Contents
|
|
C.
(P.) |
||||
|
Editorial Board |
1 |
|
|||
|
Contents |
2-5 |
||||
|
Review (Dedicated to the
birthday of I.I. Mechnikov) |
|
||||
|
Metchnikoff at Rockefeller: a
legacy of phagocyte- microbial interactions Siamon Gordon, William Dunn In 1909, Elie Metchnikoff
presented a signed portrait of himself to Simon Flexner, the first
scientific
director of the newly formed Rockefeller Institute in New York. It was
eventually passed on, at Rockefeller, to Rene Dubos, a French
microbiologist,
and then to his successors, James G Hirsch and Zanvil A Cohn;
Metchnikoff’s
spirit continued to pervade the laboratory directed subsequently by
Ralph M
Steinman. Over 50 years, 1960-2010, this became one of the premier
research
laboratories in the world to investigate the immune interactions of
microbes
with granulocytes, monocyte-macrophages and dendritic cells,
respectively, at
all times under the benign presence of Metchnikoff. I was fortunate to
join the
laboratory as a student of Zanvil Cohn during 1966-1976, which
initiated me
into a life-long love affair with macrophages, lasting to the present
day at
Oxford. In this year of his 175th birthday, I would like to
record
the legacy that Metchnikoff left to my
generation
during that period at Rockefeller University.
|
|
6-10 |
|||
|
Illyaa Ilyich Mechnikov: life and
work Minukhin V. V., Kolotova T. Yu., Skliar
N. I., Voronkina I.A., Davidenko
M.B., Kazmirchuk V.V. On May 15, 2020,
we celebrated the 175th anniversary of the Ilya Metchnikoff, the author
of the
hypothesis about parenchymella, the father of cellular immunology and
inflammation theory, founder of gerontology, aging and longevity
science. The
article discusses the main milestones in the life and scientific work
of Ilea
Metchnikoff. Ilya
Metchnikoff working originally in Russia, later in Italy, and then at the Pasteur Institute in Paris. His
initial observations on phagocytic cells were made in the marine
biology
laboratories in Messina on starfish. Ilya Ilyich, as a result of observations of intracellular
digestion in
sponges, coelenterates and some flatworms, stretches a thread between
phagocytosis and evolution
(phagocytella), inflammation, cellular immunity, regeneration and
the aging process. This thread is the quintessence of his work. Metchnikoff
devoted many years to studying the comparative development of the
embryonic
layers of lower animals. Ilya Ilyich
demonstrated that cnidarians gastrulate by introgression of cells which
move
from the blastula wall into the interior blastocoel and formed
parenchymella or
phagocytella. According to Metchnikoff, the hypothetical ancestor of
multicellular organisms was similar to phagocytella. Metchnikoff
is rightly famous for his theories of phagocytosis and inflammation. He
proposed that macrophages evolved first to regulate development, and
that these
function are the stage for their evolution into the cells of innate
immunity.
It is very importantly to aware that cells and microorganisms according
to
Metchnikoff were taken up by an active process, involving living, and
not only
dead organisms The humoral theory claimed that the phagocytes caused
the spread
of disease in the body and thus would harm the host, rather than defend
it,
against bacterial invasion. Metchnikoff
devoted much of his scientific work to the revealing of the role of
phagocytosis in inflammation. He observed diapedesis through vessel
walls and
aggregation of leukocytes at sites of inflammation. Phagocytosis
not only destructs of infectious microbes but uptake of host cells,
e.g.
erythrocytes, from diverse species as well. More broadly phagocytes are
the
cells which preserving the integrity and defining the identity of the
organism.
Metchnikoff believed that the disabilities of old age are the work of
phagocytes transformed from defenders against infection into destroyers
of
tissues by autotoxins derived from putrefactive bacteria residing in
the colon.
Such degenerative changes, he believed were nearly always premature and
potentially prevented by procedures directed against the putrefactive
bacteria. Until recently it was
generally assumed that
phagocytic removal of neurons occurs only after neuronal death. But now
it has
been convincingly proved that stressed but viable neurons reversibly
exposed
the "eat-me" signal leading to their phagocytosis by microglia; this
neuronal loss was prevented in the absence of microglia. As a result
these data
breathe life into the Metchnikoff’s ageing theory. Metchnikoff’s hypothesis from the very beginning met with fierce criticisms. It
required 25 years of in tense effort to achieve
recognition of the phagocytosis theory. This struggle culminated in
1908 with
the awarding of the Nobel Prize Keywords: evolution, natural selection,
parallel evolution, complexity, parenchymella, phagocytella, gastrula,
phagocytes, inflammation, innate immunity,
macrophage, probiotics, ageing theory
Experimental works |
|
11-34 |
|
||
|
Study
of the efficiency of using disinfectants «Adalux» to provide paper
material
with bactericidal properties Zinchenko
I., Babich O., Tsytlishvili K., Shostenko O., Kononenko K. Introduction.
The
issue of environmental management and protection of the environment
from
pollution are of paramount importance. Today, there is a big problem
associated
with the accumulation of polymer waste, which catastrophically pollutes
the
planet. Most plastic waste is not recyclable, but can be decomposed in
landfills for decades. As an alternative to plastic products, world
experts
suggest the use of paper, biodegradable (biopolymer), reusable
packaging. Many
countries are now working to develop and produce packaging from
affordable and
environmentally friendly and natural materials that can degrade in soil
or
compost. The purpose of this work is
to determine the resistance of paper samples of different densities to
microbiological contamination after treatment with bactericidal agent
«ADALUX».
Objects of research - samples of
paper which are widely used in the industry, with a density of 80 g/cm2,
52 g/cm2, 50 g/cm2; liquid bactericidal drug
«ADALUX»
(hereinafter - the drug) - a disinfectant that does not contain
chlorine
compounds. Research methods and
techniques. The paper samples were treated with a 0.1% solution of
the drug
in the form of an aerosol and stored at room temperature for a month
and
monitored. Raw paper samples were stored in the same conditions. The
study of
samples for microbiological contamination was performed for 7, 14 and
30 days
on the following indicators: total microbial count (ÒMC), bacteria of
the Escherichia coli group (BÅCG),
enterococci (EC), fungi and yeast-like microorganisms. The resistance
of paper
samples to microbiological contamination, or bactericidal properties of
the
paper treated with the drug, was determined by the following methods:
contact
(disk), agar filling, artificial contamination of the paper surface -
test
object - Escherichia coli B
(hereinafter - E. coli Â). By
comparing the number of colonies that grew in the variants with treated
and
untreated paper samples, the resistance of the test paper samples to
high
bacterial contamination was determined. Results
and discussion. On paper samples that were not treated with an
antibacterial agent, growth of saprophytic bacteria (GSB) was observed
during
the storage period, mold and yeast-like fungi were also found, and a
small
number of bacteria belonging to the group of E. coli
were found. Processing of paper samples with 0.1% solution
«ADALUX» provided bactericidal and bacteriostatic properties of the
paper. They
especially manifested themselves on the day of treatment and after 7
days of
storage. Bacteriological crops from the surface of the samples on the
day the
paper was treated with a bactericidal agent showed a complete absence
of
microorganisms on the surface of all the studied paper samples. After 7
days of
storage, the contamination of the treated samples with saprophytic
microorganisms was observed 1.6 - 2.9 times less than in untreated
ones. After
14 and 30 days of paper storage, the bactericidal effect against TMC
and BÅCG
decreased, but the development of bacteria on the surface of the
samples was
slower than on untreated paper samples. Molds and yeast-like fungi were
observed on both processed and untreated paper samples of various
densities.
Probably, the 0.1% solution «ADALUX» has
a more pronounced bactericidal effect, but its fungicidal properties
are much
less. Microscopic studies of colonies grown on a selective medium for
fungi
showed a predominance of growth of yeast-like fungi and less mold. On
all
investigated paper samples (processed and unprocessed), stored for more
than 14
days, colonies of microorganisms belonging to spore bacteria were
identified.
Morphological features and microscopy of the colonies of these
microorganisms
suggested that they belong to the spore bacteria of the genus Bacillus, tentatively of the species - Bacillus
subtilis (hay bacillus), which
are widespread in the environment. Due to the ability to form spores,
these
microorganisms easily tolerate adverse living conditions and continue
to live
on the surface of the paper. After processing paper samples with
«ADALUX»
disinfectant (0.1% solution), paper with a density of 80 g/cm2
had
the most bactericidal properties, least of all with a density of 50 g/cm2.
A study of the resistance of treated paper samples to artificial
bacterial
contamination with the Escherichia coli B
test-object (at a concentration of ~ 103 - 106
cells/ml)
showed that after 7 days of storage, there was no growth of the test
object on
paper samples with a density of 80 g/cm2 and growth
retardation on
paper samples with a density of 52 g/cm2. Studies of paper
samples
during storage for 30 days showed that all paper samples (processed and
unprocessed) did not have resistance to artificial bacterial
contamination upon
contact with the test object, which resulted in fouling of paper
samples with
colonies of E. coli
bacteria. Conclusions.
Based on the results, it was found that the disinfectant
«ADALUX» (chlorine-free) in a
concentration of 0.1%
has a bactericidal effect when processing paper samples for seven days
and
bacteriostatic effect (inhibition of bacterial growth) when stored for
a month
against saprophytic microorganisms and BÅCG, but not very effective
against
microscopic fungi. It is likely that paper products that have been
treated with
such a disinfectant, on the one hand, have bactericidal properties for
some
time, on the other hand, in case of impossibility of recycling after
their
direct use, as waste can decompose naturally without harming the
environment. Keywords:
bactericidal agent «ADALUX», microbiological contamination of paper,
bactericidal properties of paper, bacteriostatic properties.
|
|
35-40 |
|
||
|
Biopharmaceutical research
on the choice of a non-steroidal anti-inflammatory agent in the
development of
combination gel for mastopathy therapy Zuikina S. S,
Vyshnevska L. I. According to the International Agency for Research on
Cancer (IARC) at WHO, more than 1.7 million women are diagnosed with
breast
cancer annually. In Ukraine, according to the National Cancer Registry,
in
2013, BC was first identified in 16,624 women (in 2012 –
16,660), which is 72.2 cases (in 2012 – 67) for every 100,000 women in
the
country. The global death toll from this disease is growing and is
killing more
than 500,000 women worldwide annually. According to experts from the
National
Cancer Institute, a diagnosis of breast cancer by the end of 2020 may
become a
reality for almost 17% of Ukrainian women, which gives reason to view
it as a
socially significant epidemiological problem.The aim of the study was
to
substantiate the choice of NSAIDs and their concentration for use in
the
development of combination gel for the treatment of mastopathy and
prevention
of breast cancer. The methods of literary analysis, marketing research
and
biopharmaceutical methods in vitro were used. The results of marketing
studies
and pharmacological studies of the level and types of activity of
NSAIDs
allowed indometacin to be selected as the active pharmaceutical
ingredient
(API). According to the results of biopharmaceutical studies, the
concentration
of the active substance in the composition of the gel is established. Keywords: breast cancer, mastopathy, gel, indometacin,
release.
|
|
41-47 |
|
||
|
Improving vaccine efficacy
based on non-covalent photoinactivation of
microorganisms - sources vaccine antigens (MSVA) Martynov A., Farber B., Osolodchenko T., Klein I. One
of the most promising methods for non-covalent inactivation of
vaccine-producing microorganisms is the use of photoinactivation using
riboflavin derivatives. The study used a dynamic combinatorial
derivative of
riboflavin - succinyl-maleinyl riboflavin. Corpuscular
vaccines are divided into the following groups: from 2AB to 5AB -
bacteria were
inactivated by riboflavin derivative and blue light, and groups from
6AB to 9AB
were inactivated by formalin (0.1% formalin in 9 log CFU was kept for 2
weeks
in an thermostat and then sterility was determined - bacterial growth
was not
observed). A dynamic derivative of riboflavin at a final
concentration
of 0.02% can photo inactivate 6 time more bacteria P. Aeruginosa and E.
coli
than riboflavin. The minimum effective blue light emitter power (450
nm) for
the photodynamic inactivation of both P. aeruginosa and E. coli is
1024.2 mW /
cm2. In groups of mice pre-vaccinated intraperitoneally with
corpuscular photo
inactivated vaccines based on suspensions of and E. coli at doses of
0.5-1.0 ml
4 log (CFU) / mL, 100% survival of all animals was observed, whereas in
control
group with the same type of vaccines but formalin-treated vaccines, it
failed
to achieve a 100% protective effect. Keywords: vaccines; non-covalent inactivation; photodynamic; riboflavin derivatives; visible light; E. coli; P. aeruginosa, TRIZ
|
|
48-53 |
|
||
|
Study of the antibacterial
activity of new modified galenic and novogalenic phytosubstances from
vaccinium
vitis-idaea leaves Tsemenko
K.V, Kyreev I.V, Osolodchenko T.P. The purpose of the work is to study the
antibacterial activity of new modified galenic and novogalenic
phytosubstances
from Vaccinium vitis-idaea leaves. Materials
and methods. The object of
our research new modified galenic and novogalenic phytosubstances from
Vaccinium vitis-idaea leaves. Pharmacopoeia agar diffusion method
biological
method for determining the activity of antibiotics, based on the
ability of
molecules antibiotic substances diffuse in agar media and form zones of
inhibition, in which the test microorganisms used do not develop
sensitive to
the antibiotic under study. The study of antibacterial activity of the
phytosubstances was in the laboratory of biochemistry of microorganisms
and
nutrient medium of the Mechnikov Institute of Microbiology and
Immunology under
the direction of ñandidate of biological sciences Osolodchenko T.P. The
reference drug was Inurek, recommended by the European Association of
Urology
for the prophylactic treatment of urinary tract infections. Results.
We have identified the most
active phytosubstance, which is the glycosides of phenolic compounds in
combination with the arginine, dissolved in 50% alcohol. It has been
established that polysaccharides from the leaves of Vaccinium
vitis-idaea
leaves may have a low antibacterial effect, and in the complex with
phenolics,
they do not infuse an antibacterial effect on the antibacterial effect.
It has
been established that phenolics from half of the leaves of lingonberry
extraordinarily exhibit a greater antibacterial effect in the presence
of glucosides. Conclusions.
A screening study of the antibacterial activity of 13 new modified
galenic and
novogalenic phyto-substances from Vaccinium vitis-idaea leaves carried
out. The
most active was phytosubstance 12, which is a complex of glycosides of
phenolic
compounds with arginine. It has been proven that it is phenolic
compounds in
the form of glycosides that have a more pronounced effect in the main
relations
of uropathogens than their aglycones.. Keywords: new modified galenic and
novogalenic phytosubstances, leaves, Vaccinium vitis-idaea,
antibacterial
activity
|
|
54-57 |
|
|
|
|
Reproduction and apoptosis
of EBV- latent infected cells under influence a TRIZ-created antiviral
drugs Farber B, Martynov
A, Klein I. Introduction.
We
had worked persistently and in 1997, the first model of such a
structure based
on oligopeptides of horse albumin was revealed. We named this project
and
called Albuvir (combined from the word Albumin and the word virus) and
applied
in veterinary medicine, where viral infections represent more than 95%
of all
pathologies. In 2000 an application was filed for the first
modification of
this drug. Subsequently, for the production and sale of this product,
registration certificates of the State Committees in Veterinary
Medicine of
Eastern European countries were obtained.
In 2010, we signed a license agreement to transfer of
limited rights in
the field of veterinary medicine for the production and sale of Albuvir
in
Eastern Europe. The drug was produced commercially and was successfully
used to
cure hundreds of thousands of chickens, rabbits, sheeps, cows, pigs,
pigeons,
fish (industrial - sturgeon), cats, dogs, geese, ducks, and other types
of farm
birds and animals. Thus,
the task of this work was to study the ability of Albuvir to inhibit
EBV
reproduction and induce apoptosis of latently infected cells in the
culture. Materials and methods. Cell
culture. The inhibitory effect of
Albuvir on EBV was studied in the following cell cultures: Raji - cell
culture
of the B-phenotype of Burkitt's lymphoma. Namalwa is a B-phenotype cell
culture
from Burkitt's lymphoma that lacks the EBV genome. B95-8 is a marmoset
monkey
B-lymphocyte cell line containing the complete EBV genome, producing
complete
viral particles. To control cell viability, a 0.4% trypan blue dye
(Sigma,
United States) was used. EBV was isolated from a lymphoblastoid culture
of
B95-8 cells (B-lymphocytes of monkeys-marmazetka), which produces this
virus,
according to the method of Walls, Crawford. Investigated substances.
Albuvir (N.
1) - dynamic acylated acidic peptides - antagonists of signal peptides
of
nuclear (nucleolar) localization and polyribosomes. Lysine
tris-succinamide (N.
2). Acyclovir was used as a reference drug (references data) MTT test. The cytotoxic concentration was
determined in the Raji lymphoblastoid cell system using the
colorimetric MTT
method. This method is widely used to determine the CC50 of potential
drugs in
the study of the cytopathic action of viruses in vitro. Raji
cells were plated into 96 well culture plates, 100 μl per well, 25 μl
MTT (final concentration 5 μg
/ ml) was added and incubated for 3 h at 37 ° C in an atmosphere of 5%
CO2.
After incubation, cells were washed with PBS and resuspended in 96%
ethanol to
dissolve formazan. The results were analyzed spectrophotometrically on
a
Dynatech reader (Sweden) at a wavelength of 540 nm. Polymerase chain reaction. The degree of influence of
drugs on EBV reproduction was determined using PCR test systems
"AmpliSens-100-R". A fragment encoding the VCA protein of the virus
with a size of 290 nucleotide sequences was the chosen genome region of
the
Epstein-Barr virus. The control was cells that, after infection with
the virus,
were incubated in the growth medium without the addition of the
substances that
were studied. We determined the percentage of inhibition of the level
of
accumulation of viral DNA in the samples treated with the test
substances in
relation to the control sample, the value of which was taken as 100%. Results and discussion. Effect of the
dynamic antiviral drug Albuvir
on reproduction and apoptosis latently infected with the Epstein-Barr
virus
cells in vitro. Modern approaches to the treatment of herpes
infection,
in particular the Epstein-Barr virus (EBV), include the use of
ethyotropic drugs,
as well as sensitizing therapy. The range of drugs active against EBV
remains
very limited to ganciclovir and acyclovir. The search for new compounds
active
against EBV remains relevant. The aim of this study was to find out the
anti-EBV activity of the drug Albuvir in Raji, B95-8, Namalwa
lymphoblastoid
cells. The cytotoxicity index (CC50) was determined, which was 3000
ug/mL, and
the concentration of the drug that inhibits the reproduction of the
virus (EC50)
was 0.1 ug/mL. The ability of the drug Albuvir to inhibit the
reproduction of
the Epstein-Barr virus in all studied cell cultures was revealed. When the economic efficiency of creating
static drugs in accordance with the S-shaped curve decreases, the need
arises
for a transition to a supersystem, namely, the creation of dynamic
drugs
systems. It has been proven that the drug Albuvir is able to
inhibit the
reproduction of the Epstein-Barr virus in Raji, B95-8 and Namalwa cell
cultures. It is determined that the drug has a high activity in the
culture of
Raji cells (SI 8400), respectively, the drug is promising enough to
develop as
a treatment for EBV-associated diseases. Keywords: TRIZ, laws of system evolution, dynamization, S-curve, Epstein-Barr virus, cell culture, antiviral action, albumin.
|
|
58-67 |
|
||
|
Bilateral Optic Neuritis in a Child Associated Multiple
Sclerosis Dwita Permatasari, Lukisiari Agustini,
Gatot Suhartono Introduction: Optic neuritis can be associated with multiple sclerosis
(MS). Therefore,
accurate diagnosis, risk assessment and management of patients with
optic
neuritis associated multiple sclerosis should be assessed. Method: A 5 years
old girl suddenly blurred vision in both eyes and headache within 4
days before
admitted in outpatient clinic. Patient had no fever and neurologic
deficit. Visual
acuity in first day were hand movement, color vision difficult to be
evaluated
in both eyes and right eye positive relative afferent pupillary defect.
Posterior segment evaluation showed bilateral edema optic nerve. MRI
showed
bilateral optic neuritis, chronic plaque in right parietal lobe, right
and left
centrum semiovale. VEP showed demyelinating lesion in bilateral visual
pathway.
Patient was given intravenous methylprednisolone 500 mg divided 4 times
a day
and continued with oral prednisone start on the sixth days. Result:
After treatment with
intravenous corticosteroid until fifth days follow up, BCVA and color
vision
improve gradually. At the ninth days follow up, BCVA on right eye (RE)
5/5 and left
eye (LE) 5/8.5 pinhole not improve. Ishihara on RE 12/14 and LE 10/14.
Ophthalmoscopy examination showed disc edema subsided in the follow up.
A month
follow up, BCVA and Ishihara on both eye were5/5 and 14/14.
Opthalmoscopy
examination showed normal optic nerve head. Conclusion: Bilateral
optic neuritis in a child associated multiple
sclerosis is a challenging case. Intravenous methylprednisolone is the
first
line drug therapy give better visual outcome. Keywords: bilateral
optic neuritis, multiple sclerosis, methylprednisolone
|
68-72 |   |
|||
|
Study of stability when storing of tablets under the
conditional name “Ap-helmin”
as one of the factors of pharmaceutical development Semchenko K. V., Vyshnevska L. I. Introduction. According to the World Bank, economic losses from
helminthiasis of the
digestive system rank fourth in the overall structure of diseases and
injuries
of the world’s population.To meet the existing needs of the population
of
Ukraine in effective anthelmintic drugs, there were developed a complex
anthelmintic drug in the form of coated tablets under the conditional
name
“AP-helmin”, the active ingredients of which are albendazole and
praziquantel
in the ratio (1:4). One of the main ways to assess the quality of the
drug is
to maintain its stability during storage. Thus, the purpose of this
work is to
study stability during the storage of coated tablets under the
conditional name
“AP-helmin” on the basis of compliance of quality indicators with the
requirements of SPhU and the developed project of quality control
methods. Materials & methods. As the object
of the study there were investigated 5 series of coated tablets for the
treatment of helminthiasis of the digestive system under the
conditional name
“AP-helmin”. The well-known SPhU methods were used to assess the
stability of
the established indicators. Results
& discussion. The proper quality and stability of the drug is
confirmed
throughout the study period. Yet, there is a tendency to reduce the
resistance
to crushing and reduce the quantitative content of active substances
after 27
months of storage. Conclusion. It
was found that throughout the study period of storage samples of the
drug met
the requirements of the project MCYA and HFC. Therefore, the most
rational is
to establish the shelf life of coated tablets under the conditional
name
“AP-helmin” for at least 24 months in a dry dark place at room
temperature. Keywords: tablets; stability; pharmaceutical development; Ap-helmin; albendazole; praziquantel
|
73-75 | |
|||
|
Features of disease course of some forms of herpesvirus infection Sorokina O.G., Popov M.M., Liadova T.I., Malanchuk S.H., Dorosh D.M., Sorokina A.V. Among the many factors that directly affect the
immune system, infections caused by the herpes virus deserve special
attention.
In recent years, there has been an increase in the number of patients
suffering
from chronic recurrent herpesvirus infections, which in many cases are
accompanied by severe general malaise and a number of therapeutic
complaints. Today about 80-95% of the population is
infected with Epstein-Barr virus EBV. Primary infection of EBV leads to lifelong
persistence of the pathogen with possible periodic reactivation under
the
action of various immunosuppressive factors, which leads to chronic
forms of
the disease. EBV can cause chronic manifest and erased forms of the
disease,
running on the type of chronic mononucleosis. Thus, the study of the nature
of clinical and laboratory changes in patients with chronic EBV
infection and
the peculiarities of the disease is an urgent problem of our time. The
aim of this work was to study the features of the course of chronic EBV
infection.
We performed a
comprehensive clinical and laboratory examination of 128 patients with
chronic
EBV infection (reactivation period). The diagnosis of chronic EBV
infection was
established on the basis of medical history, complaints, the presence
of
specific antibodies to EBV antigens and the detection of virus DNA in
the
blood. Studies of clinical blood tests of patients with chronic EBV
infection
and the control group showed differences. Thus, in patients with
chronic EBV
infection, a significantly elevated ESR level was found - 12.6 ± 1.8
versus 4.5
± Keywords:
herpesvirus infections, chronic EBV infection, course
of the disease, clinical and laboratory parameters, immune system. |
76-78
|
|
|||