“Vasile Alecsandri” High School, Galati, Romania
The world fungus often brings to mind such unsalutary and fearsome growths as the white fuzz on a loaf of stale bread and the mildew in a moist shower stall. Farmers know fungal parasites can devastate food crops such as corn, rice, wheat and rye. But some types of fungi are not only not harmful, they are healing--notably, certain varieties of mushrooms.
Scientists have named 100,000 different species of fungi, and there are many more that have yet to be classified. While you wouldn't want to ingest many members of the fungi kingdom, some mushrooms have been valued throughout the world--particularly Asia--as both food and medicine for centuries. The Chinese, for instance, have used and revered many fungi as tonics for the immune system for more than 3,000 years, while in Japan, pushcart vendors on the streets still sell medicinal mushrooms to average citizens, who use them to maintain health and promote longevity.
One of the key conclusions that has come out of both laboratory and human clinical studies is that a number of compounds in fungi can stimulate the function of the immune system and inhibit tumor growth. In particular, compounds called polysaccharides, which are complex chain-like molecules built from many smaller units of sugar molecules, have been intensively studied since the 1950s. Their antitumor and immuno-stimulating properties have been proven repeatedly.
Further on in our project we are going to elaborate on some of the medicines developed from mushrooms:
Penicilllin
Penicillin is defined as any antibiotic drug taken from molds or made synthetically to treat different diseases and/or infections. More specifically, penicillin is the liquid which is secreted from penicillium notatum, which is the mold.
Penicilin's structure
How Penicillin was Discovered
Penicillin was discovered by complete accident in 1928 by Alexander Fleming, a medical scientist. Fleming was actually studying the different strains of staphylococci (a bacteria which causes various infections), so he had germs growing in numerous petri dishes. He added a layer of agar jelly on the bottom of each dish; this jelly would then cause the bacteria to multiply, as it was the food for bacteria. Eventually, this bacteria would develop into a spot you could see without a microscope.
Like many other scientists, Fleming had difficulty keeping germs from the air out of his bacteria cultures, and noticed this in particular in one sample. As he was looking at his samples, he noticed something important in one of them: one of his cultures had become contaminated by some kind of mold from the air. This mold, now a large spot, had a radius all around it where there was no staphylococci bacteria left. The mold had cleared the zone of bacteria surrounding it and looked like it was secreting a toxin which ate up all of the germs in its path.
Culture of peniciline
Fleming immediately set to studying and growing more of what eventually became penicillium notatum, and discovered that it belonged to the same family of molds as you find on stale bread or decayed fruit. He also found that it stopped the growth of most common disease germs. Sometimes, it would completely dissolve the germs so there were no longer any around that area.
The Journey from "Mold" to "Cure"
Though Fleming’s discovery was published, little attention was paid to him until ten years later by an Australian doctor named Howard Florey (of the University of Oxford). Florey believed that there was an antibiotic stronger than Sulfa drugs, so he was quite interested in Fleming’s finds.
Obtaining strains of penicillium notatum from Fleming (which he had kept alive from the original strain), he enlisted the help of a chemist by the name of Ernst Chain. The two then went about creating a purified form of penicillin. Months later, their hard work paid off; they then had enough purified penicillin to run tests on mice. Amazing success was found in the mice that they had given penicillin.
From the mice, they eventually advanced on to a human test. They tested the penicillin out on a forty-three year old policeman who had a bad case of blood poisoning. Within the twenty-four hours of giving the man the penicillin, he showed remarkable recovery and continued to grow healthier until they ran out of penicillin. Before they could get him a new supply, he grew worse and finally died.
Just years before, Florey only had a small team and few ways of creating penicillin. Now, with the help of many American scientists, chemists, etc. working on project penicillin, they could help save millions of lives. They didn’t know that in 1959, productions could be bigger than ever because they then began testing synthetically made penicillin (this meant getting penicillin directly from chemicals instead of mold).
What Penicillin Treats
Some of the diseases/illnesses that penicillin treats includes: pneumonia, meningitis, erysipelas, scarlet fever, diphtheria, blood poisoning, syphilis, gangrene, strep throat and gonorrhea.Penicillin works to treat illnesses/diseases by killing bacteria and arresting its growth. It only kills the bacteria that is growing and reproducing, not those which are stationery.
The Growth Process of Penicillin
A penicillin colony will begin looking like a fluffy white mass, almost resembling a cotton ball. A few days later, the colony will turn dark green. As it is turning green, it is also secreting bright yellow drops of liquid. This liquid is what we call penicillin.
Cyclosporin
The discovery of cyclosporin in 1971 began a new era in immunopharmacology. It was the first immunosuppressive drug that allowed selective immunoregulation of T cells without excessive toxicity. Cyclosporin was isolated from the fungus Tolypocladium inflatum.
Scanning electron micrograph of Tolypocladium inflatum
Cyclosporin was first investigated as an anti-fungal antibiotic but its spectrum was too narrow to be of any clinical use. J. F. Borel discovered its immunosuppressive activity in 1976.This led to further investigations into its properties involving further immunological tests and investigations into its structure and synthesis. Cyclosporin has unwanted side effects, notably nephrotoxicity. Animal testing showed cyclosporin to be sufficiently non-toxic to begin clinical trials. These initially failed due to poor absorption of the drug. Once this had been overcome, results were encouraging enough for cyclosporin to be licensed for use in clinical practice, routine transplantation of organs that until then had only been done experimentally.
What is cyclosporin and what are its uses?
Today organ and bone marrow transplants are routinely performed. Cyclosporin is still used to treat the rejection reactions that occur when a foreign organ is attacked by the body’s immune system.
Cyclosporin is at present approved for use in organ transplantation to prevent graft rejection in kidney, liver, heart, lung and combined heart-lung transplants. It is used to prevent rejection following bone marrow transplantation and in the prophylaxis of host-versus-graft disease. It is also used in the treatment of psoriasis, atopic dermatitis, rheumatoid arthritis and nephrotic syndrome.
The discovery of immunosuppression by cyclosporin in 1976 is attributed to J. F. Borel.
J. F. Borel
In 1983 cyclosporin was approved for clinical use to prevent graft rejection in transplantation. Most of the surgical problems of allograft transplantation had already been solved by this time. Since 1961 the standard method of achieving immunosuppression had been a combination of azathioprine and corticosteroids. Azathioprine inhibits cell proliferation non-selectively. Its main unwanted side effect is depression of the bone marrow, other toxic effects include increased susceptibility to infections, a mild hepatotoxicity, skin eruptions, nausea and vomiting. Corticosteroids inhibit T lymphocytes and have an anti-inflammatory effect. Side effects include diabetes, avascular necrosis of bones and increased tendency to infections.
Cyclosporin was the strongest immunosuppressor to be discovered so far, it also overcame many of the risk factors associated with azathioprine and is relatively non-toxic to bone marrow. With the introduction of cyclosporin patient morbidity fell. It became possible to transplant organs with a one year success of 20% higher than previously, and to transplant organs successfully which previously had only been done in experimentation: the heart, the liver, the lung and combined heart lung transplants.
As well as transplantation, cyclosporin has been used in most autoimmune diseases. In the 1980’s experimental treatment with cyclosporin of insulin-dependent diabetes mellitus, inflammatory bowel disease, chronic asthma, atopic dermatitis, aplastic anaemia and psoriasis supported evidence of their T cell mediated nature.
SYNTHESIS
In 1984 synthetic cyclosporin was produced.It was then possible for cyclosporin to be chemically modified in every possible way. However, none of the derivatives have been found to have greater potency or decreased side effects than cyclosporin itself. The two major limitations of cyclosporin therapy today remain its nephrotoxicity and incomplete control of chronic rejection.
In 1996 undergraduate mycology students from Cornell University on a field trip to Ithaca, New York were told to pick up anything that looked interesting. Among the findings was a mysterious fungal fruiting body in an eviscerated beetle grub. The fungus was later identified as Cordyceps subsessilis an extremely rare fungus that is the sexual state of Tolypocladium inflatum. All the cyclosporin had so far been made from Tolypocladium inflatum cultures without it ever reaching the sexual state. Cordyceps is a large genus that includes around 280 species, and may be a good place to start looking, in the estimated 90% of world fungi that have yet to be identified, for a new and improved transplantation drug.
CONCLUSIONS
Discovery of cyclosporin led the way to an era of selective lymphocyte inhibition. It enabled the expertise in clinical, technical and immunobiological aspects of transplantation to be put into practice and changed the face of transplantation. Its contribution to autoimmune therapy is less well known but in the long term will probably be of comparable importance.
Cyclosporin did not solve all the problems of transplantation. Today chronic rejection is the main problem. It is poorly understood and there is no treatment for it, although it is thought to have a large immunological component. The majority of transplant patients require long term treatment with high doses of immunosuppressives which increases susceptibility to infection and malignancies.
Thanks to the discovery and development of cyclosporin, patients are alive today years after their operation. Without cyclosporin they would not have survived.
Scientists have named 100,000 different species of fungi, and there are many more that have yet to be classified. While you wouldn't want to ingest many members of the fungi kingdom, some mushrooms have been valued throughout the world--particularly Asia--as both food and medicine for centuries. The Chinese, for instance, have used and revered many fungi as tonics for the immune system for more than 3,000 years, while in Japan, pushcart vendors on the streets still sell medicinal mushrooms to average citizens, who use them to maintain health and promote longevity.
One of the key conclusions that has come out of both laboratory and human clinical studies is that a number of compounds in fungi can stimulate the function of the immune system and inhibit tumor growth. In particular, compounds called polysaccharides, which are complex chain-like molecules built from many smaller units of sugar molecules, have been intensively studied since the 1950s. Their antitumor and immuno-stimulating properties have been proven repeatedly.
Further on in our project we are going to elaborate on some of the medicines developed from mushrooms:
Penicilllin
Penicillin is defined as any antibiotic drug taken from molds or made synthetically to treat different diseases and/or infections. More specifically, penicillin is the liquid which is secreted from penicillium notatum, which is the mold.
Penicilin's structure
How Penicillin was Discovered
Penicillin was discovered by complete accident in 1928 by Alexander Fleming, a medical scientist. Fleming was actually studying the different strains of staphylococci (a bacteria which causes various infections), so he had germs growing in numerous petri dishes. He added a layer of agar jelly on the bottom of each dish; this jelly would then cause the bacteria to multiply, as it was the food for bacteria. Eventually, this bacteria would develop into a spot you could see without a microscope.
Like many other scientists, Fleming had difficulty keeping germs from the air out of his bacteria cultures, and noticed this in particular in one sample. As he was looking at his samples, he noticed something important in one of them: one of his cultures had become contaminated by some kind of mold from the air. This mold, now a large spot, had a radius all around it where there was no staphylococci bacteria left. The mold had cleared the zone of bacteria surrounding it and looked like it was secreting a toxin which ate up all of the germs in its path.
Culture of peniciline
Fleming immediately set to studying and growing more of what eventually became penicillium notatum, and discovered that it belonged to the same family of molds as you find on stale bread or decayed fruit. He also found that it stopped the growth of most common disease germs. Sometimes, it would completely dissolve the germs so there were no longer any around that area.
The Journey from "Mold" to "Cure"
Though Fleming’s discovery was published, little attention was paid to him until ten years later by an Australian doctor named Howard Florey (of the University of Oxford). Florey believed that there was an antibiotic stronger than Sulfa drugs, so he was quite interested in Fleming’s finds.
Obtaining strains of penicillium notatum from Fleming (which he had kept alive from the original strain), he enlisted the help of a chemist by the name of Ernst Chain. The two then went about creating a purified form of penicillin. Months later, their hard work paid off; they then had enough purified penicillin to run tests on mice. Amazing success was found in the mice that they had given penicillin.
From the mice, they eventually advanced on to a human test. They tested the penicillin out on a forty-three year old policeman who had a bad case of blood poisoning. Within the twenty-four hours of giving the man the penicillin, he showed remarkable recovery and continued to grow healthier until they ran out of penicillin. Before they could get him a new supply, he grew worse and finally died.
Just years before, Florey only had a small team and few ways of creating penicillin. Now, with the help of many American scientists, chemists, etc. working on project penicillin, they could help save millions of lives. They didn’t know that in 1959, productions could be bigger than ever because they then began testing synthetically made penicillin (this meant getting penicillin directly from chemicals instead of mold).
What Penicillin Treats
Some of the diseases/illnesses that penicillin treats includes: pneumonia, meningitis, erysipelas, scarlet fever, diphtheria, blood poisoning, syphilis, gangrene, strep throat and gonorrhea.Penicillin works to treat illnesses/diseases by killing bacteria and arresting its growth. It only kills the bacteria that is growing and reproducing, not those which are stationery.
The Growth Process of Penicillin
A penicillin colony will begin looking like a fluffy white mass, almost resembling a cotton ball. A few days later, the colony will turn dark green. As it is turning green, it is also secreting bright yellow drops of liquid. This liquid is what we call penicillin.
Cyclosporin
The discovery of cyclosporin in 1971 began a new era in immunopharmacology. It was the first immunosuppressive drug that allowed selective immunoregulation of T cells without excessive toxicity. Cyclosporin was isolated from the fungus Tolypocladium inflatum.
Scanning electron micrograph of Tolypocladium inflatum
Cyclosporin was first investigated as an anti-fungal antibiotic but its spectrum was too narrow to be of any clinical use. J. F. Borel discovered its immunosuppressive activity in 1976.This led to further investigations into its properties involving further immunological tests and investigations into its structure and synthesis. Cyclosporin has unwanted side effects, notably nephrotoxicity. Animal testing showed cyclosporin to be sufficiently non-toxic to begin clinical trials. These initially failed due to poor absorption of the drug. Once this had been overcome, results were encouraging enough for cyclosporin to be licensed for use in clinical practice, routine transplantation of organs that until then had only been done experimentally.
What is cyclosporin and what are its uses?
Today organ and bone marrow transplants are routinely performed. Cyclosporin is still used to treat the rejection reactions that occur when a foreign organ is attacked by the body’s immune system.
Cyclosporin is at present approved for use in organ transplantation to prevent graft rejection in kidney, liver, heart, lung and combined heart-lung transplants. It is used to prevent rejection following bone marrow transplantation and in the prophylaxis of host-versus-graft disease. It is also used in the treatment of psoriasis, atopic dermatitis, rheumatoid arthritis and nephrotic syndrome.
The discovery of immunosuppression by cyclosporin in 1976 is attributed to J. F. Borel.
J. F. Borel
In 1983 cyclosporin was approved for clinical use to prevent graft rejection in transplantation. Most of the surgical problems of allograft transplantation had already been solved by this time. Since 1961 the standard method of achieving immunosuppression had been a combination of azathioprine and corticosteroids. Azathioprine inhibits cell proliferation non-selectively. Its main unwanted side effect is depression of the bone marrow, other toxic effects include increased susceptibility to infections, a mild hepatotoxicity, skin eruptions, nausea and vomiting. Corticosteroids inhibit T lymphocytes and have an anti-inflammatory effect. Side effects include diabetes, avascular necrosis of bones and increased tendency to infections.
Cyclosporin was the strongest immunosuppressor to be discovered so far, it also overcame many of the risk factors associated with azathioprine and is relatively non-toxic to bone marrow. With the introduction of cyclosporin patient morbidity fell. It became possible to transplant organs with a one year success of 20% higher than previously, and to transplant organs successfully which previously had only been done in experimentation: the heart, the liver, the lung and combined heart lung transplants.
As well as transplantation, cyclosporin has been used in most autoimmune diseases. In the 1980’s experimental treatment with cyclosporin of insulin-dependent diabetes mellitus, inflammatory bowel disease, chronic asthma, atopic dermatitis, aplastic anaemia and psoriasis supported evidence of their T cell mediated nature.
SYNTHESIS
In 1984 synthetic cyclosporin was produced.It was then possible for cyclosporin to be chemically modified in every possible way. However, none of the derivatives have been found to have greater potency or decreased side effects than cyclosporin itself. The two major limitations of cyclosporin therapy today remain its nephrotoxicity and incomplete control of chronic rejection.
In 1996 undergraduate mycology students from Cornell University on a field trip to Ithaca, New York were told to pick up anything that looked interesting. Among the findings was a mysterious fungal fruiting body in an eviscerated beetle grub. The fungus was later identified as Cordyceps subsessilis an extremely rare fungus that is the sexual state of Tolypocladium inflatum. All the cyclosporin had so far been made from Tolypocladium inflatum cultures without it ever reaching the sexual state. Cordyceps is a large genus that includes around 280 species, and may be a good place to start looking, in the estimated 90% of world fungi that have yet to be identified, for a new and improved transplantation drug.
CONCLUSIONS
Discovery of cyclosporin led the way to an era of selective lymphocyte inhibition. It enabled the expertise in clinical, technical and immunobiological aspects of transplantation to be put into practice and changed the face of transplantation. Its contribution to autoimmune therapy is less well known but in the long term will probably be of comparable importance.
Cyclosporin did not solve all the problems of transplantation. Today chronic rejection is the main problem. It is poorly understood and there is no treatment for it, although it is thought to have a large immunological component. The majority of transplant patients require long term treatment with high doses of immunosuppressives which increases susceptibility to infection and malignancies.
Thanks to the discovery and development of cyclosporin, patients are alive today years after their operation. Without cyclosporin they would not have survived.
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