6 replies to this topic

[birthdaysuit]

ANY LYME LITERATE PEOPLE? I believe the causative agent for my prolonged Borrelia Burgdorferi infection and or autoimmune symptoms are due in part to fungal shedding Borrelial TLR2/1-agonist antigens (OspA), which in turn has caused immune suppression, significantly low immunoglobulins and B-cell mutation. OspA, has been reported to act as a potent inflammatory stimulant through the toll like 2 receptor.

 

If anything, I believe that the infection is not what is causing my symptoms, although, there's no test to determine if the infection is cleared; secondary “Post Sepsis Syndrome" infections are the primary problem due to immune suppression from fungal shedding Borrelial TLR2/1-agonist antigens. I've been told its bio-films or spirochetes that are the reason for my persistent symptoms but honestly I believe it's a suppressed immune system, which has flared my neurological symptoms and reactivated older infections, such as Babesiosis, Herpes, Mycoplasma, Bartonella.

 

This is probably the reason why I continue to test positive for antibody OspA-31 on the IgM  and IgG test.

 

"spirochete can pinch off bits of its membrane in order to release its surface proteins. Explains Barbour: "It's like a bacterial Star Wars defense program," in which released surface proteins might intercept incoming host antibodies, keeping the spirochete safe from immunological attack.”

 

Honestly, I highly doubt Lyme disease is eradicated from antibiotics alone. Its various defense mechanisms make it hard to kill. When I stopped antibiotics my neurological symptoms flared, despite my healing immune system. I just don't know what to believe anymore and where to go from here. I don't know if anti-inflammatory herbs/drugs will help of if suppressing the immune system would be appropriate because of an autoimmune response due to a hypersensitivity from the blebs? Then again, it could still be an active infection. Would TLR2/1-antagonists help my situation, I understand they help Post Sepsis Syndrome and that could be what I have.

 

Edited by birthdaysuit, 13 October 2016 - 05:56 AM.

[birthdaysuit]

Then again, does the infection need to be active for blebs to cause symptoms? Ahh, I probably would develop MS if I took predisone. Most likely still have active infection in joints with, autoimmune problem.

Edited by birthdaysuit, 13 October 2016 - 06:07 AM.

[birthdaysuit]

Just wish they had a test that determined if the Lyme was gone. They probably do but who cares.

 

All pathogens produce a small subpopulation of dormant persister cells that are highly tolerant to killing by antibiotics. Once an antibiotic concentration drops, surviving persisters re-establish the population, causing a relapsing chronic infection. " Anther reason that abx don't work is that the molecules are too big to get in places like the joints . Rifampin and Azithromycin have Molecules about 800 daltons. http://www.ncbi.nlm.nih.gov/pubmed/10839713 "The 500 Dalton rule for the skin penetration of chemical compounds and drugs." Maybe, this is why my skin hurt for so long and I had a rash when taking both these antibiotics. Possibly, drove the infection into my dermis and epidermis. Not only do they not work but they also cause a lot of ROS which are carcinogenic molecules and "Lyme" causes a condition like cancer already called Infectious Angiogenisis. http://stm.sciencemag.org/content/5/192/192ra85 "Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells"

 

 

https://www.youtube....h?v=SVn_pG9_AQg

 

Damn, this video makes me sad. We literally have no fucking idea what Lyme really is and how to fully treat it, if at all.

Edited by birthdaysuit, 13 October 2016 - 06:15 AM.

[gamesguru]

At the bottom you can find how to submit an application, it's a clinical study about lyme: http://grants.nih.go.../PA-16-243.html

 

Lyme has reservoirs in neurons and glials, arteries and veins, other glands.. so a stem-cell or autophagy approach is helpful, just generally increasing metabolism or activity in the extracellular matrix (ECM).  And of course a careful diet to keep the immune system primed is invaluable in lyme.

Curr Drug Targets Infect Disord. 2001 Aug;1(2):171-9.

Adhesion mechanisms of the Lyme disease spirochete, Borrelia burgdorferi.

Coburn J¹.

 

Abstract

Borrelia burgdorferi (sensu lato), the spirochete that causes Lyme disease, is among the most fascinating and enigmatic of bacterial pathogens. An obligate parasite of other organisms, B. burgdorferi is maintained in the mammalian reservoir (small rodents) by tick-mediated transmission from infected individuals to other members of the population. The complex requirements that must be met to ensure survival in an immunocompetent rodent and in the tick vector, coupled with a relatively small genome, suggest that B. burgdorferi has evolved elegant strategies for interacting with its hosts. Among these strategies are several distinct mechanisms of adhesion to mammalian cells and extracellular matrix components. The mammalian receptors for B. burgdorferi that have been most thoroughly studied, and for which candidate bacterial ligands have been identified, are decorin, fibronectin, glycosaminoglycans, and beta 3-chain integrins.

 

Front Cell Infect Microbiol. 2014; 4: 175.

Mechanisms of Borrelia burgdorferi internalization and intracellular innate immune signaling

Tanja Petnicki-Ocwieja^* and Aurelie Kern

Abstract

Lyme disease is a long-term infection whose most severe pathology is characterized by inflammatory arthritis of the lower bearing joints, carditis, and neuropathy. The inflammatory cascades are initiated through the early recognition of invading Borrelia burgdorferi spirochetes by cells of the innate immune response, such as neutrophils and macrophage. B. burgdorferi does not have an intracellular niche and thus much research has focused on immune pathways activated by pathogen recognition molecules at the cell surface, such as the Toll-like receptors (TLRs). However, in recent years, studies have shown that internalization of the bacterium by host cells is an important component of the defense machinery in response to B. burgdorferi. Upon internalization, B. burgdorferi is trafficked through an endo/lysosomal pathway resulting in the activation of a number of intracellular pathogen recognition receptors including TLRs and Nod-like receptors (NLRs). Here we will review the innate immune molecules that participate in both cell surface and intracellular immune activation by B. burgdorferi.

 

PLoS Pathog. 2008 Oct 3;4(10):e1000169. doi: 10.1371/journal.ppat.1000169.

Molecular mechanisms involved in vascular interactions of the Lyme disease pathogen in a living host.

Norman MU¹, Moriarty TJ, Dresser AR, Millen B, Kubes P, Chaconas G.

 

Abstract

Hematogenous dissemination is important for infection by many bacterial pathogens, but is poorly understood because of the inability to directly observe this process in living hosts at the single cell level. All disseminating pathogens must tether to the host endothelium despite significant shear forces caused by blood flow. However, the molecules that mediate tethering interactions have not been identified for any bacterial pathogen except E. coli, which tethers to host cells via a specialized pillus structure that is not found in many pathogens. Furthermore, the mechanisms underlying tethering have never been examined in living hosts. We recently engineered a fluorescent strain of Borrelia burgdorferi, the Lyme disease pathogen, and visualized its dissemination from the microvasculature of living mice using intravital microscopy. We found that dissemination was a multistage process that included tethering, dragging, stationary adhesion and extravasation. In the study described here, we used quantitative real-time intravital microscopy to investigate the mechanistic features of the vascular interaction stage of B. burgdorferi dissemination. We found that tethering and dragging interactions were mechanistically distinct from stationary adhesion, and constituted the rate-limiting initiation step of microvascular interactions. Surprisingly, initiation was mediated by host Fn and GAGs, and the Fn- and GAG-interacting B. burgdorferi protein BBK32. Initiation was also strongly inhibited by the low molecular weight clinical heparin dalteparin. These findings indicate that the initiation of spirochete microvascular interactions is dependent on host ligands known to interact in vitro with numerous other bacterial pathogens. This conclusion raises the intriguing possibility that fibronectin and GAG interactions might be a general feature of hematogenous dissemination by other pathogens.

 

 

Found one herbal option, probably hard to buy it anywhere.

Pharmazie. 2011 Aug;66(8):628-30.

Growth inhibiting activity of lipophilic extracts from Dipsacus sylvestris Huds. roots against Borrelia burgdorferi s. s. in vitro.

Liebold T¹, Straubinger RK, Rauwald HW.

Author information

Abstract

Fresh first year roots from Dipsacus sylvestris HUDS. were extracted with 70% ethanol, ethyl acetate as well as dichloromethane. Extracts were solubilized in water (lipophilic extracts with addition of polysorbate 80) and tested for their activity against Borrelia burgdorferi sensu stricto in vitro during an eight-day period using amoxicillin as standard. The hydroethanolic extract showed no growth inhibition whereas significant growth inhibiting activity could be shown in the two less polar fractions for the first time. Strongest inhibition was found in the ethyl acetate extract. The effect of polysorbate 80 on bacterial growth was examined and found to be negligible. As the nature of bioactive constituents has not been clarified yet, a micellar electrokinetic capillary chromatography fingerprint analysis for a methanolic extract was applied including loganin, chlorogenic acid, cantleyoside and caffeic acid as marker substances.

 

 

As for your question...

J Nutr Biochem. 2013 Jul;24(7):1276-84. doi: 10.1016/j.jnutbio.2012.10.003. Epub 2013 Jan 17.

Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes.

Yoshida H¹, Watanabe W, Oomagari H, Tsuruta E, Shida M, Kurokawa M.

Abstract

Toll-like receptors (TLRs) were recently shown to be involved in obesity-induced inflammation in adipose tissue, which contributes to the development of insulin resistance and type 2 diabetes. Thus, the appropriate regulation of TLR expression or activation is an important strategy for improving obesity-related diseases. In this report, we show that naringenin, a citrus flavonoid, inhibits TLR2 expression during adipocyte differentiation. This effect is mediated in part through peroxisome proliferator-activated receptor γ activation. In addition, naringenin suppresses TLR2 expression induced by the co-culture of differentiated adipocytes and macrophages and also inhibits tumor necrosis factor-α (TNF-α)-induced TLR2 expression by inhibiting the activation of nuclear factor-κB and c-Jun NH2-terminal kinase pathways in differentiated adipocytes. Furthermore, naringenin decreases TLR2 expression in adipose tissue of high-fat diet-fed mice. These results are correlated with the improvement of hyperglycemia and the suppression of inflammatory mediators, including TNF-α and monocyte chemotactic protein-1. Taken together, these data suggest that naringenin exhibits anti-inflammatory properties, presumably by inhibiting TLR2 expression in adipocytes. Our findings suggest a molecular mechanism by which naringenin exerts beneficial effects against obesity-related diseases.

 

Inflammation. 2011 Oct;34(5):463-70. doi: 10.1007/s10753-010-9254-8.

Baicalin inhibits TLR2/4 signaling pathway in rat brain following permanent cerebral ischemia.

Tu XK¹, Yang WZ, Shi SS, Chen Y, Wang CH, Chen CM, Chen Z.

Abstract

Recent work from our laboratory demonstrated that baicalin attenuates inflammatory reaction and cerebral ischemia injury in rats. Toll-like receptor 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which mediate the inflammatory reaction, are involved in the pathophysiological processes of cerebral ischemia. In this study, we investigated whether baicalin inhibits TLR2/4 signaling pathway in a rat model of permanent focal cerebral ischemia. Adult Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administered by intraperitoneally injected twice at 2 and 12 h after the onset of ischemia. Cerebral infarct area and infarct volume were measured 24 h after MCAO. Expression of TLR2/4, NF-κB, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR or western blot. NO and PGE2 production in rat brain were measured 24 h after MCAO. Serum content of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. Baicalin reduced cerebral infarct area and infarct volume. Baicalin reduced the expression of TLR2/4 and NF-κB, decreased the expression and activity of iNOS and COX-2 in rat brain. Baicalin also attenuated the serum content of TNF-α and IL-1β. Our results suggest that baicalin inhibits the TLR2/4 signaling pathway in cerebral ischemia, which may be a mechanism underlying the baicalin's neuroprotection.

 

J Immunol Res. 2014;2014:740549. doi: 10.1155/2014/740549. Epub 2014 Jul 23.

Glycyrrhizin attenuates Toll like receptor-2, -4 and experimental vasospasm in a rat model.

Chang CZ¹, Wu SC², Kwan AL³.

Abstract

Upregulated TLRs are observed in the serum of animals following experimental subarachnoid hemorrhage. This study was to examine glycyrrhizin's effect on proinflammatory cytokines and TLRs in SAH rats. Administration with glycyrrhizin was initiated 24 hr before and 1 hr later using osmotic minipump. Basilar arteries were harvested to examine TLRs mRNA and protein (rt-PCR and western blot) and CSF cytokines (rt-PCR). Morphologically, deformed endothelium, tortuous elastic lamina, and smooth muscle necrosis were observed in the SAH rats, but were absent in the glycyrrhizin pretreatment group. The TLR-3 protein level was not increased in SAH animals, compared with the controls, while that of TLR-2 and -4 in the SAH only and SAH plus vehicle groups was significantly elevated (P < 0.01). Pretreatment and treatment with glycyrrhizin reduced TLR-2 and -4 by 28 ± 8% and 33.4 ± 9.2%, respectively. Likewise, glycyrrhizin was able to reduce the IL-1β and MCP-1 mRNA levels. This study shows glycyrrhizin exerts anti-inflammatory effects on SAH induced vasospasm and attenuates the ultrashort time expression of TLRs, like TLR-2 and -4. It corresponds to SAH induced early brain injury. These findings offer credit to the antivasospastic effect of glycyrrhizin and its effect on SAH induced early brain injury.

Edited by gamesguru, 13 October 2016 - 12:24 PM.

[birthdaysuit]

Pharmazie. 2011 Aug;66(8):628-30.

Growth inhibiting activity of lipophilic extracts from Dipsacus sylvestris Huds. roots against Borrelia burgdorferi s. s. in vitro.

Liebold T¹, Straubinger RK, Rauwald HW.

Author information

Abstract

Fresh first year roots from Dipsacus sylvestris HUDS. were extracted with 70% ethanol, ethyl acetate as well as dichloromethane. Extracts were solubilized in water (lipophilic extracts with addition of polysorbate 80) and tested for their activity against Borrelia burgdorferi sensu stricto in vitro during an eight-day period using amoxicillin as standard. The hydroethanolic extract showed no growth inhibition whereas significant growth inhibiting activity could be shown in the two less polar fractions for the first time. Strongest inhibition was found in the ethyl acetate extract. The effect of polysorbate 80 on bacterial growth was examined and found to be negligible. As the nature of bioactive constituents has not been clarified yet, a micellar electrokinetic capillary chromatography fingerprint analysis for a methanolic extract was applied including loganin, chlorogenic acid, cantleyoside and caffeic acid as marker substances.

 

 

As for your question...

J Nutr Biochem. 2013 Jul;24(7):1276-84. doi: 10.1016/j.jnutbio.2012.10.003. Epub 2013 Jan 17.

Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes.

Yoshida H¹, Watanabe W, Oomagari H, Tsuruta E, Shida M, Kurokawa M.

Abstract

Toll-like receptors (TLRs) were recently shown to be involved in obesity-induced inflammation in adipose tissue, which contributes to the development of insulin resistance and type 2 diabetes. Thus, the appropriate regulation of TLR expression or activation is an important strategy for improving obesity-related diseases. In this report, we show that naringenin, a citrus flavonoid, inhibits TLR2 expression during adipocyte differentiation. This effect is mediated in part through peroxisome proliferator-activated receptor γ activation. In addition, naringenin suppresses TLR2 expression induced by the co-culture of differentiated adipocytes and macrophages and also inhibits tumor necrosis factor-α (TNF-α)-induced TLR2 expression by inhibiting the activation of nuclear factor-κB and c-Jun NH2-terminal kinase pathways in differentiated adipocytes. Furthermore, naringenin decreases TLR2 expression in adipose tissue of high-fat diet-fed mice. These results are correlated with the improvement of hyperglycemia and the suppression of inflammatory mediators, including TNF-α and monocyte chemotactic protein-1. Taken together, these data suggest that naringenin exhibits anti-inflammatory properties, presumably by inhibiting TLR2 expression in adipocytes. Our findings suggest a molecular mechanism by which naringenin exerts beneficial effects against obesity-related diseases.

 

Inflammation. 2011 Oct;34(5):463-70. doi: 10.1007/s10753-010-9254-8.

Baicalin inhibits TLR2/4 signaling pathway in rat brain following permanent cerebral ischemia.

Tu XK¹, Yang WZ, Shi SS, Chen Y, Wang CH, Chen CM, Chen Z.

Abstract

Recent work from our laboratory demonstrated that baicalin attenuates inflammatory reaction and cerebral ischemia injury in rats. Toll-like receptor 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which mediate the inflammatory reaction, are involved in the pathophysiological processes of cerebral ischemia. In this study, we investigated whether baicalin inhibits TLR2/4 signaling pathway in a rat model of permanent focal cerebral ischemia. Adult Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administered by intraperitoneally injected twice at 2 and 12 h after the onset of ischemia. Cerebral infarct area and infarct volume were measured 24 h after MCAO. Expression of TLR2/4, NF-κB, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR or western blot. NO and PGE2 production in rat brain were measured 24 h after MCAO. Serum content of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. Baicalin reduced cerebral infarct area and infarct volume. Baicalin reduced the expression of TLR2/4 and NF-κB, decreased the expression and activity of iNOS and COX-2 in rat brain. Baicalin also attenuated the serum content of TNF-α and IL-1β. Our results suggest that baicalin inhibits the TLR2/4 signaling pathway in cerebral ischemia, which may be a mechanism underlying the baicalin's neuroprotection.

 

J Immunol Res. 2014;2014:740549. doi: 10.1155/2014/740549. Epub 2014 Jul 23.

Glycyrrhizin attenuates Toll like receptor-2, -4 and experimental vasospasm in a rat model.

Chang CZ¹, Wu SC², Kwan AL³.

Abstract

Upregulated TLRs are observed in the serum of animals following experimental subarachnoid hemorrhage. This study was to examine glycyrrhizin's effect on proinflammatory cytokines and TLRs in SAH rats. Administration with glycyrrhizin was initiated 24 hr before and 1 hr later using osmotic minipump. Basilar arteries were harvested to examine TLRs mRNA and protein (rt-PCR and western blot) and CSF cytokines (rt-PCR). Morphologically, deformed endothelium, tortuous elastic lamina, and smooth muscle necrosis were observed in the SAH rats, but were absent in the glycyrrhizin pretreatment group. The TLR-3 protein level was not increased in SAH animals, compared with the controls, while that of TLR-2 and -4 in the SAH only and SAH plus vehicle groups was significantly elevated (P < 0.01). Pretreatment and treatment with glycyrrhizin reduced TLR-2 and -4 by 28 ± 8% and 33.4 ± 9.2%, respectively. Likewise, glycyrrhizin was able to reduce the IL-1β and MCP-1 mRNA levels. This study shows glycyrrhizin exerts anti-inflammatory effects on SAH induced vasospasm and attenuates the ultrashort time expression of TLRs, like TLR-2 and -4. It corresponds to SAH induced early brain injury. These findings offer credit to the antivasospastic effect of glycyrrhizin and its effect on SAH induced early brain injury.

 

 

Thank you so much! I am taking heparin via picc line for Babesiosis, seems to also affect Burgdorferi spirochete, at least by making them more susceptible to antibiotics, plus it seems to help bring down inflammation but only for a few hours.

 

And dipsacus sylvestris is just a synonym for dipsacus fullonum or Teasal Root, which I believe can be found on amazon as extracts in tincture form. Not sure if they are equiolent to the extract used in the study you linked.

 

Highest inhibition was found in the ethyl acetate fraction (99.7± 1.0% on day 4). In this fraction all visible forms of Bbss were immobile within the first day, their number did not increase within eight days.

 

 

So ethyl acetate extract of Teasal Root would be the best bet at inhibiting growth of spirochetes in vitro, not sure in vivo but regardless patients have had good results with it.

 

What I find very interesting is that Baicalin from what I know as a chemical found in Skullcap is an inhibitor of TLR2 and so isn't Naringenin from grape fruits, both have significant killing ability in vitro against all forms of Lyme, including cystic forms! Actually, so far Baicalin is the strongest herbal plant extract that has high affinity on all forms of  B. Burgdorferi and garnii. Just a matter of administration and if it works in vivo. Hesperidin is found in plasma and tissue after ingestion so that's a plus.

 

Curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage, I've also read some studies that it works synergistically with antibiotics.

 

And in regards to antibiotics, do you know anything about Daptomycin? http://journals.plos...ne-0117207-t002

 

This study looks at various antibiotic combos against spirochetes, biofilms, etc. Right now, I have at home rifampin, Hydroxychlorquine, Doxycycline, and a PICC line administering Rocephin, which is in the same class as cefoporazone. They didn't combine Daptomycin with Rocephin and Doxy but in the chart two combo administration of Rocephin with Daptomycin had a significant reduction in live cell percentage equivalent to that of a cefoporazone, daptomycin combo.

 

I say this because cefoporazone is discontinued and I wouldn't know where to get it. I'm not sure of the side effects of daptomycin but it sure seems to be the best bet when combined with an inter-cellular like doxy and a cell wall inhibitor like Rocephin or cefoporazone.

 

 

 

 

Edited by birthdaysuit, 14 October 2016 - 08:44 AM.

[birthdaysuit]

Serum anti-NapA antibodies were found in 48% of the patients with Lyme arthritis but were undetectable in the healthy controls. T cells from the synovial fluid of patients with Lyme arthritis produced interleukin-17 (IL-17) in response to NapA. Moreover, NapA was able to induce the expression of IL-23 in neutrophils and monocytes, as well as the expression of IL-6, IL-1beta, and transforming growth factor beta (TGFbeta) in monocytes, via Toll-like receptor 2. CONCLUSION:

These findings indicate that NapA of B burgdorferi is able to drive the expression of IL-6, IL-1beta, IL-23, and TGFbeta by cells of the innate immune system and to elicit a synovial fluid Th17 cell response that might play a crucial role in the pathogenesis of Lyme arthritis.

 

Both Naringenin and Baicalin inhibit IL-17 and I&-6. Of course I need a balance between th2/th1 immune response but these two flavones possibly help lyme induced arthritis while being able to inhibit and kill many forms of Lyme.

[birthdaysuit]

And I've been referring to glucuronide of baicalein, baicalin. I've meant baicalein but they probably are similar.