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C.
(P.)
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Ðåäàêö³éíà
ðàäà (Editorial Board)
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1
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Çì³ñò
(Contents)
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2-11
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ÎÃËßÄÈ
(REVIEWS)
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ÌÅÒÎÄÈ
ÊÎÍÒÐÎËÞ
ÁÅÇÏÅ×ÍÎÑÒ² ÄÈÔÒÅвÉÍί ÂÀÊÖÈÍÈ
²ñàºíêî Î. Þ., Áàáè÷ ª. Ì., ªëèñåºâà ². Â., Æäàìàðîâà Ë. À., Á³ëîçåðñüêèé Â. ²., Êîëïàê Ñ.À.
METHODS OF
CONTROL DIPHTHERIA VACCINE SAFETY
Isayenko Ye. Yu.,
Babych Ye. M., Yelyseyeva I. V., Zhdamarova L. A., Belozersky V. I.,
Kolpak S.
A.
Vaccination success depends
not only on the timely coverage of threatened contingents, but also on
the
quality of vaccines. Every day, the requirements for security
guarantees
vaccines and their use guarantees of security increases. For the fast,
reliable
and independent scientific assessment of vaccine safety issues, WHO in
1999
created the Global Advisory Committee on Vaccine Safety. To enhance the
capacity of pharmaceutical supervision in relation to vaccines in 2012
it was
developed the Global Vaccine Safety Initiative. The main directions of
the
Global Vaccine Safety programs are considered in this review. It’s
noted more
strict requirements of Ukrainian pharmaceutical industry to produce
public
immunization drugs regulated Supplements to the State Pharmacopoeia of
Ukraine,
in comparison with other countries. This review considered diphtheria
vaccine
safety monitoring in the process of production according to the
recommendations
of the World Health Organization (WHO), described a subcutaneous method
for
determining the specific toxicity of the combined purified toxoid,
characterized an intracutaneous method of determining of the presence
of
diphtheria toxin in each sample of the combined purified toxoid, that
additionally used by some manufacturers. The definition of diphtheria
toxin in
dilutions of purified toxoid is presented.
This review considered diphtheria vaccine safety
monitoring in the
process of production according to the recommendations of the World
Health
Organization (WHO), described a subcutaneous method for determining the
specific toxicity of the combined purified toxoid, characterized an
intracutaneous
method of determining of the presence of diphtheria toxin in each
sample of the
combined purified toxoid, that additionally used by some manufacturers.
The
definition of diphtheria toxin in dilutions of purified toxoid is
presented. As methods for determination of
diphtheria
toxin must be able to detect even a small amount of toxin it's examined
the
WHO's proposal to use an intradermal method on guinea pigs and tests on
cell
cultures. Attention is drawn to the fact that the determination of
specific
toxicity in cell culture can be carried out at presence of the approval
of this
method of a national control authority and sensitivity rates no less
than in
experiments on guinea pigs. The determining of specific toxicity of
ready
vaccine by subcutaneous method is described. The publication gave a
test for
elevated toxicity of the final product by intraperitoneal infection of
mice and
guinea pigs. It’s cited the WHO recommendations aimed at removing the
possibility of recovery of the refined toxin toxicity.
Checking vaccines toxicity, pyrogenicity,
sterility, allergenicity, teratogenicity, mutagenicity and
immunogenicity
mainly performed on laboratory animals. The review examined the
unreliability
of animal experiments and the need to find alternative methods for
determining
the toxicity without their use particularly in light of the
“3R”concept.
Methods for determining diphtherial toxin using cell cultures is
considered, namely, colony overlay test
(COT), tests using a monolayer of HeLa cell culture, a culture of Vero
cells
(kidney cells of african green monkeys ), a culture of CHO cells (cells
of
Chinese hamster ovary), which are based on the toxin cytopathic effect
on
sensitive cell culture. Their advantages and disadvantages are listed. An alternative method for the quantitative
detection of C. diphtheriae toxin using the polystyrene plate coated
with
monoclonal antibody to the part of the diphtheria toxin which defines
its
binding to the cell, is described. It’s regarded the cytotoxic effect
of diphtheria
toxin on cells of the immune system of mice and guinea pigs:
splenocytes,
adhesive phagocytes i B- lymphocytes.
Keywords: diphtheria
vaccine, safety, diphtheria toxin, toxoid, cell culture, laboratory
animals.
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12-17
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ÀÍÀ˲ÒÈ×ÍÅ
ÎÁ¥ÐÓÍÒÓÂÀÍÍß ÂÊËÞ×ÅÍÍß ÏÐÎÒȲÐÓÑÍÎÃÎ ÏÐÅÏÀÐÀÒÓ Â ÑÕÅÌÓ
˲ÊÓÂÀÍÍß ÏÀÖ²ªÍÒ²Â Ç Ï²ÄÎÇÐÎÞ ÍÀ ÃÎÑÒЊ²ÐÓÑÍÅ ÇÀÕÂÎÐÞÂÀÍÍß
Ñîëîâéîâ
Ñ. Î. Äçþáëèê ².Â., Çàë³ñüêà Î.Ì., Ñàõíî Ã.
Î.
ANALYTICAL JUSTIFICATION OF
INCLUDING THE ANTIVIRAL DRUG INTO TREATMENT SCHEME FOR PATIENTS WITH
SUSPECTED
VIRAL DISEASE
Soloviov S. O., Dzyublyk I.V.,
Zaliska O.M., Sakhno A. O.
Background: Viruses play a leading
role in human pathology development, causing a large number of
infectious
diseases in acute, persistent or chronic forms. Although the number of
deaths
caused by viral infections have decreased significantly today, they
continue to
be a significant factor in reducing of the population overall
productivity.
Viral diseases cause additional losses in community related to the
duration of
the course or disease or its chronization, increased use of health
care, loss
of working hours, premature death etc. Introduction of the new
antiviral drugs
into medical practice is accompanied by the emergence of questions to
assess
its effectiveness and including into existing clinical protocols. So
the aim of
this work is the development of methodology of choosing and
justification of
optimal treatment strategy for viral diseases that could be included
into
certain clinical protocols for managing patients with certain viral
diseases.
Methodology justification: The methodology based on the method of
pharmacoeconomic analysis "cost of illness", takes into account the
economic burden of viral diseases: direct costs for treating of
disease,
indirect costs related to the disease and intangible costs. Algorithm
of
treatment scheme choice depends on the cost of treatment for the
patient
without viral disease also as for patient with viral disease. It was
proposed
to use lower limit priori probability (critical prevalence) of viral
disease as
decision rule in the choice of treatment scheme. Results: Examples of
the
proposed methodology use show that the choice of the optimal
therapeutic scheme
for patients with suspected viral disease depends on the current
prevalence of
this disease among patients with similar clinical symptoms of the
disease and
its cost, depending on the chosen strategy of therapy. The proposed
methodology
determines the critical level of viral infection prevalence, which
comparing to
the current prevalence level is the criterion for inclusion of certain
antiviral drug into treatment scheme. Conclusions: The implementation
of
developed methodology requires a dynamic and updated database of
patients with
similar clinical symptoms, which will include information of
etiological agent,
chosen treatment scheme, number of bed days and costs associated with
viral
disease for each patient.
Keywords: viral infection, treatment, cost of illness,
pharmacoeconomic
analysis, decision making.
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18-26
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ÑÎÂÐÅÌÅÍÍÛÅ
ÌÅÒÎÄÛ
ÈÑÑËÅÄÎÂÀÍÈß ÁÈÎÌÀÐÊÅÐΠÐÀÑÑÅßÍÍÎÃÎ ÑÊËÅÐÎÇÀ
Êîëÿäà
Ò.È.,
Çåëåíñêàÿ À.Ä., Òóïîòèëîâ À.Â.
CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS
BIOMARKERS
Kolyada T.I., Zelenskaya A.D., Tupotilov O.V.
Current data concerning features of multiple
sclerosis (MS) etiology, pathogenesis, clinical course and treatment of
disease
indicate the necessity of personalized approach to the management of MS
patients. These features are the variety of possible etiological
factors and
mechanisms that trigger the development of MS, different courses of
disease,
and significant differences in treatment efficiency. Phenotypic and
pathogenetic heterogeneity of MS requires, on the one hand, the
stratification
of patients into groups with different treatment depending on a number
of
criteria including genetic characteristics, disease course, stage of
the
pathological process, and forms of the disease. On the other hand, it
requires
the use of modern methods for assessment of individual
risk of developing MS, its early diagnosis,
evaluation and prognosis of the disease course and the treatment
efficiency.
This approach is based on the identification and determination of
biomarkers of
MS including the use of systems biology technology platforms such as
genomics,
proteomics, metabolomics and bioinformatics. Research and practical use
of
biomarkers of MS in clinical and laboratory practice requires the use
of a wide
range of modern medical and biological, mathematical and
physicochemical
methods. The group of "classical" methods used to study MS biomarkers
includes physicochemical and immunological methods aimed at the
selection and
identification of single molecular biomarkers, as well as methods of
molecular
genetic analysis. This group of methods includes ELISA, western
blotting,
isoelectric focusing, immunohistochemical methods, flow cytometry,
spectrophotometric and nephelometric methods. These techniques make it
possible
to carry out both qualitative and quantitative assay of molecular
biomarkers. The
group of "classical methods" can also include methods based on
polymerase chain reaction (including multiplex and allele-specific PCR)
and
genome sequencing techniques (including full genome resequencing,
targeted
resequencing of the genome). The results obtained with these techniques
became
the basis for the further development of screening technologies.
Disadvantages
of the "classical" methods are associated not only with their
resolution or other technical limitations but also to the fact that the
range
of pathological processes in MS may vary significantly from patient to
patient
and single biomarkers suitable for one group of patients may be
inappropriate
for another group of patients. Due to the complexity of MS the
reflection of
pathological changes may be determined not by single biomarkers but by
isolated
biomarkers panel from different compartments. The solution of this
problem
seems to be possible due to the development of microarray methods
including
biochips technology. Biochips are used for screening of MS patients and
allow
determining the rare MS-associated gene variants that have a
significant impact
on the development of the disease. In conjunction with the
"classical" methods, microarrays allowed to apply systems biology
approaches (i.e. genomics, transcriptomics, proteomics, metabolomics,
epigenomics) in the study of MS biomarkers. Addition of bioinformatics
methods
to "classical" and microarray laboratory methods allows not only to
find new biomarkers but to identify complex patterns of biomarkers
while single
biomarkers informative value is not sufficient. To date, the use of
genome-wide
association study (GWAS) revealed more than a hundred genetic variants
associated with the development of MS, while the total number of
investigated genetic
variants including the candidate ones exceeded two hundred. GWAS is
used to
identify correlations of genetic variants with the disease, including
the
identification of variants associated with a risk of developing MS, but
cannot
answer the question of the causal links between specific genes
polymorphism and
the pathogenesis of MS. Current studies of biomarkers of disease
severity,
progression, pathogenetic type and treatment efficacy are based on
transcriptomics, proteomics and metabolomics technologies.
Transcriptomics
includes genome-wide research of RNA sequences based on the results
obtained
with comparative genomic hybridization on biochips, massive parallel
RNA
sequencing, and measuring the amount of mRNA by real-time PCR. This
technology
is actively used in studies of gene expression profile of peripheral
blood
mononuclear cells from MS patients aimed at identifying molecular
markers of
disease status suitable for clinical use. Proteomics is a large-scale
expression and protein distribution studies in patients with MS based
on the
results obtained via microarray and mass spectrometry, liquid and gas
chromatography methods. In recent years, a growing number of MS
proteomic
studies using 2DE-MS method (two-dimensional electrophoresis coupled
with mass
spectrometry). Metabolomics studies of low-molecular-weight metabolic
profiles
based on the results obtained by mass spectrometry, liquid and gas
chromatography, nuclear magnetic resonance. However, unlike other
«-omics»-technologies, in metabolomics microarray-techniques are not
used.
Conclusion. Search, verification and clinical application of biomarkers
for
multiple sclerosis are one of the most challenging medical and
biological
problems. Its solution requires an interdisciplinary approach,
organization of
large-scale research and engagement of new research methods. In recent
years, a
significant amount of data received allowed to reveal hundreds of
candidate
biomarkers. Some of these biomarkers have significant potential for the
monitoring of disease activity and assessment of therapy efficiency.
However,
the verification is required for a widespread clinical application; it
implies
further large-scale studies in different countries. The development of
personalized medicine in Ukraine, the application of its principles to
the
management of multiple sclerosis patients, along with the use of
advanced
"classic" biomarker research methods requires the introduction of
modern methods including the use of new-generation biochips, genomics
technologies,
proteomics and metabolomics.
Keywords:
multiple sclerosis, biological markers, mononuclear phagocytes,
genomics,
proteomics, metabolomics
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27-33
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ÅÊÑÏÅÐÈÌÅÍÒÀËÜͲ
ÐÎÁÎÒÈ
Experimental papers
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COMPOSITE
MATERIALS BASED ON ZINC SULFIDE AND ZINC OXIDE: STRUCTURAL AND BIOCIDAL
PROPERTIES
Sukhodub L.B., Khrystian G.E., Sukhodub L.F., Shulga
N.M., Meshkov A.M., Kazmirchuk V.V., Martynov A.V.
Introduction. The widespread use of drugs
with antimicrobial action has led to the formation of microorganism
resistance
against wide range of antibiotics. One of the approaches to dissolving
this
problem is the substances modification by inorganic bioactive ions in
oder to
initiate a controlled reaction in the bone tissues and provision of
antimicrobial activity. It is known that ZnO-based materials have a
pronounced
biocompatibility, they are characterized by high limit strength,
absolute
mechanical hardness, as well as the ability to withstand the harsh
operating
conditions. The aim of this work is the
study of structural and biocidal properties of composite material based
on zinc
oxide and zinc sulfide (ZnS-ZnO) and its complex with an organic
substance -
sodium alginate (ZnS-ZnO-Alg) for use in biomedical purpose. Materials
and
methods. For the synthesis of ZnS-ZnO composite 50 ml 0.2M solution
zinc
nitrate was added to the 50 ml 0.2M thiourea CS (NH ₂) ₂ solution and
stirred
in a shaker for 60 minutes. The formation of the compound took place
when added
to a mixture of 25 mas.% solution of ammonia with the subsequent
heating at 80
oC for 30 minutes. Synthesis of the metalorganic complex of ZnS-ZnO-Alg
was
performed by above mentioned procedure, but to the thiourea solution
was
previously added 1 ml of 3 mas.% solution of sodium alginate under
ultrasonic
mixing.. For the next research composites were dried or lyophilized.
Study of
antibacterial activity of the ZnS-ZnO and ZnS-ZnO-Alg particles was
carried out
with the use of nutrient mediums: Muller Hinton, meat-pepton nutrient
(MPN). As
the reference cultures were used E. coli ATCC 25922, S. aureus ATCC
25923, S.
aureus ATSS 29213, S. aureus ATSS-6538, C albicans ATCC 885-653.
Determination
of the minimum bactericidal concentration (MBC) was carried out by a
modified
serial diluted method in liquid nutrient broth followed plating on
solid Muller
Hinton nutrient medium. In addition, the study of the sensitivity of
the above
listed microorganisms to the experimental samples was carried out by
the method
of diffusion in Agar in the modification of the wells. The
crystallinity and structure
of precipitates were examined using an X-ray diffractometer DRON 3. The
elemental composition of synthesized samples was studied by an X ray
fluorescence (XRF) analysis using ElvaX Light SDD spectrometer. Results
and
discussion. X-ray structural analysis indicate that in the composite
material,
synthesized both in the presence of sodium alginate (ZnS-ZnO-Alg) and
without
sodium alginate adding (ZnS-ZnO) exist two phases: ZnS and ZnO. Based
on RFA
calculations show that ZnS-ZnO sample contains up to 50 wt. % zinc
oxide. Zinc
oxide content in the ZnS-ZnO-Alg is about 25 wt.%. The MBC was
determined by
above described method placing the liquid from each tube with a sample
on a
Mueller-Hinton solid culture medium. MBC of ZnS- ZnO-Alg samples
against all studied
microorganism strains was 1,25 mg/ml. MBC of ZnS- ZnO samples ranged
from 5
mg/ml for C. albicans to 12.5 mg/ml for E. coli. It is possible that
due to
small sample solubility in experimental conditions and small ion
diffusion of
the active substance there was no full contact with the whole bacterial
cell
volume. As ZnS-ZnO-Alg samples differe from ZnS- ZnO samples by smaller
crystallite size and greater solubility, they exhibit a marked
antimicrobial
effect. At the same time in direct contact of the entire surface of the
sample
with bacterial cells under condition of the modifying method of
diffusion into
agar, both types of samples showed high antimicrobial activity.
Obtained data
can be explained by two major mechanisms of the antimicrobial action
ZnO and
ZnS: a) toxic effects of zinc ions in the cell membrane of bacteria; b)
toxicity ROS (reactive oxygen spices), formed with the participation of
ZnO and
ZnS, on components of the bacterial cell. Antibacterial activity is the
result
of the formation such ROS, as hydrogen peroxide (H2O2), peroxide anion
(O2-),
hydroxyl radicals (OH-). These particles damage cellular components
such as
DNA, lipids and proteins. Conclusion. The composites ZnS- ZnO and
ZnS-ZnO-Alg
have been obtained by the applied method of synthesis. X-ray structural
analysis of samples proved the presence of ZnO and ZnS phase with
defined
structure: ZnS has a cubic crystal structure type sphalerite (JCPDS
5-566) with
average crystallite size of 23 nm and ZnO - hexagonal structure (JCPDS
80-75 )
with an average size of about 35 nm. The introduction of sodium
alginate to the
reaction mixture during synthesis reduces the size of ZnS and ZnO
crystallites
to 10 nm and 12 nm, respectively. In the ZnS-ZnO-Alg samples,
synthesized in
presence of sodium alginate, the ZnS phase content increased for 25wt.%
compared with the ZnO phase, which was confirmed by XRF.
Microbiological
studies have shown the presence of antimicrobial activity of samples
against
Gram-positive S. aureus, Gram-negative E. coli and fungi C. albicans.
The
estimated values for the integral antimicrobial activity, calculated by
the
vector theory, are for ZnS-ZnO and ZnS-ZnO-Alg 1,57 and 1,9
respectively. It
means that both types of samples have average antimicrobial activity.
Keywords: zinc
sulfide, zinc oxide, antimicrobials,
structural properties |
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34-39
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CYTOKINE DISBALANCE AT
HERPESVIRUS MYOCARDITIS
Peremot S. D., Smilyanskaya M.
V., Volyanskiy A. Y., Kashpur N. V.
Viral
myocarditis is a heterogeneous group of diseases not only by etiologic
factors,
which belong to different families of Vira kingdom, but is also
characterized
by a unique mechanism of inflammatory process and cytokine levels
specific for
each of them. According to numerous researches in ñardio-immunology, at
herpesvirus
infection of the cardiovascular system occur both systemic and
localized
violations of the immune response. Unfortunately, the accessible
literature did
not provide the data analysis of complex cardio-immunological research
that
would take into account the features of herpesvirus myocarditis
clinical
course. This grounds relevance of immunodiagnosis directed on the
exposure of
dysimmunities by study of indices of general and local immunity with
the
estimation of the immune status in patients depending on the stage of
exasperation or relapse of chronic herpetic infection in the complex of
diagnostic tests. The purpose of our research was to determine features
of the
state of the immune system with the complex analysis of cytokine
profile data,
immune and interferon statuses in subacute and chronic forms of
herpesvirus
myocarditis. Materials and methods. 87
myocarditis patients who were receiving inpatient treatment in medical
establishments of Kharkiv were examined.
The average age was (M ± m) 36 ± 3,46 years old. The diagnosis of
myocarditis
was established according to the order ¹ 436 by the Ministry of
Healthcare of
Ukraine from 03.07.2006 of clinical findings protocol. In accordance
with the
term of myocarditis clinical course, the patients were divided in two
sub-groups: 44 patients with subacute (from 2 to 6 months), and 43
patients
with chronic (over 6 months) clinical course of viral myocarditis. The
control
group correlated with patients of basic group by age and gender and
consisted
of 40 practically healthy persons without implications of cardial
pathology.
Definition of cytokine concentration: IL-2, IL-4, IL-6, IL-10, INF-γ,
TNF-α in
blood serum was conducted by the method of solid-phase enzyme-linked
immunosorbent assay, population structure of lymphocytes with different
antigenic determinants (CD3+, CD4+, CD8+, CD16/56, CD19+, ÑD95+) was
determined
by monoclonal antibodies by cytofluorimetric assay. Obtained data
processing
was conducted with the use of parametric and non-parametric methods of
biostatistics by programs EXEL-2003® and Biostatistics 4.03. Results and discussion. The data obtained
indicates the disbalance in their system, which above all is
characterized by a
considerable level increase of pro-inflammatory IL-6 up to 134,09 ±
22,72 pg/ml
(control level 11,83 ± 1,64 pg/ml) and in relation to moderate growth
of levels
of IL-2 òà TNF-α at subacute myocarditis. Such increase in level of
IL-6 can
take place due to the change of pro-inflammatory effect to
anti-inflammatory in
a remote period. In a complex with IL-10 IL-6 limits the secretion of
TNF-α.
For this reason, its level remains high at chronic herpesvirus
myocarditis and
exceeds the level of the control group by over 8 times. In addition,
there is
an increase of levels of anti-inflammatory IL-4, IL-10 cytokines at the
chronic
form of herpesvirus myocarditis course by 2,9 and 3,1 times
respectively. At
the same time, the level of IL-10 increased not only in comparison with
the
level of the control group but also almost 2 times exceeded the proper
index at
subacute myocarditis. Instead of the predicted INF-γ level rise, its
decline
was discovered, in patients with subacute course the index value was
the
lowest. This phenomenon can be the result of mast cells activity and in
its turn
influences the synthesis of collogen and processes of myocardium
remodeling. Analysis of sub-population
composition of lymphocytes discovered the increase in number of
CD3+CD95+
lymphocytes of peripheral blood at myocarditis, especially in the group
of
patients with subacute herpesvirus myocarditis with its level exceeding
the
index of the control group by 3,3 times, and at chronic course – by 2,7
times.
We consider that determination of CD95+ expression already has a
prognostic
value during the first signs of cardiac insufficiency. An increase in
level of
the indicated receptor is the evidence of active rejection process of
defective
and infected cardiomyocytes, which clinical displays are signs of
cardiac
insufficiency and decline of myocardium retractive ability. Conclusion. Thus, determination of cytokine
in blood serum at infectious myocarditis of herpesvirus nature has a
high
diagnostic value and can compete with invasion and instrumental methods
of
diagnostics. Disbalance in the system of cytokines at herpesvirus
myocarditis
is a universal reaction of the immune system which is characterized by
the
increased levels of pro-inflammatory cytokines against the moderate
decline of
anti-inflammatory, and the increase in concentration of ²L-10 in
combination
with the level of lymphocytes of membrane phenotype CD3+CD95+ can be
used as a
diagnostic criterion of chronization course of disease. Understanding
the
pathogenesis of viral myocarditis at cellular level matters for the
development
and optimization of methods of laboratory diagnostics and forms a basis
for
determining prognosis of a disease course and choice of treatment
tactic.
Keywords: herpesvirus myocarditis, immunological disbalance.
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40-45
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VECTOR THEORY AND OPTIMAL CHOICE OF ANTIMICROBIAL DRUG FOR
LOCAL WOUND TREATMENT
Boyko, N. N., Osolodchenko, T. P., Zhilyakova, E. T.
Introduction.
One of important problems in the field of medicine and pharmacy is an
optimal
choice among several alternatives. For example, the choice of drugs for
treatment among several analogs, selection of excipients among analogs
for
development of pharmaceutical forms with optimal pharmacological,
technological
and economical parameters, etc.The aim of the work is to show the
possibility
of vector theory use for optimal choice of antimicrobial drugs for
local wound
treatment among analogs taking into account several criteria at the
same time.
Materials and methods. For our investigation we have chosen ten drugs
with
antimicrobial properties for local wound treatment in different
pharmaceutical
forms (ointment, liniment, water and glycerin solution, tincture). We have determined antibacterial activity of
drugs by agar well diffusion method on six test-stain microorganisms:
Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922,
Pseudomonas
aeruginosa ATCC 27853, Proteus vulgaris ATCC 4636, Bacillus subtilis
ATCC 6633,
and Candida albicans ATCC 885-653. Well diameter was 10 mm, the volume
of drug
in the well was 0.27±0.02 ml, microbial burden of agar upper layer was
107
CFU/ml, and total layer height in Petri dish was 4.0±0.5 mm. In order
to
integrate various qualitative and quantitative parameters into one
index
(vector object in multidimensional factors’ space) we modify these
parameters
to non-dimensional normalized values. For this purpose we use a
desirability
theory. We have chosen the following criteria for optimal choice of the
drug:
antimicrobial activity (integrated index of drug’s antimicrobial
activity),
drug’s price, pharmacological and technological index, spectrum of
drug’s
action on test strains of microorganisms studied. Results and their
discussions. Using vector and desirability theory, we have obtained the
following range of drugs in decreasing order: Laevomecol ointment,
Ioddicerinum, Tincture of Sophora japonica, Povidone-Iodine liniment,
Methyluracilum cum Myramistino ointment, Laevosinum ointment, Tincture
of
calendula, Ranostop ointment 10%, Myramistinum-Darnitsa ointment, and
Decasanum
water solution 0.02 %. Conclusions. In this paper we have shown the
possibility
of vector theory use for optimal choice of antimicrobial drugs for
wound
treatment among analogs by taking into account several criteria at the
same
time. This mathematical method together with desirability theory gives
us a
possibility to determine low values of desirability function (weak
points) for
the drug and to predict its rating when we change values of original
parameters.
Keywords:
vector theory, optimal choice of wound treatment drug.
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46-52
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HPLC FOR CONTROL STABILITY OF QUERCETIN INJECTABLE DOSAGE
FORM
Martynov A.V., Batrak E.A., Kabluchko T.V.
Introduction. Quercetin is a flavone derivatives which
known like a
substances with vitamin activity, high
antioxidant, antimutagenic and anticarcinogenic activity and many other
types
of biological activity. Wide usage of
quercetin prevents their polyphenolic nature structure which does not
allow a
high bioavailability of pure quercetin when administered orally. This
is
associated with a wide spectrum variety of chemical reactions for the
phenolic groups:
from interaction with amino acid residues in proteins to reactions with
amine
heterocyclic alkaloids and polysaccharides. In our days
Corvitin – one from the number of quercetin
based drugs with sufficiently low levels all types toxicity, allergenic
and has
no irritating action on intravenous administration. In the same time
quercetin
cannot be used in full measure because of the limited number of
publications
with analysis methods, especially HPLC. Determining the stability over
time of
concentrate quercetin solution, as well as determining the stability of
the
concentrate to the original autoclave sterilization conditions is a
promising
direction in creating new drugs. Materials and methods The objective
was to
research quercetin soluble formulation samples in different conditions:
1)
fresh dilute concentrate (0.9% sodium chloride); 2) the original dilute
concentrate, which was stored at room temperature for 14 days in light
and 3)
similar to the first sample dilute concentrate, which went before
breeding in
autoclaving at 120 0 C for 20 minutes. The objects used in the studies
were
industrial drug-substance quercetin (Sinkea manufactured (China)), the
original
pharmaceutical composition as the soluble form of quercetin for
injection and
aerosol applications, glycerol (Sigma), Polysorbat 80 (Merk), ethanol
96 %. For
the HPLC – analysis, chromatograph "Milichrom A-02" (SiChrom, Knauer)
(Econova, Novosibirsk, Russia) was used. Results and discussion
Quercetin was
identified using information on its retention time and spectral
relations in
the UV region from the database of DB-2003 spectrums. HPLC analysis
results
show that the quercetin is stable in ampouled form under autoclave and
storage
and freshly diluted quercetin concentrate for infusion are identical.
Quercetin
aqueous solution which was stored at room temperature for 14 days in
the light,
turned out to be unstable. It was found
that aqueous solutions of polysorbate-80 was full hydrolyzed to the
initial
compounds. Conclusions In this work the ability of
quercetin’s perspective concentrates to be
stable were checked. The stability of concentrates was determined by
HPLC
chromatograph "Millichrome A - 02» (SiChrom, Knauer). It is shown that
the
HPLC methods can be used to establish the smallest difference in the
samples.
The quercetin’s non-aqueous concentrate is capable of withstanding
retorting
and remains in standard indestructible state in nonaqueous media
(glycerol,
ethanol, polysorbate 80). Quercetin is unstable in aqueous solutions
and are destroyed
during prolonged storage. HPLC- chromatogram is presented in the
article and
show that gradient HPLC with UV- detection can be used for quality
control of
quercetin.
Keywords:
quercetin,
stability, HPLC, autoclave sterilization, polysorbate-80.
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53-57
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ÂÈÂ×ÅÍÍß ÁÅÇÏÅ×ÍÎÑÒ² ÅÊÑÏÅвÌÅÍÒÀËÜÍÈÕ Ë²ÏÎÑÎÌÀËÜÍÈÕ
²ÐÓÑÍÈÕ ÂÀÊÖÈÍ
Ðîìàíîâà Î. À., Äàâèäîâà Ò. Â., Êëèñà Ò. Ë.,
Êëèñà À. Î.
EXPERIMENTAL
LIPOSOMAL VIRAL VACCINE SAFETY
Romanova
O.A., Davydova T.V., Klysa T.L., Klysa A.O.
Introduction.
With the transport links development there is rather important issue
respiratory viral infections spread, especially influenza. The only
method
controlling influenza is vaccination. Search and development effective
and safe
vaccines is important. Material and
methods. In base SO "Mechnikov Institute Microbiology and Immunology
National Ukrainian Academy Medical Sciences" in the scientific theme
"Developing new approaches to creating viral vaccines and study
specific
activity depending of type and degree component`s modification" was
created several experimental influenza vaccine with subsequent
component`s
modification for selecting the most optimal pattern of safety and
immunogenicity. In assessing the influenza vaccine safety is using a
few
criteria, including, reactivity, as measured by the frequency of local
and
systemic adverse (negative) effects, which due to its introduction, and
for
lipid content drugs, ability to influence oxidation processes. At
present study
phase was determined: a) systemic reaction and local reaction of
delayed-type
hypersensitivity (foot pad swelling assay);b) lipids and proteins
peroxidation
processes after administration officinal and experimental vaccines
(content
protein’s carbonyl groups, lipid’s hydroperoxides, activity of
glutathione-peroxidase).Study
objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi
Pasteur, S.A., France), "Inflexal V" (Biotech Ltd. Berne,
Switzerland) and experimental vaccine samples. Highest immunogenicity
vaccines
had undergone improvements and modifications using adjuvant systems and
acylation influenza proteins. Liposomes 2 – the experimental influenza
vaccine
with a liposome negative charge and antigenic composition like split
vaccines
"Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza
vaccine with modifications liposomal components (etoniy and
chlorophyllipt
molecules embedded in liposomal membrane). Liposomes 2.2 - the adjuvant
experimental influenza vaccine further modification through acylation
antigenic
component.Results and discussion. Among the vaccines with the antigenic
component modification and addition of adjuvants, the highest
production of
specific influenza antibodies was observed after administration
liposomes ¹2.2
sample, which was made on the basis of antigen Vaxigrip with negatively
charged
liposomal formulation, the addition of adjuvants and modification
antigenic
composition, the second ranked liposomes ¹2.1, without antigenic
modification.
The study identified regarding the frequency of local reactions,
assessed by
visual observations, among experimental animals in injection site after
legalized vaccines or newly samples weren`t characterized by the
formation of
swelling, hardening of tissue hyperemia or painful local reactions
throughout
the observation time.Experimental mice also haven`t fever for the 5
days after
manipulation, which is the main criterion of systemic adverse reactions
after
they administered vaccine preparations. Also after use of experimental
drugs
and drug comparison, subjective, wasn`t happened abnormalities in
general
condition animals, including a decrease in appetite, digestive
disorders,
changes in activity and more. These observations, however, do not allow
to
conclude the complete safety newly created experimental vaccine and
require additional
evaluation tests. As base component for building experimental liposomal
vaccine
used the fosfatydilholin (FH).FH is a substrate for activation lipid
peroxidation. Lecithin liposomes, that are liposomal vaccine structural
and
functional components, are exposed to a variety number of physical and
chemical
factors. One of biochemical events, that happen to them, are lipid
peroxidation, accompanied by free radicals appearance in the system
and,
ultimately, causes phospholipid bi-layer membranes degradation by a
violation
of their permeability and lysis. In this regard, system safety control
and
liposomal drug efficacy should include the definition the content lipid
peroxidation products. Conclusion.Thus, experimental samples influenza
liposomal vaccine (without modification and with its for liposomal and
antigenic components) haven`t found increased levels primary products
lipid
peroxidation – lipid hydro peroxides and protein oxidation products –
carbonyl
protein and haven`t significant effects inhibition anti-oxidant enzymes
in
rat`s serum.More results the study stage the safety most effective
vaccine
samples will be present in the text.
Keywords:
influenza, liposomal vaccine, safety, adjuvants
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58-64
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ÎÐÃÀͲÇÀÖ²ß
ÄÎÑÒÓÏÍÎÑÒ² ÎÁ²ÃÓ ÀÍÒÈIJÀÁÅÒÈ×ÍÈÕ Ë²ÊÀÐÑÜÊÈÕ
ÇÀÑÎÁ²Â ÍÀ ÇÀÑÀÄÀÕ ÔÀÐÌÀÖÅÂÒÈ×ÍÎÃÎ ÏÐÀÂÀ  ÓÊÐÀ¯Í²
Çáðîæåê Ñ.²., Øàïîâàëîâà Â.Î.,
Øàïîâàëîâ Â.Â.
ORGANIZATION OF AVAILABILITY OF THE CIRCULATION OF
ANTIDIABETIC
MEDICINES BASED ON PHARMACEUTICAL LAW IN UKRAINE
Zbrozhek S.I., Shapovalova V.A., Shapovalov V.V.
Introduction. In recent
years as the global problem of healthcare in many countries acts
diabetes,
number of patients with this disease is growing and is already 4-6% of
the
population in developed countries. These indicators enable WHO experts
include
diabetes to one of the four priority non-infectious diseases and
non-infectious
epidemic of the 21st century. Because of chronic disease of diabetes
decreases
the quality of life of citizens, develops related diseases such as
stroke,
heart attack, blindness, kidney failure, amputation of the lower
extremities
causing deaths. Therefore, programs to combat diabetes and its
prevention is a
priority for national healthcare systems without exception countries.
Materials
and methods. Circulation of the registered antidiabetic medicines in
Ukraine
during pricing and delivery (example); forensic and pharmaceutical
practice of
the complaints and appeals on the availability for them of the
antidiabetic
medicines; pricing characteristics of the antidiabetic medicines over
the
period of 2012–2015. Methods: normative and legal, documentary,
bibliographic,
statistical, comparative, forensic and pharmaceutical, graphical
analysis.
Results and discussion. The study of organization of circulation of the
antidiabetic medicines requires a systematic approach from the
organizational,
legal and forensic and pharmaceutical research. Today in Ukraine the
arsenal of
drugs for the treatment of diabetes presented with more than 85
registered
antidiabetic drugs for trade names, of which 60% – insulin, and the
remaining
40% – oral hypoglycemic drugs offered in a 210 release forms. Given
forensic
and pharmaceutical example shows that the barrier, which reduces the
availability of antidiabetic medicines for diabetics at discounted
prescription
is mandatory registration of wholesale prices, because that price
mechanism of
registration by the Ministry of Healthcare of Ukraine interferes with
the right
of privileged contingent of citizens to timely access to vital
antidiabetic
drugs in full and the required range. It was also studied the
availability of
treatment antidiabetic medicines by pharmacoeconomic, forensic and
pharmaceutical indicators and found the changes to the average price of
antidiabetic drugs for the period from 2012 to 2015 according to
changes of the
US dollar exchange course, which reduced the availability of
antidiabetic drugs
for patients with diabetes. In difficult conditions, healthcare
financing of
urgent issues needs to achieve effective supplement of antidiabetic
drugs with
optimal use of funds. At the national and regional levels consistently
implemented organizational and legal measures to improve the
availability of
antidiabetic drugs in the healthcare system for patients with diabetes:
the
development of a system of recovery of insulin; pharmaceutical needs
for
support from the targeted expenditure of regional budgets; targeted
distribution of expenditures among local budgets of administrative
units;
control over pricing for antidiabetic drugs; optimization of
implementation of
the statement of the Cabinet of Ministers of Ukraine ¹ 73 "Questions of
the realization of the pilot project concerning the introduction of
state
regulation of prices for insulin" by drafting the amendments thereto.
Conclusions. Our studies indicate the need for in-depth reform of the
healthcare system by providing subsidies from the state budget of
Ukraine, the
increase the accessibility of antidiabetic medicines for diabetics.
Keywords:
pharmaceutical law, forensic pharmacy, circulation, pharmacies,
antidiabetic
medicines.
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65-71
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ÒÅÎÐÅÒÈ×ÅÑÊÈÅ È
ÏÐÀÊÒÈ×ÅÑÊÈÅ ÀÑÏÅÊÒÛ ÏÎËÓ×ÅÍÈß
ÐÅÊÎÌÁÈÍÀÍÒÍÛÕ ÀÍÒÈÃÅÍÎÂ ÄËß ÄÈÀÃÍÎÑÒÈÊÈ ËÅÉÊÎÇÀ ÊÐÓÏÍÎÃÎ ÐÎÃÀÒÎÃÎ ÑÊÎÒÀ
Øàïîâàëîâà Î.Â.
THE
THEORETICAL AND PRACTICAL ASPECTS OF THE RECOMBINANT ANTIGENS FOR
THE DIAGNOSIS OF BOVINE LEUKEMIA PRODUCTION
Shapovalova O.V.
Introduction.
Nowadays the problem of bovine leukemia (EBL) effective diagnosis in
countries
where EBL is registered and the disease-free areas remains actual. The
main
diagnostic tests are immunodiffusion reaction (AGID) and enzyme-linked
immunosorbent
assay (ELISA), which allow the identification of infected animals by
the
presence of antibodies to bovine leukemia virus (BLV)
both in serum and in milk samples. The
effectiveness of these methods depends on the quality of diagnostic
test systems
used and determines by the cultural and recombinant virus antigens
specificity.
EBL recombinant antigens have certain advantages as they are more
active and
cheap. Purpose of the work. The analysis of theoretical and practical
approaches in the bovine leukemia virus recombinant antigens
development and
its diagnostic potential evaluation. The article contains data from the
literature on the recombinant antigens of bovine leukemia virus
construction
and use. Analysis of the literature showed that the recombinant
proteins are
widely used in the serological diagnosis of bovine leukemia. Numerous
protocols
of BLV gp51 and p24 immunodominant antigens preparation has been developed in heterologous systems
(Saccharomyces cerevisiae, E. coli, vaccinia virus, baculovirus). In
order to
obtain recombinant antigens, the BLV provirus genome regions isolated
from
FLK-BLV cell culture, lymphocytes or tumor cells from naturally
infected cattle
are typically used. For the recombinant antigens labeled by
hexahistidine or Srept
II purification one-step immobilized-metal affinity chromatography IMAC
and
highly selective Strep-Tactin affinity chromatography methods are
carried out.
The end products activity and specificity are studied in the
immunoblotting,
ELISA and AGID diagnostic reactions. The
ukrainian scientists’ publications are devoted to the
clone E. coli HB101-2 transformed by the
recombinant plasmid containing fully functional BLV env and gag genes
nucleotide sequence construction. The efficiency of BLV gp51 and p24
encoding
regions fusion-sequence integration was confirmed by
the screening with the specially designed
oligonucleotides. The recombinant antigen expression was induced by
addition of
IPTG. To isolate the antigen bacterial mass was destroyed by
defrostation and
ultrasonic disintegration in the experimentally selected modes. The
activity
and specificity of the antigen was determined by AGID with the use of
the
bovine fetal serum, positive and negative
reference diagnostic serum by
unified method in comparison with the standardized
cultural BLV antigen
in AGID. The antigen specificity was
increased by adsorption with commercial anticolibacillosis serum. The
antigen
activity was confirmed by AGID. Conclusions. Nowadays the most
promising BLV
antigens expressing genetic constructions with E. coli and baculovirus.
E. coli
recombinant strains are the most
available and effective using expressing system, which allows to get an
active
and specific antigenic product if an
optimal vector constructions and commercially available systems of
metal
affinity chromatography purification and control with
appropriate Mab are used. As an
cultural and recombinant antigens
alternative the mimicking critical BLV antigenic epitopes synthetic
peptides
were tested. In recent times many
scientific works formed the basis for the bovine leukemia diagnostic
test
systems’ creation, which are now widely available on the
biotechnological
products market. Although the majority of manufacturers prefer the
recombinant
antigens of the pathogen, pilot studies on more improved and cheaper
ways to
obtain different diagnostic antigens preparations shall not lose
relevance.
Keywords: bovine
leukemia virus, bovine leukemia, recombinant antigens, diagnosis.
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72-78
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ÎÑÎÁËÈÂÎÑÒ²
ÐÎÇÏÎIJËÓ HLA Ó ÕÂÎÐÈÕ ÍÀ ϲªËÎÍÅÔÐÈÒ
Ãàéñåíþê Ô.Ç., Äð³ÿíñüêà Â.ª., Êðóãë³êîâ Â.Ò.
PECULIARITIES OF HLA-PHENOTYPES IN PATIENTS WITH
PYELONEPHRITIS
Haiseniuk F., Driyanska V., Kruglikov V.
Introduction. Of
great interest are the studies on the role of human leucocyte antigens
(HLA) in
pathogenesis of a disease. The kidneys is vulnerable to injury in the
context
of inflammatory responses, with the potential involvement of a number
of
different inflammatory processes. There are shown the associative links
of the
HLA antigens which stipulate the relative and attributive risks of some
autoimmune diseases, with immune disorder and high production of
pro-inflammatory cytokines, that confirms their important role in
immunopathogenesis. The aim was to determine the value of some HLA in
the
development of such important desease as pyelo- and glomerulonephritis.
Material
and Methods. The distribution of HLA-A, B, DR antigens in 364 patients
with
kidney diseases (120 – pyelonephritis and 244 - glomerulonephritis) was
analyzed. HLA antigens were defined using a standard
microlymphocytotoxic test
on the Terasaki´s planchette with special panels of anti-HLA serums
(20 antigens of locus A, 31 – B and 9 – DR). The control group
consisted of 350
healthy donors – students from Kiev. The HLA antigen frequencies in
normal and
deseased subjects were compared taking each antigen separately, using χ2 test. The
etiologic fraction (attributive risk more
0.1) was counted using the formula: = (x -
y)/(I- y), where x is frequency of antigen in patients and y –
frequency in
healthy. The reading was
considered reliable when it exceeded 0.1. Results and discussion. It is
advisable to associate PN are À10, À11, Â14, Â16 è Â17 (RR > 2); the causal role (σ > 0.1) was determined for À10, À11, Â14, Â16;
antigens-protectors - À2, Â21, Â35, Â40. Associated
with CGN, NS (RR > 2) are with antigens HLA- A23, 24, 28; B8, 38, 44
in
patients; the causal role (σ > 0.1) was
determined for A24, 28; B8; antigens-protectors – B12, B16. The
analysis of the
associative features of HLA-phenotype and identified pathogens in
patients with
PN is carried out. HLA-À2 ³ Â35 as protectors of PN associate with
smaller frequency of presence the E. Cîli in urine of patients. Conclusion. The article
analyzes the peculiarities of HLA-phenotypes in patients with pyelo-
and
glomerulonephritis, which allowed to establish a correlation between
certain
genes of histocompatibility complex and susceptibility to develop some
diseases
of the kidneys in humans. The HLA-phenotype analysis and infection
activators
for PN allows to take into account the additional prognostic markers
not only
of disease but also of its course, that provokes more individualized
approach
to the therapy of patients.
Key words: HLA-phenotype, pyelonephritis,
glomerulonephritis, E Coli
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79-83
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ÀÍÒÈÌÈÊÐÎÁÍÀß
ÀÊÒÈÂÍÎÑÒÜ ÑÓÁÑÒÀÍÖÈÉ, ÏÎËÓ×ÅÍÍÛÕ ÈÇ
ÑÛÐÜß ÐÀÑÒÅÍÈÉ ÑÅÌÅÉÑÒÂÀ ÁÅÐÅÇÎÂÛÅ
Ôåä÷åíêîâà Þ.À., Ñàâèíîâà Å.Ì.
ANTIMICROBIAL ACTIVITY OF THE SUBSTANCES RECEIVED FROM
RAW MATERIALS OF
BIRCH FAMILY PLANTS
Fedchenkova Yu.A., Savinova E.M.
Introduction. In
accordance with the last events in Ukraine (considering military
operations in
anti-terrorist operation in the Luhansk and Donetsk regions) the
domestic
medicine is in great need in preparations with antimicrobial activity.
Our
attention as the sources of receiving biologically active substances
with
antimicrobial activity was drawn with birch Betulaceae family plants –
hazel
ordinary Corylus avellana L. and black alder Alnus glutinosa (L.)
Gaertn. It is
known that in medicine the leaves of hazel ordinary are used as
antiseptic,
anti-inflammatory, vesselrestorative drug, and the leaves of black
alder reveal
the antiinflammatory, astringent, wound healing, spasmolytic and
choleretic
action. However, the drugs with antimicrobial action received from the
leaves
of these plants are absent on the market of Ukraine. Therefore the
studying of
antimicrobial activity of this type of raw materials received from
hazel
ordinary and black alder, for creation of new medicines, is now one of
the main
directions in pharmacy. For this purpose we have revealed tinctures,
spirit,
lipophilic and polysacharid fractions received from the leaves of hazel
ordinary and black alder. The purpose of our research is studying of
antimicrobial activity of revealed substance received from the leaves
of black
alder and hazel ordinary. Materials and methods. There were being
examined
tinctures, lipophilic, spirit and polysacharid fractions received from
the
leaves of hazel ordinary and black alder. The test of antimicrobial
effect of
substances was carried out by means of serial dilution concerning the
following
six reference cultures: Staphylococcus aureus ATCC 6538-P, Candida
albicans
ATCC 885-653, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6833,
Bacillus cereus ATCC 10702, Pseudomonas aeruginosa ATCC 9027, according
to the
State Pharmacopoeia of Ukraine, in the Department of Microbiology and
Immunology of KMAPE. For the experiment there was prepared tenfold
dilution of
extracts on meat-peptone broth 1:10 and 1:100 to which there were added
the
referential cultures which are grown up on appropriate differential
diagnostic
medium depending on a type of cultures. The crops were incubated in the
thermostat at t - 35-37 °C within 24-48 hours. For identification of
test-strain growth of E. coli there was used Endo medium, for S. aureus
–
Chistovich medium, for B. subtilis and B. cereus - meat-peptone agar,
for P. àeruginosa - 5% blood agar and for C. albicans – Saburo
medium. As the solutions remained muddy after incubation, for the
assessment of
antimicrobial action of the received fractions, there were being made
the
cloning on differential and diagnostic mediums. Results and discussion.
Data of
the conducted researches of antimicrobial activity of various
substances of
hazel ordinary and black alder leaves – tinctures, lipophilic, spirit
and
polysacharide fractions are given in the table. The obtained data
demonstrate
that lipophilic fractions of hazel ordinary and black alder leaves
possessed
the bactericidal activity when it was diluted in the ratio of 1:10 and
1:100
concerning P. àeruginosa and E. coli. These fractions also have
antimycotic activity concerning C. albicans. Concerning E. ñoli it is revealed that the spirit fractions from
black alder leaves had the bactericidal activity, and concerning P. àeruginosa and C. albicans – all studied spirit
fractions possessed. Among polysacharide fractions the antimicrobial
activity
is revealed only for this substance of hazel ordinary leaves in both
dilutions
concerning E. coli, S. aureus, P. aeruginosa. As concerning B. subtilis
and B. cereus,
bacteria of these strains were resistant to all studied fractions.
Conclusions.
Antimicrobial activity of a number of substances of hazel ordinary and
black
alder leaves is studied. As a result of the conducted researches it is
established that lipophilic and spirit fractions of hazel ordinary and
black
alder leaves, tinctures from these types of raw materials revealed
antimicrobial activity concerning P. àeruginosa,
C. àlbicans, lipophilic fraction of hazel ordinary leaves,
spirit fraction and tincture of black alder leaves– also concerning E.
coli.
The polysacharide fraction of black alder leaves doesn't possess
antimicrobial
action, and the polysacharide fraction of hazel ordinary leaves has
shown the
activity only concerning E. coli, S. àureus and P.
àeruginosa.
Keywords: antimicrobial
activity, leaf, alder, hazel, substance.
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84-87
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ÂÈÂ×ÅÍÍß Ê²ÍÅÒÈÊÈ
ÓÒÂÎÐÅÍÍß ÃÐÀÍÓË ÖÅÎ˲ÒÓ ÏÐÈÐÎÄÍÎÃÎ
ÏÐÈ Ð²ÇÍÈÕ ÑÏÎÑÎÁÀÕ ÃÐÀÍÓËÞÂÀÍÍß
Ðèáà÷óê Â.Ä.
THE
STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT
WAYS OF GRANULATION
Rybachuk V.D.
Introduction.
Active substances and excipients used in the manufacture of medicines
in tablet
form, in most cases, have poor technological properties. This fact
determines
the need for prior granulation of mass before compression. Granulators
of
various sizes and designs, running on different modes, made the
formation,
growth and consolidation of the powder particles that lead to obtain
pellets of
different shapes and sizes. From the literature it is known that
granulation
leads to two forms of granules: isodiametric and nonisodiametric. The
first
group of particles forms has globular shape with a smooth surface and
the
proportion in which the length, thickness and height are about the
same. They
are usually made by fluidized bed granulation, spray drying,
pelletizing and
granulation in dragee pan. Granules of nonisodiametric form in which
length is
several times the width and height are made mostly by extrusion and
compacting.
The geometrical parameters of obtained granules are affected by the
properties
of raw materials, the granulation modes, type and amount of added
humidifier
and so on. The shape and size of granules, from a technological point
of view,
are the key factors that contribute, except organoleptic
characteristics of the
product, its technological properties such as particle size
distribution, bulk
volume, the ability of the material to shrinkage, porosity, fluidity,
mechanical strength and so on. Properly selected for specific
conditions
granulation method is able to provide the finished product with the
specified
technological parameters depending on the needs. The aim of this work
was to
study the effect of granulation method and its conditions on the
kinetics of
growth of the natural zeolite granules and some quality characteristics
of
obtained granules. Material & methods. As objects of study served
the
natural zeolite pellets produced using 3%, 5%, 7% and 10% potato starch
paste
and solution of polyvinylpyrrolidone (PVP). Natural zeolite granules
were
prepared by wet granulation using a laboratory rotary granulator NG-12,
laboratory extruder, laboratory high-speed mixer-granulator and
laboratory
dragee pan NSD A-0.25. Microstructure and form of granules were
established by
electron microscope REM-106. Fractional composition and average grain
size was
determined using a standard set of sieves with the diameter of the
holes 2.0;
1.0; 0.5 and 0.25 mm. Porosity determined on the basis of tapped
density and
the real density, which were defined on the device Pharma Test PTF
PT-TD200,
Germany by the method. Form factor calculated as the ratio of the share
of
grains in its width. The hardness of the granules was assessed by their
ability
to withstand compression. Results & discussion. The resulting
granules have
heterogeneous porous surface. Granules obtained using rotary granulator
and
extruder have elongated form of particles with form factor 1,6-1,7 and
2,5-2,8
respectively. Granules obtained in high speed mixer-granulator and
dragee pan
have nearly round shape with form factor 1.1-1.2. The size of the
granules is
affected by the concentration of the humidifier and the way of
granulation. The
increasing of concentrations of potato starch paste from 3% to 10%,
lead to an
increase of the average size of granules according to the method in
average 3-5
times, the last was proved by the increase of fractions with a larger
particle
size. The largest average size of granules was obtained in the
laboratory
dragee pan, and the smallest - in the high-speed mixer-granulator. When
using
PVP solution of different concentrations the average grain size varied
depending on the method of granulation within 120-1464 µm. The highest
binding
capacity showed PVP solutions, as evidenced by higher values of grain
size at
the same concentrations of humidifiers. Increased concentrations of
both
humidifiers more than 10% is inappropriate, because results in large
particle
size of granules. Study of influence of quantities of added humidifier
on grain
size showed that the granulation process is absent in mixtures
containing
humidifying substance in quantities of 15-20%. The best concentration
of
humidifier should be 25-30%, which give granules with an average size
of
450-1350 µm, and a further increase of its content results in a viscous
mass
that is difficult granulated and undesirable. Experimental data of
granule
porosity indicates that increasing the concentration of binders
increases
porosity within 50-70%. The influence of granulation mode on porosity
of both
substances is different. The data of hardness of granules showed that
this
parameter is in inverse proportion to their porosity. Pellets made with
using
PVP solution demonstrated greater mechanical strength compared to
granules
containing starch potato paste. Conclusion. The influence of type and
concentration of the humidifier and the method of granulation on the
kinetics
of growth of the natural zeolite granules were studied and its
influence of
these variables on the size, porosity and mechanical strength of the
pellets
were proven. The optimum concentration of potato starch paste and
solution of
polyvinylpyrrolidone as binders for granulation of natural zeolite at
level
5-10% and optimal content of humidifier in the total mass at level
25-30% were
established. The results of experimental studies used in the
development of
technology and composition of tablets
containing natural zeolite as the main active component.
Keywords: natural
zeolite, granules, granulation, porosity, hardness
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88-96
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ÂÈÂ×ÅÍÍß Á²ÎÏ˲ÂÊÎÓÒÂÎÐÅÍÍß ÅÍÒÅÐÎÊÎʲ ÔÎÒÎÌÅÒÐÈ×ÍÈÌ ÌÅÒÎÄÎÌ Ç ÌÎÄÅËÞÂÀÍÍßÌ Á²ÎÏ˲ÂÎÊ ÍÀ ÀÁ²ÎÒÈ×ÍÈÕ ÏÎÂÅÐÕÍßÕ Ç ÏÎ˲ÑÒÈÐÎËÓ
Ìèðîíåíêî Ë.Ã., Ïåðåòÿòêî Î.Ã., ßãíþê Þ.À.
STUDY OF ENTEROCOCCI BIOFILM FORMATION USING PHOTOMETRIC
METHOD WITH
BIOFILM MODELING ON ABIOTIC POLYSTYRENE SURFACES
Myronenko L.G., Peretyatko O.G., Iagniuk J.A.
Introduction.
Static photometric method is widely used to determine the ability of
biofilm
formation. The essence of this method is to measure the optical density
of the
dye, eluated with a solvent from the biofilm. The aim of the study was
to
conduct a comparative analysis of the results of determining the
enterococci
biofilm formation using photometric method with biofilm modeling in
96-well
microtiter plates and 4-section Petri dishes. Material and methods. The
study
was conducted using 61 strains of microorganisms genus Enterococcus,
taken from
the clinical material of patients with purulent-inflammatory
infections. To
perform the study of biofilm formation using 96-well microtiter plates
technique, 100 μl of TSB with 1% glucose and 10 μl of enterococci daily culture suspension with density
of 0.5 units by Mc Farland, prepared using the Densi-La-Meter II
device, were
placed in each well. The plates were incubated at 37 °C for 48 hours,
washed
three times in phosphate-buffered saline (pH 7.2-7.4) of 200 μl volume, dried at 37 °C for 15 minutes. The biofilms
were stained with crystal violet 1% aqueous solution, washed with
distilled
water. 100 μl of ethanol/isopropanol mixture (1:1) were added to
the wells. The optical density of wells content was measured with the
AIF-C-01S
reader at a wavelength of 570 nm and 620 nm. The results were analyzed
using
Stepanovic S. et al. recommendations, according to which enterococci
were
divided into strains with high, medium and low degree of biofilm
formation. To
study the enterococci ability of biofilm formation in 4-section Petri
dishes,
1.75 ml of TSB with 1% glucose and 0.25 ml of enterococci microbial
suspension
with density of 0.5 units by Mc Farland were added in each sector, 0.25
ml of
medium were added to the control sector. The dishes were incubated at
37 °C for
48 hours, washed three times in phosphate-buffered saline (pH 7.2-7.4),
dried
at room temperature for 30 minutes. The biofilms were stained with
crystal violet
1% aqueous solution. The dye eluation from the biofilm was performed
twice with
2 ml of ethanol/isopropanol mixture (1:1) for 20 minutes. The optical
density
of eluates was measured with the SF-56L spectrophotometer at a
wavelength of
590 nm. Results and discussion. Analysis of the results of the study on
enterococci ability to form biofilms with biofilm modeling in 96-well
polystyrene microplates revealed that, when using light filters with a
wavelength of 570 nm, optical density rate ranged from 0.001 to 1.256
OD570
with an average value of (0.264±0.04) OD570. It was found that the
number of
strains capable of biofilm formation amounted to (68.8 ± 5.9)% of all
strains
used in the study. Enterococci distribution by intensity of biofilm
formation
was as follows: number of strains with high degree equaled (90.4±4.5)%,
share
of strains with medium and low degree was significantly lower – each
amounted
to (4.8±3.3)% (ð<0.05). When measuring the optical density of
eluates using the AIF-C-01S reader with light filter at a wavelength of
620 nm,
it was found that the indicators ranged from 0.001 to 0.436 OD620 with
an
average value of (0.077±0.01) OD620. While analyzing the results with
consideration of the above criteria, it was found that the share of
strains
capable of biofilm formation equaled (60.7±6.3)%. The number of strains
with
high degree of biofilm formation amounted to (75.6±7.1)%, with average
and low
degree – (13.5±5.6)% and (10.9±5.1)% respectively. The performed
statistical
analysis showed no significant difference between the number of strains
capable
of biofilm formation and intensity of biofilm formation when applying
light
filters with a wavelength of 570 nm and 620 nm (p>0.05). When
modeling the
enterococci biofilms in 4-section Petri dishes, it was found that the
eluates
optical density rates ranged from 0.161 OD590 to 3.294 OD590 with an
average
value of (1.387±0.14) OD590. Analysis of the results showed that the
number of
enterococci strains capable of biofilm formation equaled (62.3±6.2)%
and did
not differ significantly from the corresponding indicator in the study
with
96-well polystyrene microplates (p>0.05). Conclusion. Static
photometric
method is widely used to determine the enterococci ability of biofilm
formation
due to its convenience, high performance, and clearness. Microbial
biofilms are
mostly modeled in 96-well polystyrene microtiter plates. Our study
showed the
feasibility of also using 4-section polystyrene Petri dishes for
enterococci
biofilm modeling. It was confirmed that it is necessary to use light
filters
with a wavelength range from 570 nm to 620 nm when measuring the
optical
density of the enterococci eluates with a reader, if using the crystal
violet
dye.
Keywords:
enterococci, biofilm modeling, 96-well microplates, polystyrene Petri
dishes.
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97-101
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ÀÍÒÈÁÀÊÒÅвÀËÜͲ
ÂËÀÑÒÈÂÎÑÒ²
ÃÅÏÀÒÎÏÐÎÒÅÊÒÎв ÔÀÐÌÀÖÅÂÒÈ×Íί
ÊÎÌÏÎÇÈÖ²¯ «ËÀÂÀÔËÀÌ»
Àñëàíÿí Ì. À., Áîáðèöüêà Ë. Î., Îñîëîä÷åíêî Ò.
Ï.
ANTIBACTERIAL PROPERTIES OF PHARMACEUTICAL COMPOSITION OF
HEPATOPROTECTORS
Aslanian M. A., Bobrytska L.O. , Osolodchenko T.P.
Pathology
problemof hepatobiliary system (HBS) of contagious origin becomes
relevant with
the increase of disturbance and complications of lipid metabolism and
bile
pigments among young people. Leading role in prophylaxis and treatment
in the context
of this pathology belongs to antibacterialc hemotherapeutic agents.
However,
along with antimicrobial activity, numerous side effects can be
observed during
treatment with antibacterial agents. According to the recent study on
hepatobiliary system (HBS), therapeutic effect can be seen only while
using
herbal medicine with choleretic action as well as their various
compositions.Amountof medicine with the appropriate effect is
insufficient,
that is why the study was conducted towards finding effective
combinations of
plant substances of different groups for the purpose of creatingan
effective
medicine for treatment of hepatobiliary system (HBS) of contagious
origin. Aim
of the work The purpose of study was to examine antibacterial
properties of
different combinations with flamin and lavender oil in combined
medicine during
the course of treatment of cholecystitis and cholangitis. Materials and
methods. It the result of study 61 microbial strains were distinguished
and
identified from the pathological material taken from 53 patients with
cholecystitis and cholangitis. All distinguished clinical microbial
strains
taken from the patients were tested for sensitivity to combined
medicine in the
form of tablets with flamin and lavender oil.
Minimal inhibitory concentration for S.
aureus ÀÒÑÑ 25923 amounted to 250-350 ug/ml, for E.
coli ÀÒÑÑ 25922 - 350±50,0 ug/ml, for P. aeruginosa ÀÒÑÑ 27853 750±100,0 ug/ml, for Ð. vulgaris ÀÒÑÑ 4636 - 850±100,0 ug/ml, minimal inhibitory concentration to the
tablets ¹ 2 òà ¹ 3 amounted to > 1000 ìêã/ìë. Minimal inhibitory concentration for B. subtilis ÀÒÑÑ 6633 amounted to 250±50,0 ug/ml, for C. albicans ATCC 885/653
300±50,0 ug/ml. Compared to the tablets No. 2 and No. 3,
where minimal
inhibitory concentration was higher and amounted to 350-550 ug/ml.
Results and
discussion. Minimal inhibitory concentration for S.
aureus amounted to 250-300 ug/ml, for S.
epidermidis 150-250 ug/ml, for S. agalactiae and E. faecalis
300-400 ug/ml, for E.
coli, K. pneumonia, E. cloaceae – 400-750 ug/ml. Minimal
inhibitory concentration for anaerobic bacteriae (P.
niger,
P. anaerobius,
Fusobacterium
spp, B. fragilis) -300-550 ug/ml , minimal inhibitory
concentration to
the tablets ¹ 2 òà ¹ 3 amounted to
450-650ug/ml. Minimal inhibitory concentration for C. albicans
300-400 ug/ml. Compared to the tablets No. 2 and No. 3,
where minimal
inhibitory concentration was higher and amounted to 450-600 ug/ml. To
sum up
the results of the conducted experimental studies of combined capsules
with
flamin and lavender oil we can make a conclusion that the most
effective
against the different clinical microorganism andfungi strains is a
combination
of flamin 0.05 g, 0.02 g lavender oil (tablets No. 1), which makes it
possible
to preparecombined medicine for pathologies of
hepatobiliary system (HBS). Conclusions. To sum up the
results of
experimental studies of combined capsules which consist of flamin and
lavender
oil we can make a conclusion that the most effective remedy for
different
clinical microorganism and fungi strains is a combination of flamin
0.05 g,
0.02 g lavender oil (tablets No. 1), which gives the opportunity to
prepare
combined medicine for pathologies of
hepatobiliary system (HBS).
Keywords: antibacterial
properties, hepatoprotektors, lavender
oil, flamin, tablets
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102-106
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ÂÒÎÐÈÍÍÀ ËÀÊÒÀÇÍÀ
ÍÅÄÎÑÒÀÒͲÑÒÜ ÒÀ ¯¯ ÊÎÐÅÊÖ²ß Ó Ä²ÒÅÉ
ÐÀÍÍÜÎÃΠ²ÊÓ, ÕÂÎÐÈÕ ÍÀ ÐÎÒÀ²ÐÓÑÍÓ ²ÍÔÅÊÖ²Þ
ʳðñàíîâà Ò.Î., Êóçíºöîâ Ñ.Â.
SECONDARY LACTASE DEFICIENCY AND ITS CORRECTION IN
INFANTS ILL WITH
ROTAVIRUS INFECTION
Kirsanova T.A., Kuznetsov S.V.
Introduction.
Cardinal changes in medicine during recent years have made the problem
of
disorders in digestion and carbohydrate absorption one of the most
crucial.
Lactose intolerance (lactase deficiency) is a clinically revealed
inability of
intestinal enzymatic systems to break down lactose, where secondary
lactose
deficiency results from damage of erythrocytes against a background of
some
disease, including that of an infectious origin, particularly in viral
intestinal
infections. Purpose of the study. To study the efficacy of taking
lactase
preparations by infants during the first year of their life, who are
breast fed
and ill with rotavirus infection. Materials and methods. The study
involved 28
naturally fed infants of the first year of life with rotavirus
infection. The
diagnosis was made by revealing the virus antigen in the patients’
faeces and
antibodies to it in their blood. Besides the standard methods of
examination
the faeces were analysed for carbohydrates and pH values. The patients
were
divided into two groups: the first group of infants did not receive
lactase-containing drugs in their combined therapy; the second group
took them.
Results. Damage of the gastrointestinal tract of the retrovirus
aetiology was
characterized by the following signs: vomiting, abdominal distention,
diarrhoea
with watery frothy stool having sour odour and undigested boluses. In
the group
of infants, whose combined therapy used lactase-containing drugs,
regression of
their clinical signs passed reliably more rapidly than in the group of
infants,
who did not receive the above medicines. Conclusion. The use of
lactase-containing preparations in the treatment of infants, who are
breast fed
and ill with rotavirus infection, is undoubtedly effective in order to
correct
lactase deficiency, since it causes a more rapid disappearance of
clinical
manifestations of the disease, thereby making it possible to examine
the
possible inclusion of these drugs into the scheme of combined therapy
for the
above category of infants.
Keywords: lactase
deficiency, infants, rotavirus infection, treatment.
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107-111
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ÈÇÓ×ÅÍÈÅ
ÀÍÒÈÌÈÊÐÎÁÍÎÃÎ ÄÅÉÑÒÂÈß ÊÎÌÁÈÍÈÐÎÂÀÍÍÎÉ
ËÅÊÀÐÑÒÂÅÍÍÎÉ ÊÎÌÏÎÇÈÖÈÈ ÄËß ËÅ×ÅÍÈß ÊÈØÅ×ÍÛÕ ÈÍÔÅÊÖÈÉ
Ôàðåñ Ð., Áîáðèöêàÿ Ë. À., Îñîëîä÷åíêî Ò. Ï., Ãðèöåíêî
Â. È.
STUDY OF ANTIMICROBIAL ACTION OF COMBINED DOSAGE FORM FOR
THE TREATMENT
OF INTESTINAL INFECTIONS
Fares R., Bobritskaya L.A., Osolodchenko T.P., Grytsenko V.I.
Intestinal
infection (II) of various etiologies is among to the most widespread
diseases
in the world. The treatment regimen bacterial etiology involves the
suppression
of pathogenic and conditionally pathogenic with the restoration of the
normal
intestinal microflora. For effective antibiotic pharmacotherapy of
intestinal
infections are widely used drug combinations with the additionof
nifuroxazide,
as well as enzymatic and normalizing bowel motility broad-spectrum
drugs.
Intestinal antiseptics nifuroxazide characterized by broad spectrum of
antibacterial action against Staphylococcus spp, Clostridium spp, E.
coli,
Salmonella spp, Shigellaspp, Proteus spp, Klebsiellaspp, Enterobacter
spp, V.
cholerae, H. pylori, Yersinia spp, and also the lack of effect on the
normal
intestinal flora, high safety profile. Recently, for the treatment of
intestinal infections nifuroxazide often combined with pre- and
probiotics for
complex correction of the intestinal microflora disorders. For complex
therapy
of intestinal infections, we have developed an original combined
medicine
"Diaplant", in the form of capsules, comprising as active ingredients
nifuroxazide (200 mg) in combination with plant substance plantaglucide
(200
mg). Plantaglucide drug obtained from Plantago major has spasmolytic,
antimicrobial and anti-inflammatory activity, normalizes bowel
peristalsis,
while reducing the tone of smooth muscles of the stomach and
intestines,
reduces swelling folds of the gastric mucosa, and contained therein
polysaccharides in the form of pectins have properties of prebiotic and
have
immunostimulatory effects. Aim of the
work – study of antibacterial action of combined drug "Diaplant"
containing nifuroxazide and plantaglucide in regard to test strains and
clinical strains of microorganisms allocated from patients with
bacterial
diarrhea. Materials and methods.
Estimation of antimicrobial activity was performed under conditions in
vitro by
method of serial dilutions. The object of research is a combined drug "
Diaplant ", a reference drug"Enterofuril" manufacture
of ("Bosnalijek" Bosnia and Herzegovina).
For the evaluation of drugs samples activity
used the following test strains: Staphylococcus aureus ATCC 25923,
Escherichia
coli ATCC 25922, Basillus subtilis ATCC 6633, Proteus vulgaris ATCC
4636, Pseudomonas
aeruginosa ÀÒÑÑ 27853, Candida albicans ATCC 885/653. Clinical
material comes from the Center of medical and environmental research to
the
bacteriological laboratory. Was allocated and identified 109 strains of
conditionally pathogenic microorganisms.
Results and its discussion. For clinical and test strains
S. aureus MIC
indicators for combined drug «Diaplant" were 15.0 mg / l, whereas the
reference drug "Enterofuril" MIC equaled 30.0 mg / l. For E. coli -
MIC indicators for combined drug «Diaplant" was 7.5 mg / l, for an
"Enterofurila" - 15.0 - 30 mg \ l. MIC for combined drug
"Diaplant" against different clinical strains of Enterobacteriaceae
species ranged from 15.0 mg / l to 30.0 mg / l in comparison with
"Enterofurilom", where the MIC was 30mg / l - 60mg / l. For yeasts
and clinical strains C.albicans MIC combination drug "Diaplant"
product is 15.0 mg / l, whereas equal to 30.0 mg / l for the control
drug
"Enterofuril" MIC. For test strains, such as P. aeruginosa ATCC
27853, P. vulgaris ATCC 4636, MIC "Diaplant" drug was 100.0 mg / l,
whereas control drug "Enterofuril" MIC
was above > 100.0 mg / l. For clinical strains of P. mirabilis and
P.
vulgaris MIC "Diaplant" was 30.0 mg / l, whereas the MIC
"Enterofuril" equal to 60.0 mg / l. For clinical P.
aeruginosa strains MIC "Diaplant" was 100.0 mg / l, whereas control
drug
"Enterofuril" MIC was above > 100.0 mg / l. It has been
established that 80-95% of clinical microbial strains showed
sensitivity to
combined preparation "Diaplant". The highest index of sensitivity has
next strains: S. aureus - 92,8% of strains, S. epidermidis - 100% of
the
strains, E. coli (lactose-negative) - 100% of the strains, K.
pneumoniae, and
K. mobilis 85-87% of the strains. Conclusions. 1. As a result of the
conducted
research was found, that the combined drug "Diaplant", containing as
active ingredients nifuroxazide in combination with herbal substances
plantaglucide, has a pronounced antibacterial activity against the
reference
strains and clinical strains of microorganisms, the main pathogens of
bacterial
diarrhea. 2. Plantaglucide substance
which is part of the capsules is enhances the antimicrobial effect
nifuroxazide
at the expense of its own antibacterial properties of phenolic
compounds,
polysaccharides and their possible synergies.
Keywords:
intestinal infection, nifuroxazide, plantaglucide, capsules.
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112-116
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ÂËÈßÍÈÅ
ÊÎÌÏËÅÊÑÍÎÉ ÒÅÐÀÏÈÈ Ñ ÈÑÏÎËÜÇÎÂÀÍÈÅÌ
ÈÌÌÓÍÎÌÎÄÓËßÒÎÐΠÍÀ ÑÎÑÒÎßÍÈÅ ÌÅÑÒÍÎÃÎ ÈÌÌÓÍÈÒÅÒÀ ÁÎËÜÍÛÕ ÕÐÎÍÈ×ÅÑÊÈÌ
ÃÅÍÅÐÀËÈÇÎÂÀÍÍÛÌ ÏÀÐÎÄÎÍÒÈÒÎÌ ²-²² ÑÒÅÏÅÍÈ ÒßÆÅÑÒÈ Ñ ÝÍÒÅÐÎÁÈÎÇÎÌ
Ñàâåëüåâà
Í.Í.
STUDY OF THE INFLUENCE OF COMPLEX TREATMENT USING
IMMUNOMODULATORS ON
THE STATE OF LOCAL IMMUNITY IN PATIENTS WITH CHRONIC GENERALIZED
PERIODONTITIS
I-II SEVERITY ON ENTEROBIASIS
Savel’eva N. N.
Introduction. Due
to the high prevalence of chronic generalized periodontitis there is a
need for
a broader analysis of the causes and development of diseases, as well
as the
search for effective treatments for etiopathogenetical. The aim of this
work
was to study the effect of newly developed therapy on local immunity in
patients CGP I and II severity with enterobiasis. Material &
methods. The
main group consisted of 32 people with ÑGP I degree and 60 people with
ÑGP II
severity who were treated according to our scheme. The control group
consisted
of 30 people with ÑGP I degree and 58 people with ÑGP II severity,
treated with
conventional treatment. The control group consisted of 30 people
without
periodontal disease and chronic diseases of other systems. All patients
were
studied the main group and the comparison group conducted a basic local
therapeutic
treatment of periodontal disease, including professional oral hygiene,
temporary splinting of teeth, selective prishlifovyvanie teeth. For
medical
treatment of periodontal tissues using 0.05% - 0.2% solution of
chlorhexidine
bigluconate. Further treatment of patients of the main group carried
out in 2
stages. At the first stage the main group received: irrigation and
instillation
of periodontal tissue in periodontal pockets antiseptic preparation
"Dekasan" application keratoplastic drug "Katomas". Systemically
administered drug tonic "Sage oil" probiotic "Kvertulin"
immunomodulator "Erbisol". In the second phase, patients received:
applications on the gums periodontal gel "Lizomukoid" systemically
complex preparation "Îil extract from pumpkin seeds." All patients of
the main group used toothpaste "Lacalut flora" and rinse
"grapefruit". In the
comparison group, patients received applications in periodontal pockets
(drug
Dalatsin C) application to the gums (keratoplastic drug Aekol) system -
a
probiotic Linex, immunomodulator "Echinacea compositum Ñ". All
patients with the comparison group used toothpaste and rinse "Forest
Balsam" for the duration of treatment and 1 month after the end of
therapy. The effect of the proposed and conventional therapy on local
immunity
judged on the content of lysozyme, sIgA, mIgA, IgG, total protein,
extracellular peroxidase activity and bactericidal oral secretions.
Statistical
processing of materials made using mathematical statistical methods for
data
analysis. Results & discussion. Under the influence of the proposed
therapy
in patients of the group increases the activity of local immunity
factors and
attenuates the inflammatory process in the periodontium. On the 1st day
of the
end of therapy in this group of patients significantly increases the
content of
lysozyme in the oral secretions and sIgA to normal values, with
elevated levels
of IgG and mIgA, which differed before treatment, reduced to normal
values
(p˂0,05) and remain so the entire period of observation for 6 months.
Patients
comparison group in the application of traditional therapy of total
protein
content in the oral secretions to the 6-month observation is not
reduced to
normal, but there was a positive trend in the growth of the content of
sIgA and
lysozyme and decreased total protein levels in the oral secretions. The
level
in the oral secretions mIgA and IgG in patients with the comparison
group were
not significantly changed the whole period of study. Patients of the
main group
under the influence of the therapy took place dynamic normalization of
extracellular peroxidase activity, whereas in patients with comparison
groups
to restore the values of the rate of extracellular peroxidase activity
did not
occur. Between indicators peroxidase activity of patients of the main
group and
the comparison group, respectively, in all periods of the study were
significant differences (p˂0,05). Study of the bactericidal activity of
saliva
showed that the study group patients who received the combined
treatment
immunokorregirujushchej therapy by the end of the treatment of
bactericidal
action of saliva increased to values of norms and remained so the
entire period
of observation. In the comparison group, the bactericidal action of
saliva
significantly increased from 30 days last treatment. Conclusion It was
found
that the proposed two-stage combined therapy with the use of
immunomodulators
has a significant normalizing effect on the activity of local immunity
of
patients CGP I and II degree of severity of the disease with
enterobiasis.
Under its influence there is dynamic recovery by the end of the
treatment the
activity of lysozyme, sIgA content, Miga and bactericidal oral
secretions. It
is shown that such action does not have a common set of traditional
therapy.
These results demonstrate the high efficiency of this method of
treatment of
chronic generalized periodontitis I and II of Article severity in
patients with
enterobiasis and point to the possibility of its application in
clinical
practice.
Keywords: Dekasan,
Katomas, Lizomukoid, Lacalut flora, immunomodulators, periodontitis
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117-122
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ÌÈÊÐÎÔËÎÐÀ
ÍÀÄÃÎÐÒÀÍÍÈÊÀ Ó ÂÇÐÎÑËÛÕ ÁÎËÜÍÛÕ ÎÑÒÐÛÌ
ÝÏÈÃËÎÒÒÈÒÎÌ
Ãîëîâêî Í.À., Äàâèäåíêî Â.Ë., Íåì÷èíîâè÷ Í.Ä., Øèáàåâà
È.Á., Æèäêîâà Í.Ô.,
Ðàñïîïîâà È.Þ.
EPIGLOTTIS MICROFLORA OF ADULT PATIENTS WITH ACUTE
EPIGLOTTITIS
Golovko N.A., Davydenko V.L., Nemchinovich N.D., Shibayeva I.B., Jidkova N.F., Raspopova I.Y.
Introduction.
Nowadays acute infectious-inflammatory processes of upper respiratory
tract,
including acute epiglottitis retain a high proportion among human
pathology. In
the literature acute epiglottitis is allocated into an independent
nosology as
severe acute phlegmonous bacterial inflammation of the epiglottis and
hypopharynx. There are currently no clear guidelines on how to classify
an
acute epiglottitis, as well as protocols for patients at various stages
of the
pathological process. According to common belief, Haemophilus
influenzae type
-B (Haemophilus influenza type b (Hib)) is the most common cause of
epiglottitis.
At present, the main etiological role in the genesis of acute
epiglottitis in
children belongs to haemophilus influenzae. In adults the causes of the
disease
are beta hemolytic streptococci groups A, B, pneumococcus, Klebsiella,
Pseudomonas, Staphylococcus aureus, herpes simplex virus (type 1) and
parainfluenza, and others.The aim of this work is to study: the mucosal
microflora of the epiglottis in adult patients with acute epiglottitis
and to
study sensitivity of certain isolates to antimicrobial agents. Material
&
methods. 86 adult patients with acute epiglottitis were observed: 36
with
abscess form of epiglottitis and 50 - with infiltrative.
Microbiological
analysis of mucosal swab samples taken from hypopharynx were conducted
by the
conventional technology: for seeding solid or liquid nutrient medium,
followed
by allocation of isolith and its microscopic, biochemical and
serological
identification. Microorganisms were classified according to schemes of
Bergy.
Antimicrobial susceptibility of each strain was determined in
accordance with
the guidelines. We used discs with antibacterial drugs. The
availability of
sensitive and resistant strains of microorganisms to antibiotics was
assessed.
A mucous membrane of the epiglottis was analyzed through
microbiological
investigation in 86 patients with acute epiglottitis. As a result, 169
strains
of microorganisms were sowed from mucous membrane of epiglottis.
Results &
discussion. In patients with acute epiglottitis Streptococcus progenies
dominated in 33 (23.7%) of cases, H. influenza was detected in 27 cases
(19.4%), Streptococcus pneumonia strain was in 21 (12.4%) of cases, 4th
place
-. Staphylococcus aureus -9.3%. There are different types of:
staphylococci
strains -29, of Enterococcus spp - 11, gram-negative bacilli -41.
Noteworthy
fact is the high degree of microbial contamination of patients 107-109
CFU.
Conclusion. Acute epiglottitis highest sensitivity was observed to the
following medications as cephalosporin, namely cefotaxime while it is
variable
within the same group (1,2,3 cephalosporin’s generation). The isolated
strains
showed almost 99,4±1,2% sensitivity to fluoroquinolones, especially to
levofloxacin and others (S. aureus, S. pyogenes, S. pneumoniae, H.
Influenzae). There was a high sensitivity
to lincosamides
- clindamycin; fluoroquinolones- levofloxacin. In 50% of cases, a
resistance to
the antibiotic penicillin; and macrolide antibiotic, especially the
last
generations was observed. According to the obtained findings on the
sensitivity
of microflora to antibiotics cephalosporin’s II- III generation with
moderate
and severe degrees of severity in combination with fluoroquinolones
(all
administered parenterally) are used in acute epiglottitis. Use of
fluoroquinolones (levofloxacin, ciprofloxacin, and others) is
recommended in
case of Cephalosporin intolerance, as well as lincosamides
(clindamycin,
dalatsin, lincomycin).
Keywords: acute ep³glott³tis, m³croflora.
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123-127
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