Metal-non-metal transition in lead-bismuth eutectic.

Thermodynamic functions and electrical resistivity of Pb-Bi eutectic alloy have been measured over wide ranges of specific volume and pressure in the liquid and gaseous state. The experimental data show a crossover from metallic to insulating behavior in the electrical resistivity of the alloy when its specific volume increases. It is found that in the crossover region the constant volume temperature coefficient of resistivity changes sign from positive to negative and passes through zero at a value of the specific volume which is 2.4 times larger than that in normal state. The second salient feature of the alloy revealed by these experiments is that the isochores plotted in the specific internal energy-pressure plane are straight lines. Based on these experimental data and using an earlier developed approach, an equation of state (EOS) of the alloy has been constructed whose accuracy is determined mainly by the errors of the measurements. It is shown that this EOS can be used to obtain direct estimates of the specific volume and pressure at the critical point of the liquid-gas transition as well as the critical volume for the metal-non-metal (M-NM) transition observed in this eutectic. The results indicate that the critical specific volumes for these two transitions are equal, and the M-NM transition can be described by the classical percolation theory.

[Magnetic resonance spectroscopy data in the prognosis of consciousness recovery in patients with vegetative state]. / Prognozirovanie vosstanovleniia soznaniia u patsientov v vegetativnom sostoianii s primeneniem metoda vodorodnoi magnitno-rezonansnoi spektroskopii.

AIM: To study the prognostic value of magnetic resonance spectroscopy (MRS) in patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). MATERIAL AND METHODS: Thirty-four patients with VS/UWS underwent multi-voxel MRS (thalamus, globus pallidus, putamen, internal capsules, fornix, brainstem, temporal and frontal cortex). Subjects were grouped according to etiology: 22 patients with traumatic brain injury (TBI) (group 1) and 12 patients with a hypoxia (group 2). The groups were matched by age and duration of UWS (mean 2, 3 months). The CRS-R was used to identify the first signs of consciousness during hospitalization and 6-12 months later. Outcomes of the patients with TBI were as follows: chronic VS/UWS (n=6), minimally conscious state (MCS) plus (n=9), emergence from MCS (EMCS) (n=7). Outcomes of the patients with hypoxia were: chronic vegetative state (n=10), minimally conscious state (MCS) (n=2). RESULTS: The decrease in the NAA/Cr ratio in thalamus, capsula interna, temporal cortex are correlated with poor outcome in both groups. Higher rates of NAA/Cr in these structures are correlated with further recovery of consciousness. The decrease in the ratio of NAA Cr and NAA/NAA+Cho+Cr in the midbrain is correlated with poor outcome only in UWS with hypoxia. CONCLUSION: The results suggest that the MRS allows to more accurately predicting the outcome in VS/UWS patients with hypoxic brain damage, as well as in UWS patients with TBI, who have recovered consciousness to the level of EMCS.

Melting Line of Graphite.

A thin plate of highly oriented pyrolytic graphite (HOPG) with the hexagonal axis (c axis) perpendicular to its surface was sandwiched between two plates of the window material and heated by an electric current pulse. The quasistatic heating process has been affected, in which the graphite sample undergoes thermal expansion only along the c axis and is melted at a pressure of 0.3-2 GPa. The set of thermodynamic quantities characterizing completely the thermodynamic states of the sample in such a process (specific volume, enthalpy, temperature, and pressure) as well as the electrical resistivity, were measured with an uncertainty <5%. It has been found that under the above pressures the HOPG melts at the temperatures of 6.3 to 6.7 kK, which are substantially higher than the literature values derived from indirect measurements. The jumps in the volume, resistivity and enthalpy of carbon on melting have been determined as well as values of the isochoric heat capacity and the sound velocity of the graphite and liquid carbon. The heat capacities in the vicinity of the melting line turned out to be close to the Dulong-Petit value while the sound velocity of liquid carbon clearly demonstrates an increase with volume indicating a change from the planar sp^{2} to tetrahedral sp^{3} covalent bonding.

Experimental study of liquid carbon.

Direct measurements of the functional dependencies of the electric resistivity and the molar volume on enthalpy and pressure have been performed for graphite and liquid carbon. It has been found that for graphite at the pressures P ⩽ 1 GPa the isochoric temperature coefficient of resistance is positive, while for liquid carbon it is negative over the entire pressure range investigated where P = 0.5-3.5 GPa. These observations probably indicate that graphite is a metal whereas liquid carbon is not a metal, so that the melting of graphite under such pressures coincides with a metal-to-nonmetal transition.

[Vegetative State: Difficulty in Identifying Consciousness and Predicting Outcome].

Article consists of literature review, authors experience of the application of neurovisualization and neurophysiological research methods to predict the recovery of consciousness in patients in vegetative state (VS). According to the literature data PET with FDG has higher sensitivity in the detection of signs of consciousness, then functional MRI (fMRI). The method fMRI allows assessing the functional activity of the brain in a state of rest and in response to stimulation with different modalities ­ visual, auditory, etc (with the application of active and passive paradigm). A higher specificity in the detection of signs of consciousness have the methodology of fMRI with the active paradigm, at the same time, the absence of signs of consciousness according to the fMRI can not be charged as a basis for the conclusion of a poor prognosis in a particular patient. Neurophysiological tests (EEG, TMS, EP, etc) are more readily available and quite effective. Based on the literature analysis, the authors comes to the conclusion that neurovisualization and neurophysiological tests used in the prediction of the outcome of VS reflects the residual functional activity of different brain areas, in a context of diffuse brain damage, and the recovery of consciousness is usually combined with the restoring of the functional activity off the thalamocortical tracts, which activity, indirectly, is evaluated using these methods. In the authors' opinions, the main disadvantage in the interpretation of the is the lack of a common pathophysiological concept of the organization of brain functions in VS patients. The authors offer for the discussion their concept of stable pathological states of the brain, which is based on the works of Russian pathophysiologists.

Neonatal exposure to phenobarbital potentiates schizophrenia-like behavioral outcomes in the rat.

Previous work has indicated an association between seizures early in life and increased risk of psychiatric disorders, including schizophrenia. However, because early-life seizures are commonly treated with antiepileptic drugs (AEDs) such as phenobarbital, the possibility that drug treatment may affect later-life psychiatric outcomes needs to be evaluated. We therefore tested the hypothesis that phenobarbital exposure in the neonatal rat increases the risk of schizophrenia-like behavioral abnormalities in adulthood. Thus, in this study, we examined the effects of a single acute neonatal exposure to phenobarbital on adult behavioral outcomes in the rat neonatal ventral hippocampal (nVH) lesion model of schizophrenia. We compared these outcomes to those in rats a) without nVH lesions and b) with nVH lesions, without phenobarbital. The tasks used for behavioral evaluation were: amphetamine-induced locomotion, prepulse inhibition, elevated plus-maze, and novel object recognition task. We found that neonatal phenobarbital treatment (in the absence of nVH lesions) was sufficient to disrupt sensorimotor gating (as tested by prepulse inhibition) in adulthood to an extent equivalent to nVH lesions. Additionally, neonatal phenobarbital exposure enhanced the locomotor response to amphetamine in adult animals with and without nVH lesions. Our findings suggest that neonatal exposure to phenobarbital can predispose to schizophrenia-like behavioral abnormalities. Our findings underscore the importance of examining AED exposure early in life as a potential risk factor for later-life neuropsychiatric abnormalities in clinical populations.

Mathematical modeling of thrombus growth in mesenteric vessels.

Richardson's phenomenological mathematical model of the thrombi growth in microvessels is extended to describe the realistic features of the phenomenon. The main directions of the generalization of Richardson's model are: (1) the dependence of platelet activation time on the distance from the injured vessel wall; (2) the non-homogeneity of the platelet distribution in blood flow in the vicinity of the vessel wall; (3) the adequate choice of the phenomenological function describing the dependence of blood velocity on the thrombus size. The generalization of the model corresponds to the main experimental results and theoretical considerations concerning thrombus formation obtained in recent years. The extended model permits to achieve qualitative agreement between model and experimental data.

Time-dependent increase in basic fibroblast growth factor protein in limbic regions following electroshock seizures.

Brief experimentally induced seizures have been shown to increase the expression of mRNA encoding basic fibroblast growth factor (FGF-2) in specific brain regions. However, the extent to which this change in mRNA affects the expression of FGF-2 protein in these brain regions has not been examined. In the present study, we exposed rats to brief non-injurious seizures to determine whether this treatment would lead to an increase in FGF-2 protein expression in selected brain regions. Because initial results indicated that the elevation of FGF-2 protein was not significant following acute seizure exposure, we examined both acute and chronic seizure treatment to determine whether FGF-2 protein expression could be increased under conditions of repeated seizures. Brief limbic seizures were induced by minimal electroconvulsive shock (ECS) given as daily treatments for 1 (acute) or 7 (chronic) days. FGF-2 protein was measured in hippocampus, rhinal cortex, frontal cortex, and olfactory bulb at 20, 48, and 72 h following the last seizure. No significant increases in FGF-2 protein were observed in any region following acute ECS. In the chronic ECS-treated groups, significantly elevated FGF-2-like immunoreactivity was found in the frontal and rhinal cortex as compared with the same regions from both control and acute ECS animals. Increases after chronic ECS were maximal at 20 h, and remained significantly elevated as long as 72 h. These increases were predominantly observed for the 24-kDa and 22/22.5-kDa FGF-2 isoforms. Because chronic ECS, which has been shown to be protective against neuronal cell death, induced significantly more FGF-2 immunoreactivity than did acute ECS, we suggest that FGF-2 expression may be an important substrate for the neuroprotective action of non-injurious seizures. A prolonged induction of the high molecular weight isoforms of FGF-2, as occurs after chronic ECS, may selectively reduce the vulnerability of certain brain regions to a variety of neurodegenerative insults.

The effects of repeated minimal electroconvulsive shock exposure on levels of mRNA encoding fibroblast growth factor-2 and nerve growth factor in limbic regions.

Chronic, but not acute, exposure to minimal electroconvulsive shock (ECS) has been shown to decrease vulnerability to neuronal cell death, without itself causing neuronal damage. One potential mechanism for the neuroprotective effect of ECS is the increase in fibroblast growth factor-2 (FGF-2) which occurs after chronic, but not acute, ECS exposure. This raises the possibility that repeated seizures over a period of several days may alter the transcriptional regulation of FGF-2. To test this hypothesis, the present study compared the effect of acute (1 day) vs. chronic (7 days) ECS treatment on levels of mRNA for FGF-2 in rhinal and frontal cortices, hippocampus, and olfactory bulbs. In addition, mRNA for another prominent neurotrophic factor, nerve growth factor (NGF), was assayed concurrently. At 8 h after acute ECS, mRNA levels increased by 60% for FGF-2 and 136% for NGF in rhinal cortex, 32% for FGF-2 and 36% for NGF in frontal cortex, and by 13% for NGF in hippocampus. After 7 days of ECS treatment the respective increases were 72% and 80%, 53% and 38%, and 28%. No increases were observed in olfactory bulbs after either treatment regimen. The peak increases in FGF-2 mRNA were consistently greater after chronic treatment, but the differences from those seen acutely reached significance in frontal cortex only. However, the duration over which mRNA for FGF-2 was elevated did not differ between the acute and chronic ECS groups. NGF mRNA induction was neither enhanced nor prolonged as a result of chronic ECS as compared to acute ECS treatment. These results suggest that chronic ECS treatment may lead to an enhanced rate of transcription of message for FGF-2 but not for NGF, in selected brain regions. At the same time, the results indicate that chronic ECS treatment induces FGF-2 and NGF mRNA expression in a tissue-specific manner and that this induction is maintained over the 7-day treatment period. The sustained increases in mRNAs for these trophic factors may contribute to the neuroprotective actions of chronic ECS treatment.

Temporal and spatial patterns of DNA fragmentation following focally or systemically-evoked status epilepticus in rats.

Status epilepticus (SE) triggers neuronal degeneration comprised of both necrotic and apoptotic components. Here we determined whether internucleosomal DNA fragmentation reflects the severity of SE-induced neuronal damage. We utilized both a systemic (kainic acid) and a focally-induced model of SE in rats. DNA fragmentation was analyzed in rhinal cortex and hippocampus at various time points following SE episodes of varying durations (30-120 min). Radioactively labeled DNA fragments were analyzed by agarose gel electrophoresis and quantified by liquid scintillation counting. The spatial and temporal characteristics of the SE-evoked DNA fragmentation indicated that this marker of apoptosis appears as early as 8 h after SE and reaches peak expression at 48 h. This method permitted us to quantitatively monitor the evolution of the apoptotic component of cell death over the acute post-injury period (8-72 h). Moreover, in both models of SE, the DNA fragmentation varied directly as a linear function of the duration of SE between 30 and 120 min suggesting that this marker should be highly responsive to neuroprotective intervention.

Electroconvulsive shock exposure prevents neuronal apoptosis after kainic acid-evoked status epilepticus.

In the aftermath of prolonged continuous seizure activity (status epilepticus, SE), neuronal cell death occurs in the brain regions through which the seizure propagates. The vulnerability to adrenalectomy-induced apoptotic neuronal death was recently reported to be reduced by prior exposure to repeated daily noninjurious electroconvulsive shock (ECS). The present studies identified apoptosis and apoptosis-associated gene products in the neurodegenerative response to experimentally controlled periods (1 or 2 h) of SE in the rat, and determined whether exposure to ECS can interrupt these apoptotic responses mechanisms. Internucleosomal DNA fragmentation and the presence of apoptotic-like neurons (as assessed by in situ double labeling technique) was detected in hippocampus and rhinal cortex at 24 h after SE. Under these conditions, levels of both mRNA and protein encoded by the 'death promoting' bcl-XS gene were increased in the same brain areas. Pretreatment of animals for 7 days with low intensity (minimal) ECS conferred resistance to SE-evoked neurodegeneration, as assessed histopathologically by silver staining. Associated with this neuroprotective action was a reduction in the incidence of apoptosis-like neuronal morphology and DNA fragmentation, and a prevention of the increase in Bcl-XS protein and mRNA in hippocampus and rhinal cortex. These data suggest that pre-exposure to controlled, brief noninjurious seizures decreases vulnerability to programmed neuronal cell death, that this neuroprotective action occurs upstream from Bcl-XS, and that increases in bcl-XS gene expression may serve as a sensitive indicator of neurodegeneration following SE.

Intracerebral injection of caspase-3 inhibitor prevents neuronal apoptosis after kainic acid-evoked status epilepticus.

In the aftermath of prolonged continuous seizure activity (status epilepticus, SE), neuronal cell death occurs in the brain regions through which the seizure propagates. Recent studies have implicated apoptotic processes in this seizure-related injury. Because activation of caspase-3-like cysteine proteases plays a crucial role in mammalian neuronal apoptosis, we explored the possibility that activation of caspase-3 is involved in the neuronal apoptotic cell death that occurs in rat brain following SE induced by systemic kainic acid. Caspase-3 activity was determined immunocytochemically using CM1 antibodies specific for catalytically active subunit (p17) of the enzyme. We found an induction of caspase-3 activity in rhinal cortex and amygdala at 24 h after SE. To determine whether activation of caspase-3-like proteases is a necessary component of the injury process, we delivered a caspase-3 inhibitor, z-DEVD-fmk, into the lateral ventricle prior to, and following SE. z-DEVD-fmk treatment substantially attenuated apoptotic cell death after SE, both in hippocampus and rhinal cortex, as evaluated by analysis of internucleosomal DNA fragmentation and neuronal nuclear morphology. Our findings implicate caspase-3 cysteine protease in the neurodegenerative response to SE and suggest that this degeneration can be attenuated by inhibition of caspase-3-like enzyme activity.

ATM gene product phosphorylates I kappa B-alpha.

The recently cloned ATM gene is mutated in patients with ataxia telangiectasia, but its biological functions remain to be experimentally determined. Structural analysis has revealed ATM sequence similarities to the catalytic domains of phosphatidyl-3 kinase and other members of this family of yeast and mammalian proteins. Rabbit polyclonal antibodies raised against polypeptide regions unique to the COOH terminus and to the NH2 terminus of the published ATM sequence confirm ATM as M(r) approximately 350,000 protein in normal cells, which is missing in AT cells. Immunoprecipitated protein(s) is capable of phosphorylating I kappa B-alpha in an in vitro kinase assay. However, we did not observe a phosphatidyl-3 kinase or a DNA-dependent protein kinase function by ATM immunoprecipitates. These data support a protein kinase activity for ATM and suggest a role in NF-kappa B activation.

Identification and characterization of a radiation-inducible glycosylated human early-response gene.

A radiation-inducible immediate-early gene, IEX-1, was identified and characterized in human squamous carcinoma cells. Sequence analysis revealed 156-amino acid nucleotides, encoding a protein of Mr 20,000. The protein is glycosylated (Mr approximately 27,000) in the presence of microsomal membranes. Northern analysis reveals a 1.2-kb transcript. Treatment with cycloheximide was associated with superinduction of this transcript suggesting that it is an immediate-early gene. The abundance of IEX-1 mRNA increased rapidly after exposure of the cells to ionizing radiation (2-10 Gy), reaching a maximum by 15 min and returning subsequently to basal levels by 4 h. Expression of IEX-1 was also induced significantly by the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA), the protein phosphatase inhibitor okadaic acid, and tumor necrosis factor-alpha, whereas treatment of cells with UV light and H2O2 had little effect on IEX-1 expression. Cells depleted of PKC by prolonged incubation with TPA showed no attenuated IEX-1 response to tumor necrosis factor-alpha. This is the first report of IEX-1, a radiation-inducible glycosylated human protein, whose expression can be mediated through multisignal transduction pathways.

Elongation factor 1 delta is enhanced following exposure to ionizing radiation.

We have used the technique of differential display of mRNA to investigate gene expression patterns in a human squamous carcinoma cell line, SCC-35, following exposure to ionizing radiation. We observed that elongation factor 1 delta (EF-1 delta) expression increased within 2 h of radiation exposure with maximum expression at 8 h. These data identify EF-1 delta as a radiation-inducible gene. Cell cycle analysis shows that EF-1 delta expression enhancement precedes G2 arrest in these cells, suggesting that EF-1 delta may participate in the G2-M cell cycle checkpoint.

Nerve growth factor stimulates protein kinase C translocation in PC12 cells.

The effect of nerve growth factor (NGF) on the activity and intracellular localization of protein kinase C (PKC) in pheochromocytoma PC12 cells was studied. By using immunoblotting, immunofluorescence method and phorbol ester binding, NGF was found to induce PKC translocation from the cytoplasm into the cell membrane. This process was accompanied by an increase in the protein kinase activity in the membrane fraction. Translocation was completely blocked by H-7, a protein kinase inhibitor potentiating the neurite-stimulating activity of NGF.

Immunofluorescence localization of the regulatory subunit type II of cAMP-dependent protein kinase in PC12 and 3T3 cells in different proliferative states.

Localization of the regulatory subunit of cAMP-dependent protein kinase type II was studied in proliferating and quiescent fibroblasts 3T3 and in a cell line of neural origin pheochromocytoma PC12. In actively proliferating PC12 cells the regulatory subunit was found to be localized in the nucleus. Transition of these cells into a quiescent state was accompanied by a regulatory subunit translocation to the cytoplasm. In 3T3 cells the regulatory subunit was localized in the cytoplasm both in the quiescent and proliferating (though less actively than PC12 cells) states. Similar results were obtained both with monoclonal antibodies and with rabbit monospecific antiserum raised against the regulatory subunit type II from pig brain.

Effect of protein kinase modulators on the induction of morphological differentiation of pheochromocytoma PC12 cells by nerve and fibroblast growth factors.

The effect of protein kinase modulators on the ability of nerve and fibroblast growth factors to induce neurite outgrowth in pheochromocytoma PC12 cells was studied. The protein kinase inhibitor H7 increased the neurite-stimulating capacity of these factors. The effect of H7 was observed within 1 h and was dose-dependent. HA 1004, an inhibitor of cAMP- and cGMP-dependent protein kinases, did not affect the neurite-stimulating activity of NGF. Substances inhibiting protein kinase C, ganglioside GT1b and quercetin, acted in a similar way whereas sphingosine had an opposite effect.

The influence of nerve growth factor on the activities of adenylate cyclase and high-affinity GTPase in pheochromocytoma PC12 cell.

The influence of nerve growth factor (NGF) on the activities of adenylate cyclase and high-affinity GTPase in pheochromocytoma PC12 cells was studied. Incubation of cells with nerve growth factor led to a rapid activation of adenylate cyclase accompanied by an inhibition of high-affinity GTPase. By the 10th min of incubation the activity of adenylate cyclase had been reduced 2-fold when compared to the control. The activity of GTPase, however, increased. No significant changes in the cAMP level were detected. The data obtained indicate that NGF interaction with PC12 cells induces changes in the adenylate cyclase system and this process involves G-proteins that regulate the adenylate cyclase activity.