[Serum creatine phosphokinase as a predictor of upper limb amputation in electrical trauma]. / Soderzhanie kreatinfosfokinazy v plazme krovi kak prediktor amputatsii verkhnei konechnosti pri elektrotravme.

OBJECTIVE: To study the relationship between serum creatine phosphokinase and outcomes of injury in victims with electrical burns. MATERIAL AND METHODS: Among 40 patients with electrical injury, 7 (18%) ones underwent upper limb amputation. There were 37 (92.5%) men and 3 (7.5%) women aged 37 (28; 47) years. We analyzed total serum creatine phosphokinase and MB fraction on the first day in patients with and without amputations. RESULTS: Total serum creatine phosphokinase exceeded the upper reference value in 11 out of 33 patients without amputation and in all 7 patients with limb amputation (p=0.001). Patients with limb amputation had significantly higher total serum creatine phosphokinase and MB fraction (p<0.001 and p=0.030, respectively). Logistic regression equation showed that high total serum creatine phosphokinase significantly influenced amputation rate (p<0.001), as evidenced by odds ratio (42.7, 95% CI 3.5-514.8). ROC analysis revealed the cut-off value of total serum creatine phosphokinase (950 IU/L). Sensitivity was 100% (63; 100), specificity - 94% (86; 94), positive predictive value - 78% (49; 78), negative predictive value - 100% (92; 100). CONCLUSION: Total serum creatine phosphokinase depends only on severity of electrical and flame burns. Serum creatine phosphokinase is a predictor of upper limb amputation in patients with electrical injury. Total serum creatine phosphokinase ≥ 950 IU/L is significant for upper limb amputation (in CK-MB fraction within the reference values).

A Long Short-Term Memory neural network for the detection of epileptiform spikes and high frequency oscillations.

Over the last two decades, the evidence has been growing that in addition to epileptic spikes high frequency oscillations (HFOs) are important biomarkers of epileptogenic tissue. New methods of artificial intelligence such as deep learning neural networks can provide additional tools for automated analysis of EEG. Here we present a Long Short-Term Memory neural network for detection of spikes, ripples and ripples-on-spikes (RonS). We used intracranial EEG (iEEG) from two independent datasets. First dataset (7 patients) was used for network training and testing. The second dataset (5 patients) was used for cross-institutional validation. 1000 events of each class (spike, RonS, ripple and baseline) were selected from the candidates initially found using a novel threshold method. Network training was performed using random selections of 50-500 events (per class) from all patients from the 1st dataset. This 'global' network was then tested on other events for each patient from both datasets. The network was able to detect events with a good generalisability namely, with total accuracy and specificity for each class exceeding 90% in all cases, and sensitivity less than 86% in only two cases (82.5% for spikes in one patient and 81.9% for ripples in another patient). The deep learning networks can significantly accelerate the analysis of iEEG data and increase their diagnostic value which may improve surgical outcome in patients with localization-related intractable epilepsy.

[Positional changes of the magistral blood flow of the left kidney in men with varicocele and infertility].

This paper proves the correlation between characteristics of blood flow rate in the renal veins and resistance indices of the renal arteries. As a result of polypositional assessment of venous blood flow, it was found that the violations of magistral venous blood flow in the left kidney can affect the formation and progression of varicocele, and the severity of disorders of spermatogenesis. The necessity of assessment of testicular veins and the pressure in left renal vein not only in clin- and orthostasis or Valsalva maneuver, but in the six static positions is discussed; this can allow to register the violations of magistral renal blood flow at the early stages important for fertility disorders, improve the efficiency of diagnosis and treatment of patients with varicocele.

[Thoracotomy and thoracoscopy in the treatment of patent arterial duct in infants weighing less than 2500 g].

BACKGROUND: Thoracoscopic clipping of the patent ductus arteriosus is an alternative to conventional surgical closure via thoracotomy in low birth weight infants. The aim of this study is to compare of these two groups of patients for the last 11 years. METHODS: We reported the data of 127 small children's who underwent standard transaxillary thoracotomy (101 patients - Group I) and video-assisted thoracoscopic surgery for patent ductus arteriosus clipping (26 patients - Group II). The two groups were compared for patients demographics, operative report and postoperative parameters. RESULTS: The groups were similar in terms of demographics and preoperative parameters. There was significant difference in mean operative time between open and thoracoscopic procedure (44.65 min vs 38.46 min; p<0.05). Duration of care in neonatal intensive unit and length of hospital stay were significantly shorter in the Group II (16.44 d vs 8.77 d; p<0.05 and 40.13 d vs 33.65 d; p<0.05). Early complication rates were equivalent between groups (6.93% vs 3.85%; p>0.05). Rate of long-term complications was dominated in the thoracotomy group (19.80% vs 0%; p=0127). CONCLUSION: Thoracoscopic ligation of the patent ductus arteriosus in infants less than 2500 g gave results better than open surgery.

[Vascular depressions].

The notion of vascular depression (VD) includes depressive disorders resulting from organic cerebral lesions of vascular genesis. Two types of VD are distinguished: post-stroke VD (PSD) and VD proper (SDP). VD develops in case of clinically manifest (neurologic) lesions in cerebral vessels that simultaneously act as psychogenic (nosogenic) factors. SDP is associated with clinically latent vascular disorders ("silent" infarctions and white matter ischemia). VD is characterized by multiple phenomenological convergence of vascular signs and symptoms inherent in both PSD and SDP. Whatever the type of VDs, they are associated with frequent cognitive problems with a variety of dynamic patterns, viz. reversible, relatively stable, and progressing.

Algorithm for automatic detection of pentylenetetrazole-induced seizures in rats.

Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation (TFS) system through our novel concentric ring electrodes to control seizures. Here we report on the development of a seizure detecting algorithm to be used for automatic application of TFS. A cumulative sum (CUSUM) algorithm was evaluated that detected the electrographic seizure activity in all experiments well in advance of the behavioral seizure activity.

[Intraabdominal pressure alterations in ruptured abdominal aortic aneurysms].

The authors investigated the dependence of intraabdominal pressure on the volume of a retroperitoneal haematoma. The study included a total of thirty-four patients in whom elevation of intraabdominal pressure had solely been caused by haemorrhage into the retroperitoneal space. The volume of the retroperitoneal haematoma was calculated based on the findings of spiral computed tomography, whereas intraabdominal pressure was measured using the methods suggested by Sugrue M. and Kron I. L. The statistical analysis showed a moderate positive correlation between the retroperitoneal haematoma volume and the level of intraabdominal pressure. With the volume of the retroperitoneal haematoma approximating to 2,000 ml, intraperitoneal pressure was at the upper limit of the norm. Of the patients examined, none turned out to have developed the high intraperitoneal pressure syndrome.

[Vascular dental anaesthesias and their mechanism].

By their mechanism of action local anaesthesia methods were divided into diffused and vascular. Intraosseous, intraseptal and intraligamental anesthaesias are vascular ones at capillary-venous system level. Circulatory mechanism besides effectiveness increased more than 2-fold and also promotes enhancement of cardiovascular system responses.

Emitting a-SiO(x)(Er) films and a-SiO(x)(Er)/a-Si:H microcavities doped with Er by remote magnetron sputtering technique.

We have developed the technique of growing amorphous a-SiO(x)(Er) films and a-SiO(x)(Er)/a-Si:H multilayer structures based on spatially separating the processes of the decomposition of an oxygen-silane gas mixture in an rf glow discharge plasma and remote magnetron sputtering of an Er target. This approach allows us to control independently the film deposition rate, the Er-ion concentration and its depth distribution in the film. Time-resolved photoluminescence measurements have shown that films and planar microcavities with an Er-doped active layer exhibit internal quantum efficiency for Er ion emission of ∼75%. The method that we suggest is a way of producing effectively emitting microcavity structures, in which the distribution profile of emission centers coincides with that of the electromagnetic field in individual layers of the structure.

Polarization splitting of optical resonant modes in a-Si:H/a-SiO(x):H microcavities.

We present experimental and theoretical results on polarization splitting of optical resonant modes in a-Si:H/a-SiO(x):H microcavities. It is shown experimentally that the splitting sign and value can be controlled by varying the active layer thickness. The polarization splitting achieved in the microcavities is about 8 meV owing to a large optical contrast, which is the ratio of film refractive indices in the distributed Bragg reflectors. The experimental data and theoretical analysis show that the polarization splitting may be zero at a certain angle of incidence of light determined by the microcavity parameters. The measured and calculated resonant frequency values for TM and TE polarizations were used to find the optical thickness of the active layer and the stop-band center frequency of the Bragg reflector. The account of the active layer thickness fluctuations along the lateral direction provides a better fit between the experimental and theoretical spectra.

Persistent abnormality detected in the non-ictal electroencephalogram in primary generalised epilepsy.

OBJECTIVES: Gamma oscillations (30-100 Hz gamma electroencephalographic (EEG) activity) correlate with high frequency synchronous rhythmic bursting in assemblies of cerebral neurons participating in aspects of consciousness. Previous studies in a kainic acid animal model of epilepsy revealed increased intensity of gamma rhythms in background EEG preceding epileptiform discharges, leading the authors to test for intensified gamma EEG in humans with epilepsy. METHODS: 64 channel cortical EEG were recorded from 10 people with primary generalised epilepsy, 11 with partial epilepsy, and 20 controls during a quiescent mental state. Using standard methods of EEG analysis the strength of EEG rhythms (fast Fourier transformation) was quantified and the strengths of rhythms in the patient groups compared with with controls by unpaired t test at 1 Hz intervals from 1 Hz to 100 Hz. RESULTS: In patients with generalised epilepsy, there was a threefold to sevenfold increase in power of gamma EEG between 30 Hz and 100 Hz (p<0.01). Analysis of three unmedicated patients with primary generalised epilepsies revealed an additional 10-fold narrow band increase of power around 35 Hz-40 Hz (p<0.0001). There were no corresponding changes in patients with partial epilepsy. CONCLUSIONS: Increased gamma EEG is probably a marker of the underlying ion channel or neurotransmitter receptor dysfunction in primary generalised epilepsies and may also be a pathophysiological prerequisite for the development of seizures. The finding provides a new diagnostic approach and also links the pathophysiology of generalised epilepsies to emerging concepts of neuronal correlates of consciousness.

Adrenoceptors, uncoupling proteins, and energy expenditure.

Interest in the biology of adipose tissue has undergone a revival in recent years with the discovery of a host of genes that contribute to the regulation of satiety and metabolic rate. The catecholamines have long been known to be key modulators of adipose tissue lipolysis and the hydrolysis of triglyceride energy stores. However, more recent efforts to understand the role of individual adrenergic receptor subtypes expressed in adipocytes and their signal transduction pathways have revealed a complexity not previously appreciated. Combined with this interest in the modulation of adipocyte metabolism is a renewed focus upon brown adipose tissue and the mechanisms of whole body thermogenesis in general. The discovery of novel homologs of the brown fat uncoupling protein (UCP) such as UCP2 and UCP3 has provoked intensive study of these mitochondrial proteins and the role that they play in fuel metabolism. The story of the novel UCPs has proven to be intriguing and still incompletely understood. Here, we review the status of adipose tissue from inert storage depot to endocrine organ, interesting signal transduction pathways triggered by beta-adrenergic receptors in adipocytes, the potential of these receptors for discriminating and coordinated metabolic regulation, and current views on the role of UCP2 and UCP3 based on physiological studies and gene knockout models.

Temporal binding at gamma frequencies in the brain: paving the way to epilepsy?

Fast (beta-gamma band 20-100 Hz) rhythms of electrical activity of the brain have been suggested to play an important role in perception, cognition and consciousness providing temporal binding of neural activities and allowing the formation of mental representations. The recent advances in the concept of temporal binding and their relation to the theory of neural networks (connectionism) are reviewed here as well as some experimental results concerning the intensified gamma rhythms and epilepsy. The hippocampal-neocortical gamma rhythms are extremely intense and hypersynchronous at onset of the epileptiform discharges induced by systemic kainic acid in the rat. Those gamma rhythms are followed by a slow rhythm of epileptiform spikes/sharp waves or spike-wave complexes ('spike-wave' activity). During spike-wave activity, gamma synchronisation is significantly decreased. A novel unifying concept is proposed which relates the associative principle of neural networks to the mechanism of temporal binding at high frequencies. It suggests that for each memory stored in an associative network there is a corresponding quasi-stable state of synchronous oscillation at some frequency within the gamma band. It also suggests that excessive temporal binding ("over-binding") occurs at seizure onset when abnormally intensified and globally synchronous fast activity is often observed. "Over-binding" may cause the undesirable formation of false associations due to inadequate synaptic modifications. To prevent this process, spike-wave discharge develops as an extreme activation of the mechanism capable to desynchronise and eventually suppress fast activity and erase the spurious modes of activity associated with hypersynchronous gamma rhythms. Thus, spike-wave activity is suggested to be the "anti-binding" mechanism. This mechanism is also related to the spikes/sharp waves normally occurring in the brain mostly in sleep. It is qualitatively similar to the "unlearning" mechanism of Crick and Mitchison presumably associated with the PGO spikes of the REM sleep.

beta-Adrenergic activation of p38 MAP kinase in adipocytes: cAMP induction of the uncoupling protein 1 (UCP1) gene requires p38 MAP kinase.

Because of increasing evidence that G protein-coupled receptors activate multiple signaling pathways, it becomes important to determine the coordination of these pathways and their physiological significance. Here we show that the beta(3)-adrenergic receptor (beta(3)AR) stimulates p38 mitogen-activated protein kinase (p38 MAPK) via PKA in adipocytes and that cAMP-dependent transcription of the mitochondrial uncoupling protein 1 (UCP1) promoter by beta(3)AR requires p38 MAPK. The selective beta(3)AR agonist CL316,243 (CL) stimulates phosphorylation of MAP kinase kinase 3/6 and p38 MAPK in a time- and dose-dependent manner in both white and brown adipocytes. Isoproterenol and forskolin mimicked the effect of CL on p38 MAPK. In all cases activation was blocked by the specific p38 MAPK inhibitor SB202190 (SB; 1-10 microm). The involvement of PKA in beta(3)AR-dependent p38 MAPK activation was confirmed by the ability of the PKA inhibitors H89 (20 microm) and (R(p))-cAMP-S (1 mm) to block phosphorylation of p38 MAPK. Treatment of primary brown adipocytes with CL or forskolin induced the expression of UCP1 mRNA levels (6.8- +/- 0.8-fold), and this response was eliminated by PKA inhibitors and SB202190. A similar stimulation of a 3.7-kilobase UCP1 promoter by CL and forskolin was also completely inhibited by PKA inhibitors and SB202190, indicating that these effects on UCP1 expression are transcriptional. Moreover, the PKA-dependent transactivation of the UCP1 promoter, as well as its sensitivity to SB202190, was fully reproduced by a 220-nucleotide enhancer element from the UCP1 gene. We similarly observed that increased phosphorylation of ATF-2 by CL was sensitive to both H89 and SB202190, while phosphorylation of cAMP-response element-binding protein was inhibited only by H89. Together, these studies illustrate that p38 MAPK is an important downstream target of the beta-adrenergic/cAMP/PKA signaling pathway in adipocytes, and one of the functional consequences of this cascade is stimulation of UCP1 gene expression in brown adipocytes.

Transcriptional regulation of the mouse uncoupling protein-2 gene. Double E-box motif is required for peroxisome proliferator-activated receptor-gamma-dependent activation.

Uncoupling protein-2 (UCP2) is present in many tissues with relevance to fuel metabolism, and its expression is increased in fat and muscle in response to elevated circulating free fatty acids resulting from fasting and high fat feeding. We proposed a role for peroxisome proliferator-activated receptor-gamma (PPARgamma) as a mediator of these physiological changes in UCP2, because thiazolidinediones also increase expression of UCP2 in these cell types (). To determine the molecular basis for this regulation, we isolated the 7.3-kilobase promoter region of the mouse UCP2 gene. The -7.3-kilobase/+12-base pair fragment activates transcription of a reporter gene by 50-100-fold. Deletion and point mutation analysis, coupled with gel shift assays, indicate the presence of a 43-base pair enhancer (-86/-44) that is responsible for the majority of both basal and PPARgamma-dependent transcriptional activity. The distal (-86/-76) part of the enhancer specifically binds Sp1, Sp2, and Sp3 and is indistinguishable from a consensus Sp1 element in competition experiments. Point mutation in this sequence reduces basal activity by 75%. A second region (-74/-66) is identical to the sterol response element consensus and specifically binds ADD1/SREBP1. However, deletion of this sequence does not affect basal transcriptional activity or the response to PPARgamma. The proximal portion of the enhancer contains a direct repeat of two E-Box motifs, which contributes most strongly to basal and PPARgamma-dependent transcription of the UCP2 promoter. Deletion of this region results in a 10-20-fold reduction of transcriptional activity and complete loss of PPARgamma responsiveness. Point mutations in either E-Box, but not in the spacer region between them, eliminate the stimulatory response to PPARgamma. However, gel shift assays show that PPARgamma does not bind to this region. Taken together, these data indicate that PPARgamma activates the UCP2 gene indirectly by altering the activity or expression of other transcription factors that bind to the UCP2 promoter.

[The aged patient's first visit to the outpatient psychiatric clinic]. / Vpervye obrativshiesia v psikhonevrologicheskii dispanser bol'nye pozdnego vozrasta.

160 patients over 60 years of age appealed to gerontologic unit of out-patient psychiatric clinic for the first time. The patients were divided into two main groups: with organic mental disorders (OMD) and with functional mental disorders (FMD) (79 and 81 patients, respectively). In the group of OMD the main form of disturbances were cases with dementia (74.4%) mainly of the Alzheimer's type, and cerebral vascular dementia. In 25.3% of the patients the cognitive disturbances didn't attain the level of dementia. In a group of patients with different forms of dementia a high frequency of comorbid mental pathology was observed (83%)--confusional states, delusions, depressive conditions as well as disturbed behavior (67.7%) that was one of the reasons for consulting a psychiatrist. In FMD group the prevailing pathology were depressions, both of the major (37.1%) and mild (34.6%) forms. The remaining cases were characterized by delusions (10.1%), anxiety-phobic (7.6%) states and somatoform disturbances (5.1%). Among the patients both of OMD and FMD groups it was possible to diagnose approximately 3-4 different somatic diseases; vascular and gastrointestinal disorders were met more frequently. The study of contribution of brain computer tomography (CT) to diagnosis of mental pathology (according to ICD-10), has demonstrated that in 30.8% of the cases it was decisive, in 41% it confirmed the clinical data and in 21.8% CT provide additional data (detecting latent cerebral vascular damage). And only in 6.4% of the cases CT fails to give definite information in diagnostically complicated cases. In 26.6% of the patients with FMD, CT of brain had detected symptoms of mild vascular pathology.

Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation.

Both beta(2)- and beta(3)-adrenergic receptors (ARs) are able to activate the extracellular signal-regulated kinase (ERK) pathway. We previously showed that c-Src is required for ERK activation by beta(2)AR and that it is recruited to activated beta(2)AR through binding of the Src homology 3 (SH3) domain to proline-rich regions of the adapter protein beta-arrestin1. Despite the absence of sites for phosphorylation and beta-arrestin binding, ERK activation by beta(3)AR still requires c-Src. Agonist activation of beta(2)AR, but not beta(3)AR, led to redistribution of green fluorescent protein-tagged beta-arrestin to the plasma membrane. In beta-arrestin-deficient COS-7 cells, beta-agonist-dependent co-precipitation of c-Src with the beta(2)AR required exogenous beta-arrestin, but activated beta(3)AR co-precipitated c-Src in the absence or presence of beta-arrestin. ERK activation and Src co-precipitation with beta(3)AR also occurred in adipocytes in an agonist-dependent and pertussis toxin-sensitive manner. Protein interaction studies show that the beta(3)AR interacts directly with the SH3 domain of Src through proline-rich motifs (PXXP) in the third intracellular loop and the carboxyl terminus. ERK activation and Src co-precipitation were abolished in cells expressing point mutations in these PXXP motifs. Together, these data describe a novel mechanism of ERK activation by a G protein-coupled receptor in which the intracellular domains directly recruit c-Src.

[The use of clopixole in therapy of aged mental patients]. / Ispol'zovanie klopiksola pri lechenii psikhicheskikh bol'nykh pozdnego vozrasta.

On the base of clinical psychological and electrophysiological studies of 34 patients with primary manifestations of brain circulation insufficiency good tolerance and high efficiency of Tanakan course treatment (3 x 40 mg/day for 3 months) were showen. Tanakan decreased manifestations of clinical syndrome, improved psychological functions and electrophysiological parameters. Prospective study supported the stability of positive changes in the status of patients for 12 months after Tanakan course treatment.

E1A + cHa-ras transformed rat embryo fibroblast cells are characterized by high and constitutive DNA binding activities of AP-1 dimers with significantly altered composition.

Transcription factors of the AP-1/ATF family, including c-Fos, c-Jun, and ATF-2, play an important role in the regulation of cell proliferation and differentiation, and changes in their levels and/or activities may contribute to oncogenesis. We analyzed the alterations of AP-1/ATF transcription factors upon immortalization and transformation in a panel of cell lines derived from rat embryo fibroblast (REF) cells. The tumorigenic E1A + cHa-ras cells are characterized by high and constitutive DNA binding activities of AP-1, in contrast to nontransformed cells and the E1A cells. The expression of c-fos and c-jun genes was affected differently by the oncogenic transformation. By using antibodies to c-Jun and c-Fos proteins in electrophoretic mobility shift assays (EMSA), we showed that E1A + cHa-ras transformants did not contain c-Fos under any condition of cell cultivation and growth factor stimulation, whereas c-Jun was constitutively upregulated. In the absence of c-fos gene expression, c-Fos protein appears to be replaced by proteins of Fos family (Fra-1) and ATF family (ATF-2 and ATFa). To determine the possible mechanisms of c-fos downregulation in E1A + cHa-ras transformants we have obtained populations of geneticin-resistant clones containing integrated reporter construct -711fos-CAT and its mutants in serum-responsive element (SRE) and cAMP-responsive element (CRE). Data obtained show that the mutations within the SRE lead to a manifold activation of fos-CAT expression. This allows to suggest that c-fos downregulation in E1A + cHa-ras transformants is provided by a negative control mediated through the SRE regulatory region. The profound differences in regulation and composition of transcription factors of the AP-1 family probably play a pivotal role in the transformation of REF cells by E1A and cHa-ras oncogenes.