewhere online or in newspapers and magazines (I will cite my sources below my posts). 

Thank you for bearing with me, and hope you enjoy my future posts.