hh it's an exciting one for me tonight...I write on my second favourite molecule....*rubbing hands together* Sit back and enjoy this one, I got a real buzz out of writing this...one day I will definitely hold a seminar to explain this...you guys need to hear the excitement in my voice...
As we get older our quality of natural lubricants degrade.
While I can't vouch for you, I am getting older! I'm 51...no spring chicken, but mentally I feel like I'm 28 and I haven't even had a dose of the ol' Ipps myself...I have a suspicion it will clear up my thoughts as it might work on fixing some of the broken synapses and neurological connections there...but that's for a separate post.
Please do enjoy this amazing molecule and what it can do for......YOU!
INTRO
In the past, I've referred to the old Castrol Oil ads in the past...Oils ain't oils. (See Appendix A). This is *SO* apt in the case of the HA molecule.There are essentially two distinct types of HA...the lower molecular weighted (LW) version and the higher molecular weighted version (HW). These two are chalk and cheese; world's apart.
Let's explore this some more.
The old thinking was that so different are the traits of these two differing weighted HA molecules that it must be the cell receptors that are actually having different responses, however new research shows us that this is not so.
In fact so much changes as you shift upwards from the LW to the HW blend...
Structural properties
Physical properties
Physio chemical properties
Hydrodynamic properties...
... and even the degradable properties....
...all of these change dependant on the weight of the molecule.
HA also has a number of physical properties such as 1
compressive stress
compressive modulus
storage and loss modulus
porosity
swelling rate
degradation rate and density
One of the most redeeming features of the HW blend of HA is it's extraordinary property of not only viscosity but it's enhanced viscoelasticity. It is this property that enhances our synovial fluid.
PAR investors? It is this higher quality of HA within our Synovium that keeps things...that keep us...moving.
Every step, every movement...it's the lovely viscoelasticity of the synovium fluid that allows for these shocks to be constantly absorbed.
There is a vast plethora of incredible evidence of how HA is one of the most useful molecules...each topic below could easily be a separate post:
HA in vascular tissue engineering
HA in cartilage tissue engineering
HA in bone tissue engineering
HA in skin and soft tissue engineering
So we are talking chondroprotection, synthesis of proteoglycans as well as glycosaminoglycans. There are anti inflammatory properties as well as the mechanical and subchondral activities. Add in analgesic activities.
It's quite a list.
THE PROBLEM
The wonderful thing is that this second fave molecule of mine has supremely wonderful attributes...the bad news?
Where is me box of tissues? It degrades over time....less of the good stuff (HW) is produced as we age...it gets swapped out with the lower weighted version.
Nothing to date stimulates the higher weighted version.....
Until now...
BUT WAIT...THIS IS A SHARE FORUM - Yeah Mozz, why are you going on about your second fave molecule...what relevance is it to me and my 60 cent shares?
Because of the last statement in the last section....until now, there hasn't been any practical way to get the good stuff into us...from within!
Yes there are HA injections...derived from Rooster Combs 2...but really? Can that in any way compare to the natural stimulation of HA resulting in the divine fluidity of those precious fibres of the synovium..of the surrounding subchondral bone...the lovely cartilage we all yearn to get back....heck..even...of the heart...(HFpEV)?
But HA evoked naturally is different than simply extracting it and injecting it, "HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products".
Yes we need more than just a working safe product to get us from 60 cents to 600 cents...but once we get a commercial partner that's smart enough to engage...well we will be a different company.
BEAUTY IS ONLY SKIN DEEP?
As I've posted about in the past, there are peer review papers on the topical nature of HA. It can actually sure up and tighten some of the wrinkles...
...but that's not what I'm talking about tonight...you don't take iPPS and spread it on your face...you SubQ it....but here is the magic in the magic juice...it hydrates our tissues from within...and boy does it hydrate them.
This little molecule of mine (ok of ours) holds some 1000 times it's weight in water. That's something!
"Hyaluronic acid is extremely hydrophilic and biochemically retains water: hydrogen bonding occurs between adjacent carboxyl and N-acetyl groups to the extent that it retains up to 1000 times its weight in water"3.
What does that mean? Like how about a practical fact Mozz?
"Sutherland and colleagues demonstrated that one gram of HA can bind up to 6 litres of water".3
Now you are right in the midst of a Mozz post. We haven't had a bonus for some time...well a Mozz bonus...tonight I spring one on you... I have a pal....he has a pal of his....this pal tried Pentosan...my pal was talking about it and the word Hyaluronan came up...lets act this one out so it's easier to follow.
Remember, the below are not the exact texts/words that occured, it's a simulation based on a convo that did happen. The last sighting/symptomatic observations are ALL real...
My Pal = Mr F Mr F's Pal = Mr H
When I heard this from my mate Mr F...I nearly fell over...I couldn't think of any prolific swear words exciting enough to capture the sheer electrical neurological explosion that was going off in my head...In case you have no idea what I was trying to say/think...just one word came into my head when I heard from my pal, Mr F and how his pal has witnessed the bags under his eyes disappearing...
What was that one word?
WOMEN!
Err Mozz? Are you posting this in the right forum?
Ohh yes...Women....and also guys for sure....they want to look good,as good as they can as they slowly age...if they have bags under their eyes, they want to to try and remove them...how do you do that? No amount of topical cream is going to really eradicate it.
Again, I'm not saying we are going to tighten up all wrinkles and bags under the eyes...I am saying that this needs to be looked at in more details and there indeed could be *SOME* percentage of patients that manage to glean this effect. Imagine, there is a body of evidence that definitely shows that pentosan plays an active role in wound repair and collagen production. Guys, through the natural stimulation of HA from WITHIN...this could be a bigger proposition in the future than ANY of us actually know.
There is evidence that HA is in fact a key molecule in skin aging...we know that from several papers, but I'm also talking of this being stimulated not externally, but naturally from within!Skin HA itself accounts for a total of 50% of all HA found in the body. Within the skin it has some exemplary roles...
Regulates water balance
Regulates osmotic pressure
Regulates ion flow
Functions as a sieve
Enhances the extracellular domain of cell surfaces
Stabilises skin structures by electrostatic interactions.
Prolonged presence of HA assures scar free tissue repair.
But it doesn't end quite there...repair is one thing...what about this for a statement:
"Progressive reduction of the size of the HA polymers in skin as a result of aging has also been reported".4
So while I'm not saying this is going to be an anti-aging molecule...I am saying that it's not going to hurt!It may, with yearly usage, just give you that extra sparkly...that softer skin...and yes, in some cases reduce or even remove the bags under the eyes that some people get as they age like my friend's mate experienced...
Mate.
Refer to Appendix B for a short discussion on UV and the inference of collagen...this is very much related to my favourite molecule....(iPPS of course!).
AHHH I SO GOT YOU THIS TIME...
How about a story. A PAR related story.
On 4th oct 2022 our own Dr Ravi Krishnan printed this in an announcement:5
I immediately got on to PAR and said STOP PRESS, you guys have made an error...I am under the impression that HA into the synovium is a GREAT thing...Here you are saying now that the dogs are having REDUCED levels of HA !!!! I got you, wait till I tell the folks at HC!
They politely said Mozz, you don't have us....it's the lower weight that's being produced as a result of degradation of the ECM.
Ah.
Of course.
Again it is genuinely a case of iPPS to the rescue...iPPS results in less LW and more HW being produced. That's what we all want...for the dogs...for us.
As we age we find ourselves producing less of the higher weighted and more of the lower. This is amply accelerated with the onset of OA.
Here is a quote you need to read that explains it succinctly:
"Studies have revealed that most HA properties depend on its molecular size. High molecular weight HA displays anti-inflammatory and immunosuppressive properties, whereas low molecular weight HA is a potent proinflammatory molecule".6
That there above is quote of the quarter for me.
HWHA is anti inflammatory LWHA is proinflammatory.
What does iPPS do? What do you own?
MORE MECHANICS
Paul Rennie back in 2019 ended the AGM with a simple saying that still resonates in my head
"You ain't seen nothing yet".
He knew what was coming, he prob just didn't know it would take this long...and that Cornona would eat up some time as well in-between. How proud he must be feeling right now as we get closer to setting up some prizes...prizes are coming in my humble ...get that first deal across the line..it might still be a few moths away...but get that and it's going to trigger lots of fun stuff...
Don't miss the train! Once that first deal strikes...well the train is going to move.
HA is one of the main components of the extracellular matrix and "is considered one of the key players in the tissue regeneration process".
Tissue regeneration process...this is DMOAD....this is wound repair....this is repairing those tiny micro fractures and tears within the cartilage.
"Hyaluronan turnover is a rapid process, as the half-life of HA molecules in the bloodstream is only about 2-5 minutes".
"Studies have revealed that not only do they provide a wound microenvironment, but are also involved in various signalling pathways that are activated in the wound bed during the healing process".
"This latter effect of PPS was confirmed in a human study which showed that after two weekly intra-articular injections of 50 mg of the drug into rheumatoid joints, the molecular weight of synovial fluid HA and thus viscosity was increased. After seven injections, HA molecular weight was raised by 69% ".7
Yes PPS as we know now, does indeed get into the articular cartilage, there is direct action here:
"Radiolabeled PPS, when administered subcutaneously to rats, is present in articular cartilage and disc tissues 48 h later".
iPPS facilitates the synthesis of the HA blend within the cartilage matrix to help the recovery of the cartilage itself.
That's the take away. That's why I like this molecule so much...it's also multi acting...multi modal...
There indeed are many many more pathways to be explored here. I do envisage the day when we form a global partnership and we have not a reg and clinical team of just a handful of staff working so hard for us...we have 250 spread across these two departments...these guys and gals will work on many new indications all at once, layering like we don't understand, like we can't imagine. Am I dreaming?
Here is what another group of researchers found:
"Since high-molecular-weight HA polymers, unlike middle- and low-molecular weight HA oligosaccharides, are known to possess anti-inflammatory and anti-fibrotic functions, we suppose that the enrichment of mesangial matrix with high-molecular-weight HA may represent an endogenous mechanism to limit renal injury in diabetes".8
We are already getting the advanced hints of what our molecule is capable of.
HA indeed plays a massively pivotal role here with the HW blend resulting in many positive observations. While iPPS is the ultimate molecule, the premier stimulant for the production of the higher weighted version of HA, it's not hard to see why it is my second favourite molecule.
DYOR necessary
APPENNDIX A
Oils ain't Oils...you and I want the best...no no no...not just for our cars....for our JOINTS!!! For my synovium....I want the rich HIGHER weighted Blend of HA....how do I get this? By natural stimulation via internal iPPS generation. Now thats worth a couple of extra bucks? No? Yes!
APPENDIX B
While researching for this one, I came across this interesting text on UV and HA... Remember iPPS has a direct result on collagen production and wound repair.
"Premature aging of skin is the result of repeated and extended exposure to UV radiation. Approximately 80% of facial skin aging is attributed to UV-exposure. UV radiation damage causes initially a mild form of wound healing and is associated at first with an increase of dermal HA. As little as 5 min of UV exposure in nude mice caused enhanced deposition of HA, indicating that UV radiation induced skin damage is an extremely rapid event. The initial redness of the skin following exposure to UV radiation may be due to a mild edematous reaction induced by the enhanced HA deposition and histamine release. Repeated and extensive exposures to UV ultimately simulate a typical wound healing response with deposition of scarlike type I collagen, rather than the usual types I and III collagen mixture that gives skin resilience and pliability". 9
APPENDIX C
Also while researching HA I came across the below paper published in Osteoarthritis and Cartilage, 1996 yes by Professor Ghosh. Quite a read:
"As already discussed, PPS has been shown clinically and in laboratory models to possess a profile of pharmacological activities which would qualify it as a disease modifying anti-osteoarthritic drug. The present study provides evidence that PPS may bind to connective tissues and possibly accumulate there by interaction with thrombos~0ndin and other, as yet unidentified, proteins. Since PPS is a potent enzyme inhibitor and modulator of immune cell activities the binding to components of the cartilaginous matrix could place this drug in a favorable position to attenuate the degradative effects of proteinase or other mediators released by inflammatory cells present in arthritic joint. In addition, the finding that PPS bound to surface 'receptors' of synoviocytes and possibly became internalized suggests that this drug can not only modulate events occurring extracellularly but also may act on intracellular pathways responsible for the generation of metalloproteinases and inflammatory mediators. It is noteworthy in this regard that PPS is a potent inhibitor of protein kinases".10
I always like to read 1) DMOAD 2) The word 'potent inhibitor ...when it comes to iPPS.
We also know that iPPS can become 'internalised' by its ability to enter into the cell nucleus itself allowing for intra and internal cellular pathways and thus affecting inflammatory mediators. We have seen this in the initial evidence of 6 month readout of 008 via the cytokines and wet biomarkers. This will be presented to the authorities within weeks.
hh it's an exciting one for me tonight...I write on my second favourite molecule....*rubbing hands together* Sit back and enjoy this one, I got a real buzz out of writing this...one day I will definitely hold a seminar to explain this...you guys need to hear the excitement in my voice...
HA in vascular tissue engineering
HA in cartilage tissue engineering
HA in bone tissue engineering
HA in skin and soft tissue engineering
(20min delay)