Controlling Inflammation & Connective Tissue

If you accept that we are in the order of 100 trillion cells.

That each one of those cells relies on up to 90 nutrients, fresh air and potable water for survival.

That cellular malnutrition is the major cause of illness and death.

That optimizing cellular nutrition guarantees better health.

Then will you appreciate what is to follow. If you do not accept the foregoing stop reading now!

The following of necessity, deals with some of the processes of inflammation. However, some relatively new anti-inflammatory and naturally derived substances are changing the way we have regarded inflammation in the past.

DEFINITION
Acute Inflammation: The initial response to injury to tissues.
This stage is mediated by Histamine, Serotonin, Bradykinin, Prostaglandins and Leukotrienes.

Immune Response: Occurs when Cells of the Immune System are activated in response to Antigens liberated during either the Acute or Chronic stages of Inflammation. This can be beneficial when Antigens are neutralized (i.e. phagocytosed). This can be detrimental if it leads to Chronic Inflammation without the resolution of the underlying cause of Inflammation.

Chronic Inflammation: Involves the release of Interleukins 1,2 and 3; Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF); Tumour Necrosis Factor Alpha; Interferon's and Platelet-Derived Growth Factor.

In the past, control of inflammation in body organ/tissue has relied mostly on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs),  a large group of pharmaceutical Drugs that inhibit inflammation by inhibiting the endogenous enzymes that catalyse the production of prostaglandins, which are  are a group of endogenous fatty acids normally manufactured within the body and very rarely obtained via the diet.

All Prostaglandins have 20 Carbon atoms, a 5-membered ring, and 2 side chains. They differ in the number of double bonds in their side chain. Prostaglandins act in a manner similar to that of hormones, by stimulating target cells into action. However, they differ from hormones in that they act locally on cells, near their site of synthesis, they are short-lived and therefore metabolized very rapidly.

Another unusual feature of prostaglandins is that the same prostaglandins function differently in different tissues. Some prostaglandins are stronger in their function than others.

Prostaglandin E2 (PGE₂) is the one we are discussing here, and only as it relates to the musculoskeletal system for the present. PGE₂ is formed  in a variety of cells from PGH₂ which itself is synthesized from Arachidonic Acid (AA), this is what we call a bad although necessary, hormone (eicosanoid), which in small amounts is not a problem. However, when we get too much omega-6 and not enough omega-3 in our diet we manufacture excessive amounts of AA and that is what builds PGE₂ the inflammatory factor.

We need a ratio of 2 parts omega-6 to one part omega-3 (2:1) for anti-inflammatory control. Most people in our society have 20-50 to 1 if they are eating some fish or flax seed. Thus we are a society riddled with inflammation. Worse; elevated levels of PGE₂ interferes with the formation of bones and increases bone resorption rate.

However, we know that optimally low levels of PGE₂, on the other hand, stimulate bone formation, and are therefore a double edged sword.

PGE₂ is also involved in the onset and progression of cachexia an ailment involving abnormally low weight, excessive weight loss, loss of appetite, weakness and general bodily decline. In fact most individuals who die of cancer, actually die of Cachexia

One of the most telling effects of PGE₂ in excess is that it is involved in the breakdown of cartilage in every joint in the body, especially the weight bearing and articular joints. It is a fact that the need for joint replacement is due mostly to wearing out of the articular cartilage.

It gets worse because excessive PGE₂ activity increases the risk of osteoporosis in that PGE₂  promotes the maturation of osteoclasts from precursor cells. Osteoclasts continually travel through bone tissue seeking out old or diseased  bone that has become demineralized and in need of renewal. Osteoclasts act by dissolving the  mineralized tissues leaving unfilled spaces behind, for filling by osteoblasts.

Excessive production of PGE₂ stimulates the degradation of skeletal muscle which therefore interferes with muscle growth

Rheumatoid arthritis more than osteoarthritis is caused by excessive production/activity of PGE₂, with consequent inflammation. These actions of PGE₂we know as an inflammatory cascade.

The NSAIDs work by knocking out (INHIBITING) both types of PGE, (1 & 2). PGE 1 is a friendly prostaglandin and as a result of a scarcity caused by the NSAIDs the joints are further compromised. In the long-term destroyed by the very medicine supposed to help.

NEWS Flash

BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086.

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P.

Institute of Social and Preventive Medicine, University of Bern, Switzerland.

Comment in:

·                         BMJ. 2011;342:c6618.

Abstract

OBJECTIVE: To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.

DESIGN: Network meta-analysis.

DATA SOURCES: Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.

STUDY SELECTION: All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.

DATA EXTRACTION: The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.

DATA SYNTHESIS: 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.

CONCLUSIONS: Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

PMID: 21224324 [PubMed - indexed for MEDLINE]PMCID: PMC3019238Free PMC Article

COMMENT: and you can see TV advertisements every night claiming that Nurofen is kind to the stomach and knows when to leave the body, or words to that effect, and they promote these dangerous drugs for infants and children.

ProResolvin TO THE RESCUE.
A clinical study was conducted by Dr. Andrew Flowers at Southern Cross University (Australia) in 2001 to assess the anti-inflammatory action and potency of  a Glycosaminoglycan Complex (APO1000946) now named ProResolvin,compared to Aspirin (Aspirin 50µM), Glucosamine, Chondroitin Sulphate powder (APO 1000943), Chondroitin sulphate tablets (APO 1000944), and Bovine Tracheal Cartilage (liquid), (APO 1000945).

The solvent control was 5µL H₂0. (23187)

The final result demonstrated that ProResolvin was up to a massive 32 times the anti-inflammatory action of the other substances tested. Hereunder is the Table of comparisons.

Understanding that these statistics may mean little or nothing to the non-mathematical, what is interesting if not a revelation, is the fact that Aspirin obviously inhibits the conversion of PGE₂ thus exhibiting its anti-inflammatory action.

In contrast the Chondroitin's and Cartilage which contains Chondroitin exert a different action and therefore must act through a pathway other than the synthesis of PGE₂ from PGH_{2 .} Dr Flowers stated: "These results show that these products (Chondroitin’s & Cartilage), although successful (in clinical trials) in the treatment of inflammatory processes, must act through a pathway other than the synthesis of PGE₂ from PGH₂."

ProResolvin is extracted from the tracheal cartilage of bovine calf less than 18 months days old. Then through its unique production method as never before, the *Glycosaminoglycans are extracted in their entirety.

*Glycosaminoglycans are a group of polysaccharides that are usually comprised of two repeating sugar units, one of which is a hexosamine (an amino sugar - often glucosamine or galactosamine) bound to sulphur.

Most people are not aware of the very effective anti-inflammatory role of glycosaminoglycans, which include but are not confined to:
Cardiovascular System:
Glycosaminoglycans maintain the elasticity of blood vessels.
Glycosaminoglycans also lower LDL cholesterol and raise HDL cholesterol,
and therefore effectively treat and prevent Heart disease.
Musculoskeletal System:
Glycosaminoglycans are a major constituent of the proteoglycans content of cartilage, and are present in the extra cellular matrix in most regions of the body. Depletion of glycosaminoglycans from cartilage is in fact the primary underlying mechanism during the progression of osteoarthritis.
Skin:
Glycosaminoglycans help to retain water in the skin and thereby help to prevent dry skin, and associated problems.
It is the endogenous glycosaminoglycans that are involved in the wound healing process, including post-operative wound healing where they contribute to the formation of the matrix of scar tissue.

Glycosaminoglycans enhance the function of proteoglycans, which are composed of glycosaminoglycans bound to proteins. Chondroitin Sulfate comprises approximately 92% of the proteoglycans content of normal cartilage, and Keratan Sulfate comprises approximately 8% of the proteoglycans content of normal cartilage. All of the abovementioned beneficial substances are found in ProResolvin

Therefore ProResolvin may be indicated in all of the following:

As modern research methods increase in sophistication, Inflammation has been tentatively linked as an underlying cause of various ailments that were previously believed to be unrelated to Inflammation including:

Aging Process
Alzheimer’s Disease
Atherosclerosis
Cancer
Congestive Heart Failure
Osteoporosis
Periodontal Disease
Stroke
Thrombosis

SUMMARY
ProResolvin does not reduce inflammation along the same pathway as the Non-Steroidal-Anti-inflammatories (NSAIDs), which in the long term destroy joint function.

ProResolvin is specially formulated and produced by a unique extraction method from totally natural substances and therefore is free of untoward side effects.

 •        The recommended dosage of ProResolvin  is 10ml once daily from a spoon, in water, milk, juice or food, however, this can be safely increased to twice daily initially for maximum effect

•        Many patients have reported a reduction in discomfort as soon as 7 days after beginning ProResolvin, but results will  obviously vary between individuals.

The price per 200ml bottle is $45.00 including pack & post

The price per 500ml bottle is $70.00 including pack & post

We welcome distributors and especially worldwide.

We are proud to be a major distributor.
 

Proceeds to medical research and health promotion.

Order. proresolvinfirst@gmail.com

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