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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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Review
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AID/APOBEC–dependent
somatic hypermutation and DNA rearrangements of immunoglobulin and
non-immunoglobulin genes
Kolotova T. Yu., Makarenko V.D., Sorokoumova L.K.,
Davidenko M. B.
Editing Ig genes by activation induced
deaminase (AID) initiates
the antibody diversification process in B lymphocytes. In mammalian B cells, this
process includes somatic hypermutation (SHM) and class switch recombination
(CSR). The activity of AID is largely
confined to switch regions and Ig variable regions but now it is well established that AID/APOBEC-dependent damage and double DNA
breaks leading to genome rearrangements and somatic mutagenesis are pervasive throughout the B cell
genome. In
this review, we focus on the molecular mechanisms that guide AID/APOBEC
mutator to physiological and non-physiological targets. Epigenetic modifications,
such as histone post-translational modifications and DNA methylation, cis-elements of DNA and the
transcription factors that bind to it, which form regulatory clusters and
superenhancers, synthesis of non-coding RNA and features of the transcription
mode are involved in targeting of AID/APOBEC deaminases to Ig and non-Ig locus.
However, not one of the studied factors is specific for the AID target loci.
Thus, to date, there is insufficient clarity on the question of what determines
the genetically programmed activity of AID in Ig loci and the genetically
unprogrammed activity of AID/APOBEC family deaminases in non-Ig loci. The study
of AID/APOBEC-dependent somatic hypermutation and rearrangements of Ig and
non-Ig locus have both fundamental biological and applied medical significance.
The fundamental significance is that the mechanisms of genetic rearrangements
in somatic cells can provide a key to understanding the patterns of
evolutionary variability of living organisms. The applied value is that based
on the data obtained on the genomic instability of non-Ig loci, methods can be
developed that suppress the instability of the genome during carcinogenesis and
slow down the formation of chemotherapy resistant variants.
Keywords: AID/APOBEC family of deaminases; DNA editing; Ig genes somatic hypermutation;
Ig class switching recombination gene; AID/APOBEC off-targets; double-stranded
DNA breaks; superenhancers; transcription factors; histone epigenetic
modifications; non-coding RNA.
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6-19
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Relationship of viral infections and multiple sclerosis. Modern trends
in the diagnosis and treatment of multiple sclerosis
Davydova T., Volyanskiy A.
Multiple sclerosis (MS) is a polyethiological disease that develops as
an interaction between the immune system and external factors in genetically
susceptible individuals. There is growing evidence that viruses can play a role
in the pathogenesis of MS, acting as external triggers. However, it is not
fully known whether a single virus is causal or several viruses can act as an
impulse to the development of the disease. We examined the association of various viruses with
MS, focusing on two herpesviruses: human herpesvirus 6 (HHV-6) and Epstein-Barr virus
(EBV). In recent years, the researchers
have indicated that these two agents had the greatest impact as possible
co-factors in the development of the disease. The most important evidence in
favor HHV-6 and EBV
association is the link between symptoms infectious mononucleosis and the
persistent chronic process caused by EBV and HHV-6 with MS, serological data
and viral load detection in MS patients. But it is know that the mononucleosis
symptoms can be caused by other members of the herpes group. HHV-6 is
significantly more likely detected in MS plaques, in contrast to EBV, in
comparison with the results studies brain tissue and non-MS patients. And it
was observed HHV-6 activation during MS relapses. Herpes viral load peripheral
blood mononuclear cells (PBMCs), primarily EBV and HHV-6, was significantly
higher in patients with MS than in the control group and was combined with
changes in some parameters cellular and humoral immunity, significantly
increasing in relapse periods of the disease. In this review, we propose new
strategies, including the development of promising directions virological and
immunological protocols MS diagnosis and treatment and formation clinical
trials tactics, to find out the roles of different viruses and autoimmune
processes in the MS pathogenesis to find a recovery algorithm for improving the
life quality and possible MS problem solution. For the large-scale clinical
studies that could confirm or refute viruses participation in the MS
pathogenesis, especially herpes, the advisability of antiviral and
immunotherapy, we offer the method of direct immunofluorescence, which has a
number of advantages: speed processing; the ability to investigate the viral
load in the affected cells in the body fluids and tissues; highly specific;
informative and economically sound. Conclusions. This review discussed the
role of infectious agents, mostly viruses, in the MS development and
pathogenesis. Despite the presence links between MS and several viruses, it has
not been proven that the virus is the cause of this neurological disease.
Recently strong evidence focuses on the herpesvirus family member, such as EBV
and HHV-6. Because these viruses are widespread among humankind, it creates
unique challenges in establishing causation with MS. The isolation of the
predicted agent from MS affected tissue, such as active plaques in the CNS;
viral load PBMCs; and increasing the humoral and cellular immune response to
these viruses in peripheral blood and liquor are strong arguments in support
these viruses as triggers in the disease process. After all, only due to
well-controlled trials of antiviral treatment causative or other pathogenetic
link between these viruses and MS can be established.
Keywords: multiple sclerosis; herpes;
Epstein-Barr virus
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20-35 |
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Experimental works
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The effects of
cryopreservation conditions on viability of escherichia and staphylococcus
genus
Peretyatko O.G., Yagnuk Y.А., Pakhomov A.V., Sklyar N.І., Krestetska
S.L., Bolshakova G.М., Cholodna T.V., Markovich I.G., Kalinichenko S.V.,
Panchenko L.A.
Maintaining the collections
of microorganisms requires the long-term conservation of strains in viable
state without changes in their biological properties. Cryopreservation is
considered as one of the most effective means of long-term storage of
microorganisms. The use of cryoprotective compounds ensures new possibilities
to protect microbial cells from cold shock and alterations at freezing
procedure. Specification of the preservation methods adapted for a specific
type of microorganisms, that would provide high viability and stability of
biological properties, is an actual task of modern microbiology. Objective. This study aimed to
investigate the effect of cooling regiments, composition of conservation
medium, and low temperature storage on the viability of different types of
microorganisms. Methods. The
study was conducted on 5 strains of E.coli and 5 strains of Staphylococcus spp.
Cryoprotective mediums comprising 1% glucose or 10 % glycerol were used for
deep freezing. Two cooling modes were used: mode 1 - direct immersion of the
samples in liquid nitrogen; mode 2 - cooling with programmable freezer from 20
to −70 ° C with a speed of 10 ° C / min, followed by a temperature stop at −70
° For 10 min and further immersion. The samples were thawed in a water bath at
a temperature of +37 ° C for 120 seconds. Viability of tested strains was
tested by the Koch method after 3 and 6 month of storage in liquid nitrogen. Statistical
analysis was performed with nonparametric methods using MX Excel 2007 and
STATISTICA 6.0 software. Results. Significant strain-specific differences in
survival rates were established. At both cooling modes adding of the glycerol
as a cryoprotectant provided significantly higher viability of bacterial cells
then adding of glucose. The average number of viable cells after freezing was
8.1 × 108CFU / ml vs 1.3 × 108CFU / ml for glycerol and glucose respectively (p
<0,05). There was no significant difference in viability of strains after
deep frozen storage for 3 and 6 month. All strains had similar viability rates
when glycerol was used as a cryoprotectant. Staphylococci were less vulnerable
to freezing stress at both cooling modes when medium with glucose was used. Conclusion. High efficiency of one step
deep freezing with 10 % glycerol as a method for preserving of Staphylococcus
and Escherichia collection strains has been demonstrated. The viability of
bacteria during cryopreservation was influenced by the composition of the
preserving medium, the cooling mode and the species and stain-specific
morpho-functional features. Glycerine was found to be the optimal
cryoprotectant at both single-stage and two-stage cooling mode. The one stage
freezing was much more preferable when a cryoprotective medium with glucose was
used. Duration of the sample storage in liquid nitrogen did not affect the
number of viable cells.
Keywords: cryopreservation;
freezing; cryopreserving formulation; staphylococci; Escherichia.
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36-41
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Justification of the gel formers selection in the development of oromucosal
drug in the form of troches
Semchenko K. V., Vyshnevska L. I.
Introduction. Troches deserve
special attention among the existing oromucosal dosage forms. They have good consumer
characteristics and an adequate level of bioavailability, which makes it
expedient to expand the range of medicines to be used in the form of troches,
especially for pediatric use. The purpose of this work is to justify the optimal
composition of troches by selecting the most rational gel-forming agent and its
concentration. Materials & methods. Gel formers gelatine (250 g/cm2, according
to Bloom), agar (800 g/cm2, according to Bloom) and apple pectin
were used as objects of the study. The ratio of the ingredients was investigated in 6
samples. Samples with
gelatine and agar were prepared as follows: the calculated amount of gelatine
or agar was poured with the calculated amount of purified water and left for
swelling. When gelatine/agar swelled, it was melted in a water bath and mixed
with concentrate of citric acid, glucose syrup, glycerol, fruit flavouring and
food colouring. Samples with apple pectin were prepared as follows: the
calculated amount of apple pectin was mixed with half the sugar and heated to
(50.0 ± 2.0) °C with water purified with vigorous stirring. After swelling, it
was mixed with concentrate of citric acid, glucose syrup, glycerol, fruit
flavouring and food colouring. The resulting mass was poured into silicone form
and placed in a refrigerator for hardening. Results & discussion. The obtained
troches were evaluated by such quality indicators as organoleptic control,
uniformity of dosage units, dissolution time. It was found that sample No. 5 shows the best consumer
characteristics, while the other samples do not meet the requirements of the
studied quality indicators. For example, sample No. 1 was not formed, the
texture remained semi-solid; samples No. 2 and No. 3 were formed, but were
opaque and easily destroyed when pressed; samples No. 4 and No. 6 contained too
much gelatine, some of which remained undissolved, resulting in deterioration
of taste characteristics (less pleasant taste, "crunch", sticking
during chewing). The critical parameters of the technological process of troches
preparation are time of gelatine swelling, temperature of gelatine melting,
time of troches hardening. Conclusion. The findings showed that samples of gelatine-based
troches with its content of 8.65 mass. % have the best consumer
characteristics. The resulting troches are homogenous, with a pleasant fruity
aroma and sweet taste. They meet the requirements of SPhU by the quality
indicators organoleptic indicators, the uniformity of the dosage units and the
dissolution time. The established critical parameters of the technological process and
their values were established.
Keywords: gel; oromucosal; troches; gel formers
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42-44
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Study of antibacterial
properties of the emulgel with Scutellaria
baicalensis extract
Slipchenko G.D., Osolodchenko
T.P., Ruban O.A.
Introduction. One of the important problems of medicine for many
years remains the search for effective treatments for infected wound processes.
Semisolids remain an indispensable dosage form in the treatment of wound
injuries, the interest in which has increased recently due to the new tend of
including phytopreparations, providing soft action and low toxicity against the
background of high efficiency, and the complex of biologically active
substances has a versatile and complementary effect. This makes it possible to
use them for a long time with a minimal number of side effects. Particular attention is paid to the properties of the
Scutellaria baicalensis among the plants. Considering the variety of compounds
and the action inherent in the raw material, we have developed an emulgel based
on the dry extract of Scutellaria root and rhizomes. The purpose of our work is
to study the antimicrobial activity of the created emulgel and to choose a
preservative. Materials and methods. For the study of microbiological purity, three samples
of emulgel with extract content of 1%, 2% and 2.5% were taken. The following test
strains were used to evaluate the activity of the drug samples: Staphylococcus
aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC
27853, Bacillus subtilis ATCC 6633, Proteus vulgaris ATCC 4636, Candida
albicans АТСС 885/653. Determination of antibacterial activity of the study
drug was carried out by the method of diffusion into agar (method of
"wells") on two layers of agarised nutrient medium on Petri dishes.
Cultivation media were used according to the type of microorganisms in
accordance with existing methodological developments and recommendations. Antimicrobial and
anticancer effects of new drugs were determined by the standard method of
two-fold serial dilutions in nutrient broth (macromethod). Microbiological
purity tests were performed by direct cropping on liquid nutrient media. The
soybean-casein broth, thioglycol medium and Sabouraud liquid medium were
sterile poured into tubes of 10.0 ml. The most common substances that are
authorized for use in pharmacy in Ukraine were used to select a preservative.
Parabens derivatives (Nipagin, Nipasol, germaben) and glycol (euxyl) were
selected for the research. Results and discussion. As a result of the study, it was found that the
samples of the emulsifier based on the dry extract of Scutellaria root (1%, 2%
and 2.5%) possess antibacterial action against the test strains. The diameters of growth retardation zones were 20-23
mm relative to Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC
6633, 18-20 mm - to Escherichia coli ATCC 25922, to Proteus
vulgaris ATCC 4636 and Pseudomonas aeruginosa ATCC 27853 - the diameter was 16
- 19 mm, relative to the fungus Candida albicans ATCC 653/885 the
zone was 16-17 mm. In comparison drug, the solution of chlorophyllin the
diameter of the growth retardation zone was smaller, and with respect to
Proteus vulgaris ATCC 4636 and Pseudomonas aeruginosa ATCC 27853 antibacterial
properties were not registered. It was also found that the samples had antibacterial
activity against clinical strains. The diameters of growth inhibition zones
were 15–20 mm relative to Pseudomonas aeruginosa 46, Proteus vulgaris
18, Staphylococcus aureus 25, Escherichia coli 7. In the study of
microbiological purity by direct sowing on the dishes it has been found that
the growth of fungi was absent in the study of all samples. The number of
microorganisms that grew on 0.1 g samples of the preparation did not exceed 10 3
CFU / ml, which meets the requirements of the State Pharmacopoeia of Ukraine. Microscopy showed
the presence of a gram-positive vegetative spore bacillus in the 2.0% emulgel
samples based on the dry extract of Scutellaria. Confirmation was obtained by
cropping on differential nutrient media. Obtained data showed that in
morphology of the colonies and some biological properties the isolated
microorganisms found in the study belong to the genus Bacillus sp. On
differential media (Chistovich medium and Endo medium) for the isolation of
intestinal group and pathogenic staphylococci the growth among other
microorganisms was not observed. The next step was to investigate the effectiveness of
the antimicrobial preservatives (Nipagin + Nipasol, germaben and euxyl). Based on the studies
and according to the literature, euxyl has been chosen as a preservative, as it
has the widest spectrum of antimicrobial activity against gram-positive and
gram-negative bacteria, yeast and fungi in the pH range of 3.0-12.0 and is a
safer and economically reasonable option. Conclusions. According to the results of the study of the
antimicrobial activity of samples of emulgel with Scutellaria baikalensis
extract, it has been found that the optimal content of dry extract in the
developed drug is 2%. The microbiological purity of the freshly made specimen was investigated
and antibacterial activity against a wide range of microorganisms of different
taxonomic groups has been proven. Studies on the preserving ability of antimicrobial
preservatives (Nipagin + Nipasol, germaben and euxyl) have established the
effectiveness of all selected substances. All samples met the requirements of
SPU (criterion "A"). As the most promising one Euxyl preservative has
been selected, which is the safest and most economically reasonable with a
wider pH range.
Keywords: antibacterial; emulgel; Scutellaria baicalensis; extract
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45-50
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Lethal activity of the museum and clinical strains of C. Difficile
Voronkina I. A., Kheder S. S., Biryukova S. V., Maryuschenko A. M., Dyachenko V. F., Panchenko L.O.
Introduction. At present С. difficile infection (CDI) is considered to be nosocomial worldwide, this problem is studied in depth and currently there are large-scale monitoring studies being carried out. There is a considerable quantity of
different tests for CDI diagnosis. These tests include the cytopathogenic test
and the toxin neutralization reaction (determination of toxin B), latex
agglutination (determination of the glutamatedehydrogenase), ELISA test
(determination of the A or B toxins, or determination of the A and B toxins
simultaneously), PCR. At the same time, it is known that the isolation of the
agents and its identification without determination of the ability of the
latter to produce toxins is insufficient, as the non-toxicogenic strains do not play any role in the human pathology. The
modern diagnostic methods present in Ukraine (PCR, ELISA, etc.) have not become
widespread in the laboratories of the state health establishments because of
their complexity and cost, moreover, they cannot provide for all aspects
required for the solution of this problem, such as the study of the properties
and variability of the agent itself. The toxins A
and B have powerful cytotoxic and pro-inflammatory properties. These toxins are
glycosyltransferase enzymes that catalyze the inactivation of Rho proteins
responsible for actin cytoskeleton organization and epithelial barrier function. The destruction of the epithelial cells leads to the disruption of the water-electrolyte exchange, which facilitates the
secretion of the fluid into the intestinal space. The modern studies confirm
the important role of both toxins A and B, and the distribution of the clinical
symptoms beyond the intestine to other organs (heart, kidneys, brain), which points to the presence
of the systemic toxemia and plays the main role in the prognosis of the CDI
development. In the laboratory of the anaerobic infections of the SI “IMI NAMS” in the 2017-2019
years, studies devoted to the identification and study of the circulating
clinical C. difficile strains were carried out. Aim of the study. To verify the toxin-producing properties of the clinical and museum strains of C. difficile in different nutrient media. Materials&methods. The toxin producing properties were verified in 7 isolated clinical strains and 2 museum strains (C. difficile №258, №281 А), obtained from the L. V. Tarasevich SISK in 1988. In order to isolate the toxin, the microorganisms
were cultivated on the liver and heart-brain broth (HBB) in anaerobic conditions.
After 72 hours of cultivation, bacterial cells were isolated with the help of
centrifugation for 30 minutes at 8 000 rpm with the subsequent filtration of the supernatant through 0, 45 μm membranous filters (Sartorius) [2, 18]. Lethal activity was determined in the experiments on white mice with the
help of the LD50/ml determination method [18, 19]. The animal experiments were carried out according to
the requirements of the European Convention of the Protection of Vertebrate
animals that are used for research and other scientific purposes and practical scientific recommendations [20-21]. Results&discussion. The carried out experimental studies have shown tha the museum strains of C. difficile produced toxins with different lethal activity. In the cultural filtrate of the museum strain № 258, obtained on the liver broth, the lethal activity was 7,9 LD50/ml (LD50 max = 1:5,4 ml; LD50 mіn = 1:9,5 ml, р = 0,05), on the heart-brain broth – 10,0 LD50/ml (LD50 max = 1:8,3 ml; LD50 mіn = 1:12,5 ml, р = 0,05). Museum strain № 281 А produced a more active toxin. Its lethal activity was correspondingly 12,5 LD50/ml (LD50 max = 1:10,0 ml; LD50 mіn = 1:14,8 ml, р = 0,05), and – 19,9 LD50/ml (LD50max = 1:17,8 ml; LD50 mіn = 1:20,5 ml, р = 0,05). Conclusion. Filtrates obtained from clinical strains of C. difficile have not demonstrated lethal activity after an intraperitoneal injection into mice, which allows us to consider them non-toxicogenic in advance and as such as those that do not have epidemic significance. The studies museum strains of C. difficile № 258 and 281 А produced lethal toxins of different activity. The
toxin-producing activity of the C. difficile 281 А strain was reliably (р≤0,05) higher than that of the C. difficile № 258 strain. The toxin-producing activity of both strains was reliably higher on the heart-brain broth compared to the data obtain on the liver broth.
Key words. C. difficile, toxin-producing activity, nutrient media.
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51-54
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Study of the
antimicrobial activity of phytoointment for treatment of mechanical damages of
dairy tissue
Zuikina S.
S., Vyshnevska L. I., Silaeva L. F.
Introduction. One of the common
pathologies found in gynaecological practice is cracking nipples, which
represent the rupture of an external sensitive epidermis due to its mechanical
damage. Cracks have different shapes (straight and stellar), as well as
different depths (superficial and deep). The nature of cracks is quite diverse:
poor quality personal care products or non-compliance with personal hygiene
rules, low-quality gels and cosmetics, improper breastfeeding, vitamin A and E
deficiency, early use of hormonal contraceptives and other medicines, tanning
bed, improperly selected linen and other. Diagnosis is performed only when
there are complaints, namely: when the nipple swells, blushing, pain and heaviness
in the chest are felt. The treatment is prescribed by the doctor depending on
the duration of the disease and its severity. If the disease lasts up to three
days, then wound healing, antiseptic and palliative drugs are prescribed. If
the disease lasts more than three days, then antibiotic therapy is added to
these agents, as there is a secondary infection. In such cases, the
breastfeeding of the baby stops.Taking into account the above, the composition
of the soft dosage form for use in gynaecology, which has reparative, wound
healing action, was developed. Ointment under the conventional name
"Phytolan" contains in its composition vegetable oils: amaranth, sea
buckthorn, parsley leaves, melaleuca and lanolin anhydrous as the basis. The aim
of the research was comparative study of the spectrum and level of
antimicrobial activity in vitro ointment "Phytolan", the comparator
preparation - the analogue by the action of the cream "Mama care" and
specimens containing ointment base - anhydrous lanolin and a separate phytooil
in a concentration of 10%. Material&methods. As test
strains we took standard strains from the American standard collection of
microorganisms: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922,
Pseudomonas aeruginosa ATCC 9027, Bacillus subtilis ATCC 6633, Candida albicans
ATCC 885-653. Cultivation of cultures was carried out by traditional methods in
nutrient media with subsequent confirmation of morphological, cultural and
biochemical properties (3). In the course of research, appropriate nutrient
media indicated in the national part of the SPHU were used: medium # 1 - in the
study of antibacterial activity and medium # 2 - in the study of antifungal
activity of the samples. The antimicrobial activity of the drugs was studied in
vitro in commonly accepted in microbiological practice method of diffusion in
agar in the modification of wells. This method is based on the ability of
active substances to diffuse into agar medium, which is pre-sown with the test
culture. The molten agar nutrient medium was cooled to 45° C, poured into the bottom
layer into Petri dishes in a volume of 10 ml. After hardening of the agar on it
were placed six sterile cylinders of stainless steel 10 mm in height and an
internal diameter of 8 mm, around which the second layer of medium was poured
into a volume of 15 ml, seeded with appropriate cultures of microorganisms. The
microbial load was 0,5 units. Mc Farland turbidity per 1 ml of medium. After clamping the upper layer of agar, the cylinders were removed with
sterile tweezers and in the formed wells, the test specimens were administered.
Petri dishes were kept for one hour at room temperature, after which they were
placed in a thermostat and incubated for 24 hours at a temperature of 37° C
with Muller -
Hinton agar and 25° C with Sabur agar. The level of antimicrobial
activity of the developed ointment, experimental specimens and the comparison
preparation was evidenced by the diameter of zones of growth retardation of
microorganisms around the well. The research was conducted in
six-time repetitions for each test culture. Statistical processing of the
results of the study was carried out according to Student's criterion (P
<0.5). Results&discussion. According to the results of the research, ointment samples
exhibited a moderate level of antimicrobial activity against Staphylococcus
aureus culture and practically no activity compared to other cultures. Thus,
the growth retardation zone of S. aureus culture around the ointment samples
was 13,6 mm, around other cultures 12,1 – 12,2 mm. Other study samples: the comparison drug
"Mama care" (analogue by effect) and individually samples with
lanolin and amaranth, sea buckthorn, parsley, tea tree almost did not exhibit
antimicrobial activity to used test cultures.Despite the known antimicrobial
properties of essential oils, in particular tea tree (6), the absence of a
pronounced effect in vitro may be due to the technological difficulties of
creating an effective antimicrobial concentration in the ointment. The tendency
towards the manifestation of antistaphylococcal activity of the ointment may be
related to the effect of synergy of essential oils in the composition, in
particular the influence of tea tree oil and requires further study of the
mechanism of this phenomenon. Conclusion. 1. The
use of essential oils in the treatment of mastopathy is substantiated. 2.
Antimicrobial activity of the developed ointment in relation to S. aureus
culture was established and the synergistic effect of essential oils in the
composition of the designed drug was revealed. 3. The promise of the
application of the developed preparation for the treatment of mechanical damage
to the tissues of the mammary gland, complicated by bacterial infections, and
the prevention of mastopathy has been proven.
Key words: mastopathy,
ointment, antimicrobial activity, synergism, phytooil.
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55-61
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Spectrum and levels of antimicrobial activity of
modified amino acids
Osolоdchenko T. P., Andreieva I. D., Zavada N. P., Ryabova I. S., Volyansky A. Yu.
Introduction. Antimicrobial resistance
threatens the effective prevention and treatment of an ever-increasing
range of infections and is rising to
dangerously high levels in all parts of the world. The search among the natural
and synthetic biologically active compounds that influence the development of
resistance in against antibacterial agents in the clinically relevant strains
acquires increasingly greater significance. Material & methods. Were studied the spectrum and levels of antimicrobial activity of 10 synthetic
amino acid derivatives, the most active according to the results of the primary
screening study. Investigations of the degree and spectrum of antimicrobial
activity selected on the basis of screening of promising substances were
performed on 40 museum and clinical strains of microorganisms, among them 17
gram-positive, 13 strains of gram-negative bacteria and 10 strains of fungi of the genus Candida. Determination of antimicrobial and anticandidisis effects of new
compounds was carried out using the standard method of double serial dilutions. Results & discussion. It has been established that synthesized derivatives of lysine and arginine
possess high in vitro activity against gram-positive microorganisms with MIC
values in the range of 3.9-31.25 μg / ml. Among the investigated substances,
the most active compounds, namely the derivatives of lysine 6.1 and arginine
7.1.5 (MIC and MBCB in the range 3.9-15.6 μg / ml), were determined according
to their degree of influence on gram-positive microorganisms. The effect of
modified amino acids relative to P.
aeruginosa ATCC 27853 was demonstrated at concentrations of 15.6-62.5 μg /
ml. The MIC synthetic derivatives of amino acids relative to E.coli ATCC 25922 were within the range
of 7.8-15.6 μg / ml. Indicators of MIC of synthesized substances for strains S. enteritidis gr. P, Y / ratin No. 27, S. flexneri DSIK 170 and S. sonnei DISK 5772 were in the range of
15.6 - 31.25 μg / ml., The most active for
strain P. aeruginosa ATCC
27853 were derivative of lysine 6.6 and derivative of arginine 7.1.6. For
representatives of the Enterobacteriaceae
family were the most active derivative of
lysine 6.3 and derivative of arginine 7.1.5. The activity of modified
amino acids relative to fungi of the genus Candida was not high. The inhibitory
growth of the concentrations of the tested substances was in the range of
62.5-125.0 μg / ml. According to the degree of antifungal activity, none of the
studied substances did not show better than others. Conclusion. The obtained results confirmed the promising research of modified amino
acids with the ultimate goal of creating new antimicrobial agents on their
basis.
Keywords: modified amino acids; microorganisms; antimicrobial activity
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62-65
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Clinical case of multiple sclerosis associating with persistent herpes
virus infection: dynamics on the background of antiviral and immunocorrective
treatment
Davydova T.
Rationale: Multiple sclerosis (MS) is a chronic inflammatory disorder of the
central nervous system. Infectious triggers of MS are being actively
investigated. Substantial evidence supports the involvement of the Epstein-Barr
virus (EBV), though other viruses, bacteria, protists, and fungi are also being
considered. For many years, researchers have discussed the relationship of
demyelinating processes and development of multiple sclerosis (MS) associated
with the activation and persistence of herpes viruses. In recent years, studies have increasingly proved the
pathogenetic role herpes viruses in the development of this disease, but this
requires further study. There is growing evidence that viruses can play a role
by acting as external triggers. However, it is not known, one virus is the
cause MS or several viruses can act as an impulse to the development the
disease. Clinical case: Patient N.,
female, 35 years old, was diagnosed with multiple sclerosis, disseminated,
relapsing remitting, exacerbation stage with moderately expressed right-sided
paraparesis, with motor and sphincter disorders, pronounced vestibule-ataxic
(vestibulocerebellar) syndrome, cognitive impairment, EDSS 4.5–5.0 in 2013. A brain
and spine MRI showed numerous bilateral hyperintense (17) T1, and several (5)
T2 lesions and FLAIR contrast-enhancing over the hemispheres and cerebellum and
several (6) T1, (4) T2 lesion in her cervical spinal cord sizes from 0.3 cm to
1.1x0.6x1.1 cm individual foci with signs of perifocal edema. At the time of diagnosis
complaints of dizziness, shakiness when walking, weakness and a feeling of
numbness in the limbs, discoordination of movements, impaired urination by the
type of delay with frequent urges, decreased performance, fatigue, unstable
gait, muscle cramps, decreased muscle strength (4), slight speech disturbances,
depression and anxiety. She treated with pulses of corticosteroids (1.5 g methylprednisolone) and plasmapheresis with gradual tapering of the
steroids over a period of 4 weeks according to standard treatment protocols in
the neurological department Kharkiv Regional Clinical Hospital. The first
symptoms appeared 6 months before the diagnosis was established and gradually
increased. Complaints were preceded by an episode of acute viral infection and
prolonged low-grade fever for 3 months. We consider the clinical case patient
with MS, it was detection the abnormalities in the immune status and viral load
(herpes type 4 – Epstein-Barr virus, EBV and human herpes virus 6 – HH6), and
positive dynamics was observed in condition of patient and MRI data after
antiviral and immunocorrective therapy. Interventions:
We administered valacyclovirum as the first therapy in combination with
recombinant interferons α2b and cridanimodum. Additionally was recommended high
doses of vitamins. Outcomes: The
patient's condition improved after treatment: EDSS 3.0–3.5. MRI also showed
positive dynamics: several small lesions in the brain disappeared, large MS
lesions became smaller in size. (11) T1, and several (5) T2 over the
hemispheres and cerebellum and FLAIR contrast-enhancing and several (4) T1, (3)
T2 lesion in her cervical spinal cord sizes from 0.3 cm to 0.7x0.4x0.8 cm
individual foci without signs of perifocal edema. Conclusion: Early diagnosis and active antiviral and
immunocorrective therapy is important when herpes are detecting in MS patients
for treating and preventing further development of the disease, so we would
like to highlight some aspects of the therapy carried out in this case for the
perspective planning relevant clinical studies in the similar direction.
Keywords:
Circulating immune complexes
(CIC); Central nervous system (CNS); Epstein – Barr virus (EBV); Human
herpesvirus 6 (HH6); Herpes simplex virus 1 (HS1) ;
Immunofluorescence coefficient (Ic); Magnetic resonance imaging (MRI); Multiple
sclerosis (MS); Optical density units
(Op.d.u ); Peripheral blood mononuclear
cell (PBMCs); Varicella – Zoster virus (VZV)
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