Showing posts with label cancer. Show all posts
Showing posts with label cancer. Show all posts

February 09, 2010

Mobile Phones' Impact on Health

Mobile phones have drastically transformed our lives. Also known as cellular phones or cell phones, these gadgets not only incorporate a phone, as the name suggests, but also a lot of other technologically advanced features. They include a camera, a sound recorder cum music system, a Bluetooth device and many more depending on the model and the maker of the phone. They are called mobile phones since they can be used while on the move.

A mobile phone maintains a two way (transmit and receive) communication with the nearby tower within a cell. Even when you are not talking on your mobile, it is constantly in touch with its ‘cell’. A cell may be thought of as the operational unit of a ‘base station’. A city or area may be likened to a bee hive, each hexagon representing a ‘cell’ having its own tower. As you move from one honeycomb to other, your mobile will change contact from one tower to another (another cell).

Cell phones radiate high frequency (hence, microwave, as wavelength is inversely proportional to the frequency) electromagnetic radiation as a means of communication. One could easily demonstrate this electromagnetic emanation by putting a mobile flashing sticker close to a phone when it’s being used. This radiation can pierce our body tissues, particularly the head. But they could also microwave our scrotum if we keep them inside our pant pocket, as the phone is constantly in touch with the tower and emitting radiation unceasingly.

The rapidly alternating electromagnetic field makes the polar molecules in our body move back and forth, as a tiny magnetic compass would move if the external magnetic field was allowed to change. This molecular movement results in heating of the tissues. Scientists were curious if this could harm us.

Previously, it was thought that they could cause brain cancer but it was later found out that there was no significant relationship. There were some unconfirmed reports suggesting an association between mobile phone usage and an increase in the incidence of acoustic neuroma, a benign tumor of auditory nerve. The thermal effects arising out of the to-and fro effects of the polar molecules could give rise to the increased production of a class of proteins, called ‘heat shock proteins’ or stress proteins.

Some drugs (like glucocorticoids, estrogen and progesterone) enter inside the cells where they combine with molecules called receptors, in the cytosol. This drug-receptor complex then translocates to the nucleus and commands the DNA into producing protein molecules by transcription. The resulting proteins typically account for the actions of these steroidal drugs. Heat shock proteins (like Hsp90) cover the DNA binding domain of the cytosolic receptors, preventing interaction with the DNA. When a steroid molecule attaches with the receptor, a conformational change occurs in the receptor releasing the Hsp, thereby freeing the DNA binding domain. Naturally, more stress proteins would mean more blocking of steroid receptors.

Studies have also shown that microwave radiation at doses considered harmless caused DNA damage after two hours of exposure. All these led authorities in some countries advice Bluetooth usage and to keep your head away from your mobile. Read the next few lines if you really should keep your head away!

Having said all those, let me state that the WHO, the American Cancer Society and the National Institute of Health have concluded that there was no scientific evidence that cell phone use had any adverse health risks.

A University of South Florida research team wanted to find out any association of Alzheimer’s disease with cell phone usage. In the past, several studies have hinted at a possible increased risk of Alzheimer’s disease in humans with low frequency electromagnetic radiation, such mains power line frequency. But as they went on with their research, they were surprised at what they saw.

Electromagnetic mobile phone radiation and Alzheimer's in miceThey employed about 100 mice and subjected them to a daily radiation of 1 hour by an antenna that was kept in the center of the cage as shown. Some of these mice were 2 month old, which were genetically programmed to develop Alzheimer's disease like symptoms and signs with age; and some 4 month old, which already had the symptoms. They also placed normal healthy mice in the same cage. The electromagnetic field was made to emulate the radiation received by a man as he talked on his mobile phone and the wavelength was the same as that of the mobile phones. The mice’s memory was checked by maze tests.

They were astonished to find that the electromagnetic field (EMF) not only boosted memory in both healthy and transgenic mice (compared to other mice who did not receive radiation) but also they actually reversed symptoms of Alzheimer’s. EMF seemed to break up tell-tale beta-amyloid plaques, a histopathologic marker of Alzheimer’s disease in mice which already expressed them. There was no evidence of increased tumour/cancer formation, DNA damage or behavioral changes.

While what exactly cleared the plaques was not certain, but to quote Gary Arendash of the University of Southern Florida: "One thing is clear, however -- the cognitive benefits of long-term electromagnetic exposure are real”. Arendash also wondered if the preferential use of one of our ears in holding the phone could have asymmetric outcomes in the brain in terms of the plaques. He also observes: "It might also be useful in traumatic brain injury, which is also characterised by plaques, or just to improve cognitive performance”

While it’s too premature to use your phone too close to your head to get a boost in your exams in the near future, its possible use as a “nootropic” is certainly encouraging.

Mobile phones have a lot of other usable paraphernalia, some of which I pointed earlier. These features and the availability of inexpensive high-efficiency light emitting diodes (LEDs) inspired Breslauer et al to construct a microscope that would be helpful in developing countries.

They have developed a high-resolution microscope attachment that is meant for camera- mobile phones as microscopesphones (picture on the left; click to enlarge). Their microscope can capture colour images of the malignant malaria causing parasite Plasmodium falciparum, red blood cells sickling in peripheral blood smear in homozygous sickle cell anemia (hemoglobin SS ) using brightfield microscopy. When fluorescence microscopy was performed with the sputum of tuberculosis patients using Auramine-O stain, the device captured Mycobacterium tuberculosis as well. The resolution was sufficient for the identification of single TB bacterium. The contraption was also good enough to highlight the rod shaped morphology of the acid-fast aerobic bacteria. In addition, epidemiological studies could be easily performed given that the individual mobile cells had their own identification codes and was under GPS location monitoring.

Thus, we can create a cheap and efficient brightfield and fluorescent microscope out of a simple mobile phone (they used Nokia N73 camera phones, equipped with a 3.2 megapixel CMOS camera) and some easy to obtain components. To end up, there seems to be more to cheer than fear.

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ResearchBlogging.orgReferences:
Gary W. Arendash, Juan Sanchez-Ramos, Takashi Mori, Malgorzata Mamcar, Xiaoyang Lin, Melissa Runfeldt, Li Wang, Guixin Zhang, Vasyl Sava, Jun Tan, & Chuanhai Cao (2010). Electromagnetic Field Treatment Protects Against and Reverses Cognitive Impairment in Alzheimer's Disease Mice Journal of Alzheimer's Disease, 19, 191-210

Breslauer DN, Maamari RN, Switz NA, Lam WA, Fletcher DA (2009) Mobile Phone Based Clinical Microscopy for Global Health Applications. PLoS ONE 4(7): e6320. doi:10.1371/journal.pone.0006320

Cell Phone Radiation Reverses Alzheimer's and Boosts Memory in Mice

Cellphone radiation is good for Alzheimer's mice

December 05, 2008

PET Scan: Particle Physics And Electronics in Medical Imaging

Numerous imaging modalities are there to view anatomical structures in our body. They include X rays, Ultrasound imaging, MRI and many other procedures where we can see normal or diseased tissues in our body. They tell us ‘the location’ (position) in the body the image corresponds to. If we wanted to see what were happening in these locations, we would then need to perform functional imaging techniques like PET scan or fMRI.

In Positron Emission Tomography or PET, a radioactive isotope that decays by positron emission is introduced into the body. Positron emitting radioisotopes are prepared by bombarding stable atomic nuclei by protons. Protons are speeded up in a particle accelerator called cyclotron which then impinge upon the stable nuclei, and knocks out one neutron from its nucleus. The proton now occupies the position where the ousted neutron once stayed. But this atomic configuration is unstable, so the proton now decays. It decays by emitting positron, a particle resembling an electron in all aspects except that the charge is positive and not negative. In other words, a positron is an antimatter: an anti-electron.

positron annihilation and formation of two collinear gamma ray photonsMany different radioisotopes are there, such as Fluorine18, Oxygen15, and Carbon11. 18F is the most commonly used isotope. It replaces hydroxyl (OH) group in molecules of interest. We can use 18F Fluorodeoxyglucose (18FDG) an analog of glucose for probing the activity of brain. Our brain uses glucose for its metabolism, so when it encounters 18FDG, it stores them. The FDG in the brain begins emitting positrons. These particles travel only a short distance before they meet nearby electrons and annihilate. Two gamma ray photons, each having 511 keV of energy are produced--- Photons because they are electromagnetic waves, and gamma ray because the frequencies correspond to the gamma ray spectrum of electromagnetic waves.

So by detecting these photons, we can find out where they came from, since we know that these photons are emitted back to back, 180 degrees apart. (They aren’t exactly collinear as their initial velocity is not zero, and some computational error always creeps in). For the detection part, we need a detection array which will convert these photons into electrons. This is done by scintillators. Bismuth germanate, Luterium oxyorthosilicate (LSO) are some of them. Photons which are incident on them produce electrons by photoelectric effect. These electrons are then guided through a vacuum tube, which has many positive electrodes (dynodes) held at successively higher voltages. These dynodes of this photomultiplier tube accelerate these electrons, which in turn knock-off more electrons from the dynode plates. Thus we get more electrons than what we started with. The signal has now been amplified and we now have a measurable current.

With advancement in detection technology, silicon avalanche photodiodes (silicon APD) has now shown promise to replace the vacuum technology (photomultiplier tube). As the name suggests, APDs work in a similar way an avalanche gains its momentum as it descends from the mountain-avalanche effect. Detecting photons aren’t sufficient. We need to detect only co-linear (coincident) photons. Each collinear photon pair (i.e. 180 degrees apart) will constitute an event. All other photons (noise) must be rejected. About 10^7 to 10^8 or more ‘events’ must be registered in order to have a good signal to noise ratio. Image faithfulness varies proportionally with the square root of the number of events.

By acquiring a large number of events, the computer software is able to determine exactly where these radioactive tracers are located. This, in our case, means the locations where the neurons are accumulating (accumulation is a function of utilization of glucose) 18FDG. Thus we get a functional map. In order to know ‘what’ these structure were, we need to combine anatomical imaging like MRI or CT with PET. This combined PET-CT or PET-MRI let us know what structures are doing how much.

PET scan is very useful in neuroscience researches, clinical diagnoses like cancer detection, receptor analyses and even watching gene expression in molecular biology.

References: A good site with animation: PET animation
Physicsworld

Last Mod: 10 Mar, 2014

October 04, 2008

Smelling The Intentions Of Olfaction

a boy smelling a red roseOne simple thing puzzles me as to why the olfactory pathway has to bypass thalamus while most pathways from sensory receptors and sensory organs say hello to the thalamus, as they pass to the cortex. In fact, the cortex and thalamus are so intricately connected to each other, in a bidirectional way, they are sometimes referred together as thalamocortical system. Thalamic excitation of the cortex is necessary is necessary for almost all cortical activity. Why is there an exception in the case of olfaction (smell)?

How do we smell things? It is believed that volatile odorant molecules first mix ResearchBlogging.orgwith the mucus in the nose. They then interact with receptors in the olfactory cilia, called G-Protein coupled receptors. An enzyme called adenyl cyclase is produced as a result, which opens up a sodium channel. Sodium ions (Na+) pour into the olfactory cells, which then fire and smell is thus created. Marshall Stoneham and colleagues, at University College London, propose that olfaction may involve quantum mechanics. The odorant molecules, in addition to having a shape, have another property called vibration. They argue that this (vibration) property may allow electrons to tunnel through to the receptors within the nose to evoke the sense smell. They found phonon assisted electron tunneling, from a donor to an acceptor, mediated by the odorant activated a receptor, in perfect harmony with present physics provided the smell receptors fulfilled some criteria.

We all know that rats fear cats and avoid them so that they are not harmed. They can smell cat’s urine and don’t tread their paths. However, when cats are infected with the parasite Toxoplasma gondii, the rats no longer fear the cats’ urine. The parasite possibly alters the rats’ perception of smell in such a way, so that the intrinsic avoidance becomes passionate attraction. Manipulation of smell sensing thus ensures that the parasite is transmitted from their definitive host (cat) to their intermediate host (rat), thus completing its life cycle. In a similar way it has been conclusively found that dogs can smell some human cancers like lung cancer, breast cancer and skin cancer.

Scientists now can measure minute amount of acetaldehyde, a biomarker of lung cancer. Using tunable diode laser absorption spectroscopy, they could ‘smell’ the telltale signature of those odorant biomarkers in the exhaled breath of the patients. May be they would be able to devise practical explosive smelling devices as well. Sniffing with reliable accuracy and precision would herald a new era in diagnostic oncology.

Apart from its bypassing the thalamus, olfaction puzzles at another point: its stem cell reserve. Why out of the whole brain has it been selected to hold an adult neural stem cell reserve? May be it’s just a coincidence. These cells may come in very handy in the treatment of a variety of diseases.

While a newer pathway of olfaction has been discovered in the monkeys which pass through the thalamus, olfaction on the whole continues to elude me.

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Reference: Diagnostic Accuracy of Canine Scent Detection in Early- and Late-Stage Lung and Breast Cancers;
DOI: 10.1177/1534735405285096
Perception without a Thalamus How Does Olfaction Do It?
doi:10.1016/j.neuron.2005.03.012
Jennifer C. Brookes, Filio Hartoutsiou, A. P. Horsfield, A. M. Stoneham (2006). Could humans recognize odor by phonon assisted tunneling? arXiv:physics/0611205v1

May 31, 2008

When Bullets Lose Their Magic

German chemist Paul Ehrlich coined the term 'magic bullets' (he also used the term chemotherapy), in connection with the dyes used to visualize histology samples. He assumed that if these dyes could specifically stain the pathogens then these substances could also be used to deliver toxins that would specifically kill the rogue cells. Based on these assumptions, he developed Salvarsan (arsphenamine), a drug used in syphilis.

Medicines do not always act so magically. Sometimes medicines end up doing just the same thing it was made to cure. Such boomeranging is not uncommon. Consider the case of aspirin (acetyl salicylic acid). It is used in the treatment of fever and inflammation, among others. It inhibits the enzyme cyclo-oxygenase (COX 1 &2), thereby reducing the production of prostaglandins which works on the hypothalamus to bring about fever. Thus it acts as an antipyretic. However, in higher doses, it causes fever. This occurs as uncoupling of oxidative phosphorylation occurs at higher doses, liberating free energy in the form of heat. Oxidative phosphorylation is normally associated with the formation of ATP (high energy phosphates, the energy currency of the cells).

In cancer chemotherapy drugs used to treat cancer (usually given to lessen the tumor burden, these drugs rarely cure cancer) often cause cancer themselves. Nitrogen mustards such as lomustine (or carmustine) are examples of such antimalignancy drugs. Historically, sulfur mustard was used on the British by Germans in 1917, in a chemical warfare. It caused blisters on the skin and mucus membranes and bone marrow suppression. Its effectiveness in cancer was discovered later, nitrogen mustards came in. These agents are alkylating since they form highly reacting immonium ions in neutral or alkaline water. These immonium ions being nucleophilic, attack the DNA of the malignant cells and cross links them. The cell replication stops; the reckless and relentless progress of cancer growth is tamed.

But the most heart rendering of these are, funnily enough, the medicines for the heart themselves. Nitrates are used in angina pectoris, a medical term for chest pain or discomfort due to coronary heart disease. Nitroglycerin explodesThese compounds liberate nitric oxide or EDRF(Endothelium Derived Relaxing Factor) in our bodies, which then increase the amount of one intracellular compound called cyclic GMP (cGMP). cGMP acts on the vascular smooth muscle cells and these relax. This vasodilation brings relief in painful occlusive (spastic, atherothrombotic) coronary heart diseases. (vasodilation, incidentally, is also the basic principle of action of Sildenafil citrate, known popularly as viagra). But nitrates (polyol esters of nitric acid) such as Nitroglycerine (known variously as NTG, GTN or NG) are explosives too. Alfred Nobel found a way to stabilize this, in his discovery dynamite. Another highly explosive antianginal drug is Pentaerythrityl tetranitrate or PETN (also spelled Pentaerythritol tetranitrate). This drug (or substance!), a terrorist's pet, is often used in the making of Semtex, a deadly plastic explosive which is very tough to detect. Thus it appears that what appears life saving may be a killer too. By the way, you can safely touch (or kiss) a person who is on PETN or GTN. He (she) won't blow up, I can assure you this.

September 15, 2007

Microtubules: The Cytoskeletal Rail-Road

The cells have a rich cytoskeletal network, consisting of microfilaments, microtubules, intermediate filaments, and proteins that hold them to the interior of the cell. These cytoskeletal structures subserve various functions such as giving the cells its shape and allows small organelles inside the cells to go to other places in the cells. For example, in a nerve cell, the synaptic vesicles, which contain neurotransmitters, are synthesized in the cell bodies. These neurotransmitter filled vesicles are then transported by 'molecular motors' form the cell body to the synaptic knobs, situated at the other end of the neuron.

Not only do they (microtubules) serve as a 'rail line' on which molecular motors move (walk), they also act as 'traction wires' which pull chromosomes apart during cell division (mitosis). Thus in cancer, when cell division is excessive, drugs which interfere with microtubule formation (polymerization) can be employed effectively to curb this cell replication gone haywire. Vinca alkaloids (obtained from the Vinca rosea plant) such as vincristine (used in Hodgkin's Lymphoma, small cell lung cancer etc.), vinblastine (used in ALL or acute lymphoblastic leukemia in children), vinorelbine (used in NSCLC or non small cell carcinoma of the lung); and taxanes such as taxol (paclitaxel, used for the treatment of cancers of the breast and ovary) extracted from the western yew tree, are molecules which stabilize microtubules and thus arrest cell division.

Microtubules are composed of smaller subunits made of proteins, alpha tubulin and beta tubulin. Alpha and beta tubulins together form a heterodimer (hetero since alpha and beta tubulins are different molecules). 13 such hetero dimers join to form a ring and many such rings are joined in a stacked manner to form this hollow structure called microtubules. Microtubules are dynamic structures with one end forming by polymerization (+end) and the other end destroying by depolymerization (-end), as this 10 second video clip illustrates.

August 29, 2007

Height of Compression: Look at this DNA Video

...and you thought that data compression softwares like win zip, 7-zip or win-rar were great! Well, they are; but when you are talking about hardware compression, you just simply can't beat nature at it.

Here, we can see, the DNA molecules, comprising of 4 nitrogenous bases (Adenine, Guanine, Thymine and Cytosine), deoxyribose sugars and phosphoric acid, are packed so compactly, so as to fit into the nucleus. They wrap around the histone proteins, to form nucleosomes, coil upon themselves to ultimately form chromosomes. The reverse of this is to occur, when a cell needs to multiply. To begin with, the heavily folded DNA molecules will need to be unwound first. This is done by enzymes called helicases. When this enzyme is defective (due to a mutation in the helicase gene), the DNA molecule can no longer be unwound. They can no longer be "read and copied" and even 'repaired' as the DNA needs to unfold, to show its faulty codes. Hence, in helicase deficiency, errors accumulate within the DNA molecule and replication is inefficient. This leads to accelerated aging, diseases called segmental progerias. Werner's syndrome (adult onset progerias, seen mostly in the Japanese; often presents with cancer) and Hutchinson-Gilford progeria (childhood onset progerias) are two common examples. In these diseases the persons age very fast; the skin wrinkles faster and there is rapid overall decline in health. There may also be a component of free radical injury or telomere shortening in these diseases. In fact, cells with much shorter telomeres have been observed in these diseases. 

Onto the video now. Its showtime folks!

August 17, 2007

Hayflick limit, Telomere and Aging

DNA double helixWe keep our pens capped so that the pen tips don't get damaged and the ink doesn't dry. Similarly, the DNA in the chromosomal ends are 'capped' by protective molecules, called the telomeres. Telomeres consist of about 1000 repeats of 'TTAGGG" sequence, where T stands for Thymine, A for Adenine and G for Guanine. All these are nitrogen containing molecules (nitrogenous bases).

During replication, the double helical DNA molecule is first unwound by an enzyme called helicase, it is then split by another enzyme, gyrase (=type 2 topoisomerase: it does it by un-twisting the DNA helix in the opposite direction, by introducing negative supercoils, and then makes a nick in one DNA strand, so that it can be copied), and only after all this can DNA polymerase copy the DNA template.

But after each replication, some of this telomere, the so called 'non functional strand' of DNA, is lost. This occurs, since DNA polymerase can not copy one end of the DNA (the 5' end). Thus it has been seen that after about 50 cell divisions, the cell dies (Hayflick limit). When the telomeres are shortened up to a certain limit, the cell sends a signal to p53 protein (known as the guardian of the genome), and the cell then stops dividing and goes into 'replicative senescence'. Stem cells, germ cells and cancerous cells can bypass this limit by the help of telomerase, an enzyme capable of replenishing lost telomeres. Telomerase is actually a reverse transcriptase (normally DNA generates RNA and this process is called transcription. When RNA generates DNA it is thus reverse transcription. In AIDS, another reverse transcriptase wrecks havoc). Telomerase (hTERT= human telomerase reverse transcriptase) and a RNA template (template=dice, just like webpage templates) is enough for telomere reconstruction. However, the idea of restoring telomerase for cellular 'immortality' is not assuring enough as immortality in cells other than stem cells or germ cells means malignancy.

Some substances like alpha hydroxy acids (AHA) glycolic acids, when applied on the skin (face) promotes cell division, thus prompting the growth of new cells, the facial skin gets a cosmetic lift; but due to enhanced cell division, after a certain stage, cells approach the Hayflick limit, and the skin gets aged and wrinkled.

Thus telomerase manipulation should be cautiously weighted against its accompanying risks.

Related article: Aging: From a General and Evolutionary Perspective
Aging, Mitochondria and Free Radicals