General Pathological Processes Research Articles

Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)

The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of “inflammatory systemic microcirculation”. The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.

Sepsis-3: new edition — old problems. analysis from the perspective of general pathology

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a nonhomogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the proinflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology.

Histopathological features of liver tissue in non-alcoholic and alcoholic steatohepatitis depending on the presence of concomitant anemia

The aim: to study some histopathological changes in the liver affected by steatohepatitis of various etiologies with the presence of anemia. Material and methods. Liver biopsies were analyzed in 30 patients with non-alcoholic steatohepatitis (NASH) and 20 patients with alcoholic steatohepatitis (ASH). The morphological examination of the liver was carried out according to the standard methods. The histopathological features of the liver were established on the basis of hematoxylin and eosin staining method, with confirmation, if necessary, by the histochemical methods - staining for fat (method with Sudan-III) and collagen fibers (method with chromotropic-water blue by NZ Slinchenko). Microspectrophotometric studies were performed using a cytological analyzer with software "VideoTest - Size 5.0" (2000). Results. A number of parameters revealed the statistical differences in the average trends with the use of the nonparametric Mann-Whitney method (p<0.05). The highest rate of hepatocyte necrosis was observed in the patients with ASH with anemia, in particular, more than a third of hepatocytes in these patients had signs of colic necrosis, which was more pronounced in ASH than in NASH. NASH with anemia was accompanied by more pronounced necrosis of hepatocytes than NASH without anemia. In ASH without anemia, the percentage of affected hepatocytes was on average approximately the same as in NASH without anemia. Fatty dystrophy of hepatocytes was observed in all the patients with NASH and ASH, but the severity of the general pathological process was not the same. Conclusions. Due to the comorbidity of fatty liver disease with anemia in both NASH and ASH, a much higher percentage of hepatocytes affected by reversible swelling are formed, which coincides with the tendency for hepatocyte oncosis. Anemia affects the nature of connective tissue growth in NASH and ASH (in ASH, the specific volume of connective tissue was higher than in NASH). At the same time, the intensity of regenerative processes in the liver (ductal reactions of the liver) is most pronounced in patients with anemia, and most - in ASH.

Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model

Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model.A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 ​mg/kg), SLN-CRYP (5 ​mg/kg), ABZ (50 ​mg/kg) DXM (0.5 ​mg/kg), and PHE (30 ​mg/kg).were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains.All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p ​< ​0.0001); as were frequency (p ​< ​0.0001) and duration (p ​< ​0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p ​= ​0.0016) and IFN-γ (p ​< ​0.0001).Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model.

MORPHOLOGICAL FEATURES OF CELLULAR INFILTRATION IN THE MUCOSA OF LARGE INTESTINE IN ULCERATIVE COLITIS AND IRRITABLE BOWEL SYNDROME

The aim is to improve morphological diagnostics, including differential, of UC and IBS, identifying morphological features of cellular infiltration in the mucous membrane ofthe large intestine. Material and methods: Autopsy and biopsy material - fragments of the mucous membrane of the large intestine was used in this study. All the material was divided into 5 groups. Group 1 included autopsy material from 6 cases, in which no general pathological processes in the gastrointestinal tract were detected during autopsy and microscopic examination. Group 2 included biopsy material from 34 patients with diagnosed UC of the 1st activity degree. Group 3 included the biopsy material of 27 patients with UC of the 2nd degree of activity. Group 4 included biopsy material from 19 patients, diagnosed with UC of the 3rd degree of activity. Group 5 included biopsy material from 82 patients with clinically diagnosed IBS. Histological, morphometrical, immunohistochemical and statistical methods of investigation were used. Results: The mucous membrane of the large intestine in patients with ulcerative colitis of varying degrees of activity, compared with the physiological norm, has pronounced infiltration by plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes in the superficial parts of the epithelium, crypts,lamina propria. There is also an increase in the number and size of lymphoid follicles in the lamina propria. Predominant cellular elements in the infiltrate are plasma cells, T-lymphocytes, eosinophilic and neutrophilic leukocytes. The growth of ulcerative colitis activity leads to an increase the inflammatory cell infiltration in the mucous membrane of the colon, as evidenced an increase the density of cellular infiltrate; the severity of inflammatory changes in crypts and an increase in the number of crypt abscesses; a decrease the number of cases with focal infiltration in the lamina propria and an increase the number of cases with diffuse infiltration; the spread of inflammatory cell infiltration from the superficial parts of the lamina propria to its deep parts with the subsequent involvement of its entire thickness; an increase the central trends of the indexes of the severity of all cellular infiltration, infiltration by plasma cells, T-lymphocytes, macrophages, neutrophilic leukocytes. The mucous membrane of the large intestine in patients with irritable bowel syndrome has moderately pronounced cellular infiltration in the superficial epithelium andlamina propria, in comparison with the physiological norm. The number and size of lymphoid follicles increase. Inflammatory cell infiltration often spreads to the upper onethird or two thirds of the thickness of the lamina propria, characterized by the presence of plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes. In this case, plasma cells, T-lymphocytes, mast cells and macrophages dominate. The indexes of the severity of all cellular infiltration, as well as infiltration by plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes, increases in the mucous membrane of the large intestine in irritable bowel syndrome in comparison with the norm. In the mucous membrane of the large intestine in irritable bowel syndrome compared with ulcerative colitis of varying degrees of activity inflammatory cell infiltration is less pronounced. It often extends to one third or two thirds of the thickness of the lamina propria. There are fewer lymphoid follicles, cryptitis and crypt abscesses are not determined. The indexes of the severity of all cellular infiltration, as well as infiltration by plasma cells, T-lymphocytes, eosinophilic and neutrophilic leukocytes are lower. Conclusions: The revealed features of cellular infiltration in the mucous membrane of the large intestine make it possible to improve morphological diagnostics, including differential, of ulcerative colitis of varying degrees of activity and irritable bowel syndrome.

Creating cell lines for mimicking diseases.

Cell lines can be good models for the disease they are derived from but can also be used to study general physiological and pathological processes. They can also be used to generate cell models of diseases when primary cultures are not available. Recent genome editing tools have been very promising tools toward creating cell models to mimic diseases in vitro. In this chapter, we highlight techniques used to obtain genome-edited cell lines, including cell line selection, transfection and gene editing tools available, together with methods of phenotype characterization and, lastly, a few examples of how in vitro disease models were created using CRISPR-Cas9.

MODERN MORPHOLOGICAL DIAGNOSTICS OF ULCERATIVE COLITIS AND IRRITABLE BOWEL SYNDROME: HISTOLOGICAL, HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL CRITERIA

The aim is to establish diagnostic and differential-diagnostic criteria for UC and IBS based on a complex morphological (histological, histochemical, immunohistochemical) study. Materials and methods: In this study, it was used autopsy and biopsy material - fragments of the mucous membrane of the large intestine. The material was divided into 5 groups. The first group (G 1) included autopsy material from 6 cases, in which, during autopsies and microscopic examination, we found no general pathological processes in the gastrointestinal tract. The second group (G 2) included biopsy material from 34 patients with diagnosed UC of the 1st activity degree. The third group (G 3) included the biopsy material of 27 patients with UC of the 2nd degree of activity. The fourth group (G 4) included biopsy material from 19 patients, diagnosed with UC of the 3rd degrees of activity. The fifth group (G 5) included biopsy material from 82 patients with clinically diagnosed IBS. Histological, histochemical, immunohistochemical, statistical research methods were used. Results: There are characteristic morphological changes in the mucous membrane of the large intestine in UC of varying degrees of activity, such as changes in the architectonics of crypts of varying severity; presence of erosive and ulcerative defects. Inflammatory and desquamative-dystrophic changes take place in the epithelial layer adjacent to erosive and ulcerative defects. The number of goblet cells of crypts decreases and the size of vacuoles in goblet cells reduces. The intensity of mucin secretion contained in the vacuoles of the goblet cells lowers; there is a partial or complete loss of pericryptal myofibroblasts; the proliferative potential of the intestinal crypts epithelium activates. Conclusions: Differential diagnostic criteria, revealed by the author, improve the morphological diagnosis of UC and IBS, optimizing the tactics of managing patients with this colorectal pathology.

MORPHOLOGICAL JUSTIFICATION OF THE SALIVARY GLAND TISSUE RESECTION BOUNDARIES DURING SURGICAL TREATMENT OF PATIENTS WITH PLEOMORPHIC ADENOMAS

The aim is to substantiate morphologically the resection boundaries of the salivary gland tissue in the surgical treatment of patients with pleomorphic adenoma of different histological variants. Materials and methods: The study used autopsy, surgical and biopsy material, divided into 2 groups. Group 1 included autopsy material (n=6), represented by tissue fragments of the parotid salivary gland, in which macroscopic and microscopic examination did not reveal any general pathological processes. Group 2 included surgical and biopsy material from 30 patients, represented by pleomorphic adenomas with adjacent tissue of the salivary gland at a distance of 0.5 cm and 1.0 cm. Histological, morphometric and statistical research methods were used. Results: The morphological features of the salivary gland tissue which was adjacent to the pleomorphic adenoma at a distance of 1.0 cm, practically corresponded to the physiological norm. However, the tissue of the salivary gland, bordering the tumor at a distance of 0.5 cm, was characterized by pronounced changes. These changes were: violation of the ratio of the specific volumes of the parenchyma and stroma; atrophy of the terminal sections and ducts with cystic expansion of some ducts; thickening of the secretion and formation of calculi in the lumen of some ducts; atrophic and alterative changes in the epithelial lining the terminal sections and ducts; sclerosis and lipomatosis, areas with hyalinosis and dystrophic calcification in the stroma; hemodynamic disturbances in the stroma with a decrease in the number of vessels; pronounced focal or diffuse immune infiltration in the stroma in some areas with the lymphoid follicles formation. Conclusion: The comprehensive study has confirmed that removal of the tumor with the adjacent tissue of the salivary gland at a distance of 1.0 cm in patients with pleomorphic adenoma of various histological variants is the most justified from the morphological point of view.

Collagen hydrogels loaded with fibroblast growth factor-2 as a bridge to repair brain vessels in organotypic brain slices

Vessel damage is a general pathological process in many neurodegenerative disorders, as well as spinal cord injury, stroke, or trauma. Biomaterials can present novel tools to repair and regenerate damaged vessels. The aim of the present study is to test collagen hydrogels loaded with different angiogenic factors to study vessel repair in organotypic brain slice cultures. In the experimental set up I, we made a cut on the organotypic brain slice and tested re-growth of laminin + vessels. In the experimental set up II, we cultured two half brain slices with a gap with a collagen hydrogel placed in between to study endothelial cell migration. In the experimental set up I, we showed that the number of vessels crossing the cut was tendencially increased with the addition of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor, or platelet-derived growth factor-BB compared to the control group. In the experimental set up II, we demonstrated that a collagen hydrogel loaded with FGF-2 resulted in a significantly increased number of migrated laminin + cells in the gap between the slices compared to the control hydrogel. Co-administration of several growth factors did not further potentiate the effects. Taken together, we show that organotypic brain slices are good models to study brain vessels and FGF-2 is a potent angiogenic factor for endothelial cell proliferation and migration. Our results provide evidence that the collagen hydrogels can be used as an extracellular matrix for the vascular endothelial cells.

USING OF BIOCORRECTORS IN REGENERATION PACING OF MECHANICALLY INJURED RATS’ FETAL HEPATIC

The article is devoted to studying the influence of biologically active substances on the regeneration of internal organs in mammals at the early stages of development. Complete recovery of the organ after damage does not occur. It is necessary to look for new ways that reveal the processes that contribute to regeneration. The study of processes that occur in the body before birth allows understanding the mechanisms of what happens in the postnatal period in general pathological processes. It was studied the mechanical damage to the liver in rat fetuses under the influence of biocorrectors “Trepel” and “Suvar.” Morphological, morphometric, histochemical, and immunohistochemical methods were used for processing the material. The results of the work indicate that the combined use of these biocorrectors after the development of a necrosis focus in the liver reduces alternative manifestations of hepatocytes, inhibits reactive inflammation around the injury site, slows down the recruitment of fibroblasts to the injury zone, and inhibits collagen genesis. At the same time, biocorrectors have a pronounced stimulating effect on proliferation of hepatocytes, which, against the background of increased enzymatic activity, manifests itself in the form of mitotic division activation and polyploidization of hepatocytes. Despite the signs of regenerative stimulation, as a result, complete recovery of the liver in the site of the dead tissue in experimental rats does not occur; there is only a 34.7% decrease in the focus of fibrosis formed in the place of dead liver tissue, compared to control animals.

The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats

Aim . To develop a pathogenetically reasonable model of type 2 diabetes with marked peripheral insulin resistance and relative insulin deficiency in rats using a high-fat diet and a single injection of streptozotocin in the low dose. Materials and methods. Experiments were conducted on 16 outbred male rats. Type 2 diabetes model in experimental animals was achieved by feeding them with high-fat diet (55% of energy from fat) for 28 days followed by a single injection of streptozotocin (35 mg/kg). The serum glucose and insulin concentrations in rats were measured before streptozotocin administration and at the end of the experiment. To estimate insulin resistance, insulin tolerance test and glucose tolerance test were performed. Total protein, albumin, total and direct bilirubin, urea, uric acid, total cholesterol, high-density lipoproteins and low-density lipoproteins, and activity of alanine aminotransferase and aspartate aminotransferase were measured in the blood serum. Results . A high-fat diet with a single injection of streptozotocin resulted in lipid and protein metabolism disorders and peripheral tissues insulin resistance in experimental animals. Basal insulin levels did not change against the backdrop of high glucose level. Conclusions . These results indicate that feeding rats with a high-fat diet (55% of calories from fats) and a single administration of streptozotocin at a low dose (35 mg/kg) reproduce general pathological processes of type 2 diabetes. This model can be used to study the pathogenesis of type 2 diabetes as well as to investigate the effect of potential hypoglycemic agents.

ANÁLISE MORFOLÓGICA DOS PROCESSOS PATOLÓGICOS GERAIS EM RINS DE RATOS OBESOS E SUA RELAÇÃO COM O EXERCÍCIO FÍSICO

The objective of the study was to compare the morphological findings, quantify the inflammation and renal fibrosis in obese rats submitted to physical exercise. Male Wistar rats were used. Control animals were fed standard feed and tap water, and the obese were fed a hyperlipidic diet. These animals were submitted to intermittent training, where the movement of complete extension of the paw was performed, lifting a load positioned at the back of the vest. The animals' kidneys were collected to evaluate the findings. Regarding the histopathological analysis, no general pathological processes were evidenced. When the fibrosis quantification was performed, no significant results were observed between the groups. It was concluded that no general pathological processes were observed in the kidneys of obese rats and their relationship with physical exercise. In this way, it is suggested to carry out new studies with longer protocols in order to better elucidate the results. KEYWORDS: Obesity, Kidney, Inflammation, Fibrosis, Exercise.

Although with intact mucosa at colonoscopy, chagasic megacolons have an overexpression of Gal-3.

ABSTRACTObjectiveTo evaluate the density of anti-galectin-3-immunostained cells, collagen percentage, mast cell density and presence of pathological processes in intestinal muscle biopsies of patients.MethodsThirty-five patients who underwent intestinal biopsy were selected from 1997 to 2015. Patients were divided into three groups: chagasic patients with mucosal lesion (n=13), chagasic patients with intact mucosa (n=12) and non-chagasic patients with no mucosal lesion (n=10). Histological processing of the biopsied fragments and immunohistochemistry for galectin-3 were performed. Additional sections were stained with hematoxylin and eosin to evaluate the general pathological processes, picrosirius for evaluation of collagen and toluidine blue to evaluate the mast cell density.ResultsPatients of mucosal lesion group had a significantly higher frequency of ganglionitis and myositis when compared to the chagasic patients with intact mucosa and non-chagasic group. The density of anti-galectin-3-immunostained cells was significantly higher in the chagasic patients with intact mucosa group when compared to the non-chagasic group. The group of chagasic patients with intact mucosa presented a higher percentage of collagen in relation to the patients with mucosal lesion and to the non-chagasic group, with a significant difference. There was no significant difference in mast cell density among the three groups.ConclusionThe higher density of anti-galectin-3-immunostained cells in patients in the chagasic patients with intact mucosa group suggested the need for greater attention in clinical evaluation of these patients, since this protein is associated with neoplastic transformation and progression.

The role of systemic inflammation in the pathogenesis of hemorrhagic stroke in the presence or absence of effective brain blood flow

To identify the likelihood of developing systemic inflammation (SI) as a general pathological process in severe haemorrhagic intracerebral stroke with and without the phenomenon of ineffective cerebral blood flow. Three groups were examined: 1) 89 blood donors (controls), 2) 15 patients with severe haemorrhagic stroke without the phenomenon of ineffective brain blood flow; 3) 26 patients with severe haemorrhagic stroke with ineffective cerebral blood flow. Ineffective cerebral blood circulation was recorded on the basis of transcranial Doppler ultrasound data; 87% of patients had clinical signs of brain death. All patients in the groups with haemorrhagic stroke had signs of multiple organ dysfunction according to the Sepsis-related Organ Failure scale, all of them received intensive care. An integrated scale based on the determination of plasma concentrations of cytokines (IL-6, IL-8, IL-10, TNF-α), procalcitonin, cortisol, D-dimers, myoglobin, troponin I was used to verify systemic inflammation. Systemic inflammation or borderline state (pre-SI) was identified in all patients of the second group both on 1-3 days from the onset of haemorrhagic stroke, and on 5-8 days. On the contrary, in the third group, there were no signs of SI on 1-3 days. On 5-8 days, signs of SI and pre-SI were recorded only in 18.2% of patients. Apparently, the reason for these differences is the blockade of the passage of tissue decay products and other pro-inflammatory factors into the bloodstream from the damaged brain in the third group.

Cellular Stress and General Pathological Processes.

From the viewpoint of the general pathology, most of the human diseases are associated with a limited number of pathogenic processes such as inflammation, tumor growth, thrombosis, necrosis, fibrosis, atrophy, pathological hypertrophy, dysplasia and metaplasia. The phenomenon of chronic low-grade inflammation could be attributed to non-classical forms of inflammation, which include many neurodegenerative processes, pathological variants of insulin resistance, atherosclerosis, and other manifestations of the endothelial dysfunction. Individual and universal manifestations of cellular stress could be considered as a basic element of all these pathologies, which has both physiological and pathophysiological significance. The review examines the causes, main phenomena, developmental directions and outcomes of cellular stress using a phylogenetically conservative set of genes and their activation pathways, as well as tissue stress and its role in inflammatory and para-inflammatory processes. The main ways towards the realization of cellular stress and its functional blocks were outlined. The main stages of tissue stress and the classification of its typical manifestations, as well as its participation in the development of the classical and non-classical variants of the inflammatory process, were also described. The mechanisms of cellular and tissue stress are structured into the complex systems, which include networks that enable the exchange of information with multidirectional signaling pathways which together make these systems internally contradictory, and the result of their effects is often unpredictable. However, the possible solutions require new theoretical and methodological approaches, one of which includes the transition to integral criteria, which plausibly reflect the holistic image of these processes.

Basis of the general theory of pathology (Part 3. Sepsis as an adaptive protective response of organism)

A problem of the essence of sepsis remains unresolved. Sepsis isseen as inadequate, insufficient, or perverted body's response to microbial invasion. The authors analyze the problem of sepsis from the opposite (paradoxical) position based on the well-known postulate that any pathological process (disease) is an adaptation i. e. a protective mechanism. The authors describe known antimicrobial protective barriers ("physiological" and "pathological") and determine a role of different variants of sepsis in protective reactions of human body. The article describes the nature and mechanisms of adaptation under the different variants of sepsis: Wissler – Fanconi’ssubsepsis, intravascular infection, septicopyemia, septicemia and septic shock. These mechanisms might form the basis of pathogenetic therapy. The authors believe that a degree of effectiveness of "pathological" protection of the internal environment is determined by time, i. e. by a duration of a protective effect. In the launch of a septic reaction an important role belongs to a massive invasion of microorganisms into the internal environment of a host by unnatural way – bypassing protective barriers created by evolution. Thus, from the authors' point of view, sepsis is a general pathological process ("pure" infection). Sepsis is a non-specific adaptive (defensive) reaction of human body to a massive microbial invasion.

Basis of the general theory of pathology (Part 3. Sepsis as an adaptive protective response of organism)

A problem of the essence of sepsis remains unresolved. Sepsis isseen as inadequate, insufficient, or perverted body's response to microbial invasion. The authors analyze the problem of sepsis from the opposite (paradoxical) position based on the well-known postulate that any pathological process (disease) is an adaptation i. e. a protective mechanism. The authors describe known antimicrobial protective barriers ("physiological" and "pathological") and determine a role of different variants of sepsis in protective reactions of human body. The article describes the nature and mechanisms of adaptation under the different variants of sepsis: Wissler – Fanconi’ssubsepsis, intravascular infection, septicopyemia, septicemia and septic shock. These mechanisms might form the basis of pathogenetic therapy. The authors believe that a degree of effectiveness of "pathological" protection of the internal environment is determined by time, i. e. by a duration of a protective effect. In the launch of a septic reaction an important role belongs to a massive invasion of microorganisms into the internal environment of a host by unnatural way – bypassing protective barriers created by evolution. Thus, from the authors' point of view, sepsis is a general pathological process ("pure" infection). Sepsis is a non-specific adaptive (defensive) reaction of human body to a massive microbial invasion.

Histopathologic aspects of experimental cysticercosis and in situ cytokines profile in C57BL/6 mice.

Neurocysticercosis (NCC) is one of the parasitic infections that most affects the central nervous system. The knowledge regarding its immunopathogenesis and pathophysiology needs broadening. Taenia crassiceps cysticerci are used as the NCC experimental model. The aim of this work was to describe the general pathological processes and the in situ cytokine profile in C57BL/6 mice inoculated intracranially with viable T. crassiceps cysticerci. The histopathology analysis showed cysticerci in the extraparenchymal and intraventricular region, mononuclear inflammatory infiltration surrounding the parasite, microgliosis and meningitis. The analysis of the in situ immune profiles showed a predominance of the Th2 response. The IL-4 and IL-10 dosages were significantly increased in the infected group. The decrease in the INF-gamma dosage reflects the immunomodulation from the cysticerci. In conclusion, a T. crassiceps NCC infection in C57BL/6 mice triggers an inflammatory response, a predominance of Th2 type in situ profile, with mononuclear inflammatory cell infiltration, meningitis and microgliosis.

The Prospect of Cluster Analysis’ Use to Obtain the New Scientific Results at the Example of Urotheliocytes’ Study in Experimental Diabetic Cystopathy

During the experiment on 70 adult male rats of the Wistar line the priority mechanisms of development of streptotrozotocin diabetic cystopathy were determined. It’s morphometrically and statistically proved that the imbalance of the systemic mechanisms of the functioning of the transitional epithelium of the bladder starts from the first stages of the development of diabetic cystopathy and is not restored to the end of the experiment; it is associated with a violation of the structural and functional balance between the uroletocytes of clusters 4 and 1 and clusters 2 and 3, as well as with a loss of urothelial bladder of morphological stratification.The general pathological processes accompanying the diabetic cystopathy of a bladder development were revealed. According to the results of histological, morphometric, ultrastructural methods, biochemical studies of blood and urine, determination of water balance and cluster analysis, the main systemic and non-systemic factors that cause the development of these pathological processes were established.

Parasites of unionid molluscs (Bivalvia, Unionidae) and their effect on the body of molluscs

Among the molluscs of the family Unionidae extensivity of infestation by the helminth Aspidogaster conchicola (Trematoda, Aspidogastridae) is the highest in Unio tumidus and Anodonta anatina, and the lowest – in U. pictorum. The mites of the genus Unionicola (Arachnida, Unionicolidae) occur more often in species of the genus Anodonta and Pseudanodonta complanata than in species of Unio. The larvae of trematodes Bucephalus polymorphus (Trematoda, Bucephalidae) are more often identified in species of the genus Anodonta. The intensity of invasion of molluscs by the helminth A. conchicola was 1.0–5.6 ind./ind. (Unio – 1.0–3.3, Pseudanodonta – 3.0–5.6, Anodonta – 1.3–4.0 ind.), by the water mites Unionicola – 1–69 ind./ind. (Unio, Pseudanodonta – 1–11, Anodonta – 1–69). Due to the influence of aspidogastreans, the cytoplasmic vacuolization and hypertrophy of the cells of the pericardial epithelium and the layer of connective tissue was observed, which leads to a shrinkage of the upper side of the pericardium. Often, there was a nuclear pyknosis and, with deeper violations, their karyorrhexis and karyolysis. In the layer of connective tissue of pericardium of A. anatina encapsulated larvae of aspidogastereans were found. An increase in the cardiac index was observed in molluscs infested by aspidogastreans: the change in the index was the smallest in U. crassus (at 11.5%) and the largest in U. tumidus (at 54.1–61.0%). Smaller cardiac indexes are typical for molluscs with a lower intensity of infestation by aspidogastreans. Moderate intensity of infestation by this helminth (6–10 ind./ind.) caused an increase in the heart rate in molluscs (18.6–29.6%), high intensity (&gt;10 ind./ind.) caused the decreasing of this indicator (14.5–24.0%). At low intensity of the mite (up to 20 individuals) and invasion of the trematode B. polymorphus (minor infections; part of the reproductive glands, populated by parasites, is less than 50%) the acceleration of ciliary beating and increasing of the duration of ciliary beating of the ciliated epithelium (1.4–2.6 times) were observed in species Anodonta and U. pictorum, at high intensity of invasion the inhibition of beating and reduction of the duration of ciliary beating of the ciliated epithelium in these species (45.9–57.4%) was observed. In the case of the general pathological process in the body of molluscs , the influence of parasites can cause the elimination of individuals with high intensity of infestation , which affects the absolute number and population density of molluscs.