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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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2-9
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ÅÊÑÏÅÐÈÌÅÍÒÀËÜͲ
ÐÎÁÎÒÈ, ÌÅÄÈÖÈÍÀ
Experimental papers, medicine
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MICROORGANISMS ANTIBIOTIC SENSITIVITY DETERMINATION
IN URINARY TRACT INFECTIONS
Shapovalova O.V., Shevcova
Î.V.,
Sokolova O.L.
Introduction. Nowadays Urinary tract
infections (UTI) are considered to be the most common
bacterial infections. Escherichia
coli is the most frequently uropathogen. Other microorganisms of the
genera Enterococcus, Klebsiella,
Enterobacter, Proteus, Morganella, Citrobacter, Serratia, Pseudomonas,
Streptococcus, Staphylococcus, Candida are also isolated with variable
frequency. In recent years there has been a decreasing tendency of the
causative agents of UTI sensitivity to various antibiotics, which causes
growth of an inefficiency treatment
risk. In connection with the above the investigations were carried out with
the purpose to identify the actual causative agents of bacteriuria and their
sensitivity to antibiotics and antifungal drugs. Materials and methods. Bacteriological examination of urine was
performed at 42 patients of SI "Sytenko Institute of Spine and Joint
Pathology, AMS of Ukraine" clinic. The bacteriological method for
determining the number of bacteria in the test material, cultural and
bacterioscopic methods for identifying microorganisms and disk-diffusion
method for sensitivity of microorganisms to antibiotics determining were
used. The clinical material for
the study was an average portion of the morning urine or urine collected by
catheter. The biological material collection and bacteriological examination
was carried by quantitative method, the isolated microorganisms
identification and their sensitivity to antibiotics determining was performed
by standard methods in accordance with current guidelines. We used the
following antibiotics group to determine the microorganisms sensitivity:
penicillin, cephalosporin, karbapenems, tetracyclines, aminoglycoside,
fluoroquinolones, oxazolidinones, macrolides, lincosamides, glycopeptides,
antifungal antibiotics. Results and
discussion. During the biological material study 55 isolates of bacterial
and fungal pathogens were obtained. The microorganisms’ concentration in
urine was in the range of 3,0x106 CFU/ml to 3,0x109
CFU/ml, and the most bacterial isolates content was equal 1,5x109
CFU/ml. Among the most commonly identified microorganisms Escherichia coli and Staphylococcus spp. were often
detected in 5,3x108 CFU/ml concentrations. For Streptococcus spp. and Proteus mirabilis that value was
1,5x109 CFU/ml; for Klebsiella
pneumonia - 3,0x108 CFU/ml; for Candida spp. - 3,0x106 CFU/ml respectively. The most
common microorganisms (which frequency of occurrence in urine was ≥ 5%)
were: E. coli (14,5±4,7)%, Str. agalactiae and St. haemolyticus (10,9±4,2)%; St. aureus and Pr. mirabilis (7,3±3,5)%; St. epidermidis, Kl. pneumoniae, St.
hominis, Candida spp. (5,4±3,0)%.
While analyzing obtained results we concluded
that meropenem was the most effective drug, 78,7% of all cultures had
the sensitivity to it. The sensitivity to gatifloxacin had 73,7% of cultures;
to tigecycline – 71,1% of isolates; to amikacin -67,3% of cultures; to moxifloxacin – 59,6% of isolates; to two
drugs (levofloxacin and
pefloxacin) - 55,8% of isolates
respectively. It was found that Staphylococcus
aureus appeared to be resistant to vancomycin, ampicillin, cefuroxime,
cefazolin, azithromycin, linezolid. This species and St. epidermidis and St.
hominis isolates were multi-drug resistant to four or more drugs from
different groups. All Streptococcus
agalactiae isolates were insensitive to cefuroxime. All Escherichia cultures were resistant to
cefuroxime, Proteus - to
cefuroxime, ampicillin and cefazolin. E. coli, Pr. mirabilis, K. pneumoniae, Ps. aeruginosa, Ac. haemolyticus had multi-drug
resistance. In addition, (73,1 ± 6,1)% of all 52 bacterial isolates obtained
were resistant to amoxiclav. Conclusions.
1. The most common microorganisms (which incidence in urine were ≥ 5%)
are: Escherichia coli (14,5±4,7)%, Streptococcus agalactiae and Staphylococcus haemolyticus
(10,9±4,2)%; Staphylococcus aureus and
Proteus mirabilis (7,3±3,5)%; Staphylococcus epidermidis, Klebsiella pneumoniae, Staphylococcus hominis, Candida spp. (5,4±3,0)%. 2. The most
effective antibacterial drug is meropenem. 78,7% of all isolates have
sensitivity to it. The sensitivity to gatifloxacin have 73,7%; to tigecycline
71,1%; to amikacin – 67,3%, to moxifloxacin – 59,6% of cultures, to two agents (levofloxacin and pefloxacin)
– 55,8% of cultures respectively. 3. 100% of the family Micrococcaceae isolates were resistant to benzylpenicillin, 95,8%
- to ampicillin, 87,5% - to amoxicillin and cefuroxime, 83,3% - to
azithromycin, erythromycin and lincomycin. Members of the Streptococcaceae family were resistant
to cefuroxime. 100% of the family Enterobacteriaceae
isolates had no sensitivity to carbenicillin, 87,5% of isolates - to
cefuroxim and gentamicin, 81,2% - to amoxicillin and ampicillin, 75,0% - to cefazolin, 50,0% - to ceftriaxonum
and aztreonam. 4. Staphylococcus
aureus, Staphylococcus epidermidis, Staphylococcus hominis Escherichia coli,
Proteus mirabilis, Klebsiella
pneumoniae, Pseudomonas aeruginosa, Acinetobacter haemolyticus isolates
were multi-drug resistant.
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10-15
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DEPENDENCE
BETWEEN ACYLATION DEGREE AND SPECIFIC LYSIS ACTITIVY OF THE PSEUDOMONAS AERUGINOSA Ì6 BACTERIOPHAGE
Martynov
A. V., Farber B. S., Osolodchenko T. P., Farber S. B., Kabluchko T. V.
Introduction. The purpose of this work is to
study the influence of various degrees of protein’s acylation on lytic
activity and other biological properties of Pseudomonas M6
bacteriophage. Materials and methods. The
subject of the study were samples of the Pseudomonas O 12
bacteriophage, hereinafter named the M6 phage. Pure phage lines were obtained from
individual standard-morphology phage plaques (plaque-forming units, or PFUs)
after ten passes over the indicator strain. In subsequent experiments, M6
phage samples were selected that had a sufficient level of purity
(homogeneous in the morphology of virions that inactivated the homologic
antiphage serum by no less than 99.0% and the heterologic antibacterial serum
by no more than 1%), and a titer no lower than 10 PFU per ml (PFU/ml).
Titration of the phages was conducted using the standard bilayer agar. The
crude protein content in the phage suspensions was determined using the
spectroscopic method (at 280 and 260 nm). Succinylation of the phage samples
was conducted according to the method developed by T.J. Molenaar. The phage’s
lytic activity spectrum was determined through spot tests on 224 strains of
the Pseudomonas genus and 106 strains of other genera
(correspondingly, of strains Enterobacter -40, Escherichia -10,
Citrobacter -8, Hafnia -7, Serratia -6, Shigella
-10, Salmonella -8, Proteus -7) through the use of a phage
suspension containing 10 5 - 10 6 PFU/ml. (This
concentration of infectious phage corpuscles corresponds with the critical
distribution of the M6 phage). The results of the research were subjected to
statistical processing using single-factor dispersion analysis. Results and discussion. One hundred
percent phage protein acylation leads to a loss of adsorption ability on
sensitive cells and is accompanied by a significant (more than 103
times) decrease in the level of specific lytic activity in the phage
preparations. The succinylation type being studied does not cause changes to
the morphology or antigen structure of phage virions and does not
substantially affect the lytic activity spectrum or the average yield of
infectious phage corpuscles on a single sensitive bacterial cell. Considering
the relative uniqueness of any biological object (including the M6 phage
being studied), the authors recognize the advisability of verifying the
established patterns of the effect of various acylation levels on the
biological properties of other types and morphological groups of viruses. It
was proven that at phage sample acylation levels of 5%, 10%, and 20%, the
specific lytic activity increased by a factor of ninety, twelve, and eight
respectively. The adsorption speed constant increased by a factor of nine,
eight, and eight respectively. And the duration of the latent period fell by
20% in all cases with the development of a productive infection caused by the
acylated samples of the phages. The
use of this chemical modification method does not cause changes to the
morphology or antigen structure of phage virions and does not substantially
affect the average yield of infectious phage corpuscles on a sensitive
bacterial cell.
Key words: acylation, adsorption speed, lytic activity, Pseudomonas
M6 bacteriophage.
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16-20
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ÎÏÐÅÄÅËÅÍÈÅ ÑÏÅÊÒÐÀ ÃÅÍΠÐÅÇÈÑÒÅÍÒÍÎÑÒÈ Ê ÀÍÒÈÁÈÎÒÈÊÀÌ Ó ÔÅÍÎÒÈÏÈ×ÅÑÊÈ
ÐÅÇÈÑÒÅÍÒÍÛÕ ØÒÀÌÌΠÏÐÈÑÒÅÍÎ×ÍÎÉ ÊÈØÅ×ÍÎÉ ÌÈÊÐÎÁÈÎÒÛ Ó ÊÐÛÑ ÌÅÒÎÄÎÌ ÏÖÐ-ÐÂ
Áóêèíà Þ.Â., Êàìûøíûé À.Ì., Ïîëèùóê Í.Í.
DETERMINATION
OF THE SPECTRUM OF ANTIBIOTIC RESISTANCE GENES HAVE PHENOTYPIC RESISTANT
STRAINS OF PARIETAL INTESTINAL MICROBIOTA IN RATS BY RT-PCR
Bukina
Y.V., Kamyshny A.M., Polishchuk N.N.
Introduction.
The problem of formation of bacterial resistance to glycopeptides and
beta-lactam antibiotics (cephalosporins and carbapenems) are used worldwide
for the treatment of severe community acquired and nosocomial infections,
especially caused by polymicrobial flora has become global and is a major
factor limiting the effectiveness of antibiotic therapy. In this regard, the
study of genetic microbial resistance determinants allows not only to carry
out an effective antibiotic therapy, but also to identify two main processes
leading to the development of epidemiologically significant events: the
introduction of the agent in the risk population from the outside and in situ
pathogen (spontaneous genetic drift) targeted restructuring of the
population. Therefore, the aim of our study was to investigate the resistance
genes to carbapenems, cephalosporins, glycopeptides have clinically important
phenotype of resistant strains of microorganisms families Enterobacteriaceae,
Pseudomonadaceae, Bacteroidaceae, Enterococcaceae, Peptostreptococcaceae. Materials and methods. As a material
for PCR studies 712 phenotypically resistant strains of microorganisms
isolated from 80 rats "Wistar" line in microbiological study
microflora of the wall were used. During the investigation 474 isolates of
bacteria of the family Enterobacteriaceae, 39 - Pseudomonadaceae, 71 -
Bacteroidaceae, 96 - Enterococcaceae, 32 - Peptostreptococcaceae were
studied. Isolation of DNA from bacteria in the study was performed using
reagents "DNA-Express" ("Litekh", Russia). For the
detection of resistance genes by PCR in real time (RT-PCR) reagent kits
"FLUOROPOL-RV" ("Litekh", Russia) were used. During the
experiment, the VIM genes, OXA-48, NDM, KPC, responsible for the resistance
of microorganisms to carbapenems, CTX-M - resistance to cephalosporins, as
well as genes Van A and van B, the development of resistance to glycopeptides
(vancomycin and teicoplanin) were determined. Analysis of the results of
amplification was performed using the program Bio-Rad CFX Manager 3.0 under
the "Guidelines on the application of Fluoropol format sets - PB." Results and discussion. During the
study of 474 cultures of microorganisms - representatives of the
Enterobacteriaceae family, KPC - in 7,81% and OXA-48 - in 8,44%, VIM detected
in 14,14% of the strains, NDM – 8,23% in the studied crops. These genes were
detected in E.coli strains (6,74%, 7,87%, 14,61%, 4,49%, respectively), from
microorganisms of the genus Klebsiella (13,85%, 1,54%, 15,38% , 12,31%),
Salmonella (7,03%, 10,16%, 13,28%, 8,59%), Enterobacter (4,76%, 14,29%,
15,87%, 4,76 %), Proteus (7,89%, 10,53%, 14,47%, 6,58%) and Shigella (7,55%,
3,77%, 11,32%, 15,09%). In the study of Bacteroides (Bacteroides spp.) Genes
KPC, OXA-48, the VIM and NDM were identified in 9,86 %, 4,23%, 9,86 % and
12,68% of the strains, respectively. PCR study of 39 isolates of
P.aeruginosae showed the presence of only VIM gene and only 15,38% of the
cultures. In the family Enterococaceae and Peptostreptococaceae these genes
were not found. According to Russian researchers have identified strains of
Enterobacteriaceae only genes OXA-48 (43,7%) and VIM (17,6%), and VIM gene
detection rate in P.aeruginosae was 62.9%. CTX-M gene was detected in 10,97%
of the strains of the family Enterobacteriaceae (Klebsiella spp. - 13,85%,
Salmonella spp. - 14,6%, Enterobacter spp. - 7,93%, Proteus spp. - 6,58% ,
Shigella spp. - 13,21%), Bacteroidaceae - 15,49%, Peptostreptococcaceae -
6,25%. In Pseudomonas and Enterococcus CTX-M is not revealed. At the same
time, according to the literature, the frequency of detection of gene CTX-M
in the family Enterobacteriaceae strains circulating in the Russian
Federation, in some regions reaches 100%, thus, the gene is not detected in
enterococci and Pseudomonas. In Enterococcaceae phenotypically resistant
strains of microorganisms of the family genes in identifying Van A and Van B
11,46% and 6,25% causing resistance to glycopeptides, particularly
vancomycin. Thus, of the 46 strains studied E.faecalis, 10,87% of isolates
possessed Van A genes and 8,7% - Van B. Out of 50 studied cultures E.faecium
12% were in their genotype Van A and 4% - Van B. However, the frequency of
detection of genes Van A and Van B in E.faecalis strains circulating in
Russia, 1,7% and 2,2%, while E.faecium - 9,3% and 11,5% respectively.
Bacteria of the family Peptostreptococcaceae these genes were not identified.
During the molecular genetic studies we have not detected phenotypically
resistant strains that have combined carbapenemases activity. Conclusions. The findings of the
research results indicate the presence of carbapenem resistance genes in
strains of microorganisms families Enterobacteriaceae, Bacteroidaceae and
Pseudomonadaceae (P. aeruginosae), to cephalosporins - Enterobacteriaceae,
Bacteroidaceae and Peptostreptococcaceae, vancomycin - from family
Enterococcaceae bacteria. Phenotypically resistant strains that have combined
carbapenemases activity, not revealed. Despite the wide range of activity of
appointment carbapenems, cephalosporins and vancomycin should take into
account the results of determination of resistance genes causing resistance
to these drugs. It is advisable to creating circulation monitoring program of
antibiotic-resistant strains, including those with ñarbapenemases activity in
humans and in the environment.
Keywords:
antibiotic resistance, gene indication, resistance genes, RT-PCR, parietal
microflora.
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21-27
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ÝÔÔÅÊÒÈÂÍÎÑÒÜ
BACILLUS COAGULANS
 ËÅ×ÅÍÈÈ
ÀÍÒÈÁÈÎÒÈÊ-ÀÑÑÎÖÈÈÐÎÂÀÍÍÎÉ ÄÈÀÐÅÈ ÍÀ ÔÎÍÅ ÈÍÄÓÖÈÐÎÂÀÍÍÎÃÎ
ÈÌÌÓÍÎÄÅÔÈÖÈÒÀ Ó ÌÛØÅÉ
Íîñàëüñêàÿ Ò.Í.,
Ìàðòûíîâ À. Â., Áîìêî Ò.Â., Êàáëó÷êî Ò.Â.
BACILLUS COAGULANS
EFFICIENCY IN TREATING ANTIBIOTIC-ASSOCIATED DIARRHEA IN IMMUNODEFICIENCY
MICE
Nosalskaya T.N., Martynov A.V., Bomko T.V., Kabluchko T.V.
Introduction. One of the most promising probiotic including spore-forming
microorganisms is a lactobacilli Bacillus
coagulans (BC). In the spore form, it is resistant to technological
processes and storage, it does not collapse under the influence of gastric
juice and bile. After getting into the duodenum, the BC spores can germinate
into vegetative bacteria in the human intestine and exert their probiotic
effects. BC is not a part of dietary supplements. Recently, many drugs with
proven clinical efficiency, based on BC, in the global pharmaceutical market
are present. Based on the BC, the drug Laktovit Forte’s influence on the digestive
disorders and intestinal dysbiosis caused by streptomycin chronic
administration in immunodeficiency mice was investigated in this study. Materials
and methods.
Work carried out on white outbred
mice weighing 20-22 g to simulate digestion disorders characterized by
diarrhea in mice for 9 days through streptomycin administered
intragastrically at a dose of 2 g / kg of body weight. Disorders in the
immune status were modeled by a single subcutaneous injection of
cyclophosphamide at a dose of 250 mcg / kg. A Bacillus coagulans from
Laktovit Forte was administered to the animals of experimental groups
intragastrically at a dose of 46 mg / kg. Comparison
drugs were capsules containing Lactobacillus acidophilus (LA-5) and
Bifidobacterium animalis subsp. lactis (BB-12). Comparison drugs were also
administered intragastrically at a dose of 42 mg / kg. Both drugs were
administered beginning from day 6 after antibiotic was started to be
administered, the treatment duration was for 7 days. Animals were randomized into groups by 12 animals each:
1 - intact control; 2 - control disease (only streptomycin administered); 3 -
pathology with immunosuppression (both streptomycin and cyclophosphamide
administered); 4 - streptomycin + Laktovit Forte; 5 - pathology immunosuppression
+ Laktovit Forte; 6 - streptomycin + reference drug; 5 - pathology
immunosuppression + reference drug. Results and discussion. Laktovit Forte (BC) showed pronounced
Antidiarrheal effect - the effect was 75%, and in immunodeficiency conditions
only 50%. The antidiarrheal effect of the drug based on comparison
lactobacilli was 60% in both groups. Similar trends were observed in level of
intestinal motility. The Laktovit Forte decreased high intestinal motility
during pathology at 61%; in immunosuppression conditions - only 54%.
Comparing the drug produced a less pronounced effect, but similar in the
groups with and without immunosuppression - respectively 44.5 and 45.9%. BC effects differently under immunosuppressant conditions
and without; indicating the importance of immune component in the mechanism
of its action in antibiotic-associated diarrhea. The drugs based on
comparison bacteria have less pronounced effect, indicating that its
probiotic effects and the absence of immune system direct stimulation. The
Laktovit Forte is also more effective in preventing body weight loss in
animal than comparison drug on the background of the development pathology.
For all studies indicates Laktovit Forte was significantly more effective
than the drug on the other lactobacillus. Conclusion. Bacillus coagulans from Laktovit Forte
provided antidiarrheal effect not only due to the antagonistic probiotic
action, but also due to direct stimulation of the immune system.
Key
words: Bacillus
coagulans, probiotic , immunodeficiency mice, antidiarrheal
effect
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28-33
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̲ÊÐÎÅÊÎËÎòß
ÑËÈÇÎÂί ÎÁÎËÎÍÊÈ ÀËÜÂÅÎËßÐÍÈÕ ÃÐÅÁͲ  ÏÅвÎÄ ÀÄÀÏÒÀÖ²¯ ÄÎ ÏÎÂÍÈÕ ÇͲÌÍÈÕ
ÏÐÎÒÅDzÂ
ßí³øåí ².Â.,
Ñîõàíü Ì.Â., Îñîëîä÷åíêî Ò.Ï., Ïîíîìàðåíêî Ñ.Â.,
Ìåæèáåöüêèé Ä.Î.
MICROECOLOGY OF THE MUCOUS
MEMBRANE OF THE ALVEOLAR RIDGES IN THE PERIOD OF ADAPTATION TO COMPLETE
DENTURES
Yanishen I. V., Sokhan M. V., Osolodchenko T. P., Ponomarenko S. V., Mezhybetskyi D. O.
Introduction. The oral cavity
is an open ecosystem for various microorganisms and is one of the most
populated biotopes of human. Removable dental prosthesis creates favorable
conditions for the breeding of various microorganisms, including fungi.
Stomatitis of dentition (SOD) refers to a group of the most frequent
pathologies of the mucous membranes of the oral cavity inflammatory character,
due to the presence of the patient's dental prosthesis. For the prevention of
SOD due to removable prostheses are used proper hygiene of dental prostheses,
manufacture of technologically optimal designs of dentures, the shielding of
the prosthesis and the use of cushioning materials. In this regard, the aim
of this work was to study the dynamics characteristics of the microbiota of
the mucous membranes of the oral cavity when performing prosthetic
rehabilitation of patients with complete removable acrylic dentures with the
use of adhesive and without its use. Materials and methods. The
formation of the clinical groups of the patients occurred according to the
following criteria: the study group comprised 23 patients with complete
edentulous upper and lower jaw, which produced full removable laminar
dentures on the upper and lower jaw, which used water-resistant adhesive
based on polyvinylacetate and carboxymethilcellulose (cushions and/or cream
"Fittydent") according to the instructions of the manufacturer, the
control group consisted of 12 patients with complete edentulous upper and
lower jaw, which produced full removable laminar dentures on the upper and
lower jaw, in the period of adaptation to removable dentures has not applied
the adhesive to improve the fixation of dentures. Microbiological examination
of patients was carried out in dynamics before developing the prosthesis, after a week and after a month's stay of the
prosthesis in the oral cavity. Results and discussion. Microbiological
studies included determination of the qualitative and quantitative
composition of the biocenosis. It is established that the microflora of the
alveolar ridge in patients with edentulous consisted of associations of
yeasts from 2-5 representatives of the microbial world. It is established
that in patients of the experimental group on the 7th day of withdrawal
3-component microbial associations has decreased in 1.3 times, whereas the
4-component associations were recorded in 1.4 times more often compared with
the initial period of observation. For patients with adhesive frequency of
detection of 2-component microbial associations 30-the day of the research
was 1.3 times higher than prior to the setting of the prosthesis. Identify 5
component associations for 30-the day, has decreased in 2 times. In patients
without adhesive (control group) 4-component microbial associations in the
mouth after a week of adaptation to the prosthesis were detected in 1.6
times, and 30 days – in 2 times more often than to prosthetics. The weight 5
component associations through the week remained at the initial level, while
after 30 days has increased in 1,5 times. The structure
microbiocenosis the mucous of the oral cavity patients with edentulism are
represented 13 genera of bacteria and morilioid fungi of the genus Candida,
allocated in secondary amounts by lg (2,5±0,19) to lg (5,4±0,17) CFU/g. When
adhesive between denture base and mucosa of the alveolar ridge frequency of
withdrawal and the density of microbial colonization in the adaptation period
were not statistically different. But the density of the microbial population
among the control group increased 1.5 times for Enterococcus spp, 1.4
for the Klebsiella spp and 1.6 times for yeast fungi Candida spp.
Found a significant decrease in microbial density of the representatives of
the resident microflora in 1.4 times for Neisseria spp, 1.6-fold for Lactobacillus
spp (p<0.05). Conclusion. The results of these studies indicate
significant changes of qualitative and quantitative structure of microbiocenosis
of oral cavity in patients with edentulous representatives Moraxella spp,
Klebsiella spp and E. coli Comparison of frequency of discharge
and the density of microbial colonization showed persistence in a given
habitat representatives of 13 genera of bacteria and yeast fungi of the genus
Candida in medium quantities from lg (2,5±0,19) lg to (5,4±0,17)
CFU/g. For patients who used adhesive (fixative cream and/or cushions
Fittydent) on the basis of carboxymethilcellulose and polivinilatsetat in the
period of adaptation to removable prosthesis characteristic was reduced in 2
times revealing the 5 component associations on 30 the day. Frequency of
withdrawal and the density of microbial colonization of the experimental
group were not statistically different. Among patients in the control group
increased the density of microbial colonization for Enterococcus spp, Klebsiella
spp and yeasts of Candida spp. Found a significant decrease in
microbial density of the representatives of the resident microflora in 1.4
times for Neisseria spp, 1.6-fold for Lactobacillus spp.
Identified microbiological characteristics dictate the need for inclusion in
the treatment of patients with edentulous circuit correction of
microbiocenosis of the oral cavity, with the use of the funds are directed
anti-inflammatory action and ensure the restoration and preservation of
normal biocenosis of the specified biotope.
Key
words: microecology, adaptation, adhesive, complete dentures.
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34-39
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ÂÈÂ×ÅÍÍß
ÏÐÎÒÈ̲ÊÐÎÁÍί ÀÊÒÈÂÍÎÑÒ² ÊÎÌÁ²ÍÀÖ²É ÔÎÑÔÎ̲ÖÈÍÓ Ç ÖÅÔÅϲÌÎÌ ÒÀ
ÔÎÑÔÎ̲ÖÈÍÓ Ç Ò²ªÍÀÌÎÌ ÙÎÄÎ ÏÎ˲ÀÍÒÈÁ²ÎÒÈÊÎÐÅÇÈÑÒÅÍÒÍÈÕ ØÒÀ̲Â
ÅÍÒÅÐÎÁÀÊÒÅвÉ
Äÿ÷åíêî Â.Ô.,
Ìàðþùåíêî À.Ì.,
×èãèðèíñüêà Í.À.,
Êóöàé Í.Ì.
THE STUDY OF ANTIMICROBIAL ACTIVITY OF COMBINATIONS
OF FOSFOMYCIN WITH CEFEPIME AND FOSFOMYCIN WITH TIENAM IN RESPECT
POLYANTIBIOTIC-RESISTANT STRAINS OF ENTEROBACTERIA
Dyachenko V.F. Mariushchenko A.M., Chygyrynska
N.A., Kutsay N.
Introduction. The rapid decrease in sensitivity of pathogens of
septic infections to antimicrobial agents has led to significant difficulties
in the treatment of antibioticresistant infections. One solution of this
problem is the method of combining of antimicrobial medications from
different pharmacological groups. Antimicrobial synergy resulting from
antibiotic combination therapy is often important in the treatment of serious
bacterial infections. The aim of the study is investigation of combined
antimicrobial action of fosfomycin with cefepim and fosfomycin with tienam in
respect polyantibiotic-resistent strains of enterobacteria. Materials and methods. The
polyantibioticresistant strains used in this study were isolated from
patients hospitalised in the Hospital of Kharkov. The study of combinations
of antibiotics efficacy was carried out by determining the minimum inhibitory
concentrations using routine in vitro “checkerboard” method. Results and discussion. Calculation
of the fraction inhibitory index showed that the combination of fosfomycin
with cefepime demonstrated synergistic inhibitory activity against 71,43 % of
enterobacteria strains tested; combination of fosfomycin with tienam result
in summation or indifferent effect against 71,43 % polyantibioticresistant
strains of enterobacteria. Conclusion.
Thereby combination of fosfomycin with cefepime may be considered as
synergistic and perspective for further experimental in vivo studies and
studies of their clinical effectiveness against polyantibioticresistant
strains of enterobacteria – causative agents of pyoinflammatory diseases.
Key words: combinations of the antibiotics, polyantibioticresistant strains,
"checkerboard" method.
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40-42
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ÅÊÑÏÅÐÈÌÅÍÒÀËÜͲ
ÐÎÁÎÒÈ, ÔÀÐÌÀÖÈß
Experimental papers, pharmacy
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COMPARATIVE STUDY OF ANTIBACTERIAL ACTIVITY OF PEROXYDISUCCINIC ACID,
HYDROGEN PEROXIDE AND THEIR MIXTURE
Blazheyevskiy M. Ye., Boyko N. N., Prysiazhniuk Î. V.
Introduction. It is known that reactive oxygen species (ROS) generated in vivo by
cell aerobic metabolism cause multiple damage in different cell organelles
and kill not only obligate anaerobes and microaerophilles, but also aerobes.
ROS generated by phagocytes and representatives of normal microflora are an
important component of macroorganism defense from most pathogens, which is
explained by their ability to damage different biological structures. ROS have high reactivity and let us use them
in vitro as effective biocides. Hydrogen peroxide is widely used in many
industries, in particular, in medicine and veterinary as antiseptic and
disinfectant agent due to its safety for environment and broad spectrum of
antimicrobial activity including spore-forming bacteria. However, in the recent
years certain decrease of background sensitivity of microorganisms to
hydrogen peroxide and occurrence of resistant strains of pathogenic
microorganisms to this agent has been noted. The aim of this work is to carry out a comparative study of antimicrobial
activity of hydrogen peroxide, peroxydisuccinic acid (PDSA),
monoperoxysuccinic acid (MPSA), and mixture of PDSA and hydrogen peroxide
(Í2Î2). Materials and methods. The
substances of peroxydisuccinic acid (PDSA) and monoperoxysuccinic acid (MPSA)
were prepared by well known methods. The following test-strains were used to
assess antimicrobial activity of the agents: Staphylococcus aureus ÀÒÑÑ
25923, Escherichia coli ÀÒÑÑ 25922, Pseudomonas aeruginosa ÀÒÑÑ 27853,
Pseudomonas aeruginosa ÀÒÑÑ 9027, Basillus ñereus ÀÒÑÑ 10702, Basillus ñereus
ÀÒÑÑ 96, Basillus subtilis ÀÒÑÑ 6633, Proteus vulgaris ATCC 4636, Candida
albicans ÀÒÑÑ 885/653, and Candida albicans ÀÒÑÑ 10231. All disinfectant agents were diluted in
distilled water at 40 ºÑ and stirred. The microbial burden was 2∙109 CFU/ml
of the medium, and for kinetic studies 105 CFU/ml of the medium, it was
standardizing according to McFarland standard. Microorganisms’ resistance to
disinfectant agents was determined by seeding of the diluted cell suspension
on agar medium after their incubation with MPSA, PDSA, Í2Î2, and also after
MPSA generation in the reaction between PDSA and Í2Î2, and seeding of the
cell suspension with exclusion of these factors was taken as control.
18-24-hour microorganism culture was taken into work. Mueller-Hinton agar and
MPA were used for bacteria. Sabouraud agar was used for Candida albicans.
Agar well diffusion method was applied. Determination of antimicrobial
activity of the agents were carried out on two layers of solid medium in
Petri dishes. In kinetic study of microorganism’s death rate due to
incubation period with peroxide solution tested, the bactericidal action was
stopped with 5 % sodium thiosulfate sterile solution. All studies were
carried out in 3 replicates. In statistical analysis methods, significance
level P was equal to 0.95. Student’s test was used for statistical processing
of the data obtained. Results and
discussion. It has been found that treatment of S. aureus ÀÒÑÑ 25923, E.
coli ÀÒÑÑ 25922 test-strains for 60 min with 3% (and even 6% Í2Î2 for E.
coli) does not cause total death of microorganisms. The fact of resistance of
spore-forming cultures B. cereus, P. aeruginosa and C. albicans to hydrogen
peroxide should be noted, in 60 min of their incubation with 6% Í2Î2, the
number of viable cells decreased from 5.0 to 1.58 lg CFU/ml, as well as to
3.00 (to 1.84 for 120-min exposition) and 1.65 lg CFU/ml, respectively. However,
pretreatment of test-stains by 5-fold diluted mixture of 3% Í2Î2 and 1% PDSA
for 60 min caused total death of S. aureus and E. ñoli, and decreased the
number of viable cells of B. cereus spore-forming cells and relatively
resistant to hydrogen peroxide cultures of P. aeruginosa è C. albicans from
5.00 to 1.34 and 0.95 lg CFU/ml, respectively, and in 120 min to their total
death. Conclusions. The study have determined that antimicrobial effect
of reactive oxygen species (ROS) produced by interaction of hydrogen peroxide
and peroxydisuccinic acid (PDSA) mixture in the synergistic system is many
times higher and faster achievable than hydrogen peroxide or peroxydisuccinic
acid only. We have determined the principles of optimum conditions for ROS
generation by choice of respective concentrations of peroxydisuccinic acid
and hydrogen peroxide. ROS demonstrate high biocidal activity and short
lifetime, which allows us to consider the combination of hydrogen peroxide
and peroxydisuccinic acid as a promising means for development of a highly
efficient disinfectant with a broad spectrum of antimicrobial activity and
without a tendency to accumulate in the environment.
Key words: reactive oxygen species (ROS), bacteria,
biocide, disinfectant, hydrogen peroxide, peroxydisuccinic acid, synergetic
composition.
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43-49
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DEVELOPMENT OF METHOD OF
QUALITATIVE ANALYSIS OF BIRD CHERRY FRUIT FOR INCLUSION IN THE MONOGRAPH OF
STATE PHARMACOPOEIA OF
UKRAINE
Lenchyk L. V., Kotov A. G., Kyslychenko V. S., Kotova E. E.
Introduction. Bird cherry Padus avium Mill, Rosaceae, is widespread in Ukraine, especially in forests and
forest-steppe areas. Bird cherry fruits have long
been used in medicine and is a valuable medicinal raw materials. They stated to posess astringent, anti-inflammatory, phytoncidal
properties. Bird cherry fruits are included in the USSR Pharmacopoeia
IX ed., The State Pharmacopoeia of the Russian Federation, The State
Pharmacopoeia of Republic of Belarus. In Ukraine there are no contemporary normative
documents for this medicinal plant material, therefore it is the actual to
develop projects in the national monographs "dry bird cherry
fruit" and "fresh bird cherry fruit" to be included in the
State Pharmacopoeia of Ukraine. According to European Pharmacopoeia recommendation
method of thin-layer chromatography (TLC) is prescribed only for the
identification of the herbal drug. The principles of thin-layer chromatography and application of the
technique in pharmaceutical analysis are described in State Pharmacopoeia of Ukraine. As it
is effective and easy to perform, and the equipment required is inexpensive,
the technique is frequently used for evaluating medicinal plant materials and
their preparations. The TLC is aimed at elucidating the chromatogram of
the drug with respect to selected reference compounds that are described for
inclusion as reagents.
Aim of this study was to develop methods of qualitative analysis of bird
cherry fruits for a monograph in the State Pharmacopoeia of Ukraine (SPU). Materials and Methods. The object of our study was dried bird cherry fruits
(7 samples) and fresh bird cherry fruits (7 samples) harvested in 2013-2015
in Kharkiv, Poltava, Luhansk, Sumy, Lviv, Mykolaiv regions and the city
Mariupol. Samples were registered in the department of SPU State Enterprise
"Pharmacopeia center". In accordance with the Ph. Eur. and SPU
requirements in "identification C" determination was performed by
TLC. TLC was performed
on glass-backed silica gel F254Merck plates, size 20x10 cm. Test solutions from samples of dried raw material
were prepared by extraction of 1% solution of hydrochloric acid in 95%
ethanol with ultrasound for 60 minutes at 50º C. As mobile phase solvent
mixture ethyl acetate - anhydrous acetic acid - formic acid - water ratio
(100: 10: 10: 25) was selected. For preparation the reference solution 1 mg
chrysanthemin was dissolved in 10 mL of 1% solution of hydrochloric
acid in 95% ethanol. Fresh bird cherry fruits test solutions of the samples
were crushed to mash (free of seeds), 10 mL of methanol was added and treated with
ultrasound for 15 minutes. As mobile phase solvent mixture formic acid
anhydrous-water-butanol ratio (16:19:65) was selected. Two reference solutions were used.
First was prepared from 2 mg chrysanthemum dissolved in 5 mL of methanol and
second was Pharmacopoeial Reference Standard SPU of bird cherry
extract dissolved in 0.2 mL of
methanol with ultrasound bath. Test solutions and the reference solutions
were placed onto the chromatographic plates and placed into the chamber. When the chromatograms developed, the plates were
taken out, then observed the spots in daylight. Results
and discussion. In
the chromatogram it was observed for all dry bird cherry fruits samples two
pink-red color zones, one of which coincided for Rf and color of chrysanthemin, and the other one was slightly
lower. The chromatogram for all samples of fresh raw material showed two
pinkish-violet zones, one of which had Rf and color corresponded
chrysanthemin, and the second one was slightly lower. Compared with bird
cherry extract, it was observed two pinkish-violet zones, coincided with Rf
and color of bird cherry (SPU) extract
zones. In accordance with the requirements of Ph. Eur.
identification by TLC is obligatory. Division of anthocyanins of plant raw materials was observed
sufficiently in our chosen solvent systems and methods of analysis that
allows to recommend these systems and methods of analysis for inclusion in
the relevant sections of monographs for bird cherry fruit, dried and fresh
for SPU. Conclusion. It was confirmed the opportunity to include in
the national monographs "Bird cherry fruits fresh " and " Bird
cherry fruits dry" in section "Identification C" analysis of
anthocyanin by TLC in chosen systems and methods.
Key words: bird cherry, TLC, State
Pharmacopoeia of Ukraine
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50-53
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ÂÎÇÌÎÆÍÎÑÒÜ
ÏÐÈÌÅÍÅÍÈß ÑÆÈÆÅÍÍÛÕ ÃÀÇΠÄËß Î×ÈÑÒÊÈ ÀËÊÀËÎÈÄΠÁÀÐÁÀÐÈÑÀ
Äåìüÿíåíêî Ä.
Â., Äåìüÿíåíêî Â. Ã.
POSSIBILITY FOR APPLICATION OF LIQUEFIED GASES FOR
PURIFICATION OF BARBERRY ALKALOIDS
Demyanenko D. V., Demyanenko V. G.
Introduction. Biologically active
substances (BAS) of barberry roots represented by alkaloids of isoquinoline
group are perspective substances for development of preparations with
multiple pharmacological activities. However, now
manufacture of them in Ukraine is stopped. One of the reasons of this is out-of-date production technologies of alkaloids
involving use of toxic and/or flammable solvents.
In the article possibility for application of liquefied gases in technology
of obtaining of alkaloids from barberry roots has been studied. Materials
and methods. Initial raw herb drug were
barberry (Berberis vulgaris) roots
harvested in spring on the territory of
Southern Ukraine. Their moisture content was
11%, comminuting degree was 0,5-1,4 mm. At the first stage purification
of raw herb drug from lipophilic impurities (defatting) was made with use of some liquefied gases: tetrafluoroethane, isobutane,
difluorochloromethane and difluoromethane.
Extraction of the alkaloid sum was made with difluoromethane mixed with
various quantities of liquid ammonia or diethylamine as alkaline agent. Crude
extracts were exposed to two-level liquefied-gas purification. At
first the alkaloid bases were transformed
into saline forms with aqueous solutions of acids and purified from ballast impurities
with liquefied freon-22. Then alkaloid
salts were reextracted from aqueous phase in the
base form with liquefied mixture of difluoromethane
and ammonia. Mixing of liquid phases was provided by creation of alternate
gradients of temperatures and, as consequence,
pressures between separators feeding alternately
cool water into jacket of one of them, and warm water – into jacket of another
one. Quantity of lipophilic ballast
impurities and also weight of extractives were determined gravimetrically.
Quantitative analysis of the alkaloid sum
was made by titrimetric method after sedimentation of alkaloids with
volumetric solution of phosphomolybdic acid. Results and
discussion. It has been found that at stage of
degreasing of raw crude drug the most selective solvent to lipophilic ballast
compounds was isobutane and
difluorochloromethane, but the latter was more rational for using in
industrial scale concerning its fire-safety and economic availability. It has been also
found that efficiency of the purification stage of Berberis alkaloids appreciably
depends on
composition of extracting solvent while obtaining of crude extracts. The best
parameters in the finished product have been revealed after purification of
the extracts obtained with difluoromethane containing 12% of liquid ammonia:
quantity of BAS (alkaloids) in the finished product reached 95%, and their losses were insignificant – 3,5%. Increasing of
cosolvent (ammonia) content in the extracting solvent considerably complicated
purification of extractives, and losses of
alkaloids raised to 13,2%, obviously as a
result of presence of considerable quantity of hydrophylic ballast substances. Reducing of
the ammonia content in the extracting solvent down to 1% also caused negative
impact on process of obtaining of the alkaloids
which yield was the lowest among investigated
assays. It’s possible to explain this by lower ðÍ value in extracting medium, change of solvent polarity, therefore
middle-polar and hydrophobic compounds
preferably passed into composition of crude extracts. Conclusions. Acceptability
for use of liquefied gases and their mixtures for purification of the
alkaloid sum from barberry roots has been proved. It has been shown that
prior to stage of extraction of these BAS it’s expedient to withdraw lipophilic
impurities from the crude herbal drug with liquified difluorochloromethane
(freon-22). Purification efficiency of the finished product considerably depends
on composition of extracting solvent during obtaining of crude extracts. The
best parameters were found after purification of the extracts taken with
difluoromethane containing 12% of liquid ammonia. It’s the most
expedient to purify crude extracts by two-step procedure using on the first
step liquefied difluorochloromethane (freon-22) as organic phase and on the
second one – difluoromethane mixed with 10% of ammonia, and as aqueous phase
– 10 % acidic solutions; at the second step it’s necessary to provide liquid
re-extraction of the alkaloid bases in triplicate.
Keywords: barberry roots, alkaloids, liquefied
gases, purification.
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54-58
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ÄÎÑ˲ÄÆÅÍÍß
̲ÊÐÎÕÂÈËÜÎÂί ÑÓØÊÈ ÃÐÀÍÓË ÖÅÎ˲ÒÓ ÏÐÈÐÎÄÍÎÃÎ ÒÀ ¯¯ ÂÏËÈÂÓ ÍÀ ÒÅÕÍÎËÎò×Ͳ
ÂËÀÑÒÈÂÎÑÒ²
Ðèáà÷óê Â.Ä.
RESEARCH OF MICROWAVE DRYING OF NATURAL ZEOLITE GRANULES AND ITS INFLUENCE
ON THE TECHNOLOGICAL PROPERTIES
Rybachuk V.D.
Introduction. The wet
granulation technique is often used in the preparation of free-flowing
granules in the manufacture of tablets and capsules. It is very important
that granules obtained by this technology be dried before further processing.
And also, it is important that the method of drying is entirely controlled
and managed and the result is quite predictable. In recent years, microwave
drying of granules make a considerable interest. Microwave drying is
especially useful for moisture sensitive materials which are mostly
pharmaceutical substances. Microwave drying technology is useful for dosage
forms with high purity, since this method provides the possibility of drying
in the same container production, which reduces the chance of cross
contamination of matter and its direct contact with staff. The aim of this work was to study the effect of
microwave radiation on the technological properties of natural zeolite peets
compared to traditional convection method and to determine the optimal drying
modes and specific humidity of the
material. Material & methods. Granules
were prepared by wet granulation technology by using a laboratory granulator
NG-12. As the humidifier we used potato starch gel and PVP in an amount of 25% by weight of the dry
product. The resulting granules were divided into two equal parts and
subjected to drying in a microwave oven (Delfa D20MW) of installed capacity
(119 W, 280 W, 336 W, 462 W, 595 W and 700 W)
and shelf dryer to a residual moisture level of 0.01 g.w./g.d.m. or less.
Determination of the specific humidity of granules was carried out by mass
loss on drying. Fractional composition of granules was determined using a
standard set of sieves with the diameter of the holes 2.0; 1.0; 0.5 and 0.25
mm. The friability of the granules was determined using friabilator Pharma
Test PTF 10E / ER, Germany. To characterize the fluidity of granule Carr`s
indicator (IC) and coefficient Hausnera (HR). Results & discussion. The
results of experimental studies have shown a significant impact of intensity
microwave radiation on the rate of drying material. With an increase in power
from 119 watts to 700 watts time spent on drying decreased more than twice.
Changing the speed of drying material took place in two periods. In the first
period (humidity of 0,29-0,05 g.w./g.d.m.) free moisture located mainly on
the surface of the granules is removed in the first period, in the second
period (0,04-0,05 g.w./g.d.m.) moisture from the inner pores of the material is removed. Type of drying does not significantly affect the
distribution of particle size. Different amounts of microwave radiation also
not significantly affect the size and rheological properties of the granules.
The last one was confirmed by values of Carr`s index and coefficient of
Hausner. Both indicators showed that all series of obtained granules have
very good flowability. Study of the
influence of specific humidity values on the mechanical strength of granules
and tablets obtained on the basis showed that its most optimal level, which
can be recommended both for granules and for tablets, is based on their range
of 0,03-0,05 g.w./g.d.m. Knowing the limits of specific humidity allows to
choose optimal modes of power microwave radiation for drying a natural
zeolite granules. Conclusion. The effect of
microwave radiation on the dynamics of natural zeolite pellets drying on the
value of their technological properties. Optimal levels of specific humidity
for granules and tablets, providing the best technological properties, is
0,03-0,05 g.w./g.d.m. On the basis of data obtained, the reasonable duration
of the process of drying, depending on the power of the microwave radiation,
is 3-14 minutes.
Keywords: natural zeolite, granules, microwave drying, humidity,
technological properties
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59-64
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ÐÎÇÐÎÁÊÀ
ÑÊËÀÄÓ Â²Ò×ÈÇÍßÍÎÃÎ ²ÍÔÓDzÉÍÎÃÎ
ÏÐÅÏÀÐÀÒÓ ÍÀ ÎÑÍβ ÏÀ-ÐÀÖÅÒÀÌÎËÓ
Àëìàêàºâà Ë.Ã., Íàóìåíîê Ë.Ã., Áºãóíîâà Í.Â., Äîëÿ
Â.Ã., Àëìàêàºâ Ì.Ñ.
DEVELOPMENT OF DOMESTIC INFUSION DRUGS BASED ON PARACETAMOL
Almakaeva L.G, Naumenok L.G., Begunova N.V. Dolya V.G., Almakaev M.S
The
intravenous form of paracetamol compared with oral more reliably supports
effective drug concentration in blood plasma that promotes a higher
therapeutic effect. Recent studies have
confirmed that the use of the intravenous form of paracetamol to deal with
postoperative pain multimodal analgesia modes results in reducing the
frequency and quantity of opioids administered , and, as a consequence, its
associated side effects. The drug Paracetamol , infusion solution 10 mg / ml to 100 ml glass
bottles is a drug - generic . His qualitative and quantitative composition is
developed from the study of literature data about the drug - similar to
" Perfalhan , 10 mg / ml solution for infusion in 100 mL " company
Bristol - Myers Squibb, France and experimental work. The aim of our study is development and support of the national composition of the infusion of
the drug on the basis of paracetamol, selection of excipients that provide stability of
the active substances. Materials and methods. The object of the study
was the substance of paracetamol manufactured by Zhejiang Kangle
Pharmaceutical Co. , Ltd, China. During the work conducted qualitative and
quantitative monitoring sample preparation for indicators of stability: pH
content of the active ingredient , transparency, color, impurities ,
contamination by the methods described in the SFU [and nor- ral documentation
to the drug . One potential factor of instability is the effect of
paracetamol oxygen, due to the presence in the molecule of paracetamol and
-NH possibility of oxidation. Results and Discussion. Paracetamol is
derived atsetamina . Substance acetylation are p - aminophenol with acetic
anhydride . Saturated aqueous solution has a pH of paracetamol - ment about 6 . Paracetamol is a
crystalline white powder , sparingly soluble in water, soluble in 96%
alcohol, very slightly soluble in metilenhloride . . Active substance enters in comparison
drug in the concentration of 10 mg/ml. Stable aqueous solution decreases in
acidic and alkaline environments where paratse - tamol gradually destroyed to
acetic acid or p - aminophenol To prevent oxidation of the drug administered
antioxidant - sodium metabisulfite in concentrations generally 1.0 g / l. In
order to prevent the negative - tive impact of oxygen on paracetamol solution
10 mg / mL drug preparation was conducted under nitrogen gas protection . It
is established that the use of nitrogen gas protection affects the quality of
the drug. Prepared sample preparation without nitrogen gas protection did not
meet project MKYA in terms of " 4 - aminophenol " and " color
", besides a slight tendency pH change and reducing quantitative content
of active ingredient. Therefore, the production of the drug "
Paracetamol , infusion solution 10 mg / ml. in bottles of 100 ml "
necessary solution prepared bubbling nitrogen for 20 minutes. It is
established that the use of nitrogen gas protection affects the quality of
the drug. the manufacture of the drug " Paracetamol , infusion solution
10 mg / ml. in bottles of 100 ml " necessary solution prepared bubbling
nitrogen for 20 minutes. Calculated theoretical osmolarity of the drug- 299,47 ìÎsì / l. Solution osmolarity close to osmolarity of blood, which is
an important criterion when used in injection therapy. Conclusions. Theoretically grounded and experimentally confirmed rational composition drug infusion composition
based on paracetamol. Selected
auxiliaries and processing methods in the preparation of the solution ,
prevents oxidation of the main active ingredient , and also provide the
optimum level of osmolarity solution. Results of this development are used during compile of registration
dossier of preparation, analytical and technological normative documents on
his production and control of quality of intermediate products and prepared
products.
Keywords: infusion solution , paracetamol , osmolarity
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65-68
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ÀÍÒÈÌÈÊÐÎÁÍÛÅ
ÑÂÎÉÑÒÂÀ «ËÈÏÈÍÀ» ÏÐÈ
ÈÍÃÀËßÖÈÎÍÍÎÌ
ÈÑÏÎËÜÇÎÂÀÍÈÈ Ó ÄÅÒÅÉ, ÁÎËÜÍÛÕ ÁÐÎÍÕÈÀËÜÍÎÉ ÀÑÒÌÎÉ
×åðíóñêèé Â.Ã.,
Ïîïîâ Í.Í., Ãîâàëåíêîâà Î.Ë., Ëåòÿãî À.Â.,
Êàøèíà-ßðìàê Â.Ë.,
Åâäîêèìîâà Ò.Â.
ANTIMICROBIAL
PROPERTIES «LIPIN» INHALATION USE IN CHILDREN WITH ASTHMA
Chernusky V.G., Popov
N.N., Govalenkova O.L., Letyago A.V., Kashina-Yarmak V.L.,
Evdokimova T.V.
Introduction. Problems of modern
pharmacotherapy of bronchial asthma (BA) in children is largely reduced to
the establishment of effective dosage forms that provide the delivery of
drugs in the bronchopulmonary system without affecting other organ systems. A
promising area in addressing the causal treatment of asthma in children is
the use of the formulation «Lipin», which is a liposome, arising by
self-assembly of amphiphilic lipid complexes. Material & methods. The study of antimicrobial properties
«Lipin» on microorganisms isolated from sputum in 135 children are
hospitalized in the pulmonology department of GU «Children's Hospital road»
Kharkiv about asthma in the period of exacerbation. Age was surveyed children
from 5 to 14 years on average - 11 ± 0,12 years. The diagnosis of bronchial
asthma (BA) is set according to GINA guidelines. The treatment groups were
representative, rondomizirovany by age, sex, severity of the disease.
Patients with asthma in all forms (atopic, non-atopic, mixed) and severity
(mild, moderate, severe) received basic asthma treatment according to the
Ministry of Health of Ukraine ¹ 4.01.12-8.1178 order dated 14.12.2009, which
was supplemented by liposomal formulation «Lipin» inhalation through an
ultrasonic nebulizer in age dosage. All drugs used in accordance with
instructions for their use, approved by the Ministry of Health of Ukraine.
Microbiological examination of sputum was performed by conventional methods:
for seeding solid or liquid nutrient medium, followed by isolation and
isolates microscopy, biochemical and serological identification.
Identification of the isolates was performed according to the position of the
Ministry of Health USSR order number 535 and respectively toksonomicheskih
determination tests bacteria Burgi. The antimicrobial activity of the
preparation «Lipin» was determined by the level of the minimum inhibitory
concentration (MIC) - twofold serial dilution method in medium
Mueller-Hilton, the minimum bactericidal concentration (MBC) - was carried
out on crops of solid growth medium by the method of S. Navashin.
Statistical analysis of the results was performed
using Exel applications, Statgrafics-5 with the definition average value (M)
and standard error (m). The obtained data were statistically processed by
parametric mathematical statistics (t-Student criterion) when < 0,05.
Results & discussion. While recognizing the
authority of the International (GINA, 2012) and a national protocol on the principles
of asthma therapy in children, it should be noted that the recommended
therapy is mainly focused on the achievement of symptomatic and pathogenetic
effects. In principle this is not considered part of the microbial factor not
only in the induction, but also burdening the pathogenesis and clinical
course of the disease in children. In this connection, studies on the effect
of non-allergic (infectious) factors on the development of asthma as a
multi-stage, sequential pathological process and the development of
additional methods of basic therapy is relevant and allows individualized
therapy protocols in relation to the etiological factors of the disease. The
study showed that in the sputum of children with asthma in all forms of the
disease were determined by the following organisms: S. pyogenes, S. aureus,
E.coli, Pr. Mirabilis, Ps. aeruginosa. In 29.6% of children with asthma from
sputum were sown Association: S. aureus + S. pyogenes; S. aureus + E. coli;
S. aureus + Ps. aeruginosa; S. aureus + Pr. Mirabilis. The use of
corticosteroids in treatment of asthma in children contributes to the
activity of biological and pathogenic properties of indigenous, transient and
exogenous microflora, mainly by reducing its control alfeolyarnymi phagocytic
macrophages. As a result, the activation of pathogenic and conditionally
pathogenic microflora, leading to the development of processes in dysbiotic
bronchopulmonary system and disbionty on a new bio-based implement relapse.
From this it follows that even effective sanitation agents in
bronchopulmonary system, the traditional routes of administration of
antibacterial drugs, properly selected, taking into account the sensitivity
of pathogens to them, does not prevent it from subsequent reinfection
relevant pathogens located in the throat and in the bronchopulmonary system.
One way to solve this problem is to use as the dosage form liposomes, which
are limited microvolumes arising by self-assembly of amphiphilic lipid
complexes. The basis of selection of such a drug we used in the clinic used
liposomal preparation «Lipin» inhalation at dosages of age through an
ultrasonic inhaler in addition to basic therapy recommended by GINA (2012) in
two stages. The first stage is achieved by using «Lipin» in 135 children with
asthma, aged 5 to 14 years in acute inhalation through an ultrasonic
nebulizer in age dosage of 5-10 mg / kg, depending on the age of one
inhalation 2 times a day for 7-10 days in children with asthma. This is the
effect of biocompatibility with enzymatic and immunological systems of the
body, it is anti-microbial and anti-inflammatory effect «Lipin» due to their
constituent natural phospholipids - phosphatidylcholine. The second stage of
antimicrobial therapy for supporting sanitizing effect is based on the
ability to «Lipin» in saline to accumulate on the damaged parts of mucous
bronchopulmonary tree and provide prolonged antimicrobial effect and thus
prevent the proliferation of pathogenic and opportunistic microorganisms. Comparison
of the spectrum of antimicrobial activity of liposomal drug «Lipin» in saline
to microorganisms isolated from the sputum of an inhalation after treatment
showed that antimicrobial activity «Lipin» advantageously provides
bactericidal effect against pathogenic and conditionally pathogenic microorganisms.
It should be noted that this formulation does not have a significant impact
on the indigenous microflora of the mucous bronchial tree. Conclusions. 1. BA in children is
characterized by a complex structure combining etiologic gram-positive, gram-negative
microorganisms, fungi of the genus Candida, and their associations, isolated
from sputum and can be defined as the induction and relapse. 2. Liposomal
preparation «Lipin» inhalation through the use of an ultrasonic nebulizer has
a direct bactericidal effect on pathogenic and opportunistic pathogenic
microorganisms isolated from the sputum of children suffering from asthma in
the period of exacerbation (MIC - 2,12-3,43 mcg/ml, MBC - 3,41-12,6 mcg/ml).
3. «Lipin» pronounced bactericidal effect is in direct proportion to the dose
of the drug used and the time of its effects on the microorganisms isolated
from the sputum of children suffering from asthma. 4. Inhaler use liposomal
drug «Lipin» at a dose of 5.10 mg / kg body weight per inhaled three times a
day for 8-10 days causes bactericidal activity against Gram positive, Gram
negative microorganisms and fungi of the genus Candida, isolated from the
sputum children with asthma.
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69-74
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ÎÐÃÀͲÇÀÖ²ÉÍÎ-ÏÐÀÂβ ÒÀ ÌÅÄÈÊÎ-ÔÀÐÌÀÖÅÂÒÈ×Ͳ ϲÄÕÎÄÈ ÄÎ ÎÏÒÈ̲ÇÀÖ²¯
ÎÁ²ÃÓ Ë²ÊÀÐÑÜÊÈÕ ÇÀÑÎÁ²Â ÄËß Ë²ÊÓÂÀÍÍß Ã²ÏÅÐÒÎͲ¯ ÍÀ ÑÅ˲
Øàïîâàëîâà Â.Î., Õìåëåâñüêèé Ì.Î., Øàïîâàëîâ Â.Â.
Organizational, legal, medical and pharmaceutical
approaches to optimization of medicines’ circulation for hypertonia treatment
in countryside areas
Shapovalova V.O.,
Khmelevsky N.A., Shapovalov V.V.
Introduction. Parliaments of both Ukraine and the EU have
ratified Association Agreement (hereinafter – Agreement), a comprehensive
document which envisages bringing all areas of the law of our country in line
with European Union norms. Therefore, chapter 22 of the Agreement
"Public Health" gave attention as one of the most important areas
of implementation. That is, the need for introduction in Ukraine of the
approach, called "Health in all policy areas” provides consider of the
interests of public healthcare in approving of political solutions in any
area of the state activities. The organizational, medical and pharmaceutical
approaches to optimization of the medicines’ circulation is the improvement
of the legal system of regulation of prescription and OTC medicines (drugs),
determination of the circulation of drugs of different classification and
legal groups, assigning drugs to one of nomenclature and legal groups
(prescription or non-prescription). Materials and methods.
Forensic and pharmaceutical researches conducted in countryside areas at the
regional level on example of the Kharkiv region based on 54 communal health
institutions (CHI). Materials of the research: legal framework for the organization
of pharmacy of the CHI; forensic and pharmaceutical practice for the period
of 2012-2015 concerning the provision with the medicines of all legal,
nomenclature and classification groups for the pharmacotherapy of
hypertension in the village. In conducting the research, we used the
following methods: legal, documentary, comparative analysis, forensic and
pharmaceutical monitoring. Results and
discussion.
According to the Statement of the Cabinet of Ministers of Ukraine from
17.08.1998 N1303 was sorted the procedure of the concessional dispensing of
the drugs (for free or at 50% discount). The procedure applies to certain
categories of the population and some diseases for which benefits established
by applicable law. Despite the potential of this mechanism, it does not work
within the budget funding. Thanks to the work of the Department on the final
stage of the pilot project during the circulation of drugs and their
reimbursement attracted 575 pharmacies of different ownership forms and 1253
pharmacy points, whose work is in the village carried out by medical points,
general practice and family medicine. The conducted monitoring shows us that
during the pilot project 72 doctors of the CHI issued more than 265.2
thousand recipes. Hypertension drugs at discount prices began to sell from
pharmacies of Ukraine from 01.08.2012. Drugs released by prescription, which
could only write some doctors, family doctor, cardiologist, internist and
neurologist. To control this process created a single electronic register of
doctors and patients. Reimbursement cost of drugs for the treatment of
essential hypertension conducted from the state budget. During the
implementation of these measures was made following. Order from 23.05.2012
N331 "On creation of working groups” Department organized a telephone
hotline (057)705-10-64 for providing citizens, patients, most doctors,
physicians, pharmacists and others with advices on the introduction and
implementation of pilot projects involving scientific department of medical and
pharmaceutical law, general and clinical pharmacy of the Kharkiv Medical
Academy of Postgraduate Education. Order of the Department of Healthcare of
Kharkiv Regional State Administration from 10.09.2014 N560 "On approval
of the register of pharmacies" approved list of pharmacies and their
departments participating in the pilot project, which has 576 outlets
realization of drugs. Conclusions. Proposed the organizational, legal, medical and
pharmaceutical approaches to optimization of medicines’ circulation for the
treatment of hypertonia in countryside areas. Studied the existing
legislative and regulatory framework of Ukraine on providing ofor
concessional patients with hypertension drugs. Analyzed forensic and
pharmaceutical risks that cause problems in access for the patients to needed
medicines. Studied the example of forensic and pharmaceutical practice of
imperfections in pilot project among the countryside population. Studied the
system of interaction between specialists of medicine, pharmacy, state government
and other industries in the area of public access to essential medicines. A
review of the pilot project of reimbursement of the cost of antihypertensive
medications features in the Kharkiv region, the consequences of this project
for patients and healthcare of Ukraine and Kharkiv region.
Keywords: countryside area,
pharmacies, circulation, medicines, drugs, hypertonia, forensic pharmacy,
pharmaceutical law, medical law.
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75-85
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Þ²Ëů, ANNIVERSARY
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Ïðîôåñîð Ïàë³é
Ãîðä³é Êîíäðàòîâè÷
Ñëàâíèé þâ³ëåé
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86-87
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ÐÅÖÅÍDz¯,
REVIEWS
ÐÅÖÅÍDzß
íà ï³äðó÷íèê äëÿ ñòóäåíò³â âèùèõ ìåäè÷íèõ íàâ÷àëüíèõ çàêëàä³â ²V ð³âíÿ àêðåäèòàö³¿ «Ìåäè÷íà ì³êðîá³îëîã³ÿ, â³ðóñîëîã³ÿ
òà ³ìóíîëîã³ÿ» çà ðåäàêö³ºþ àêàäåì³êà ÍÀÍ ³ ÍÀÌÍ Óêðà¿íè Â.Ï. Øèðîáîêîâà
³ííèöÿ: Íîâà
êíèãà, 2011. - 952 ñ.: ³ë..
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88-90
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