Risk Factors and Mechanisms of Cardiovascular Diseases in Posttraumatic Stress Disorder Model in Wistar Rats as Dependent on Stress Resistance and Age.

The article focuses on the pathogenetic mechanisms of posttraumatic stress disorder (PTSD), which is associated with psychological stress because of the coronavirus pandemic. The molecular mechanisms responsible for disease susceptibility in some individuals and stress resistance in others are amongst crucial research interests of experimental and clinical medicine. Priority data were obtained to indicate that distortions of synthesis and metabolism and, most significantly, a switch between two energy transport forms, glucose and lipids, underlie myocardial dysfunction in young and old stress-sensitive Wistar rats in a PTSD model. Histochemistry and polarization microscopy showed energy deficit in cardiomyocytes and signs of ischemic and hypoxic areas emerging in the myocardium as a result of an accumulation of NADH and NADPH, which initiate excessive production of reactive oxygen species.

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger.

For the first time in modeling posttraumatic stress disorder (PTSD), we have described the morphofunctional state of adrenal glands in Wistar rats resistant and sensitive to predator stress (rodent fear of the predator). Despite the evident signs of adrenal dysfunction in both phenotypes, we have discovered the thickening of undifferentiated cell zone and high indices of functional activity of stem cells in resistant animals, suggesting ample adaptation. The most important data demonstrate the direct relationship between the reduction of corticosterone and testosterone levels and adrenal dysfunction in PTSD models. The study results allow considering the adrenal stem cells as potential therapeutic targets.

Physical Fatigue and Morphofunctional State of the Myocardium in Experimental Chronic Stress.

The relationship between the development of skeletal muscle fatigue of a specific type in male Wistar rats and morphofunctional alterations in the myocardium in the posttraumatic stress disorder (PTSD) model has been investigated for the first time. The aggravation of oxidative stress in the cardiomyocytes and the related transformation of the cell structural components and the depletion of energy reserves in PTSD has been identified as one of the main factors that accelerate the onset of musculoskeletal fatigue.

Adoption of Lung Protective ventilation IN patients undergoing Emergency laparotomy: the ALPINE study. A prospective multicentre observational study.

BACKGROUND: Emergency abdominal surgery is associated with a high risk of postoperative pulmonary complications (PPCs). The primary aim of this study was to determine whether patients undergoing emergency laparotomy are ventilated using a lung-protective ventilation strategy employing tidal volume ≤8 ml kg-1 ideal body weight-1, PEEP >5 cm H2O, and recruitment manoeuvres. The secondary aim was to investigate the association between ventilation factors (lung-protective ventilation strategy, intraoperative FiO2, and peak inspiratory pressure) and the occurrence of PPCs. METHODS: Data were collected prospectively in 28 hospitals across London as part of routine National Emergency Laparotomy Audit (NELA). Patients were followed for 7 days. Complications were defined according to the European Perioperative Clinical Outcome definition. RESULTS: Data were collected from 568 patients. The median [inter-quartile range (IQR)] tidal volume observed was 500 ml (450-540 ml), corresponding to a median tidal volume of 8 ml kg-1 ideal body weight-1 (IQR: 7.2-9.1 ml). A lung-protective ventilation strategy was employed in 4.9% (28/568) of patients, and was not protective against the occurrence of PPCs in the multivariable analysis (hazard ratio=1.06; P=0.69). Peak inspiratory pressure of <30 cm H2O was protective against development of PPCs (hazard ratio=0.46; confidence interval: 0.30-0.72; P=0.001). Median FiO2 was 0.5 (IQR: 0.44-0.53), and an increase in FiO2 by 5% increased the risk of developing a PPC by 8% (2.6-14.1%; P=0.008). CONCLUSIONS: Both intraoperative peak inspiratory pressure and FiO2 are independent factors significantly associated with development of a postoperative pulmonary complication in emergency laparotomy patients. Further studies are required to identify causality and to demonstrate if their manipulation could lead to better clinical outcomes.

[Ocular lesions in HIV-infected patients of the ophthalmic hospitals]. / Porazhenie organa zreniia u VICh-infitsirovannykh patsientov oftal'mologicheskikh statsionarov.

PURPOSE: To analyze ophthalmic pathologies in HIV-infected patients of the ophthalmic hospitals of Perm city. MATERIAL AND METHODS: Medical records of 75 HIV patients registered in Perm Regional Centre for Prevention and Control of AIDS and Infectious Diseases who had received treatment in ophthalmic in-patient clinics of Perm in 2005-2015 years were analyzed retrospectively. Patient examination included traditional ophthalmological methods, as well as immunological (determination of CD4 cells and viral load), serological (detection of antibodies to herpes simplex virus, cytomegalovirus, chlamydia, toxoplasma), general clinical methods, and consultations by allied specialists. RESULTS: Ophthalmopathology requiring in-patient care was detected in 75 people (84 eyes). Men comprised 76%, women - 24%; average age was 32.82±8.68 years. The stage of HIV infection was known in 78.66% of patients: stage II - in 5% of cases, stage III - in 32%, stage IV - in 63%. Co-infection (hepatitis B and C, syphilis, tuberculosis) was detected in 81% of patients. HIV-related diseases (cytomegalovirus and herpes infection, candidiasis, toxoplasmosis) were observed in 48% of individuals. The time of emergence of ocular pathology from the time of HIV detection ranged from 1 day to 14 years. Inflammatory ocular diseases occurred in 55% of cases, dystrophic disorders - in 18%, eye traumas - in 24%, and strabismus - in 3% of patients. Reduced level of CD4 (less than 500 cells/mm3) was more prevalent (72.13%) among the study patients. As of the time of the study, only 36.4% of patients were receiving antiretroviral therapy. CONCLUSION: Among the studied individuals, eye lesion was mostly severe, inflammatory in nature; it occurred more frequently in stage IV HIV patients with reduced number of CD4 lymphocytes who was not receiving antiretroviral therapy.

Regulation of the peritoneal macrophage functional activity by the MP-5 and MP-6 myelopeptides under stress.

In mice, two-hour immobilization stress inhibited zymosan-induced production by macrophages of the oxygen radicals and cytokine IL-1ß. After myelopeptides MP-5 and MP-6 were administered into mice, the stress-induced inhibition of the reactive oxygen species (ROS) and IL-1ß was abrogated. MP-5 peptide stimulated spontaneous ROS production by macrophages and reduced IL-10 production under stress. Thus, under in vivo conditions and under stress, the effect of MP-5 and MP-6 myelopeptides modulates the peritoneal macrophage activity.

[The concentration of cerebral natriuretic peptide in tear and blood serum.]

The natriuretic peptides regulate pressure and water metabolism in human organism. The concentration of N-thermal cerebral natriuretic propeptide (NT-proBNP) in tear and blood serum was analyzed. The sampling included 49 patients divided on three groups. The group I (main) included 14 patients with primary open-angle sub-compensated glaucoma degree I-III. The group II (comparative group) included 15 patients with age-related immature cataract. The group III (control) included volunteers without any visual organ diseases. The concentration of NT-proBNP in tear and blood serum was detected by solid-phase enzyme-linked immunosorbent assay technique using test system NT-proBNP - IFA - BEST¼ («Vektor-Best¼, Russia). The median of content of NT-proBNP in tear turned out to be less than in blood serum in all groups (р1 = 0,00763; р2 = 0,00452; р3 = 0,00029) and made up to in patients with glaucoma 41,3 pg/ml, with cataract - 37.5 pg/ml, in healthy people 0 25.0 pg/ml (inter-quartile range made up to 20-60 pg/ml, 20-65 pg/ml, 10-49,5 pg/ml correspondingly). No differences in concentration of NT-proBNP were established in all groups both for blood serum (p = 0,494) and tear (p = 0,388). The concentration of NT-proBNP in tear correlated with its concentration in blood serum (r = 0,694). However, no dependencies were established from value of intra-ocular pressure (r = 0,168). Therefore, the concentration of NTproBNP in tear is not a perspective laboratory arker for diagnostic of increased intra-ocular pressure and stratification of development of glaucoma.

[THE ANALYSTS OF PROCALCITONIN IN LACRIMAL FLUID AND BLOOD SERUM UNDER UVEITIS].

The analysis was applied to concentration of procalcitonin in lacrimal fluid and blood serum in 15 healthy persons (control group), 16 patients with uveitis (main group) and 14 patients with non-inflammatory pathology of organ of vision (comparison group). The concentration of procalcitonin was detected by immunoenzyme method using commercial test-system "Procalcitonin-IFA-BEST" ("Vector-Best", Russia). The content of procalcitonin in blood serum was low (75% quartile--0.031 ng/ml) and had no significant difference between groups (H-criterion of Kruskal-Wallis test, p = 0.0872). The level of procalcitonin in lacrimal fluid 8-11 times exceeded its concentration in blood serum of all groups (Wilcoxon criterion, p < 0.005). The least content of procalcitonin is detected in lacrimal fluid of patients of comparison group (0.072 ± 0.064 ng/ml). In main and control groups its level was reliably higher (H-criterion of Kruskal-Wallis test, p = 0.0002) and amounted to 0.257 ± 0.146 and 0.198 ± 0.151 ng/ml correspondingly. The correlation analysis established no dependencies between concentration of procalcitonin in tear and blood serum (Spearman correlation coefficient had no exceeding |0.1| in all groups). The development of uveitis is not accompanied by alteration of concentration of procalcitonin in both blood serum and lacrimal fluid. The absence of correlation and higher concentration of procalcitonin in tear as compared with blood serum testify availability of additional source of this protein in lacrimal fluid.

[Study of etiologic factors of infectious diseases of respiratory tract in school-age children during period of remission of a respiratory disease].

AIM: Detect features of microflora of upper respiratory tract on the example of flora of palatine tonsils and level of antibodies against intracellular parasites as markers of etiologic factors of respiratory infections in school-age children in remission period. MATERIALS AND METHODS: 466 children from frequently and episodically ill groups were examined. Bacteriologic study of smears from the surface of palatine tonsils was carried out in all the children. By using EIA with the corresponding commercial test systems IgG level against Herpes simplex virus, Cytomegalovirus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Human respiratory syncytial virus was determined in blood sera according to instruction manual. RESULTS: During remission period of infectious process in the structure of microflora of upper respiratory tract in frequently ill children characteristic differences from their episodically ill peers were detected. In children with frequent respiratory infections a higher occurrence of antibodies against intracellular causative agents of these diseases was also detected. In the group of frequently ill, a direct correlation between frequency of infectious diseases of respiratory tract and occurrence of carriage of pathogenic and opportunistic microorgan isms as well as increase of antibodies against Herpesviridae, Cytomegalovirus, C. pneumoniae and M. pneumoniae was detected. CONCLUSION: Higher occurrence ofintra- and extra-cellular infectious agents as well as their associations may be considered as one of the reasons of insufficient effectiveness of prophylaxis measures in frequently ill children.

[The methods of prognostic evaluation of risk of child joining the dispensary group of frequently ill children].

The study was organized to develop the formalized diagnostic methods and computer program to evaluate the risk of child joining the dispensary group of frequently ill children. The sampling included 2742 children of different age groups. It is established that size of groups of frequently ill children consists 38.2% among children of preschool age, 32% among children of early school age and 21% among adolescents of senior school age. The risk factors of development of frequent respiratory diseases in child are revealed. The impact of these factors on the rate of respiratory diseases depending on the age of child is established. The methods and computer program are developed for prognostic evaluation of risk of child joining the dispensary group of frequently ill children according the results of analysis of hereditary factors, pathology of delivery and pregnancy, characteristics of breast feeding and conditions of life. The methods are approved during additional examination of 400 children of different age.

Proliferative response of lymphocyte to pokeweed mitogen depends on the concentration of endogenous cortisol in the early post-traumatic period in patients with penetrating eye injury.

The intensity of lymphocyte proliferation in response to pokeweed mitogen depends on cortisol level in the peripheral blood in the early post-traumatic period of penetrating eye injury. Lymphocyte proliferation in 72- and 96-h cultures from patients with high levels of endogenous hormone was suppressed. In 120-h cultures, the intensity of proliferation remains unchanged. Lymphocyte blast transformation was increased in 120-h cultures from patients with normal cortisol concentration and remained unchanged in case of low cortisol level.

Expression of TLR9 and BD-2 protein genes in corneal cells of mice of different strains with herpetic keratitis.

The dynamics of gene expression of two proteins, TLR9 (one of the key receptors recognizing CpG repeats of herpes virus DNA) and ß-defensin 2 (antibacterial peptide), was studied on the model of herpetic keratitis in C57Bl/6 and BALB/c mice. New data on differences in TLR9 gene expression in mice of the two strains infected with the virus were obtained. Reduced TLR9 gene expression in the cornea of C57Bl/6 mice was associated with their high sensitivity to infection caused by herpes simplex 1 virus.

[Effect of myelopeptides on reactive oxygen species generation and IL-1beta and TNF-alpha production by peripheral blood cells].

Myelopeptides MP-3, MP-5, and MP-6 were found to suppress zymosan-induced production of reactive oxygen species by leukocytes both under one-way introduction and under pretreatment. All of myelopeptides under examination in case of one-way introduction in cultures with zymosan demonstrated a decrease in zymosan-stimulated (1500 mkg/ml) production of IL-1beta, and activation of spontaneous production of this cytokine by whole blood cells. TNF-alpha production under myelopeptide effect was lowered in cultures with 150 mkg/ml zymosan. Under pretreatment myelopeptides did not render effect on IL-1beta and TNF-alpha production, with the exception of single stimulating effect of MP-5 on IL-1beta level in spontaneous cultures. Using comparative analysis the difference in direction and expressivity of effects of various myelopeptides was not revealed that suggests the existence of common mechanism of action in this group of peptide bioregulators.

[Changes in expression level of TLR9 and BD-2 genes in cornea of mice with viral keratitis].

AIM: Study of innate immunity genes expression (TLR9 and BD-2) in epithelial cells of mice cornea on the model of viral keratitis during the application of immunotherapy. MATERIALS AND METHODS: RNA isolation from cornea cells was performed by using RNeasy Mini Kit (Qiagen) and "RIBO-sorb" (ILS, Russia) reagent kits. "Kit for performing PCR-RT in the presence of intercalating dye SYBR Green I" (Syntol, Russia) was used for performing PCR. Data on gene expression is presented in decimal logarithms (relatively to 1 million of beta-actin gene copies). RESULTS: In C57B1/6 mice line at day 1 post infection the virus was detected in 33% of animals, at 3 days - in 90%, at 7 days the number of infected mice started to decline. In cornea of the mice infected with HSV-1 a significant decrease of TLR9 gene expression was observed. Administration of a complex of natural cytokines and antimicrobial peptides (Superlimf preparation) caused statistically significant increase of expression levels of the studied TLR9 and BD-2 genes. CONCLUSION: The model of viral keratitis and expression analysis of recognizing receptor TLR9 and defensin (BD-2) genes can be used to study mechanism of action of various preparations during infection in eye tissues and evaluation of possibility of their use in complex therapy of ophthalmic herpes.

Effects of myelopeptides on immune response and morphometrical manifestations of inflammation in experimental penetrating wound of the eye.

Myelopid and MP-1 myelopeptide increase the count of antibody-producing cells, reduced under the effect of injury and standard therapy, and do not modify the suppression of delayed hypersensitivity. Injections of myelopid and MP-3 together with standard drugs optimized the traumatic inflammation processes.