Научная статья на тему 'Effect of niosomal antimicrobial peptide hBD-1 on the healing rate of infected wounds in rats'

Effect of niosomal antimicrobial peptide hBD-1 on the healing rate of infected wounds in rats Текст научной статьи по специальности «Клиническая медицина»

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Ключевые слова
ANTIMICROBIAL PEPTIDE / DEFENSIN / NIOSOME / ANTIBIOTIC RESISTANCE / HBD-1 / АНТИМИКРОБНЫЕ ПЕПТИДЫ / ДЕФЕНЗИНЫ / НИОСОМЫ / АНТИБИОТИКОРЕЗИСТЕНТНОСТЬ

Аннотация научной статьи по клинической медицине, автор научной работы — Bolatchiev Albert Dobaevich, Baturin Vladimir Aleksandrovich, Bazikov Igor Aleksandrovich, Maltsev Alexander Nikolaevich

In this study we investigated the effect of an antimicrobial peptide hBD-1 capsulated in organosilicon nanocontainers (niosomes) on the healing rate of experimental wounds infected with the clinical strain of Staphylococcus aureus. It was shown that the niosomal gel containing recombinant hBD-1 (1 |jg/ml) increases the linear healing rate of infected wounds in rats compared to the control group.

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ВЛИЯНИЕ НИОСОМАЛЬНОГО АНТИМИКРОБНОГО ПЕПТИДА HBD-1 НА СКОРОСТЬ ЗАЖИВЛЕНИЯ ИНФИЦИРОВАННЫХ РАН У КРЫС

Определялось влияние антимикробного пептида из класса бета-дефензинов (hBD-1), инкапсулированного в кремнийорганические наноконтейнеры (ниосомы), на скорость заживления экспериментальных ран, инфицированных клиническим штаммом Staphylococcus aureus. Было показано, что ниосомальный гель, содержащий рекомбинантный hBD-1 (1 мкг/мл), увеличивал линейную скорость заживления инфицированных ран у крыс по сравнению с контрольной группой.

Текст научной работы на тему «Effect of niosomal antimicrobial peptide hBD-1 on the healing rate of infected wounds in rats»

МЕДИЦИНСКИЙ ВЕСТНИК СЕВЕРНОГО КАВКАЗА

2018. Т. 13. № 3

medical news of north caucasus

2018. Vоl. 13. Iss. 3

About authors:

Bykov Ilia Mikhaylovich, MD, PhD, Professor, Head of the Department of Fundamental and Clinical Biochemistry; tel.: +79182125530; e-mail: [email protected]

Popov Konstantin Andreevich, PhD, Assistant; tel.: +79288824941; e-mail: [email protected] Berberidi Hristina Panaetovna, Post-graduate student; tel.: +79189045555; e-mail: [email protected]

Tsymbalyuk Igor Yuryevich, Laboratory assistant in the Department of Surgery № 2; tel.: +79284300769; e-mail: [email protected]

Ermakova Galina Аlekseevna, PhD, Assistant in the Department of Psychiatry; tel.: +79182125530; e-mail: [email protected]

Pavlyuchenko Ivan Ivanovich, MD, PhD, Professor, Head of the Department of Biology; tel.: +79183668281; e-mail: [email protected]

Storozhuk Petr Grigorievich, MD, PhD, Professor of the Department of Fundamental and Clinical Biochemistry; tel.: +78612680230; e-mail: [email protected]

Ovsyannikov Viktor Grigorievich, MD, PhD, Professor, Head of Department of Pathophysiology; tel.: +78632014412; e-mail: [email protected]

© Group of authors, 2018 UDC 615.28

DOI - https://doi.org/10.14300/mnnc.2018.13093 ISSN - 2073-8137

EFFECT OF NIOSOMAL ANTIMICROBIAL PEPTIDE hBD-1 ON THE HEALING RATE OF INFECTED WOUNDS IN RATS

Bolatchiev A. D.1, Baturin V. A 1 2, Bazikov I. A. 1, Maltsev A. N. 1

1 Stavropol State Medical University, Russian Federation

2 Center of Clinical Pharmacology and Pharmacotherapy, Stavropol, Russian Federation

ВЛИЯНИЕ НИОСОМАЛЬНОГО АНТИМИКРОБНОГО ПЕПТИДА hBD-1 НА СКОРОСТЬ ЗАЖИВЛЕНИЯ ИНФИЦИРОВАННЫХ РАН У КРЫС

А. Д. Болатчиев 1, В. А. Батурин 1 2, И. А. Базиков 1, А. Н. Мальцев 1

1 Ставропольский государственный медицинский университет, Российская Федерация

2 Центр клинической фармакологии и фармакотерапии, Ставрополь, Российская Федерация

In this study we investigated the effect of an antimicrobial peptide hBD-1 capsulated in organosilicon nanocontainers (niosomes) on the healing rate of experimental wounds infected with the clinical strain of Staphylococcus aureus. It was shown that the niosomal gel containing recombinant hBD-1 (1 цд/ml) increases the linear healing rate of infected wounds in rats compared to the control group.

Keywords: antimicrobial peptide, defensin, niosome, antibiotic resistance, hBD-1

Определялось влияние антимикробного пептида из класса бета-дефензинов (hBD-1), инкапсулированного в кремнийорганические наноконтейнеры (ниосомы), на скорость заживления экспериментальных ран, инфицированных клиническим штаммом Staphylococcus aureus. Было показано, что ниосомальный гель, содержащий рекомби-нантный hBD-1 (1 мкг/мл), увеличивал линейную скорость заживления инфицированных ран у крыс по сравнению с контрольной группой.

Ключевые слова: антимикробные пептиды, дефензины, ниосомы, антибиотикорезистентность, hBD-1

For citation: Bolatchiev A. D., Baturin V. A., Bazikov I. A., Maltsev A. N. EFFECT OF NIOSOMAL ANTIMICROBIAL PEPTIDE hBD-1 ON THE HEALING RATE OF INFECTED WOUNDS IN RATS. Medical News of North Caucasus. 2018;13(3):515-517. DOI - https://doi.org/10.14300/mnnc.2018.13093

Для цитирования: Болатчиев А. Д., Батурин В. А., Базиков И. А., Мальцев А. Н. ВЛИЯНИЕ НИОСОМАЛЬНОГО АНТИМИКРОБНОГО ПЕПТИДА hBD-1 НА СКОРОСТЬ ЗАЖИВЛЕНИЯ ИНФИЦИРОВАННЫХ РАН У КРЫС. Медицинский вестник Северного Кавказа. 2018;13(3):515-517. DOI - https://doi.org/10.14300/mnnc.2018.13093

AMP - Antimicrobial Peptide hBD-1 - Human Beta-Defensin-1

EUCAST - European Committee on Antimicrobial Susceptibility Testing

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ

Экспериментальная медицина

ORiGiNAL RESEARCH

■ Experimental medicine

The steady growth of antibiotic resistance is a global threat. To overcome this problem, it is necessary to study compounds having a pronounced antimicrobial activity [1]. Recently, the possibility of using antimicrobial peptides as promising antibiotics has been actively discussed. However, the practical application of these peptides is complicated because of their rapid degradation and therefore a short period of action [2]. To increase antimicrobial peptides' time of action it is possible to capsulate them in silicone nanocontainers (niosomes) [3]. Niosomes could become a tool that protects antimicrobial peptides from destruction, increase the duration of their action, improve the penetration into tissues. The aim of this study is to investigate the ability of recombinant human beta-defensin-1 (hBD-1) capsulated in niosomes to heal infected wounds in rats.

Material and Methods. Methicillin-sensitive Staphylococcus aureus clinical strains were isolated from patient with diabetic foot syndrome. Strain identification and susceptibility testing were determined in accordance with the EUCAST protocol.

Niosomal topical gel with 1 ig/ml recombinant hBD-1 (Cloud-Clone Corp., USA) was prepared by using method described us earlier [4]. Animal studies were conducted according to Geneva Convention of «International Principles of biomedical research using animals» (1985). Male Wistar rats weighing 180-200 g was used for the study. The site of hair was removed with the help of a cosmetic cream for depilation. Sterile instruments for punch biopsy (Medax, Italy) were used for wound defects. All the wounds were inoculated with 1 ml of S. aureus suspension with a turbidity of 0.5 McFarland units (108 CFU/ml) on day 1 of the experiment. The animals were divided into two groups: 1 - without treatment (control, n=10) and 2 - treated on the wound area with the topical niosomal gel with 1 |ig/ ml hBD-1 once a day (n=10). Treatment started on day 2 of the experiment and ended on day 14 - the full course of treatment was 13 days.

Wound area (mm2) and perimeter (mm) was calculated by using Wound Pro Application on day 2, day 7 and day 14 of the experiment. Linear speed of wound healing (V, mm2/day) was used to compare the rate of wound regeneration between groups:

V=2*(So-St)/t*(Po-Pt), (1)

P0 and S0 - are the perimeter and area of the wound surface at the previous measurement, Pt and St -

perimeter and area of the wound surface after a time interval t.

For statistical analysis was used SPSS Statistics (IBM Corp.), the Mann - Whitney U test and Fisher's exact test.

Results and Discussion. All the animals studied tended to heal infected wounds. The linear speed of wound healing (V, mm2) from day 2 to day 7 of the experiment (the first 5 days from the start of treatment) was calculated. Mean of V in the control group was 0.0053±0.0154 mm2/day. The rats treated with the niosomal 1 ig/ml hBD-1 gel showed a high rate of wound healing - mean V=0.0208±0.0130 mm2/day (p<0.05).

When calculating the rate of wound regeneration from day 7 to day 14, similar data were obtained. Mean of Vin the control group was 0.0049±0.0086 mm2/day. Mean of V in the niosomal hBD-1-treated group was 0.0241±0.0175 mm2/day. Differences between the groups were statistically significant (p<0.05).

Also, it must be noted that the average area of wounds in the control group on the last day of experiment was 4±1.9 mm2. In this case, the maximum wound area was 8 mm2 (in one rat), one had 6 mm2, two had 5 mm2, four rats had 3 mm2 and two animals had 2 mm2. While animals treated with the topical niosomal 1 ig/ml hBD-1 gel demonstrated a better regeneration - the average wound area on day 14 was 1.3±1.2 mm2. Wherein, in three rats wounds were completely healed, in three the area of wounds was 1 mm2, in three - 2 mm2, and for one animal -4 mm2. For Fisher's exact test it was accepted that if the area of wound <1 mm2, the wound healed completely. If more than 1 mm2, the wound is not healed. According to this analysis, it was proved that the regeneration of infected wounds on day 14 was statistically significant in the group receiving the antimicrobial gel (p<0.05). There was no wound healing in the control group.

Conclusions. In this work we have demonstrated for the first time that recombinant antimicrobial peptide -human beta-defensin-1 (1 ig/ml) - capsulated in organosilicon nanocontainers when used as the topical gel once a day could be an effective medicine for the healing wounds infected with S. aureus. The data obtained show that the antimicrobial gel we developed significantly increases the linear speed of healing of S. aureus-infected wounds compared to control. Human beta-defensin-1 capsulated in niosomes demonstrated a high activity in the healing of infected wounds. This may be due, firstly, high defensin antimicrobial activity, secondly with immunomodulating and regenerative properties of the compound.

Disclosures:

The authors declare no conflict of interest.

Acknowledgments. The work was supported by Russian Foundation for Basic Research in the framework of a scientific project № 18-315-00081/18.

References

1. Prestinaci F., Pezzotti P., Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog. Glob. Health. 2015;109(7):309-318. https://doi.org/10.1179/2047773215Y.0000000030

2. Steckbeck J. D., Deslouches B., Montelaro R. C. Antimicrobial peptides: new drugs for bad bugs? Expert Opin. Biol. Ther. 2014;14(1):11-14. https://doi.org/10.1517/14712598.2013.844227

3. Watermann A. Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer. Nanomaterials. 2017;7(7):189. https://doi.org/10.3390/nano7070189

4. The patent of the Russian Federation for the invention № 2655522 / 28.05.2018 Bulletin № 16. Bolatchiev A. D., Baturin V. A., Bazikov I. A. Antimicrobial gel for the treatment of infected wounds, burns and trophic ulcers. Available at: http://www1.fips.ru/fips_servl/fips_servle t?DB=RUPAT&DocNumber=2655522&TypeFile=html. Link is active on 03.08.2018.

МЕДИЦИНСКИЙ ВЕСТНИК СЕВЕРНОГО КАВКАЗА

2018. Т. 13. № 3

medical news of north caucasus

2018. Vоl. 13. Iss. 3

About authors:

Bolatchiev Albert Dobaevich, PhD-student of the Department of Clinical Pharmacology; tel.: +79288205551; e-mail: [email protected]

Baturin Vladimir Aleksandrovich, MD, Professor, Head of the Department of Clinical Pharmacology; Chief Physician; tel.: +78652713466; e-mail: [email protected]

Bazikov Igor Aleksandrovich, MD, Professor, Head of the Department of Microbiology; tel.: +78652352475, +79188664027; e-mail: [email protected]

Maltsev Alexander Nikolaevich, PhD, Senior researcher at the Laboratory of nanotechnology drugs; tel.: +78652352475

© Group of authors, 2018

UDC 616.147.22-007.64:613.95

DOI - https://doi.org/10.14300/mnnc.2018.13094

ISSN - 2073-8137

MORPHOLOGIC EVALUATION OF THE DILATED SPERMATIC VEINS IN CHILDREN WITH VARICOCELE

Shamsiev А. M. \ Kodirov N. D. \ Baybekov I. M. 2, Shamsiev J. А. \ Tereshchenko O. A. 3

1 Samarkand State Medical Institute, Uzbekistan

2 Republican specialized center of surgery named after academician V. Vakhidov, Tashkent, Uzbekistan

3 Kuban State Medical University, Krasnodar, Russian Federation

МОРФОЛОГИЧЕСКАЯ ОЦЕНКА РАСШИРЕННОЙ ЯИЧКОВОй ВЕНЫ ПРИ ВАРИКОЦЕЛЕ У ДЕТЕЙ

А. М. Шамсиев 1, Н. Д. Кодиров 1, И. М. Байбеков 2, Ж. А. Шамсиев 1, О. А. Терещенко 3

1 Самаркандский государственный медицинский институт, Республика Узбекистан

2 Республиканский специализированный центр хирургии им. акад. В. Вахидова, Ташкент, Республика Узбекистан

3 Кубанский государственный медицинский университет, Краснодар, Российская Федерация

Morphological method is one of the most objectives in assessing the condition of both varicose and convoluted veins in varicocele. In the present study fragments of varicose veins from children 12-18 years old with varicocele were investigated. The SEM studies showed numerous clusters on the clear surface of erythrocytes and other blood cells with strands of fibrin that may be precursors of the thrombi formation. Erythrocytes are the most numerous among the clusters of blood copuscles, echinocytes being their pathological forms. The data obtained should be considered in finding the method of surgical correction of this pathology.

Keywords: varicocele, children, morphology

Морфологический метод - один из самых объективных методов в оценке состояния варикозных вен и извитых вен при варикоцеле. Для изучения варикозного расширения вен были получены оперативно удаленные фрагменты у детей от 12 до 18 лет. Исследования SEM показали многочисленные скопления на прозрачной поверхности эритроцитов и других клеток крови с нитями фибрина, которые могут быть предвестниками образования тромбов. Среди кластеров образующихся элементов крови преобладают эритроциты и их патологические формы - эхиноциты. Выявленные особенности следует учитывать при выборе хирургической тактики коррекции этой патологии.

Ключевые слова: варикоцеле, дети, морфология

For citation: Shamsiev А. М., Kodirov N. D., Baybekov I. М., Shamsiev J. А., Tereshchenko O. A. MORPHOLOGIC EVALUATION OF THE DILATED SPERMATIC VEINS IN CHILDREN WITH VARICOCELE. Medical News of North Caucasus. 2018;13(3):517-519. DOI - https://doi.org/10.14300/mnnc.2018.13094

Для цитирования: Шамсиев А. М., Кодиров Н. Д., Байбеков И. М., Шамсиев Ж. А., Терещенко О. А. МОРФОЛОГИЧЕСКАЯ ОЦЕНКА РАСШИРЕННОЙ ЯИЧКОВОй ВЕНЫ ПРИ ВАРИКОЦЕЛЕ У ДЕТЕЙ. Медицинский вестник Северного Кавказа. 2018;13(3):517-519. DOI - https://doi.org/10.14300/mnnc.2018.13094

SEM - scanning electron microscopy NO - Nitric Oxide

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