Intact Controls Research Articles

Markers of Pain in 3 Different Murine Models of Posttraumatic Osteoarthritis: A Comparison Using Gait Analysis, Imaging, Histology, and Gene Expression

Background: Animal models play an important role in studying posttraumatic osteoarthritis (PTOA) disease progression. Different models exist, such as destabilization of the medial meniscus (DMM), anterior cruciate ligament (ACL) surgical transection (ACLs), and noninvasive ACL rupture. Purpose: To study the effects of PTOA on nociception in 3 different murine models and to relate these findings to macroscopic and microscopic changes in joint tissues. Study Design: Controlled laboratory study. Methods: A total of 42 male C57BL/6 mice, 12 weeks old, were randomly assigned to 4 groups: intact control (n = 10), DMM (n = 10), ACLs (n = 11), and closed ACL rupture (ACLc; n = 11) groups. Gait analysis was performed on 5 mice from the DMM group and 6 mice from ACLs and ACLc groups at 0, 1, 2, 4, 8, and 12 weeks after injury. At the 12-week time point, all mice underwent radiographs and then either micro–computed tomography imaging followed by histology and immunohistochemistry or gene expression analysis of the dorsal root ganglion and tibialis anterior muscle. Results: The peripheral and central pain markers were expressed at significantly higher levels in the synovium of both ACL injury groups when compared with the DMM group. Muscle atrophy genes were significantly upregulated in the ACL injury groups. Pain-related gait behavior started at 4 weeks for the ACL rupture groups and at 12 weeks for the DMM group. High-resolution radiographic imaging and histology demonstrated divergent changes in bone microstructure between the ACLs and DMM groups, suggesting different mechanical loading environments in these models. Conclusion: The principal finding of this study is the presence of markers of nociception at both the gene and the protein levels, with earlier expression in the ACL injury groups when compared with the DMM group. The second finding of this study is that the noninvasive ACL rupture model demonstrated changes comparable with those of the commonly used surgical ACL transection model, supporting use of this clinically realistic model in future studies of PTOA. Clinical Relevance: Quantitative clinical outcomes (imaging, pain scale, gait changes) related to osteoarthritis severity in an animal study, allowing for better understanding of clinical outcomes of osteoarthritis progression after ACL injuries in humans.

Suppression of Fibroblast Growth Factor Receptor-5 (FGFR5) has no Impact on Axon Regeneration after SCI.

One of the most common forms of the mammalian central nervous system (CNS) injuries is spinal cord injury (SCI), and any lesion to the CNS can result in a lifelong functional impairment since CNS axons cannot regenerate. The relative axon regenerating genes following spinal SCI were examined using the regenerative SN, pSN + DC, and non-regenerating DC lesion models. By using qRT-PCR, we discovered that fibroblast growth factor receptor-5 (FGFR5) was 4.2-fold more highly expressed in non-regeneration lesions compared to intact control and regenerating animals. Furthermore, in cultured dorsal root ganglion neurons (DRGN), short interfering RNA (siRNA)-mediated knockdown of FGFR5 had no effect on DRGN neurite outgrowth, indicating that the gene's suppression has no effect on axon regeneration and may play other roles in the CNS besides axon regeneration.

LIPID PEROXIDATION AND ANTIOXIDANT PROTECTION SYSTEM IN RATS UNDER CONDITIONS OF ISCHEMIC STROKE ON THE BACKGROUND OF ANXIETY-DEPRESSIVE DISORDERS

Background. Acute disorders of cerebral blood circulation are one of the most important medical and social problems, due to their high share in the structure of morbidity and mortality of the population, significant indicators of temporary loss of working capacity and primary disability. At the same time, the World Health Organization estimates that by 2021, 615 million people (about 10% of the world's population) will have symptoms of depressive or anxiety disorders. Therefore, the study of the pathogenetic links of comorbidity of anxiety-depressive disorders against the background of ischemic stroke is relevant.
 Aim: to study changes in antioxidant protection and lipid peroxidation under conditions of experimental ischemic stroke comorbid with anxiety-depressive disorders.
 Materials and methods. Experimental studies were conducted on 30 non-linear laboratory rats, which were divided into 3 groups: 1 group – intact control, 2 group – animals of the group with simulated ischemic stroke; Group 3 – rats with simulated ischemic stroke and anxiety-depressive disorders. Reproduction of ischemic stroke in rats was carried out using the model of endovascular occlusion of the middle cerebral artery (focal ischemia) according to E. Z. Longa. A model of reserpine-induced depression in rats was chosen for an in-depth study of the pathophysiological links of anxiety-depressive disorders.
 To assess the state of lipid peroxidation and the antioxidant defense system, the level of malondialdehyde, catalase, superoxide dismutase, and reduced glutathione in brain tissue homogenate and circulating blood was studied.
 Results. A sharp depletion of the body's protective reactions was established in rats with both ischemic stroke and under conditions of comorbid pathology, which was confirmed by a probable decrease in the level of catalase, superoxide dismutase and an increased level of malondialdehyde. In particular, the level of catalase and superoxide dismutase decreased in the brain tissue homogenate of rats with comorbid pathology; the level of malondialdehyde increased. At the circulating level, there was a 40-fold increase in the level of catalase (p<0.05) compared to intact animals, which indicated a compensatory reaction of the body to the activation of free-radical oxidation, since this enzyme neutralizes hydrogen peroxide.
 Conclusions. The obtained data indicate a more severe course of ischemic stroke against the background of anxiety-depressive disorders and the involvement of both pro- and anti-inflammatory cytokines in the development mechanism, as well as a violation of the balance between the processes of lipid peroxidation and antioxidant protection.

Morphological structure of testicles under conditions of experimental gonadopathy and after the administration of cholecalciferol in comprehensive correction schemes

The problem of male infertility is relevant and calls for a solution. The use of the D3 vitamin in infertility treatment schemes has a potentially positive effect on reproductive health in male individuals. The present study aims to examine the effect of vitamin D3, administered alone or in combination with a preparation containing the extract of Tribulus terrestris on the changes in the histological picture of testicular morphology in rats with experimental gonadopathy. Male rats with modeled reproductive function pathology (Serotonin-induced gonadopathy) were divided into groups receiving correction using cholecalciferol alone or in combination with the reference drug Tribestan (Tr), which contains an extract of Tribulus terrestris. In addition to observational microscopy, morphometric evaluation of spermatogenesis was performed on sections of the testicles stained with hematoxylin and eosin. The statistical analysis was performed using the standard software package “Statistica 6.0” with the utilization of the Student’s t-test and its nonparametric counterpart, the Kruskal-Wallis test for one-way analysis of variance, followed by the Mann-Whitney test. It was found that the seminiferous tubules of rats with Serotonin-induced gonadopathy are significantly reduced in size, and their tunica propria is thickened. Sertoli cells are often destructively altered, and the uniformity of their arrangement is disrupted. A decrease in the weight of the gonads, epididymis, prostate gland, and hypoandrogenization was observed as well as a decline in spermatogenesis indicators. An improvement in the morphological characteristics of the gonads was noted following the administration of vitamin D3 in the presence of pathology. The seminiferous tubules had a normal histological structure. The germ cells were arranged in concentric rows according to their developmental stages, and the Sertoli cells appeared visually unchanged. The population of Leydig cells appeared visually more heterogeneous than in the control animals. However, occasionally seminiferous tubules with focal necrobiosis of germ cells and dystrophy of Sertoli cells, as well as a reduction in rows of germ cells, were observed. Overall, the quantitative indicators of spermatogenesis improved after the administration of vitamin D3 compared to rats with experimental gonadopathy, although they did not reach the levels of the intact control. The administration of a combination of vitamin D3 and Tribestan in the presence of gonadopathy resulted in a greater positive effect compared to their individual use. The microscopic condition of the testicular tissue in rats was fully recovered. The combined use of vitamin D3 with Tribestan normalized the weight of the gonads and their appendages, significantly reduced the manifestations in the histological sections of degeneration and damage in the reproductive cells during the period of growth and differentiation, improved the relative level of androgen status in the organism and had a positive effect on spermatogenesis in the gonads. Thus, we have established that the combined use of Сholecalciferol and Tribestan for correcting experimental gonadopathy was more effective than either of the mentioned components alone.

Pathogenetic characteristics of the hormonal profile in rats subjected to restraint stress of different duration

The aim of the work is to ascertain the character of changes in the hormonal profile (concentrations of corticosterone, insulin, and adrenocorticotropic hormone) in conjunction with metabolic alterations and elevated blood pressure, which are induced in rats by restraint stress at 6th, 15th and 21st weeks of environmental space restriction.
 Materials and methods. A total of 55 normotensive male Wistar rats, aged 6–10 months, were assigned into 4 experimental groups (1 – intact control (10 rats); 2, 3 and 4 (15 rats each exposed to restricted space allowance)). All the animals were subjected to blood pressure (BP), blood glucose level and body weight measurements twice: at the stage of forming groups and at the 6th, 15th and 21st weeks. Plasma hormone concentrations (insulin, corticosterone, and ACTH) were examined by the immunoenzymatic method using commercial kits (Monobind, USA).
 Results. The body weight of the animals was significantly reduced by 20.72 % after 6 weeks of space allowance restriction, it was restored to baselines by the 15th week and exceeded control values by 26.1 % at the 21st week. BP levels showed an increasing trend, a dynamic increase in systolic pressure by 7 %, 17 % and 26 % was detected, respectively, as well as diastolic from the 15th week to the 21st week by 21.4 % and 37.0 %, respectively. Glucose concentration was within the euglycemic range. Changes in the hormonal profile showed an increase in the concentration of ACTH by more than 50 % and a decrease in insulin – by 34 % at the 6th week with a subsequent twofold decrease in the insulin concentration (at week 15) and a further more than twofold increase in ACTH at the 21st week. As for changes in the concentration of corticosterone, a peak increase of 3.77 times was noticed at the 15th week, followed by a decrease and restoration to the normative values by the 21st week.
 Conclusions. Even minor and unremarkable continuously acting stressors, which cannot be coped, become important triggers for hormonal profile and carbohydrate metabolism alterations as well as for a persistent increase in blood pressure, which manifest first by hypoinsulinemia, an increase in the level of ACTH, and a constant concentration of corticosterone. Long-term stress exposure contributes to a transient “peak” increase in the corticosterone level, a significant increase in insulin and a sustained increase in ACTH. Multidirectional changes in the levels of the studied hormones occur amidst a gradual increase in blood pressure and a stable increase in the level of glycemia.

Neural oscillations reveal disrupted functional connectivity associated with impaired speech auditory feedback control in post-stroke aphasia

The oscillatory brain activities reflect neuro-computational processes that are critical for speech production and sensorimotor control. In the present study, we used neural oscillations in left-hemisphere stroke survivors with aphasia as a model to investigate network-level functional connectivity deficits associated with disrupted speech auditory feedback control. Electroencephalography signals were recorded from 40 post-stroke aphasia and 39 neurologically intact control participants while they performed speech vowel production and listening tasks under pitch-shifted altered auditory feedback (AAF) conditions. Using weighted phase-lag index, we calculated broadband (1–70 Hz) functional neural connectivity between electrode pairs covering the frontal, pre- and post-central, and parietal regions. Results revealed reduced fronto-central delta and theta band and centro-parietal low-beta band connectivity in left-hemisphere electrodes associated with diminished speech AAF compensation responses in post-stroke aphasia compared with controls. Lesion-mapping analysis demonstrated that stroke-induced damage to multi-modal brain networks within the inferior frontal gyrus, Rolandic operculum, inferior parietal lobule, angular gyrus, and supramarginal gyrus predicted the reduced functional neural connectivity within the delta and low-beta bands during both tasks in aphasia. These results provide evidence that disrupted neural connectivity due to left-hemisphere brain damage can result in network-wide dysfunctions associated with impaired sensorimotor integration mechanisms for speech auditory feedback control.

Characteristics of morphological changes in the skin of patients with allergodermatoses during long-term external application of fluorined steroids

The article presents the results of studies of the effect of applying topical fluorinated glucocorticosteroids in combination with ceramides on the barrier function of the skin of experimental animals with allergic dermatoses (guinea pigs). The purpose of the work: substantiation of the inclusion of ceramides in the base of topical fluorinated steroid preparations for the treatment of allergic dermatoses by studying the morphological changes in the skin of guinea pigs after the application of the indicated means of various compositions. Materials and methods. Histological research was carried out on outbred guinea pigs of the same sex and condition (74 individuals). The animals were divided into separate groups depending on the applied drugs. The following combinations of drugs and, accordingly, guinea pigs were selected, which were divided as follows: IC – intact control (15 animals); O – base application (14); OC – base containing ceramides (15); FSt/kr – fluorinated steroids of strong action (betamethasone) (16); FStK/kr – fluorinated steroids of strong action (betamethasone) + ceramides (14). Results. In order to study the traumatic effect of topical steroids on the skin and the possibility of preventing morphological (atrophic) disorders, an experimental study of the morphology of the skin of guinea pigs was carried out on a model of atrophy caused by long-term (14 days) application of topical fluorinated steroids of various compositions. Applying the foundation to animals led to some thickening of the epidermal layer, while the morphology of the epidermis and the skin itself was not disturbed. The addition of ceramides led to the acceleration of proliferative processes and the development of proliferative acanthosis. Changes induced by betamethasone were noted mainly in the epidermis in the form of local atrophy of the epidermal layer. The addition of ceramides to a potent fluorinated steroid to some extent smoothed out the negative effects of the corticosteroid hormone. The average thickness of the epithelial layer increased by 2 times compared to the thickness of the epithelial layer of animals of the FSt/kr group and even slightly exceeded the indicators of intact animals. Vacuolar dystrophy of the cells of the spinous and granular layers occurred in all animals of the FStK/kr group. Lymphoid infiltration of the dermis, parakeratosis and acantholysis were not noted. Conclusions. The results of an experimental study of the effect of topical fluorinated steroids of different composition on the skin of guinea pigs indicate the existence of differences between the drugs in terms of their degree of action on the intensity and development of pathological processes in experimental animals. A comparison of the effect on the skin of classic topical steroids and those additionally containing ceramides indicates the possibility of preventing the traumatic effect of hormones, which is especially important for patients with filaggrin gene mutations.

Cognitive control moderates the maturation of relational aggression in adults

Relational aggression (RA) is a covert form of social aggression consisting of reactive and proactive subtypes. Little is known about RA in adults, and less so about the association with cognitive control. We hypothesised greater levels of proactive but lower levels of reactive RA in adults with intact cognitive control. MethodsAn adult sample (N = 769) completed a cognitive control task and self-report RA survey. Two robust ANOVAs examined proactive and reactive RA levels between participants with intact and impaired levels of cognitive control, with the role of age in such associations explored in a post-hoc analysis. ResultsWe observed greater reactive but not proactive RA levels in established adults with impaired cognitive control. Further, younger participants tended to report higher levels of both RA subtypes. ConclusionsFindings support theories of cognitive control as a mitigating factor for RA and suggest the influence of age may be subordinate to developmental maturation and cognitive control.

К ПРОБЛЕМЕ ДИАГНОСТИКИ В ПРЕВЕНТИВНОЙ ЭНДОДОНТИИ

Subject. The most significant problem of modern preventive endodontics is to determine the vitality of the pulp and, accordingly, to make a decision about the choice of treatment method. The early stages of inflammation in the pulp may not be fully detected clinically and require the inclusion of additional examination methods that assess the state of microcirculation in the neurovascular bundle, as well as the severity of the immune response. These methods include: clinical and immunological examination of the gingival fluid (GF), as well as the assessment of tissue perfusion using laser Doppler flowmetry (LDF). 
 Objectives. The purpose of the study is to optimize the diagnostics of the dental pulp condition in the context of implementing the concept of preventive endodontics.
 Methodology. 37 patients aged 19–29 years with a diagnosis of K 04.00 "Pulp hyperemia" were examined. In addition to the basic methods of examination, LDF and immunological study of GF (IL-1β, TNF-α, IL-4) were used. In each patient, 1 tooth with pulp hyperemia and 1 intact (control) tooth were examined.
 Results. In the immunological analysis of DF in the area of teeth with pulp hyperemia, higher values of cytokines were obtained compared to intact teeth (p < 0.05). At the same time, in the area of 2 teeth with pulp hyperemia (5.4%), the level of cytokines was higher than their average values in the group of carious teeth. LDF of teeth with pulpal hyperemia also revealed higher values of M and σ compared with similar parameters in control teeth (p < 0.05). At the same time, in 2 cases, the highest levels of LDF were noted, which was consistent with the previously observed high values of cytokines in the gingival fluid in these loci. Moreover, after 2 weeks, a clinic of irreversible pulpitis was observed in these 2 teeth.
 Conclusion. When diagnosing reversible forms of pulpitis and deciding on the possibility of biological treatment of pulp hyperemia, it is necessary to assess the state of microcirculatory changes that have occurred in the pulp tissue, as well as the level of local immunological reactions.

In vitro gastric digestion of an experimental infant formula containing both intact and hydrolyzed milk proteins

Milk protein hydrolysates may have several benefits for digestion and digestion-related complications in infants, whereas intact milk proteins have been demonstrated to provide functionality beyond their nutritional value. In this study, in vitro digestion of an experimental infant formula containing both intact milk proteins and a milk protein hydrolysate was determined. Relative to an intact milk protein control formula, the experimental formula displayed a higher initial protein digestion during simulated gastric digestion as illustrated by a larger proportion of smaller peptides and higher level of available amino groups during digestion. Gastric protein coagulation was not affected by the hydrolysate addition. Further in vivo studies should demonstrate whether partial replacement of the protein source by a hydrolysate and observed differences in in vitro protein digestion result in overall altered protein digestion and absorption kinetics or affect functional gastrointestinal disorders as has been demonstrated for full hydrolysate formula.

Respiration in isolated cardiomyocytes and microviscosity of their membranes in rats of different ages with heart failure

Background. According to the latest epidemiological data, heart failure (HF) is diagnosed in 10% of adult population over 70 years old. However, currently this diagnosis is being increasingly made in young and middleaged people. The pathogenesis of HF may be based on a decrease in respiration in cardiomyocytes with age, which affects the function of energy-dependent processes in cells.Aim. To study respiration in cardiomyocytes and microviscosity of their membranes in rats aged 2 and 15 months with heart failure.Materials and methods. The study was carried out on male Wistar rats. The animals were divided into 4 groups: 2 groups of intact rats aged 2 and 15 months (n = 12) and 2 groups of animals of similar ages (n = 10) with a model of HF. In the latter, HF formed by day 28 after a double subcutaneous injection of isoproterenol hydrochloride at a dose of 170 mg / kg with an interval of 24 hours. Isolated cardiomyocytes were obtained from enzyme-washed rat hearts. Cell respiration was studied in a thermostated chamber in an incubation medium supplemented with phosphorylation (ADP) and oxidation (succinate) substrates. The respiratory control (RC) ratio was calculated by dividing V3 respiration state to V4. Membrane microviscosity characteristics were assessed by the eximerization coefficient of pyrene fluorescence in the areas of protein – lipid and lipid – lipid interactions.Results. RC in cardiomyocyte membranes of intact animals did not change with age. In 2-month-old rats with HF, respiratory control ratio (RCR) did not change compared with the intact age-matched controls. In 15-month-old rats with HF, there was a significant decrease in RC of cardiomyocytes (CM) compared with the intact animals of this age and 2-month-old rats with HF. An age-dependent decrease in the microviscosity of CM membranes in the areas of lipid – lipid interactions and no significant changes in the parameter at the sites of protein – lipid interactions were noted. In 2-month-old animals with HF, the microviscosity of CM membranes in the areas of protein – lipid interactions significantly decreased, and in 15-month-old rats it increased, compared with the intact controls. When carrying out an intergroup comparison, an age-dependent increase in the microviscosity of CM membranes in the areas of protein – lipid interactions and no differences in the parameter in the areas of lipid – lipid interactions were revealed.Conclusion. In the intact rats, the absence of significant changes in respiration with age was revealed. In the 15-month-old animals with HF, respiration in CM was significantly lower than in the intact controls and 2-monthold animals with HF. These changes may be due to the differences in the membrane microviscosity characteristics in different periods of ontogenesis.

TBC1D4-S711 Controls Skeletal Muscle Insulin Sensitization After Exercise and Contraction.

The ability of insulin to stimulate glucose uptake in skeletal muscle is important for whole-body glycemic control. Insulin-stimulated skeletal muscle glucose uptake is improved in the period after a single bout of exercise, and accumulating evidence suggests that phosphorylation of TBC1D4 by the protein kinase AMPK is the primary mechanism responsible for this phenomenon. To investigate this, we generated a TBC1D4 knock-in mouse model with a serine-to-alanine point mutation at residue 711 that is phosphorylated in response to both insulin and AMPK activation. Female TBC1D4-S711A mice exhibited normal growth and eating behavior as well as intact whole-body glycemic control on chow and high-fat diets. Moreover, muscle contraction increased glucose uptake, glycogen utilization, and AMPK activity similarly in wild-type and TBC1D4-S711A mice. In contrast, improvements in whole-body and muscle insulin sensitivity after exercise and contractions were only evident in wild-type mice and occurred concomitantly with enhanced phosphorylation of TBC1D4-S711. These results provide genetic evidence to support that TBC1D4-S711 serves as a major point of convergence for AMPK- and insulin-induced signaling that mediates the insulin-sensitizing effect of exercise and contractions on skeletal muscle glucose uptake.

Morphological Features of the Synovial Membrane and Articular Cartilage in Rats under Simulated Adjuvant Arthritis and Application of Allogeneic Biomaterial

The aim of research was to study morphological features of the synovial membrane and articular cartilage of rats under simulated adjuvant arthritis and application of allogeneic biomaterial.Material and methods. To simulate rheumatoid arthritis, 12 white outbred female rats were injected 100 μl of complete Freund's adjuvant into the plantar surface of the hind paw. In 7 days, 5 mg of the allogeneic biomaterial “Regeneration stimulator” dissolved in physiological solution was injected into the periarticular bursae of the right knee joint and surrounding tissues in the rats of the main experimental group (n=6). Saline solution was injected into animals of the main control group (n=6). Intact rats (n=6) were included in the intact control group. All the animals were withdrawn from the experiment in 37 days after the onset of the experiment. The knee joints of rats were examined using standard histological, morphometric and statistical methods.Results. Animals of the main control group manifested signs of degenerative changes of varying degrees in the articular apparatus. Proliferation of the synovial cells and tissue hyperplasia were detected in the synovial membrane, these leading to the formation of pannus. There was disorganization of the connective tissue: they were thinned, the fibrous layer was separated, the cartilage and bone tissue were destructed. In animals of the experimental group, there were no signs of tissue hyperplasia and edema, pronounced pannus were not detected after the introduction of the allogeneic biomaterial in the synovial membrane. Mild signs of arthritis manifested as slightly increased processes of the synovial cell proliferation and moderate perivascular infiltration with cellular elements were detected in 2 rats. There were no changes in the structure of the cartilage and bone in the knee joint.Conclusion. Intraarticular injection of the allogeneic biomaterial "Regeneration Stimulator" in rats with simulated autoimmune rheumatoid arthritis is accompanied by a decreased external manifestations of a generalized inflammatory process in the knee joints, and by a decreased inflammation and degenerative changes in the articular apparatus at the tissue level. Notably, the structures of the synovial membrane, the articular cartilage of the knee joint and the underlying subchondral bone are preserved compared with animals of the control group.

STUDY OF ENDOTHELIAL DYSFUNCTION INDICATORS IN RATS WITH EXPERIMENTAL PERITONITIS

Background. In the structure of purulent complications, peritonitis, destructive lesions of abdominal organs, and, as a rule, advanced forms of these diseases occupy one of the first places - 15-25% of urgent surgical diseases are complicated by peritonitis. It is generally known that the leading role in the triggering mechanism of the development of peritonitis belongs to the systemic inflammatory reaction, a component of which is phagocytosis, cellular and humoral immunity. However, the results of research on the state of functional activity of the endothelium in experimental peritonitis are limited.
 Aim: to study the activity of NO-synthase, FV and endothelin-1 in rats with experimental peritonitis.
 Materials and methods. Experimental studies were conducted on 24 non-linear laboratory rats, which were divided into 2 groups: 1 group – intact control (animals received distilled water), 2 group – animals of the control pathology group. According to the "Methodological recommendations for preclinical study of medicinal products", experimental peritonitis was studied on the model of V. A. Lazarenko. Indicators of vascular-platelet and coagulation hemostasis were determined according to generally accepted methods. Indicators characterizing endothelial dysfunction were studied according to generally accepted methods.
 Results. The most likely mechanism that is damaged in the endothelium during peritonitis is the activation of the synthesis of inducible NO-synthase by neutrophils/macrophages in response to infection. It is possible that the hyperproduction of nitric oxide, on the one hand, is aimed at destroying microflora and oxidizing toxins, and on the other hand, at suppressing the expression of tissue factor and cell adhesion molecules. platelet aggregation and cascade disorders in the hemostasis system. In animals with experimental peritonitis against the background of oxidative stress, there was an increase in the number of circulating desquamated endothelial cells in the blood, which is a highly specific marker of endothelial dysfunction. The level of the Willebrand factor also increased, which indicates the pathogenetic dependence of the factors that damage the endothelium of the vascular wall on the concentration of the Willebrand factor, which helps to reduce the permeability of blood vessels by adhesion of platelets to the endothelium. Confirmation of the development of endothelial dysfunction in peritonitis is an increase in the concentration of endothelin-1, which is a regulator of the process of vascular neoangiogenesis in response to endothelial damage.
 Conclusion. Hyperproduction of nitric oxide not only reflects the processes that occur in the focus of vascular endothelium damage, but also affects the severity of the inflammatory process and the consequences of the disease.

STUDY OF THE ROLE OF HEMOCOAGULATION DISBALANCE AS A KEY PATHOGENETIC PREDICTORS IN THE FORMATION OF SYSTEMIC DISORDERS IN EXPERIMENTAL PERITONITIS

Background. Peritonitis today continues to be one of the most difficult problems of both abdominal surgery and theoretical pathophysiology. One of the leading pathogenetic mechanisms of peritonitis is disorders in the hemostasis system and the development of dissemination vascular syndrome. Blockade of microcirculation caused by the development of dissemination vascular syndrome leads to tissue hypoxia and, as a result, to dysfunction of organs and body systems.
 Aim: is to study changes in vascular-platelet and coagulation hemostasis under conditions of experimental fecal peritonitis in rats.
 Materials and methods. Experimental studies were conducted on 24 non-linear laboratory rats, which were divided into 2 groups: 1 group – intact control (animals received distilled water), 2 group – animals of the control pathology group. According to the "Methodological recommendations for preclinical study of medicinal products", experimental peritonitis was studied on the model of V. A. Lazarenko. Indicators of vascular-platelet and coagulation hemostasis were determined according to generally accepted methods.
 Results. On the first day of experimental peritonitis, a sharp increase in the rate of blood clotting and changes in the quality properties of platelets were noted, affecting their aggregation ability and retraction of an already formed blood clot. On the 4th day of the experiment, changes in the vascular-platelet link were established, indicating the exhaustion of the platelet potential, due to a decrease in blood clotting time, platelet aggregation ability, and blood clot retraction against the background of a probable increase in the number of blood platelets, which probably by now had time "get" to the bloodstream from the depot. Changes in the coagulation hemostasis system against the background of experimental fecal peritonitis indicate the development of hypercoagulation already on the first day, which is replaced by a hypocoagulation state, which indicates the exhaustion of the enzymatic systems of blood coagulation potential (as early as on the 4th day), which lasted until the end of the experiment.
 Conclusion. In the development of disorders of the hemostasis system in fecal peritonitis, the key role belongs to both the internal and external mechanisms of activation of the blood coagulation system.

The Differential Role of Executive Apathy in Alzheimer's Disease Dementia, Mild Cognitive Impairment and Healthy Cognitive Ageing.

The objective of the present work was to compare the levels of executive, emotional, and initiation apathy in individuals with mild cognitive impairment (MCI), mild Alzheimer's disease dementia (ADD), and cognitively intact healthy controls (HCs). Fifty-two patients with mild ADD, 40 individuals with MCI, and 37 cognitively intact individuals were included in the current study. The participants were consecutive visitors to the Outpatient Memory Clinic of "Nestor" Alzheimer's Center. The symptoms of apathy were measured with the dimensional apathy scale. Analyses showed that ADD patients had significantly higher degrees of executive, emotional, initiation, and overall apathy compared with both the MCI group and the HCs. Additionally, a significant difference was observed in the dimension of executive apathy between individuals with MCI and the HCs. In conclusion, the dimension of executive apathy was the most sensitive measure regarding the differentiation of individuals with mild ADD or MCI and HCs. Hence, detailed evaluation of executive apathy in older individuals referred to a memory clinic may provide useful information contributing to their diagnostic categorization and to the differentiation between neurocognitive disorders and healthy cognitive ageing.

Effect of ethylthiosulfаnylate in combination with vitamin E on certain biochemical blood parameters and hematological indicators in rats under the influence of Cr(VI)

The aim of our study was to investigate the effect of ethylthiosulfаnylate, a representative of the class of thiosulfonate compounds, in combination with vitamin E on certain biochemical blood parameters, hematological indicators and total Chromium content in liver of rats exposed to Cr(VI). Laboratory rats were divided into 8 groups of 5 animals each. Animals of group I (intact control) were injected daily intraperitoneally with 150 μl of physiological saline solution for 7 days. Rats of III/IV groups received intraperitoneal daily administration of K2Cr2O7 (diluted in physiological saline solution at a dose of 2.5 mg Cr(VI)/kg) for 7/14 days. Animals of the II experimental group were injected daily intragastrically with 1000 μl of sunflower oil for 14 days. Rats of V/VI experimental groups were administrated daily intragastrically with 1000 μl of an oil solution of vitamin E (20 mg/kg)/vitamin E (20 mg/kg) in combination with ethylthiosulfаnylate (100 mg/kg) for 14 days. Animals of VII/VIII experimental groups were injected daily intragastrically with 1000 μl of an oil solution of vitamin E (20 mg/kg) in combination with ethylthiosulfаnylate (100 mg/kg) for 14 days, after which a 7-day/14-day period of intraperitoneal K2Cr2O7 administration was performed. Exposure to Cr(VI) led to a decrease in the number of erythrocytes, leukocytes, content of hemoglobin, phospholipids, total protein against the background of the accumulation of total lipids, mono- and diglycerides, non-esterified fatty acids, and creatinine in blood of rats. Chromium concentration significantly increased in the liver of rats after administration of Cr(VI). The combined effect of vitamin E and ethylthiosulfаnylate contributed to the partial compensation of Cr(VI)-induced disturbances of the number of leukocytes and content of total proteins, phospholipids, non-esterified fatty acids in blood of rats. Vitamin E and ethylthiosulfаnylate pretreatment also contributed to the reduction of the percentage accumulation of Chromium in liver of rats injected with Cr(VI).

Protecting nature's most effective carbon sink: an important role for fungi in peatlands.

This article is a Commentary on Shao et al. (2023), 238: 80–95.

The Impact of Indigenous Different Methods of Caponization on Sensory Characteristics of Selected Cockerels Breeds

The study was conducted to evaluate the sensory characteristics of different methods of caponization of selected locally bred cockerels. A total of ninety (90) healthy 2 weeks old chicks were purchased from a farmer in Wenchi, (45 plymouth rock chicks and 45 hypeco chicks) and were fed on commercial starter, grower and finisher diets ad libitum until 14 weeks. At 8 weeks of age, the cockerels were individually weighed and randomly assigned to three groups for each of the breeds, open caponization, close caponization, and intact (Control) in cages with 3 replicates. Caponization was conducted by a licensed veterinary officer after the weighing. Two birds each were slaughtered on the 14th week for the sensory evaluation on grilled breast meat. The two caponization methods significantly enhanced the palatability, juiciness, flavour and tenderness of the meat. Open capon performed better among the caponization methods and the breeds. Open caponization of the cockerels had a great beneficial effect on the product intended to buy and consumers preference. In conclusion, the evaluators reorganized capon meat to be most preferred to intact cockerels and should be adopted to develop the poultry industry. The quality of chicken meat can be influenced by the caponization methods to meet the demand for safe and healthy poultry products by the consumers. A further study should be carried out on the nutritional profiles of the capons.

Effects of Positive Fighting Experience and Its Subsequent Deprivation on the Expression Profile of Mouse Hippocampal Genes Associated with Neurogenesis.

The hippocampus is known as the brain region implicated in visuospatial processes and processes associated with learning and short- and long-term memory. An important functional characteristic of the hippocampus is lifelong neurogenesis. A decrease or increase in adult hippocampal neurogenesis is associated with a wide range of neurological diseases. We have previously shown that in adult male mice with a chronic positive fighting experience in daily agonistic interactions, there is an increase in the proliferation of progenitor neurons and the production of young neurons in the dentate gyrus (in hippocampus), and these neurogenesis parameters remain modified during 2 weeks of deprivation of further fights. The aim of the present work was to identify hippocampal genes associated with neurogenesis and involved in the formation of behavioral features in mice with the chronic experience of wins in aggressive confrontations, as well as during the subsequent 2-week deprivation of agonistic interactions. Hippocampal gene expression profiles were compared among three groups of adult male mice: chronically winning for 20 days in the agonistic interactions, chronically victorious for 20 days followed by the 2-week deprivation of fights, and intact (control) mice. Neurogenesis-associated genes were identified whose transcription levels changed during the social confrontations and in the subsequent period of deprivation of fights. In the experimental males, some of these genes are associated with behavioral traits, including abnormal aggression-related behavior, an abnormal anxiety-related response, and others. Two genes encoding transcription factors (Nr1d1 and Fmr1) were likely to contribute the most to the between-group differences. It can be concluded that the chronic experience of wins in agonistic interactions alters hippocampal levels of transcription of multiple genes in adult male mice. The transcriptome changes get reversed only partially after the 2-week period of deprivation of fights. The identified differentially expressed genes associated with neurogenesis and involved in the control of a behavior/neurological phenotype can be used in further studies to identify targets for therapeutic correction of the neurological disturbances that develop in winners under the conditions of chronic social confrontations.