Contra-Darwinian evolution, or devolution theory

It is not known yet whether Darwin himself or any of the classical theorists recognized and ever discussed the opposite process by which living organisms lose both form and function in the passage of time. The orthodox doctrine of biological evolution projects a progressive course, in the sense that organisms develop finer forms and functions to survive within hostile environments around them as time passes. The changing environment makes it imperative for living organisms to develop adaptive characteristics in order to survive, and organisms that are unable to adapt to a changing environment in accordance with this natural law are exterminated from existence. An inherent presumption in the classical theory of biological evolution is that living organisms progressively become better in both form and function in respect to the external environment within which they live.

The opposite process whereby living organisms lose form and function, that which in this piece is described as contra-Darwinian evolution or devolution theory, perhaps, has evaded general attention. At least this latter process is not as so much discussed as classical evolutionary theory. However, it will be a mistake of immense proportion to assume that extinction of biological species consequent in Darwinian evolution always occur spontaneously through catastrophic causes. Although natural catastrophes are not excluded from the possible mechanisms of natural selection, of greater importance is the subtle process of devolution (deterioration) through which living organisms are stripped of vital characteristics which deprive them of the capacity to survive within their environments. The devolution of living organisms, which by reason of its occurrence at the cellular level is imperceptible to the observer, mostly accounts for the periodic changes in form and function that affect all living organisms.

Therefore, not only do biological species evolve in the passage of time. They also devolve. The opposite biological processes of evolution and devolution are in constant parity, and together regulate form and function in the biosphere. Both processes are ever occurring at the subcellular and cellular levels in opposite directions, in response to ever changing environmental conditions, and culminate in periodic changes in the structure and functions of biological species.

The devolution theory has practical significance a sketch of which is discussed in the following sections.

 

Origin of unicellular species

Unicellular species are relics of multicellular organisms and emerge in the process of devolution of higher living organisms. Each individual cell of multicellular organisms are self-sustaining to some extent and can survive for a limited period independently of other cells in the tissues in which they co-occur. In the cellular economy of multicellular tissues each cell is constantly exposed to threats from both the extracellular and external environments, albeit in various degrees, which makes them susceptible to devolution. The cells that are impinged the hardest tend to lose some of their original functions and structure. If during this process the essential structures which enable the affected cell to attach to other cells to participate in the cellular economy are lost, that cell is sloughed from within the tissue. This does not mean instant cell death. Subsequently the sloughed cell can continue to live independently for a time, the length of which time depends on the prevailing environmental conditions. Apart from unicellular species emerging from this endogenous route from living higher organisms, the decay of dead multicellular organisms is another important mechanism which adds to the pool of unicellular species.

The fate of cells after detachment from source tissues may be any of the following; firstly, instant cell death can occur. Secondly, other intervening conditions within the environment drive further the process of devolution. The cell continues to lose essential organelles and vital structures and in the process changes to completely new cellular species. In the terminal stage the unicellular species that finally emerge will be very dissimilar to cells of the source tissue. Or thirdly, the process of devolution halts and, if the surrounding environment is favourable for it, the entrant species begins to replicate more of its kind. The gist of this discussion is that unicellular species emerge from multicellular organisms through the process of devolution and not in the reverse direction as is posited in classical evolutionary theory.

 

Medical significance

The theory of biological devolution may be applied in the fields of medical microbiology, oncology and rheumatology. The search for effective treatment options for the medical conditions which occur in these three fields should be pursued bearing in mind their pathological convergence in the devolution of the human body and physiology. In medical microbiology recognition to endogenous infection states is necessary, apart from the already known fact that infectious agents may also intrude the human body from the external environment. Thus, an infectious agent may devolve internally from normal cells of the human body and not always have to invade from outside the body. The common feature in both cases is that the infectious agent has reserved ability to attach to normal cells of the body.

Oncological and rheumatic lesions similarly arise from normal cells in the process of devolution of the human body, with degeneration in rheumatic diseases advanced to such an extent that cellular debris produced during devolution contribute substantially to disease development. The deductive proposition in this discussion is that any therapeutic option which works for medical conditions in one of these fields may equally be effective for conditions occurring in the other two fields.

Glucosamine: a drug or toxin?, Part I

 

As a basic principle in pharmacotherapy a drug should have a favourable cost-benefit ratio to justify its usage in medical practice. This means that the cost to the patient for using the drug should be overridden by benefits derived. Cost is not determined by the nominal value of the drug product only, but includes missed opportunities as a result of using scarce financial resources to purchase the drug, as well as the harms potentially sustained from the usage of the drug.

Glucosamine is currently widely prescribed for the treatment of arthritis. There is however no pharmacological basis to support its application in therapeutics, and proof of its efficacy is lacking in the available pharmaco-medical literature.

The commonly projected claim that glucosamine stimulates the regeneration of worn-out cartilaginous tissues in the joints is dubious and not supported by any known scientific evidence. Rather, what has been demonstrated is that glucosamine is embedded in the structure of polymers which form the essential substance of cartilaginous tissues, it occurring together with several other molecular entities.

But between the discovery of glucosamine in cartilage and its current usage as a drug in treatment of arthritis there are still many unanswered scientific questions. A few of these questions are the following: Knowing that glucosamine is a metabolite of glucose how sure are we about the origin of the former in cartilage tissues? Is glucosamine converted from glucose and subsequently embedded in cartilage, or that already embedded glucose in cartilage is modified to glucosamine to strengthen the tissue? Also, like mucus, is it not likely that cartilage itself is an excretory product that is deposited on the bony surfaces at the joints, and that glucosamine is an unwanted metabolite in the human body that through evolutionary adaptation some mechanism has evolved to trap this molecule in cartilage? Until these possibilities have been investigated and excluded we cannot say for certain that glucosamine is a useful metabolite to the human body, much less to talk of loading the body with it from an exogenous source in an attempt to treat some disease condition.

The lack of efficacy of glucosamine as an analgesic has already been established, and there is currently no evidence for the claim that this substance stimulates the regeneration of cartilage. This unfavourable analysis is compounded by evidence accumulating to show that glucosamine is potentially toxic to the body.

Glucosamine has been known for decades to cause insulin resistance in healthy humans and to cause a deterioration of diabetic cases. On-going research and a lot of already published scientific papers have dealt with this matter, only that the topic has evaded general attention. Maybe it is because glucosamine was not used widely in the past as now. And therefore with lots and lots of people taking this substance now the subject matter merits a second look.

 

The first inkling of probable toxicity of glucosamine will arise after juxtaposing the structure of glucosamine against that of streptozotocin.

 

                                                                                                  GLUCOSAMINE

                                                                                                  STREPTOZOTOCIN

 

Streptozotocin was first isolated from cultures of the microorganism Streptomyces achromogenes. In addition to the fermentation pathway the compound is currently also synthesized through two other mechanisms, both using glucosamine as a precursor molecule; either by synthesis from tetra-O-acetylglucosamine hydrochloride, or by reaction of glucosamine with N-nitrosomethylcarbamylazide or N-methylisocyanate.

Streptozotocin is used in biomedical research to induce diabetes mellitus in healthy mammals. A single intravenous injection of 50 – 200mg/Kg/BW of streptozotocin causes destruction of pancreatic β-cells resulting in classic diabetes mellitus in mammals including dogs, rodents and monkeys.

The extent to which the methylnitrosocarbamoyl substituent at position C2 of streptozotocin contributes to its diabetogenic properties is uncertain, but emerging evidence points to the fact that glucosamine itself induces insulin resistance and impairs glucose uptake by skeletal muscles. Therefore a possible mechanism to account for the effect of streptozotocin is that there is first a cleavage by hydrolysis of the amide bond at position C2 forming free glucosamine molecules after administration. Considering the fact that the dosage level of streptozotocin stated above is more than twice the molar equivalent of the usually recommended adult daily dose for glucosamine, that toxic dose could result in a toxic response in the acute phase.

But what if the said substituent is solely responsible for the diabetogenic action of streptozotocin? Can we not reasonably anticipate the risk of that substituent getting bonded to glucosamine in vivo by some yet unknown mechanism after administration?

Time may prove glucosamine an actual toxin and deficient of any real pharmacological effect. For the present, however, we can only safely conclude that the usage of glucosamine is attended with considerable hazards, and for a substance which has not yet been proven to be effective, the prudent course of action is to avoid it.

 

REFERENCE:

Baron AD, Zhu J-S, Zhu J-H, Weldon H, Maianu L, and Garvey T. Glucosamine induces insulin resistance in vivo by affecting GLUT4 translocation in skeletal muscle: Implications for glucose toxicity. J. Clin. Invest. 1995; 96: 2792 – 2801.

A Preliminary Report on The Pharmaceutical Importance Of Vernonia Products

 

The Bitter Leaf plant is an indigenous African plant, its natural habitat spanning along the equatorial belt of Africa, commonly found as a broad-leaved shrub with tender twigs, but matures into a small tree. The epithet “Bitter Leaf” that has come to be the common name of this plant derives from the fact that its leaves are extremely bitter to taste; leaves that are characteristically deep green on the upper surface, pale and pubescent on the underside, not scented, simple in formation, mature leaves approximating the size of the palm of an adult male person, and ellipsoid in shape with pointed ends. The leaves are arranged in alternate pattern on slender twigs of the shrub.

Botanical classification has assigned to this plant the name Vernonia amygdalina Delile, and recently a concern has been raised that it is the same species of plant which was also named and described in a later publication as Gymnanthemum amygdalinum (Delile)Sch.Bip.¹ The plant has been put into the following taxons;

 

Kingdom:  Plantae

 Phylum:  Tracheophyta

  Class:  Magnoliopsida

  Order:  Asterales

 Family:  Asteraceae

 

The fresh leaves of Vernonia amygdalina Del. are consumed as a vegetable in West Africa. This and other organs of same plant have been    attributed with a plethora of medicinal activities and have been put to several medical applications by the native folks. The monograph about this plant in the Ghana Herbal Pharmacopoeia² and the review literature published by Ijeh and Ejike³ are recommended for detailed information on the botanical, ethnomedical, and pharmacological studies that have been conducted on Vernonia amygdalina Del. In the present publication the author seeks to build on the vast wealth of knowledge that has   accumulated about this plant so far. A first attempt is here made to introduce, define and describe finished products obtainable from this plant, and to briefly discuss how these products can be put to useful pharmaceutical application.

 

 

1. CORTEX VERNONIAE

Cortex Vernoniae is defined as the dried stem bark of Vernonia amygdalina (Fam. Asteraceae). The fresh stem bark is collected from the    mature trees and grated or otherwise reduced into small pieces before drying in the sun. In contrast to the leaves of the same plant Cortex Vernoniae is only faintly bitter to taste.

Cortex Vernoniae is the material basis for the preparation of Vernonia Tincture and Vernonia Fluidextract.

 

 

2. VERNONIA TINCTURE

Vernonia Tincture is an alcoholic extract prepared from Cortex Vernoniae. Its colour is straw to dark yellow and essentially composed of the saponins of the plant.

Vernonia Tincture is recommended as an excipient in pharmaceutical and food preparations, to be applied as emulsifying, foaming or wetting agent. It is a suitable local alternative to Quillaia saponins and  Yucca schidigera juice. Studies by this author has shown that Vernonia Tincture could effectively substitute for Quillaia Liquid Extract in the formulation of Concentrated Peppermint Emulsion BPC 1973.

 

Method:

Cortex Vernoniae, in moderately coarse powder …………………………. 1,000g

Alcohol USP, sufficient quantity to obtain …………………………………. 1,000mL

 

Macerate the Cortex Vernoniae powder with 1,100mL of Alcohol USP in a suitable covered vessel for 4hours, gently agitating the vessel at  regular intervals. Transfer the materials to a percolator and carefully perform the percolation at slow rate to obtain 1,000mL of tincture,  using Alcohol USP as solvent.

Reserve the residue for the preparation of Vernonia Fluidextract     according to the method below.

 

 

 

3. VERNONIA FLUIDEXTRACT

Vernonia Fluidextract is recommended as an active ingredient in oral pharmaceutical preparations intended for the treatment of cough and  related respiratory tract diseases. It is a dark brown, slightly    viscous liquid product prepared from Cortex Vernoniae after partial  extraction of its saponins with Alcohol USP.

Prepare Vernonia Fluidextract by using the residue obtained from     extraction of Vernonia Tincture according to the following method: Fill residue into a percolator and carry out percolation at a fast rate   using boiling Purified Water USP as solvent, until the plant material clearly has been exhausted. Combine the percolates and evaporate on steam bath to obtain a volume of 700mL. Add to this and mix 300mL of freshly prepared Vernonia Tincture, and a sufficient quantity of Purified Water USP to obtain 1,000mL of fluidextract.

 

 

REFERENCES:

1. The International Plant Names Index, accessed at www.powo.science.kew.org/taxon/257798-1 on 2021-02-19.

2. Bitter Leaf. Ghana Herbal Pharmacopoeia, 2nd edition(2007). Ed. Kofi Busia. CSIR, Ghana. Pp 30—35.

3. Ijeh, I.I. and Ejike, C.E.C.C.(2011). Current perspectives on the  medicinal potentials of Vernonia amygdalina Del. J. Med. Plant. Res. 5(7): 1051—1061.

 

CITATION:

Adjei, M. A preliminary report on the pharmaceutical importance of Vernonia products. Paracelsus Transactions, 2021: pp 1—4.

 

Magnesium Trisilicate Mixture: A Pharmaceutical Profile

 If prepared in accordance with the method of the British Pharmacopoeia Magnesium Trisilicate Mixture is composed of the active ingredients magnesium trisilicate, light magnesium carbonate, and sodium bicarbonate, with peppermint oil and chloroform as flavouring substances. The insoluble magnesium compounds are suspended in the aqueous vehicle and, as a criterion of quality, these magnesium substances form almost half the volume of this liquid product upon allowing to rest undisturbed for a sufficient time.

Magnesium Trisilicate Mixture is used in therapeutics as an antacid. Its pharmacological action is biphasic, exhibiting a time course of an immediate action coupled with a long term and residual action.

Its immediate action

The dissolved bicarbonate ions mop up preexisting gastric acid in keeping with the following chemical reaction;

A therapeutic response based on this pharmacological action manifests within a few minutes subsequent to oral administration and because of this action the use of parenteral proton-pump inhibitor in a non-emergency situation may not be necessary.

Residual action

Both magnesium carbonate and magnesium trisilicate neutralizes excess gastric acid in a slow running chemical reaction that can span over several hours. In the case of the latter, reaction with gastric acid splits the complex compound producing silicic acid and magnesium oxide. The silicic acid formed, otherwise known as hydrated silica or colloidal silica, has a very fine texture with particle sizes within the nanometer scale range. Colloidal silica is known to bind tenaciously to proteins, hence the theory that that produced in situ from the hydrolysis of magnesium trisilicate binds to ulcerated lesions located within the lumen of the gastrointestinal tract. The commonly accepted theory is that Magnesium Trisilicate Mixture additionally acts by forming a protective coat of colloidal silica over gastric and duodenal ulcers, this colloidal silica layer proving an effective mechanical barrier against contact of these ulcer lesions with gastric acid. This is what has been described as the long term and residual action of Magnesium Trisilicate Mixture.

Administration

The usually recommended adult dose of Magnesium Trisilicate Mixture is 10 - 20mL, repeated three times a day or as required. As a practice, each dose should be mixed with a small quantity of water to increase its bulk.

Magnesium Trisilicate Mixture is prescribed for treatment in various options. In a popular treatment option touted as the Fordtran regimen Magnesium Trisilicate Mixture may be administered four times within a day; three times within the day, preferably between 1 - 2 hours after a meal, and the last dose taken at bedtime. This regimen may suffice for treatment of peptic ulcer and dyspeptic ailments as monotherapy. In current practice the proton-pump inhibitors have supplanted antacids from the enviable place they once held and have lessened their importance in the treatment of peptic ulcer and other dyspeptic ailments. Now, Magnesium Trisilicate Mixture may still be added to a proton-pump inhibitor to achieve synergistic effect according to the mechanisms already discussed, albeit the frequency of its administration will have to be reduced dramatically.

The most controversial treatment option is when Magnesium Trisilicate Mixture, or any other antacid, is added to a triple therapy regimen for treatment of confirmed cases of peptic ulcer disease. Otherwise, the concurrent usage of a proton-pump inhibitor with Magnesium Trisilicate Mixture, or another antacid, is very reasonable and may even allow less frequent administration of both drugs.