A QUANTITATIVE ASSESSMENT OF THE TOPICAL ANTI-PHILOGISTIC POTENCIES OF CORTICOSTEROIDS AND NON-STEROIDS
ATTENTION:
BEFORE YOU READ THE CHAPTER ONE OF THE PROJECT TOPIC BELOW,
PLEASE READ THE INFORMATION BELOW.THANK YOU!
INFORMATION:
YOU CAN GET THE COMPLETE PROJECT OF THE TOPIC BELOW. THE FULL
PROJECT COSTS N5000 ONLY. THE FULL INFORMATION ON HOW TO PAY AND GET THE
COMPLETE PROJECT IS AT THE BOTTOM OF THIS PAGE. OR YOU CAN CALL: 08068231953,
08168759420
A
QUANTITATIVE ASSESSMENT OF THE TOPICAL ANTI-PHILOGISTIC POTENCIES OF
CORTICOSTEROIDS AND NON-STEROIDS
TABLE OF
CONETENT
Abstract
Chapter one: Introduction
Chapter two: Materials and methods
2.1
substances
2.2
solvents
2.3
animals
2.4
procedure
2.5
calculation of result
Chapter three: Result
Chapter four: discussion and conclusion
Appendix
I: list of figures
Appendix
II: List of tables
References
ABSTRACT
A
phi logistic response was induced by topical application of croton oil dissolved
in suitable vehicles. This response was quantitated by cutting out the ears
6hrs later, weighing, and evaluating the increases in weight relative to the
controls (contralateral unapplied ears). Co-application of increasing doses of
the drugs (corticosteroids and Non-steroids) resulted in grossly related
decreases of the phlogistic response. Reduction of the inflammation was
observed to be relatively higher with the steroids, especially the novel
derivatively higher with the steroids, especially the novel derivatives
(dexamethasone, beta-methionine and fluocortolone mono-acetate) than the
natural glucocorticoids and the Non steroids. Their effectiveness correlated to
the finding that relatively smaller doses are required to achieve 50% reduction
of the response.
It
is concluded that the 6 and 9 fluorinated corticoids exhibited higher
potencies and thus will be of much significant benefit in inflammatory
reactions of the skin.
CHAPTER
ONE
INTRODUCTION
Injury
to the body is inevitable. This could be consequent upon physical, chemical,
biological or any other stimuli of sufficient intensity.
Attempts
by the body to limit the spread of the injury and/or the injurious agent as
well as to resolve any consequent damage is referred to as inflammation.
Inflammatory reactions are necessary for the maintenance of life and therefore
for the continuity of the species (i). the diversity of the causative factors,
makes inflammation one of the commonest and most important conditions in the
clinics.
Observational
interests on inflammation is probably as old as man, but the earliest known
descriptions by Edwin Smith’s Egyptian – papyrus dates from about 1550 B.C.
(2). More documents from Egypt and other early civilizations leave no doubt
that inflammation was recognized from very early times. However, the
under-standing of the process took a long time. Calcium (BC 30 – AD 38) and
Galen (AD 130 – 200) were among the first to appreciate the cardinal signs of
inflammation=redness, heat, selling and pain (23)
Thereafter,
several investigations over the centuries have equipped us with a greater and
appreciable under=standing of the inflammatory process.
MAIN EVENTS OF THE INFLAMMATORY PROCESS
Subsequent
to injury, the inflammatory response results from the summation of small
distinct local reactions in the injured tissue. Some of these events are
illustrated in the Lewis’ ‘’Tripple response’’ as flush, flare and wheal (4).
These being descriptions based on macroscopic observation. Macroscopic
investigations have revealed that the responses of the vessels and other local
components of the damaged tissue are far more complex than might be thought of
from macroscopic observation.
Although
the inflammatory process in its entirety has been extensively studied over the
past years, its complexity has prevented full elucidation of the various
mediators and mechanism of mediation.
However,
auto pharmacological methods and the use of specific pharmacological
antagonists have elaborated a serious of putative mediators of inflammation.
Many of these agents share several common properties and may produce distinct
and rele4vant signs and symptoms of the process. Some have been extensively
studied, several are still not completely characterised.
Inflammation
therefore is a multi-mediated process and its signs and symptoms can be
regarded as the expression of the pharmacological effects of endogenously
mobilized materials acting locally (5).
Immediately
upon impact (as in physical stimuli), there is transient Ischaemia from
vasoconstriction. Then follows a progressive dilatation of the blood vessels
due to release of histamine and other vasoactive substances from resident cells
(6). By anti-dromic stimulation of sensory nerve endings supplying the blood
vessels, histamine produces a secondary vasodilatation there is evidence that
ATP or ‘substance p’ may be the release vasodilator at this stage (7). These
events lead to an increased local blood flow resulting in local heat and redness.
Increased
vasocular permeability with exudation of plasma proteins and fluid from the
circulation into the adjacent extravascular tissue, is responsible for the
local oedema seen during the process. Release of chemo-tactic factors
(8,9,10,11.) enhance the emigration of blood leukocytes into the injured
tissue, where they display increased pseudopodia movements, phagocytising
foreign materials and cellular debris and releasing enzymes that are
potentially tissue damaging (12). The pain of inflammation may be due to
stimulation of sensory nerve endings by substance such as histamine, 5 –
hydroxyl tryptamine (5HT), Kinins, low PH and ions from damaged cells (13, 14).
Tissue damage and pain are largely responsible for the loss of function that
may accompany the inflammatory process.
THE ROLE OF ARACHIDONIC ACID METABOLITES IN
INFLAMMATION
Although
many mediators take part in the complex process of inflammation, some of the
most important precursor (arachidonic acid), stored predominantly as an
esterified component of cell membranes in most tissues (15). Archidonic acid is
cleaved from its ester linkage and released by the enzymatic action of
phospholipase A2 in response to the inflammatory stimuli. Since PG’s
are not stored intracellular, they must be synthesized locally immediately
following the release of arachidonic acid. This synthesis is achieved by multi enzyme
complexes located in the microsomal fraction of the cell.
Arachidomic
acid metabolites are obtained via two different pathway (Fig. I).
1.
The cyclo-oxygenase
enzymatic pathway, which results in the synthesis of the leukotrienies (LTS).
The association between PG’s with
inflammation has been demonstrated by a number of investigators (16, 17, 18).
In addition to producing the classical signs of inflammation, PG’s also induce
fever (1920) and potentiate the effects of histamine and brady kinin (21, 22).
Another cyclo-oxygenase product
thromboxane A2 has also been implicated in inflammation (23).
Leukotrienes, as shown in fig. 1 are
the most recently discovered compounds associated with inflammation that are
derived via the lipoxygenase pathway. This pathway has been shown to be highly
active in human skin. LPB4 is the most potent chemotactic agent
known. LTC4 and LTD4 are inducers of increased vasoular
permeability in the skin (27).
Co-production
of cytotoxic oxygen radicals, also cause damage to surrounding tissue.
ANTI-INFLAMMATORY
AGENTS
Fundamentally, inflammation is a
protective and often life-saving process serving, to remove or neutralize
exogenous and endogenous noxious agents; to dispose of cells and other
constituents of the host tissue which have been killed or damaged in the
defence reaction; and to repair the damage sustained either by complete
restoration (regeneration) of the affected tissue or by scar formation.
Although of great importance for survival, it may occasionally cause harmful
effects. The inflammatory responses intended to destropy hostile elements may
damage the body itself and excessive and prolonged inflammation is likely to
occur when the offending agent cannot be eradicated. In often useful.
NON-STEROIDAL
ANTI-INFALMMATORY DRUGS (NSAID’S)
Many pharmacological agents that
produce anti-inflammatory activity, do so by inhibiting the synthesis of PG’S.
There is a strong correlation between anti-inflammatory activity and inhibition
of PG synthesis as indicated by the action of the NSAID’S.
The
NSAID’S cause a blockade of only the cyclooxygenase pathway of arachidonic acid
metabolism by inactivating the enzyme – cyclo-oxygenase. Other
anti-inflammatory effects of NSAIDS, some of which are associated with PG
inhibition include the inhibition of: hyaluranidase enzymes activity, migration
and phagocytic activity of polymorphs, the complement system, plasmin, kinin
formation and platelet aggregation. NSAID’S may antagonize Algeria by
depressing pain stimuli at a sub-cortical site. Their anti-pyretic potency is
of benefit in reducing the pyrexia that may accompany the inflammatory response
(24, 25, 26, 27).
The side effects of the use of NSAIDS
in inflammation ironically results from the mechanism by which they achieve
their therapeutic effect, that is, by PG inhibition and include gastro
intestinal irritation, ulceration dyspepsia, nephrotoxicity, prolonged
bleeding, prolonged gestation heache, dizziness, tinnitus and blurred vision
(28, 29).
CORTICOSTEROIDS
The corticosteroids are steroid
hormones produced by the cortex of the adrenal gland. Those with
anti-inflammatory activity are the glucocorticoids (30, 31, 32), while those
with significant inneralocorticoid activity have no effective anti-inflammatory
actions (33).
Modifications of the natural
glucocorticoid structure yields derivative whose anti-inflammatory actions are
more pronounced. However the means whereby anti-inflammatory potency is
enhanced by these structural modifications are not yet understood.
The glucocorticoids act by protein
synthesis. They have been shown to block the production of arachidonic acid
metabolites by inhibiting the enzyme phospholipase A2 (34, 35, 36).
By this action both pathways (Cyclo-oxygenase and lipoxygenase) are
automatically and simultaneously blocked.
Other actions of the corticosteroids
include the stimulation of adeny cyclase enzyme, stabilization of cellular and
lysosornal membranes, inhibition of collagenase activity, depression of
vascular reactivity modification of immune responses and blockade of pyragenic
reactions.
However, the use of steroids as anti-inflammatory
drugs predispose patients to various types of adverse effects which include
adrenal suppression, peptic ulceration, increased susceptibility to infection, rogenic
Cushing syndrome, hypo kalaernia, alkalosis, oedema, myopathy, nervousness,
insomnia and growth retardation (especially in children)
The glucocorticoids show an increased
activity over the non steroidal agents. This could be partly explained by the
fact that steroids block both the cyclo and lipoxygenase pathways.
Having examined the therapeutic basis
of these agents, their potential toxicity following systemic administration as
well as well as the greater anti-inflammatory activity of the cortico-steroids
over the non-steroids, it became necessary to synthesize new glucorcorticoid
preparations that possess different and variable degrees of such
pharmacological properties as potency, duration of action, lipid solubility,
plasma porotein binding and gastro intestinal tract stability.
This study therefore compares the
topical antiplogistic efficacy of some glucocorticoid derivatives
(dexamethasnone, betamethasone, fluocortolone moneacetate, hydrocortisone and
cortisone) relative to that of the non steroidal agents (acetyl salicyclic acid
and indomethacin).
HOW TO GET THE FULL PROJECT WORK
PLEASE, print the following instructions and information if you
will like to order/buy our complete written material(s).
HOW TO RECEIVE PROJECT MATERIAL(S)
After paying the appropriate amount (#5000) into our bank Account
below, send the following information to
08068231953 or 08168759420
(1) Your project topics
(2) Email Address
(3) Payment Name
(4) Teller Number
We will send your material(s) immediately we receive bank alert
BANK ACCOUNTS
Account Name: AMUTAH DANIEL CHUKWUDI
Account Number: 0046579864
Bank: GTBank.
OR
Account Name: AMUTAH DANIEL CHUKWUDI
Account Number: 2023350498
Bank: UBA.
HOW TO IDENTIFY SCAM/FRAUD
As a result of fraud in Nigeria, people don’t believe there are
good online businesses in Nigeria.
But on this site, we have provided “table of content and chapter
one” of all our project topics and materials in order to convince you that we
have the complete materials.
Secondly, we have provided our Bank Account on this site. Our Bank
Account contains all information about the owner of this website. For your own
security, all payment should be made in the bank.
No Fraudulent company uses Bank Account as a means of payment,
because Bank Account contains the overall information of the owner
CAUTION/WARNING
Please, DO NOT COPY any of our materials on this website
WORD-TO-WORD. These materials are to assist, direct you during your
project. Study the materials carefully and use the information in them to
develop your own new copy. Copying these materials word-to-word is CHEATING/
ILLEGAL because it affects Educational standard, and we will not be held
responsible for it. If you must copy word-to-word please do not order/buy.
That you ordered this material shows you have agreed not to copy
word-to-word.
FOR MORE INFORMATION, CALL:
08068231953 or 08168759420
AFFILIATE LINKS:
myeasyproject.com.ng
easyprojectmaterials.com
easyprojectmaterials.net.ng
easyprojectsmaterials.net.ng
easyprojectsmaterial.net.ng
easyprojectmaterial.net.ng
projectmaterials.com.ng
googleprojectsng.blogspot.com
myprojectsng.blogspot.com.ng
https://projectmaterialsng.blogspot.com.ng/
Comments
Post a Comment