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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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PROPHYLAXIS OF INFLUENZA IN THE ELDERY. IS THERE ANY ALTERNATIVE?
Grishyna O. I., Babinets O. M., Menkus O. V., Kalchenko G. R.
The benefits of influenza vaccination in the elderly individuals are the
subject of serious discussion. Evidence-based medicine can not boast of a large
number of randomized clinical trials of the anti-influenza vaccine
effectiveness in the elderly due to ethical issues. Over the past 20 years, the
only large randomized clinical trial was to investigate an inactivated
anti-influenza vaccine in adults aged ≥60 years, which was performed during one
season and limited to healthy subjects. This trial demonstrated a 58% reduction
in the risk of serologically verified uncomplicated influenza infection in the
patients aged 60-69, but no conclusive findings were made for the individuals
aged ≥70 years, because the capacity of this study was insufficient to
investigate the vaccination efficiency in this age group. Moreover, an evidence
of efficacy in healthy subjects aged 60-69 can not be related to the elderly at
the age of 70, since elderly age and concomitant diseases are associated with
an increased risk of complications and the immune system weakening. With
respect to the lack of an evidence, based on randomized clinical trials, we use
the results of observational, usually retrospective cohort trials that may be
biased. We analyzed the results of randomized multicenter vaccine trials
including Fluzone High-Dose Vaccine, meta-analysis data, and concluded that evidence
for protection in adults aged 65 years or older is lacking. As an alternative,
the results of clinical trials and a meta-analysis of the effectiveness of
vitamin D3 for the prevention of influenza / influenza-like illnesses are
considered. The extraskeletal effects of vitamin D are analyzed. The interest
in vitamin D extraskeletal effects has rapidly grown over the last thirty years
due to the identification of Vitamin D receptors (VDRs) in different systems,
organs, and cell types. The effects of 1.25 (OH) 2D3 on regulation of both
inherent and adaptive immune systems are string and their evaluation has been
just started. VDR was detected in activated CD4+ and CD8 + T cells, B cells,
neutrophils, monocytes, macrophages, and dendritic cells. The results of the
meta-analysis twenty five randomized controlled trials (11,321 participants
aged from 0 to 95 years) published by Adrian R. Martineau et
al. were presented. The meta-analysis has found that adding vitamin D
reduced the risk of acute respiratory infections among all the participants
(0.88 corrected odds ratio, 95% 0.81-0.96 confidence interval, P for
heterogeneity <0.001). Vitamin D did not affect a part of participants who
experience at least one serious adverse event (corrected odds ratio of 0.98,
0.80-1.20, P=0.83). It was finally concluded that the vitamin D supplement was
safe and generally protected against acute respiratory infections. A conclusion was drawn on the need for a
large clinical trial comparing the efficacy and safety of a flu vaccine and
vitamin D3.
Key words: influenza, flu-related illness, flu vaccine, elderly, vitamin D3, extraskeletal effects.
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6-12
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VITAMIN D3: RESEARCH BREAKTHROUGHS
AND THERAPEUTIC USE
Pohorila Ì.S., Martynov A.V.,
Romanova E.À., ²gumnova N.²., Sidorenko Ò.À., Yukhimenko V.²., Shcherbak O.M.
Vitamin D3 (cholecalciferol),
the natural form of vitamin D, is produced in the skin from
7-dehydrocholesterol. The synthesis of vitamin D in the skin is the most
important source of vitamin D. Vitamin D can also be taken through nutrition,
in the diet, but it is present in only a few food sources, containing relevant
levels of vitamin D. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
is the hormonally active form of vitamin D.
Novel researches show it generates a number of extraskeletal biological
responses including inhibition of variety types cancer progression, effects on
cardiovascular disorders and mediates a protection against a number of
inflammatory, autoimmune and infection diseases The biological actions of 1,25(OH)2D3 are
mediated by the VDR. The genomic mechanism of 1,25(OH)2D3 action
involves the direct binding of 1,25(OH)2D3 activated
VDR/RXR to specific DNA sequences in and
around target genes resulting in either activation or repression of
transcription [7] VDR modulates the expression of genes involved in immune
function and cytokine production. The VDR and
CYP27B1, the enzyme located in kidneys and
target organs, are present in immune competent cells, bronchial and
pulmonary epithelial cells, among others, and is up-regulated following the
ligation of specific toll-like receptors by extracellular pathogens,
implicating vitamin D in innate immunity. By binding the VDR, calcitriol induces several
endogenous antimicrobial peptides (AMP) in monocytes, neutrophils and
epithelial cells including cathelicidin LL-37, α-defensin, β defensing and
neutrophil gelatinase-associated lipocalin and up-regulates nitric oxide (NO)
synthase. Since the inflammatory response associated with
infections such influenza, pneumonia and sepsis increases both clinical
severity and mortality, the ability to reduce inflammation may allow vitamin D
to decrease mortality and disease burden in certain infections. Notwithstanding the width of possible
vitamin D application field, which being known now, large-scale clinical trials
are still demanded. Our review has the aim to summarize current scientific
understanding of Vitamin D3 effects on the immunological field with
the focus on its capacity to enhance the anti-infection and anti-inflammatory
immune reactivity. Vitamin D and Tuberculosis. Vitamin D has been widely studied in the
prevention and treatment of tuberculosis. Current studies were
focused on how calcitriol enhances the antimicrobial effects of macrophages and
monocytes – important effector cells, fighting against pathogens such as Mycobacterium tuberculosis (MBT). Several studies tracked the impact of vitamin D on
cytokines that promote anti-MTB activity and the resolution of infection.
Suppression of antigen-stimulated pro-inflammatory cytokines, attenuation of
anti-inflammatory cytokines, and a more rapid treatment-induced resolution of
lymphopenia and monocytosis associated with TB infection occurred following
100,000 IU doses of vitamin D3 given monthly for 4 months.
Conversion of sputum smear or sputum culture was used to measure response to
treatment in several studies, though only sputum culture conversion is
independently linked to long-term risk of treatment failure and relapse. Also
it was found that 10,000 IU of vitamin D3 given
daily for 6 weeks to significantly increase sputum smear conversion (100 % in
the treatment group vs. 76,7 % in the placebo group, p=0,002). IFN-γ levels were impacted variably: 2 doses of vitamin D3 (600,000 IU))
led to increasing of IFN-γ expression , while a single 100,000 IU dose of
vitamin D2 showed no change . Negative results in some studies could be
explained by variability of the Taq1 vitamin D receptor genotype polymorphism.
It was shown that significantly accelerated conversion is appropriate of
patients who have a tt genotype
compared to those with the Tt or TT genotype. But these results were not confirmed by another study,
where were founded no interaction between VDR genotype effectiveness of vitamin
D. Several trials show vitamin D
given largely as an adjunctive therapy with traditional anti-tuberculosis
regimens in a variety of dose and dosing schedule has some impact on clearance
of MBT from sputum in the wide number randomized controlled multicenter trials
of patients with active tuberculosis infection. Patients with infection of MBT with different strains of tuberculosis can take
benefits from Vitamin D3 consumption due to its effect on the
clearance of MTB from sputum and on dampening the inflammatory response or
anthropometric changes that may help tuberculosis patients recover. A
significant microbiologic effect of vitamin D3 was indicated in
several trials that, also, sustained by in vitro tests, where its
antimycobacterial effects in cultured macrophages was shown. Antimycobacterial
effect is provided enhances the expression of the anti-microbial peptide human
cathelicidin (hCAP18) in cultured macrophages. The clinical benefit after high
vitamin D3 doses administrating to patients does not depend of their
vitamin D3 marked deficiency. The cause of this variation remains
unexplained. The role of genetic polymorphisms in the vitamin D receptor, or in
the multiple enzymes involved in its metabolism in vitD3
effectiveness remains unproved. Measurement of calcitriol-induced
antimycobacterial activity in ex vivo whole blood culture in future studies may
help in understanding the functional effects of specific genetic polymorphisms.
So, big attention will be required in future studies to determine mechanism of
vitamin effect on patients with tuberculosis.
Keywords: Vitamin D3,
cholecalciferol, VDR, infection, pulmonary disease, tuberculosis, innate
immunity, adoptive immunity, antimicrobial effect
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13-20
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Experimental papers
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DISEASE-ASSOCIATED HLA-DR POLYMORPHISM, CLINICAL AND IMMUNOLOGICAL
CHARACTERISTICS OF MULTIPLE SCLEROSIS PATIENTS
IN THE NORTHEASTERN REGION OF UKRAINE
Kolyada T. ²., Negreba T. V., Tupotilov O. V., Bilozorov O. P., Zelenska
A. D., Kolyada O. M.,
Shvydka O. V., Belyavtseva O. I.
The development of multiple sclerosis is the result of complex
interactions between environmental factors, genetic factors that determine
individual disease susceptibility, and immunological and physiological
characteristics of the patient. multiple sclerosis treatment requires obtaining
information about the main pathological processes, therefore, the evaluation of
biochemical, immunological, and genetic markers of such processes, and not just
clinical indicators, can become the basis of improved approaches for diagnosis
and monitoring of the disease. Polymorphism of the disease-associated genes is
considered as one of the key factors in multiple sclerosis pathogenesis,
capable of influencing the risk of development, clinical manifestations and
nature of the course of the disease, treatment response. The HLA genes
polymorphism was found to be the most important and playing an essential role
in the development of autoimmune diseases. There are data on the population
characteristics of these types of polymorphisms, which require conducting
relevant research in Ukraine and its regions to identify relevant genetic
markers. The aim of the study was to
provide a comparative clinical and immunological characteristic of multiple
sclerosis patients in the northeastern region of Ukraine, depending on the
presence of the disease-associated HLA-DR polymorphism. Materials and methods. 39 patients with multiple sclerosis, inhabitants of Kharkiv and Kharkiv region, were examined, of which 7 men and 32
women of medium age of 33.7 ± 7.7 and 42.1 ± 11.9 years, respectively; control
group was consisted of 27 practically healthy persons of both sexes with an
average age of 30.1 ± 8.2 years. Clinical characteristics of multiple sclerosis patients included the
determining the form and the actual type of the disease, its duration, and
disability assessment based on the EDSS scale. The rate of the disease progression
was determined as the ratio of the EDSS score to the duration of the disease. Biological material was blood and buccal epithelium
samples from multiple sclerosis
patients and practically healthy people. In addition to assessing the clinical
status of the patients, design of the study also included evaluation of the
systemic immunity indicators, levels of nonspecific and antinuclear antibodies
in the serum, and analysis of HLA polymorphism, in particular, detection of the
HLA-DR15 haplotype for its specific marker SNP rs9271366. Isolation of high
molecular DNA was performed on a magnetically sensitive sorbent using the
NeoPrep100 DNA Magnet kit (NeoGene, Ukraine). SNP polymorphism rs9271366 A/G
was typed by the allele-specific amplification method with subsequent electrophoretic
detection of the results. Primer selection was performed using the method by
Liu Jing et al.
(2012) adding a mismatch in the third position at the 3’ends. The primers MS92ÀF
5`-CACGTAATATAA- ATGGTTGCAAAGGA-3`, MS92GF 5`-CACGTAATATAAA TGGTTGCA-AAGGG-3` and MS92R5`
AACCCTGATGTAACAGA(C/T)CTCTA-3` (Eurofins Genomics),
as well as Taq-mut polymerase (Liteh, Russian Federation), were used in the
study. The amplification was performed on the multichannel amplifier Tercyc
(Russian Federation). Amplification mode: denaturation at 96°C for 3 minutes
and 35 cycles that included denaturation at 95°C for 30 seconds, annealing at
58°C for 30 seconds, and synthesis at 72°C for 30 seconds. The length of the
amplicon was 233 bp. Electrophoresis was performed in 2% agarose gel in TAE
buffer. Electrophoregram analysis was carried out on transilluminator UVT 1
(Biocom, Russian Federation). Serum IgM, IgG, IgA levels were evaluated by
ELISA using a test system by NPL Granum (Ukraine) and the immunoassay analyzer
Stat-Fax 303 (USA). The determination of peripheral blood lymphocytes
subpopulations was carried out using the test systems by NPL Granum, Ukraine in
accordance with the manufacturer's instructions. Circulating immune complexes
in serum were evaluated by selective precipitation of antigen complexes with
3.5% PEG-6000 solution (AppliChem GmbH, Germany). The content of
lymphocytotoxic autoantibodies was determined by a lymphocytotoxic macrotest.
The complementary activity of the blood serum was evaluated by means of 50% of
sheep erythrocytes hemolysis in the presence of homologous antibodies. The statistical treatment was performed using
STATISTICA 11.0 (StatSoft, Inc). To determine the reliability of the
differences between the indexes in the studied samples, the non-parametric
Mann-Whitney's criterion was used, while the Student's T-criterion was used for
the normal distribution. Results. At the stage of clinical examination of multiple sclerosis patients, 25
patients (64.1%) were diagnosed with RRMS, 4 patients (10.3%) with PPMS, and another 10 persons (25,6%) with SPMS. The familial
form of the disease was established in 11 cases (28.2%), in 28 cases (71.8%)
the form of the disease was classified as sporadic. The average disease
duration of the examined persons was 10.16 ± 9.57 years. The disability score
assessed according to the EDSS scale was 3.54 ± 1.67 points; the rate of
progression of the disease was 0.93 ± 1.26 and 0.83 ± 0.85 points,
respectively. Analysis of the HLA polymorphism indicated that the disease-associated (minor)
allele G SNP rs9271366 was present in 43.6% of the subjects examined (haplotype
AG, G+ group), and another 56.4% of the patients were homozygous by the major
allele A (haplotype AA, G- group). The form of
the disease, the EDSS score, and the rate of the disease progression in the
examined patients did not have association with the allele G SNP rs9271366.
Patients with familial and sporadic forms of multiple sclerosis did not have
significant differences in immune status and clinical indicators. The average
EDSS score was 3.45 ± 1.95 points in G+ patients and 3.65 ± 1.26 points in G-
patients and the rate of disease progression was 0.83 ± 0.85 points and 0.93 ±
1.26 points, respectively. The study of cellular immunity indicators revealed a
decrease in relative number of CD4+ and CD8+ lymphocytes in multiple sclerosis
patients compared to that in control group, and it was more pronounced in
subjects with the presence of the SNP rs9271366 minor allele. The relative
content of CD4 + cells was 28.00 ± 3.45% in heterozygous patients, 30.94 ±
4.42% in patients homozygous for allele A, in the control group 42.3 ± 1.8%
(p<0.05), and the CD8+ cells content was 18,55 ± 4.08%, 20.65 ± 3.52% and
29.4 ± 2.2%, respectively (p<0.05). At the same time, the reduction in the
relative number of CD4+ lymphocytes was observed in 90.9% of G+ patients, and
in 64.7% cases in G- patients (p<0.05). Decreased CD8+ lymphocyte content
was also more common in patients with G+ (77.3% of cases) than in G- (41.2% of
cases), p<0.05. Acute inflammatory process was determined in 38.5% of
patients with multiple sclerosis, as evidenced by an elevated IgM level in
20.5% of cases, as well as an increase in complement activity in 62.5% of
subjects. The levels of lymphocytotoxic
autoantibodies in patients with multiple sclerosis were
significantly higher compared to the control group (18.33 ± 3.67% of subjects
and 5.82 ± 3.12% of subjects, respectively, p<0.05), and the levels of
circulating immune complexes were elevated in 10.3% of patients. The study of the levels of
antinuclear antibodies in multiple sclerosis patients revealed a diagnostically
significant levels of antibodies to native DNA found in 92.3% of the cases,
including all G + patients and 83.3% of G- patients. In this case, 16.7% of
patients homozygous for allele A and 14.3% heterozygous patients were also
positive for the presence of antibodies to denatured DNA. Similar results were
also obtained concerning the presence of antibodies to formalinized DNA - 16.7%
positive results in G- patients and 28.6% in G+ patients (p<0.05). At
the same time, elevated levels of antibodies to native, denatured, and
formalinized DNA were determined predominantly in patients with SPMS and PPMS
(15.4% of the number of examined patients). The elevated levels of antinuclear
antibodies may indicate an unfavorable course of the disease or its transition
to the active phase. Conclusion. In the surveyed multiple sclerosis patients from the northeastern region of Ukraine, the prevalence
of SNP rs9271366 and its association with a decrease in the relative number of
CD4+ and CD8+ cells against the background of elevated levels of antinuclear
and lymphocytotoxic antibodies were detected. Keywords: multiple
sclerosis, disease-associated polymorphism of genes, immunopathogenesis.
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21-25
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THE ANALYSIS OF THE THREAT OF REUSING PET BOTTLES FOR THE STORAGE OF
DRINKING WATER
Manuilov A.M., Martynov A.V.
Introduction. According to a sociological survey of about 86% of Kharkiv (Ukraine)
residents reuse PET bottles for a drinking water storing. This type of reuse of
PET bottles isn't safe and the results of numerous research unequivocally
confirm this assertion. The largest hazard of plastic bottles reuse for
drinking water storage is biological film on the internally surface of bottle.
This biofilm may contain pathogenic microorganisms which can migrate from
biofilm to fresh water. Human, who drinking contaminated water, may drink
microorganisms in common with this water. It's very dangerous, because the
numerous strains of pathogens may migration in water and infect from
gastric-bowel tract to the humans.
Scientists from National technical university "Kharkiv polytechnic
institute" in common with experts from Mechnikov institute of microbiology
and immunology explored this problem and devised the apparatus, which can
destroy a biofilm on polymer or another surface. Materials
& Methods. The tested apparatus
was the electrical device consisting of a block with electrodes, an electronic
control, a water pump and a sprinkler for spraying the disinfectant. The
electrode was made of 925˚ silver (sterling silver). Water for the preparation
of a disinfectant was tap water and wasn't treated additionally. The sprinkler for spraying the
disinfectant was placed in the neck of the infected bottle. Disinfectant
solution was sprayed inside the bottle for 4 seconds. The water pressure was
about 1.5 atmospheres. After that, the sprinkler was removed and the
disinfectant was drained. A smear
for microbiological composition was taken from three parts of the bottle - the
neck, the middle part and the bottom. Growth of microorganisms and their
detections was fixed by classic microbiological methods. Results
& Discussion. In the article the
scheme of the most probable and widespread way of infection of PET-bottles by
pathogens and the way of minimization of this danger is given. Investigation of
the contamination of the inner surface of the bottle by infected dust was
carried out. It is determined that contaminated dust can cause a very serious
infection contamination of inner surfaces of PET bottles and, subsequently, of
water. In laboratory conditions and on the real object, a device for sanitizing
surfaces was tested. It is established that the prototype of the device
generates a disinfectant that destroys the most of known strains of
microorganisms. This disinfectant is not toxic and is not dangerous to humans,
the only product of evaporation of this product is water. With this
disinfectant, the infection contamination on the inside of the PET bottle was
completely eliminated. Thus, the use of a prototype device to minimize the
threat of contamination of water consumers from recycled PET bottles is
possible and very effective. Conclusions. 1.Potable water storage
containers made of PET contain threats, the most serious of which is
microbiological. 2. Without conducting
regular disinfection or inactivation treatment of PET containers may be
potential spreaders of human diseases. 3.The formed biological film cannot be
destroyed or inactivated by means and substances that are at home. Potentially
dangerous is the use of special, concentrated disinfectants at home. 4. Ions of
silver are acknowledged in the world of practice antiseptic. 5. The use of silver ions to inactivate
the biological film, while complying with state standards and methods of
treatment, is safe and effective, which has been proved by research. 6. The developed method and apparatus are
effective against the formed biological film and comply with the current
legislation of Ukraine and some other countries, in particular the USA and
Canada.
Keywords: threat, reusing pet bottles,
drinking water
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26-32
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ORGANIZATIONAL AND LEGAL REGULATION PROCEDURE FOR
CIRCULATION OF EXTEMPORAL MEDICINES BASED ON PHARMACEUTICAL LAW
Shapovalov V. V., Zbrozhek S. I.,
Shapovalova V. O., Shapovalov V. V.
Introduction. The paper studied
the situation regarding the production of medicines in pharmacies. Established
that the presence of the pharmacy manufacture of medicines, patients entitled
to receive medicines made to the needs of individuals. Goal – to study the
organizational and legal procedure of regulation of extemporal medicines by
developing of the algorithm for determining the legal act used in the event of
conflict based on the law pharmaceutical law. Materials and methods. The materials of the study were
legal acts of Ukraine: Laws of Ukraine, Decrees of the Cabinet of Ministers of
Ukraine, Orders of the Ministry of Healthcare of Ukraine. The research methods
were legal, documentary and comparative analyzes. Results and discussion. However, production of
extemporaneous preparations in the pharmacy requires a production base and the
appropriate staff. Therefore, the authors based on pharmaceutical law proposed
organizational and legal procedure regarding the regulation of extemporaneous
preparations by developing the algorithm for determining the legal act which
should follow in the event of conflicts concerning the law. Conclusions. Based on pharmaceutical
law held organizational and legal procedure for the regulation of circulation
of extemporal medicines. Proposed the algorithm
for determining of the legal act used in the practice of pharmacy
professionals. Considered the professional status of an authorized person on
the stage of quality control of extemporal medicines in their treatment in
healthcare institutions of private property.
Keywords: the legal procedure, circulation, extemporal medicines, pharmaceutical law.
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33-37
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AFTER KNEE AND HIP JOINTS ENDOPROSTHESIS REPLACEMENT AND THEIR
DIAGNOSTIC EVALUATION
Shevtsova O.V., Marushchak O.P., Shapovalova O.V., Kuznetsova N.V.
Introduction. Presently in the inflammatory joint diseases diagnosis
and treatment microbiological examination plays a leading role. This is due to
the infectious diseases frequency general increase, the hospital infections incidence rise risk, the widespread use of
antimicrobial agents in medical practice and the change in the infectious foci
microbiocenosises structure.
Microbiological and, if necessary, serological studies of articular fluid are
fundamental components of diagnosis and inflammatory joint diseases effective
treatment selection. Etiological agents of inflammatory processes in joints can
be microorganisms of different groups. According to the literature, up to 80%
of bacterial arthritis cases cause gram-positive cocci, among which S.aureus predominates. At the same time,
the number of methicillin-resistant strains of this pathogen (MRSA) increases
annually. Less commonly, from the affected joints β-hemolytic streptococcus
group A and other groups streptococcus, gram-negative rods, microscopic fungi
and anaerobic bacteria are isolated. In view of the microorganisms biological
nature characteristic, microbiological studies do not always make it possible
to isolate the causative agent of infection. A major problem in bacteriological
diagnostics is the periprosthetic and hematogenic infections low-grade
causative microorganism, as well as subacute and chronic processes course
presence. These include coagulase-negative staphylococcus (for example, Staphylococcus epidermidis) and
anaerobic bacteria. Diagnostic and therapeutic difficulties can also be due to
the pathogens ability to form antimicrobial therapy resistant microbial
biofilms. It is reported that an antibacterial drugs uncontrolled intake, the
biofilms formation, errors in the collection and transportation of biological
material, can cause a situation when the joint infection infectious agent can
not be detected in approximately (10-20) % of the cases. Materials and methods. The material for the studies, were synovial fluid
samples collected from 64 patients of the SE "Sytenko Institute of Spine and Joint Pathology, NAMS Ukraine"
clinic. The patients’diagnosis were status after knee
and hip joints endoprosthesis replacement with inflammatory complications. The biological material was tested in the 2015-2017
period. The synovial material collection was
conducted by the attending physician by the joint puncture method. The
articular fluid withdrawn into the syringe was immediately got to a
microbiological laboratory. The biological samples inoculation was carried out into a fluid thioglycollate storage
medium, then to obtain the aerobic and facultative-anaerobic microorganisms
pure cultures the isolate passage were conducted to Columbia blood agar, salt
agar and Endo medium. Further isolated microorganisms identification was performed by standard methods in accordance
with current guidelines. The microorganisms
cultures were observed for 14 days. In
the absence of microflora’s growth, a preliminary negative result for all synovial material was
given after 5-7 days. If there was a based on the disease anamnesis and clinic suspicion on the slowly growing
pathogens presence the timing of the
studies was increased.The isolates sensitivity to antimicrobial agents was
determined by the disc-diffusion method.In
determining the microorganism’s sensitivity 29 antibacterial drugs from 8
chemical groups were used: β-lactams, fluoroquinolones, macrolides,
aminoglycosides, tetracyclines, lincosamides, glycopeptides, oxazolidinones,
glycylcyclines. Results and
discussion. As a result of the microorganisms’ identification, 68 cultures
of facultative-anaerobic bacteria and microscopic fungi were isolated from the
joint fluid. 82.3% of bacterial isolates were obtained in monoculture (n = 56).
Of these, 25.0% of the cultures (n = 14) were staphylococcus species with
ability to coagulate the blood plasma (S. aureus (n = 9), S. intermedius (n = 5)), other staphylococcus isolation rate was
60.7% (S. epidermidis ( n = 21), S.
haemolyticus (n = 9), S.
simulans (n = 4)). Pathogenic streptococcus species was
isolated from 5.4% of the samples (S. pyogenes
(n = 3)). K. pneumonia cultures
were isolated from 8.9% of biological material samples (n = 5). Mixed
microcenosises were detected in 6
samples of the biomaterial. The cultures associations consisted of two
microorganisms species with the associations S.
intermedius - S. pyogenes,
C. lusitania and C. neoformans
(n = 4) prevailing. Two other microbiocenoses were represented by Candida with S. pyogenes and S.
haemolyticus. The bacterial
cultures sensitivity to antimicrobial agents
analysis showed that all S. aureus isolates were sensitive to linezolid, levofloxacin and the ceftriaxone-sulbactam combination.
Generally it was determined that the most effective
drugs for gram-positive cocci are linezolid, to which 88.1% of the studied
isolates are sensitive, including all S.
aureus and S. haemolyticus
cultures, and tigecycline, which has
activity against 78.0% of gram-positive cocci isolates. The estimated
aminoglycosides efficacy is 73.7%. The fluoroquinolones, carbapenems and the
third generation cephalosporins with sulbactam combinations antimicrobial
activity is manifested for 50% of all isolates obtained. About 30% of cultures
were sensitive to lincomycin and the third generation cephalosporins -
ceftriaxone, cefixime and cefoperazone. Conclusions. 1. Microflora isolated from synovial fluid in case of
the knee and hip joints is inflammatory
diseases is represented by gram-positive cocci (86.8%) in most cases, gram-negative rods amount is
7.3% and fungi of Candida and Cryptococcus genera are made 5.9%. 2.
The isolated microorganisms species antimicrobials sensitivity is characterized
by individual diversity with a tendency to vancomycin resistance increasing in
44.4% of coagulase-positive staphylococcus isolates, of which 28.6% are S. aureus strains; 28.5% o are other
staphylococcus species cultures and 16.7% are S.
pyogenes isolates. This indicates
the exactly appropriate antibiotic therapy conducting necessity. 3. When
choosing antibiotic therapy in patients in case of coxarthrosis and
gonarthrosis it is recommended to take into account the bacterial isolates
antibiotic resistance formation actual trends.
Keywords: periprosthetic infections, synovial fluid,
microbiological examination
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38-42
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THE
STUDY OF SOME PROMISING PHARMACEUTICAL COMPOSITIONS WITH UREASE
INHIBITORY ACTIVITY FOR THE TUBERCULOSIS REACTIVATION PREVENTION
Bomko T.V., Martynov A.V., Nosalskaya T.N.
Introduction. The aim of the study was to study the ability to inhibit
urease by some pharmaceutical compositions that are promising in the
prevention of tuberculosis reactivation . In particular, according to a
number references sources, quercetin is able to successfully inhibit
urease by a non-competitive mechanism. Another compound - dipyrone
(metamizol sodium) according to preliminary molecular modeling has a
pharmacophore structure similar to urea. Materials and methods. The
biochemical studies (urease activity) of some substances effect on
urease was carried out. As the leader substances – inhibitors was used
quercetin and metamizole, another substances are not shown inhibition
activity on the urease. As the substrate a 0.5% aqueous urea
solution was used. The reaction was carried out at a temperature of 37
° C, the incubation time was 10 minutes. The activity of urease was
determined by the color reaction with the hypochlorite reagent.
Photometry was performed on a FEK-3M photoelectric colorimeter at a
wavelength of 590 nm. Results and discussion. Quercetin and
metamizole sodium have the strongest inhibitory properties for urease,
since the lowest values of semi-inhibitory concentrations are obtained
for them. In the presence of chlorophyllipt, the inhibitory activity of
quercetin against urease is not suppressed. Metformin showed no
inhibitory activity against urease, and it was low for other
substances. Conclusion. The highest anti-urease activity showed a
composition based on metamizole sodium and quercetin, a little less -
based on quercetin and vitamin D. Also interesting for further research
is the composition of quercetin and chlorophyllipt.
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43-45
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THE USE OF BACTERIAL LYSATES IN THE COMPLEX TREATMENT OF PATIENTS WITH CHRONIC DECOMPENSATED TONSILLITIS
Manee Hans, Sklyar N.I., Kalinichenko S.V., Markovich I.G.
Introduction. Chronic tonsillitis (CT) occupies a leading place in the
structure of general Oto-rhino-laryngology (ORL) pathology which is
characterized by a tendency to an increase in the number of patients
with recurrent course, the development of complications and the
diversity of etiopathogenetic mechanisms of onset. It has been
established that the most acceptable tactic for the prevention of
exacerbations of chronic tonsillitis is the use of various groups of
drugs that enhance the humoral immunity of the mucous membranes. The
drug Ismigen is an immunostimulant based on a bacterial lysate, which
increases the body's resistance to infections due to an increase in
serum and secretory antibodies, activation of cellular and humoral
factors of nonspecific immunity. The aim of the study was to
evaluate the effectiveness of the use of Ismigen in the complex
treatment of patients with chronic decompensated tonsillitis by
studying the dynamics of microbiological indicators. Materials and
methods. To achieve this goal, 31 patients with chronic decompensated
tonsillitis (CDT) were examined. Patients were divided into 2 groups
depending on the proposed treatment regimen: Group A: patients with
chronic decompensated tonsillitis who underwent laser tonsillotomy - 15
patients; Group B: patients with chronic decompensated tonsillitis who
underwent laser tonsillotomy with further immunostimulation with the
drug Ismigen - 16 patients. The control group (CG) consisted of 17
practically healthy individual. Patient in group B had sublingual
Ismigen postoperatively: once daily for a period for a period of 10
days. Microbiological examination of the material from the mucous
membranes of the tonsils or oropharynx was carried out in dynamics
before the treatment, 7 days after the treatment and 1-2 months after
the end of the course of treatment. A comprehensive assessment of
the status of the oropharynx microbiocenosis was carried out in
accordance with the criteria described earlier. According to these
criteria, the status of the microbiocenosis of the oropharynx was
divided into: eubiosis, dysbiosis of the 1st degree, dysbiosis of the
2nd degree and dysbiosis of the 3rd degree. Results and
discussion. Before treatment, in the decompensated state of CT
(59.7±2.8) % of the examined subjects was accompanied by dysbiotic
manifestations and were classified to grade 3: 60.0% of patients in
group A and in 62.5% of patients in group B. In no case pathology of
the tonsils did not reveal the microbiological picture of eubiosis.
Carrying out various types of therapeutic measures for patients with
CDT positively affected the microbiocenosis status of the studied
biotope in comparison with the initial data. Comparison of the results
of microbiological examination of patients in groups A and B showed the
advantages of using immunocorrection after laser tonsillotomy. Thus, in
81.3% of the examined group B microbiocenoses of the mucous membranes
of preserved tonsils are represented by eubiosis, compared with 26.7%
in group A (p<0.01). The rest of the patients (18.7%) of group B
showed dysbiotic phenomena of 1st degree, against 53.3% of persons in
group A (p<0.05). The study of the species composition of the
oropharynx microbiota of patients with CDT before treatment and its
comparison with bacterial antigens that are part of the preparation of
Ismigen showed that practically every patient had persistent one or two
respiratory pathogens, which are eliminated by bacterial lysates of
Ismigen. Immediately after the treatment, there were
no significant differences in the incidence of the above-mentioned
bacteria between groups of patients. Respiratory pathogens were
detected in 5 patients of group A and 3 patients of group B. The
density of seeding of the biotope decreased significantly compared to
baseline values and averaged lg (4.1±0.2) CFU/g (p <0.01). 1-2
months after the treatment in none of the patients who received the
preparation of «Ismigen», the indicated bacteria were detected in the
microbiocenosis of the mucous tonsils, against 66.7% of the group A
patients who did not undergo sublingual immunization (p<0.01) .
«Sanitizing», with respect to the microbial factor of CT, the
effectiveness of performed tonsillotomy in a third of patients of group
A was lost. The aforementioned respiratory pathogens are most often
encountered in chronic inflammatory processes in the upper respiratory
tract. Long-term persistence of microorganisms is accompanied by
aggravation of immunological disorders and an increased risk of
recurrence of the disease [14]. Our studies confirmed the above for
patients in Group A, who underwent adequate pathogenetic organ-sparing
treatment of the tonsils, but without subsequent immunocorrection.
Conclusions. 1. Ismigen, administered to patients with chronic
decompensated tonsillitis as part of complex treatment provided a more
pronounced antimicrobial effect and promoted restoration of the
normocoenosis of the oropharynx. 2. Laser tonsillotomy performed with
further immunomodulation with the help of immunostimulant on the basis
of bacterial lysates Ismigen, allows to achieve the indices of
microbial communities of the mucous membranes of preserved tonsils,
which did not differ statistically from the microbiota of the control
group of practically healthy persons: in 81.3% of patients, eubiosis
and in 18.7% of the dysbiosis of the 1st degree. In persons without
pathology of the tonsils, these indicators were 88.2% and 11.8%,
respectively. 3. Ismigen has a selective antimicrobial effect against
the most common respiratory pathogens, which is objectively manifested
by the restoration of the eubiotic colonization profile of the
oropharynx in patients with CDT 1-2 months after treatment.
Keywords: chronic decompensated tonsillitis, complex treatment, Ismigen, microbiocenosis.
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