2016 - Przelom w leczeniu.Dr Horowitz zwolal konferencje.Jest nowy lek,ktory skutecznie niszczy PERSISTER ( cysty) nazywa sie - Dapsone albo Pirazynamid (łac. pyrazinamidum).U ludzi szybko po podaniu ( juz od miesiaca) mijaja objawy !!! przeprowadzono badania
DR.Horowitz mowi ze Dapson + Rifampicyna powinno się podawac przez 12 miesięcy
https://www.lymedisease.org/touched-by-lyme-dapsone/
----------------------------------------------------------------------
Inny lekarz Ilads poleca takie zestawy.
Dapsone podaje się np. w zestawie :
Mycobutin 1x150mg (pochodna ryfamycyny S)
Klabax 2x1/2 tab ( klarytromycyna)
Duracef 2x 500 mg ( Cefadroxilum )
Dapson 2x50
Plaguenil 2x1
Dapson (diaminodifenylowy sulfon, czyli DDS) jest powszechnie stosowany w leczeniu schorzeń dermatologicznych - takich jak :trądzik, opryszczkowe zapalenie skóry i trąd. Testowany przy leczeniu w Borrelia burgdorferi na persister.
Cele: Przetestowaliśmy skuteczność DAPSONE -DDS u pacjentów z przewlekłą Boreliozą i Babeszjoza
Wniosek: Dapson lub Pirazynamid ( łac. pyrazinamidum) jest nowym i skutecznym lekiem na "persister"
skutecznie poprawia stan pacjentow - dotyczy to wszystkich objawow.
----------------------------------------------------------------------------------
Nazwy : Disulone / Dapson /Avlosulfon/Disulone /Pirazynamid
-----------------------------------------------------------------------------------
Patients were assigned to one of
several different treatment groups based on their prior response to
antibiotics for Lyme and associated co-infections. Patients who had
significant Jarisch-Herxheimer reactions to a tetracycline,
macrolide, and/or rifampin, were not given that particular drug
combination. A previous positive clinical response to any or all of
those medications allowed us to include them in our trial, unless
there were potential adverse drug interactions.
-------------------
http://webcache.googleusercontent.com/search?q=cache:0kKKusKcoM0J:www.omicsonline.org/open-access/the-use-of-dapsone-as-a-novel-persister-drug-in-the-treatment-of-chroniclyme-diseasepost-treatment-lyme-disease-syndrome-2155-9554-1000345.pdf+&cd=1&hl=nl&ct=clnk&gl=nl
-----------------------------------------------------------------------------------------------
Pirazynamid jest szybko i całkowicie wchłaniany z przewodu pokarmowego. Maksymalne stężenie we krwi osiąga po 1–2 h, natomiast jego czynny metabolit – kwas pirazynowy – po 4–5 h. Pirazynamid przenika do płynu mózgowo-rdzeniowego oraz do wszystkich tkanek, osiągając tam 87-105% wartości stężenia w osoczu. Lek przenika również do makrofagów oraz do wydzieliny płucnej i oskrzelowej. Pirazynamid wiąże się z białkami osocza w 10-20% (kwas pirazynowy w 31%). Lek w niewielkim stopniu przenika przez łożysko i do mleka matki. Metabolizm pirazynamidu odbywa się głównie w wątrobie, gdzie jest on hydrolizowany, a następnie przekształcany przez oksydazę ksantynową do kwasu 5-hydroksypirazynowego, który jest głównym wydalanym metabolitem.
https://pl.wikipedia.org/wiki/Pirazynamid
--------------------------------------------------------------------------------------------
Abstract
Dapsone (diaminodiphenyl sulfone, i.e., DDS) is commonly used to treat dermatological conditions including acne, dermatitis herpetiformis, and leprosy. Mycobacterium leprae, a known "persister" bacteria, requires long-term treatment with intracellular medications including rifampin and Dapsone.
Other "persister" bacteria recently have been identified, including Borrelia burgdorferi, the agent of Lyme disease.
Objectives: We tested the efficacy of DDS in patients with chronic Lyme disease/PTLDS with tick-borne coinfections including Babesiosis, who failed commonly used antibiotic and antimalarial protocols.
Methods: 100 patients with Lyme disease, 56 of who were Babesia positive, were placed on Dapsone and folic acid in combination with either one or two other intracellular drugs, including rifampin, tetracyclines, and/or macrolide antibiotics. Several patients also took cephalosporins, and all patients were on protocols to treat cystic forms of Borrelia and biofilms.
\
Results: Patients completed a symptom severity survey before beginning treatment with Dapsone and then again after at least one month of treatment scoring their complaints from 0 indicating “none” to 4 indicating “severe” for symptoms including fatigue, joint and/or muscle pain, disturbed sleep, and cognitive difficulties. Results demonstrated that Dapsone significantly improved all patients’ clinical symptoms except for headache, where changes did not reach statistical significance. In addition, Dapsone, known to have anti-malarial effects, helped resistant Babesia symptoms of sweats, chills, and flushing. Lyme positive, Babesia positive patients also demonstrated significant changes in pain, disturbed sleep, and cognitive difficulties. Side effects included macrocytic anemia and rare cases of methemoglobinemia, which resolved by either decreasing the dose of Dapsone or increasing folic acid.
Conclusion: Dapsone is a novel and effective “persister” drug for those with PTLDS and associated tick-borne co-infections who have failed classical antibiotic protocols. Further prospective trials must determine the DDS dose,length of treatment and best combination antibiotic therapy in order to effect a long-term health benefit.
http://www.omicsonline.org/open-access/the-use-of-dapsone-as-a-novel-persister-drug-in-the-treatment-of-chroniclyme-diseasepost-treatment-lyme-disease-syndrome-2155-9554-1000345.pdf
---------------------------------------------------------------------------------------
Richard Horowitz, MD, and his wife, the lovely Lee, kicked off the weekend conference “Beyond Lyme & Other Chronic Illnesses: Reclaiming Your Health and Well-Being,” on the evening of Friday, December 4th. It was “healing with the Horowitz’s” at it’s finest.
We huddled eagerly–my girlfriend Dana and I among fifty or so professionals and patients–in the Sunset Room at the world renowned Kripalu Center for Yoga & Health, founded on the teachings and principles of Swami Kripalu, for a weekend of both retreat and research.
That evening, Dr. Horowitz and Lee established the foundation for the next few days, including first grounding us all in meditation and blessings from their years studying Tibetan Buddhism. It was science meets spiritualism in scenic and secluded Stockbridge, MA.
Second that evening, they established Hope.
Dr. Horowitz and Ying Zhang from John Hopkins, it seems, are on the verge of a breakthrough. Using mycobacterium drugs–like those used in leprosy and tuberculosis–in hope of cleverly and mercilessily attack the four main persisters: Borrelia, Babesia, Bartonella and mycoplasma. As Dr. Horowitz explains, he is typically successful in getting 92% of his patients better. But there is an “8%” that are the most difficult to treat. Could this breakthrough break the code for closing in on the 8% of people that are most difficult to get better? It could. I’ll never forget those chilling yet cheerful words: “We are closing in on the 8%,” Dr. Horowitz whispered.
It works like this. Dr. Horowitz first combines 2-3 intracellular antibiotics to reach the persister bacteria hiding in cells. This would be the “triple persister” cocktail. Then he pulses with a cellular antibiotic. This pulsing has been shown to be effective based on the incredible work of professor and researcher Kim Lewis of Northeastern University. Dr. Horowitz has found this regimen to be very successful for people who continue to have symptoms or relapses. BUT FURTHERMORE, he has now found with the help of the work from Dr. Zhang that adding dapsone (pyrazinamide) to this regimen for the most difficult of cases…could be THE key to perishing the persisters for once and for all. Dapsone being that potential mycobacterium super drug used against Tuberculosis and leprosy.
Dapsone, or prazinamide, targets tuberculosis bacteria that have become “persisters,” which don’t respond to typical antibiotics. Zhang and Horowitz’s hunch that this will also work to combat “persister” bacteria associated with lyme and co-infections…has been promising. Very promising. And it is likely that Dr. Horowitz will publish work being conducted on his patients in the upcoming year. For more on the work being conducted by Dr. Kim Lewis and Dr. Zhang, read here:
Dr. Lewis:
http://www.northeastern.edu/news/2015/06/researchers-discovery-may-explain-difficulty-in-treating-lyme-disease/
Dr. Zhang:
http://beforeitsnews.com/health/2015/10/lyme-disease-persister-drugs-dr-ying-zhang-2593390.html
http://magazine.jhsph.edu/2013/fall/news-briefs/two-takes-on-lyme/
http://www.jhsph.edu/news/news-releases/2014/new-test-shows-promise-in-identifying-new-drugs%20to-treat-lyme-disease.html
Remember, however, that based on Dr. Horowitz’s own experience, about “92%” can get better with the approach of “hitting all targets” and combining antibiotics that work on the spirochete, cell-wall deficient (or “L-form”) and cyst forms of Borrelia. To help understand what that means, the first link below provides a table comparing Borrelia’s multiple forms, and the second link below provides a helpful overview regarding which antibiotics target which different forms.
Overview of different forms of Borrelia:
http://www.lymebook.com/top10forms
Overview of antibiotics that attack different forms:
http://www.treatlyme.net/treat-lyme-book/kills-lyme-germs-a-brief-antibiotic-guide
AND specific examples of some of Dr. Horowitz’s favorite combinations for attacking the various forms of Lyme (as well as co-infections like bartonella and mycoplasma) are shown in the pictures below.
https://lymewhisperer.com/2015/12/13/kripalu-closing-in-on-the-8/
-----------------------------------------------------------------------------------
Przy stosowaniu w dawce dziennej 3 g dłużej niż poł roku następują nieodwracalne zmiany w miąższu wątroby. Obecnie jest stosowany w chemioterapii krotkotrwałej i przerywanej [4,6]. W wyniku przemian metabolicznych lek ten wydzielany jest z moczem w postaci kwasu pirazynowego [7].Pirazynamid (2) otrzymuje się w reakcji amonolizy estru metylowego (3a) lub etylowego kwasu pirazynokarboksylowego (3b) (schemat 1) [8-10].
W innej metodzie syntezy 7 pirazynamid (2) poddaje się najpierw kondensacji Mannicha z formaliną i dietyloaminą, a następnie otrzymany //(dietyloaminometylo)-pirazynokarboamid (8) poddaje reakcji z morfoliną (schemat 2) [13].
Wprowadzone w kolejnych latach mniej toksyczne sulfony (np. 4,4 ’-diacetyloaminodifenylosulfon - radilon) są, w przypadku gruźlicy ludzkiej zbyt mało aktywne.Synteza dapsonu (9) polega na kondensacji chlorku kwasup-chlorobenzenosulfonowego (10) z chlorobenzenem w obecności chlorku glinu, a następnie substytucji nukleofilowej otrzymanego 4,4’-dichlorodifenylosulfonu (11) (schemat 3) [3,18].
http://www.google.nl/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&ved=0ahUKEwjKhI7x4tHMAhUrMJoKHUa1A8IQFgguMAI&url=http%3A%2F%2Fwww.dbc.wroc.pl%2FContent%2F3270%2Fwch_2003_9_10.pdf&usg=AFQjCNFikqXe2RUqdXovY5Ar696GBSRhTQ&sig2=hwk78Zh11oUh6GOzL1ZRtA&cad=rjt
--------------------------------------------------------------------------- Dapsone
is a drug that has been used since the 1940s to treat leprosy and a few other conditions. According to Horowitz, leprosy has long been known as a “persister”—a bacterial infection that can survive initial treatments by antibiotics. Since research indicates that Lyme and co-infections can similarly persist after treatment, he had theorized that Dapsone might be useful in this case as well.
In a preliminary clinical trial of 100 patients at his Hyde Park medical office, Horowitz gave Dapsone in combination with assorted other antibiotics. He found that patients reported significant improvement of ALL symptoms, except for headache. He told of one woman who, after being on Dapsone for five weeks, said this was the best she’d felt in 12 years. Her brain fog had cleared and her joint and muscle pain had diminished considerably.
However, Horowitz found that patients who stopped treatment after they began to feel better would relapse. This was true in leprosy as well. He says successful leprosy treatment uses a 12-month regimen of Dapsone and rifampin. He is now extending the protocol with his patients to see if 12 months is the right length of treatment for them as well.
Alas, Dapsone is not without a downside. It can cause serious side-effects, such as anemia, which must be closely monitored during treatment. Furthermore, Horowitz says, there are many unanswered questions about the use of persister drugs such as Dapsone to treat chronic Lyme, and much more research is needed.
You can read Dr. Horowitz’s published journal article about the Dapsone trial here. More about who should consider using Dapsone, and how best to minimize side-effects, will be included in his forthcoming book to be released at the end of 2016, “How Can I Get Better? An Action Plan for Treating Resistant Lyme and Chronic Disease.”
---------------------------------------------------------------------
Artykuł przeglądowy
http://www.termedia.pl/Czasopismo/Przeglad_Dermatologiczny-56/Streszczenie-27310
--------------------------------------------------------------------------------------------
DR.Horowitz mowi ze Dapson + Rifampicyna powinno się podawac przez 12 miesięcy
https://www.lymedisease.org/touched-by-lyme-dapsone/
----------------------------------------------------------------------
Inny lekarz Ilads poleca takie zestawy.
Dapsone podaje się np. w zestawie :
Mycobutin 1x150mg (pochodna ryfamycyny S)
Klabax 2x1/2 tab ( klarytromycyna)
Duracef 2x 500 mg ( Cefadroxilum )
Dapson 2x50
Plaguenil 2x1
Dapson (diaminodifenylowy sulfon, czyli DDS) jest powszechnie stosowany w leczeniu schorzeń dermatologicznych - takich jak :trądzik, opryszczkowe zapalenie skóry i trąd. Testowany przy leczeniu w Borrelia burgdorferi na persister.
Cele: Przetestowaliśmy skuteczność DAPSONE -DDS u pacjentów z przewlekłą Boreliozą i Babeszjoza
Wniosek: Dapson lub Pirazynamid ( łac. pyrazinamidum) jest nowym i skutecznym lekiem na "persister"
skutecznie poprawia stan pacjentow - dotyczy to wszystkich objawow.
----------------------------------------------------------------------------------
Nazwy : Disulone / Dapson /Avlosulfon/Disulone /Pirazynamid
-----------------------------------------------------------------------------------
The Use of
Dapsone as a Novel “Persister” Drug in the Treatment of Chronic
Lyme Disease/Post Treatment Lyme Disease Syndrome
Combinations
of medications used in our pilot study included Dapsone between 25 to
100 mg per day, with or without rifampin, with either a tetracycline
(doxycycline, minocycline) and/or a macrolide (azithromycin,
clarithromycin) and a cephalosporin (cefuroxime axetil,cefdinir,
cefixime), or patients took Dapsone as a sole intracellular agent.
-------------------
http://webcache.googleusercontent.com/search?q=cache:0kKKusKcoM0J:www.omicsonline.org/open-access/the-use-of-dapsone-as-a-novel-persister-drug-in-the-treatment-of-chroniclyme-diseasepost-treatment-lyme-disease-syndrome-2155-9554-1000345.pdf+&cd=1&hl=nl&ct=clnk&gl=nl
-----------------------------------------------------------------------------------------------
Pirazynamid jest szybko i całkowicie wchłaniany z przewodu pokarmowego. Maksymalne stężenie we krwi osiąga po 1–2 h, natomiast jego czynny metabolit – kwas pirazynowy – po 4–5 h. Pirazynamid przenika do płynu mózgowo-rdzeniowego oraz do wszystkich tkanek, osiągając tam 87-105% wartości stężenia w osoczu. Lek przenika również do makrofagów oraz do wydzieliny płucnej i oskrzelowej. Pirazynamid wiąże się z białkami osocza w 10-20% (kwas pirazynowy w 31%). Lek w niewielkim stopniu przenika przez łożysko i do mleka matki. Metabolizm pirazynamidu odbywa się głównie w wątrobie, gdzie jest on hydrolizowany, a następnie przekształcany przez oksydazę ksantynową do kwasu 5-hydroksypirazynowego, który jest głównym wydalanym metabolitem.
https://pl.wikipedia.org/wiki/Pirazynamid
--------------------------------------------------------------------------------------------
Dapsone (diaminodiphenyl sulfone, i.e., DDS) is commonly used to treat dermatological conditions including acne, dermatitis herpetiformis, and leprosy. Mycobacterium leprae, a known "persister" bacteria, requires long-term treatment with intracellular medications including rifampin and Dapsone.
Other "persister" bacteria recently have been identified, including Borrelia burgdorferi, the agent of Lyme disease.
Objectives: We tested the efficacy of DDS in patients with chronic Lyme disease/PTLDS with tick-borne coinfections including Babesiosis, who failed commonly used antibiotic and antimalarial protocols.
Methods: 100 patients with Lyme disease, 56 of who were Babesia positive, were placed on Dapsone and folic acid in combination with either one or two other intracellular drugs, including rifampin, tetracyclines, and/or macrolide antibiotics. Several patients also took cephalosporins, and all patients were on protocols to treat cystic forms of Borrelia and biofilms.
\
Results: Patients completed a symptom severity survey before beginning treatment with Dapsone and then again after at least one month of treatment scoring their complaints from 0 indicating “none” to 4 indicating “severe” for symptoms including fatigue, joint and/or muscle pain, disturbed sleep, and cognitive difficulties. Results demonstrated that Dapsone significantly improved all patients’ clinical symptoms except for headache, where changes did not reach statistical significance. In addition, Dapsone, known to have anti-malarial effects, helped resistant Babesia symptoms of sweats, chills, and flushing. Lyme positive, Babesia positive patients also demonstrated significant changes in pain, disturbed sleep, and cognitive difficulties. Side effects included macrocytic anemia and rare cases of methemoglobinemia, which resolved by either decreasing the dose of Dapsone or increasing folic acid.
Conclusion: Dapsone is a novel and effective “persister” drug for those with PTLDS and associated tick-borne co-infections who have failed classical antibiotic protocols. Further prospective trials must determine the DDS dose,length of treatment and best combination antibiotic therapy in order to effect a long-term health benefit.
\
Horowitz RI, Freeman PR (2016) The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic Lyme Disease/Post
Treatment Lyme Disease Syndrome . J Clin Exp Dermatol Res 7: 345. doi:10.4172/2155-9554.1000345http://www.omicsonline.org/open-access/the-use-of-dapsone-as-a-novel-persister-drug-in-the-treatment-of-chroniclyme-diseasepost-treatment-lyme-disease-syndrome-2155-9554-1000345.pdf
---------------------------------------------------------------------------------------
Richard Horowitz, MD, and his wife, the lovely Lee, kicked off the weekend conference “Beyond Lyme & Other Chronic Illnesses: Reclaiming Your Health and Well-Being,” on the evening of Friday, December 4th. It was “healing with the Horowitz’s” at it’s finest.
We huddled eagerly–my girlfriend Dana and I among fifty or so professionals and patients–in the Sunset Room at the world renowned Kripalu Center for Yoga & Health, founded on the teachings and principles of Swami Kripalu, for a weekend of both retreat and research.
That evening, Dr. Horowitz and Lee established the foundation for the next few days, including first grounding us all in meditation and blessings from their years studying Tibetan Buddhism. It was science meets spiritualism in scenic and secluded Stockbridge, MA.
Second that evening, they established Hope.
Dr. Horowitz and Ying Zhang from John Hopkins, it seems, are on the verge of a breakthrough. Using mycobacterium drugs–like those used in leprosy and tuberculosis–in hope of cleverly and mercilessily attack the four main persisters: Borrelia, Babesia, Bartonella and mycoplasma. As Dr. Horowitz explains, he is typically successful in getting 92% of his patients better. But there is an “8%” that are the most difficult to treat. Could this breakthrough break the code for closing in on the 8% of people that are most difficult to get better? It could. I’ll never forget those chilling yet cheerful words: “We are closing in on the 8%,” Dr. Horowitz whispered.
It works like this. Dr. Horowitz first combines 2-3 intracellular antibiotics to reach the persister bacteria hiding in cells. This would be the “triple persister” cocktail. Then he pulses with a cellular antibiotic. This pulsing has been shown to be effective based on the incredible work of professor and researcher Kim Lewis of Northeastern University. Dr. Horowitz has found this regimen to be very successful for people who continue to have symptoms or relapses. BUT FURTHERMORE, he has now found with the help of the work from Dr. Zhang that adding dapsone (pyrazinamide) to this regimen for the most difficult of cases…could be THE key to perishing the persisters for once and for all. Dapsone being that potential mycobacterium super drug used against Tuberculosis and leprosy.
Dapsone, or prazinamide, targets tuberculosis bacteria that have become “persisters,” which don’t respond to typical antibiotics. Zhang and Horowitz’s hunch that this will also work to combat “persister” bacteria associated with lyme and co-infections…has been promising. Very promising. And it is likely that Dr. Horowitz will publish work being conducted on his patients in the upcoming year. For more on the work being conducted by Dr. Kim Lewis and Dr. Zhang, read here:
Dr. Lewis:
http://www.northeastern.edu/news/2015/06/researchers-discovery-may-explain-difficulty-in-treating-lyme-disease/
Dr. Zhang:
http://beforeitsnews.com/health/2015/10/lyme-disease-persister-drugs-dr-ying-zhang-2593390.html
http://magazine.jhsph.edu/2013/fall/news-briefs/two-takes-on-lyme/
http://www.jhsph.edu/news/news-releases/2014/new-test-shows-promise-in-identifying-new-drugs%20to-treat-lyme-disease.html
Remember, however, that based on Dr. Horowitz’s own experience, about “92%” can get better with the approach of “hitting all targets” and combining antibiotics that work on the spirochete, cell-wall deficient (or “L-form”) and cyst forms of Borrelia. To help understand what that means, the first link below provides a table comparing Borrelia’s multiple forms, and the second link below provides a helpful overview regarding which antibiotics target which different forms.
Overview of different forms of Borrelia:
http://www.lymebook.com/top10forms
Overview of antibiotics that attack different forms:
http://www.treatlyme.net/treat-lyme-book/kills-lyme-germs-a-brief-antibiotic-guide
AND specific examples of some of Dr. Horowitz’s favorite combinations for attacking the various forms of Lyme (as well as co-infections like bartonella and mycoplasma) are shown in the pictures below.
https://lymewhisperer.com/2015/12/13/kripalu-closing-in-on-the-8/
-----------------------------------------------------------------------------------
W roku 1936 do lecznictwa wprowadzono amid kwasu pirazynokarboksylowego (pirazynamid, PZA) (2) [5] lek, ktory szczegolnie korzystnie działa w terapii gruźliczego zapalenia opon mozgowo-rdzeniowych. Pirazynamid (2) łatwo wchłania się z przewodu pokarmowego.
Przy stosowaniu w dawce dziennej 3 g dłużej niż poł roku następują nieodwracalne zmiany w miąższu wątroby. Obecnie jest stosowany w chemioterapii krotkotrwałej i przerywanej [4,6]. W wyniku przemian metabolicznych lek ten wydzielany jest z moczem w postaci kwasu pirazynowego [7].Pirazynamid (2) otrzymuje się w reakcji amonolizy estru metylowego (3a) lub etylowego kwasu pirazynokarboksylowego (3b) (schemat 1) [8-10].
Inne
metody otrzymywania 2 polegają na reakcji kwasu
pirazyno-2,3-dikarboksylowego(4) (lub jego soli amonowej) z
mocznikiem w podwyższonej temperaturze [11] lub na dekarboksylacji
monoamidu kwasu pirazyno-2,3-dikarboksylowego (5)otrzymywanego w
wyniku selektywnej hydrolizy diamidu kwasu
pirazyno-2,3-dikarboksylowego(6) (schemat 1) [12].
Pirazynamid
(2) znajduje rownież zastosowanie w syntezie morinamidu -^ -(4
-morfolinometylo)amidu kwasu pirazynokarboksylowego (7) [13,14],
ktory charakteryzuje się silniejszym efektem terapeutycznym oraz
mniejszą toksycznością w porownaniu z 2. Obecność III rzędowej
grupy aminowej w cząsteczce 7 pozwala na przeprowadzenie go w łatwo
rozpuszczalny w wodzie chlorowodorek dzięki czemu zwiększa się
jego przyswajalność. Zastosowanie 2 w syntezie 7 polega na jego
reakcji z formaliną i morfoliną lub z A^-hydroksymetylomorfoliną
(schemat 2) [10].
W innej metodzie syntezy 7 pirazynamid (2) poddaje się najpierw kondensacji Mannicha z formaliną i dietyloaminą, a następnie otrzymany //(dietyloaminometylo)-pirazynokarboamid (8) poddaje reakcji z morfoliną (schemat 2) [13].
Levaditi
i Veissman w 1937 roku wykazali, że niektore pochodne sulfonowe
silnie oddziałująna prątki gruźlicy i trądu.
Dwa
lata poźniej wprowadzono do lecznictwa 4,4 ’-diaminodifenylosulfon
(dapson) (9) [7,15]. Związek ten charakteiyzuje się znaczną
toksycznością i obecnie jest stosowany głownie w leczeniu trądu.
Dapson (9) wchodzi także w skład przeciwgruźliczych lekow
złożonych, np. izoprodian firmy Saarstickstoff-Fatol) [16, 17].
Wprowadzone w kolejnych latach mniej toksyczne sulfony (np. 4,4 ’-diacetyloaminodifenylosulfon - radilon) są, w przypadku gruźlicy ludzkiej zbyt mało aktywne.Synteza dapsonu (9) polega na kondensacji chlorku kwasup-chlorobenzenosulfonowego (10) z chlorobenzenem w obecności chlorku glinu, a następnie substytucji nukleofilowej otrzymanego 4,4’-dichlorodifenylosulfonu (11) (schemat 3) [3,18].
--------------------------------------------------------------------------- Dapsone
is a drug that has been used since the 1940s to treat leprosy and a few other conditions. According to Horowitz, leprosy has long been known as a “persister”—a bacterial infection that can survive initial treatments by antibiotics. Since research indicates that Lyme and co-infections can similarly persist after treatment, he had theorized that Dapsone might be useful in this case as well.
In a preliminary clinical trial of 100 patients at his Hyde Park medical office, Horowitz gave Dapsone in combination with assorted other antibiotics. He found that patients reported significant improvement of ALL symptoms, except for headache. He told of one woman who, after being on Dapsone for five weeks, said this was the best she’d felt in 12 years. Her brain fog had cleared and her joint and muscle pain had diminished considerably.
However, Horowitz found that patients who stopped treatment after they began to feel better would relapse. This was true in leprosy as well. He says successful leprosy treatment uses a 12-month regimen of Dapsone and rifampin. He is now extending the protocol with his patients to see if 12 months is the right length of treatment for them as well.
Alas, Dapsone is not without a downside. It can cause serious side-effects, such as anemia, which must be closely monitored during treatment. Furthermore, Horowitz says, there are many unanswered questions about the use of persister drugs such as Dapsone to treat chronic Lyme, and much more research is needed.
You can read Dr. Horowitz’s published journal article about the Dapsone trial here. More about who should consider using Dapsone, and how best to minimize side-effects, will be included in his forthcoming book to be released at the end of 2016, “How Can I Get Better? An Action Plan for Treating Resistant Lyme and Chronic Disease.”
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Artykuł przeglądowy
Dapson – mechanizm działania, bezpieczeństwo stosowania oraz rola w leczeniu pemfigoidu pęcherzowego w świetle najnowszych wytycznych
Magdalena Żychowska, Aleksandra Batycka-Baran, Jacek Szepietowski, Wojciech Baran Przegl Dermatol 2016, 103, 176–184
Od ponad 50 lat dapson jest stosowany w leczeniu pemfigoidu pęcherzowego (BP). Zgodnie z europejskimi wytycznymi z 2015 roku w terapii BP zaleca się stosowanie miejscowych preparatów glikokortykosteroidowych (GKS) (0,5% propionianu klobetazolu). Ogólne GKS w dawce 0,5–0,75 mg/kg m.c. mogą być podawane w ciężkich postaciach choroby, natomiast dapson jest wskazany jako terapia drugiego rzutu lub leczenie adiuwantowe. W artykule przedstawiamy dane z piśmiennictwa dotyczące mechanizmu działania, skuteczności i bezpieczeństwa dapsonu w terapii BP. Po dokonaniu przeglądu medycznej bazy danych PubMed znaleźliśmy jedną metaanalizę oraz 7 badań klinicznych bez randomizacji oceniających skuteczność dapsonu w BP, która w monoterapii mieści się w granicach 20–45,4%. W przypadku stosowania dapsonu w połączeniu z miejscowymi GKS skuteczność wzrasta do 63–76%. Połączenie doustnych GKS z dapsonem umożliwia osiągnięcie remisji w 92–100% przypadków. Wielu autorów sugeruje, że dapson może być skutecznym i bezpiecznym lekiem adiuwantowym, pozwalającym na redukcję dawek GKS, jednak wciąż brakuje randomizowanych badań oceniających jego skuteczność w terapii BP.http://www.termedia.pl/Czasopismo/Przeglad_Dermatologiczny-56/Streszczenie-27310
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