Note again the reference to bismuth (ingredient pepto-bismol!!) Salvarsan was Paul Ehrlichs (yes, ehrlichiosis ehrlich) magic bullet for syphillis made of an arsenic drug!!!))))))) *******************************************
1: Scand J Infect Dis. 1996;28(2):155-7.
Antibiotics and increased temperature against Borrelia burgdorferi in vitro.
Reisinger E, Wendelin I, Gasser R, Halwachs G, Wilders-Truschnig M, Krejs G. Department of Medicine, Karl Franzens University, Graz, Austria.
In 1917, spirochaetal neurosyphilis was treated successfully with malariotherapy in combination with salvarsan or bismuth.
Malariotherapy for spirochaetal Lyme disease has been discussed, but the mechanism of an antispirochaetal effect remains unclear.
We cultured Borrelia burgdorferi at different temperatures, alone and in combination with antibiotics.
Our data demonstrate that growth of the strains PKo and ATCC 35210 (B31) was impaired at temperatures of 37 degrees C and inhibited at 39 degrees C and 40 degrees C, respectively.
Strain ATCC 35211, however, grew well up to 39 degrees C but did not multiply at 40 degrees C. A bactericidal effect was seen at 41 degrees C for the strains B31 and PKo and at 42 degrees C for all strains.
The susceptibility of all strains to penicillin and ceftriaxone was increased up to 16-fold by an elevation of temperature from 36 degrees C to 38 degrees C.
These in vitro data suggest that elevated body temperature may be beneficial during antimicrobial treatment of Lyme disease.
This may be particularly important in tissues where high concentrations of antibiotics are difficult to achieve.
PMID: 8792482
(re salvarsan just fyi- Arsphenamine From Wikipedia, the free encyclopedia Jump to: navigation, search
The structure of arsphenamine was believed to be A until 2005, when new research suggested the true structure was in fact a mixture of the trimer B and the pentamer CArsphenamine is a drug that was used to treat syphilis and trypanosomiasis. It was the first modern chemotherapeutic agent. Sahachiro Hata discovered the anti-syphilitic activity of this compound in 1908 in the laboratory of Paul Ehrlich, during a survey of hundreds of newly-synthesized organic arsenical compounds. Ehrlich had theorized that by screening many compounds a drug could be discovered with anti-microbial activity. Ehrlich's team began their search for such a magic bullet among chemical derivatives of the dangerously-toxic drug atoxyl. This was the first organized team effort to optimize the biological activity of a lead compound through systematic chemical modifications, the basis for nearly all modern pharmaceutical research.
Arsphenamine was marketed under the trade name Salvarsan in 1910. It was also called 606, because it was the 606th compound synthesized for testing.
Posted by Annxyz (Member # 9097) on :
Does this require a prescription? Very Interesting article. Possibly something to add to the anti lyme arsenal.
Posted by MommaK (Member # 10376) on :
Can anyone convert the temp to farenheit for me? How hot are we talking!
Thanks!
Posted by treepatrol (Member # 4117) on :
This is all been brought up before.
41 Celsius = 105.8 Fahrenheit 42 Celsius = 107.6 Fahrenheit
Posted by CaliforniaLyme (Member # 7136) on :
Yup, tree, it has almost ALL been brought up ALL before!!!! I don't think I have read a new hting here except for Marnie & Caves posts in years- but the new people tend not to have read stuff- !!!
Thank you for the conversions!!! Best wishes, Sarah
Posted by johnlyme1 (Member # 7343) on :
The one thing that I have not seen is stats on if temp will kill any of the co-infections?
Posted by aklnwlf (Member # 5960) on :
Does anyone know how long it would take to receive any benefit from being exposed to such a high heat?
I was receiving fever bath treatments for awhile where they induced a fever of 104 F. for at least 10 minutes.
Obviously this was not adequate.
What's the protocol?
I've heard recently in the past 2 weeks of 104 F. for about 3-5 hours but don't want to try it if the temp isn't high enough.
It's so expensive.
Any help out there?
Posted by treepatrol (Member # 4117) on :
quote:Originally posted by CaliforniaLyme: Yup, tree, it has almost ALL been brought up ALL before!!!! I don't think I have read a new hting here except for Marnie & Caves posts in years- but the new people tend not to have read stuff- !!!
Thank you for the conversions!!! Best wishes, Sarah
I guess iam just getting worn down again I hope you know I didnt mean anything by the sleepy guy Posted by Karenelee (Member # 11044) on :
So here is a question.
In the explanation regarding western blot by Dr C of Missouri:
<<45: Heat shock protein. This helps the bacteria survive fever. The only bacteria in the world that does not have heat shock proteins is Treponema pallidum, the cause of syphilis.>>
So doesn't this heat shock protein protect borreliosis from heat?
Karen
Posted by CaliforniaLyme (Member # 7136) on :
Tree, I *was* crushed momentarily. See, I am like the newbies in a way because I forget all the details of these things and *I* get so excited to see a good abstract again- it's like a good steak (Tofu steak of course*)!!!! But I'm ok*)!!! Thank you for asking!!
Karen, YES, this is why treponema pallidum is particularly susceptible although one researcher did think they found an hsp candidate!!! But there is an enzyme- will post below- involved as well-!!!
1: J Bacteriol. 1990 Jun;172(6):2862-70. Links
Isolation and characterization of a Treponema pallidum major 60-kilodalton protein resembling the groEL protein of Escherichia coli.
Houston LS, Cook RG, Norris SJ. Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston 77025.
A native structure containing the major 60-kilodalton common antigen polypeptide (designated TpN60) was isolated from Treponema pallidum subsp. pallidum (Nichols strain) through a combination of differential centrifugation and sucrose density gradient sedimentation.
Gel filtration chromatography indicated that this structure is a high-molecular-weight homo-oligomer of TpN60. Antisera to TpN60 reacted with the groEL polypeptide of Escherichia coli, as determined by immunoperoxidase staining of two-dimensional electroblots. Electron microscopy of the isolated complex revealed a ringlike structure with a diameter of approximately 16 nm which was very similar in appearance to the groEL protein.
Comparison of the N-terminal amino acid sequence of TpN60 with the deduced sequences of the E. coli groEL protein, related chaperonin proteins from mycobacteria and Coxiella burnetti, the hsp60 protein of Saccharomyces cerevisiae, the wheat ribulose bisphosphate carboxylase-oxygenase-subunit-binding protein (alpha subunit), and the human P1 mitochondrial protein indicated sequence identity at 8 of 22 to 10 of 22 residues (36 to 45% identity).
We conclude that the oligomer of TpN60 is homologous to the groEL protein and related chaperonins found in a wide variety of procaryotes and eucaryotes and thus may represent a heat shock protein involved in protein folding and assembly.
PMID: 1971618
1: J Bacteriol. 2001 Aug;183(16):4702-8. Links
Treponema pallidum 3-phosphoglycerate mutase is a heat-labile enzyme that may limit the maximum growth temperature for the spirochete.
Benoit S, Posey JE, Chenoweth MR, Gherardini FC. Department of Microbiology, University of Georgia, Athens, Georgia 30602, USA.
In the causative agent of syphilis, Treponema pallidum, the gene encoding 3-phosphoglycerate mutase, gpm, is part of a six-gene operon (tro operon) that is regulated by the Mn-dependent repressor TroR.
Since substrate-level phosphorylation via the Embden-Meyerhof pathway is the principal way to generate ATP in T. pallidum and Gpm is a key enzyme in this pathway, Mn could exert a regulatory effect on central metabolism in this bacterium.
To study this, T. pallidum gpm was cloned, Gpm was purified from Escherichia coli, and antiserum against the recombinant protein was raised.
Immunoblots indicated that Gpm was expressed in freshly extracted infective T. pallidum. Enzyme assays indicated that Gpm did not require Mn(2+) while 2,3-diphosphoglycerate (DPG) was required for maximum activity. Consistent with these observations, Mn did not copurify with Gpm.
The purified Gpm was stable for more than 4 h at 25 degrees C, retained only 50% activity after incubation for 20 min at 34 degrees C or 10 min at 37 degrees C, and was completely inactive after 10 min at 42 degrees C.
The temperature effect was attenuated when 1 mM DPG was added to the assay mixture. The recombinant Gpm from pSLB2 complemented E. coli strain PL225 (gpm) and restored growth on minimal glucose medium in a temperature-dependent manner. Increasing the temperature of cultures of E. coli PL225 harboring pSLB2 from 34 to 42 degrees C resulted in a 7- to 11-h period in which no growth occurred (compared to wild-type E. coli).
These data suggest that biochemical properties of Gpm could be one contributing factor to the heat sensitivity of T. pallidum.
PMID: 11466272
Infect Immun. 1990 April; 58(4): 1038-1042
Thermoregulation of protein synthesis in Borrelia burgdorferi. R G Cluss and J T Boothby Department of Biological Sciences, San Jose State University, California 95192.
ABSTRACT
Borrelia burgdorferi, the etiological agent of Lyme disease, infects humans via the bite of a tick. The microbe survives in at least two vastly different environments: an arthropod vector and a warm-blooded host. We examined protein synthesis in B. burgdorferi B31 in response to sudden heat stress, which is similar to that which occurs during the transmission from vector to host. Proteins synthesized after shifts from 28 degrees C to higher temperatures and in pulse-chase experiments were labeled with 3H-labeled amino acids for 4 h and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. The synthesis of four proteins we designated as heat stress proteins (HSPs) was increased by shifts to higher temperatures (HSP-1, 75 kilodaltons [kDa]; HSP-2, 42 kDa; HSP-3, 39 kDa; and HSP-4, 27 kDa); and the amount of one protein we designated as heat-labile protein 1 (29.5 kDa) was decreased at higher temperatures. At 37 to 40 degrees C, the major heat stress protein, HSP-1, represented 14 to 18% of the total cell protein compared with 1 to 2% of the total cell protein at 28 degrees C. HSP-1 was stable during a 4-h chase at either 40 or 28 degrees C. Demonstration of similar HSPs in low-passage, pathogenic strains of B. burgdorferi suggests that the heat stress response may be common among B. burgdorferi strains and may play a role in Lyme disease.
Characterization of the heat shock response and identification of heat shock protein antigens of Borrelia burgdorferi. M M Carreiro, D C Laux and D R Nelson Department of Microbiology, University of Rhode Island, Kingston 02881.
ABSTRACT
The heat shock response of Borrelia burgdorferi B31 cells was characterized with regard to the heat shock proteins (Hsps) produced. Five to seven Hsps were detected by sodium dodecyl sulfate-gel electrophoresis and fluorography of proteins from cells labeled with [35S]methionine after shifts from 33 degrees C to 37 or 40 degrees C or from 20 degrees C to 33, 37, or 40 degrees C. Analysis of [35S]methionine-labeled Hsps by two-dimensional electrophoresis and autoradiography revealed 12 Hsps. Western immunoblot analysis with antisera to highly conserved Escherichia coli and Mycobacterium tuberculosis Hsps revealed a single 72-kilodalton (kDa) protein band that reacted with antibodies to E. coli DnaK and with antibodies to the M. tuberculosis 71-kDa Hsp homolog of E. coli DnaK. Two proteins with apparent molecular masses of 66 and 60 kDa reacted with antibodies against the M. tuberculosis 65-kDa Hsp homolog of E. coli GroEL. Human immune sera collected from patients with Lyme disease reacted with both the 66-kDa Hsp and the 60-kDa Hsp but failed to react with the 72-kDa Hsp. These data are discussed with regard to the possibility that host recognition of highly conserved epitopes of GroEL homologs of B. burgdorferi may result in autoimmune reactions causing arthritis and other pathologies.
Serum hemolytic activity of Babesia gibsoni-infected dogs: the difference in the activity between self and nonself red blood cells.
Onishi T, Suzuki S, Horie M, Hashimoto M, Kajikawa T, Ohishi I, Ejima H. Department of Veterinary Science, College of Agriculture, University of Osaka Prefecture, Japan.
The serum hemolytic activity of Babesia gibsoni-infected dogs varied when assayed with nonself red blood cells from different dogs, whereas it did not vary when assayed with red blood cells, irrespective of self or nonself, from a particular dog throughout the experiment. The variety in activity determined with nonself red blood cells was not related to the type of red blood cell by DEA, D and J systems. Serum hemolytic activity with self red blood cells was different in the course of infection from that with nonself red blood cells, especially in the late stage of infection, when the activity with self red blood cells decreased more rapidly than that with nonself red blood cells. The results indicate that the serum hemolytic activity of B. gibsoni-infected dogs determined with self red blood cells probably reflects the in vivo activity, suggesting that the rapid decrease in activity in the late stage of infection is a way of acquired resistances for the host to recover from hemolytic anemia in the infection. The facts that the hemolytic activity increased by heating the serum at 56 degrees C, that the osmotic fragility of red blood cells remained almost on the same during the course of infection and that Coombs' test for red blood cells of the infected animal was negative suggest that the immune-mediated hemolytic anemia is not a possible mechanism for the progressive and severe anemia in B. gibsoni-infection. The present results support the previous notion that the increased serum hemolytic activity is at least one of the causes of anemia in canine B. gibsoni-infection.
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