Characteristics of the Antitumor Effect of Doxorubicin and Pegylated Hyaluronidase on Models of Rat Brain Tumors.

Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8.

[Chronic gastric ulcer in a child not diagnosed during life]. / Khronicheskaya yazva zheludka u rebenka, ne diagnostirovannaya pri zhizni.

Chronic gastric ulcer is a rare disease in childhood. The article presents data on the epidemiology and etiology of the disease in children, describes the case of a chronic gastric ulcer complicated by penetration into the liver, perforation, development of abdominal sepsis, with a fatal outcome in a 7-year-old girl.

Study of the Morphogenesis of Granulomas in the Liver of Mice in Different Age Periods Treated with Oxidized Dextran.

We studied granuloma formation and its outcomes in BCG-induced granulomatosis in the liver of mice of different age periods treated with oxidized dextran. Newborn C57BL/6 mice were intraperitoneally injected with BCG vaccine on the first day of life (group 1) or BCG vaccine solution on first day of life and oxidized dextran on the second day of life (group 2). Analysis was carried out on 3, 5, 10, 28, and 56 days of life. After injection of BCG vaccine, granulomas in the liver appeared starting from the day 28. In mice treated with oxidized dextran, granulomas on day 28 were smaller and less numerous than in group 1 animals. In BCG granulomatosis, fibroplastic processes in the liver develop mainly at the site of granulomas. Injection of oxidized dextran under conditions of BCG granulomatosis reduced the manifestations of fibrosis in the liver.

Structural Changes in the Liver in Post-Toxic Cirrhosis and Its Treatment with Oxidized Dextran. Immunohistochemical Research.

In adult Wistar rats, post-toxic liver cirrhosis was induced by intraperitoneal injection of 50% oil solution of CCl4 and peroral administration of 6.5% aqueous solution of ethyl alcohol over 60 days. Histological examination of the liver revealed vacuolar degeneration and necrosis of hepatocytes, formation of false lobules, expression of collagens I and III periportally and in interlobular spaces, ascites, and hydrothorax. Then, oxidized dextran with a molecular weight of 40 kDa (2 ml of a 5% aqueous solution) was intraperitoneally injected every fourth day over 30 days. Against the background of treatment with oxidized dextran, the volume density of collagens I and III decreased by more than 2 times, the "collagen-producing" activity of fibroblasts decreased by 47%, and the number of fibroblasts decreased, including by the mechanism of apoptosis. The decrease in the collagen content in the liver of rats treated with oxidized dextran was apparently associated with blockade of collagen assembly due to the aldehyde-aldehyde interaction of tropocollagens and oxidized dextran.

Postpartum Involution of Mouse Myometrium in Acute CCl4-Induced Hepatosis and Its Correction with Immobilized Hyaluronidase.

We studied structural rearrangement of the myometrium of C57BL/6 mice during the postpartum period under conditions of acute toxic hepatosis induced by CCl4 injection and its correction with immobilized hyaluronidase. In contrast to physiological pregnancy, involution of the myometrium in mice under conditions of acute toxic hepatosis were not completed by the 10th day of the postpartum period. When toxic hepatosis was corrected with immobilized hyaluronidase, the main mechanism of postpartum involution of the mouse myometrium was clasmacytosis, the process of postpartum involution was significantly accelerated, but not completed by the 10th day, probably due to reduced vascularization of the myometrium.

[Morphological diagnosis of obstetric pulmonary embolism]. / Morfologicheskaya diagnostika akusherskoi tromboembolii legochnoi arterii.

Pulmonary embolism (PE) is one of the most common fatal complications in a wide variety of pathologies along the most common death causes of the population - diseases of the circulatory system and oncology. The development of PE in the postoperative and postpartum periods can also be fatal. The diagnosis of PE is very difficult and in 50-80% of cases it is not diagnosed at all. During autopsies it is important not only to diagnose PE but also to establish the source of its origin. An example of PE in a 34-year-old pregnant woman is given; the PE source was thrombosis of the right deep femoral vein facilitated by varicose veins of the lower extremities and severe preeclampsia. The presence of severe preeclampsia in a pregnant woman caused the development of venous sinus thrombosis accompanied by bilateral exophthalmos, necrosis of a pituitary gland part and progressive cerebral edema.

[Fatal dengue fever]. / Likhoradka denge s letal'nym iskhodom.

Dengue fever is acute zooanthroponic infection from a group of vector-borne viral hemorrhagic fevers. Since 2013, Russia has introduced the mandatory registration of dengue fever cases. The paper presents data on the epidemiology, etiology, and pathogenesis of Dengue fever and describes a case of a fatal outcome in severe dengue fever and morphological changes in organs and tissues.

[Extragenital diseases, comorbidities, and polymorbidity in maternal death]. / Ékstragenital'nye zabolevaniia, komorbidnye sostoianiia i polimorbidnost' pri materinskoi smerti.

OBJECTIVE: To study the structure and significance of comorbidities and polymorbidity in maternal death. MATERIAL AND METHODS: Sixty-five autopsy protocols of maternal deaths in the Novosibirsk Region in the period of 1994 to 2018 were analyzed. RESULTS: Extragenital diseases are the leading diseases in the nosological structure in maternal mortality. Preeclampsia/exlampsia and obstetric hemorrhages lost their leading positions. The increasing role of extragenital pathology in the structure of maternal mortality is due to many factors, such as a larger number of comorbidities and polymorbidity, in pregnant women. Infectious diseases, benign and malignant tumors, and diseases of the heart and blood vessels are the main diseases in the structure of extragenital diseases.

[Nosological structure of congenital malformations in the fetuses and babies of the Aral Sea Region(the Republic of Kazakhstan)]. / Nozologicheskaia struktura vrozhdennykh porokov razvitiia plodov i detei v Priaral'e (Respublika Kazakhstan).

OBJECTIVE: To study the trend in the incidence and nosological structure of congenital malformations (CMFs) in the fetuses and babies of the Kyzylorda Region (Aral Sea Region) of the Republic of Kazakhstan in the period 2016-2018. MATERIAL AND METHODS: Over 2016-2018, the investigators analyzed 550 childbirth histories, the protocol (records) of autopsy in fetuses and babies who had died at the maternity hospitals and children's hospitals of the Kyzylorda Region (Aral Sea Region, Kazakhstan). RESULTS: Throughout the follow-up period, the structure of CMFs in the Kyzylorda Region, the Republic of Kazakhstan, was found to have 3 major systemic defects: multiple defects; cardiovascular defects, and central nervous system defects, which can be considered as an indicator for environmental problems in the region. There was a preponderance of hydrocephalus and anencephaly among the CMF of the central nervous system and that of interventricular and interatrial septal defects and combined defects among the cardiovascular CMFs. In the considered period of time, malformations of the urinary system, gastrointestinal tract, and lungs were often observed as part of multiple malformations. In the considered period of time, defects of the urinary system, gastrointestinal tract, and lungs were often observed as part of multiple malformations. The postmortem findings indicated that the conformity of clinical and postmortem CMF diagnoses in the Kyzylorda Region were more than 77%.

[Cardiovascular syphilis (current state of the problem and analysis of own observations)].

A description of two cases of cardiovascular syphilis is presented. The introduction discusses the relevance of visceral syphilis. The literary review is constructed in a chronological format and reflects the stages of studying the problem of cardiovascular syphilis. It emphasizes that cardiovascular syphilis is currently a rare pathology and internists are more likely to encounter it. Verification of the pathology of the cardiovascular system, including aortic aneurysm, during the early stages of syphilis (early latent) does not exclude the option of combined pathology. Early forms of syphilis in patients with diseases of the cardiovascular system should be considered a factor that complicates diagnosis. Such patients should be carefully examined to determine the cause of the disease. Rationale for the diagnosis of cardiovascular syphilis requires a comprehensive assessment of the results of clinical, laboratory and instrumental examination of the patient. A preliminary diagnosis of the specific etiology of an aortic aneurysm should be based on the following criteria: 1) relatively young age of patients with socially inappropriate sexual behavior; 2) sudden onset and rapid progression of the main signs of the disease. All patients with newly diagnosed aortic aneurysm at the outpatient stage should perform a serological examination. The diagnosis of cardiovascular syphilis, namely a syphilitic mesaortitis, can be established or confirmed by an autopsy.

[Preventability of perinatal losses by the example of the large industrial cities Chelyabinsk and Novosibirsk]. / Predotvratimost' perinatal'nykh poter' v Cheliabinske i Novosibirske.

Perinatal mortality rate is an indicator that characterizes the quality of medical care, as well as the social and economic situation in the region. OBJECTIVE: to audit perinatal losses in large regional centers of the Russian Federation with a population of over 1 million inhabitants, such as Chelyabinsk and Novosibirsk. MATERIAL AND METHODS: A comprehensive postmortem examination of 309 cases of perinatal losses in 2016 was made, which was supplemented with an assessment of preventability according to the Scandinavian-Baltic classification. RESULTS: The rate of preventable deaths in Chelyabinsk and Novosibirsk amounted to 91 and 81.5% of cases, respectively; the deaths were due to stillbirths at more than 28 weeks' gestation and to dead newborns in almost half of cases. The proportion of intranatal deaths was shown to increase in Chelyabinsk; the number of neonatal deaths at more than 33 weeks' gestation rose in Novosibirsk. CONCLUSION: Supplementing the traditional clinical and postmortem analysis with an assessment of the preventability of perinatal loss makes it possible to ensure a unified approach to evaluating these conditions and the comparability of autopsy results in different subjects of the Russian Federation and to determine regional reserves for reducing perinatal mortality rates.

[Liver disease and maternal mortality]. / Patologiia pecheni i materinskaia smertnost'.

Liver diseases associated (acute fatty liver of pregnancy) and unassociated (liver hemangioma) with pregnancy and complications due to liver failure are serious conditions and can lead to maternal death. The paper describes two maternal deaths related to liver pathology.

Morphological Characteristics of the Cartilaginous Tissue of Human Auricle in Different Age Periods.

A complex morphological study of the auricle to determine the human age was performed by evaluating the metric sizes between fixed points in each auricle with axial guidelines. The auricular elastic cartilage in different age periods was characterized by thickening of the cartilaginous plate, different mature and immature cartilage zone ratio, variations in the volume density of the intercellular substance and elastic fibers, and change in the numerical density of individual chondrocytes and isogroups. Aggrecan content in the cartilage was shown to increase in different age periods. Age-related structural changes in the auricular cartilage expand the possibilities of forensic medical examination and hold much promise for the identification of personality.

[On the occasion of the 80th anniversary of the Department of Pathologic Anatomy, Novosibirsk State Medical University].

The paper gives a brief overview of the history of the Department of Pathologic Anatomy, Novosibirsk State Medical University, which is 80 years old in 2015.

[CLINICAL CASE OF CROHN'S DISEASE: A DIFFICULT PATH TO DIAGNOSIS].

This article presents a case of Crohn's disease in a man who was veracity of 30 years from the onset of the disease. This case demonstrating complexity of diagnostic search, even with the classic version of the disease. And it demonstrates the need for a thorough medical history, differential diagnosis.

[Amniotic fluid embolism as a cause of maternal death].

This article reports the case of death of a puerperal woman resulting from amniotic fluid embolism. The diagnosis was established based on the results of the pathohistological study that revealed the presence of mucoproteides and epithelial scales in pulmonary blood vessels and capillaries.

[The expert observation of myocardial contusion in a child].

A case of the myocardial contusion associated with the closed blunt chest injury in the girl aged 1 year 7 months is presented. The autopsy revealed hemorrhage of an irregular oval shape, coloured dark-red, and confined to the region with the area of 4.0 x 3.5 cm. It penetrated throughout the entire thickness of the lower part of the left atrial myocardium and the upper and middle parts of the left ventricle. No other changes were found in the heart, nor were congenital cardiac and vascular malformations documented. The main factors playing an important role in the formation of the myocardium contusion are discussed. The authors emphasize that it is the children having the narrow chest with the pliable wall who constitute the group at the highest risk of accidents resulting in the chest injury and myocardial contusion.

[Role of cytokines in cell differentiation in the paraventricular region of the brain in fetuses with in utero encephalitis].

OBJECTIVE: To examine the specific features of cell differentiation and migration of neuroepithelial cells of the paraventricular region (PVR) in human fetuses with in utero encephalitis. MATERIALS AND METHODS: A morphometric technique was used to investigate the expression of vascular endothelial growth factor, tumor necrosis factor-alpha, and transforming growth factor-beta in the structures of the PVR of the thalamus in 47 fetuses with signs of in utero encephalitis and in 10 healthy fetuses at 26-27 weeks' gestation. RESULTS: In utero encephalitis was characterized by productive and productive-and-necrotic inflammation and in most cases it was a manifestation of generalized in utero infection. In in utero encephalitis, diminished PVR cellularity, a larger number of neurons and glial cells in the thalamic region, and that of glial fibrillary acidic protein-expressing cells, and enhanced cellular proliferative activity in the PVR implied the accelerated maturation of its cells. The decrease in the number of vessels in the PVR was caused by the lower cellular expression of vascular endothelial growth factor and transforming growth factor. CONCLUSION: In in utero encephalitis, there are significant changes in the processes of cell differentiation and migration in the fetal PVR, which was associated with a number of cytokines regulating an intercellular interaction.

[A case of congenital Coxsackie B virus infection].

The paper describes a clinical case of congenital Coxsackie B virus infection in a girl aged 1 month and 15 days of life who has undergone a detailed postmortem examination.

[Urinary excretion of fibrogenic and antifibrotic growth factors in type 1 diabetic patients: the interrelationship with diabetic nephropathy].

AIM: To assess the relation between urinary excretion of profibrotic and antifibrotic growth factors, albuminuria and glomerular fibrosis in type 1 diabetic patients. MATERIALS AND METHODS: 64 patients with diabetes were examined, including 25 ones with normal albumin excretion rate (AER), 30 microalbuminuric and 9 macroalbuminuric patients. Urinary excretion of type IV collagen, transforming growth factor-beta 1] (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF) and bone morphogenetic protein-7 (BMP-7) was determined by ELISA and compared to control (10 healthy subjects). Renal biopsy specimens were assessed in 7 patients with normal AER and in 14 microalbuminuric patients. RESULTS: Type IV collagen, TGF-beta1 and TNF-alpha excretion was increased significantly in patients with micro- and macroalbuminuria as compared to control (all p<0.05). Excretion of FGF-2 was increased in macroalbuminuric patients only (p=0.003). No marked changes in excretion of antifibrotic growth factors (HGF and BMP-7) were observed. TNF-alpha and FGF-2 correlated positively with urinary type IV collagen (r=0.37 and r=0.31, respectively). The presence of glomerular fibrosis in renal biopsy specimens was associated with higher excretion of TGF-beta1, TNF-alpha and FGF-2 (all p<0.05). CONCLUSION: The results suggest that unbalance between profibrotic and antifibrotic growth factors in the kidneys plays an important role in pathogenesis of diabetic nephropathy. Urinary TGF-beta1, TNF-alpha and FGF-2 may offer new possibilities for detection of renal fibrosis in diabetic patients.