1Department of Pharmacology and Toxicology, Nnamdi Azikiwe University Awka, Anambra state Nigeria,
Corresponding author details:
Ihekwereme Chibueze
Department of Pharmacology and Toxicology
Nnamdi Azikiwe University Awka
Anambra state Nigeria,
Copyright:
© 2018 Chibueze I, et al. This is
an open-access article distributed under the
terms of the Creative Commons Attribution 4.0
international License, which permits unrestricted
use, distribution, and reproduction in any
medium, provided the original author and source
are credited.
Gastrointestinal (GI) toxicity associated with non-steroidal anti-inflammatory drugs
(NSAIDs) is still an important medical and socio-economic problem - despite recent
pharmaceutical advances. Furthermore, no monotherapy has been able to eradicate
Helicobacter pylori bacteria which have been reported to be the major cause of peptic ulcer
disease. In recent time, a lot of attention has been focused in developing new treatment and
preventive options for peptic ulcer disease. This review also illustrates the current status
of the available techniques in endoscopy with a focus on screening for peptic ulcer disease.
There is the need for the review of these recent approaches and breakthroughs hence, this
literature review.
COX/5-LOX; H. pylori; Prevention; NO-NSAID; NSAIIDs; Modern endoscopy
Peptic ulcer diseases comprise heterogeneous disorders, which manifest as a break in the lining of the gastrointestinal mucosa bathed by acid and pepsin. It is the most predominant of the gastrointestinal diseases with a worldwide prevalence of about 40% in the developed countries and 80% in the developing countries [1,2]. It is generally recognized that peptic ulcer is caused by a lack of equilibrium between the gastric aggressive factors(acid-pepsin secretion, parietal cell) and the mucosal defensive factors (mucosal barrier, mucus secretion, blood flow, cellular regeneration and endogenous protective agents e.g prostaglandins) [3] Figure 1.
It is a well-known phenomenon that non-steroidal anti-inflammatory drugs (NSAIDs)
cause gastric mucosal damage. Topical damage caused by NSAIDs includes the accumulation
of ionized NSAIDs in the gastric epithelial cell called ‘ion trapping’ effect, the reduction of the
hydrophobicity of the gastric mucosal surface and uncoupling of oxidative phosphorylation
[4-6]. Disruption of the epithelial barrier allows back-diffusion of acid into the mucosa.
Since the identification of H. pylori as a causative agent in peptic ulcers by Barry Marshall
and Robin Warren in the late 20th century, the gastroenterological practice worldwide
has changed [7]. However, only a combination of antimicrobials can be used in vivo to
eradicate H. pylori and none of the antimicrobials is effective enough to eliminate H. pylori
when given as monotherapy [8]. Helicobacter pylori infection is reported to account for
more than 70% of cases of peptic ulcer diseases [9]. Currently the pathogenic effect of the
peptic ulcer disease due to recurrence after cessation of the treatment is yet to be resolved.
The emergence of antibiotic resistance, the high cost of the currently available treatment
measures, and the increase in the number of reported relapses highlight the need for new
alternative therapeutic approaches [10]. New treatment and preventive strategies for
peptic ulcer disease are steadily being discovered, adopted and evaluated in clinical studies
with very promising results. They include strategies for the prevention of NSAIDs-induced
upper digestive injury, maintenance of gastric mucosal balance, development of nano
bodies against UreC subunit of urease enzyme and research towards vaccine development
against H. pylori bacteria.
NSAIDs are known to cause gastrointestinal (GI) toxicity that often leads to ulceration
or perforation of the GI mucosal lining, a factor that limits their use. The major concern with
the chronic usage of aspirin or other NSAIDs is that 30 to 40% of patients using NSAIDs
have a GI intolerance to the drugs and suffer from a spectrum of symptoms ranging from
dyspepsia to peptic ulcer disease, the latter which may be associated with life-threatening
episodes of hemorrhage [11]. One clinical study demonstrated that 30% of chronic NSAIDs
users had at least one gastroduodenal ulcer, as observed via endoscopy [12]. Furthermore, a
retrospective study restricted to rheumatoid arthritis patients in the U.S. concluded that GI
complications as a result of NSAIDs usage are responsible for 400,000 hospitalizations and
16,000 deaths annually in this patient population [12]. At present, novel pharmacological strategies are being investigated to counteract the detrimental
actions of traditional NSAIDs on the gastrointestinal tract. The main
options currently under active evaluation are the formulation of fixed
combinations of NSAIDs with a gastro protective drug.
Figure 1: Schematic diagram of Peptic ulcer disease manifestations
PC is the most active form of gastric phospholipids which
protects the gastro-intestinal track (GIT) from ulcerogenic conditions
or compounds including NSAIDs. NSAIDs such as aspirin disrupt
the natural barrier mechanism of the gastric epithelium because
they bind to the mucosal surfactants (phospholipids). When
NSAIDs associate with surface phospholipids the hydrophobic
barrier becomes hydrophilic allowing acid to permeate the mucosal
lining resulting in disruption of mucosal integrity [13] (Figure 2).
Exogenous Phosphatidyl-choline is a functional excipient that plays
a key role as a solubilizing agent via the formation of a non-covalent
complex with the active ingredient NSAID. By association with the
active ingredient, the PC-NSAID complex becomes markedly more
lipophilic [14]. This enhanced lipid solubility of the drug promotes
its transit across the hydrophobic mucus gel layer of the upper GI
tract, presumably the stomach, with reduced surface mucosal injury.
The PC- containing oil excipient neither impedes the bioavailability
of the NSAID nor changes the pharmacological activity. The PC
lipid based NSAID products currently being developed by Plx
Pharma offer lower risk of gastrointestinal erosion and ulceration
while maintaining the pharmacological activity and bioavailability
demonstrated by the commercial NSAID drug products [15]. Thus
this new class of PC associated NSAIDs appears to offer lower risk
of GI erosion and ulceration while maintaining the pharmacological
activity and bioavailability demonstrated by the commercial NSAID
drug products.
NSAIDs are rapidly absorbed from the GIT and in many cases
undergo enterohepatic circulation. Bile plays important role in the
ability of NSAIDs to induce small intestinal injury. Bile acids are
synthesized in the liver. Bile salts (conjugation of bile acid and taurin
or glycin) are known to destroy the permeability barrier of gastric mucosa and increase mucosal permeability to acids. Biliary PC is
important in detoxification of bile salts. NSAIDs that are secreted
in the bile injure the intestinal mucosa by their ability to chemically
associate with biliary PC which forms toxic mixed micelles and limits
the concentration of biliary PC available to interact with and detoxify
bile salts. Thus NSAIDs with extensive entero-hepatic cycling are more
toxic to GIT and are capable of attenuating the surface hydrophobic
properties of the mucosa of lower GIT. Hence, pre associating the
NSAIDs with exogenous PC prevents a decrease in the hydrophobic
characteristics of the mucus gel layer [16].
These classes of NSAIDs have been developed exploiting the
concept that NO released locally in the gastric mucosa, would
enhance the mucosal blood flow and reduce leukocyte adherence in
the gastric microcirculation. This new class of NO-NSAIDS is prepared
by adding a radical, nitro butyl or nitrosothiol by using a short chain
ester linkage. This exhibits reduced gastrointestinal toxicity while
enhancing vasodilatation, reducing blood platelet adhesion and
acting as a buffer against memory loss [17]. They are synthesized by
ester linkage of a NO- releasing moiety to conventional NSAIDS, such
as aspirin (NO-Aspirin), flurbiprofen (NO-flurbiprofen), naproxen
(NO-naproxen), diclofenac (Nitrofenac), lbuprofen (NO-lbuprofen)
and indomethacin (NO-indomethacin). An experimental study
with NO-NSAID showed their ability to spare the gastrointestinal
tract after either acute or chronic use in animals; NO-naproxen is
completely devoid of ulcerogenic activity [18]. Similar results have
been reported with NO-Aspirin after single dose administration in
rats, Nitrofenac, NO-indomethacin [19-22]. The capacity of NO-NSAID
to release NO appears to affect the gastrointestinal toxicity [22]. NOaspirin accelerated the healing process; NO-aspirin showed a dose
dependent decrease in the severity of HCl/ethanol induced stomach
lesions in rats [23]. NO-NSAID may be valuable in the treatment of
existing ulcers and are likely to be of greater therapeutic benefit than
classical NSAID for the treatment of inflammatory disease in patients
with pre existing gastric damage. COX inhibiting NO-donating drug
(CINOD) inhibits COX-1 and COX-2 activities, has less adverse effect
on gastrointestinal tract and reduces systemic blood pressure. NOASA (Acetyl Salicylic Acid) maintains gastric mucosal blood flow
and reduces leukocyte – endothelial cell adherence [22]. A recently published study involving a total of 31 volunteers supported the
data obtained in animal studies showing significantly reduced but
not completely abolished GI toxicity associated with NO-naproxen
compared with conventional naproxen in humans [24].
Figure 2: The mechanism by which non-steroidal anti-inflammatory drugs (NSAIDs) may compromise the surface barrier by
disrupting the PC layer allowing luminal agents access to the epithelium.
Hydrogen sulfide (H2S) is a gaseous mediator actively involved
in the maintenance of digestive mucosal integrity and blood flow
[25]. This gaseous compound, previously regarded as a toxic agent, is
emerging as an endogenous modulator which seems to share almost
all the beneficial actions of NO on several physiological processes.
In particular, it has been demonstrated that H2S is produced by the
gastric mucosa, and that it contributes to the ability of this tissue
to resist damage induced by luminal agents [26]. Interestingly,
several lines of evidence have shown that H2S donors can prevent
the decrease in gastric blood flow induced by NSAIDs and reduce
NSAIDs-induced leukocyte accumulation and adhesion in gastric
micro vessels, thus providing a rationale for the synthesis of H2Sreleasing NSAID derivatives as novel anti-inflammatory drugs [26].
As previously observed with CINODs, an H2S-releasing derivative
of diclofenac was shown to be better tolerated in terms of gastric
damage as traditional NSAIDs and the addition of the H2S- releasing
moiety has been found to increase the anti-inflammatory activity of
diclofenac. Additional strategies for the prevention of NSAID-induced
upper digestive damage include the ongoing clinical development of
pharmaceutical products containing fixed combinations of NSAID
with a gastro protective drug, such as naproxen/omeprazole,
naproxen/lansoprazole, naproxen/esomeprazole and ibuprofen/
famotidine [25].
gastric mucosal integrity; vitamin C is actively secreted into the
gastric lumen of healthy subjects and its concentrations are decreased
in patients with gastroduodenal diseases such as peptic ulcer disease
and gastric malignancy [27]. The underlying molecular mechanisms,
however, are not fully understood. The activity of protective antioxidizing enzymes like superoxide dismutase and glutathione
peroxidase, intra gastric vitamin C levels in the stomach were
impaired by Asprin [28]. Co-medication with vitamin C abolished
these effects, was able to scavenge free radicals, and significantly attenuated gastric damage [28]. It has been recently shown that the
gastroprotective effects of vitamin C as observed in humans might at
least in part be mediated by haeme-oxygenase-1 (HO-1) [29]. HO-1
is ubiquitous and crucial tissue-protective enzyme with vasodilative,
anti-inflammatory and antioxidant properties. Vitamin C has been
identified as a potential non-stressful inducer of HO-1 in the stomach
[30].
The development of osteoarthritis may be accompanied by
increased production of leukotrienes (LTs) and prostaglandins (PGs)
from arachidonic acid. These products contribute to joint damage,
pain and inflammation. Cyclooxygenase, COX-1 and COX-2 are
responsible for the production of PGs. Inhibition of these enzymes
by non-steroidal anti-inflammatory drugs and selective COX-2
inhibitors reduce the levels of PGs, resulting in a reduction in pain
and inflammation. This inhibition can cause alternative processing of
arachidonic acid via the 5-lipoxygenase (5-LOX) pathway, resulting
in increased production of proinflammatory and gastro toxic LTs.
Hence dual inhibitors of COX/5-LOX have been developed in order
to achieve enhanced anti-inflammatory activity while sparing gastric
mucosa [31]. Licofelone (or ML3000) was demonstrated to exhibit
these properties in animal trials [31]. Licofelone is a competitive
inhibitor of 5-LOX, COX-1 and COX-2 that is currently being developed
for the treatment of osteoarthritis. Licofelone decreases the
production of both LTs and PGs, and thereby reduces inflammation
and pain with low gastro toxicity. Unlike selective COX-2 inhibitors,
co administration of licofelone and aspirin does not appear to be
associated with an increase in gastrointestinal adverse events, at
least under experimental conditions. Furthermore, there is evidence
from animal models to suggest that Licofelone may stop disease
progression [32]. Phase II trials have indicated that this COX/5-LOX
inhibitor spares human gastric mucosa Licofelone has been shown to
retain its GI safety profile when taken together with low-dose aspirin
in a study involving 75 patients [33,34].
Peptic ulcer disease is caused by a lack of equilibrium between the gastric aggressive factors and the mucosal defensive factors [35]. The various aggressive factors include bile, bacteria, enzymes, pepsin-HCL secretion and defensive factors include mucosal barrier, mucus secretion, blood flow, cellular regeneration, bicarbonate and endogenous protective agents (prostaglandins and epidermal growth factors [3]. When the latter cannot keep up with the former, the stage is set for stomach wall disruption and ultimately ulceration. Though it is logical to focus on reducing acid production and eliminating H. pylori, the question remains as to why the mucosal lining was compromised in the first place. Given that many more individuals carry than have ulcer disease, it is clear that other factors influence the onset of the disease process. Even with the best pharmacotherapy, ulcer recurrences are common, suggesting that acid suppression and eradication of microbial pathogens is insufficient. The current therapeutic challenge is to restore the delicate balance by addressing the factors that impair healing of the gastric lining, and improving mucosal integrity. Zinc carnosine was developed in an effort to close that gap, by providing a therapy that bolsters the ability of the gastric lining to repair and protect itself. Carnosine is a naturally-occurring dipeptide, comprised of β-alanine and L-histidine. It is a chelate of elemental zinc and car nosine in a 1:1 ratio. It is a strong freeradical scavenger capable of blocking free radical chain reactions, thus inhibiting lipid peroxidation [36]. H. pylori cannot survive at low pH without producing urease which catalyzes the hydrolysis of urea to ammonia and CO2 . In the stomach, the organism creates an ammonia-rich “bubble” which neutralizes gastric acid, allowing it to embed in the gastric epithelium. To date, there have been 8 clinical trials of zinc carnosine for the treatment of peptic ulcers [37]. It is marketed in Japan under the trade name of Polaprezinc and in the US it is marketed as ZinLori 75 in tablets and capsules by Metagenics.
Helicobacter pylori infection of the gastric mucosa remains a
cause of significant morbidity and mortality almost 30 years after its
discovery [7]. The vast majority of H. pylori infections are acquired
during childhood and the most frequent route of infection is oral-tooral transmission [38]. Unless successfully eradicated either by anti
microbial treatment or via host inflammatory and immune responses,
most infections persist for life. In developed countries, it has been
calculated that a 10-year vaccination program would significantly
reduce the prevalence of H. pylori-related peptic ulcers and gastric
cancer in the population and related morbidity and economic costs
associated with these diseases [39]. For these reasons, research
towards a vaccine against H. pylori infection for use in humans has
been ongoing since shortly after the isolation of H. pylori in 1984 [7].
Numerous vaccination studies have now been performed in rodents
using either Helicobacter felis or H. pylori as challenge organisms
[40]. H. felis lacks many of the virulence mechanisms identified in
H. pylori but it induces significant levels of histologic gastritis and
has many features resembling H. pylori-induced gastritis in the
human stomach. Survey of studies of candidate vaccines reveals that
it is possible to induce some level of immunity against H. felis or H.
pylori infection by use of any one of various vaccination strategies
[41]. Significant reductions in bacterial load have been achieved in
vaccinated mice following challenge of their immune system with H.
pylori or H. felis organisms [42].
Clinical trials with prototype H. pylori vaccines began at about the same time as some of the nonhuman primate studies. Given the nature of most of the animal model studies performed during the 1990s, these clinical trials have predominantly focused on H. pylori urease-based vaccines delivered orally. The first clinical trial tested the therapeutic efficacy of an H. pylori vaccine administered to H. pylori- positive individuals [43]. 180 mg, 60 mg, or 20 mg doses of H. pylori urease were administered in combination with either 5 μg or 10 μg according to an immunization and booster regime previously shown to be successful in mice. Immunogenicity was determined by measuring the number of urease-specific antibody-producing cells in the blood. Disappointingly, no sterilizing immunity was observed in vaccinated individuals, but a significant reduction in bacterial load was observed in individuals given the 20 mg dose of H. pylori urease. Gastric inflammation was unaltered by vaccination. However, when the results of these studies are combined, some important summations can be made that may be applicable to humans:
Urease is a nickel-containing enzyme found in H. pylori that catalyzes the hydrolysis of urea to ammonia and carbon dioxide in the acid environment of the stomach [47]. The products of this reaction, bicarbonate and ammonia, are strong bases that further protect the bacteria from the stomach acid because of their acid-neutralizing capability.
\[ urea + stomach acid + water\rightarrow bicarbonate + ammonia\]
\[C =O.2NH_{2} + H^{+} + 2H_{2}O\rightarrow HCO_{3} + 2NH_{4}^{+}
\]
The enzyme Urease therefore plays an important role in the infection capabilities of H. pylori. It allows this pathogen to survive, grow, and multiply at the low pH of the stomach, spreading infection to the inner layers of gastro duodenal mucosa, resulting in gastritis and peptic ulceration, which in some cases leads to gastric cancer [48]. Urease constitutes 10–15% (w/w) of the total proteins produced by H. pylori, and presents in both the cytoplasmic and surface-associated forms [49].
UreC is one of the urease enzyme subunits. UreC is an antigenic protein that can stimulate a specific and innate response and contains an enzyme active site [50]. Nanbody is a single domain antibody (sdAb) fragment consisting of a single monomeric variable antibody domain. These antibodies have a single chain variable domain referred to as VHH or sdAb or nanobody. Like a whole antibody, it is able to bind selectively to a specific antigen. Nanobodies have better tissue penetration and effective pharmacodynamics with less interference with the host immune system [51]. The greater therapeutic value of nanobodies over conventional antibodies is due to their small size (2.5 nm in diameter and nearly 4 nm high) high stability at extreme temperatures and PH, physical stability, capability of refolding and binding to unique epitopes inaccessible to conventional antibodies [52]. The administration of antibody against H. pylori is a new effective therapeutic strategy. Based on previous research [53]. UreC-specific antibodies can neutralize H. pylori urease enzyme and reduce bacterial colonization in an invitro environment [53]. Antibodies, unlike antibiotics, can recognize certain antigens on the microorganism and neutralize virulence factors that enable the host immune system to interact with the microorganism and furthermore prevent relapses [54]. Several nanobodies against urease enzyme have been produced [55]. But due to problems such as low stability and low yield of production and immunogenicity, the need for a new generation of antibodies seems necessary [56]. A novel single variable domain of heavy chain antibody against recombinant UreC has been successfully developed [57]. This particular work is an improvement over previous work in this field in the following areas:
Hence nanobody could be a great therapeutic strategy for the
eradication of H. pylori infection considering its advantages over
conventional antibody.
The growth of peptic ulcer disease with time is complex and
interesting. Although its incidences were rare before 1800 century,
with time and change in life style its incidences have increased
significantly [59]. Several therapeutic strategies have evolved over
time for its management. Research for development of antiulcer
agents usually aims to address one or more of these factors (pepsinHCL), muscarinic -M1 receptors, gastrin receptors, histamine-H2
receptors and proton pumps, analogues of prostaglandins, mucosal
protection and eradication of H. pylori. Considering the involvement
of multiple factors in its etiology, it has not been possible to provide
an ideal solution to completely cure peptic ulcer disease occurrence.
Traditional use of antacids and use of histamine inhibitors have
become insufficient in the management of peptic ulcer. Irreversible
inhibition of proton pump although reduces ulceration in the long
run leads to adverse issues. It has not been possible to develop an
ideal proton pump inhibitor. In this scenario, search for alternatives
by capitalizing on the multifactorial etiology of ulceration holds
promise. However, these searches are far from over and require
further investigations to develop ideal antiulcer agents. Moreover,
application of some of the new strategies is still limited due to lack of
research for several reasons. Such reasons being that the prevalence
of peptic ulcer disease in Western countries is low (limited access to
volunteer participants for clinical trials), the high costs of performing
such studies on a large scale in developing countries where there is
high prevalence of infection is high and there is inadequate facilities
to carry out these clinical trials studies in these countries.
Endoscopy is a procedure in which an instrument is introduced
into the body to give a view of its internal parts. Rapid advancements
in computer and chip technology and the resulting technical
options in imaging and image processing have influenced modern
endoscopy today as never before in the past. A large number of
technical innovations have been introduced in diagnostic endoscopy
in the last few years, with the aim of improving the detection and
characterization of pathological changes in the gastrointestinal
track. High-resolution image display in endoscopes of the newest
generation is supported by virtual chromoendoscopy, a type of
staining of mucous membranes at the press of a button. Classical
chromoendoscopy is also significant for specific indications. Recent
microscopic procedures such as endomicroscopy and endocytoscopy
are able to not only predict pathological changes on the basis of their
surface or vascular pattern, but also directly visualize the cellular architecture of the mucosa. The better the quality and clarity of
images, the better the patient can be cared for. Thus, the main purpose
of endoscopy can be achieved, which is early and timely detection of
peptic ulcer disease.
High definition became a catchword after the introduction of
high definition television (HDTV) in television and entertainment
technology. It produced high-resolution images that were practically
incomparable with, and unobtainable by, the previously used
transmission technology (PAL) in endoscopy. Further development of
chip technology (CCD chip), by which more than one million pixels per
image can be analyzed today, led to the achievement of much greater
resolution in so-called high-resolution endoscopy than in video
endoscopy of the first generation [60]. The most recent color chips,
although miniaturized, currently permit greater pixel density and a
resolution of more than one million pixels per video image, which can
now be visualized by the new television standard of HDTV [60]. This
has greatly enhanced image quality compared to standard resolution
(SR). Combined with conventional or virtual chromoendoscopy,
preliminary clinical data indicate that the technical advancement of
HD endoscopy is a decisive element of better diagnostic investigation,
and is thus able to exert an immediate impact on the prognosis of the
disease for patients [61].
The color dyes or pigments used in chromoendoscopy either
react with intracellular structures of mucosa (absorption) or
remain on the mucosal surface (contrast stain).The most commonly
used staining materials in the upper gastrointestinal tract are
Lugol’s solution (changes in squamous epithelium) and acetic acid
(changes in the columnar epithelium). In the lower gastrointestinal
tract one usually employs indigo carmine or methylene blue [62].
The somewhat greater expenditure of time and the large number
of available staining materials, as well as uncertainty about the
quantity and concentration of staining materials have prevented
chromoendoscopy from being established in the Western world.
However, the knowledge of the morphology of the diseases of the
upper and lower gastrointestinal tract has been enhanced very
markedly by the use of chromoendoscopy, and has sensitized
clinicians to the necessity of early detection, particularly that of
flat lesions [63]. Chromoendoscopy is currently experiencing a
renaissance because the combination of high-resolution endoscopy
and intravital staining provides an especially detailed view of the
surface structure of mucosa.
Owing to the previously described modern processor technology
of high-resolution endoscopy systems and the possibility to add color
by pressing a button and activating a color filter, virtual coloring is
currently receiving special attention in endoscopy. The procedure
of so-called virtual chromoendoscopy modulates, by the press of a
button and with no loss of time, the spectrum of visible light so that
the mucous membranes can be visualized in various “missing colors”
[60]. The effect of such color accents is that individual components of
the mucosa, such as the surface pattern or vascular structures of the
mucous membranes can be depicted more clearly [61]. The different
color spectrums are produced either by modulating the incoming
light with filters (NBI technique), or by software-based processing
(so-called post-processing) of the reflected light (FICE, i-scan
technique or SPIES) [61]. Thus, modern filter technology is replacing,
to an increasing extent, the more time-consuming procedure of
chromoendoscopy.
The filters i-scan (Pentax, Europe), SPIES (Karl Storz, Europe)
and FICE (Fujinon, Europe) are based on processor-integrated
software applications that alter the wavelength ranges of reflected
light and thus, in contrast to NBI technology, offer a number of filter
options [61]. In addition to depicting vessels, portions of tissue and
surface structures can be visualized in a selective and accentuated manner. I-scan technology is based on an integrated software tool
that enhances the surface with the aid of the function of “surface
enhancement” and, by additionally switching on specific color
filters, permits virtual chromoendoscopy to be performed. Initial
published studies have confirmed the efficacy of this procedure.
Thus, reflux lesions in the upper gastrointestinal tract (UGI) could be
diagnosed more accurately by the use of surface enhancement [64].
FICE (Fujinon Intelligent Color Enhancement System) and SPIES
(STORZ Professional Image Enhancement System) are other types of
computer-assisted virtual chromoendoscopy.
Auto fluorescence endoscopy is another advancement in
endoscopy, which is playing an increasingly significant role in
the early detection of gastro intestinal damage. The principle of
fluorescence diagnosis is based on the fact that light of a specific
wavelength (approximately 400-500 nm) is not merely absorbed
and reflected in tissue, but also causes fluorescence produced by
auto fluorophores or exogenously introduces fluorophores [65]. A
variety of pathological processes such as inflammation, ischemia, and
a dysplasia demonstrate different fluorescence behavior compared to
normal tissue. Therefore, this technology is also known as red flag
technology. However, a disadvantage of the method is the fact that
auto fluorescence is associated with a high rate of false positive
diagnoses. To enhance the specificity of this method, it is usually
combined with HD endoscopy and NBI for characterization of the
detected lesions; this is known as endoscopic trimodal imaging [66].
Molecular imaging gives rise to early detection of disease
condition of gastro intestinal track because it renders pathological
changes visible at the cellular level [67]. The optic form of molecular
imaging, which provides colored views of suspicious areas on the
endoscopy image, can already be used in vivo for various types of
tumors. By the use of molecular probes usually applied exogenously,
one can visualize specific surface molecules or metabolic processes
that occur selectively in the target tissue. Thus, by marking antibodies
to epitopes like the epidermal growth factor receptor (EGFR) or the
vascular endothelial growth factor (VEGF); this was achieved in
mouse models as well as in human tissue. The advantage of antibodies
is their highly specific binding to their target structure, which causes
marked contrast between (stained) diseased and (non-stained)
healthy tissue. Molecular imaging requires special endoscopes
that either permits the detection of lesions on the overview image
or microscopic characterization of molecular processes during
endoscopy. As a result, the use of molecular imaging for endoscopy
has not been established in large patient populations, but is very
likely to fundamentally influence future clinical algorithms and has
already brought about a significant advancement in clinical and
basic research by enhancing our comprehension of gastrointestinal
diseases.
The prevalence of antibiotic-resistant by H. Pylori strains, the
high cost of treatment, and the risk of relapse, have led to the need
for a new approach to the treatment of H. pylori-related diseases. Use
of NSAIDs-PC, NO-NSAIDs, H2S-NSAIDs formulations, maintenance of
gastric mucosal balance, development of nanobody and vaccination
are potential options for the treatment and prevention of peptic ulcer
disease. NO-NSAIDs represent a promising therapeutic alternative
to conventional COX1and COX-2 selective NSAIDs. NO-NSAIDs not
only reduced profile of GI side-effects but also ameliorated power
of desired effects. Large, randomized studies are needed to evaluate
definitively the clinical benefit of NO-NSAIDs in humans. Therefore,
all levels of research, including basic, clinical, and population level, need continued support to facilitate development and
implementation of these novel breakthroughs. In addition to the
fact that simultaneous histological investigation can be performed
along with endoscopy, some diseases can now be diagnosed reliably
for the first time, and physiological as well as pathophysiological processes can be observed. This development has caused molecular
imaging to gain center stage in endoscopy. Apart from the fact that
it has simplified better detection of suspicious lesions, oncological
therapy approaches can be planned and understood better. Although
gastrointestinal endoscopy has become much more complex now,
the optic details provided by the new technologies will contribute
significantly to improving the efficiency of the diagnosis and
treatment of gastrointestinal endoscopy.
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