Elevated vascular level of ortho-tyrosine contributes to the impairment of insulin-induced arterial relaxation.

Previous studies have shown that in diabetes mellitus, insulin-induced relaxation of arteries is impaired and the level of ortho-tyrosine (o-Tyr), an oxidized amino acid is increased. Thus, we hypothesized that elevated vascular level of o-Tyr contributes to the impairment of insulin-induced vascular relaxation. Rats were fed with o-Tyr for 4 weeks. Insulin-induced vasomotor responses of isolated femoral artery were studied using wire myography. Vascular o-Tyr content was measured by HPLC, whereas immunoblot analyses were preformed to detect eNOS phosphorylation. Sustained oral supplementation of rats with o-Tyr increased the content of o-Tyr in the arterial wall and significantly reduced the relaxations to insulin. Sustained supplementation of cultured endothelial cells with o-Tyr increased the incorporation of o-Tyr and mitigated eNOS Ser (1 177) phosphorylation to insulin. Increasing arterial wall o-Tyr level attenuates insulin-induced relaxation - at least in part - by decreasing eNOS activation. Elevated level of o-Tyr could be an underlying mechanism for vasomotor dysfunction in diabetes mellitus.

A chronic generalized bi-directional brain-machine interface.

A bi-directional neural interface (NI) system was designed and prototyped by incorporating a novel neural recording and processing subsystem into a commercial neural stimulator architecture. The NI system prototype leverages the system infrastructure from an existing neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing predicate therapy capabilities, the device adds key elements to facilitate chronic research, such as four channels of electrocortigram/local field potential amplification and spectral analysis, a three-axis accelerometer, algorithm processing, event-based data logging, and wireless telemetry for data uploads and algorithm/configuration updates. The custom-integrated micropower sensor and interface circuits facilitate extended operation in a power-limited device. The prototype underwent significant verification testing to ensure reliability, and meets the requirements for a class CF instrument per IEC-60601 protocols. The ability of the device system to process and aid in classifying brain states was preclinically validated using an in vivo non-human primate model for brain control of a computer cursor (i.e. brain-machine interface or BMI). The primate BMI model was chosen for its ability to quantitatively measure signal decoding performance from brain activity that is similar in both amplitude and spectral content to other biomarkers used to detect disease states (e.g. Parkinson's disease). A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection. These techniques have the potential to be generalized beyond motor prosthesis, and are being explored for unmet needs in other neurological conditions such as movement disorders, stroke and epilepsy.

Changes in motor cortex excitability with stimulation of anterior thalamus in epilepsy.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders and pain. Recently, bilateral DBS of the anterior nucleus of thalamus (AN) was performed for the treatment of intractable epilepsy. This surgery reduced seizure frequency in an initial group of patients. However, its physiologic effects on the cortex and mechanisms of action remain poorly understood. Different classes of antiepileptic drugs (AEDs) have distinct effects on the excitatory and inhibitory circuits in the motor cortex, which can be studied noninvasively by transcranial magnetic stimulation (TMS). OBJECTIVE: To examine the effects of bilateral AN DBS on motor cortex excitability in epilepsy and compare these to the known effects of AEDs. METHODS: Cortical excitability was assessed in five medicated epilepsy patients with bilateral stimulators implanted in the anterior thalamus and nine healthy controls. Single and paired TMS were used to examine cortical inhibitory and facilitatory circuits. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex. Patients were studied during DBS turned off (OFF condition), DBS with cycling stimulation mode (1 minute on, 5 minutes off; CYCLE), and DBS with continuous stimulation (CONTINUOUS) in random order on 3 consecutive days. RESULTS: Motor thresholds were increased in the patients regardless of DBS condition. Active short-interval intracortical inhibition (SICI) was significantly reduced in the OFF and CYCLE conditions but returned toward normal levels in the CONTINUOUS condition. Rest SICI, long interval intracortical inhibition, and silent period duration were unchanged. CONCLUSIONS: Increased short-interval intracortical inhibition with continuous deep brain stimulation (DBS) suggests that thalamic DBS might drive cortical inhibitory circuits, similar to antiepileptic drugs that enhance gamma-aminobutyric acid inhibition.

Changes in cortical excitability with thalamic deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for several movement disorders. However, its mechanism of action is largely unknown. Both lesioning and DBS of the ventralis intermedius (VIM) nucleus of thalamus improve essential tremor. Although DBS was initially thought to inhibit the target neurons, recent studies suggest that DBS activates neurons. OBJECTIVE: To test the hypothesis that thalamic DBS activates the target area in patients with essential tremor. METHODS: Cortical excitability was assessed in seven unmedicated patients with essential tremor using unilateral stimulators implanted in the VIM of the dominant hemisphere and in 11 healthy controls using transcranial magnetic stimulation (TMS). Patients were studied during optimal DBS (ON condition), half the optimal frequency (HALF), and with DBS off (OFF) in random order. Tremor was assessed after a change in DBS setting. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex using single and paired pulses to elicit motor evoked potentials (MEPs). MEP recruitment was determined using stimulus intensities from 100% to 150% of motor threshold. RESULTS: Tremor scores were significantly improved with DBS ON. Analysis of variance showed a significant interaction between condition (ON, HALF, OFF, Normal) and stimulus intensity on MEP amplitude. During DBS ON MEP amplitudes were significantly higher compared with controls at high but not at low TMS intensities. CONCLUSION: Because the ventralis intermedius (VIM) projects directly to the motor cortex, the high motor evoked potential amplitude with deep brain stimulation ON suggests that VIM DBS activates rather than inhibits the target area.

Differences in neuronal firing rates in pallidal and cerebellar receiving areas of thalamus in patients with Parkinson's disease, essential tremor, and pain.

The motor symptoms of Parkinson's disease (PD) are thought to result from increased inhibitory outflow from the basal ganglia to the pallidal receiving areas of thalamus (ventral oral anterior and posterior-Voa,Vop). To test this hypothesis, we examined the firing rates of neurons in pallidal and cerebellar receiving areas of thalamus in five PD patients and compared them to those of neurons in comparable regions of motor thalamus in two other patient groups where hyperactivity of GPi is not believed to occur [essential tremor (ET), pain]. Neuronal recordings were made during microelectrode-guided functional stereotactic neurosurgery. The mean spontaneous firing rate (MSFR) of neurons classified as voluntary neurons and presumed to be in pallidal receiving areas of thalamus in PD patients [7.4 +/- 1.0 (SE) Hz] was significantly lower (P < 0.01) than in the ET (18.1 +/- 3.0 Hz) and pain (19.0 +/- 1.9Hz) groups. In contrast, the MSFR of neurons classified as kinesthetic and presumed to be primarily in the cerebellar receiving area of thalamus (ventral intermediate-Vim), although some are probably in the deep shell region of the ventrocaudal nucleus (VPLa), was significantly greater in ET patients (25.8 +/- 3.5 Hz) than in the PD (14.3 +/- 1.6 Hz; P < 0.01) and pain (16.1 +/- 1.5 Hz; P < 0.05) groups. Similar findings were obtained when the neurons were grouped according to their estimated locations in Voa/Vop and Vim of motor thalamus. These data provide support for the prediction of the classical pathophysiological model of PD and moreover suggest that pathophysiology in the cerebello-thalamo-cortical pathway may be a possible cause of tremor in ET patients.

Thalamic deep brain stimulation activates the cerebellothalamocortical pathway.

To investigate the mechanism of action of deep brain stimulation (DBS), the authors studied the effects of thalamic DBS on the cerebellothalamocortical (CTC) pathway. With DBS turned off, excitability of the CTC pathway was reduced. Turning DBS on resulted in facilitation of the CTC pathway. Therefore, thalamic DBS appears to activate rather than inhibit the target area.

Influence of thermal quenching on the thermostimulated processes in alpha-Al2O3. Role of F and F+ centres.

Anion deficient alpha-Al2O3 is highly sensitive to ionising radiations and is widely used as a thermoluminescence and optically stimulated luminescence dosemeter in environmental monitoring. Two types of alpha alumina were studied and it was observed that both were affected by thermal quenching of luminescence. This effect, which manifests itself by the decay of the TL response when the heating rate increases, can be described by the Mott-Seitz theory. It was observed that thermostimulated exoemission response increased when the heating rate increased, whereas thermostimulated conductivity remained constant. However, none of the available theories could explain the dependence of the F- centre emission on the heating rate. A model is proposed to describe simultaneously the various thermally stimulated processes.

Influence of the irradiation temperature on the dosimetric and high temperature TL peaks of Al2O3:C.

The TL glow curves of Al2O3:C crystals have been investigated as a function of the irradiation temperature. The nature of the observed TL peaks has been studied by optical annealing. The filling of traps was found strongly dependent on the irradiation temperature in the case of UV exposure, which has been explained by the temperature dependence of the photoionisation of F centres. This latter phenomenon could have a part in the luminescence quenching and UV bleaching of F centres.

Comparative studies on potato tuber development using an in vitro tuber induction system.

A method for synchronized in vitro tuber induction in a Hungarian cultivar of Solanum tuberosum designated "Keszthelyi 855" has been developed. It was shown that in this system tuberization and stolon elongation primarily depend on the level of sucrose in the medium. The cytokinin, 6-bensylaminopurine (BAP), also enhances the efficiency of tuber formation, however, only at sucrose concentration above 4% (w/v). The synchronized plant culture provided starting material for isolation of genes specifically expressed in tuberizing Solanum species during the early stage of tuber development. In comparison with the non-tuberizing Solanum brevidens, three types of specific transcripts have been obtained by differential screening. Based on DNA sequence analysis the genes isolated code for the major tuber proteins, patatin and proteinase inhibitors.

Starch synthesis, and tuber storage protein genes are differently expressed in Solanum tuberosum and in Solanum brevidens.

Studying in vitro stem cuttings of Solanum tuberosum induced for tuberization and those of a non-tuberizing Solanum species, differences both in morphology and in gene expression were detected. Stolon formation essentially depended on light while tuberization was triggered by the elevated level of sucrose in the medium. Genes involved in starch synthesis were induced by sucrose in both species, however, starch granules were detected only in potato. A new tuber specific cDNA clone, GM7, encoding a putative metallocarboxypeptidase inhibitor and the cDNA of a proline rich cell wall protein with S. brevidens specific expression were isolated by differential screening. Sucrose mediated transcription of the tuber storage proteins like patatin and proteinase inhibitors (Kunitz-type, winI, GM7) failed in S. brevidens.

The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity.

Free radicals are thought to be involved in the onset of neuronal disturbances such as Alzheimer's disease, Parkinson's disease, and neuronal ceroid lipofuscinosis. It is also assumed that they play a role in cerebral injury caused by ischemia or trauma. Plasma and cerebrospinal fluid (CSF), Total (peroxyl) Radical-trapping Antioxidant Parameter (TRAP), and the known antioxidant components of TRAP, for instance, ascorbic acid, uric acid, protein sulfhydryl groups, tocopherol, and ubiquinol were analyzed and the remaining unidentified fragment was calculated in five healthy volunteers before and after 4 weeks of ascorbate and ubiquinone (Q-10) supplementation. In CSF, TRAP was significantly lower than in plasma. The major contributor to plasma's antioxidant capacity was uric acid (UA), whereas in CSF it was ascorbic acid (AA). In CSF, AA concentrations were four times higher than in plasma. Oral supplementation of AA (500 mg/d first 2 weeks, 1,000 mg/d following 2 weeks) and Q-10 (100 mg/d first 2 weeks, 300 mg/d following 2 weeks) induced a significant increase in plasma AA and Q-10. Surprisingly, in spite of the high lipophilicity of Q-10, its concentration did not change in CSF. The supplementation of AA increased its concentration in CSF by 28% (p < .05). However, the increase in AA did not result in an increase in CSF TRAP. This indicates that AA had lost one-third of its radical trapping capacity as compared to that in plasma. The facts that AA is the highest contributor to CSF TRAP and its effect on TRAP is concentration dependent could indicate that the peroxyl radical-trapping capacity of CSF is buffered by AA.

The medical-psychiatric unit: a novel psychosomatic approach.

A retrospective chart review of 600 general hospital patients, of whom 200 had been admitted to a medical-psychiatric unit, 200 to a conventional psychiatric unit and 200 to medical-surgical units, and for whom psychiatric consultation had been requested, disclosed significant differences in the patient populations of these services. The data suggest that consultation psychiatry and medical-psychiatric units serve two different subgroups of patients with combined physical and psychiatric illness. A comprehensive model of clinical psychosomatic medicine encompassing consultation psychiatry, liaison psychiatry, medical-psychiatric units and after-care medical-psychiatric clinics, is proposed.