Bulletin of the Russian Military Medical Academy

Background: This study reviewed the hematological and biochemical changes in phallacidin-intoxicated outbred rats and their potential roles in thanatogenesis. The established laboratory correlates of phallacidin intoxication are inconsistent and controversial, indicating an understudied toxicity produced by this peptide. Therefore, hematological and biochemical changes in rats associated with extremely severe phallacidin intoxication should be assessed at three median lethal doses (6.3 mg/kg).

Materials and methods: This two-stage study included 27 outbred male rats weighing 300–350 g. In stage 1, postmortem changes in complete blood count and blood chemistry were examined, whereas during stage 2, changes in plasma hemoglobin and glucose concentrations at different time points after peptide administration were evaluated. The toxic effects of phallacidin at three median lethal doses (6.3 mg/kg) following intraperitoneal administration is associated with severe intoxication with 100% mortality within 5 hours.

Results: The animals developed myoplegia, coma, moderate seizures manifested as pawing-type periodic clonus of the forelimbs, fulminant hepatic failure with cytolysis, cholestasis, hypoglycemia, and hemorrhage in the liver tissue with massive blood loss accompanied by consumptive thrombocytopenia. Visual examination of the dead rats revealed pale mucous membranes of the nasal and oral cavities and skin of the ears and tail. Skeletal muscle spasm was observed in rats who experienced seizures. Urgent hypoglycemia was established as the immediate cause of rat mortality. Hypoglycemia was related to seizures and occurred before onset and severity of the concurrently massive hemorrhage.

Conclusions: Thus, сarbohydrate metabolism disorders in phallacidin intoxication determine the condition severity and time of death in rats, whereas blood loss events potentiate сarbohydrate metabolism disorders. The mechanisms of hypoglycemia in rats and neurologic impairment in a short time require a more detailed review.

Background: This study evaluated scientific and methodological approaches for evaluating the effectiveness of pharmaceutical supply in medical organizations, including the Sverdlovsk Regional Clinical Psychiatric Hospital, and developing measures for its optimization by integrating a quality management system (QMS) and a lean management system (LMS).

Materials and methods: Content analysis, structural and functional analysis, logical analysis, and observation, comparison, and descriptive methods were utilized in this study. Furthermore, process design and modeling approaches were applied to evaluate pharmaceutical supply management. The study focused on pharmaceutical and medical device supply processes within medical organizations (using the Sverdlovsk Regional Clinical Psychiatric Hospital as an example).

Results: Considering the specifics of the hospital’s operations and applying the provisions of the ISO 9001:2015 standard (Quality Management Systems—Requirements) and ICH Q10 (Pharmaceutical Quality System), an internal quality management policy was developed to regulate the pharmaceutical supply process within hospitals. The study identified the primary responsibilities of a pharmaceutical quality officer in overseeing compliance with internal pharmaceutical protocols in hospital departments, units, and branches. As part of QMS and LMS implementation in pharmaceutical supply management, an original checklist was designed to facilitate multistage compliance monitoring at temporary storage areas, nurse stations, and procedure rooms. The core principles of lean management are integrated at each stage of the internal quality control of pharmaceutical supply, demonstrating the integration of QMS and LMS.

Conclusions: Thus, the study demonstrates that integrating QMS and LMS allows medical organizations to optimize pharmaceutical supply processes and achieve a synergistic effect by eliminating functional and documentation redundancies. This enhances the efficiency of medical organizations and improves the quality of healthcare delivery without increasing resource consumption.

Background: The role of extragenital pregnancy-related complications in the development of late cardiovascular disease is being widely investigated. The prevalence of heart failure, specifically the form with preserved ejection fraction, is higher among females. The association between gestational hypertension and heart failure with preserved ejection fraction has been the subject of extensive research.

The aim of the study was to investigate the morphofunctional parameters of the heart in women with a history of gestational hypertension.

Methods: This study investigated the morphofunctional parameters of the heart in 102 women aged 45–59 years with a history of arterial hypertension during at least one completed pregnancy. The participants underwent transthoracic echocardiography and were then interviewed regarding their history of hypertension during pregnancy. Twenty-six women had a history of arterial hypertension during pregnancy, whereas 70 women did not. Subsequently, the echocardiographic parameters between the groups were compared.

Results: Among participants with a body mass index >25 kg/m², the left ventricular myocardial mass index, which was adjusted for body surface area and height, was significantly higher in the those with a history of hypertension during pregnancy than in those without hypertension (88.6 ± 24.3 vs. 71.7 ± 15.3; p = 0.002 and 44.6 ± 14.3 vs. 32.8 ± 42.4 ; p = 0.004, respectively). Mitral annulus velocity was lower in women with pregnancy-related hypertension, which is a characteristic of impaired left ventricular relaxation. The detection rate of diastolic dysfunction was higher in the group of women with hypertension during pregnancy: 10 (38.5%) compared to 12 (17.1%) (p = 0.03). Moreover, significant differences (p = 0.003) in epicardial adipose tissue thickness were identified: 7.5 (5.5; 9) mm in the group of women with hypertension during pregnancy compared to 5 (4; 7) mm in those without.

Conclusions: In middle-aged women, the most pronounced changes were observed in diastolic dysfunction parameters and in cardiac morphometric characteristics. Furthermore, hypertension complications during pregnancy influence epicardial adipose tissue thickness, a key predictor of cardiovascular complications.

Background: The destruction of chemical weapons stored in the Russian Federation was completed in 2017. However, remediation activities at these facilities continue, including decontamination and dismantling of process equipment, rehabilitation of buildings and sites, waste disposal and burial, and land reclamation within and around the former chemical weapon destruction facilities. Upon completion of these phases, the facilities will be subject to re-profiling or complete liquidation.

Aim: The aim of the study was to examine the nonspecific immune defense of military personnel engaged in remediation activities at hazardous chemical facilities.

Materials and methods: This study examined the nonspecific immunity of military personnel engaged in the remediation of chemical weapon destruction facilities at Kizner, Maradykovsky, and Leonidovka. Long-term exposure to hazardous chemicals was found to induce functional impairments in polymorphonuclear neutrophils, exhibiting a phased response pattern.

Results: The oxygen-dependent microbicidal activity of neutrophils, assessed using the nitroblue tetrazolium test, was significantly lower than both the control group values and standard reference ranges, regardless of occupational roles. This indicates a functional deficiency in neutrophils and their impaired activation, possibly due to environmental and occupational stress affecting this component of the immune system. Conversely, the oxygen-independent microbicidal activity, assessed using the lysosomal-cationic test, demonstrated consistent tolerance to adverse chemical factors. Assessment of neutrophil phagocytic activity in response to Staphylococcus aureus revealed a significant decrease in the number of cells capable of engulfing foreign agents compared to the control group, whereas their functional capacity remained preserved. The proportion of phagocytic cells was not associated with the degree of exposure to toxic substances.

The leukocyte migration inhibition test showed functional impairments in immunocompetent cells, indicating maladaptation, which was notable in personnel with direct exposure to toxic agents. Data from the period of active operation of chemical weapon destruction facilities exhibited no improvement in immune function markers.

Conclusions: This indicates that chemical disposal operations and remediation activities at hazardous facilities place a significant strain on the immune system. This requires continued monitoring with the integration of immunological surveillance into the medical support system for personnel working at hazardous chemical facilities.

Background: This study examined the early recurrence (within the first 3 months) of atrial fibrillation (AF) in patients with persistent AF, focusing on the effective refractory period (ERP) of the left atrium and pulmonary veins and clinical and laboratory comorbidities. Furthermore, the study evaluated outcomes 12 months after treatment.

Materials and methods: Sixty patients with persistent AF refractory to antiarrhythmic therapy were included. Each patient underwent ERP assessment of the left atrium and pulmonary veins, followed by radiofrequency antral isolation of the pulmonary vein ostia. The patients were grouped into two based on ERP values: group 1, patients with average ERP values of the left atrium and pulmonary veins ≥ 240 ms and group 2, those with average ERP values < 240 ms. The incidence of early AF recurrence was assessed within the first 3 months based on ERP values, and the efficacy of catheter ablation was evaluated at 12 months.

Results: No significant differences were found in instrumental parameters (echocardiography and multislice computed tomography), laboratory findings (serum creatinine and glomerular filtration rate), and comorbidities between patients with and without early AF recurrence. However, the risk of early AF recurrence in group 2 was 6 times higher compared to that in group 1 (p = 0.04), and the risk of recurrence within 12 months after catheter ablation was 4 times higher (p = 0.02).

Conclusions: These findings indicate that an ERP of the left atrium and pulmonary veins below 240 ms may predict early AF recurrence (p = 0.04), AF recurrence within 12 months (p = 0.03), and the need for repeated ablation (p = 0.02). Clinical and laboratory comorbidities were not found to be significant predictors of early AF recurrence following interventional therapy in patients with persistent AF.

Background: This study substantiated the development of a mathematical model for predicting acute kidney injury (AKI) at the stage of qualified medical care and a diagnostic method for early detection of this complication in trauma-related disease using immunochromatographic test strips for cystatin C detection in single urine samples.

Materials and methods: The study involved two phases. In phase 1, upon hospital admission, the patients’ condition was assessed using a military field surgery scale for severity evaluation. A complete blood count and urinalysis were performed, as well as three sequential biochemical blood tests to determine standard AKI markers. Obtained data were used to develop a predictive formula for AKI. In phase 2, retrospectively, after preliminary sample preparation, an AKI diagnostic method was employed using the developed immunochromatographic test strips for cystatin C detection in a single urine sample.

Results: Upon applying a urine sample to the test strip, it interacts with a conjugate, and a control marker appears. If cystatin C binds to specific antibodies, two lines appear, indicating a positive test result. The method allows for the verification of AKI with > 80% accuracy in the early phase of trauma-related disease.

Conclusions: This study highlights the importance of a comprehensive approach that incorporates a predictive model on hospital admission of wounded patients. Implementing rapid diagnostic methods using cystatin C in the early stages of medical care improves triage efficiency, facilitates intensive therapy, and optimizes patient management during evacuation delays.

This review presents data from current Russian and international scientific studies on the causes and pathogenetic mechanisms of dementia in patients with type 2 diabetes mellitus (T2DM). Currently, T2DM is regarded as an independent risk factor for cognitive impairment and various dementia types, including vascular, mixed, and Alzheimer disease-related dementia. Dementia is a polyetiologic syndrome, and Alzheimer’s disease and cerebrovascular pathology are considered the predominant causes in the elderly. Several studies reported an association between diabetes mellitus and neurodegenerative processes in the central nervous system. Cognitive impairments caused by suboptimal neurogenesis, brain tissue insulin resistance, dysglycemia, oxidative stress, chronic systemic inflammation, β-amyloid peptide accumulation, and structural and functional changes in the cerebral vasculature are prevalent in the elderly, who are more frequently diagnosed with both dementia and T2DM. Key contributors to dementia include genetic predisposition, environmental factors, lifestyle, and diet. However, growing evidence indicates additional risk factors such as insulin resistance, hypertension, obesity, dyslipidemia, amylin metabolism disorders, and gut microbiota imbalance. Brain tissue insulin resistance, often called “type 3 diabetes mellitus” and closely associated with cognitive impairment, is particularly significant. Moreover, poor glycemic control and recurrent hypoglycemic episodes play a role in cognitive deficits in patients with diabetes mellitus. Nevertheless, the molecular and cellular mechanisms underlying dementia in T2DM remain unclear.

This study examined the pathogenetic mechanisms of burn wound deepening and confirmed approaches for optimizing local burn treatment strategies. In Russia, approximately 300,000 burn cases are registered annually, the majority of which are superficial and partial-thickness burns. A well-studied occurrence in burn pathology is the progressive deepening of wounds over time. Fundamental principles explaining this phenomenon were established long ago. Some tissues undergo instantaneous necrosis due to thermal exposure (primary necrosis zone), whereas other tissues undergo progressive necrosis caused by a cascade of complex pathogenetic changes (secondary necrosis zone). Understanding the early pathogenetic mechanisms initiated in the early phase of thermal injury may contribute to the development of new therapeutic approaches. A comprehensive literature review was conducted using electronic databases (i.e., eLibrary, PubMed, Scopus, Google Scholar, ResearchGate, and ScienceDirect) to analyze Russian and international studies on burn necrosis progression. The primary contributors to secondary necrosis in skin burns (i.e., tissue hyperthermia, microcirculatory dysfunction, and inflammation) are associated with inflammatory cascade reactions involving multiple mechanisms, including reactive oxygen species-mediated cell damage, apoptosis initiation, neutrophil extracellular trap formation, autophagy, and other processes. Burn-induced cell death leads to the release of damage-associated molecular patterns, whereas skin barrier disruption facilitates the penetration of pathogen-associated molecular patterns into tissues, amplifying the inflammatory response. These processes may be prevented, which may help reduce the depth of the burn. Experimental and clinical studies on various pharmacological agents and drug formulations aimed at stopping necrosis progression indicate that erythropoietin derivatives, anti-cytokine agents and their combinations, complement activation inhibitors, antioxidants, mitophagy stimulators (e.g., PTEN-induced kinase 1 and ubiquitin ligase), and other active compounds reduce necrotic expansion. Furthermore, nanoemulsions and hydrogels developed using microfluidic technology, along with other modern drug formulations, potentially prevent progressive tissue necrosis and enhance the biological availability of active substances. Therefore, multi-targeted therapies that address all pathogenetic components of necrosis progression should be developed.