Distinctions in burst spiking between thalamic reticular nucleus cells projecting to the dorsal lateral geniculate and lateral posterior nuclei in the anesthetized rat.

Thalamic cell activity is under a significant influence of inhibition from the thalamic reticular nucleus (TRN) that is composed of domains connected with first and higher order thalamic nuclei, which are thought to subserve transmission of sensory inputs to the cortex and cortico-thalamo-cortical transmission of cortical outputs, respectively. Provided that TRN cells have distinct activities along with their projections to first and higher order thalamic nuclei, TRN cells could shape cell activities of the two thalamic nuclei in different manners for the distinct functions. In anesthetized rats, visual response and spontaneous activity were recorded from TRN cells projecting to the dorsal lateral geniculate (first order) and lateral posterior (higher order) nuclei (TRN-DLG and TRN-LP cells), using juxta-cellular recording and labeling techniques. TRN-DLG cells had a higher propensity for burst spiking and exhibited bursts of larger numbers of spikes with shorter inter-spike intervals as compared to TRN-LP cells in both visual response and spontaneous activity. Sustained effects of visual input on burst spiking were recognized in recurrent activation of TRN-DLG but not of TRN-LP cells. Further, the features of burst spiking were related with the locations of topographically connected cell bodies and terminal fields. The difference in burst spiking contrasts with the difference between thalamic cells in the DLG and LP, which show low and high levels of burst spiking, respectively. The synergy between thalamic and TRN cell activities with their contrasting features of burst spiking may compose distinctive sensory processing and attentional gating functions of geniculate and extra-geniculate systems.

Sub-threshold cross-modal sensory interaction in the thalamus: lemniscal auditory response in the medial geniculate nucleus is modulated by somatosensory stimulation.

Recent studies have highlighted cross-modal sensory modulations in the primary sensory areas in the cortex, suggesting that cross-modal sensory interactions occur at early stages in the hierarchy of sensory processing. Multi-modal sensory inputs from non-lemniscal thalamic nuclei and cortical inputs from the secondary sensory and association areas are considered responsible for the modulations. On the other hand, there is little evidence of cross-sensory modal sensitivities in lemniscal thalamic nuclei. In the present study, we were interested in a possibility that somatosensory stimulation may affect auditory response in the ventral division (MGV) of the medial geniculate nucleus (MG), a lemniscal thalamic nucleus that is considered to be dedicated to auditory uni-modal processing. Experiments were performed on anesthetized rats. Transcutaneous electrical stimulation of the hindpaw, which is thought to evoke nociception and seems unrelated to auditory processing, modulated unit discharges in response to auditory stimulation (noise bursts). The modulation was observed in the MGV and non-lemniscal auditory thalamic nuclei such as the dorsal and medial divisions of the MG. The major effect of somatosensory stimulation was suppression. The most robust suppression was induced by electrical stimuli given simultaneously with noise bursts or preceding noise bursts by 10 to 20 ms. The results indicate that the lemniscal (MGV) and non-lemniscal auditory nuclei are subject to somatosensory influence. In everyday experience intense somatosensory stimuli such as pain interrupt our ongoing hearing or interfere with clear recognition of sound. The modulation of lemniscal auditory response by somatosensory stimulation may underlie such cross-modal disturbance of auditory perception as a form of cross-modal switching of attention.

Urinary biomarker of oxidative stress in patients with psoriasis vulgaris and atopic dermatitis.

BACKGROUND: The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine. OBJECTIVE: This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients. METHODS: Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker. RESULTS: Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level. CONCLUSIONS: Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.

Effects of magnetic fields on the accumulation of thiobarbituric acid reactive substances induced by iron salt and H(2)O(2) in mouse brain homogenates or phosphotidylcholine.

In this study, we examined the effects of magnetic fields (MFs) on the generation of thiobarbituric acid reactive substances (TBARS) in the mouse brain homogenates or phosphotidylcholine (PC) solution, incubated with FeCl(3) and/or H(2)O(2). Active oxygen species were generated and lipid peroxidation was induced in mouse brain homogenates by incubation with iron ions, resulting in the accumulation of TBARS. Lipid peroxidation was induced in PC by incubation with iron ions and H(2)O(2). Exposure to sinusoidal MFs (60 Hz, 0.2-1.2 mT), symmetric sawtooth-waveform MFs (50 Hz, 25-600 mT/s), rectangular MFs (1/0.4-1/16 Hz, 3.3 mT) and static MFs (1, 5-300 mT) had no effect on the accumulation of TBARS in brain homogenates induced by FeCl(3). In contrast, when the homogenates were incubated with FeCl(3) in static MFs (2-4 mT), the accumulation of TBARS was decreased. However, this inhibitory effect disappeared when EDTA was added to the homogenate and incubated with H(2)O(2). The accumulation of TBARS in PC solution incubated with FeCl(3) and H(2)O(2) was also inhibited by the static MF. These results indicate that only static MFs had an inhibitory effect on iron-induced lipid peroxidation and the effectiveness of this magnetic field on iron ion-induced active oxygen species generation is restricted to a so called 'window' of field intensity of 2-4 mT.

Detection and a possible mechanism of magnetic field effect on the crystal growth of sedimentary calcium carbonate.

Sedimentary calcium carbonate was grown at a physiological pH6.8 from a mixture of equivolume of 70 mM Ca(NO(3))(2) and 70 mM NaHCO(3) aqueous solution. The kinetics of the crystal growth was monitored by means of turbidity measurement. The apparent absorption is gradually increased with the elapsed time after the mixing and reaches its maximum at t(max). The average t(max) is significantly decreased from =467 s (for n=13 runs) to 408 s (n=13) by application of the static magnetic field (SMF) of H=400 mT to the precipitating solution. The application of SMF at 120 s later the mixing shows the same =396 s (n=9) as that of 408 s. It has been thus detected that the application of SMF is ineffective in the stage of the nucleation or the earlier stage of the crystal growth but effective in the Ostwald ripening stage of the growth nucleus or the later stage of the crystal growth where large numbers of the growing crystalline particles seem greater than a few hundred nanometers. A possible mechanism for the SMF effect is as follows. An ion escaping from the growing crystal surface with a certain 'migration velocity' due to a random walk process has significant probability to drift onto the identical surface or at least the identical crystal by means of Lorentz force, because the translational displacement of the crystal during a cycle of the cyclotron motion of the ion is smaller than the size of the growing crystal. This type of drift results in the suppression of re-dissolution of the ions on the growing surface and in the acceleration of the growth in the later stage of the crystal growth. The undetected SMF effect in the earlier stage of the crystal growth can be partly attributed to the re-dissolution due to the thermodynamic instability of the small nuclei which predominates over the presumable SMF effect. This can be partly ascribed to the large translational displacement of the small particle. The application of this mechanism to an oscillating magnetic field will predict the presence of a window for the frequency of the oscillating magnetic field.

An idea for a relation between the frequency and intensity of the optimal oscillating magnetic field for the magnetic effects.

An idea for a relation between the frequency and intensity of the optimal oscillating magnetic field for the magnetic effects has been presented. An estimated optimal frequency is about 150 Hz for a system containing ions of effective molecular weight of M approximately 100 under a square pulsing magnetic field of intensity H=1 mT.

The magnetic field effect affecting on the metallic chemical components of egg shell as demonstrated for breeding chicken.

The chickens were raised under fixation of the permanent magnet (80 mT) and the effect of extra magnetic field, which affects on the content of the several inorganic chemical elements of egg shell, was investigated by X-ray fluorescence spectroscopy. From 3 days after fixing the magnet, the relative concentration of Ca begun to increase. After 10 days, the relative contents of Ca were decreased, while conversely the contents of K were increased. Though there was a linear relationship between Ca content and P content in inner layer of chicken egg shell, the relationship was greatly hindered by applying the static magnetic field. The experimental result suggests that both Ca and K ion transport can be perturbed by addition of extra magnetic field in the incubation processes of chicken egg, and that Ca, P and K ions play the important role in egg shell formation.

Alternate magnetic fields potentiate monoamine oxidase activity in the brain.

Catecholamines and serotonin, which act as neurotransmitters and regulate blood circulation, are degraded by monoamine oxidase (MAO) [EC 1.4.3.4.] which exists two iso-enzymes named MAO-A and MAO-B. In this study, the effects of magnetic fields on MAO activity in the rat brain were examined. MAO-A activity was not changed in static magnetic fields (0.1-340 mT) or in 10-500 mT/s of alternate isosceles triangular magnetic fields (AITMF) (50 Hz). MAO-B activity was not changed in static magnetic fields (0.1-340 mT) and in 10, 34, 340, 95, 105, 110, and 340 mT/s of AITMF. However, it was increased to 114% in the 100 mT/s of AITMF. In 100 mT/s, Michaelis constant (K(m)) significantly decreased to 72%, suggesting that the affinity of the substrate to the enzyme also increased. These results indicate that only MAO-B was influenced by AITMF with 'active window' phenomenon, and suggest that AITMF might affect neural activity and hemodynamics by altering MAO-B.

Effects of an in vivo 60 Hz magnetic field on monoamine levels in mouse brain.

We studied the effects of electromagnetic fields (EMF) on mouse brain monoamine levels in models of (1) chronic exposure (7 days) of EMF (60 Hz, 10 Gauss) to mice in a vertical orientation, (2) prolonged chronic exposure (84 days) of EMF (60 Hz, 10 Gauss) to mice in a horizontal mode, (3) acute exposure (6 h) of EMF (60 Hz, 10 Gauss) to senescence accelerated mice (SAM-P8) at ages 1, 3, 6, 9 and 12 months in the horizontal mode, and (4) acute exposure (1 h) of EMF (60 Hz, 1, 3.3 and 10 Gauss) to restrained mice in the horizontal mode. No model except the restrained one changed their monoamine or metabolite levels by exposure to EMF. In the restrained group, dihydroxyphenylacetic acid (DOPAC) was significantly increased in the hippocampus (HP) and hypothalamus (HY), homovanillic acid (HVA) was significantly increased in HY, and 5-hydroxyindolacetic acid (5-HIAA) was significantly increased in HP and thalamus-midbrain (TM). None of these monoamine metabolite levels were changed when the mouse was restrained without EMF exposure. These results suggest that monoamine metabolism is influenced by EMF only when the exposure is in the same direction as the mouse position. Another possibility is that EMF enhances the restraint stress since stress is known to increase monoamine metabolism.

Continuous monitoring of nitric oxide release induced by cholecystokinin from the choledochal sphincter in guinea pigs.

BACKGROUND/AIMS: Many in vitro studies in the choledochoduodenal junction of the guinea pig have shown that cholecystokinin (CCK) contracts the sphincter of Oddi (SO). This study, using the choledochal sphincter of the guinea pig as the SO, evaluates the hypothesis that effects of CCK on the SO were mediated by nitric oxide (NO). METHODS: Spontaneous motility and effects of CCK on the choledochal sphincter were recorded using a constant-perfusion technique, and direct measurement of NO release using a specific NO sensor was performed at the same time. RESULTS: CCK-8 decreased the phasic wave amplitude of the choledochal sphincter, and increased NO release. N(G)-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, increased the spontaneous motility and converted the CCK-induced inhibitory response into an excitatory response. L-NAME also reduced NO release and abolished the increase of NO that had been caused by CCK-8. These effects were reduced by treatment with L-arginine (L-Arg). L-Arg application enhanced NO release, and recovered the increase of NO by CCK-8. CONCLUSION: These studies demonstrate that CCK relaxes the choledochal sphincter and this relaxant response is mediated by NO.

EPC-K1, a hydroxyl radical scavenger, prevents 6-hydroxydopamine-induced dopamine depletion in the mouse striatum by up-regulation of catalase activity.

We examined the effect of pretreatment with EPC-K1, a potent hydroxyl radical scavenger, on 6-hydroxydopamine (6-OHDA)-induced reduction of dopamine (DA) and its metabolites in the mouse striatum. EPC-K1 was mixed with diet (0.2%, wt/wt) for 1 or 2 weeks, and then 6-OHDA (60 microg in 2 microl of saline solution) was injected intracereberoventricularly. Mice continued to be fed EPC-K1-containing diet for another one week before they were sacrificed. The concentrations of DA and its metabolites in the striatum were measured by high performance liquid chromatography. 6-OHDA reduced the level of DA and its metabolites in the striatum. Pretreatment with EPC-K1 for 2 weeks, but not for 1 week, abrogated the neurotoxic effect of 6-OHDA on striatal concentrations of DA and its metabolites. Measurement of striatal concentrations of thiobarbituric acid reactive substances, glutathione, and malonaldehyde plus 4-hydroxynonenal, and the activities of superoxide dismutase and catalase in EPC-K1 treated mice showed an increase in catalase activity after 2 weeks of such treatment. No other changes in anti-oxidants levels were noted. Our results suggest that EPC-K1 counteracts the neurotoxicity of 6-OHDA by increasing catalase activities.

Effects of kynurenine metabolites on the electrocorticographic activity in the rat.

We examined the effects of kynurenine metabolites administered into the right cerebroventricle (1 micromol) on the electrocorticogram (ECoG) of rats to establish the role of kynurenines on brain function. Kynurenine, anthranilic acid, quinaldic acid, xanthurenic acid or 8-hydroxyquinaldic acid showed no effect on ECoG throughout the recording period of 4 hours. 3-Hydroxykynurenine had a transient suppressive effect on the ECoG, while kynurenic acid caused a slight suppression of ECoG activity. 3-Hydroxyanthranilic acid (3-OH-An), a metabolite of 3-hydroxykynurenine, induced spike discharges with a long latency (60-230 min). 3-OH-An is thought to be metabolized to o-aminophenol, 3-methoxyanthranilic acid, quinolinic acid, 2-ketoadipic acid and picolinic acid. Among 3-OH-An metabolites, only o-aminophenol induced spike discharges several minutes after administration, lasting for 60 min. On the other hand, quinolinic acid suppressed ECoG, though 3-methoxyanthranilic acid, 2-ketoadipic acid and picolinic acid had no effects on ECoG. These electrocorticographic findings suggest that 3-OH-An may induce spike discharges after it is metabolized in the brain to o-aminophenol.

Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation.

PURPOSE: Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of posttraumatic epilepsy. The involvement of iron-mediated oxygen free radical species and neuronal lipid peroxidation in iron-induced seizure has been suggested. Melatonin exerts free radical scavenging properties. In this study, we examined the protective effect of melatonin against iron-induced seizures. METHODS: We examined the protective effect of melatonin against in vitro iron-induced oxidative damage in homogenates from rat cerebral cortex, by measuring the concentration of thiobarbituric acid reactive substances (TBARS), as an index of oxidative damage. We also examined the effect of melatonin on the appearance of epileptic discharges in the EEG following injection of FeCl3 into the sensorimotor cortex in anesthetized rats, and by measuring the concentration of TBARS in the brain tissue. RESULTS: FeCl3 increased the concentration of TBARS in brain homogenates in a concentration-dependent manner, and melatonin reduced FeCl3-induced rise in TBARS in a dose-response fashion. Pretreatment with melatonin suppressed or delayed the development of FeCl3-induced epileptic discharges and decreased the concentration of TBARS in brain tissues. CONCLUSIONS: Our results suggest that iron ion generates oxygen free radical species that induce neuronal macromolecular peroxidation and seizure, and that melatonin inhibits iron-induced seizures by scavenging free radicals.

Free radicals in the cerebrospinal fluid are associated with neurological disorders including mitochondrial encephalomyopathy.

The free radical levels in the cerebrospinal fluid of 8 patients with neurological diseases and 9 undergoing lumbar anesthesia for surgery were measured. The ascorbate free radical level 10 min after lumbar puncture showed a positive correlation with the hydroxyl radical level. In the patient with mitochondrial encephalomyopathy, the levels of hydroxyl and ascorbate free radicals increased upon discontinuation of treatment and decreased upon its resumption, and the ascorbate free radical levels without therapy fell after lumbar puncture. The free radical levels in the cerebrospinal fluid may reflect the degree of oxidative stress in the central nervous system.