Anti-inflammatory effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in neuronal cultures of dorsal root ganglia and myelinating cells of the peripheral nervous system

Anti-inflammatory effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in neuronal cultures of dorsal root ganglia and myelinating cells of the peripheral nervous system

Geeta Ramesh, Olivia C. Meisner and Mario T. Philipp
Journal of Neural Inflammation, online first, December 23, 2015.

http://doi.org/10.1186/s12974-015-0461-y


Abstract

Background
Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), could result in cognitive impairment, motor dysfunction, and radiculoneuritis. We hypothesized that inflammation is a key factor in LNB pathogenesis and recently evaluated the effects of dexamethasone, a steroidal anti-inflammatory drug, and meloxicam a non-steroidal anti-inflammatory drug (NSAID), in a rhesus monkey model of acute LNB. Dexamethasone treatment significantly reduced the levels of immune mediators, and prevented inflammatory and/or neurodegenerative lesions in the central and peripheral nervous systems, and apoptosis in the dorsal root ganglia (DRG). However, infected animals treated with meloxicam showed levels of inflammatory mediators, inflammatory lesions, and DRG cell apoptosis that were similar to that of the infected animals that were left untreated.

Methods
To address the differential anti-inflammatory effects of dexamethasone and meloxicam on neuronal and myelinating cells of the peripheral nervous system (PNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in rhesus DRG cell cultures and primary human Schwann cells (HSC), using multiplex enzyme-linked immunosorbent assays (ELISA). We also ascertained the ability of these drugs to modulate cell death as induced by live Bb in HSC using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay and the potential of dexamethasone to modulate Bb-induced apoptosis in HSC by the TUNEL assay.

Results
Earlier, we reported that dexamethasone significantly reduced Bb-induced immune mediators and apoptosis in rhesus DRG cell cultures. Here, we report that dexamethasone but not meloxicam significantly reduces the levels of several cytokines and chemokines as induced by live Bb, in HSC and DRG cell cultures. Further, meloxicam does not significantly alter Bb-induced cell death in HSC, while dexamethasone protects HSC against Bb-induced cell death.

Conclusions
These data help further explain our in vivo findings of significantly reduced levels of inflammatory mediators, DRG-apoptosis, and lack of inflammatory neurodegenerative lesions in the nerve roots and DRG of Bb-infected animals that were treated with dexamethasone, but not meloxicam. Evaluating the role of the signaling mechanisms that contribute to the anti-inflammatory potential of dexamethasone in the context of LNB could serve to identify therapeutic targets for limiting radiculitis and axonal degeneration in peripheral LNB.

http://doi.org/10.1186/s12974-015-0461-y

Free, full text (pdf file, 2.7 MB):
http://www.jneuroinflammation.com/content/pdf/s12974-015-0461-y.pdf

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Lyme and Other Tick-Borne Diseases: Science Bridging the Gap: 

Summary Report from:

Lyme Disease Association 16^th Annual Conference, November 14 & 15 2015, Rhode Island, USA

Report from Dr Sandra Pearson, Lyme Disease Action's Medical Director, who attended the conference.

The conference was opened by Patricia Smith, President of the Lyme Disease Association, who gave an overview of the spread of Lyme disease and increase in tick-borne diseases in the USA. Pat detailed the work of the Lyme Disease Association in raising awareness and the significant support and fund-raising undertaken for important research projects.

Read the rest of the report:
http://www.lymediseaseaction.org.uk/latest-news/report-from-usa-conference/

Could Claritin Cure Lyme Disease?

I have posted about this before, but here is another publication on the same topic:

An OTC allergy medication may be able to kill the bacteria behind Lyme disease, bringing researchers closer to developing the first targeted therapy for the debilitating infection.

Since Lyme-causing Borrelia burgdorferi survive on manganese (Mn), researchers from the Stanford University School of Medicine hypothesized that blocking the bacteria's Mn transport protein, Borrelia metal transporter A (BmtA), would starve the bacteria and ultimately help cure the infection.

Among a shortlist of FDA-approved compounds that could potentially bind to the BmtA structure, the investigators determined that the antihistamine loratadine (Claritin)—and specifically its metabolite, desloratadine—were able to inhibit Mn from entering the cell walls of Borrelia, causing the bacteria to die in test tubes.

Read the full story:
http://www.pharmacytimes.com/news/could-claritin-cure-lyme-disease

Medical brain teaser from a colleague...

Okay. So I love to play Scrabble on my computer, early in the morning, with a cup of coffee. 

This morning I played the word "pint" and the computer added an "a" to the word on the next round.  

Pinta? As in Nina, Pinta and the Santa Maria???

I was lost for a definition. So I asked the program to define the word and it came back: skin disease.

Well you all know how I love Google. And guess what, pinta is a skin disease caused by a spirochete -Treponema pallidum (as many of the docs here might well know).

From the Merck Manual:

Bejel, pinta, and yaws (endemic treponematoses) are chronic, tropical, nonvenereal spirochetal infections spread by body contact. Symptoms of bejel are mucous-membrane and cutaneous lesions, followed by bone and skin gummas. Yaws causes periostitis and dermal lesions. Pinta lesions are confined to the dermis. Diagnosis is clinical and epidemiologic. Treatment is with penicillin.

From the Encyclopedia of Children's Health.

Definition

Pinta is a bacterial infection of the skin that causes lesions, red to bluish-black colored spots and splotches, and discoloration of the skin.

Description

Pinta is a skin infection caused by the bacterium Treponema carateum , a relative of the bacterium that causes syphilis. The word "pinta" comes from Spanish and means "painted." Pinta is also known as "azula" (blue), and "mal de pinto" (pinto sickness). It is one of several infections caused by different Treponema bacteria, which are called "endemic" or "non-venereal" treponematoses.

Transmission

Pinta is spread from one person to another by direct skin-to-skin contact. The bacteria enter the skin through a small cut, scratch, or other skin damage. Once inside the body, warmth and moisture allow the bacteria to multiply. The bacterial infection causes red, scaly lesions on the skin.

The disease is also known as endemic syphilis. According to Medscape,

"Treponemes are highly sensitive to azithromycin and penicillin, which remain the drugs of choice. Yaws, pinta, and endemic syphilis are treated with azithromycin or penicillin G benzathine. Alternatives are appropriate only if penicillin cannot be used. Tetracyclines or chloramphenicol have been used. Treatment failures with penicillin have been reported, but reinfection could not be ruled out."

And look at this photo of rashes caused by the disease posted at a site run by BRIAN L. ALTONEN, MS MPH.  It resembles a bull's eye.

Here is Altonen's description of the disease:

Pintos Malady

Pinta is a skin condition that occurs in Mexico, Central America and South America.  It is caused by Treponema pallidum carateum, an organism quite similar in biology and genetics to the Treponema pallidum associated with syphilis.   The ability for a bacterium to evolve within a given region is obviously quite possible, and this version of Treponema is no exemption to this evolutionary concept.   The prevalence of  this version of Treponema is not unique to Mexico's epidemiological history.  As early as Chris Colon's arrival to the New World in 1492, it was possible for this form of sexually transmitted disease to make its way around the world in exchange for equally contagious forms of measles and small pox left behind by the same sailing crew.

The most noticeable feature of those infected by this bacterium is the mottled skin, with varying colors and sizes of the patches that are formed.  The resemblances of these patches to the mottled, marble-like patterns found on Pinto horses naturalizing to this region is the source of the name for this condition.  Pinta is transmitted through direct skin-to-skin contact rather than through mucosal membranes like the related Treponema pallidum when it is responsible for syphilis.  Two to three weeks following transmission the area in and around the point of contact erupts to form a papule, which ultimately becomes dry and scaley enabling the skin to flake off.  Three to nine months later, thick, flat patches are formed all over the body which can remain there permanently at times resulting in reductions and increases in the natural pigmentation process scattered about the body's surface irregularly.

What I haven't seen yet is how people come in contact with this bacteria in the first place.The disease common in childhood. Here's a 2014 article on the topic from Clinical Microbiology Reviews. 

I guess this rambling also speaks to six degrees of separation for bacteria too. And certainly provides food for thought about the rashes, sexual transmission and other issues we have discussed here.

PA woman says she was sickened by risky Lyme treatment

Mon Dec 14, 2015 12:24 pm (PST) . 

*Pa. woman says she was sickened by risky Lyme treatment*
Tom Avril, /The Philadelphia Inquirer/, Philadelphia, Pennsylvania

December 8, 2015
http://www.philly.com/philly/health/20151208_Pa__woman_says_she_was_sickened_by_risky_Lyme_treatment_.html
or http://tinyurl.com/jo9k45k

Ashley Pettis started to have trouble concentrating at the end of spring 
semester in 2013 at Lancaster Bible College, and soon began to feel 
sluggish and achy.

Exhausted by the end of the summer, she was found to have mononucleosis. 
But later, she still felt sick, and went that fall to Haverford Wellness 
Center in the Montgomery County town of Harleysville, seeking answers.

Clinicians there said she had late-stage Lyme disease, a chronic form of 
the tick-borne illness that is diagnosed in an estimated 300,000 
Americans a year.
...
The treatment they administered was controversial: five months of 
heavy-duty oral and intravenous antibiotics costing tens of thousands of 
dollars that her insurance would not cover.

Pettis did not have Lyme disease at all.

*Full story & comments*: http://tinyurl.com/jo9k45k

*Letters*: inquirer.letters@phillynews.com 
<mailto:inquirer.letters@phillynews.com>

What do you think? Leave comments!

-Bob

Ticks in Christmas trees

ALBANY, N.Y. (NEWS10) – An unseasonably warm winter could see ticks and mites in Christmas tree branches.

Every year, hundreds of thousands of trees are cut, sold, and stood up in houses all over the world. But this season has been abnormally warm, and experts say that can bring some unwanted insects hidden in the branches.

Christmas season is an industry all on its own. Troy's Landscaping in Albany New York sells over 1,500 trees each year. This winter is off to a mild start, and without snow to brush off the branches, some trees may have insects, such as ticks and mites, settled in for the winter.

"They can shake them out," tree salesman Justin Burbube said. "If they are nervous, they can go home, set it up in their garage for a day or two. If your garage is warm enough, if there are ticks, that may help them get out."

If you do find bugs in your tree, don't spray pesticides on the tree. It's toxic to breathe in and could cause the tree to catch on fire if it has Christmas lights.

Burbube said there's no way to know exactly what, if anything, is living in a Christmas tree, so it's important to remain observant.

"Just be vigilant," he said. "You check your kids and your dog that you aren't getting anything like that. A lot of places are like us. They do a good job of making sure that you don't get the ticks."

See the article:

http://wdtn.com/2015/12/09/warm-winter-could-mean-unwanted-insects-like-ticks-in-christmas-trees/

Isolation of live Borrelia burgdorferi sensu lato spirochetes....

Isolation of live Borrelia burgdorferi sensu lato spirochetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis — ScienceDirectThis is groundbreaking, if confirmed!

http://www.sciencedirect.com/science/article/pii/S1198743X1500991X

Austrailian soldier claims antimarial drug mefloquine caused brain damage

This story is relevant to Lyme because of the references to doxycycline (the antibiotic most often used for treating Lyme disease) and anti-malarial drugs such as Lariam. That drug brings to mind other antimalarials such as Mepron and Malarone, both used for treating Babesia in the brain.

http://www.abc.net.au/news/2015-12-11/former-soldier-comes-forward-over-adf-drug-trial-brain-injury/7008620

A West Australian former soldier has spoken out over fears an anti-malaria drug he took as part of a pharmaceutical trial while serving has left him with a permanent and debilitating brain injury.

Former rifleman Mathew Emerson came forward after another high-ranking currently serving soldier gave evidence at a Senate inquiry last week,detailing concerns hundreds of soldiers may have suffered severe long-term side effects from the drug mefloquine, including depression, anxiety, vertigo, nightmares and suicidal thoughts.

Mr Emerson, 35, said his battalion was offered the choice of mefloquine, marketed as Lariam, or the older more established drug doxycycline, prior to a planned deployment to East Timor in 2001.

"They said 'it's got less side effects than doxycycline, and you only need to take it once a week', so most of the people I knew decided to take the mefloquine," he said.

"I felt perfectly safe and that the Army had my life as their best interest. They trained me, they're meant to look after me, but in this case, they didn't."

He said he was told to sign a consent form, and that if he did not sign it he could not deploy.

He stopped taking the drug after experiencing nausea, but then was placed back on it for another five weeks.

In 2003, Mr Emerson said he started to "go downhill" mentally.

"I started to feel depressed. I wanted to kill myself, had constant thoughts about it," he said.

"I went to see the Army psychiatrists, and it sounded stupid when I went to say the words so I didn't say anything, I just kept my mouth shut.

"I put on a rosy exterior, just tried to keep a smile on my face all the time."

He also started having nightmares and outbursts of anger, and in 2004 had a complete nervous breakdown where he woke up in hospital with no memory of the previous few days, despite being conscious and alert during that time.

Mefloquine use in Australia

• Mefloquine approved for use by Australian Therapeutic Goods Administration (TGA) in 1993
• Drug's factsheet from manufacturer Roche notes neuropsychiatric effects including anxiety, paranoia, depression and psychotic behaviour have been reported to occur long after the drug has ceased to be taken
• The ADF continues to prescribe mefloquine, but says it is a "third-line agent", and only used when one of two other TGA-approved medications are not appropriate
• ADF says prescriptions have averaged 25 per year for the past five years

Treatment for MS does well in phase 3 trials

(since this is one of the misdiagnoses of Lyme, maybe it will interest some)

Anti-CD20 antibody wows in multiple sclerosis

• Cormac Sheridan

Nature Biotechnology

33,

1215–1216

(2015)

doi:10.1038/nbt1215-1215

Published online

09 December 2015

Article tools

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Jessica Wilson / Science Source

MRI of normal brain (left) and one with multiple sclerosis (right).

Roche plans to seek approval early in the new year for its anti-CD20 antibody ocrelizumab as therapy in both forms of multiple sclerosis (MS)—primary progressive and relapsing remitting—following positive outcomes from recent phase 3 trials.

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CFS = HHV6 IN VAGUS NERVE

Is chronic fatigue syndrome (CFS) actually an infection by a type of herpes virus?

CFS: a herpesvirus infection of the vagus nerve?

				CFS: a herpesvirus infection of the vagus nerve? CFS: a herpesvirus infection of the vagus nerve? Michael VanElzakker, a researcher affiliated with the Tufts University PTSD neuroimaging laboratory as well as the ...
				View on hhv-6foundation.org	Preview by Yahoo

Dolores Claesson, FL 

German sudy finds Lyme disease in mosquitoes

Ticks Tick Borne Dis. 2015 Nov 12. pii: S1877-959X(15)30032-7. doi: 10.1016/j.ttbdis.2015.10.018. [Epub ahead of print]

Occurrence of Borrelia burgdorferi s.l. in different genera of mosquitoes (Culicidae) in Central Europe.

Melaun C¹, Zotzmann S¹, Santaella VG¹, Werblow A¹, Zumkowski-Xylander H², Kraiczy P³, Klimpel S⁴.

 

Author information

http://www.sciencedirect.com/science/article/pii/S1877959X15300327

 

Abstract

 

Lyme disease or Lyme borreliosis is a vector-borne infectious disease caused by spirochetes of the Borrelia burgdorferi sensu lato complex. Some stages of the borrelial transmission cycle in ticks (transstadial, feeding and co-feeding) can potentially occur also in insects, particularly in mosquitoes. In the present study, adult as well as larval mosquitoes were collected at 42 different geographical locations throughout Germany. This is the first study, in which German mosquitoes were analyzed for the presence of Borrelia spp. Targeting two specific borrelial genes, flaB and ospA encoding for the subunit B of flagellin and the outer surface protein A, the results show that DNA of Borrelia afzelii, Borrelia bavariensis and Borrelia garinii could be detected in ten Culicidae species comprising four distinct genera (Aedes, Culiseta, Culex, and Ochlerotatus). Positive samples also include adult specimens raised in the laboratory from wild-caught larvae indicating that transstadial and/or transovarial transmission might occur within a given mosquito population.