PAR and BP---- Posted on 14th of June 2021...

PAR and BP

---- Posted on 14th of June 2021 ------------------------

Errr...nope...tonight, not this....







This....





Not sure if you missed it but I was inspired by the below statement, here it is in case you missed it, thanks @hamman and very glad to hear your wife had this wonderful result.


"My wife had high blood pressure for 10 years she had Zilosul treatment twice and it's now normal."
Hamman - 10/06/21 - post 53764064



Know economically I stand to gain by such future observations on mass but I do also truly appreciate the human side and the actual benefit we one day also may impart on society and the millions suffering such conditions.

Right...so what's the evidence in this area? So compelling it deserves another pass at it...I initially covered this topic under PAR and the Filter, that post covered a bit on what the kidneys are all about, how they play important multiple roles in our bodies and some evidence of the effect of PPS in this important area. The link to that post is here: PAR and the Filter



Tonight I will add to the material.

Please now enjoy.




INTRO

What is Blood pressure anyway? It's the pressure of the blood pushing against the walls of your arteries. It fluctuates during various times of the day but if it stays high for too long it can lead to damage of the heart.^0.5 Known also as a 'silent killer', there aren't always a lot of symptoms especially initially when one has higher blood pressure.

Without spending too much time as we have covered this in the past, it is the kidneys that play a vital role and regulation of blood pressure but did you know this is just one of the functions of this important organ?Yes the kidneys do a lot for us, just some of these critical functions include:


Regulation of extracellular fluid volume.

This is all about blood flow to the vital organs we have. We all know a bit more about this 'extracellular matrix' now...its a vital component and lots of research on the interactions of our PPS and this area.


Regulation of osmolarity.

Speaking of extracellular material, it's the kidneys that are ultimately responsible for ensuring that the extracellular fluid is not too concentrated or too dilute...the conditions here have to be right if we are to feed those cells with the nutrients they need for survival.


Regulation of ion concentrations.
Who are the ions? No it's not some comic strip superheroes...well actually, maybe they are, examples include: sodium, potassium and calcium.



_{Sodium Potassium and Calcium? Doesn't quite have the ring/look of the above three characters...but prob their role and regulation is just as useful and important!}



Excretion of wastes and toxins.

You know waste management is one of the key invesmtent thesisies I'm actually starting to look at a tiny bit more closely of late, I recently read as economies expand (come out of Covid) it's these kinda companies that tend to prosper...Nice thesis Mozz, what's it to do with Kidneys? Well it's the Kidneys that are the waste manager professionals in our body. With their help, waste and toxins are filtered into the urine for extraction. And you know what, doesn't matter what the economies of the world are doing, it's the kidneys that must do this job day in day out....if PPS can help in this area, well more power to it!


Production of hormones.

In this subsection I must drop two names for you:

1. Erthryopoietin
2. Renin

What are these two names then?

Erthryopoietin has the very important role of stimulating red blood cell synthesis.

The other name on my elite guest list is Renin which helps control salt and water balance and blood pressure. If there were ever two names I wanted in the Mozz Kidney club, it's these two...You want to look after your kidneys!



_{The Mozz's Kidney club, the above members may one day find out about iPPS and what it can do...}




THE PROBLEM WITH NSAIDs

@Denial stated it just the other day...NSAIDs actually can lead to increase in blood pressure ^0.6 and affect overall cardiovascular risk!

Why do we care about NSAIDs? Well if you don't know, it's one of the so called standard of care for OA! So potentially iPPS can not only address your OA...it might, at least in some cases aid to lower blood pressure and remove the reliance on these nasty NSAIDS. I say 'nasty' as there is also evidence that NSAIDs lead to an increase in the rate of cartilage loss again in some patients. Sure NSAIDS may result in some good pain relief but I for one think it comes at too high a cost. Another reason to wait patiently for iPPS to firmly hit the market.


CURRENT REMEDIES

Well there could be a couple Mozz posts just discussing and presenting the standard of care here so I'll just limit it to high level material.

Published in the American Heart Association journal Hypertension, the results of a large study conducted some years ago involved some 42 trials and around 12,000 patients.¹ The results demonstrated that better and safer results could be obtained from getting a lower dose from a couple of different medications in this area. Indeed it is the side effects are important here as this condition is to be addressed over longer periods of time. You want a drug that can either be used in moderation over a long course of time, OR you want a safe drug that can potentially address BP...

There are a number of classes of treatments in this area and within each there could be a number of different drugs that act in various ways, here is a grouping, note the overlap with some of the treatments used in heart failure:

• Diuretics
• Beta-blockers
• ACE inhibitors
• Angiotensin II receptor blockers
• Calcium channel blockers
• Alpha blockers
• Alpha-2 Receptor Agonists
• Combined alpha and beta-blockers
• Central agonists
• Peripheral adrenergic inhibitors
• Vasodilators

PREVALENCE

Ok so now we know a bit more about what blood pressure is and some possible current treatments. Next question, how many people are affected by it? Of course there is only one best way to deliver that answer.

Yes, you are quite right and you are quite lucky, a fine and timely opportunity for a Mozz Quiz ®


MOZZ QUIZ QUESTION - What is the estimate for number of Americans that have Blood pressure?



A) Well it's going to be a decent chunk of the population....3 million...a solid answer A)



B) Double A...I give you 7 million?




C) Double again????




Paradimers, the estimates are off the charts...



_{Oops wrong thread..that was supposed to be posted in the Humour thread at HC...}



Answer to Mozz Quiz?

Paradigmers, there is an estimated 108 million Americans that potentially have Higher Blood Pressure readings....That's a 2018 statistic. Probably more concerning than that one is this fact:

Only about 1 in 4 adults (24%) with hypertension have their condition under control. ^0.5


Now any of you that are seeing distant dollar signs in your eyes...don't forget there will be a fairly decent overlap in patients that have OA and blood pressure...and even in union with other indications such as ARDS or patients that are in pain, these figures aren't at all cumulative. What is probably prudent here is to remind you that though we may be able to address some part of this market one fine day, it doesn't at all mean we will cure this disease totally nor am I implying we may address even more than a handful of % of the total BP patients.

The road to OA Gold is long enough, but despite having a bigger R & D team one day, it will still be some time before iPPS may be duly researched for it's human effect in such areas as BP.



EVIDENCE OF PPS AT WORK?

*Rubbing hands together* Right, let's tackle PPS and what it can do for you, well for your kidneys anyway...

Back in 2001 a group of researchers experimented with Rats and our hero, PPS.I could get stuck into the methods and materials but I'll cut to the chase....What were the aims of this research?
Let's list them:


To to determine whether PPS prevents glomerulosclerosis


Can it address interstitial inflammation


Investigate fibrosis induced by subtotal renal ablation


Determine whether the protective effect of PPS is associated with prevention of glomerular hemodynamic and morphologic alterations.


(Are my corny bullet points driving you a bit crazy? They are supposed to be mildly entertaining! Don't even ask me where I get images of Kidneys with stethoscopes).



RESULTS

As a background, Proteinuria means proteins found in the urine, you don't want too much of this as it can be an indication of underlying disease or medicinal side effects. (Note: levels of Proteinuria do vary from person to person).

Nephrons (which I will also refer to later in this section) are the actual filtering units within the kidneys. Yep, we have a few of these...about one million in each kidney. You want to preserve these, keep as many as possible!

Let me quote from the research itself:

"PPS treatment resulted in marked reduction of proteinuria throughout the study."⁰


In terms of Systolic pressure, I give you a graph:





I've added the coloured lines to highlight the data change, see below.

Ok the Y axis is Blood Pressure, X axis is weeks....Control were rats that were normal rats, "Five/Six nephrectomy" = rats that had one kidney removed, PPS treated rats were the same as the Five/Six group but treated with PPS.Clearly you can see the red line going up indicating blood pressure going up in the 5/6 rats, but the PPS treated cohort (Green line) going the other way, blood pressure was reduced. (Control - Blue line, as you'd expect was fairly consistently flat).


Protein levels in urine? Remember, less is better...






Outstanding.

The results showed that Glomerular filtration rate (GFR) which is a measure used to detect how well the kidneys are performing in the PPS treated rats were only decreased by 45% despite some 80% of renal mass was ablated (removed)! The research paper stated that "... a larger number of nephrons was preserved by PPS treatment ".

The more the nephrons that are preserved, the better the patient outcome.


HISTOLOGICAL CHANGES

Histological changes refer to the pathology of tissues changing. We have had clear evidence of the wondrous effects of PPS on tissue remodelling. In this area there was extensive dilation of tubules and tubular atrophy in the kidneys of the untreated rats. Not only that but "the tubules were separated by areas of interstitial widening, which contained many inflammatory cells. Mesangial sclerosis was also present".

What then was the effect on PPS treated rats? Again I quote directly from the researchers, "PPS treated animals had considerably less tubular dilatation and tubular atrophy". These are the words we want to see...and furthermore, "Interstitial infiltration and fibrosis were nearly completely absent " and the glomerular lesions? "The glomerular lesions also appeared to be much less marked in PPS-treated rats".

Is it just me that can see how early we are in this story? What the science is saying. Sure we need much more research in this area, we need to see how it translates to human clinical studies....but in some ways I really do feel I'm part of the BP exploratory team searching for new wells of Black gold....yes that is the BP - British Petroleum reference I'm making now!


MORE?


Paradigmers, this is the evidence we have. How many investors (leave aide non investors) know this, understand this and can forecast where this MAY head one day?PPS achieved three more amazing observations here:


A) The untreated rats had a significantly higher increase in glomerular volume (+46%) compared to the control rats. How about compared to the PPS treated rats? This increase was prevented in the PPS treated rats.


B) Some 94% increase was noted in fractional mesangial areas of the untreated rats, "PPS treatment largely prevented this increase".


C) "Capillary area was decreased in the untreated group and this was also prevented by PPS."




A SECONDARY SOURCE

You guys now know how I love my second source of data, here is a back story on another source...

While researching for material on the initial research (see Main Reference in Reference section below) I came across another researcher that was independently trying to fund a different study back in 2010 still focusing on PPS and kidneys of rats.⁵ At that stage in 2010 the researcher said he would get funding...He finally got it some 5 years later, they did the experiments, the next Mozz section summarises the results...




HOW DOES IT WORK?

1) "Glycosaminoglycan is considered an important constituent, forming an endothelial surface glycocalyx layer to protect endothelial cells from cytokine and leukocyte adhesion under inflammatory conditions." ⁶

Paradigmers, look at the cross over we have here. We have seen time and time again PPS's relationship and working to reduce inflammation, addressing cytokines (more to be possibly observed when 008 data comes out later this year potentially)...and it's dealing with interleukin.

2) It is this so called glycocalyx layer that acts as "an important micro vascular permeability barrier that prevents albumin filtration." Remember, we do NOT want to see this albumin in the urine , it's a sign of kidney damage, a sign of the balance out of whack, it's also a sign of systemic inflammation.

Pentosan indeed to the rescue in my opinion.




THE OTHER ROUTE

Of course the science above is fairly compelling, but the other way Pentosan can directly help is easing the pain and potentially addressing the OA of so many patients that no doubt also suffer from high blood pressure. My link to another route is by aiding patients to be able to walk again, to be able to exercise again, to be able to play sport once more, this has a DIRECT impact on the health of our organs and of course...the kidneys are central.

Yes walking (even modestly at an older age) can have benefits in terms of lowering blood pressure.⁴

Sure sample size of one is one thing, but I can't help but quote Hamman:


"The Doctor told my wife no [one] gets off blood pressure tablets especially after 10 years and he couldn't believe it."


...and this is why eventually we will have a trial set up to explore this (my views)...can you just imagine taking 100 patients that have been on blood pressure tablets/treatments for 10 years plus and observing the effects of iPPS solely on this marker? On Blood pressure phenotypes....Again I'm not saying we are going to reduce blood pressure in each and every hypertensive patient, but what if we can affect just 5% of the market?

What if we bring down their blood pressure even by just 10 or 15 mmHg on average and we do that safely without the adverse effects over time? Or prevent/reduce kidney damage over the longer term?

Mind boggling potential. It's these such trials and research we have to potentially look forward to way down the track. Sure we need to bed down OA and we have some hurdles and time to pass in the more immediate future...but I'm loving the future possibilities.









Forward looking statements may be contained in this post - Never rely on one source of information, never invest too much in one investment vehicle no matter how ace it sounds and always be prepared/consider the worst.



REFERENCES


MAIN REFERENCE

0] https://www.researchgate.net/publication/11786413_Pentosan_Polysulfate_Prevents_Glomerular_Hypertension_and_Structural_Injury_Despite_Persisting_Hypertension_in_56_Nephrectomy_Rats/download


OTHER REFERENCES USED:

0.5] https://www.cdc.gov/bloodpressure/facts.htm
0.6] https://www.uptodate.com/contents/nsaids-and-acetaminophen-effects-on-blood-pressure-and-hypertension#:~:text=All%20nonsteroidal%20antiinflammatory%20drugs%20(NSAIDs,considerably%20%5B2%2D4%5D.
1] https://www.cardiosmart.org/news/2017/7/lowdose-meds-promising-for-patients-with-high-blood-pressure
2] https://www.kidney.org/atoz/content/proteinuriawyska
3] http://mcb.berkeley.edu/courses/mcb135e/kidneys.html
4] https://www.healthline.com/health/high-blood-pressure-hypertension/lower-it-fast#:~:text=Aerobic%20exercise%2C%20resistance%20training%2C%20high,in%20older%20adults%20(10).
5] https://www.rdworldonline.com/pentosan-polysulfate-prevents-kidney-damage/
6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796270/
7] https://thehealthnexus.org/half-of-americans-have-high-blood-pressure-are-you-at-risk/