Early chemotherapy

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Information about Early chemotherapy

Published on October 15, 2007

Author: Alohomora

Source: authorstream.com

Slide1:  Antibiotics Biosynthesis, mechanism of action and resistance Malcolm G. P. Page malcolm.page@basilea.com Slide2:  Early chemotherapy and antibiotic discovery Antibiotic classes by target Antibiotic discovery today Topics for Discussion Timetable:  Timetable 12 th December Introduction 19th December No lecture 9th January Antibiotics 16th January Antibiotics 23rd January No lecture 30th January Antibiotics 6th February Conclusion & Exam Exam format: multiple-choice questionnaire 2000 Years of Infectious Disease:  2000 Years of Infectious Disease 2000 1000 0 Bubonic plague Smallpox Measles Smallpox? Leprosy Bubonic plague Smallpox? Measles Bagdad School of Medicine Bubonic plague Mumps Leprosaria 19,000 by 1200s Leper colonies Bubonic plague Travel ban Quarrantine WC, (England) Variolation Vaccination Hand washing Pasteurization Immunization 1971 smallpox vaccination discontinued in US Bubonic plague pandemic Influenza Influenza HIV Japan China Middle East Roman Empire Global Slide5:  Ancient civilizations around the world independently discovered that moulds could be used to cure infections. The people believed the moulds drove away evil spirits that cause disease. 3000 Years of Chemotherapy Chinese used mouldy soybean curd to treat boils, furuncles and carbuncles. (S. aureus infections). South American Indians wore sandals furry with mould to treat and prevent foot infections (Fungal infections). Central Europeans kept stocks of mouldy bread for treating cuts, sores and fevers (Bacterial infections). Slide6:  Medieval Chemotherapy Strong tradition for using plants to treat infections developed in China, Asia and Americas. Less common in Europe, where the attention was on other diseases: Foxglove (digitalin), willow bark (salicylates). In the European Middle Ages focus was on inorganic treatments (e.g. mercuric chloride for syphilis) S. American Indians chewed roots, bark and leaves and berries of many plants of: cinchona tree for malaria coca bush for rheumatism & altitude sickness ipecac plant for dysentery 1627 Interest re-awakened by Jesuit missionaries in Peru who noted the Amerindian use of Cinchona bark as an anti-malarial agent. Evolution of Gin & Tonic:  Evolution of Gin & Tonic “Jenever“ distilled by dutch herbalist from grain & juniper berries (blood purifier) Gin & lime juice adopted by Royal Navy (Gimlet) Tonic water Extract of javan C. natida bark Used to treat malaria and fevers by British Indian Army 17th century 19th century 18th century Cinchona bark extract first used to treat malaria by europeans 1747, proved that fresh fruit prevents scurvy 1795, Royal Navy starts routine issue of lime juice Gin, lime & tonic water combined to take away the bitter taste of quinine Milestones in Public Health:  Milestones in Public Health ISOLATION & CONTROL 1200s Approximately 19,000 leprosaria have been established throughout Christendom. 1377 A temporary 40-day ban on travel and trade is imposed in North Italian cities and especially in Ragusa (Dubrovnik, Croatia) to control bubonic plague. 1465 Quarantine of plague patients instituted in Ragusa 1485 Plague quarrantine rules instigated in Venice 1530 Fracastoro claims syphilis is spread by “seeds distributed by intimate contact” 1601 German authorities shut down brothels due to spread of venereal disease Milestones in Public Health:  Milestones in Public Health INOCULATION/IMMUNIZATION 1718 English noblewoman Lady Mary Wortley Montagu reports that the Turks have a habit of deliberately inoculating themselves with fluid taken from mild cases of smallpox. Lady Montague inoculates her own children in this manner. Mid-1700s Lady Montagu's method of variolation is refined by the Suttons, who used only slight pricking of the skin. However, variolation remains controversial because the recipient can develop the full-blown disease and trigger an epidemic. 1796 Edward Jenner notes that variolation fails in individuals who have previously suffered from cowpox. He subsequently vaccinates healthy individuals (including his own son) by scratching cowpox exudate into their skin. The technique prevents variolation and also protects against smallpox. Milestones in Public Health:  Milestones in Public Health INOCULATION/IMMUNIZATION 1880 Louis Pasteur develops immunization techniques 1890 von Behring & Kitasato describe immunization of animals against diptheria and tetanus 1891 Diptheria antiserum given to an acutely ill child 1901 von Behring wins Nobel Prize for Medicine 1938 Jonas Salk works on influenza vaccine 1952 Salk develops Polio vaccine 1963 Measles vaccine licensed in US 1971 Smallpox vaccination discontinued 2003 US plans to re-introduce smallpox vaccination Milestones in Public Health:  Milestones in Public Health HYGEINE 1596 First water closets introduced in England 1825 Labarraque recommended sodium hypochlorite for treatment of wounds 1835 Oliver Wendel Holmes recommended hand washing 1847 Ignaz Semmelweiss recommends disinfection of physicians hands with chlorine water. 1854 John Snow demonstrates the link between cholera and drinking water supplies. 1860 Lemaire noted use of phenol as antiseptic 1863 Louis Pasteur invents pasteurization 1867 Joseph Lister champions the use of phenol for disinfection The Rediscovery of Antibiotics:  The Rediscovery of Antibiotics 1871 Lister noted that bacteria did not grow in urine samples contaminated with mould. 1877 Pasteur showed that anthrax bacilli in animals could be rendered harmless by injections of soil bacteria and moulds. 1887 Emmerich & Low developed a cell extract that became the first antibiotic substance to be used in hospitals. 1889 Vuillemin noted that fungi and yeasts could destroy bacteria - a process he called antibiosis. 1897 Kronig, Paul & Ehrlich started systematic testing of chemicals for their activity against bacteria and other microbes. 1924 Gratia & Dath started screening soil microbes for antibacterial activity. Discovery of Synthetic Antibiotics – Sulfonamides:  Discovery of Synthetic Antibiotics – Sulfonamides 1913 Eisenberg discovered the antibacterial properties of the dye chrysoidine – but it was too toxic to use. 1932 Domagk showed that the bright red dye prontosil rubrum was relatively non-toxic and protected mice against streptococcal infections. 1935 Domagk, Klarer and Mietzsch identified a breakdown product of prontosil rubrum that was formed in the mice (sulfonamide) and had antibiotic activity. 1939 Domagk received the Nobel Prize in Medicine for discovering the sulfonamides. By 1945 the pharmaceutical industry had produced 5488 sulfonamides. Discovery of Natural Antibiotics - Penicillins:  Discovery of Natural Antibiotics - Penicillins 1929 Alexander Fleming demonstrated inhibition of Staphylococcus aureus by the mould Penicillium notatum. Fleming noted tiny droplets of fluid began to form on the mould. He drew off the liquid and found that it could kill germs in a test-tube. Discovery of Penicillin:  Discovery of Penicillin 1932 Country doctor Cecil Paine tried “Fleming’s droplets” on patients. Showed his successful results to Howard Florey who was looking for a new project. 1938-40 Florey & Chain isolated the active principle - penicillin - from the droplets and tested it. The first patients treated showed improvement but it was not possible to make enough material to complete the cure. 1945 Fleming, Chain and Florey received the Nobel Prize in Medicine. Industrial Exploitation of Penicillin:  Industrial Exploitation of Penicillin 1941 Penicillin production transferred to US Low yield remained a problem. 1942 New isolate discovered ona mouldy canteloupe. Produces 200 times as much. Pfizer starts industrial fermentation The "Golden Era" of Antibiotic Discovery:  The "Golden Era" of Antibiotic Discovery 1940 Selman Waksman systematically isolates antimicrobial substance from soil organisms actinomycin (1940) clavacin (1942), streptothricin (1942), streptomycin (1943) grisein (1946) neomycin (1948), Proposed term "antibiotic" Streptomycin and neomycin make major contribution to the treatment of Gram-negative bacteria and tuberculosis 1952 Waksman receives the Nobel Prize in Physiology or Medicine Sources of Natural Antibiotics:  Sources of Natural Antibiotics Mouldy food Penicillin Andean soil Streptomycin Mediterranean sewage Cephalosporin Cemetery soil Chlorotetracycline Forest soils Erythromycin Chloramphenicol Vancomycin Infected wounds Bacitracin Antibacterial Agents Available Today:  Antibacterial Agents Available Today Sulfonamides 1930 1940 1950 1960 1970 1980 1990 2000 Penicillins Aminoglycosides Tetracyclines Macrolides Chloramphenicols Vancomycin Cephalosporins Lincosamides Fluoroquinolones Carbapenems Trimethoprim Quinolones Cephamycins Streptogramins Oxazolidinones Daptomycin Synthetic Natural origin Discovered but not used Traditional Sources:  Traditional Sources Origins of medicines derived from nature Anti-protozoan Human medicines Antibacterials Antifungals Non-Actinomycetes Actinomycetes Fungi Higher Plants Targets for Anti-bacterial Drugs :  Targets for Anti-bacterial Drugs Ribosome Macrolides Tetracyclines Nucleoid Fluoroquinolones Cell wall Cephalosporins, Penicillins Vancomycin Cell membrane Antiseptics Triclosan Metabolism sulfa drugs, anti-folates Cell division Registrations of New Antibiotics:  Registrations of New Antibiotics

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