http://www.youtube.com/watch?v=Mm60ZIVnXZw
This video is perhaps my most favorite video on youtube. The music is perfect to the plot, it creates the feeling of a cold descend down stairs into a hell. A hell consumed in hysteria, of insanity, the mind of a psychopathic surgeon in a dungeon of captivated patients. The ambitions of a psychiatrist to his lobotomies, the symbols of all that is come to be known as unmitigated departure from the mind.
Whenever I watch this video, it moves me so - it can turn my emotions at once from a still lake into a primitive, raging, flushing river full of rancor and passion. Whoever created this video should do more - Undoubtedly on the French Revolution.
Saturday, March 20, 2010
Wednesday, March 17, 2010
On Maraviroc
Maraviroc to me represents progress, I can faintly remember in my youth the news about the (then new) protease inhibitors and that mankind had finally found a way to stay (or perhaps more accruately subdue) the wild raging beast that was HIV/AIDS. To me, this new generation of treatment will be the "cure" of the disease.
Maraviroc has a simple formulation that has a binds highly selectively to the CCR5 also recently defined as CD195 "cluster of differentiation" 195. Upon binding to this chemokine receptor it blocks it! I don't know, ask a biochemical major. What I do know is that CCR5 is a corecepter used by HIV-1 to gain access into the cell. CCR5 is (coincidentally) present on all major classes of cells that HIV-1 infects - that is, CD4+ T cells, dendritic cells, microgliac, as well as macrophages. Studies in years past have shown that northern european men and women who had double homozygous mutations of the delta-32 gene (the gene that expresses CCR5) could not be infected by HIV-1. Indeed, a patient in Germany three years ago who had HIV as well as late stage leukemia was given a bone marrow transplant with a donor who had the delta-32 mutation. The operation was successful and the man has not had detectable levels of HIV.
The human body can no doubt live without a functional CCR5 chemokine receptor and as such it basically represents a naked vulnerability that must be perged, blocked, and destroyed. Ideally doctors could give bone marrow transplants to everyone - but of course even with modern technology a bone marrow transplant has a survival rate around 33% and donors are certainly not universal.
However, Maraviroc is universal. Studies have shown that it is highly tolerated with minimal side effects and with high binding efficiency. It was only recently released (2008 I believe) and so studies have not shown its efficiency when used as post prophylaxis treatment or as a general preventive drug.
However, theoretically and perhaps with a small dose of faith, I believe this drug can, will, and should be used for preventive care. If one is on a constant dose of this medication, the amount of cells an introduced HIV vector could potentially infect is dramatically lessened. If the virus is unable to achieve reproduction quickly enough the body will remove the inert substance by natural means - this is the theory behind current protease prophylaxis treatment. However, giving Maraviroc as a single pill at a precautionary dose is much more practical than the expensive combination of HAART preventative treatment and is without the severe side effects.
Unfortunately the second strain of the virus, HIV-2 predominatly located in west Africa does not use the CCR5 chemokine receptor and so maraviroc would be of little use. However, the theory should the same - the coreceptor is known for HIV-2 and a drug could be synthesized - perhaps outside of the united states where regulations are not so costly..
I've been working on a chemical compound using the same ideas from the maraviroc formulation - but without any means of testing and with very little current knowledge of biochemistry I feel it's hopeless. Also my general ignorance of pharmacuetical regulation. These problems can be remedied with time and effort. Perhaps I'll have to wait until medical school.
but the thoughts of the suffering. Pneumocytosis pneumonia, toxoplasmosis, ADC, induced cancers, tuberculosis, Kaposi sarcoma, Flu, rheumatic fevers - all multiplied in the thousands of people suffering.
One wonders if those who work on pharmaceuticals - the scientists not the businessmen - feel the collective pains, the souls in need of a hero. Does it keep them up at night?
Maraviroc has a simple formulation that has a binds highly selectively to the CCR5 also recently defined as CD195 "cluster of differentiation" 195. Upon binding to this chemokine receptor it blocks it! I don't know, ask a biochemical major. What I do know is that CCR5 is a corecepter used by HIV-1 to gain access into the cell. CCR5 is (coincidentally) present on all major classes of cells that HIV-1 infects - that is, CD4+ T cells, dendritic cells, microgliac, as well as macrophages. Studies in years past have shown that northern european men and women who had double homozygous mutations of the delta-32 gene (the gene that expresses CCR5) could not be infected by HIV-1. Indeed, a patient in Germany three years ago who had HIV as well as late stage leukemia was given a bone marrow transplant with a donor who had the delta-32 mutation. The operation was successful and the man has not had detectable levels of HIV.
The human body can no doubt live without a functional CCR5 chemokine receptor and as such it basically represents a naked vulnerability that must be perged, blocked, and destroyed. Ideally doctors could give bone marrow transplants to everyone - but of course even with modern technology a bone marrow transplant has a survival rate around 33% and donors are certainly not universal.
However, Maraviroc is universal. Studies have shown that it is highly tolerated with minimal side effects and with high binding efficiency. It was only recently released (2008 I believe) and so studies have not shown its efficiency when used as post prophylaxis treatment or as a general preventive drug.
However, theoretically and perhaps with a small dose of faith, I believe this drug can, will, and should be used for preventive care. If one is on a constant dose of this medication, the amount of cells an introduced HIV vector could potentially infect is dramatically lessened. If the virus is unable to achieve reproduction quickly enough the body will remove the inert substance by natural means - this is the theory behind current protease prophylaxis treatment. However, giving Maraviroc as a single pill at a precautionary dose is much more practical than the expensive combination of HAART preventative treatment and is without the severe side effects.
Unfortunately the second strain of the virus, HIV-2 predominatly located in west Africa does not use the CCR5 chemokine receptor and so maraviroc would be of little use. However, the theory should the same - the coreceptor is known for HIV-2 and a drug could be synthesized - perhaps outside of the united states where regulations are not so costly..
I've been working on a chemical compound using the same ideas from the maraviroc formulation - but without any means of testing and with very little current knowledge of biochemistry I feel it's hopeless. Also my general ignorance of pharmacuetical regulation. These problems can be remedied with time and effort. Perhaps I'll have to wait until medical school.
but the thoughts of the suffering. Pneumocytosis pneumonia, toxoplasmosis, ADC, induced cancers, tuberculosis, Kaposi sarcoma, Flu, rheumatic fevers - all multiplied in the thousands of people suffering.
One wonders if those who work on pharmaceuticals - the scientists not the businessmen - feel the collective pains, the souls in need of a hero. Does it keep them up at night?
Monday, March 15, 2010
I will bear witness.
Currently I'm reading a translated version of Victor Klemperer's personal diary of life in Nazi Germany. Of course the majority of the diary entries are constrained to personal influences of the Nazi regime it nevertheless provides sufficient broad details of the systematic choking of the Jewish people under Hitler's political machine. Klemperer was a literary professor at a technical institute in Germany who had an interest in the French enlightment particularly with famous writers such as Voltaire. It is no wonder then, that his diaries contain sufficient and often candid depictions of life as a Jew.
If read in the right frame of mind, one begins to live the life in situ of a Jewish citizen. Such a horrid existence, early on Klemperer knew from 1933 at the beginning of it all, that impending doom would come to him and his people. Einstein had the same insight and left Germany that year. The freedoms were taken quite suddenly actually. Jews in professorships were quickly removed of their posts within weeks of Hitler's rise to power. Jewish professors were not allowed to give examinations to students (one colleague of Klemperer's did and was subsequently removed from his post) Telephone calls and letters from Jews were monitered by state agencies. In this year Jewish people did not necessarily fear for their lives in so much as worry about their livelihoods. Klemperer however wrote of accounts of men within only a month of time wearing SA uniforms and swatiska's although still treating him politely the writing was on the wall.
... when you turn on the news and you hear someone was murdered, your heart feels for the victim and their family and rage builds against the aggressor. This is a very natural instinct, because one recognizes injustice based off an internally and externally grounded sense of morality and virtue. Men fight wars voluntarily based off their grounded ideals of virtue. Cultures across the world adopt laws protecting their people from crimes against humanity such as murder, rape, burglarly - these concepts of morality are not new to modern civilization it can be shown since Hammurabi's code and Roman and Greek as well as Egyptian law that men have shared common sense of virtue for millenia.
One thing that has always confounded me is that people can be programed so easily to turn against their long grounded and perhaps even natural belief in morality. When Stalin called his fellow communists to pillage and burn at the stake the Kulaks and other "rich" persons people of course followed his orders and slaughtered them. Hitler infected millions of Germans to share his hell borne ideas of Jews to the point where they willingly slaughtered them as if they were less than animals. Mao convinced the Chinese communists to purge each other in the great cultural revolution. All of these dictators were able to spread a message that was completely against what is the natural and grounded beliefs in morality.
But how? Psychologists describe the phenomenon known as group think and obviously this is what was going on in each of these tyrannies, however if the original group thought was inclined to morality - what change in that group think allowed the tyrants to gain power?
Clearly in Nazi Germany it was the fall of Germany in WWI, the treaty of Versailles, the French occupation of German territory, as well as the bout of hyperinflation these seemingly unrelated phenomena is what cracked the German people and allowed their normal equilibrium of thought and practice to be guided by..well Hitler.
It leaves one to wonder, that the true threat to freedom is not necessarily to tyrants themself for they exist indefinitely within a population. Rather the true threat to freedom is extreme environmental conditions to a culture. Like the financial collapse of 2008. Obama is too stupid to take advantage of the American people(well in the sense of becoming a dictator), but one must wonder what future hell can await modern civilization if America were to suffer a catastrophe similar to what happened in the 1920s to Germany.
If read in the right frame of mind, one begins to live the life in situ of a Jewish citizen. Such a horrid existence, early on Klemperer knew from 1933 at the beginning of it all, that impending doom would come to him and his people. Einstein had the same insight and left Germany that year. The freedoms were taken quite suddenly actually. Jews in professorships were quickly removed of their posts within weeks of Hitler's rise to power. Jewish professors were not allowed to give examinations to students (one colleague of Klemperer's did and was subsequently removed from his post) Telephone calls and letters from Jews were monitered by state agencies. In this year Jewish people did not necessarily fear for their lives in so much as worry about their livelihoods. Klemperer however wrote of accounts of men within only a month of time wearing SA uniforms and swatiska's although still treating him politely the writing was on the wall.
... when you turn on the news and you hear someone was murdered, your heart feels for the victim and their family and rage builds against the aggressor. This is a very natural instinct, because one recognizes injustice based off an internally and externally grounded sense of morality and virtue. Men fight wars voluntarily based off their grounded ideals of virtue. Cultures across the world adopt laws protecting their people from crimes against humanity such as murder, rape, burglarly - these concepts of morality are not new to modern civilization it can be shown since Hammurabi's code and Roman and Greek as well as Egyptian law that men have shared common sense of virtue for millenia.
One thing that has always confounded me is that people can be programed so easily to turn against their long grounded and perhaps even natural belief in morality. When Stalin called his fellow communists to pillage and burn at the stake the Kulaks and other "rich" persons people of course followed his orders and slaughtered them. Hitler infected millions of Germans to share his hell borne ideas of Jews to the point where they willingly slaughtered them as if they were less than animals. Mao convinced the Chinese communists to purge each other in the great cultural revolution. All of these dictators were able to spread a message that was completely against what is the natural and grounded beliefs in morality.
But how? Psychologists describe the phenomenon known as group think and obviously this is what was going on in each of these tyrannies, however if the original group thought was inclined to morality - what change in that group think allowed the tyrants to gain power?
Clearly in Nazi Germany it was the fall of Germany in WWI, the treaty of Versailles, the French occupation of German territory, as well as the bout of hyperinflation these seemingly unrelated phenomena is what cracked the German people and allowed their normal equilibrium of thought and practice to be guided by..well Hitler.
It leaves one to wonder, that the true threat to freedom is not necessarily to tyrants themself for they exist indefinitely within a population. Rather the true threat to freedom is extreme environmental conditions to a culture. Like the financial collapse of 2008. Obama is too stupid to take advantage of the American people(well in the sense of becoming a dictator), but one must wonder what future hell can await modern civilization if America were to suffer a catastrophe similar to what happened in the 1920s to Germany.
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