The neuroinflammatory component of negative affect in patients with chronic pain.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region's functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

[Congenital immature teratomas. Two case reports]. / Vrozhdennye nezrelye teratomy. Opisanie dvukh nablyudenii.

Teratomas belong to a group of germ cell tumors and consist of tissues that are derived from 3 germ layers. The localization of teratomas is extremely diverse. The main task of a morphological study is to diagnose the type of teratoma. According to the WHO classification, there are mature and immature teratomas (ICD-O codes 9080/0 and 9080/3, respectively). It is deemed that the disease prognosis does not depend on the composition of mature tissue components. This paper describes two sectional observations of congenital immature teratomas in a premature live birth infant and a stillborn one. One teratoma, such as epignathus, is a very rare tumor in localization. Emphasis is laid on the need for a thorough teratoma morphological study that defines the tactics of patient management. The described observations demonstrate the importance of timely prenatal diagnosis and an interdisciplinary approach, as well as the need for clear routing of patients with diagnosed fetal space-occupying lesions.

[Morphopathology of myocardial hypoxic-ischemic injuries in newborns at 22-27 weeks' gestation]. / Patomorfologiya gipoksicheski-ishemicheskikh povrezhdenii miokarda u novorozhdennykh 22­27 nedel' gestatsii.

OBJECTIVE: To determine the parameters of myocardial structural injuries developed in chronic intrauterine hypoxia conditions in newborns at 22-27 weeks' gestation. MATERIAL AND METHODS: A battery of morphological techniques, including organometry studies and separate weighing of the heart; 3D histology; morphometry with the determination of the area of cardiomyocyte nuclei, the specific area of the muscular and interstitial components of the right ventricular myocardium; immunohistochemistry with monoclonal antibodies to transforming growth factor ßi (TGF-ßi), cardiac troponin T (cTnT), and transmission electron microscopy, was used to examine heart samples from 30 deceased newborns at 22-27 weeks' gestation who developed in chronic intrauterine hypoxia conditions. A control group consisted of hearts from 20 extremely low body weight (ELBW) newborns, the main cause of whose death was asphyxia caused by the premature detachment of a normally positioned placenta. RESULTS: Analysis of the organometric parameters of heart samples from newborns at 22-27 weeks' gestation, who had experienced chronic intrauterine hypoxia, revealed right ventricular hypertrophy with increases in the area of cardiomyocyte nuclei and in the specific area of the muscle component compared to the control group. Impaired myocardial microcirculation and destructive changes in cardiomyocytes were diagnosed in conjunction with the decreased troponin T and increased TGF-ß1 expressions. Incomplete differentiation of cardiomyocytes and their myofibrillar component was revealed at the myocardial ultrastructural level in ELBW newborns who had experienced chronic intrauterine hypoxia. CONCLUSION: The parameters of myocardial structural rearrangement in ELBW newborns who had experienced chronic intrauterine hypoxia are compensatory right ventricular hypertrophy, microcirculatory disorders, destructive changes in cardiomyocytes, decreased cTnT and increased TGF-ß1 expressions in conjunction with impaired cardiomyocyte differentiation.

BIOMARKER SST2 AS AN EARLY PREDICTOR OF ACUTE RENAL INJURY IN PATIENTS WITH ST-SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION.

One of the serious complications of ST-segment elevation myocardial infarction (STEMI) is acute kidney injury (AKI). Promising in this respect is the stimulating growth factor sST2. A sharp increase of ST2 level in case of injury is accompanied by inhibition of IL-33 favorable antihypertrophic effects. The purpose - to analyze the prognostic significance of sST2 biomarker in identifying the risk of AKI development in patients with STEMI. The study included 103 patients with STEMI, of which 75 patients were men (72.8%) whose mean age was (61.85±12.23) years. Patients were hospitalized at the intensive care unit during the first day of the disease. Patients were subjected selective coronary angiography (SCAG) with subsequent stenting of the infarct-related artery. Criteria for inclusion into the study concerned patients with STEMI, who arrived in the hospital during 24 hours after the onset of the symptoms and agreed to participate in the study. The level of sST2 was determined during the first 24 hours after the event. In multivariate regression analysis, we found that sST2 and blood glucose are the only significant predictors of acute kidney injury during the first 48 hours (R2=0.437, P<0.001) among the parameters included into the study, such as the NT-pro BNP biomarker, ejection fraction, E/A ratio, end diastolic volume and hemoglobin level. The first time a prognostic model has developed and this model used simple, but significant factors. The role of the biomarker ST2 in the early stratification of reduced kidney function in patients with STEMI suggests the development of AKI.

[Pathomorphology of the ventricular germinal zone and neocortex in newborn infants with posthemorrhagic hydrocephalus]. / Patomorfologiia ventrikuliarnoi germinativnoi zony i neokorteksa u novorozhdennykh pri postgemorragicheskoi gidrotsefalii.

AIM: Тo study the morphological features of the ventricular germinal zone and neocortex in newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus. MATERIAL AND METHODS: The brains of fetuses and newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus (n=12) were examined; a control group included the brains with a lateral ventricle lumen width of not more than 0.5 cm (n=30). The investigators conducted a comprehensive pathomorphological study of the ventricular germinal zone and neocortex in the projection field No. 6. RESULTS: Posthemorrhagic hydrocephalus is characterized by a deceleration in the reduction of the ventricular germinal zone and by the corresponding level of differentiation of the cortex and neurons to gestational age in the presence of the physiological expression of reelin in the Cajal-Retzius neurons and in that of the impaired expression of matrix metalloproteinase 9 (a decrease) and the glial protein S-100 (an increase) in the cells of the ventricular germinal zone. CONCLUSION: The morphological features of the ventricular germinal zone and neocortex of fetuses and newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus should be considered as morphological differential diagnostic criteria for the disease.

[Specific features of reelin expression in the brain of fetuses and newborns with internal hydrocephalus].

AIM: to study reelin expression in the neocortex of fetuses and newborns with internal hydrocephalus (HC) and to reveal its features in relation to the etiology of HC. MATERIAL AND METHODS: The brains of fetuses and newborn at 22-40 weeks' gestation with internal HC associated with Sylvian aqueduct malformation (n=9), post-inflammatory (n=4) and post-hemorrhagic (n=5) HC were examined. In a comparison group, the fragments of brain tissue with a slit-like lumen of the lateral ventricles were no more than 0.5 cm (n=20). A standard immunohistochemical method was used to reveal reelin expression in the neocortex of the anterior third of the precentral gyrus. RESULTS: HC associated with Sylvian aqueduct malformation is characterized by a negative reelin immunoexpression. In postinflammatory HC, the expression of reelin decreases significantly (p=0.025) with respect to the conditional norm and, in posthemorrhagic HC it is comparable with that in the comparison group. CONCLUSION: The features of reelin expression in the brain of fetuses and newborns at 22-40 weeks' gestation with internal HC should be considered as morphological differential and diagnostic criteria for the disease in relation to its etiology.

[Morphological changes in ventricular germinal zone and neocortex of the cerebral hemispheres in human fetuses and newborns on weeks 22-40 of prenatal development].

In this study, we investigated the morphology of the ventricular germinal zone and neocortex of the cerebral hemispheres in the projection field no. 4 of the motor area in human fetuses in dynamics from week 22 to 40 of fetal development. Morphological study allowed us to clarify the following patterns of prenatal ontogeny of the human CNS. On weeks 22-27, an intensive formation of the main sulci of the first order, differentiating the brain into lobes, is observed. By weeks 28-32, the formation of all sulci of the first order is completed; and on weeks 33-37, additional sulci characteristic of an individual are formed. The spurt of gyrification of the cortex (weeks 22-27) practically coincides with the completion of neuronal differentiation and formation of the motor neocortex. The structure of the latter is characterized by a clear stratification of cytoarchitectonic layers and modular organization of neurons with their vertical orientation in cell columns (weeks 25-27). In subsequent weeks of prenatal development until birth, no significant changes in the topography and structure of the neocortex are observed. Structural rearrangement of the ventricular germinal zone on weeks 22-40 of prenatal development consists in its gradual reduction and is completed on weeks 37-40. The criteria of physiological reduction of this area are the zonal location of glioblasts and a progressive decrease in its thickness on weeks 33-37 of prenatal development.

[Structural changes in the germinal matrix of the brain of fetuses and neonatal infants with ventriculomegaly and congenital hydrocephalus].

OBJECTIVE: To study structural changes in the germinal matrix (GM) in 22-to-40-week fetuses with ventriculomegaly (VM) and hydrocephalus (HC). MATERIAL AND METHODS: The width of the ventricular groove was borne in mind while forming study groups (the brain in VM (n = 30), HC (n = 20)) and a comparison group (n = 30). To trace changes in GM transformation, each group was divided into 4 subgroups according to the gestational sign. Materials were excised in the projection of the lateral ventricles onto the convexital surface of the brain. After the use of conventional methods, the specimens were stained with hematoxylin and eosin or Nissl. RESULTS: VM was found to be characterized by the early (at 22 weeks' gestation) regionalization of glio- and neuroblasts and by the completion of GM reduction at 35 weeks of intrauterine development. In HC, GM in all ventricular system regions was preserved and its structure was virtually unchanged at 22 to 40 weeks' gestation. CONCLUSION: The found structural changes may be used as diagnostic criteria for VM and HC and to elucidate gestational age in forensic medical practice.

[S-100 protein expression in the different brain structures of fetus and newborns suffering from ventriculomegalia and hydrocephaly].

Parenchyma of brains from fetus and newborns (22-40 weeks of gestation), suffering from dilatation of the ventricular system has been studied by immunohistochemical method. The increasing of S-100 expression in germinal matrix and subcortex under hydrocephaly was significantly higher than in cases of ventriculomegalia (p < 0.01) and control group (p < 0.05). The index of S-100 expression could be use as prognostic criteria of neuron and neuroglia mortality for differential diagnosis of hydrocephaly.

[Pathomorphology of congenital ventriculomegaly].

The paper gives the results of a morphological investigation using ventricular system embedding, organometry, light and electron microscopies, histostereometry and immunohistohemistry of brains from 50 fetuses and neonatal infants of 22-27 weeks gestation. The comprehensive investigations revealed the morphological features of intrauterinally acquired ventriculomegaly, which reflect tissue immaturity of the parenchyma and the vascular component of the brain.

[Guidelines for pathomorphological study of the brain of fetuses and neonatal infants with hydrocephalus].

Guidelines are proposed to study the brain of fetuses and neonatal infants with hydrocephalus. Some of them (evaluation of the rate of gyrification and its correspondence to the gestational period of the fetus, by visualizing the cerebral hemisphic surface; perfusion of cerebral vessels by the Karaganov fixator) are original, informative, and developed by the authors and are successfully used in the scientific and practical work of pathologists.

[Morphologic and dopplerometric characteristics of spiral arteries in chronic placental insufficiency].

Placental basal membrane of 156 females of the reproductive age with various forms of placental insufficiency was quantitatively studied. Dopplerometry of spiral arteries with calculation of the resistance index (RI) was performed longitudinally at 20-40 weeks of the pregnancy. Non-complete gestational restructurisation resulted in the decrease of circulation in these vessels with high values of RI and this is one of causes in delay of fetus development. High values of RI is an additional criterion of differential diagnosis of chronic placental insufficiency.

[Morphology of the cerebral cortex in fetuses and extremely low weight newborns in normal pregnancy and miscarriage of hormonal etiology]. / Morfologiia kory golovnogo mozga plodov i novorozhdennykh s ékstremal'no nizkoi massoi tela pri neoslozhnennoi beremennosti i nevynashivanii gormonal'nogo geneza.

Complex histologic, histostereometric and electron microscopic study of fields 4 and 6 of the brain cortex in fetuses and newborns with an extremely low body weight allowed to specify formation of histoarchitectonics of the motor analyser during the second trimester of perinatal ontogenesis. Stages of differentiation (20-23 weeks) and maturation (24-27 weeks) of neurons and cytoarchitectonic layers of the motor zone in uncomplicated pregnancy as well as slow maturation of this cortex region in incomplete pregnancy of hormonal genesis were discovered. In this condition, there are lengthening of the neuron differentiation stage up to 26 weeks of gestation and important reduction of histostereometrical values (thickness of individual cytoarchitectonic layers and that of all the cortex) and cytokaryometrical values (volume of neuron nuclei) as compared to those in uncomplicated pregnancy.

[Formation of cerebral cortex relief in newborns with extremely low birth weight in the physiologic pregnancy and premature birth]. / Osobennosti formirovaniia rel'efa kory polusharii bol'shogo mozga u novorozhdennykh s ékstremal'no nizkoi massoi tela pri fiziologicheskom techenii i nevynashivanii beremennosti.

The course of cortical gyrification of the brain hemispheres in foetuses and newborns with an extremely low body weight in physiological pregnancy and premature birth. Topographical formation of the hemisphere cortex is completed by the 28th week of the intrauterine life. There exists a direct correlation between the period of the pregnancy and a certain spectrum of gyri. Two-three weeks retardation in the gyri and cortex relief formation in premature birth is observed. The results obtained can be used as additional criterion for determination of the gestational periods in foetuses and diagnosis of the disturbances in the brain formation in foetuses and newborns.

[Lysosomal and cytoplasmic enzymatic activity under the experimental action of carbon disulfide]. / Aktivnost' lizosomal'nykh i tsitoplazmaticheskikh fermentov pri éksperimental'nom deistvii serougleroda.

Activity of lysosomal enzymes and content of carbohydrate containing biopolymers (glycosaminoglycans, glycoproteins) were altered in various tissues (liver, kidney, brain, aorta) of experimental animals intoxicated with carbon disulfide. Possible role of the impairments observed, related to neurotropic and hepatotoxic effects, is discussed. Subsequent development of atherogenic and embryotoxic effects of carbon disulfide--one of contaminators of surroundings--are considered.

[Changes in the course of atherosclerosis occurring over a 25-year period in the male population of 9 cities of the CIS and Baltic countries]. / Izmeneniia v techenii ateroskleroza, proizoshedshie za 25-letnii period, u muzhskogo naseleniia 9 gorodov SNG i stran Baltii.

The trends in atherosclerosis presentation were followed up pathomorphologically in a two-stage epidemiological survey performed in 9 cities of CIC and Baltic states at 25-year interval. The investigations were conducted in accordance with WHO program. Stage 1 (1963-1968) covered 6121 cases, stage 2 (1985-1989) included 9201 cases. The material was collected on the condition of aortas and coronary arteries from 20-59-year-old males who were residents of the cities of Irkutsk, Yakutsk, Tallin, Tartu, Riga, Kharkov, Yalta, Ashkhabad, Bishkek. The 2-stage examinations gave evidence for growing severity of atherosclerosis. Risk factor analysis demonstrated an increase in the percentage of males with diabetes mellitus and arterial hypertension, in the percentage of overweight males and of those with atherosclerosis engaged in mental work. It is found that atherosclerosis undergoes changes within the life of one generation (for 20-25 years).