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C. (P.)
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Editorial
Board
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1
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Contents
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2-5
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Reviews
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Perspective of
tinalized microorganisms in the development of safe probiotics
Bomko T.V., Martynov
AV, Nosalskaya T.M.
Introduction: The use of probiotics is a common method of influencing
the intestinal microbiota. But oral administration of live probiotic bacteria
has significant disadvantages. First, live probiotic bacteria in
gastrointestinal tract are exposed to acidic environment and gastric pepsin,
then the destructive effects of bile acids and pancreatic enzymes. As a result,
most microorganisms die, and the remaining ones are not always able to restore
their number. There are also difficulties with the integration of surviving
bacteria into the biofilms of the parietal microflora, which has protective
antagonistic properties against exogenous microorganisms. In the case of survival of a significant part of the introduced
microorganisms and their reproduction, one of the safety problems is the
possibility of penetration of live bacteria from the intestine into the tissues
and blood, with the occurrence of bacteremia, especially in patients with
impaired epithelial barrier function. Another
problem with the use of live probiotics is the possible transfer of antibiotic
resistance genes by probiotic strains in the human digestive tract by
horizontal gene transfer. In newborns,
probiotics can interfere with normal bowel colonization. Rationale: In recent years, there has been interest in heat-killed
probiotics, including through the use of tyndallization. But the viability of bacteria or the integrity of their
cell wall is not an important condition for the intestinal effects of
probiotics. There is a considerable amount of experimental in vitro and animal model studies that
show that after heat treatment, bacterial extracts and supernatant in most
cases retain their basic probiotic properties. Experimental evidence for the protective effect of various heat-killed
probiotic bacteria against intestinal pathogens is presented. Thus, killed
lactobacilli or their purified structures competed for adhesion sites at the
gastrointestinal level with E. coli-ETEC,
Campylobacter and H. pylori. In a model of salmonellosis
in mice, heat-killed lactobacilli, alone or in combination, reduced pathogen
invasion and inflammation. Oral administration of inactivated bifidobacteria to
mice also resulted in increased resistance to Salmonella infection. In
vitro heat-inactivated Bifidobacterium
BB12 prevented the formation of Streptococcus
mutans biofilms. Immunomodulatory
effects of heat-killed probiotics have been found in both innate and acquired
immunity. Effects such as induction of IL-12 secretion, stimulating
effect on macrophages, enhancement of IgA production, etc. are given. Heat-killed probiotic bacteria help support the integrity
of the intestinal barrier, which has been proven in a number of studies on
intestinal cell monolayers (Caco-2 / TC7, HT29-MTX, CacoGoblet), as well as in
studies in rats with acute alcoholic intestinal lesions. The effects of some active components of heat-killed bacteria are
considered. The main components of the cell wall of gram-positive bacteria are
peptidoglycans and lipoteichoic acids. They can be considered key components of
the immunomodulatory action of most probiotics. Lipoteichoic acids of L. plantarum on cultures of dendritic
cells of mice spleen showed the properties of an IL-12 inducer, had an
anti-inflammatory effect on the lines of epithelial cells of the pigs
intestine, inhibiting the induced field I:C production of IL-8. Peptidoglycan
from L. rhamnosus improved the innate
immune response in mice with weakened immunity after infection with S. pneumoniae. Peptidoglycans isolated
from different species of Lactobacillus
have the ability to inhibit the LPS-induced release of inflammatory cytokines
in mice RAW 264.7 macrophage-like cells. Polysaccharide-peptidoglycan complexes
from L. casei YIT9018 were active against L. monocytogenes and P. aeruginosa. A large amount of
research has been devoted to the effects of exopolysaccharides isolated from Bifidobacterium and Lactobacillus strains in in
vitro and in vivo experiments.
Heat-killed Bifidobacterium longum
BCRC 14634 or exopolysaccharides isolated from them increased the proliferation
of J77A.1 macrophages and the secretion of the anti-inflammatory cytokine
IL-10. Exopolysaccharides coagulate with pathogens, which reduces the
availability of the latter to the intestinal epithelium, forming the films that
protect intestinal cells from damage by pathogens or their toxins. In animal
studies, probiotics strains that produce exopolysaccharides reduced intestinal
colonization by pathogens compared to non-producing strains. Cell-free supernatants of probiotic bacteria contain a wide range of
compounds with antimicrobial properties, including organic acids, hydrogen
peroxide, reuterin and bacteriocins. They are also
present in heat-inactivated probiotic products because they can withstand
temperatures up to 100 ° C. A number of clinical data, including high-quality studies, on the efficacy
of heat-killed probiotics are presented. 20-day use of tyndallized L. reuteri and B. breve
with the polymer xyloglucan reduced the severity of the syndrome of excessive
bacterial growth in the small intestine in adults diagnosed with functional
bloating (double-blind randomized study). Tyndallized L. reuteri SGL01 and B. breve
SGB01 reduced the duration of colic (crying attacks) in 46 infants. In a
randomized controlled trial, tyndallized L.
acidophilus HA122 with chamomile and melissa extracts
significantly reduced the mean daily infant crying time compared to
simethicone. Heat-killed L. acidophilus LB
significantly reduced clinical symptoms in patients with chronic diarrhea, and
the effect was superior to that of live lactobacilli. In a placebo-controlled study in children with acute
diarrhea caused by rotavirus, lyophilized, heat-killed L. acidophilus LB significantly reduced the number of children with
loose stools and significantly reduced the duration of diarrhea. In a randomized, double-blind, placebo-controlled clinical trial in
children with persistent non-rotavirus diarrhea, the use of lyophilized,
heat-killed bacteria L. acidophilus
LB reduced the recovery time of normal stool. In a multicenter, randomized, double-blind, controlled study, the use of
formula containing heat-killed B. breve
C50 and S. thermophilus 065 in
children at high risk of atopy reduced the incidence of digestive and
respiratory allergic events. Recently, products
containing various tyndallized probiotics strains have appeared on the market.
These are L. reuteri, B. breve and xyloglucan for the
treatment of colic in adults and children, L.
acidophilus HA122 with extracts of chamomile and lemon balm for the
treatment of colic in children, a complex of tyndalized lacto- and
bifidobacteria with gelatinate tanat for the treatment of intestinal
dysbacteriosis associated with diarrhea. Conclusion. Heat-killed probiotics are no less effective than live
bacteria and have benefits such as greater safety, ease of standardization,
transportation, and storage. They are an alternative to live probiotics and
open up the possibility of using them to treat various diseases and conditions.
Keywords: stress-factors, probiotics, metabiotics, heat-killed
probiotics, review
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6-14
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Ivermectin - molecular
mechanisms of antivirus and antiparasitic effects
Nosalska T.N., Martynov A.V., Bomuko
T.V.
Specific highly affinity recognition of imports is crucial for the viral
proteins nuclear localization. One of the drugs that affects the viral nuclear
localization signal is ivermectin. It is shown that the addition of 5 mcM
ivermectin to Vero-hSLAM cells 2 hours after SARS-COV-2 infection
led to a decrease in the viral RNA load by 99.98% after 48 hours. Ivermectin
for treatment SARS-COV-2 people have already approved in a number of states and
countries, including Peru and the Northeastern region of Beni in Bolivia. It is
important to note that about 70 tests around the world are currently checking
the clinical efficacy of ivermectin for the treatment or prevention of
SARS-COV-2; They include variations in dosing modes, combined therapy and
prophylactic protocols. Scientists suggested that this drug can reduce viral
load in infected patients with potential influence on the progression and
dissemination of the disease. Possible directions for the further study of the
recruitment of Ivermectin for the treatment of SARS-COV-2 may be in the
development of an inhalation preparation for the effective delivery of high
local concentration into the lungs with minimal systemic exposure and
estimating the synergistic effects of ivermectin with other connections that
also inhibit SARS-COV-2 replication.
Keywords: ivermectin, SARS-COV-2, nuclear signal localization
inhibitor, cells culture, pilot clinical trials
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15-24
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Experimental
works
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Formulation and evaluation of the nanosilver gel using bioreductor
ethanol extract of Katuk leaf (Sauropus
androgynus (l) Merr) as antibacterial
Nurfadilah, Yunahara Farida,
Faizatun
Introduction:
The current type of nanoparticle that attracts a lot
of attention in the pharmaceutical field is Nanosilver. Nanosilver can be acted
as an antimicrobial. The aim of this study is to obtain the Nanosilver gel
preparation from katuk leaf extract, which is effective as an antibacterial
agent against acne. Materials and Methods:
Katuk leaf extract remains as a reducing agent in the
synthesis of Nanosilver using a green synthesis method. Nanosilver
characterization was performed using PSA, FTIR and TEM. Results
and Discussions: Particle size of
Nanosilver (Katuk leaf extract concentration 0.16% with a silver nitrate volume
of 10 mM is 1: 9) of 164.40 nm, Nanosilver (Katuk leaf extract Concentration
0.32% with silver nitrate volume 10 mM is 1: 9) of 176.47 nm and Nanosilver
(0.48% katuk leaf extract concentration with a volume of 10 mm silver nitrate
of 1: 9) of 194.95 nm. Antibacterial activity using the Well method was shown
that the nanosilver gel from Katuk leaf extract had an inhibitory effect on P. acnes bacteria with an inhibition
zone of 26 mm classified as very strong,
and 12 mm was strongly categorized against S.
aureus bacteria, namely in Formula 1. Conclusion:
A variation in the concentration of katuk leaf extract
influences the size of the particles formed. The Nanosilver of katuk leaf extract has an antibacterial cause for acne
with a very strong category.
Keywords: Acne; Nanosilver gel;
Antibacterial; Katuk leaf.
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25-31
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Comparative
analysis of the antibiotic sensitivity level of Escherichia coli strains of
different isolation periods
Peretyatko O. G., Yagnyuk
Yu. A., Sklyar N. I., Bolshakova G. M., Kholodna T. V.
Introduction. The problem of the
spreading of the microorganisms resistance to antimicrobial drugs is so acute
nowadays, that the XXI century can rightly be called the "era of
antibiotic resistance". In our opinion, to study the mechanisms of
antibiotic resistance in the population of microorganisms, it is important to
analyze the antibiotic sensitivity of microorganisms isolated during different
periods of antibiotics use in clinical practice. The aim of the study was to compare antibiotic sensitivity
profiles of E. coli strains isolated in the preantibiotic,
metaantibiotic and modern periods. Material
& methods. Objects of
the study: 41 E. coli museum strains from the collection of the Museum
of microorganisms stored in a lyophilized state for 44-73 years, and 55 circulating
E. coli strains. Determination of the sensitivity of microbial cultures
to antibiotics was performed using disco-diffusion method, serial broth
dilution method and serial agar dilution method. Statistical data processing
was performed using computer programs Microsoft Excel 2007, STATISTICA 6.0. Results & discussion. A comparative analysis of the
results of the study of antibiotic sensitivity of E. coli of different
isolation periods demonstrated significant decrease in activity of the
antibiotics of aminopenicillin group (ampicillin, ampicillin-sulbactam),
generation I-III cephalosporins, tetracycline, chloramphenicol against modern
clinical E. coli strains. In contrast to the museum strains, the
circulating population of E. coli showed resistance to carboxy- and
ureidopenicillins, generation IV cephalosporins, carbapenems, aminoglycosides,
doxycycline, fluoroquinolones, and cotrimoxazole. The vast majority (70,0%) of
the antibiotic-resistant museum strains showed resistance to 1–3 antibiotics
groups, while 52,2% of the modern strains showed resistance to antibiotics of
the 4–7 chemical groups. Conclusion. Comparative
analysis of the antibiotic sensitivity profiles of E. coli isolated
during different historical periods showed an increase in the proportion of
resistant strains among circulating E. coli and an expansion of the
range of antibiotics groups for which resistance was identified.
Key words: E. coli strains isolated
during different historical periods, antibiotics, antibiotic
sensitivity.
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32-35
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Carbapenem Resistance of
OXA-48 Gene Coding in Klebsiella Pneumoniae and Escherichia Coli
Nita Parisa, Muhammad
Fitrizal, Ella Amalia
Introduction: Bacteria that treated with antibiotics has ability to adapt or mutate
due to form a defend mechanism. OXA-48 produces isolate that have ability as a
resistance to drugs and all β-lactam, including
cephalosporin, cephamycin, monobactone,
and carbapenem. This study aims to
identify the availability of OXA-48 gene as Carbapenem
resistance in Klebsiella pneumonia
(K.pneumoniae) and Escherichia coli
(E.coli) from patient in Dr. Mohammad Hosein Hospital in Palembang,
Indonesia. Method: The isolate
bacteria from patients in Dr. Mohammad Hosein Hospital who infected with K.pneumoniae and E.coli in September
until November 2017 were identified using Vitek 2 Compact. Polymerase Chain
Reaction (PCR) used to detect the presence of bla OXA-48 to compare the pattern
of antibiotic resistance. Result:
The result showed that from 24 samples, there was 1 sample (4.7%) who positive
with OXA-48 gene from K.pneumoniae bacteria
and no positive gene found in E.coli bacteria.
While the rest of the samples (95.3%) had negative OXA-48 gene. Conclusion: Therefore, the OXA-48 gene
was only identified in K.pneumoniae.
Keywords: Klebsiella
pneumonia, Escherichia coli, OXA-48, Carbapenem resistance, PCR.
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36-40
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Formulation and activity test of extract seaweed lip balm ( Sargassum
binderi ) and kenanga oil ( Cananga oil ) as lip moisturizer
Apriyani P, Yunahara Farida,
Faizatun
Introduction: This research is
about formulation and activity test of seaweed extract (Sargassum binderi) and
sunflower oil kenaga (Cananga oil) as lip moisturizer. The purpose of this
study was to utilize natural ingredients and determine the evaluation of
lipbalm from seaweed and cananga flower oil which has a function to increase
the moisture level of lip. Methods:
The formulation of lipbalm was made by three concentrations, formulation 1,
formulation 2 and formulation 3. Evaluation was done to test the skin
irritation, skin hydration and hedonic test. The method of skin hydration helps
to enhancer and moisture the skin by TEWL (transepodermal water loss) tool of
derma lab combo. Results: The result
of this research showed that all the formulas does not irritate the skin,
moisturize and preferred by the panelists. In the third formula, it has a
result to increase the humidity of skin within the high significant differences
among the three formulas. Conclusion:
Therefore, the lip balm formulation increase humidity of skin within the high significant differences among
the three formulas.
Keywords: Seaweed; Ylang flower
oil; Lipbalm formula; Moisture.
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41-44
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Protective
properties of designed samples of a Pseudomonas aeruginosa vaccine
(experimental studies)
Dercach
S.A., Martynov AV, Gorodnitskaya N.I., Katsay N.M., Gabysheva L.S.
Introduction. One of the main pathogens of purulent and
inflammatory diseases, including multi-different serum groups specificity,
remains a P. aeruginosa. The pathogen has a wide serogroup landscape,
has polyresistance to antibiotics, high resistance to disinfectants, aseptives,
external factors. Clear progress in the treatment of this infection is not
observed. In a very actual problem of antibiotic resistance, an urgent
necessity is the creation of vaccine preparations for the prevention and
treatment of pseudomonosis. The search for new approaches to the creation of
immune drugs continues in different countries of the world. In Ukraine, vaccine
preparations for the prevention and treatment of pseudomonosis infection are
absent, so their development and domestic production is promising, relevant and
socially grounded. One of the modern directions of research of scientists from
different countries is the use of bacteria decontamination technologies and obtaining immunogens from its by
inactivating the original microbial producer with a photodynamic method. We
have developed and a patented method for obtaining a synogogeneous vaccine by
using bacteriophages adapted to specific freshly used P. aeruginosa strains,
use as photosensitizers - vikasol and riboflavin followed by irradiation by
light. Materials and methods. For the production of vaccine samples,
cultures of freshly branched from various biotopes of patients with purulent
inflammatory diseases of P. aeruginosa strains, specific adapted
bacteriophages, 0.1% solution of riboflavin and 1.0% vikasol. The irradiation
was carried out using a photopolymer lamp "Luxior" and ultraviolet
bactericidal lamp in laminar box. The protective properties of vaccine drugs
were studied in an experiment on non-inbred mice by determining animal survival
rates after control infection with homologous and heterogeneous P.
aeruginosa strains. The protective activity of vaccine samples was
evaluated in comparison with the control (non-vaccinated) group of infected
animals. Statistical methods determined the reliability of the difference in
indicators (X2). Results and discussions. In laboratory conditions, 3
series of monovaccines and 2 series of multistrain vaccines (out of 5 strains
were obtained P. aeruginosa). The comparative study results of the
vaccine monopeparates series received from strains with different baseline
characteristics have shown that all of them provided approximately the same
protective effect of infection with homologous strains. The high efficiency of
vaccination of experimental mice is shown, as a result of which the mortality
in the infestation by auto-strain due to different periods after immunization, starting
from 3 days, was insignificant (10%) and compared with non-vaccinated -
reliably less (P <0.01). Number of animals surviving after infection with
heterogeneous strains P. aeruginosa in all experiments was also
significantly smaller than in the control (non-vaccinated) group (P <0.05).
Taking into account the wide serogroup landscape P. aeruginosa, the main
task was to develop a method for obtaining a phagolysate multistrains
pseudomonosis vaccine based on the application of the method of photodynamic
inactivation of P. aeruginosa candidate strains and determined
experimentally with its protective properties. Infection of experimental
animals was carried out as strains involved in obtaining a multi-strains
vaccine and other heterogeneous strains. In all cases there is a significant
difference in comparing survival rates in vaccinated and non-vaccinated animals
(p <0.01). The multistrain vaccine protected immunized mice from infection
both by autostrain and from heterogeneous strains P. aeruginosa, which
were not included in the vaccine. Conclusion. The resulting phagolisis
multistrain vaccine has protective properties as relative to homologous and
heterogeneous P. aeruginosa strains, was non-toxic and non-reactive. The
survival rate of vaccinated mice in infection with a homologous strain has
28.9%, heterogeneous - 78.6%. It is important to emphasize that the strain
composition of the developed immunufacturer may vary, supplemented with new,
relevant for a particular region or, even, clinical department, etc.
Keywords: pseudomonas infection,
photodynamic inactivation of bacteria, vaccine, protective properties of the
vaccine.
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45-49
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Features of microbiocenosis of female genital organs and immune factors
in patients with adenomiosis
Scherbina N.A., Chekhunova A.O.
Endometriosis
is one of the most enigmatic gynecological diseases. An analysis of modern concepts of etiology and
mechanisms of endometriosis development, published in PubMed, UpToDate,
eLibrary databases over the past 10 years, indicates the theory of bacterial
contamination as one of the factors of endometriosis. The purpose of the study. To study the state of microbiocinosis of women's genital organs and immune
factors in patients with adenomiosis. Materials and
methods. A survey of 65
women of reproductive age was conducted. Based on the clinical course of the
disease, the data of genital status are formed by 2 groups: I group amounted to
35 (53.8%) patients with adenomiosis and degree of distribution. Group II
(control) amounted to 30 (46.2%) gynecologically healthy women. In order to assess the content of microorganisms in the secrets of the
genital organs of women, the material was taken from the cervical channel and
the posterior vault of the vagina and subjected to a bacteriological study. In
the detection of infections of the urogenital sphere, a polymerase chain
reaction (PCR) and ELISA was used. Research results. By studying the microscopic characteristic of the vaginal biocenosis in
women with adenomiosis prevailing the ²²-²²² degree of purity of the vagina
with the “intermediate” type of biocenosis
(43.3%), which is characterized by a reduced content of lactobacillus, the
presence of various types of morphotypes of gram-positive and gram-negative rods and cocci and “dysbiosis” (50.0%) when mixed
bacterial microflora prevails. Microbiological researches of vaginal allocation
showed the presence of dysbiosis in all examined women, which was manifested by
a significant decrease in the number of lactobacillus or their absence and
increasing the content of conditionally pathogenic microbes. In 17 (48.6%)
patients, Staphylococcus aureus was isolated at a concentration of 102
‒ 103 cfu/ml, ó 12 (34,3%) ‒ enterococcus: Enterococcus faecalis ó 7
(20,0%) in an amount of 102 cfu/ml; Enterococcus faecium in 2 (5,7%) in an
amount of 103 cfu/ml; Enterococcus
sp in 3 (8,5%) in an amount of 103 cfu/ml; in 9 (25,7%) withdrawn Escherichia coli 103 cfu/ml, in 2 (5,7%) patients ‒ Klebsiella
spp 102 cfu/ml, in 4 (11,4%) Proteus spp in the amount of 102 cfu/ml; in 16 (45,7%) ‒ Mobiluncus in the amount
of 103 – 104 cfu/ml; in 5 (14,3%) Peptococcus sp. in the amount of 103 cfu/ml; in 13 (37,1%) patients were isolated Candida
albicans, 104 ‒ 105
cfu/ml, in 15 (42,8%) ‒ Gardnerella vaginalis (CFUs were not
determined, fixed the presence of "key cells" and a change in the pH
of discharge). In 9 (25,7%) patients were isolated asporogenic anaerobic bacteria: Bacteroides spp ‒ 6 (17,1%). The PCR diagnosis of the material of the cervical channel revealed: Cytomegalovirus in 4 (11,4%) patients of ² group , Virus herpes simplex in 5 (14,3%), Virus papilloma hominis ‒ 5 (14,3%). In women of the control group, the positive definition of Cytomegalovirus
and Virus Herpes Simplex amounted to 3.3% of observations. The conducted studies
have shown mixed infection in all patients of I
group. The obtained data indicate that adenomiosis proceeds against the
background of disturbed microbiocenosis of genitalia. Detected microbial
associations are able to lead to changes in physico-chemical properties and pH
of the secretions of the urogenital sphere, followed by possible penetration
into the cavity of the uterus. In peripheral blood, patients with adenomiosis showed a
reduced level LL-37 ‒ 21,4±1,3 pg/ml (in the control group
LL-37 ‒ 23,4±2,5 pg/ml respectively). With grade I
adenomyosis, a typical inflammatory reaction occurs with a decrease in the
level of antimicrobial peptides in the vaginal and cervical secretions, which
indicates their possible role in the pathogenesis of the disease.
Key words: adenomyosis, vaginal microbiocenosis, antimicrobial
peptides.
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50-55
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Case Report
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Successful Management of Isolated Optic Neuritis in Acute Diseminated
Encephalomyelitis: A Case Report
Arantrinita, Lukisiari Agustini
Background: Optic neuritis is an inflammatory disease that results in demyelination
of the optic nerve. Isolated Optic Neuritis in Acute Disseminated
Encephalomyelitis is a rare case, this disease attacks the central nervous
system. It is monophasic, and make various clinical manifestations. Early
diagnosis of Isolated Optic Neuritis due to Acute Disseminated
Encephalomyelitis is based on clinical manifestations accompanied by laboratory
and radiological investigations. In Acute Disseminated Encephalomyelitis
patient, radiological examination can shows normal result in the acute stage.
This is a challenge in establishing the diagnosis of the disease. Materials and Methods: This is a case
study in post-vaccine patient. Seven-year-old girl with complaints and typical
clinical manifestations includes high fever, sudden decrease in vision
accompanied by pain in the movement of the eyeball. Optic nerve papillary
examination shows hyperemic color with firm borders, according to the results
of optical coherence tomography examination. Laboratory examination showed an
increase in white blood cell count and C-reactive protein value, and multiple
hyperintense lesions in the subcortical temporo-parietal characteristic of
Acute Disseminated Encephalomyelitis on Magnetic Resonance Imaging. Results&Discussion : Management
guided by the Optic Neuritis Treatment Trial protocol accompanied by close
observation showed significant clinical improvement. Conclusion: Optic neuritis in Acute Disseminated Encephalomyelitis
is an acute and monophasic disease. The most common cause is inflammatory
reaction to viral and molecular mimicry reactions of the vaccine component.
Early diagnosis and proper management give good results and can prevent
recurrence.
Keywords: Isolated Bilateral Optic
Neuritis, Acute Disseminated Encephalomyelitis, central nervous system, vaccine.
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56-58
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