onight's post is a mere subset, a small fraction, of the real one I want to do at a future point. The one in the future will be big, in fact that will set a distinct Mozz record for the most amount of words, the most amount of parts, it will be the biggest project I have ever undertaken in terms of PAR research. It will literally take weeks and weeks...hope to have it out this side of Christmas?
But tonight I'm not waiting for that, this subset was just too compelling for me to wait....tonight I present to you my scientific paragraph of the year. We will get to that after some necessary background.
As always, sit back and please, do enjoy!
INTRO
In 2014 a group of Japanese scientists conducted some research into a particular condition known as HTLV-1 published in the Journal of NeuroVirology. Let's investigate what this condition is.
"HTLV-1 is a virus that infects your T-cells. T-cells are a type of white blood cellthat form part of your immune system. HTLV-1 is also called human T-cell lymphotropic virus".2
A small percentage of these patients that have HTLV-1 go on to develop what is known as an inflammatory condition HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP) .
The symptoms aren't great:
"HAM/TSP results in demyelination of the spinal cord and clinical manifestations of this disease include progressive muscle weakness and hyperreflexia of the lower limbs, sensory disturbance, urinary incontinence, and impotence. These symptoms are generally slowly progressive, while patients at older ages of onset show faster progression. Women are affected more frequently than men".3
HAM/TSP is a curious type of indication in that it affects certain communities more than others. In the Japanese population the following symptoms have also been recorded:
Different nationalities have different symptoms suggesting it's genetically and environmentally influenced?
Paradigmers, the disease is inflammatory and much of the chronic inflammation develops in the spine. It also has neurological ramifications. One of the best tests for this condition and related inference that a drug might be working is the 10 m walk test.
"Progressive neurological symptoms, such as lower extremity motor dysfunction with urinary disturbances, develop in patients with HMA/TSP and lead to deterioration in quality of life".1
How does this manifest?
Pathological changes are more prevalent in the lower thoracic spinal cord.
Stagnant lymphocytes can easily transmigrate to the tissues and evoke immune reactions because of decreased blood flow.
"Bystander damage" during the interaction between the HTLV-a infected cytotoxic T cells and the HTLV infected cells can subsist.
There are interactions between lymphocyte integrins and their receptors on vascular endothelial cells.
Remember these key points, we will come back to them.
CURRENT REMEDIES
For the poor suffering patients that have this disease the good news is that there are some drugs used to treat it...Corticosteroid hormone as well as interferon-alpha.
The bad news is that these drugs have side effects and often there is insufficient effects when using them!
The other bad news is that the present drugs are expensive for long term treatment.
PREVALENCE
To be honest, I had never even heard of this one, so I kinda assumed there wouldn't be too many suffering from this infliction? In all the research I've done with Pentosan its never come up.
So how many suffer from it?
Mozz Quiz?
Of course...
QUESTION: HOW MANY PATIENTS IN THJE WORLD HAVE HTLV-1 DISEASE?
A) Well it cant be too many, have YOU heard of it before? 1,800 people?
B) Ok step up from A) 20,000
C) Double A and B combined, around 44,000?
Again you are all wrong including me... its a fractionate more than C)...
... it's around 10 million.3 Yes that stat is from a peer reviewed paper.
The interesting thing is that this virus seems to be endemic in certain regions of the world, namely southwestern Japan, the Caribbean basin, Central Africa, South America, the Melanesian Islands, and the Middle East.
But in Iran, the infections are the greatest, almost 2-3% of the entire population! This is suggesting that the disease has a strong genetic component.
.PARAGRAPH OF THE YEAR
Yeah this next paragraph was a bit of an eye opener and again I said to myself after a few choice words..."What do we actually own?"
How many people really truly understand what we have...
The paragraph below is a little sciency, I'll break it down a bit more after you have read it.
Ok lets get on with it, here is the paragraph:
."A clinical trial was designed to test the effect of subcutaneous administration of PPS in 12 patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction in an open-labelled design. Subcutaneous PPS weekly (25 mg in week 1, 50 mg in week 2 and 100 mg in weeks 3 - 8) caused a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I pro-viral copy numbers in peripheral blood, contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-1. However, serum soluble VCAM-1 was significantly increased without significant changes in the serum level of chemokines (CXCL10 and MCP-1). There was a positive correlation between increased sVCAM-1 and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP".
Ok why did I think it was paragraph of the year?
1) Mate, iPPS is effectively assisting you to walk better, quicker, more effectively over 10 m if you have this virus. We take walking for granted, the patients with this HTLV-1 DON'T...they don't take walking for granted, they don't find it easy, their 'lower extremity motor dysfunction' prevents them from walking with a normal gait, a normal speed. To them, this would be a LIFE CHANGER.
2) Micro circulation? Put your hands up if you know what a capillary plexus is?
Ok by lack of hands I think I'm definitely going to have to spend a little time here...its worth explaining.
*clears throat*.
ONE, JUST one of iPPS's many Mechanisms of wonderful action involves facilitating the vascular pathobiology...what the heck does that mean?
Well lets take a look at an analogy. I have a mate, he likes to have a nice garden but he ain't the most motivated and industrious of fellows. He plants a new plant in the back yard and he waters it...but his hose doesn't quite reach so he takes his finger and cuts off a bit of the spray so the spray travels further and he waters his new plant from a distance ...beaut? Well yes and no. The poor plant is new, its getting bombarded by this crazy gardener's jet stream...
Less this....
More this!
Or even this...
The plant at this early and tender stage of life wants mist....drops around the foliage...it wants a small weak stream around the roots....saturation...it wants to be loved and doesn't want stress, and it yet it wants the precious water...the precious nutrients.
Enter Pentosan!
Huh?
Has Mozz had one too many tap beers at the local? No no I'm totally sober as I write this...
iPPS assists the really fine fibrous capillaries right at the end that get up close to the subchondral bone, to the cartilage and surround it....in order to be able to deliver the required nutrients as close to the site as possible...this is called a capillary plexus. So when that paragraph above talks about the micro circulation, mate they aren't kidding!
To give you an idea about how much they aren't kidding...at the very end near the cartilage, the capillary is so thin that literally only one red blood cell can pass through at a time!
. "Most capillaries are only about 8 to 10 micrometers in diameter (a micrometer is 0.001 mm). They’re so tiny that red blood cells have to pass through in a single file line". 4
7
To give you a better idea of this, these capillaries can be as thin as one seventh the width of single human hair. Literally only a few blood cells pass through...that graphic that PAR put up in their MOA video (See Appendix A below if you haven't seen this short but very insightful video)...that's how it is in some spots!
Ok here is an actual photograph of just how thin some of these capillaries actually get.. 5
A still photograph of a capillary...showing red blood cells passing through. In the case of inflammation, the capillaries can become thick and the blood cant get through.
Now imagine you can thin the blood juusssst enough to make a difference...without thinning it TOO much like Heparin does. So we get the lovely advantage of better blood flow WITHOUT the side effects of too much thinning causing all sorts of problems with excess bleeding being one of the main ones.
It was stated in the Seminars in Arthritis and Rheumatism back in Feb 1999 like this (my emphasis in red added)."NaPPS was effective against a wide range of inflammogens, possibly because of stablization of the peripheral vascular system and improvement of the microcirculation in the inflamed tissues stimulated by the drug".
As Dr Ghosh stated so succinctly, the action in the sub chondral bone is quite different compared to articular chondrocytes ... "Osteocyte viability and ability to respond to changing endocrine and mechanical demands is therefore critically depended on the patency of the vessels that serve these cells".
Its easy to understand what he means by patency, being open...when you have such incredibly tiny passages for the blood to flow, you want these beauties to be as open as possible.
Imagine this is happening inside of you dear reader...all of the time...keep tos walls thin...keep the blood flowing...this is what we own.
This is the true magic of Pentosan. Remember though, this is only ONE way in which our drug works. This entire Mozz post centres around really only one indication and principally one mechanism. The full paper I will one day get to, covers many, many more.
Surprisingly some 40 years prior to this paper (don't forget this article was published back in 1999 !), researchers experimented by deliberately inducing vascular congestion via surgery in hip and patella-femoral and tibial-femoral joints...what did they discover when the did this?
They induced OA.
Their observations included this statement:
."The venous hypertension arising in human OA joints as a consequence of a component arterial inflow coupled with increased resistance to venous outflow may be considerable".6
Paradigmers, it is our Pentosan molecule's multiple method of actions that is helping in the surrounding joint fibres and tissues...helping in this incredibly vital and pivotal vascular network feeding vital nutrients in and collecting wastes out of the surrounding joint structures... and surrounding sub structures.
What I am suggesting on the back of the scientific findings is that our drug, iPPS assists greatly in the vascular framework that's so vital in arresting the progression of OA. Nothing has ever done this before.
3) The other little hint in that paragraph above, is neurological improvement....how? By what means?
By inhibition of chronic inflammation in the spinal cord.
Again, I really don't think I have to say a lot here...but I will add that if you think OA is big....neurological ramifications and chronic inflammation in the spinal cord could really make a LOT of new investors and scientists sit up and pay attention.
.MANIFESTATIONS
Remember the manifestations of this particular virus HTLV-1 (that I haven't heard of till date?)....
Pathological changes are more prevalent in the lower thoracic spinal cord. Stagnant lymphocytes can easily transmigrate to the tissues and evoke immune reactions because of decreased blood flow. "Bystander damage" during the interaction between the HTLV-a infected cytotoxic T cells and the HTLV infected cells can subsist. There are interactions between lymphocyte integrins and their receptors on vascular endothelial cells.
IPPS addresses each point...
We have seen evidence in DDD (Degenerative disc disease) We assist to increase the blood flow. There is evidence of T cell interaction specifically in the case of HTLV "PPS also efficiently inhibited HTLV-1 cell-cell transmission in T cells".1 Finally there is also evidence of iPPS's action on endothelial cells: "The actions of PPS reported in other studies provided the rationale for it's use in ARDS, which involved anti-inflammatory actions mediated via inhibition of NF-κB activation; inhibition of complement mediated tissue injury; inhibition of endothelial cell activation".
I am, as you may have guessed by now, a massive proponent of iPPS. The incredible thing for you and I is, is that inflammation is everywhere, there are so many indications that can be addressed and yet through this naturally based molecule, it is not blocking or stopping the required pathobiology. It allows for BALANCE...this is the single most important key. In my view, you don't want a drug that fully blocks...you want a drug that downregulates...that doesn't interfere in the body's biological, chemical and immunohistochemistry processes...the body needs to do what the body needs to do...we just attempt to restore the balance to just enough extent. This is the component.
It has been used for not years, but decades and it's safety profile is exemplary. .
Yes it takes time for such incredible products to finally make it to market and be embraced by the masses...but once it does, in my view...we just won't believe the sheer adoption rates and the growth to come...
onight's post is a mere subset, a small fraction, of the real one I want to do at a future point. The one in the future will be big, in fact that will set a distinct Mozz record for the most amount of words, the most amount of parts, it will be the biggest project I have ever undertaken in terms of PAR research. It will literally take weeks and weeks...hope to have it out this side of Christmas?
component.
(20min delay)
