Anesthesia And Asbestos.

The anesthetic of choice is Isoflurane (also known as Forane). This anesthetic is effective through inhalation. The 30% v/v isoflurane in propylene glycol (1,2-Propanediol USP grade Sigma Cat no. P4347) can be administered through a nose cone system and can anesthetize the rats for a minimum of 8 minutes. The dosage of the anesthetic which is under consideration is 4% to anesthetize the rats, followed by 2% to retain the effect of the anesthetic. Multiple sources claim that administering Isoflurane requires a precision vaporizer, while others claim that a nose cone can be used for administering the anesthetic. Just to be completely sure, I’m delving deeper into both options. I will also try and ask a professional veterinarian about this for another opinion. ( a new post to come certainly)

The proper dosage of the crociodolite can only be determined from previous experimentation that involved the same carcinogen. This article states that 25 mg of crociodolite induced tumors in the rats within 6-24 months. Other doses included 50 mg, 2 mg, 50 µg and 100 µg (please refer to the graphs on page 5 for 50 µg and 100 µg)…the spectrum is clearly rather broad. However, the article above that has been included for reference was written to describe an experiment considerably similar to this one– but differs by its rather more emphasis on the toxicology and pathology analysis if the carcinomas/ carcinogen asbestos in the peritoneum– states that the rats contracted tumors in between 6-24 months with corresponding dosages of particular asbestos, and because this experiment will not last 6-24 months, it seems the dosage we will be using is at least 50 mg.

One possibility to induce the carcinogen in a more controlled fashion (in the sense administration of asbestos can be ualted or continued with he previous dosage) is to administer the carcinogen gradually over a period of time. For example, 1 mg may be administered the first week, and then 2 mg the next week, and then 4 mg the week after, etc. until signs of cancerous growth are imminent. The opposite is also possible: we could begin with 50 mg and then gradually lower how much crociodolite is administered week by week (45 mg the next week, 40 mg the week after, 35 mg after that, etc.). Either method (I personally find the latter to be more effective because it is evident that a relatively greater amount of the carcinogen will need to be administered for quicker effect) will help to determine when a proper amount of the carcinogen has finally been administered to the rats to prevent an overdose of, or too little, crociodolite. However, these methods do introduce another manipulated variable, if we have 2 variable groups hence the difference between the variable groups is a manipulated variable and the increasing or decreasing dosage gradients is another manipulated variable. It could raise an argument to the fact that since we are solely centering the project as an analytical model around irregular tissue growth in one specific organ, we only need visually apparent tumors in the CT to verify our method. We are not studying the effects of different dosages just using rats with mesothelioma to conjure a model that simulates living tissue with cancer. Mesothelioma induced with asbestos just ended up to be the best candidate.

The intraperitoneal injection is still what will likely be used to administer the crociodolite to the rats. 50 mg of crociodolite, for example, could be suspended in 2 mL of NaCl. 2 mg of crociodolite would be suspended in 2 mL of 0.9% NaCl. Saline, as mentioned in the “Thoughts For Experimentation” post on the “Biological Aspect” page, will most likely serve as the type of solution to be mixed with the crociodolite for an effective injection.

An Informal Introduction to Mesothelioma.

This is an informal, general overview of Mesothelioma. Descriptions here are taken directly form 3rd party sources for a general over view. Specific, more in depth technical details form more accurate sources will be given in due time as issues present themselves and require more detail into such specifics. Please note, the following is from Wikipedia.com for a quick reference to the topic, Specific details on this post should be viewed with caution because of the origin of this text. The purpose of this post is to establish a rough foundation to anticipated formal introduction to come on Mesothelioma.

Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, and do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Mesothelioma is a form of cancer that is almost always caused by exposure to asbestos. In this disease, malignant cells develop in the mesothelium ( the membrane that forms the lining of several body cavities), the pleura (body cavity that surrounds the lungs), peritoneum (abdominal cavity including the mesentery) and pericardium (heart sac). Its most common site is the pleura, but it may also occur in the peritoneum (the lining of the abdominal cavity), the heart, or the pericardium (a sac that surrounds the heart). The mesothelium consists of a single layer of flattened cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Note the epithelial layer is also known as mesothelium, Deposition of asbestos fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages (white blood cells within tissues, produced by the division of monocytes – another type of white blood cell) and other cells of the immune system to localized lesions (abnormal tissue) of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.

Asbestosis a naturally occurring silicate mineral with long, thin fibrous crystals. Blue Asbestos, also known as Crocidolite, CAS No. 12001-28-4 is an amphibole found primarily in southern Africa, but also in Australia. Asbestos became more widespread during the industrial revolution; in the 1860s it was used as insulation in the U.S. and Canada. Development of the first commercial asbestos mine began in 1879 in the Appalachian foothills of Quebec. By the mid 20th century uses included fire retardant coatings, concrete, bricks, pipes and fireplace cement, heat, fire, and acid resistant gaskets, pipe insulation, ceiling insulation, fireproof drywall, flooring, roofing, lawn furniture, and drywall joint compound. Approximately 100,000 people in the United States have died, or will die, from asbestos exposure related to ship building. In most developed countries, asbestos is typically disposed of as hazardous waste in landfill sites. Asbestos can also be recycled by transforming it into harmless silicate glass.

A benefit to our alternative

I just realized another benefit to using MRI’s if rats do not work out.  Once we have created a model using the method listed previously, we can begin our testing right away. All that we would require would be a mixture of a few MRI’s consisting of healthy lungs ( if a person got an MRI scan for liver cancer, then their lungs would be fine) and lungs in the very beginning stage of cancer( preferably ones that are very difficult even for the MRI to detect, because we are trying to show how our method is superior). WE could then use the model we created on these sets of lungs. WE ask the doctor not to tell us which were cancerous, run our tests using whatever method we decide on, and then decide ourselves which are cancerous and which aren’t. Then we see if our modeling worked, by checking our flagged sites with the doctors. This gives us a percent of success without having to actually track rats through their stages of development. I don’t know whether this is a good or bad idea, but it is an idea so I decided to post it. Feel free to comment

- Chris

Lung Carcinogens in Rats.

Well I thought, if we are considering the lung organ for investigation for lung cancer, what would be a good lung carcinogen to study, since the lungs have a fractal pattern they are a fair candidate to compete for which organ we specifically target to test our model with.

I found Carcinogencity by Kirk T. Kitchin to be very useful. On page 542 Section B It catagorizes rodent pulmenary carcinogens into 3 sections: 

1. Organic
   1. Theses are in the form of variety of vapors, aerosols, and dusts such as Table 8 suggests Tetranitromethane is positive carcinogen on rats, an organic compound in vapor form. Along with lung cancer, some of these types of carcinogens also induce nasal tumors and in vinyl chloride other organs are seriously affected.
   2. I think we should look into the organic carcinogens that ONLY tested positive for rats as a starting point for consideration for a ‘good’ carcinogen to use in this study, and the carcinogen that only targets the lungs not as well as other organs. 
   3. (By the way mustard gas was listed as a carcinogen in that book)
2. Inorganic
   1. Here it says lung cancer can be also induced by heavy metal inhalation. It further identifies that “the chemical form of the metal is a major factor and relates to its solubility of the compound.” This source claims that not only is solubility a source of carcinogenicity, but also particle size (as tested by finely divided particles of Titanium Dioxide vs larger particles, the bigger the more toxic.) Non metallic carcinogens however are not as toxic as metal carcinogens and take much more time to significantly develop, I guess this could be one other type we could consider to minimize the damage/ harm done to the rodent: minimize the carcinogen of a weak carcinogen with minimal affects in a short time. I am wondering….. this way the ray may ….live?
3. Complex Mixtures
   1. This category consists of the different types of radioactive materials/ compounds that induce cancer in rodents. This category is further divided in to the types of emissions the carcinogens have, Alpha, Beta, and third is plain Radon gas. This is another carcinogen that we may consider, radioactive substances that target adjacent cells. Introduce these carcinogens to the lungs and primarily, if not only, the lungs will get affected. 
   2. Lastly, mixture of gases that induce carcinogen include inorganic and organic substances found in diesel exerts, cigarette smoke, and other pollutants. 

It is sad because not all of the book is available for viewing, we must get a copy of this book if we are to go towards the rat route.

I have also decided to eliminate sex organs and the carcinogens that associate/ target them because I can’t think of any sex organ of a rat especially that would have a fractal pattern. So here is a post about the lung carcinogens.

PS: Chris I think you will like the short read form 542-546, it is biochemistry, have a look.

We’re in a pickle

 

Ok so here is the rambling train of though of a tired thinker trying to find alternatives to a potentially dead end.  Apparently ISEF rules number 3 and 4  might prevent us from using rats to determine our raw data. Our fall back was to get a hold of some MRI’s of a tissue over a period of time from healthy to cancerous. Unfortunately most people do not get MRI’s until they do have cancer. So in the case that we can only get MRI’s of people who already have cancer here is what i propose we do.  Let us say we have an image that looks like this                                                                      —————————                                                                                                                             

                                                                             ———                ———    

                                                                              —   —                   —   —                                                                                                                                     

                                                        - -  – -                 – -   - -

Now let’s pretend these separations represent the branching of a lung (which is a fractal pattern). Now lets say we are extraordinarily unlucky and the cancer has progressed rather far, and the whole right side is now useless to us ( we need a healthy long to come up with the base pattern).  Luckily, because it is a fractal we can magnify the left side, and get an exact replication of the lung. This means that we can derive the same pattern we could with a whole lung, with only the need of one extra magnification.  Of course this whole idea relies on  being able to get clear images with an MRI.

So this is my proposal to an alternate route should our original idea dead end. This too has a possibility to dead end but at least it’s an alternative.  Please ignore the blaringly obvious grammatical and mechanical mistakes as this is a post late at night when my brain tends not to stop for the pity of grammar. It also tends to ramble if you cannot already tell .

 

Indeed we are in a big pickle

Indeed  we are in a big pickle

Carcinogen’s Liver and Kidney

The following site has an extrodanary wealth of information. Unfortunatly i dont know how to make use of it. It has Does, times, precents of tumor growth, and drug used….but i dont know how to read it. Here it is try for yourself maybe youll have better luck. Uber Link

The triphenylethylene drug tamoxifen is a strong liver carcinogen. Unfortuantly it took up to six months of high dosage (45.2 mg/kg body weight/day) for cancers to be observed in about 29 % of the rats. I do not think this will work becuase we are short on time….

Dont know what to make of this link, but i think it suggests that rats are naturally suceptable to liver and kidney caner. If this is true it would remove the need for a carcinogen and make matters much easier.

This is a set of links to websites i find useful, and sites that should be tracked for bibleographical purposes.

online journal

http://carcin.oxfordjournals.org/cgi/content/abstract/14/2/315

Carcinogens.

1. Which organs have fractal patterns (look at Biological aspect)
2. Which carcinogen to Use with the organ in question.
3. Dosage, time intervals to see visible growth in 3-4 month period.  

How MRI’s Work.

The following is my understanding of how MRI’s work after some research on the subject area. Some of the information goes into areas that I do not have a great depth of knowledge, and there for might be slightly off. However, I believe that I have a solid understanding of the basics. Feel free to correct or comment on anything. I will try to not to use technical jargon, but if you need me to elaborate on anything just leave a comment. Thanks

                MRI’s rely heavily on the paramagnetic property of the hydrogen atom.  Being paramagnetic means that not all of the orbital’s in an energy level are filled.  This means that there is a net spin in the electrons.  Each orbital can have two electrons spinning in opposite directions which cancel each other out, however because electrons fill each orbital before they pair up, it is common to have orbital’s with only one electron, one spin, and therefore a net spin  This spin creates a magnetic moment that allows it to be manipulated by a magnetic field.  MRI’s manipulate these magnetic moments, by using the paramagnetic properties of the hydrogen atom and very powerful magnets.  The main electromagnet in an MRI is turned on so that all of the hydrogen atoms align in one of two ways. Most of them arrange in the longitudinal plane parallel to the electromagnetic field. Next a radio frequency tuned to a frequency know as the larmor frequency is directed at a location on the body. This frequency destroys the polarization frequency forcing the hydrogen atom to rearrange perpendicular to the external electromagnetic field ( the one produced by the main magnet).  Then when this RF (radio frequency) is turned off, the hydrogen atoms return to their normal position.  The amount of time it takes to return to their normal position is known as T₁ relaxation time, and varies with different tissues.T₂ is a measurement of a radio frequency ( similar to Lamoure) given off by the oscillation of the hydrogen atoms as they return to their original position. This process is also known as free induction decay(FID), and creates a current that is regocnized by the MRI. The T₂ varies depending on the tissue ( I believe this has to do with different electro magnetic interference based on spatial location in the body, but i am not completly sure ehh..). The MRI’s magnets are capable of measuring the time of T₁ ( time it takes for atoms to return parallel to external field) and the current produced by T₂ (FID)to reproduce an image of the body. The variation in time of T₁ and the variation of the current produced by the FID of T₂  are dependent of the tissue from which T₁ and T₂ are measured. This variation is what allows the MRI to show such great contrast of tissues.  Also because cancerous tissues have different properties, they are easily spotted by their discoloration from normal tissues on the MRI.

                That is the premise on which the MRI works, and I will discuss the disadvantages to this system and how our method of fractal detection has a possibility to be more useful on a later date.

To Do List.

1. How MRI machines work, CT scans, Ultrasound scans, and Electron Microscopy and what each one is generally used for.
2. The current method used to detect cancer, specifically suspicious tissue. (Key word Euclid geometry)
3. Lab tests associated with specific cancers, see if a sample of tissue is actually “cancerous.”
4. Chemotherapy, all sorts.
5. Confocal Microscopes.
6. Carcinogens:
   1. Rat carcinogens, organ specific.
   2. Method to diagnose cancer on animals.
   3. Accumulation of other research and their procedure on trials with animals under observations with cancer. 
7. Any other research and its procedures that used fractal geometry to diagnose cancerous tumors.