Nano-robotics & Biomedical Applications

DR. OLIVER C. EZECHI,MBB5,MPA,FwACS,FMCOG.
CONSULTANT OBSTETRICIAN AND GYNAECOLOGIST
HAVANA SPECIALIST HOSPITAL, LAGOS NIGERIA.

BEING THE TEXT OF LECTURE DELIVERED AT THE
INTERNATIONAL CONFERENCE OF WORLD
TRANHUMANIST ASSOCIATION
ROBO TICS & AFRICA

AT

AIRPORT HOTEL LAGOS NIGERIA-JANUARY 2004
HOSTED BY TRANSHUMANIST ASSOCIATION
OF NIGERIA

INTRODUCTION

Biomedical sciences being a life and dynamic subject continuously explores new frontiers, though I must confess that it is very slow in incorporating this findings into every day practice. The reasons for the slow incorporation ~of new development into medicine are basically three. As a subject dealing with humans, experimentations are strictly controlled by ethical, moral and religious guidelines and respect for human life. The second reason is that training in medicine being through apprenticeship; young graduates guard jealously what they’ve learnt from the masters” and rarely deviate from the norms set by the masters to avoid cristisms and back lash from the masters. Thirdly it takes years of trial from animal to human subjects before it certified free from dangers.

The fears of side effect and adverse out of new drugs are exemplified by the thousands of babies born with phocomelia following the use of thalidomide.

Because of above reasons experimental medicine is almost light years ahead of clinical practice.

In the recent past new technologies have been incorporated into medical practice. This new area includes:

A. FIBRE OPTICS TECHNOLOGY: Utilized in endoscopic medicine.,

Fibre optic instruments are introduce into the body cavity through a tiny hole made on the body to either to investigate or treat and ailments.

B. LASER TECHNOLOGY: Laser technology are utilized in cataract surgery and removal gall bladder stones.

C. TELEMEDICINE: With these facility doctors in remote areas can benefit from the expertise of the specialist urban centres.

D. SOUND WAVES: Utilized in investigative and therapeutic ultrasonography.
E. NUCLEAR RADIATION: Utilized in the treatment of cancer and in investigations like x-ray

In this lecture I will talking about an emerging new frontier which is still at the experimental and theoretical stage - The use of nanotechnolog”i and nanorobotics in biomedical sciences.

MEDICINE TODAY
Physicians today rely chiefly on surgery and drugs to treat illness. Surgeons have advanced from stitching wounds and amputating limbs to repairing heart and repairing of diaphragmatic hernia in utero. The hallmark of medicine up to the present time has been the establishment of a delicate synergy between the tools of the physician/surgeon and those of nature. In most cases, however, one is forced to concede that we doctors .have had to rely chiefly on the body’s own self-repair capabilities. The best example, perhaps, is the recognition that antibiotics will not perform their intended function in the absence of an intact immune system. In clinical practice, patients treatment customarily includes up to six distinguishable phases: examination, diagnosis, prognosis, treatment, validation and prophylaxis.

Examination: The first step in any treatment process. It includes individual’s medical history, personal function and structural baselines, and current complaints. In classical medicine interview and observation have long been the cornerstone of examination. Advancing technology has brought plethora of tests that contribute to accurate diagnosis.
Diagnosis: The determination of the cause and nature of a disease in order to provide a logical basis for treatment and prognosis traditionally the diagnostic process begins with a thorough history taken from the patient and relevant physical examination. Often this sufficed to make a confident diagnosis, but the cause of some illnesses remained uncertain without recourse to additional information such as blood tests or radiological examinations.

Prognosis and treatment: Prognosis Is a judgment or forecast, based upon a correct diagnosis, of the future course of a disease or injury, and of the patients prospects for partial or full recovery. But prognosis Is a function of treatment as well as disease. From the post-Hippocratic era through the 18th century, treatments were almost purely empirical and often did more harm than good. During the 19th and early 20th centuries, treatments were scientific but largely homeostatic—the medical intervention was rational but served mainly to assist the body in healing itself. Throughout the remainder of the 20th century, truly curative treatments began to rescue some patients from conditions from which their unaided bodies would not have been able to recover. 

Validation and prophylaxis: A proper therapeutic protocol will include a procedure for follow-up to ensure that the prescribed treatment was correctly executed with good results. This step is often neglected in order to save costs and may be considered unimportant by some practitioners because approximately 80%-90% of all illnesses, which take patients to the doctor, are self-curing or self-limiting. For example, the common cold, most infectious diseases and many minor injuries are problems that usually will resolve on their own even with no treatment. In these cases the purpose of treatment is not to provide a cure, but rather to speed the healing process, improve comfort, and avoid complications. Prophylaxis is the prevention of disease, typically including patient education, immunization programs, amelioration of occupational hazards, and other preventive and public health measures.

LIMITATIONS OF CURRENT MEDICINE

When the body’s working, building, and battling goes awry, we turn to medicine for diagnosis and treatment. Today’s methods, though, have obvious shortcomings.

A. Crude Methods: Diagnostic procedures vary widely, from asking a patient questions, through looking at X-ray shadows, through exploratory surgery and the microscopic and chemical analysis of materials from the body. Doctors can diagnose many ills, but others remain mysteries. Even a diagnosis does not imply understanding: doctors could diagnose infections before they knew about germs, and today can diagnose many syndromes with unknown causes. After years of experimentation and unfold loss of life, they can even treat what they don’t understand a drug may help, though no one knows why.

Leaving aside such therapies as heating, massaging, irradiating, and so forth, the two main forms of treatment are surgery and drugs. From a molecular perspective, neither is sophisticated.

Surgery is a direct, manual approach to fixing the body, now practiced by highly trained specialists. Surgeons sew together torn tissues and skin to enable healing, cut out cancer, clear out clogged arteries, and even install pacemakers and replacement organs. It’s direct, but if can be dangerous: anesthetics, infections, organ rejection, and missed cancer cells can all cause failure. Surgeons lack fine-scale control. The body works by means of molecular machines, most working inside cells. Surgeons can see neither molecules nor cells, and can repair neither.

Drug therapies affect the body at the molecular level. Some therapies - like insulin for diabetics - provide materials the body lacks. Most - like antibiotics for infections - introduce materials no human body produces. A drug consists of small molecules; in our simulated molecular world, many would fit in the palm of your hand. These molecules are dumped into the body (sometimes directed to a particular region by a needle or the like), where they mix and wander through blood and tissue. They typically bump into other molecules of all sorts in all places, but only stick to and affect molecules of certain kinds.

Antibiotics like penicillin are selective poisons. They stick to molecular machines in bacteria and jam them, thus fighting infection. Viruses are a harder case because they are simpler and have fewer vulnerable molecular machines. Worms, fungi, and protozoa are also difficult, because their molecular machines are more like those found in the human body, and hence harder to jam selectively. Cancer is the most difficult of all. Cancerous growths consist of human cells, and attempts to poison the cancer cells typically poison the rest of the patient as well.

Other drug molecules bind to molecules in the human body and modify their behavior. Some decrease the secretion of stomach acid, others stimulate the kidneys, many affect the molecular dynamics of the brain. Designing drug molecules to bind to specific targets is a growth industry today, and provides one of the many short-term payoffs that is spurring developments in molecular engineering.

B. Limited Abilities: Current medicine is limited both by its understanding and by ifs fools. In many ways, it is still more an art than a science. Mark Pearson of Du Pont points out, “In some areas, medicine has become much more scientific, and in others not much at all. We’re still short of what I would consider a reasonable scientific level. Many people don’t realize that we just don’t know fundamentally how things work. It’s like having an automobile, and hoping that by taking things apart, we’ll understand something of how they operate. We know there’s an engine in the front and we know it’s under the hood, we have an idea that it’s big and heavy, but we don’t really see the rings that allow pistons to slide in the block. We don’t even understand that controlled explosions are responsible for providing the energy that drives the machine.

Better tools could provide both better knowledge and better ways to apply that knowledge for healing. Today’s surgery can rearrange blood vessels, but is far too coarse to rearrange or repair cells. Today’s drug therapies can target some specific molecules, but only some, and only on the basis of type. Doctors today can’t affect molecules in one cell while leaving identical molecules in a neighboring cell untouched because medicine today cannot apply surgical control to the molecular level.

NANOTECHNOLOGY
The possibility of nanorobotics and nanotechnology was first proposed by Nobel prize winner Richard Feynman in his talk in 1959 titled

“There is plenty of room at the bottom”.
While many definitions of nanotechnology exist, the one most widely used is from the US Government’s National Nanotechnology Initiative (NNI). According to the NNI, nanotechnology is defined as:

“Research and technology development at the atomic, molecular and macromolecular levels in the length scale of approximately 1 — 100 nanometer range, to provide a fundamental understanding of phenomena and materials at the nanoscale and to create and use structures, devices and systems that have novel properties and functions because of their small and/or intermediate size.”

More simply put, nanotechnology is the space at the nanoscale (i.e. one billionth of a meter), which is smaller than “micro” (one millionth of a meter) and larger than “pico”(one trillionth of a meter). Nanoparticles 1— 100 nm. In comparison, representative structures and materials found in nature are typically referenced to have the following dimensions:
Atom 0.1 nm
DNA (width) 2 nm
Protein 5—50 nm
Virus 75—100 nm
Materials internalized by cells 100 nm
Bacteria 1,000—10,000 nm
White Blood Cell 10,000 nm

The size domains of components involved with nanotechnology are similar to that of biological structures. For example, a quantum dot is about the same size as a small protein (

NANOMEDICINE
The emerging teld of medical nanorohorics is aimed at overcoming this shortcomings. The medicine and nanorohorics polls within the purview of nanotechnologies. Our bodies are filled with intricate, active molecular structures. Where those structures are managed, health suffers. Modern medicine can affect the works of the body in many ways, but from a molecular viewpoint it remains crude incurred. Molecular manufacturing can construct a range of medical instruments and devices with fat greater abilities. The body is an enormously coming in world of molecules. 

To understand what nanotechnology can do for medicine, we need a picture of the body from a molecular perspective. The human body can be seen as a workyard, construction site, and battleground form molecular machines. It works remarkably well, using systems so complex that medical science still doesn’t understand many of them. Failures, though, are all too common.

Many of the cells are very tiny, but they are very active; they manufacture various substances; they walk around; they wiggle; they fight infection; pump blood and they do all kings of marvelous things- all on a very small scale. They also store information

BIOMEDICAL APPILICATIONS OF NANOROBOTICS
The enormous potential in the biomedical capabilities of nanorobots and the imprecision and side effects of medical treatments today make nanorobots very desirable. Medical treatment today involves the use of surgery and drug therapy. Surgery is a direct, manual approach to fixing the body. However, no matter how highly trained the specialists may be, surgery can still be dangerous since anesthetics, infections, organ rejection, and missed cancer cells can all cause failure. Surgeons lack fine-scale control. From the perspective of a cell, a fine surgical scalpel is as crude as a blunt tool. Invasive surgery wounds peripheral tissue and causes unnecessary harm to the patient.

Drug therapy affects the body at the molecular level. Drug molecules are dumped into the body where they are transported by the circulatory system. They may come into contact with un-targeted parts of the body and lead to unwanted side effects. Nanomedical robots, however, will have no difficulty identifying cancer cells and will ultimately be able to track them down and destroy them wherever they ma~ be growing. This is why the medical profession is looking towards the use of biomedical, nanotechnological engineering to refine the treatment of diseases.

PROPERTIES OF NANOMEDICAL ROBOTS

Nanorobots will typically be .5 to 3 microns large with 1-100 nm parts. Three microns is the upper limit of any nanorobot because nanorobots of larger size will block capillary flow. The nanorobot’s structure will have two spaces that will consist of an interior and exterior. The exterior of the nanorobot will be subjected to the various chemical liquids in our bodies but the interior of the nanorobot will be a closed, vacuum environment into which liquids from the outside cannot normally enter unless it is needed for chemical analysis. A nanorobot will prevent itself, from being attacked by the immune system by having a passive, diamond exterior. The diamond exterior will have to be smooth and flawless because past experiments have shown that this prevents Ieukocytes activities since the exterior is chemically inert and have low bioactivity. Nanorobots will communicate with the doctor by encoding messages to acoustic signals at carrier wave frequencies of 1-100 MHz. When the doctor gives a command to the nanorobots, the nanorobots can receive the message from the acoustic sensors on the nanorobots and implement the doctor’s orders. Replication is a crucial basic capability for molecular manufacturing. However, in the case of nanorobots, we should restrict manufacturing to in vitro (in laboratory) replication. Replication in the body (in vivo) is dangerous because it might go out of control. If even replicating bacteria can give humans so many diseases, the thought of replicating nanorobots can present unimaginable dangers to the human body. When the nanorobots are finished with their jobs, they will be disposed from the body to prevent them from breaking down and malfunctioning.

PRINCIPAL NANOROBOTIC APPLICATIONS

The availability of advanced nanomedical instrumentalities should not significantly alter the classical medical treatment methodology, although the patient experiences and outcomes will be greatly improved. Treatment in the nanomedical era will become faster and more accurate, efficient and effective.

A. DRUG DELIVERY

Nanotechnology provides a wide range of new technologies for developing customized solutions that optimize the delivery of pharmaceutical products.

To be therapeutically effective, drugs need to be protected during their transit to the target action site in the body while maintaining their biological and chemicals properties. Some drugs are highly toxic and can cause harsh side effects and reduced therapeutic effect if they decompose during their delivery. Depending on where the drugs will be absorbed (i.e. colon, small intestine, etc), and whether certain natural defense mechanisms need to be passed through such as the blood-brain barrier, the transit time and delivery challenges can be greatly different. Once a drug an-ives at its destination, it needs to be released at an appropriate rate for it to be effective. If the drug is released too rapidly it might not be completely absorbed, or it might cause gastro-intestinal irritation and other side effects. The drug delivery system must positively impact the rate of absorption, distribution, metabolism, and excretion of the drug or other substances in the body. In addition, the drug delivery system must allow the drug to bind to its target receptor and influence that receptor’s signalling and action, as well as other drugs, which might also be active in the body.

Drug delivery systems also have severe restrictions on the materials and production processes that can be used. The drug delivery material must be compatible and bind easily with the drug, and be bioresorbable (i.e. degrade intofragments after use which are either metabolized or eliminated via normal excretory routes). The production process must respect stringent conditions on processing and chemistry that won’t degrade the drug, and still provide a cost effective product.

Nanotechnology can offer new drug delivery solutions in the following areas.

1. Drug Encapsulation

One major class of drug delivery systems is materials that encapsulate drugs to protect them during transit in the body. Drug encapsulation materials include liposomes and polymers (i.e. Polylactide (PLA) and Lactide-co-Glycolide (PLGA)) which are used as microscale particles. The materials form capsules around the drugs and permit timed drug release to occur as the drug diffuses through the encapsulation material. The drugs can also be released as the encapsulation material degrades or erodes in the body.

Nanoparticle encapsulation is also being investigated for the treatment of neurological disorders to deliver therapeutic molecules directly to the central nervous system beyond the blood-brain barrier, and to the eye beyond the blood-retina barrier. Applications could include Parkinson’s, Huntington’s, Alzheimer’s, ALS and diseases of the eye.

2. Functional Drug Carriers

Another class of drug delivery systems where nanotechnology offers interesting solutions is in the area of nanomaterjals that carry drugs to their destination sites and also have functional properties. Certain nanostrucfures can be controlled to link with a drug, a targeting molecule, and an imaging agent, then attract specific cells and release their payload when required.

B. DRUG DISCOVERY

Nano and micro technologies are part of the latest advanced solutions and new paradigms for decreasing the discovery and development times for new drugs, and potentially reducing the development costs. Traditional trial-anderror methods have contributed to a discovery process lasting 10 years or more for new drugs to reach the market. In recent years, a number of new and complementary technologies have been developed which considerably impact the drug discovery process.

High-throughput arrays and ultra-sensitive labeling and detection technologies are being used to increase the speed and accuracy of identifying genes and genetic materials for drug discovery and development. These micro and nano technologies along with information technology solutions such as combinatorial chemistry, computational biology, computer-aided drug design, data mining, and data processing tools are addressing the challenges related to eliminating critical bottlenecks in drug discovery replacement. While most types of tissues repair the interaction of stem cells with chemical modulators, there are differences in the ways that various tissues heal.

“Hard” tissues such as bone and teeth heal by reproducing tissues indistinguishable from the original. However in cases where a dental or artificial bone implant is required, the structural material used in the implant may trigger immune rejection, corrode in the body fluids, or no longer bond to the host bone. This can require additional surgery or result in the loss of the implant’s function. In many cases, the failure occurs at the tissue-implant interface, which may be due to the implant material weakening its bond with the natural material.

To overcome this, implants are often coated with a biocompatible material to increase their adherence properties and produce a greater surface area to volume ratio for the highest possible contact area between the implant and natural tissue. “Soft” tissues such as skin, muscle, nerves, blood vessels and ligaments repair damaged areas with fibrous tissue. Damaged tissue from various sources such as burns and ulcers can be self-repaired by the body, but can also result in scar formation. Graft material using artificial sheets can replace skin and other tissue with reasonable graft stability and cosmetic outcome.

Nanotechnology can new offer new solutions for tissue repair and replacement in the following’ areas.

C. IMPLANTABLE DEVICS

Nanotechnology offers sensing technologies that provide more accurate and timely medical information for diagnosing disease, and miniature devices that can administer treatment automatically if’ required. Health assessment can require medical professionals, invasive procedures and extensive laboratory testing to collect data and diagnose disease. This process can take hours, days or weeks for scheduling and obtaining results. Some medical information is extremely time sensitive such as finding out if there is sufficient blood flow to an organ or tissue after transplant or reconstructive surgery, before irreversible damage occurs.

Certain medical tests such as biopsies are subjective and can provide inconclusive or incorrect results. In a false negative result where a needle misses the tumor and then samples a normal tissue, the cancer nay go untreated and can impact a patient’s chances for long-term survival.

Some tests such as diabetes blood sugar levels require patients to administer the test themselves to avoid the risk of their blood glucose falling to dangerous levels. Certain users such as children and the elderly may not be able to perform the test properly, timely or without considerable pain.

People who are exposed to radiation or hazardous chemicals in their work environment are at a higher risk of illness. Occasional testing is typically done but may not detect a disease in its early stage. Early detection could initiate timely treatment with a higher chance of success, and have a worker removed from the hazardous environment to prevent further damage.

Nanotechnology can new offer new implantable and/or wearable sensing technologies that provide continuous and extremely accurate medical information. Complementary microprocessors and miniature devices can be incorporated with sensors to diagnose disease, transmit information and administer treatment automatically if required.

Example applications are as follows.

I Retina Implants

Retinal implants are in development to restore vision by electrically stimulating functional neurons in the retina One approach being developed by various groups including a project at Argonne National Laboratory is an artificial retina implanted in the back of the retina. The artificial retina uses a miniature video camera.

2 Cochlear Implants
A new generation of smaller and more powerful cochlear implants are intended to be more precise and offer greater sound quality.

D. SURGICAL AIDS

1 Operating Tools

Medical devices that contain nano and micro technologies will allow surgeons to perform familiar tasks with greater precision and safety, monitor physiological and biomechanical parameters more accurately, and perform new tasks that are not currently done.

2 Surgical Robotics

Robotic surgical systems are being developed to provide surgeons with unprecedented control over precision instruments. This is particularly useful for minimally invasive surgery. Instead of manipulating surgical instruments, surgeons use their thumbs and fingers to move joystick handles on a control console to maneuver two robot arms containing miniature instruments that are inserted into ports in the patient. The surgeon’s movements transform large motions on the remote controls into micro-movements on the robot arms to greatly improve mechanical precision and safety.

E DIAGNOSTIC TOOLS

1 Genetic Testing

Nano and micro technologies provide new solutions for increasing the speed and accuracy of identifying genes and genetic materials for drug discovery and development, and for treatment-lnked disease diagnostics products.

dyes are not always precise or sufficiently sensitive

3Ultra-sensitive Labeling and Detection Technologies
Several new technologies are being developed to improve the ability to label and detect unknown target genes. At Genicon, gold nanoparticle probes are being treated with chemicals that cling to target genetic materials and illuminate when the sample is exposed to light.
Killing cancer cells.

The device would circulate freely throughout the body, and would periodically sample its environment by determining whether the binding sites were or were not occupied. Occupancy statistics would allow determination of concentration. Today’s monoclonal antibodies are able to bind to only a single type of protein or other antigen, and have not proven effective against most cancers. The cancer killing device suggested here could incorporate a dozen different binding sites and so could monitor the concentrations of a dozen different types of molecules. The computer could determine if the profile of concentrations fit a pre-programmed “cancerous” profile and would, when a cancerous profile was encountered, release the poison.

Beyond being able to determine the concentrations of different compounds, the cancer killer could also determine local pressure.

By using several macroscopic acoustic signal sources, the cancer killer could determine its location within the body much as a radio receiver on earth can use the transmissions from several satellites to determine its position (as in the widely used GPS system). .

The cancer killer could thus determine that it was located in (say) the big toe. If the objective was to kill a colon cancer, the cancer killer in the big toe would not release its poison. Very precise control over location of the cancer killer’s activities could thus be achieved. The cancer killer could readily be reprogrammed to attack different targets (and could, in fact, be reprogrammed via acoustic signals transmitted while it was in the body). This general architecture could provide a flexible method of destroying unwanted structures (bacterial infestations, etc).

Providing oxygen

A second application would be to provide metabolic support in the event of impaired circulation. Poor blood flow, caused by a variety of conditions, can result in serious tissue damage. A major cause of tissue damage is inadequate oxygen. A simple method of improving the levels of available oxygen despite reduced blood flow would be to provide an “artificial red blood cell of about a day by about a liter of small spheres.

As oxygen is being absorbed by our artificial red blood cells in the lungs at the same time that carbon dioxide is being released, and oxygen is being released in the tissues when carbon dioxide is being absorbed, the energy needed to compress one gas can be provided by decompressing the other. The power system need only make up for losses caused by inefficiencies in this process. These losses could presumably be made small, thus albwing our artificial red blood cells to operate with little energy consumption conditions of temperature and pressure. Thus, our spheres are over 2,000 times more efficient per unit volume than blood; taking into account that blood is only about half occupied by red blood cells, our spheres are over 1,000 times more efficient than red blood cells.

Artificial mitochondria

While providing oxygen to healthy tissue should maintain metabolism, tissues already suffering from ischemic injury (tissue injury caused by loss of blood flow) might no longer be able to properly metabolize oxygen. In particular, the mitochondria will, at some point, fail.

15

Increased oxygen levels in the presence of nonfunctional or partially functional mitochondria will be ineffective in restoring the tissue. However, more direct metabolic support could be provided. The direct release of ATP, coupled with selective release or absorption of critical metabolifes (using the kind of selective transport system mentioned earlier), should be effective in restoring cellular function even when mitochondrial function had been compromised. The devices restoring metabolite levels, injected into the body, should be able to operate autonomously for many hours ~depending on power requirements, the storage capacity of the device and the release and uptake rates required to maintain metabolite levels).

8. Further possibilities

While levels of critical metabolites could be restored, other damage caused during the ischemic event would also have to be dealt with. In particular, there might have been significant free radical. damage to various molecular structures within the cell, including its DNA. If damage was significant restoring metabolite levels would be insufficient, by itself, to restore the cell to a healthy state. Various options could be pursued at this point. If the cellular condition was deteriorating (unchecked by the normal homeostatic mechanisms, which presumably would cease to function when cellular energy levels fell below a critical value), some general method of slowing further deterioration would be desirable.

Cooling of the tissue, or the injection of compounds that would slow or block deteriorative reactions would be desirable. As autonomous molecular machines with externally provided power could be used to restore function, maintaining function in the tissue itself would no longer be critical. Deliberately turning off the metabolism of the cell to prevent further damage would become a feasible option. Following some interval of reduced (or even absent) metabolic activity during which damage was repaired, tissue metabolism could be restarted again in a controlled fashion.

It is clear that this approach should be able to reverse substantially greater damage than can be dealt with today. A primary reason for this is that autonomous molecular machines using externally provided power would be able to continue operating even when the tissue itself was no longer functional. We would finally have an ability to heal injured cells, instead of simply helping injured cells to heal themselves.

CONCLUSION

All of these current developments in technology directs humans a step closer to nanorobots and simple, operating nanorobots is the near future. Nanorobots can theoretically destroy all common diseases of the 2lstcenturythereby ending much of the pain and suffering. It can also have (alternative, practical uses such as improved mouthwash and cosmetic creams that can expand the commercial market in biomedical engineering. People can envision a future where people can self-diagnose their ‘own ailments with the help of nanorobot monitors in their bloodstream. Simple everyday illnesses can be cured without ever visiting the physician. lnvasivesurgery will be replaced by an operation carried out by nano-surgical robots. Although research into nanorobots is in its preliminary stages, the promise of such technology is endless.

Posted by Santiago Ochoa on 2004/06/21 • (0) Comments
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