[Total DNA methylation profile in assessing the MGMT gene promoter status in malignant gliomas]. / Rezul'taty i perspektivy ispol'zovaniya obshchego profilya metilirovaniya DNK dlya otsenki statusa promotora gena MGMT v zlokachestvennykh gliomakh.

Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter is currently the most important prognostic biomarker in therapy of IDH-wild-type glioblastoma. One can obtain information about this methylation from total DNA methylation profile. OBJECTIVE: To analyze the DNA methylation signal intensity in the MGMT gene in samples of malignant gliomas and identify the most significant genomic positions for calculating the MGMT gene promoter status for further improvement of diagnostics and prediction of therapeutic options in patients with malignant gliomas. MATERIAL AND METHODS: The study is based on 43 samples (frozen tissue or paraffin blocks) from patients with malignant gliomas. Tumor DNA samples were prepared using the Illumina Infinium MethylationEPIC BeadChip Kit and the Illumina Next-Seq 550 Sequencing System platform. DNA methylation profiles were analyzed using computational algorithms in the R language, specialized libraries minfi and mgmtstp27, as well as basic statistical functions in the Rstudio environment. RESULTS: We established the MGMT gene promoter status in 43 samples of malignant gliomas considering total DNA methylation profile. In 24 samples (55%), the MGMT gene promoter was methylated. We compared methylation signal in certain CpG islands in groups with methylated and unmethylated MGMT gene promoters and identified the most significant positions for further improvement of data analysis algorithm. CONCLUSION: These data demonstrate the possibilities and prospects for further improvement of algorithm for analysis of the MGMT gene promoter status based on total DNA methylation profile in patients with malignant gliomas as an alternative to methyl-specific PCR. Our results are consistent with data of other neuro-oncology researchers. Indeed, computational methods like MGMT-STP27 are quite powerful and can be used in scientific and clinical practice to assess prognosis and make decisions about chemotherapy with alkylating agents.

[Verification of the diagnosis of supratentorial ependymomas by real-time PCR]. / Verifikatsiya diagnoza supratentorial'nykh ependimom metodom PTsR v rezhime real'nogo vremeni.

BACKGROUND: Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic¼ morphological picture, and a nonspecific immunophenotype. Thanks to molecular genetic methods, in particular real-time PCR, it has become possible to verify supratentorial ependymomas and identify their molecular group, on which further prognosis depends. OBJECTIVE: To develop a set of molecular genetic tests based on real-time PCR to verify supratentorial ependymomas. MATERIAL AND METHODS: 56 tissue samples were collected from patients with supratentorial ependymomas, WHO Grade II, and anaplastic ependymomas, WHO Grade III. We developed primers and fluorescent TaqMan probes for real-time PCR analysis to detect the ZFTA::RELA, ZFTA::MAML2, ZFTA::NCOA2, ZFTA::MAML3, YAP1::MAMLD1, and YAP1::FAM118B gene fusions. For immunohistochemical analysis, monoclonal rabbit anti-NF-kb p65 antibodies (HUABIO, China) were used, the study was carried out on AutostainerLink 48 immunostainer (DAKO, Denmark). RESULTS: Real-time PCR was able to verify the diagnosis for 69.9% (n=39) of samples and classify them into molecular groups of ZFTA- or YAP1-positive supratentorial ependymomas. Immunohistochemically it was possible to verify 58% (n=29) ependymomas. CONCLUSION: Diagnosis by real-time PCR is a relatively fast, accessible and easily interpreted method that allows verification of the molecular group in 70% of cases of supratentorial ependymomas without the use of additional methods.

[Multiple gliomas]. / Mnozhestvennye gliomy.

The authors present 2 patients. One of them had typical multifocal primary multiple synchronous wild-type IDH1/2 glioblastoma subtype RTK1, chromosome 7 duplication, homozygous CDKN2A deletion and chromosome 10 deletion. In another patient, the nature of tumors remains debatable. We can talk about either a rare atypical case of metachronous multicentric various glial tumors (oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, WHO grade 2 and RTK2-glioblastoma) or secondary glioblastoma after previous oligodendroglioma arose a year after radiotherapy.

[The service of obstetrics in Riazan region].

The article emphasizes that the major purposes of priority national project in health care field are increase of availability and quality of primary and high-tech medical care, including period during pregnancy and delivery. The prevention and decrease of maternal, perinatal morbidity and mortality are among these priorities too. The reorganization of obstetrics service will promote rationale using of bed stock of obstetrics institutions including the optimal supply rationale structure, proper selection and regulation of flow for hospitalization and stages of medical care delivery.

Effect of exogenous calcium deficit on blood pressure and modification of brain proteins GAP-43 and BASP1 in SHR and WKY rats.

We studied the effect of drinking of low mineralized water containing 8 mg/liter Ca2+ on blood pressure and content of brain proteins in synaptosomes of SHR and WKY rats. Blood pressure increased in WKY rats, but not in SHR rats. In SHR rats, Ca2+ deficit reduced the content of GAP-43 protein and induced the appearance of its fragment GAP-43-3 in brain synaptosomes. In WKY rats, the content of this protein did not change, and its fragment GAP-43-3 was absent. No structural changes in BASP1 protein were found.

[Disturbances in the function of cardiomyocyte ryanodine receptors of spontaneously hypertensive rats revealed by 4-chloro-m-cresol].

The rates of Ca2+ release from sarcoplasmic reticulum in response to the activation of ryanodine receptors by 4-chloro-m-cresol in cardiomyocytes of three rat lines: spontaneously hypertensive (SHR) and normotensive WKY, and Wistar rats during five weeks of their growth and development have been studied to reveal differences in the function of ryanodine receptors at different stages of hypertension. Whereas the efflux of Ca2+ from sarcoplasmic reticulum in Wistar and WKY rat cardiomyocytes decreased in response to 4-chloro-m-cresol, an abrupt rise in the rate of [Ca2+]i increase was observed in myocytes of spontaneously hypertensive rats after 17 days of development. A correlation between this phenomenon and the occurrence of genetic defect of ryanodine receptors in SHR seems improbable because we did not register any differences in the rates of Ca2+ release from sarcoplasmic reticulum by the action of 4-chloro-m-cresol in concentrations 0.5-2.0 mM in the cardiomyocytes of newborn WKY and spontaneously hypertensive rats. On the other hand, pathological changes in the function of ryanodine receptors may become apparent later during ontogenesis. The connection of this phenomenon with an increase in the role of ryanodine receptors during the excitation-contraction coupling in muscle cell and an increase in the calpain expression by the age of 3 weeks in spontaneously hypertensive, but not in WKY rats, is discussed. It is supposed that the disintegration of the subunit of ryanodine receptors by calpain notably intensifies the Ca2+ release from sarcoplasmic reticulum after the activation of ryanodine receptors without affecting the characteristics of receptor binding.

[The role of neurovisualization methods in diagnosis and verification of vertigo etiology].

Roentgen computed tomography (RCT) and MR-imaging (MRI) were used in investigation of vertigo etiology and affection of the cochleovestibular analyzer in 130 patients aged 28 to 74 years with recurrent systemic rotatory vertigo or its other symptoms. All the patients have undergone comprehensive otoneurological examination, RCT and MRI which showed that peripheral cochleovestibular syndromes (PCVS) caused by arterial hypertension (AH), atherosclerosis (AS), vascular dystonia (VD) are rarely characterized by focal alterations in the brain. PCVS comparison with blood flow in the vertebral arteries (VA) detected most frequently anomalies and asymmetries of the diameters. MR-angiography plays an important role in verification of pathology of intracranial VA. In central cochleovestibular syndrome (CCVS) with AH, AS, VD, principal pathological changes were registered in the brain trunk and cerebellum by MRI. Vestibulometry and otoneurological method detect not only vascular cochleovestibular peripheral and central syndromes but also to make differential diagnosis. RCT and MRI verify cochleovestibular syndromes in patients with multiple encephalomyelitis, VIII nerve neurinoma and tumors of the posterior cranial fossa.

[Vertigo and a role of neurovisual methods in it etiology and diagnosis].

Investigation of vestibular system using a standard method of electro-nystagmography in complex otoneurologic examination does not provide enough information on the etiology of vestibular analyzer lesion, location and diffusion of the pathological process. Neurovisual methods, in particular MRI and CT, have demonstrated high diagnostic validity in such pathological states as tumors of pons cerebellum and posterior focca; infarctions in the stem and cerebellum regions. The study revealed a role of MRI and CT in etiology of vertigo and lesions of cochleovestibular analyzer. One hundred thirty patients aged 28-74 years with recurrent attacks of systemic rotary vertigo and other its appearances have been examined. In 14 (11%) patients such an attack was accompanied by loss of consciousness, falls, double-vision and other neurological symptoms. All the patients underwent otoneurological examination, computer electronystagmography, auditory evoked potentials registration, CT and MRI. It is shown that peripheral cochleovestibular syndromes caused by arterial hypertension, atherosclerosis and autonomic vascular dystonia are rarely characterized by focal cerebral changes (11 patients by CT data and 17 by MRI).

[The role of corticotropin-releasing hormone in alteration of adaptive behavior of the active and passive rats after inescapable stress].

Effects of corticotropin-releasing hormone (CRH) on the formation of post-stress psychopathology were studied using of two genetic strains KHA (Koltushi high Avoidance) and KLA (Koltushi low Avoidance) selected on high or low acquisition of active avoidance, respectively. These strains are characterized by higher (KHA) and lower (KLA) behavioral activity in open field and adopted, respectively, active and passive strategies in stressful conditions. A widely used experimental paradigm of learned helplessness where behavioral depression was produced by inescapable uncontrollable footshock has been applied in our study. KHA rats demonstrated psychopathology already 1st day following exsposure to the stress faktor, and the depression progressed by the 5th and 10th post-stress days. Intranasal application of CRH facilitated the development of depression in active rats. In KLA rats, which originally displayed low exploratory activity associated with high anxiety, the inescapable stress at first enhanced the exploratory behavior but 10 days later these rats displayed a progressive decline of exploration and locomotion. Initially, the application of CRH also enhanced the exploratory behavior in these rats, but to 10th post-stress day promoted development of depressive state. The results suggest that CRH in different ways affects the formation of depressive state in rats with different strategies of adaptive behavior.

Adaptive behavior in active and passive rats after intranasal administration of corticotrophin-releasing hormone.

Rats with high (KHA) and low (KLA) rates of acquiring active avoidance reflexes were used to study the effects of intranasal administration of corticotrophin-releasing hormone on orientational-investigative behavior in an open field and anxiety in an elevated cross maze. Administration of the neurohormone induced opposite changes in the behavior of the rats of these lines in the two tests. In KLA rats, movement and investigative activity increased, while in KHA rats these behaviors decreased. In the elevated maze, KLA rats, unlike KHA rats, showed increases in the time spent in the open arms, which was evidence for a decrease in anxiety in these animals. Thus, intranasal hormone administration completely reproduced the effects seen after administration into the striatum. It is suggested that corticotrophin-releasing hormone is an endogenous factor for the detailed and appropriate correction of adaptive behavior.

[Adaptive behavior of active and passive rats after intranasal administration of the corticotropin-releasing hormone]. / Prisposobitel'noe povedenie aktivnykh i passivnykh krys posle intranazal'nogo vvedeniia kortikotropin-rilizing gormona.

Behavioural effect of intranasal application of corticotropin-releasing hormone (CRH) was investigated in rats with high (KHA) and low (KLA) rate of learning in "open field" and plus-maze (PM) active avoidance test. The neurohormone provoked the opposed changes in behaviour of rats of this strain in both tests. The level of locomotion and exploratory activity rose in KLA rats and decreased in KHA rats. After the CRH application, the KLA rats but not KHA rats spent more time in the opened alleys of the PM than the control animals. The same behavioural changes were observed in our previous research when CRH was injected in striatum. We suppose that CRH is an endogenous factor of precise correction of the adaptive behaviour.

[The potentials for diagnosing labyrinth pathology by using objective methods]. / Vozmozhnost' diagnostiki patologii ushnogo labirinta s pomoshch'iu ob''ektivnykh metodik.

Based either on spontaneous or experimental vestibular reactions, diagnostic methods proposed by the authors seem most informative for differential diagnosis of internal ear diseases with simulating conditions. The main thing in the above diagnosis is the vestibular testing unit which provides objective synchronous registration of vestibular-somatic and vascular reactions. The necessity of comparing rotatory nystagmus to postnystagmus, the significance of latent spontaneous nystagmus interpretation are emphasized.

[Syndromology and differential treatment of secondary cochleovestibulitis in patients with early clinical forms of cerebral circulatory insufficiency]. / Sindromologiia i differentsirovannoe lechenie vtorichnogo kokhleovestibulita u bol'nykh s rannimi klinicheskimi formami nedostatochnosti krovosnabzheniia mozga.

Altogether 136 patients with cochleovestibulitis and early clinical forms of cerebral circulation insufficiency were examined. Two types of syndrome were identified that were associated with the pathogenetic development: vascular and metabolic. Different diagnostic criteria and therapeutic approaches as applied to each type of syndrome were developed.

[The genesis of early clinical forms of cerebral circulatory failure and the effectiveness of different courses of therapeutic measures]. / Genez rannikh klinicheskikh form nedostatochnosti mozgovogo krovoobrashcheniia i éffektivnost' terapevticheskikh meropriiatii razlichnoi napravlennosti.

The authors have examined 214 patients with early clinical forms of cerebral circulation insufficiency. It has been established that discirculatory encephalopathy (DE) may be formed in two ways. One way is angiogenic and it leads to DE through a stage of initial manifestations of cerebral circulation insufficiency (IMCCI), the other way is related to the neurovascular nature of the disease (vegetovascular dystonia) and may lead to DE, bypassing the stage of IMCCI. It is concluded that therapy with vasoactive drugs is the basic therapy for patients with an angiogenic origin of the disease whereas in patients with a neurovascular genesis of the disease the basic approach is the administration of metabolism-correcting drugs.