Archive for the ‘Inflammation’ Category

Joint Swelling & Inflammation Found in Bb Infected Mice After Treatment with Ceftriaxone

Targeting of vascular adhesion protein-1 by positron emission tomography visualizes sites of inflammation in Borrelia burgdorferi-infected mice

Siitonen R, Pietikäinen A, Liljenbäck H, Käkelä M, Söderström M, Jalkanen S, Hytönen J, Roivainen A.
Arthritis Research & Therapy, online first Nov 22, 2017.

https://doi.org/10.1186/s13075-017-1460-4

Abstract

Background
In the present study, we sought to evaluate the feasibility of targeting vascular adhesion protein-1 (VAP-1) by positron emission tomography (PET) for the longitudinal quantitative assessment of Borrelia burgdorferi infection-induced inflammation in mice.

Methods
Mice with B. burgdorferi infection-induced arthritis were studied. During a 7-week follow-up period, the progression of arthritis was monitored weekly with 68Ga-DOTA-Siglec-9 PET/computed tomography (CT) and measurement of tibiotarsal joint swellings. A subgroup of infected mice was treated with ceftriaxone. Finally, histopathological assessment of joint inflammation was performed and VAP-1 expression in joints were determined.

Results
Explicit joint swelling and 68Ga-DOTA-Siglec-9 uptake could be demonstrated in the affected joints from B. burgdorferi-infected mice. By contrast, no obvious accumulation of 68Ga-DOTA-Siglec-9 was detected in joints of uninfected mice. The maximum swelling and highest uptake in the affected joints were observed 4 weeks after the infection. 68Ga-DOTA-Siglec-9 uptake in joints correlated with joint swelling (P < 0.0001) and histopathological scoring of inflammation (P = 0.020). Despite short-term antibiotic treatment, the arthritis persisted, and the PET signal remained as high as in nontreated mice. Immunohistochemistry revealed strong-to-moderate expression of VAP-1 in the synovium of B. burgdorferi-infected mice, while only weak expression of VAP-1 was detected in uninfected mice.

Conclusions
The present study showed that 68Ga-DOTA-Siglec-9 can detect B. burgdorferi infection-induced arthritis in mice. Furthermore, longitudinal PET/CT imaging allowed monitoring of arthritis development over time.

Free, full text:
https://doi.org/10.1186/s13075-017-1460-4

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For more:  https://madisonarealymesupportgroup.com/2015/09/19/proof-of-borrelia-persistence/

https://madisonarealymesupportgroup.com/2017/08/18/drexel-prof-lyme-persists/

https://madisonarealymesupportgroup.com/2016/12/21/dr-zhang-on-persisters/

https://madisonarealymesupportgroup.com/2017/11/03/lyme-bug-stronger-than-antibiotics-in-animals-and-test-tubes-now-study-people/

Category:

Inflammation, Lyme, research

Bartonella: Endocarditis, Opportunistic Infection in Cancer Patients, and Eye Inflammation

https://www.ncbi.nlm.nih.gov/m/pubmed/28490579/  Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis.

Okaro U1, Addisu A2, Casanas B2, Anderson B3. Clin Microbiol Rev. 2017.

Abstract
Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana. We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella-mediated endocarditis and represents a potential reservoir for persistence by these bacteria.

https://www.ncbi.nlm.nih.gov/m/pubmed/28328183/  Seroprevalence of Bartonella species, Coxiella burnetii and Toxoplasma gondii among patients with hematological malignancies: A pilot study in Romania.

Messinger CJ1, Gurzau ES2,3, Breitschwerdt EB4,5, Tomuleasa CI6,7, Trufan SJ8, Flonta MM9, Maggi RG4,5, Berindan-Neagoe I6,10,11, Rabinowitz PM8. Zoonoses Public Health. 2017.

Abstract
Patients receiving immunosuppressive cancer treatments in settings where there is a high degree of human-animal interaction may be at increased risk for opportunistic zoonotic infections or reactivation of latent infections. We sought to determine the seroprevalence of selected zoonotic pathogens among patients diagnosed with haematologic malignancies and undergoing chemotherapeutic treatments in Romania, where much of the general population lives and/or works in contact with livestock. A convenience sample of 51 patients with haematologic cancer undergoing chemotherapy at a referral clinic in Cluj-Napoca, Romania, was surveyed regarding animal exposures. Blood samples were obtained and tested for evidence of infection with Bartonella species, Coxiella burnetii and Toxoplasma gondii, which are important opportunistic zoonotic agents in immunocompromised individuals. 58.8% of participants reported living or working on a farm, and living or working on a farm was associated with contact with livestock and other animals. 37.5% of participants were IgG seroreactive against one or more of five Bartonella antigens, and seroreactivity was statistically associated with living on farms. Farm dwellers were 3.6 times more likely to test IgG seroreactive to Bartonella antibodies than non-farm dwellers. 47.1% of the participants tested T. gondii IgG positive and 13.7% tested C. burnetii IgG positive, indicating past or latent infection. C. burnetii IgM antibodies were detected in four participants (7.8%), indicating possible recent infection. These results indicate that a large proportion of patients with haematologic cancer in Romania may be at risk for zoonotic infections or for reactivation of latent zoonotic infections, particularly with respect to Bartonella species. Special attention should be paid to cancer patients’ exposure to livestock and companion animals in areas where much of the population lives in rural settings.

https://www.ncbi.nlm.nih.gov/m/pubmed/28405890/  Seroprevalence of Bartonella Species in Patients with Ocular Inflammation.

Brydak-Godowska J1, Kopacz D1, Borkowski PK2, Fiecek B3, Hevelke A4, Rabczenko D5, Tylewska-Wierzbanowska S3, Kęcik D1, Chmielewski T3. Adv Exp Med Biol. 2017.

Abstract
Bartonella species, vector-borne etiologic agents of many systemic or self-limited infections, are responsible for a widening spectrum of diseases in humans, including inflammatory conditions of the eye. The aim of this study was to determine whether there is any relationship between uveitis and the evidence of Bartonella spp. infection in the serum, ocular fluid, and cataract mass in patients with intraocular inflammation. Polymerase chain reaction (PCR)-based tests and DNA sequencing were performed on surgery-extracted specimens of intraocular fluid and lens mass of 33 patients. Sera from 51 patients and 101 control subjects were tested for the presence of specific antibodies against Bartonella spp. Neither IgM-class antibodies against Bartonella spp. nor Bartonella spp. DNA were detected. A specific IgG-class antibody was found in 33.3% of the patients with uveitis. The rate of positive Bartonella serology was higher among the uveitis patients than that in control subjects. This high rate may in part result from unrecognized indirect mechanisms rather than the immediate presence and multiplication of Bartonella spp. in the eyeball. Nonetheless we believe that screening for Bartonella spp. should become part of the diagnostic workup in uveitis.

Another ocular study:  https://madisonarealymesupportgroup.com/2017/04/06/ocular-bartonellosis/

Category:

Bartonella, Inflammation, research

Proof of Borrelia Persistence

The following work by microbiologist Thomas Grier and pathologist Alan MacDonald should prove to the CDC that Borrelia can undoubtably persist inside the human body.

http://whatislyme.com/lyme-a-beautiful-killer-by-thomas-grier/

“For years pathologists stained for amyloid to make the diagnosis, but when the same plaques in a serial sectioning were stained for B burgdorferi or B miyamotoi, individual classical spirochetes could be seen, but more commonly a biofilm of Borrelia could be seen in the same plaques. Borrelia is a brain-pathogen.”

grier

Above:  “Borrelia miyamotoi using Alan MacDonald’s FISH stain. This is the first documented case of Bm in Minnesota.”

tom2

Above and below:  “Since Fluorescence FISH stain target species specific nucleotide sequences, it is species specific. Spirochetes are excellent subjects because the Borrelia DNA is associated with the cell wall and membrane. Another probe can isolate cytoplasmic DNA thus giving a 3-D look to it. What a beautiful killer.”

spiro

Below:  “This patient was told for 22 years that she had MS, our work on MS allowed us to determine that this brain MRI was probably a result of Lyme. Do you see the markers? This Philadelphia woman made a very good recovery from her disability and went back to work.”

Below:  “This is Borrelia burgdorferi in the brain of a man sick for two decades. The others in red were Borrelia miyamotoi. Another finding was even after treatment he had neutrophils in the brain, and indication of a breakdown of the BBB and inflammation. He was sicker than doctors realized!”

ms-lyme

“The last photo taken of Grier’s friend Scott from Twig MN.  His deathbed video is all about helping other Lyme victims.”  Scotty was a 57 year old Lumberman who lived his whole life in the forest.  Scotty was seronegative for Lyme but was bedridden with pain and neurolyme and was treated for 7+ years with aggressive antibiotics.  His brain autopsy revealed several surprises and live active Borrelia burgdorferi.”  

scott

Contact Thomas Grier M.S. at donatebrain@gmail.com to ask him about helping fund his research.

For more:  https://madisonarealymesupportgroup.com/2018/04/17/persistent-borrelia-infection-in-patients-with-ongoing-symptoms-of-lyme-disease/  Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

https://madisonarealymesupportgroup.com/2019/01/16/study-shows-diminished-pathogen-specific-antibody-production-in-coinfected-mice-contributing-to-persistent-infection/

https://madisonarealymesupportgroup.com/2018/10/30/study-shows-lyme-msids-patients-infected-with-many-pathogens-and-explains-why-we-are-so-sick/  For the first time, Garg et al. show a 85% probability for multiple infectionsincluding not only tick-borne pathogens but also opportunistic microbes such as EBV and other viruses….In addition to tick-borne co-infections and non-tick-borne opportunistic infections, pleomorphic Borrelia persistent forms may induce distinct immune responses in patients by having different antigenic properties compared to typical spirochetes32,33,34,35. Nonetheless, current LD diagnostic tools do not include Borrelia persistent forms, tick-borne co-infections, and non-tick-borne opportunistic infections.

http://norvect.no/230-peer-reviewed-studies-show-evidence-of-persistent-lyme-disease/

http://lymerick.net/persistent-borreliosis.htm  Microscopy, Culture or PCR-verified cases of persistent [seronegative] Lyme Borreliosis

https://madisonarealymesupportgroup.com/2018/04/13/chronic-lyme-post-mortem-study-needed-to-end-the-lyme-wars/

https://madisonarealymesupportgroup.com/2018/07/23/exploring-the-controversial-concept-of-chronic-lyme-disease/

 

Category:

Borrelia Miyamotoi (Relapsing Fever Group), Inflammation, Lyme, research

Herxheimer Die-Off Reaction Explained

With most infections, people feel better after starting treatment.  Often within 24 – 48 hours there is sweet relief of symptoms.  MSIDS (multi systemic infectious disease syndrome) is unique in that you often feel worse after starting treatment.  The following article written by Marty Ross, MD, explains why.

http://www.treatlyme.net/treat-lyme-book/herxheimer-die-off-reaction-inflammation-run-amok  Written by November 7, 2014

“If you feel worse after herbal anti-microbials or prescriptive antibiotics to treat Lyme are started it is likely you are having a Herxheimer die-off reaction.”

A die-off reaction, also called a Herxheimer reaction, can occur when treating the Lyme germ, some co-infections, and yeast. It occurs as bacteria or yeast die during antibiotic treatment. It is common to have Herxheimer die-off reactions when starting herbal anti-microbials or antibiotics when treating Lyme. These reactions can also occur when new antibiotics are introduced into a treatment.

In a die-off reaction, there is a release of toxins, proteins, and oxidizing agents that results in an increase in inflammatory cytokines such as tumor necrosis factor alpha, interleukin-6, and interleukin-8.

The symptoms of a die-off reaction are generally a worsening of the underlying symptoms of Lyme disease and its associated infections. A majority of Lyme disease symptoms are actually excess inflammatory cytokine symptoms. So in a die-off reaction there is a worsening of many Lyme disease symptoms including: fatigue, brain-fog, muscle and nerve pain, chills and sweats, and/or memory and thinking.

Cytokines: The Good and The Bad

Good: Cytokines are proteins made by various types of white blood cells to fight infections. They perform a number of functions that include:

  • making antibodies work more effectively,
  • increasing active white blood cells to fight infections,
  • recruiting white blood cells to the location of an infection,
  • turning on white blood cells to fight infections, and
  • decreasing viral and bacterial replication.

Bad: Too many cytokines:

  • suppress the immune system,
  • cause pain,
  • decrease hormone production from organs like the thyroid and the adrenal glands,
  • disturb sleep,
  • decrease brain function,
  • increase fatigue and tiredness,
  • waste muscles,
  • cause depression, and
  • decrease the function of various organs throughout the body resulting in many other symptoms and medical problems.

Cytokines: How They are Made

Cytokines are made when immune cells are stimulated by germs, oxidizing agents, cytokines, toxins, and other agents. Once the immune cells are stimulated an intracellular messenger called NF-kB causes genetic programming for the production of cytokines and the turning on of white blood cells to fight infections. Within the white blood cell cytokines are then produced in chemical reactions which require enzymes called kinases.

Cytokines in Lyme: What’s the Problem?

Cytokines are good, right? Well yes and no.

In the right amount they promote healing. In excess, they are harmful. The problem in chronic Lyme and associated diseases is that they are made in excess. This occurs even more so in a Herxheimer die-off reaction.

How to treat a Herxheimer Die-Off Reaction

To treat Herxheimer die-off reactions there are a number of interventions to:

  • lower oxidizing agents,
  • decrease NF-kB genetic programming of cells,
  • block kinase enzymes,
  • block inflammatory prostaglandins triggered by cytokines,
  • promote liver detoxification, and
  • lower blood acid levels.

Based on the work of Martin Pall, PhD, it is critcal to lower oxidizing agents that trigger cytokine production. Ecklonia cava extract derived from sea weed is a potent oral anti-oxidant which seems to have greater affect than other ones. In addition to this, alpha lipoic acid (ALA), n-acetyl cysteine (NAC), and glutathione are helpful. Glutathione and its precursor building blocks ALA and NAC also support liver removal of toxins. In addition the antioxidants quercetin and curcumin decrease NF-kB induced genetic signals to produce cytokines and block the production of inflammation prostaglandins. Quercetin also blocks kinase enzymes required in the production of cytokines. Blocking kinases with quercetin interferes with the cytokine production line. Prostaglandins are inflammation and pain chemicals that are triggered by inflammatory cytokines.

My Recommendations

Step 1: The Beginning of Treatment to Prevent Herxheimer Die-off Reactions.

Use a good multivitamin that includes alpha lipoic acid n-acetyl cysteine, antioxidants, and other micronutrients that decreases oxidizing agents and supports liver detoxification. I prefer multivitamin products in powder form made by Thorne or Integrative Therapeutics.

  • Curcumin 500mg 1 pill 3 times a day.
  • Multivitamin. Use multivitamin powders by Thorne or Integrative Therapeutics. Use as directed on the product label.

Step 2: Moderate Herxheimer Die-off Reactions.

For more severe cases add oral glutathione while continuing the multivitamin and curcumin. Glutathione is also a great choice if there is nerve pain or numbness. If the addition of glutathione is not effective than add ecklonia cava and consider adding quercetin. You can use all four. This combination works to block the cytokine production line and decreases oxidizing agents that trigger production. These treatments can take 1-2 weeks for maximum effect.

  • Glutathione (as oral liposomal glutathione) 500mg 1 or 2 times a day.
  • Quercetin 250mg 2 pills 3 times a day.
  • Ecklonia Cava 400mg 2 pills 2 to 3 times a day

If glutathione is not tolerated then work with one or a combination of the following anti-oxidants that are used to make glutathione.

  • Alpha Lipoic Acid 350mg 1 pill 2 times a day.
  • N-Acetyl Cysteine 500mg 1 pill 3 times a day.

Step 3: Severe Herxheimer Die-off Reactions.

For severe die-off reactions use IV glutathione as a potent antioxidant and to support liver detoxification. This is administered in an integrative medicine physician’s office. Another option is to use glutathione in a nebulizer. Glutathione IV is stronger than glutathione by nebulizer in my experience. Using a nebulizer you breath in a fine mist of the glutathione which is absorbed into the blood throught the blood vessels in the lungs. Sometimes I will start a person with four IV glutathione treatments and then change to glutathione by nebulizer to continue the treatment.

  • Glutathione IV 1200mg to 2500mg 2 times a week for a minimum of four treatments. If it helps but there are still improvements with the last treatment, consider weakly treatments until improvements plateau. You will likely feel more tired after the first treatment.
  • Glutathione by nebulizer 200mg/ml 2ml 2 times a day for adults. Children can take 100mg/ml 1ml to 2ml 2 times a day.

In addition to Ross’s suggestions, there are other methods that can help you detox which should lessen your herxes:

  1.  Take hot epsom salt baths and basically anything that makes you sweat.  Your skin is your largest organ and you can sweat toxins out.  In as hot of water as you can stand, put 1-2 Cups of Epsom Salts and try and get as much of your body to soak in the water.  Make sure you don’t burn your skin and drink plenty of good quality water.  Some people add in 1 Cup of hydrogen peroxide and a half a box of baking soda as well.  It is all helpful.  Light exercise in which you break a sweat is helpful too, but make sure your doctor is in agreement and don’t overdo it.  Walking is free and gets you out in the fresh air and sunshine – all of which are healing.  Infrared saunas, hot tubs, Biomats, anything that makes you sweat will help you detox.  https://madisonarealymesupportgroup.com/2018/06/01/yes-you-do-sweat-out-toxins/
  2. Drink lemon water.  Lemon water helps reduce inflammation by decreasing acidity and by removing uric acid from your joints.  It encourages healthy digestion by loosening toxins in your digestive tract and relieves heartburn, burping, and bloating.  It contains pectin fiber which assists in fighting off cravings and enhances enzyme function which stimulates your liver and detoxes your blood.  Lemon juice is full of Vitamin C which beefs up your immune system and it is higher in potassium than apples or grapes.  It diminishes viral infections and sore throats.  If you weigh less than 150, squeeze half a lemon in to a glass of water and drink.  If over 150lbs, use an entire lemon’s juice.  According to Dr. Sara Solomon, rinse your mouth out with water immediately after drinking lemon water as it is tough on enamel.  Do NOT brush your teeth for 60 minutes because acid leaves the enamel softened and more prone to erosion during brushing. Also, chemical reactions increase with temperature so drink it at room temperature.  http://www.drsarasolomon.com/hot-lemon-water-and-enamel-erosion/
  3. Colon Cleanses.  Since 60-70% of our immune system is in our gut, keeping this pathway going is crucial.  Some use Bentonite, psyllium husk powder (plain, no sugar or additives), chlorella, herbal bowel cleanses, coffee enemas, colonics, pro and prebiotics, Slippery elm, marshmallow root, aloe vera, plain yogurt or kefir, kombucha and fermented foods, garlic and onions, and anything else that heals leaky gut syndrome and strengthens your gut flora.  Most improve considerably by going on a no sugar no gluten diet.  Some have to remove dairy as well as any other foods that cause allergy type symptoms. (Often colonic practitioners will add anti-parasitic and/or other essential oils if you ask)
  4. Detoxing herbs:  Some have found major relief by using milk thistle, pinella, burbur, parsley, nettle, andrographis, dandelion root, and other herbs that help them detox.  http://www.nutramedix.ec/ns/lyme-protocol  When you click this link you will see the herbs used in the Cowden protocol.  Scroll down to the herbs listed in green and then read up and even watch a short video explaining the herbs that have “detox” listed after them.  If you had to pick one herb it would be Japanese Knotweed.  According to Master Herbalist, Stephen Buhner, it crosses the blood-brain barrier and is a drug and herb synergist, facilitating the movement of other herbs and drugs into hard to reach places.  It modulates and enhances immune function, is active against a number of gram-negative and gram-positive bacteria including leptospira and Treponema denticola spirochetes, is anti-inflammatory for both arthritic and bacterial inflammations, protects the body against endotoxin damage, helps reduce herxes, and protects the heart by increasing blood flow.  A very helpful, common, invasive ditch weed indeed!
  5. Diet.  Besides avoiding food allergens which cause leaky gut syndrome, many have found help by avoiding inflammatory foods.  Gluten, casein (found in dairy), and sugar cause inflammation and can make everything worse.  Eat foods high in nutrients and fiber.  Many do very well vegetable juicing which cleanses the body but makes the blood alkaline which promotes healing and prevents Herxes.  Notice I didn’t say “fruit” juicing.  Breaking down fruit and taking away it’s fiber content in juicing will spike insulin and therefore cause inflammation.  Use veggies instead.  Also, make sure you get plenty of good Omega 3 fats.  Most of us need fish oil, as well as cod liver or krill oil for vitamin D3 as we Northerners are typically abysmally low in D3 which can only be increased by getting sun onto the skin which then causes our body to make it.  Since the sun angle is so much lower here we need to supplement.  You should have your vitamin D levels checked at least yearly.
  6. Stimulate the Lymphatic System.  Exercise is listed above under sweating, but it also should be mentioned that movement causes lymph drainage, which is quite helpful in detoxing.  Jumping on a trampoline or just doing jumping jacks will assist in this.  Getting a Swedish massage feels great and also gets the lymph system working.  There is actually something called “Lymph drainage massage.”  Dry brushing does this as well.  Purchase a soft, natural brush, preferably with a long handle to reach everywhere and begin brushing at your feet and moving in long sweeping motions toward your heart, making sure to brush several times in each area, overlapping as you go.  Follow this up with your detox bath listed above, sipping on your lemon water and you really will get things moving and detoxing all in one fell swoop.
  7. Heavy Metal Detoxing.  Metals compromise our immune system and inhibit enzyme systems vital to cellular function so it only makes sense to eliminate them.  Some doctors use IV methods while others use zeolite, chlorella, citrus pectin, or HMD (a synergistic blend of chlorella growth factor, coriandrum stadium and a homaccord of chlorella pyrenoidosa).  You should also consider getting any mercury amalgams removed as mercury can cause a wide range of serious health problems, but make sure you get a qualified biological dentist who uses the correct procedures.

For more:  https://madisonarealymesupportgroup.com/2017/06/28/jarisch-herxheimer-a-review/

https://www.lymedisease.org/lymesci-herxing/

https://madisonarealymesupportgroup.com/2015/12/06/tips-for-newbies/

https://madisonarealymesupportgroup.com/2018/02/24/top-3-lyme-detox-myths-busted-dr-rawls/

 

Category:

Detoxing, diet and nutrition, Gut Health, Herbs, Inflammation, Lyme, Pain Management, Supplements, Treatment