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TOPICALLY-USED GENTAMICIN ATTACHED TO NANOFIBRE MDOCTM COMPARED WITH GARAMYCIN SCHWAMM® IN AN ACUTE WOUND INFECTION MODEL. AN EXPERIMENTAL STUDY.

Original article

Petr Lochman, Jiří Páral, Dušan Šimkovič, Jaromír Kočí

MMSL 2012, 81(1):9-15 | DOI: 10.31482/mmsl.2012.002

The aim of this study was to examine the effect of topically-used gentamicin attached to a biodegradable carrier, formed by micro-dispersed oxidised cellulose (MDOC) in nanofibre form, in acute wound infection treatment and to compare it with Garamycin Schwamm®. Twelve domestic swines were used in a model of a full-thickness infected dermal wound. The effectiveness of both materials in wound infections caused by Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli was tested. The effectiveness of both gentamicin with MDOC and Garamycin Schwamm® was comparable in Pseudomonas aeruginosa and Escherichia coli infections according to microbiological cultures findings. With Staphylococcus aureus infections there was a higher percent of negative cultures when MDOC with gentamicin was administered, but without statistical significance (p=0.069). When macroscopically assesed, 100 % of infected wounds treated by gentamicin attached to MDOC were without signs of local infection compared to only 16.7 % when Garamycin Schwamm® was used and this was statistically significant (p<0.01). For statistical analysis we used a Fisher's exact test. When combined with a nanofibre MDOC carrier, topically-used gentamicin seems to be rendered more for treatment of full-thickness skin infections. The resulting good haemostatic effect of MDOC was observed.

A HISTORICAL OUTLINE OF THE TRAINING SYSTEM FOR FRENCH MILITARY PHYSICIANS

Letter to the editor

Jean-Luc Perret

MMSL 2012, 81(2):84-86 | DOI: 10.31482/mmsl.2012.012

The story behind today's training-system for doctors serving in the French Armed Forces is embedded in a series of establishments each of which has left its mark in history, maintained the closest links with centres of improvisation, and instilled in its students a deep sense of attachment.
It was at the very beginning of the 18th century that the first such establishment dedicated to military doctors appeared in France. It strove unceasingly to adapt itself not only to the needs of the military, but to the advancement and established use of knowledge pertinent to the changing conditions of military service.
Since then, piecemeal evolution finally resulted in the amalgamation of 2011 when, on the 2nd July, one single institution responsible for basic medical training was constituted --- the Defence School of Medicine (ESA). Its inauguration co-incided with the closure of the two Military Medical ...

THOMAS PROFT (ED.). MICROBIAL TOXINS: CURRENT RESEARCH AND FUTURE TRENDS. UNIVERSITY OF AUCKLAND PUBLISHING, NEW ZEALAND 2009, VIII + 192PP. ISBN: 978-1-904455-44-8.

Book review

Jiří Patočka

MMSL 2011, 80(2):85-87

Toxins are important virulence factors responsible for microbial pathogenicity. Potential applications of toxin research extend beyond simply combating microbial virulence and include the development of novel anti-cancer drugs and other front-line medicines. No less important is the use of toxins as tools in cellular biology and neurobiology. Understanding toxin molecular and cellular biology is critical for the development of new anti-toxin strategies, particularly for those with bioterrorism capability. This well worked book not only provides a general overview of toxins but elucidates in detail recent molecular approaches, achievements and refreshing perspective on the future studies of these molecules. The book is divided into nine chapters and each chapter is written by internationally respected scientists. ...

MULTIPLE MECHANICAL AND THERMAL BLAST INJURY IN CIVILIAN INDUSTRIAL SETTING - POSSIBLE PARALLEL TO THE BATTLEFIELD BLAST SYNDROME TYPE INJURIES

Case report

Leo Klein, Eduard Havel, Karel Šmejkal, Jaroslav Cerman, Frantisek Hošek, Miloslav Hronek

MMSL 2011, 80(4):150-158 | DOI: 10.31482/mmsl.2011.021

A 43-year-old man, injured during a factory explosion on January 4, 2010, was transported to the nearest hospital. Volume resuscitation started, subclavian vein cannulation, chest tube, and covering of burns were performed. The intubated and ventilated patient was transferred by helicopter to our hospital. The leading diagnoses were: haemorrhagic - traumatic and burns shock, haemoperitoneum, pneumothorax, subtotal amputation of the left distal crus/feet, burns over 40 % of the body surface, right calcaneus fracture etc. Preliminary circulatory stabilisation with discontinuation of norepinephrine infusion was achieved within 10 hours, by excessive positive fluid balance, which took three days (22, 10 and 9 litres). Preliminary blood lactate 7 mmol/l was normalised within 24 hours. Blood albumin level 15 g/l was tolerated without any artificial replacement. The second hit appeared on day 10, in a form of septic shock caused by Aspergillus fumigatus infection from the lacerated left lower limb. High-volume continuous haemodiafiltration because of hyperpyrexia was used, after the exarticulation in the left knee-joint. An excessive proteolysis (urea loss more than 1000 mmol/day) persisted 1.5 months, with energy expenditure over 2600 kcal/day. The patient underwent multiple surgical interventions. Metabolic support using combined parenteral and enteral nutrition was performed during the first month, enteral nutrition combined with food were consequently given for more than 3 months. The patient was hospitalised until April 26, 2010. These types of traumas are fully comparable with military battlefield environment injuries. Principles of war surgery (life and limb saving, damage control surgery) should be applied also in civilian environment, particularly in disaster situations.

METHOD OF STATIC DIFFUSION CELLS FOR ASSESSMENT OF PESTICIDES SKIN PERMEATION

Original article

Jan Misík, Růžena Pavlíková, Jiří Cabal, Ladislav Novotný, Kamil Kuča

MMSL 2011, 80(2):46-51 | DOI: 10.31482/mmsl.2011.007

Usage and misusage of pesticides represent a health risk to military and civilian, especially to agricultural workers; also a possible terrorist threat is considered. The major route of low-volatility pesticides intoxication is percutaneous. Hence, skin permeation characteristics of pesticides are intensively investigated. In this study, in vitro measurement of skin permeation is presented on the example of pesticide paraoxon. Permeation experiments were performed in Franz-type of static diffusion cells using a pig skin. Paraoxon which permeated through the skin was determined enzymatically by modified Ellman's method. During 8 hours experiment, approx. 0.1 % of applied paraoxon has permeated through the skin. It was shown that pre-treatment by water simulating wet or sweated skin enhanced the paraoxon permeation.

Gunshot Wounds of the Heart - Case Report

Štefan Petrovič, Jozef Fridrich, Miroslav Danaj, Peter Belej

VZL 2007, 76(1):19-22

Gunshot wounds even in peace-time have been increasing above all due to enhanced criminality and organized terrorism. Survival rate of gunshot wounds of the heart is rare, since majority of voctims die just at the site of incident. Perforating wounds of the ventricles have a minimum chance of survival. We succeeded to save a presented patient with the penetrating wound of the right ventricle due to a fast transport to hospital, an emergency specialized care in a close cooperation with an anesthesiologist and a quality postoperative care.

Ethical Aspects of Triage

Bernd Domres, Tobias Kees, Stefan Gromer, Peter Braitmaier, Tanja Granzow

VZL 2010, 79(2):76-82

The discipline of medical ethics is concerned with morality, moral obligations and the principles of proper professional conduct concerning the rights and duties of a physician himself, his patients and fellow practitioners, as well as his actions in the care of patients and in relation with their families. Its foundations lie in the philosophical traditions of Eastern and Western thought and have strongly shaped modern codes of conduct and conventions...

Spatial Reconstruction of Histological Sections of the Temporal Bone

Bruno Ježek, Viktor Chrobok, Karel Antoš, Jan Vaněk

VZL 2009, 78(4):154-157

Technical development in computer hardware and application of new visualization algorithms allow the use of spatial visualization methods in many different branches of biological research. Computer graphics and information visualization methods became important help in the research of spatial features of medical objects. The article describes the process of studied objects visualization, used methods, data structures and software tools. Temporal bone visualization case study shows reconstruction process from acquired image data to final rendering of created computer model. Obtained results prove the possibility to combine image, surface and volume visualization methods for different researched objects.

Mobile System of Health Risk Assessment of Multiple Chemical Exposures

Zdeněk Fiala, Lenka Borská, Otakar Mika, Jan Kremláček, Tomáš Borský, Vladimír Kraják, Jan Kavalír

VZL 2005, 74(5):158-164

The proposed system of assessment enables fast screening of the actual health risk levels in situations of chemical threat. The system could facilitate and accelerate emergency management concerning application of protective devices, implementation of emergency precautions or total evacuation. The system includes analytical, physical and toxicological modules. The analytical module collects information about a form of chemical emergency event, actual air levels of selected dangerous compounds in the site of emergency event and actual atmospheric conditions. The physical module calculates the total concentration zones (the total zones of health risk) and records the zones into the map. The toxicological module enables continual assessment of actual health risk in the emergency team workplace. The system includes more than 80 dangerous chemical compounds and is still under development, with a target number of about 100 substances. After the final completion, the system could be a part of the integrated rescue system.

The Effect of Selected Demographic, Psychosocial and Healthy Aspects on Quality of Life of Patients with Multiple Myeloma and Acute Myeloid Leukaemia Undergoing Autologous Haematopoietic Stem Cell Transplantation: A Retrospective Analysis (Dissertation thesis)

Ladislav Slováček

VZL 2007, 76(5):192-199

Aim: The study analyses the quality of life (QoL) in patients with multiple myeloma (MM) and acute myeloid leukaemia (AML) undergoing autologous haematopoietic stem cell transplantation (HSCT). Patients and Methods: The total number of respondents with AML was 12 (7 male, 5 female). The total number of respondents with MM was 32 (18 male, 14 female). The average age of patients with AML was 47.5 years and average age of patients with MM was 60 years. The Czech version of an international generic European Quality of Life Questionnaire - Version EQ-5D was used. The effect of selected psychosocial, health and demographic aspects on QoL in patients was determined by means of variance analysis. The descriptive analysis was used for evaluation of QoL questionnaires. Results: The above-mentioned aspects proved a statistically significant dependence of QoL (EQ-5D score and EQ-5D VAS) on age in both cohorts (p<0,01), religion in AML cohort (p<0,05), smoking abuse in both cohorts (p<0,01), level of education in AML cohort (p<0,05), increasing number of associated diseases in both cohorts (p<0,05) and type of disease (p<0,05). Conclusion: The global QoL in patients with AML is at a higher level than in patients with MM treated by means of autologous PSCT.

The Membrane HER-2/neu Receptor - Structure and Function, Prognostic and Predictive Role for Invasive Breast Cancer Patients

Petr Cinek, Stanislav Filip

VZL 2007, 76(6):211-215

The HER-2/neu receptor, a member of transmembrane HER receptors family, plays a very important role in activation of the signalling downstream path which mediates the transfer of extracellular signal into the cell nucleus. The physiological processes, leading to receptor activation, as well as its whole signalling cascade are understood well today. The increased HER-2/neu activation, in the case of its abundance in cellular membrane, participates in complicated processes of cancerogenesis and is liable for the formation of tumor cells with a more malignant phenotype and more aggressive biological behaviour.The status of HER-2/neu expression in invasive breast cancer cells is assessed by immunohistochemical methods, and the number of encoding gene copies (c-erbB-2) by fluorescent in situ hybridization. The measurement of dividual extracellular receptor domain is possible in patients' blood serum. The increased HER-2/neu receptor expression is a negative prognostic factor for invasive breast cancer patients because these women have a higher risk for early recurrence and generalization of the disease. Moreover, HER-2/neu overexpression is also a predictive factor which helps to mark patients who benefit from the target biological treatment and anthracyclin based chemotherapy.

Smokeless Tobacco: Another Form of Hazardous Tobacco

Sajith Vellappally, Zdeněk Fiala, Jindra Šmejkalová, Vimal Jacob, Pilathadka Shriharsha

VZL 2007, 76(6):221-226

This review deals with the smokeless tobacco products, their use, composition, systemic and oral diseases associated with it. It is evident that smokeless tobacco is carcinogenic to human and causes various systemic and oral diseases. One of the major cancers caused by smokeless tobacco use is oral cancer and other oral diseases like leucoplakia, dental caries, smokeless keratosis, and other negative influences of smokeless tobacco on oral cavity including staining of teeth, bad breath, mouth sores, attrition and abrasion. This review also tries to describe the possible tobacco cessation intervention in dental office.

Alloplasty in Treatment of Hallux Rigidus

Jiří Fousek, Dagmar Kuběnová

VZL 2006, 75(3):85-91

The authors present their first experience with implantation of the total Toefit Plus endoprothesis in treatment of hallux rigidus. They show their results in implantation of this prothesis in a group of 21 implanted endoprotheses in 19 patients. The motion in the first MTP joint after the implantation of this endoprothesis has significantly improved in all the patients and the functional score according to Kitaok has significantly increased. The advantage of this endoprothesis is that it can be implanted even in patients after the previous unsuccessful operations of hallux rigidus.

AKTIVITY CENTRA URAZOVE PREVENCE V PROJEKTU BEZPECNA KOMUNITA

Veronika Benešová

VZL 2003, 72(4):194-195

Principles of Infectious Diseases Prevention during the Stay Abroad

Jan Smetana, Roman Chlíbek

VZL 2006, 75(1):32-36

In recent 10 years, the high increase of people traveling abroad has been noticed. More and more people are going to the areas with an increased risk of health damage. A potential affection by infectious disease is one of the risk factors. An introduction of appropriate preventive measures may decrease a risk of potential intoxication. The authors describe a risk of transmission of infectious diseases duriny the stay abroad. They give basic information on possibilities of health protection. These recommendations are focused on preparation before the departure, on behavior during the stay in epidemic risk areas and on prevetion against intoxications during the stay in foreign environment.

A HISTORY OF GRUINARD ISLAND - THE “ANTHRAX“ ISLAND

Miroslav Špliňo, Jiří Patočka

VZL 2002, 71(2):58-59

Gruinard Island lies in Gruinard Bay in northwest Scotland. The island is rocky in nature and about 2 km long and 1 km across at its widest point. In 1942, the War Department of UK identified Gruinard Island as a site for urgent field trials on biological warfare. It was declared a prohibited place, requisitioned and became known as "X-base". Tests of the toxicity of Bacillus anthracis spores were carried out in the summers of 1942 and 1943. The island became so contaminated that it was deemed out-of-bounds for almost 50 years. In 1986 an English company was paid half a million pounds to decontaminate the 520-acre island by Soaking the ground with 280 tones offormaldehyde diluted in 2000 tones of seawater. On I May 1990, Gruinard Island was returned to civil use.

THE ROLE OF THE LUNGS IN ANTI-INFECTIOUS IMMUNITY

Zuzana Kročová

VZL 2002, 71(5):231-236

The lungs are organs that are constantly under the attack of ubiquitous inert particles and micro—organisms. The lungs represent the natural site of entry for micro-organisms into the body and understanding the innate and adaptive immune response mechanisms after aerogenic infection is of great importance. The non-adaptive immune response is created by several basic defence mechanisms. Physical lung defence includes the removal of inhaled material by mucociliary clearance, physiological defence (mediated by soluble proteins, immunoglobulin A or complement factor C3) and bacteriostatic or bactericidal protein activity. The cell mechanisms include the activity of macrophages, neutrophils, eosinophils, mast cells, dendritic cells and epithelial cells. All these cells are able to directly eliminate some of the micro-organisms and can induce an adaptive immune response in which mainly activated macrophages and T— and B-cells participate. Such a response is antigen-specific and its aim is to eliminate encapsulated and intracellular micro-organisms and to establish a resistance to re-infection.

Charakteristika a perspektivy oboru valecne chirurgie

Leo Klein, Alexander Ferko

VZL 2005, 74(5):151-154

Biodosimetry Part I: Practical Need of Biodosimetry and the Most Important Mechanisms Activated After Irradiation

Zdeňka Vilasová, Jan Österreicher, Jiřina Vávrová

VZL 2005, 74(2):81-84

This study analyzes possibilities of the use of biodosimetric methods in military practice. It also mentions information concerning limited use of these methods. Subsequently it contains a summary of the most important facts concerning radiation-induced mechanisms at the molecular level, in paticular those concerning p53 activation, induction of G2/M cell cycle arrest and related activation of the MAP kinase pathway at the molecular level.

35. svetovy kongres vojenske mediciny ve Washingtonu

Leo Klein

VZL 2004, 73(5):208-210

Non-lethal Chemical Weapons and the Convention on Prohibition of Chemical Weapons

Ladislav Středa, Jiří Patočka

VZL 2004, 73(5):184-193

Non-lethal weapons are a combat means and weapon systems which put a human being out of combat action or other purposeful activity by causing physical or mental disablement. If chemical agents are the means of temporary incapacitation, these substances are known as non-lethal chemical agents and weapons based on this principle are known as non-lethal chemical weapons. A temporary incapacitation without a serious damage to health is a primary effect of these weapons. In this article the development of non-lethal chemical weapons is discussed in relation to the Convention on Prohibition of Chemical Weapons.

INTERNETOVE INFORMACNI STRANKY VOJENSKE LEKARSKE AKADEMIE J. E. PURKYNE V HRADCI KRALOVE

Jaroslav Pačes, Alexander Kúr

VZL 2000, 69(5):217-220

CHEMOPROTECTIVE SUBSTANCES IN THE FOOD - CONTEMPORARY STATE OF THE ART AND PERSPECTIVES

Zdeněk Zloch

VZL 2001, 70(3):132-136

Chemoprotective substances comprise a large (broad) group of natural substances occurring in plant foods. In humans, they exert a lot (plenty) of biological effects mostly by having a favourable influence on the health, especially as anticarcinogens and antiatherogenic agens. Antioxidant defense mechanisms as well as a stimulation and/or inhibition of enzymes engaged in various metabolic or regulation processes such as controlling the detoxification activities, signal transduction, cell division and apoptosis and lipid metabolism are of the particular significance regarding the biological activites of these substances. A support and promotion of health through prevention of cardiovascular and tumor diseases and the reduction of the other health risks is a very real consequence of sufi‘icient and regular intake offood containing the chemoprotective factors.

HUPERZINE A: A PROSPECTIVE PROPHYLACTIC ANTIDOTE AGAINST ORGANOPHOSPHATE NERVE AGENTS. CAPILLARY ELECTROPHORESIS DETERMINATION

Eladia M. Pena-Méndez, Tomáš Hottmar, Josef Havel, Jiří Patočka

VZL 2003, 72(1):15-20

A new, highly sensitive capillary zone electrophoresis methodfor determination of huperzine A, a perspective prophylactic antidote against militarily important nerve agents and anti-Alzheimer's disease drug, was developed. Huperzine A is an alkaloid isolated from the Chinese club moss Huperzia serrata. The absorption spectra and electrophoretic behaviour of the compound were studied. The compound shows two absorption maxima (λmax 230 and 310 nm). The protonation constant was determined by spectrophotometry and capillary zone electrophoresis (CZE) and the recommended value is pK = 7.70 ± 0.07. A CZE method for the determination of huperzine A in pharmaceutical tablets and serum has been developed. This method is based on separation of the compound as a protonated species with electrophoretic mobility determined as 50.7x 10-9 m2V-1S-1. The optimal separation conditions were.“ acetate bujfer (pH4.60,' 20 mM) as a background electrolyte, a separation voltage of 20 kV,“ a temperature of 25°C, hydrodynamic injection 10 s and detection at wavelengths 230 and 310 nm. The analyses were run in an uncoated fused-silica capillary with a total length of 47.5 cm (39.0 cm to the detector) and the 75 μm I.D. Detection limit was found to be 70 μg/l. The method of huperzine A determination was applied for analysis of two pharmaceutical products. The results were found to be in good agreement with the declared amount. The precision of the method is ± 2.30 % rel. The method for determination of huperzine A in serum was also developed with a detection limit of 110 ug/l which is applicableforpharmacokinetics and therapeutic drug monitoring of this compound

THE USE OF HYPERBARIC OXYGEN THERAPY IN MILITARY CASUALTIES, INTOXICATION AND INJURIES

Miloš Sázel, Petr Došel, Vladimír Doležal

VZL 2003, 72(2):77-81

Hyperbaric oxygen therapy (HBO2) is an important therapeutic method used all over the world and as well as in the Czech Republic. Oxygen breathed inside a hyperbaric chamber contributes to the healing of impaired tissue. HBO2 indication has a few degrees of urgency but the indication of this treatment is vital in some diagnoses. Its use in wartime conditions is particularly presumed for treatment of CO intoxication, gaseous gangrene, traumatic shock, compartment and crush syndrome, burns and chronic osteomyelitis. The experiences of some authors with HBO2 are summarized, and the values of overpressure and the time Of treatment are reported. The primary contra-indication related to HBO2 is pneumothorax. Military Medical Service field units should be equipped with a hyperbaric chamberfor HBO2. The Institute of Aviation Medicine in Prague has extensive experience with HBO2 and offers possible counselling or training in hyperbaric medicine.

DISABLED SOLDIERS’ HOSPICES IN BOHEMIA

František Dohnal

VZL 2003, 72(5):244-249

The beginning of care for disabled and sick Soldiers in the Habsburg monarchy goes back to the early 18th century. Earl Peter Strozzi was the originator of this social care. His name is also connected with the foundation for establishing and running the disabled Soldiers’ hospice for retired soldiers. A large disabled Soldiers, hospice was established and opened in Prague in 1735. In 1935 a new modern disabled soldiers’ hospice was set up in Hořice v Podkrkonoší. Apart from a break during the war, it was used till 1964. Later on, this type of care was carried out by social welfare institutions.

TELEMEDICINA

Karel Antoš, Bruno Ježek, Roman Prymula, Miroslav Procházka

VZL 1999, 68(4):107-114

FUNCTIONAL PROFILE OF FRANCISELLA TULARENSIS PROTEINS

Lenka Hernychová, Aleš Macela, Jiří Stulík

MMSL 2002, 71(S1):17-19

In spite of the enormous quantity of information from genomic and proteomic analysis the data do not mirror precisely in vivo situation in respect to functional profile of cellular system studied. Generally, the function of molecular entities is strictly associated with their tertiary structure, subcellular localization inside individual cell compartments andbasically on the consensual sequences, which compose the functional domains of protein molecule. Moreover, the metabolic and signaling cellular cascades rely on the protein-protein interactions, which are alsoout of the scope of, so called “expression proteomics”. To overcome this gap, the construction of virtual proteome using the algorithms of bioinformatics and the systematic study of protein-protein interactions through the isolation of protein complexes called “cell-maps proteomics” precedes the creation of real bacterial proteome. Moreover, the proteomic study of isolated individual cellular compartments can bring more precise information of function-related protein expression.

TOXICOKINETICS OF NERVE AGENTS

Hendrik P. Benschop, Leo P.A. De Jong

MMSL 2001, 70(S1):2-12

Toxicokinetic studies of nerve agents deal with the in vivo absorption, distribution, and elimination of these agents as a function of animal species, route of administration, dose and time after administration. Such studies provide a quantitative basis for toxicodynamic studies of nerve agents, which should result in causal treatment of intoxications with these agents. While toxicodynamic studies of nerve agents have been intensively pursued since WW II, toxicokinetic studies were only initiated in the last two decennia of the twentieth century. The late start of the latter type of research was caused by the long held but uncorrect assumption that nerve agents were so-called “hit-and-run” poisons, with extremely short in vivo persistence. 0n the other hand, such in vivo analyses had to wait for the development, in that period of time, of trace analytical methods which were needed to determine the extremely low (ng to low pg range/ml plasma) but toxicologically significant in vivo levels of the various stereoisomers of nerve agents.
This review will deal first with the development of analytical procedures for chiral trace analysis of the stereoisomers of nerve agents, as well as with the toxicology and routes of in vivo elimination of the stereoisomers. Next, results of toxicokinetic studies will be given, mainly dealing with soman but some results for other nerve agents will also be given. The effect of dose, route of adminstration (iv, inhalation, pc) and animal species will be dealt with, emphasizing the toxicokinetics after low level respiratory exposure. Finally, consequences for prophylactic and therapeutic approaches as well as future directions of research are discussed.

CYTOKINE AND CHEMOKINE MRNA EXPRESSION DURING IN VITRO INFECTION OF PHAGOCYTIC CELLS — CURRENT STATE OF STUDY

Blanka Hartmanová, Zdeněk Fiedler

MMSL 2002, 71(S1):32-35

The aim of this work is to analyze the expression of eukaryotic genome of the phagocytic cell after infection with microorganism, in particular after infection with Francisella tularensis. Mouse macrophage cell line J774 is used in experiments as a model of phagocytic cell. The first part of activities which should lead to reach the aim was selecting of suitable markers of the infection. The expression of these markers should be affected by the infection of phagocytes. We chose some cytokines, chemokines and also enzymes....

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