Frequency of non-generalized tonic clonic seizures in a referral population of dogs.

Absence seizures are a type of generalized onset seizure associated in humans with brief activity interruptions, unresponsiveness and staring. Absence seizures are infrequently reported in veterinary patients, visually indistinguishable from focal seizures, and so may be grouped as non-generalized tonic clonic seizures (non-GTCS). The objective of this retrospective study was to provide a preliminary understanding of the frequency of non-GTCS in dogs and estimate its prevalence by evaluating the distribution of seizure types presented to a referral hospital over 4 years (May 2017-April 2021), as determined from the medical record history and electroencephalography (EEG) diagnostic testing where available. A total of 528 cases were included via a medical record search for dogs with epilepsy and/or seizures presented to the neurology or emergency services. Cases were categorized into seizure types based on reported clinical signs. Each year, 53-63 % of seizure cases were described as generalized tonic clonic seizures (GTCS), 9-15 % GTCS with additional events and 29-35 % suspected non-GTCS. EEG confirmed absence seizures in 12 of 44 EEGs, 5 cases having a history of GTCS and seven without prior GTCS. This preliminary study suggests that non-GTCS may be relatively common as one third of seizure cases in the referral population presented with non-GTCS clinical signs. Prospective studies using EEG are merited to definitively determine the prevalence of these different seizure types in dogs. Acknowledging the impact of these seizures will improve awareness, aiding veterinarians in their recognition, diagnosis and potential treatment options.

NOVEL ANALYTICAL STUDY FOR REACTION INTERMEDIATES IN THE PRIMARY RADIATION INTERACTION OF DNA USING A SYNCHROTRON RADIATION-INDUCED LUMINESCENCE SPECTROSCOPY.

To identify the precise molecular processes to induce DNA lesions, we attempt a novel spectroscopy of X-ray induced luminescence (XIL) using soft X-ray synchrotron radiation, which is a non-destructive analysis of the reaction intermediates in the elementary reaction pathway of damage induction and self-organized restoration. Using a liquid micro-jet technique to introduce aqueous samples in a vacuum chamber, we measure UV-visible luminescence from nucleotide solution as a function of the soft X-ray energy from the nitrogen to oxygen K-edge region. The XIL intensities for the nucleotide solutions are significantly enhanced in the soft X-ray region (410-530 eV) which is ascribed to the K-shell excitation/ionization of nitrogen atoms in the nucleobases. Furthermore, the XIL spectra do not show any signature of X-ray absorption near-edge structure (XANES) of the nucleobases. This is because the luminescence intensities collected from the integral area of the micro-jet only reflect the quantum yield of luminescence of the absorbed X-ray into UV-visible light irrespective of the absorption cross sections, i.e. of XANES. Thus the present result is the first evidence of luminescence as a result of X-ray absorption of aqueous nucleotides.

First Determination of the Level Structure of an sd-Shell Hypernucleus, _{Λ}

We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}→1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}→1/2^{+}), E1(1/2^{-}→1/2^{+}), and E1(1/2^{-}→3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.

Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima Prefecture: The Misho Project.

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.

Unpaired electron species in thin films of calf-thymus DNA molecules induced by nitrogen and oxygen K-shell photoabsorption.

The mechanism of DNA modification induced by K-shell photoabsorption of nitrogen and oxygen atoms was investigated by electron paramagnetic resonance and x-ray absorption near edge structure measurements of calf thymus DNA. A g factor of 2.000 for the unpaired electron species, which only arises during irradiation, was measured. The EPR intensities for DNA zwere twofold times larger than those estimated based on the photoabsorption cross section. This suggests that the DNA film itself forms unpaired electron species through the excitation of enhanced electron recapturing, known as the postcollision interaction process.

Involvement of dopamine D3 and D4 receptors in the discriminative stimulus properties of cocaine in the rat.

The present study was carried out to determine the involvement of dopamine receptor subtypes D3 and D4, in the discriminative stimulus effects of cocaine in the rats trained to discriminate 10 mg/kg of cocaine from vehicle. The discriminative stimulus effects of cocaine (1-10 mg/kg) were dose-dependent. The dopamine D2 receptor agonist bromocriptine (1.25-20 mg/kg) and the dopamine D3 receptor agonist R(+)-7-OH-DPAT (0.0001-0.3 mg/kg) produced cocaine (10 mg/kg)-like discriminative stimulus effects. Both the dopamine D3 receptor antagonist GR103691 (1 mg/kg) and the dopamine D4 receptor antagonist L745870 (1 mg/kg) partially antagonized the discriminative stimulus effects of cocaine (10 mg/kg) and the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). L745870 (0.001 mg/kg) inhibited the antagonistic effects of GR103691 (1 mg/kg) on the discriminative stimulus effects of cocaine (10 mg/kg), whereas the drug (0.001 mg/kg) enhanced the antagonistic effects of GR103691 (1 mg/kg) on the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). GR103691 (1 mg/kg) in combination with L745870 (0.001 mg/kg) did not markedly affect the cocaine (10 mg/kg)-like discriminative stimulus effects of bromocriptine (20 mg/kg). These results suggest that the discriminative stimulus effects of cocaine are different from the cocaine-like discriminative stimulus effects of bromocriptine or R(+)-7-OH-DPAT, in terms of dopamine D3 and D4 receptors.

Production of the neutron-rich hypernucleus 10LambdaLi in the (pi-,K+) double charge-exchange reaction.

In order to produce a neutron-rich Lambda hypernucleus for the first time, we carried out an experiment by utilizing the (pi-,K+) double charge-exchange reaction on a 10B target. We observed the production of a 10LambdaLi hypernucleus. The cross section for the Lambda bound region was found to be 11.3+/-1.9 nb/sr with the 1.2 GeV/c incident momentum, which is compared with the 10LambdaB hypernucleus production cross section, 7.8+/-0.3 microb/sr, in the (pi+,K+) reaction with a 1.05 GeV/c incident momentum beam.

Hypernuclear fine structure in (16)(Lambda)O and the LambdaN tensor interaction.

We have observed two gamma-ray transitions in (16)(Lambda)O from the 6.6 MeV excited 1(-)(2) state to both ground-state spin-doublet members (1(-)(1),0(-)) by the (K-,pi(-)gamma) reaction. We have obtained the ground-state doublet spacing to be 26.4+/-1.6(stat)+/-0.5(syst) keV and the excitation energy of the 1(-)(2) state to be 6561.7+/-1.1(stat)+/-1.7(syst) keV. The ground-state doublet spacing provides a small but nonzero strength of the tensor interaction between a Lambda and a nucleon. This is the first experimental result on the LambdaN tensor interaction.

Effects of L-745,870, a dopamine D4 receptor antagonist, on naloxone-induced morphine dependence in mice.

We examined whether dopamine D4 receptor is involved in morphine dependence in mice. Mice pretreated with morphine (10 mg/kg, s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing, and forepaw tremors after the administration of naloxone (2 mg/kg, i.p.) on the sixth day. Such mice exhibited significant elevation of cAMP levels in the thalamus compared with the control mice. L-745,870 (1 mg/kg, i.p.), a selective dopamine D4 receptor antagonist, pretreated with morphine on the sixth day, significantly attenuated the severity of withdrawal syndromes and the increase in cAMP levels after the administration of naloxone. These results suggest that (1) the elevation of cAMP levels is involved in the expression of morphine-induced withdrawal syndromes, and (2) dopamine D4 receptor antagonists inhibit the expression of morphine-induced withdrawal syndromes accompanied with biochemical changes in mice. Furthermore, dopamine D4 receptor antagonists may be useful drugs for attenuating the expression of morphine dependence.

Tail-swing behavior: a novel animal model for anxiety.

The present study was designed to examine the effects of diazepam, nitrazepam, desipramine and haloperidol on tail-swing behavior in mice and to characterize the effects of diazepam. Mice were suspended with rubber bands tied around their upper bodies in order to force their heads upwards. The duration of tail-swing behavior was then measured. Diazepam (0.3 and 1 mg/kg) and nitrazepam (0.3 and 1 mg/kg) significantly depressed tail-swing behavior, while they did not affect ambulation or muscle tone. In contrast, desipramine (10-30 mg/kg) did not affect tail-swing behavior, but at doses of 17.5 and 30 mg/kg produced a marked reduction in ambulation. Haloperidol (0.15 mg/kg) significantly decreased both tail-swing behavior and ambulation. The benzodiazepine receptor antagonist flumazenil (1 and 10 mg/kg), the benzodiazepine receptor inverse agonist beta-carboline-3-carboxylic acid N-methylamide (beta-CCM; 3 mg/kg) and the GABA(A) receptor antagonist bicuculline (3 mg/kg) reversed the effects of diazepam (1 mg/kg) on tail-swing behavior, although administered alone they failed to influence such behavior. These results suggest that anxiety and/or fear are responsible for tail-swing behavior.

Effects of U-50,488H, a kappa-opioid receptor agonist, on the learned helplessness model of depression in mice.

We investigated the effects of U-50,488H, a kappa-opioid receptor agonist, on the learned helplessness model of depression in mice. Mice pre-exposed to inescapable electric footshock were treated with U-50,488H. Stimulation of the kappa-opioid receptor by U-50,488H (10 mg/kg/day, i.p.) attenuated the escape failure induced by pre-exposure to shock. This attenuation by U-50,488H was blocked by MR2266 (10 mg/kg/day, s.c.), an opioid receptor antagonist. These results suggest that the kappa-opioid system plays an important role in the learned helplessness depression in mice.

Endomorphin-1 improves scopolamine-induced impairment of short-term memory via mu1-opioid receptor in mice.

The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.

[Gly(14)]-Humanin improved the learning and memory impairment induced by scopolamine in vivo.

Humanin is a very recently discovered 24 amino acid linear polypeptide, which protects against cell death induced by either familial Alzheimer's disease mutant of amyloid precursor protein, presenilin-1 or presenilin-2 in vitro. However, it has remained uncertain whether humanin is a useful drug for the animal model of learning and memory deficit. In this study, we evaluated the effects of [Gly(14)]-humanin, a more potent humanin analogue, on the scopolamine HBr (1 mg kg(-1) s.c.)-induced impairment of spontaneous alternation behaviour in the Y-maze, an index of short-term memory in mice. [Gly(14)]-Humanin (1000 pmol 5 microl(-1) i.c.v.) reversed the impairment without affecting the number of arm entries. These results suggest that (I) [Gly(14)]-humanin is a beneficial drug for the impairment of learning and memory and (II) it modulates the learning and memory function mediated via cholinergic systems in mice.

Endomorphins 1 and 2, endogenous mu-opioid receptor agonists, impair passive avoidance learning in mice.

The effects of intracerebroventricular administration of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, on passive avoidance learning associated with long-term memory were investigated in mice. Endomorphin-1 (10 and 17.5 microg) and endomorphin-2 (17.5 microg) produced a significant decrease in step-down latency in a passive avoidance learning task. beta-Funaltrexamine (5 microg) almost completely reversed the endomorphin-1 (17.5 microg)- and endomorphin-2 (17.5 microg)-induced shortening of step-down latency, although neither naltrindole (4 ng) nor nor-binaltorphimine (4 microg) produced any significant effects on the effects of endomorphins 1 and 2. These results suggest that endomorphins 1 and 2 impair long-term memory through the mediation of mu-opioid receptors in the brain.

Is rabbit CLCA1 related to the basolateral Ca2+ -dependent Cl- channel of gastric parietal cells?

An expression of mRNA coding the calcium-activated Cl- channel-1 (CLCA1) in rabbit gastric parietal cells was examined to verify the possibility that the CLCA1 mediates housekeeping Cl- channels in the basolateral membrane. In whole-cell voltage-clamp experiments of rabbit parietal cells, A23187 (2 microM), a Ca2+ ionophore, activated the basolateral Cl- channels. The partial cDNA fragment of rabbit CLCA1 could be amplified from the total RNA of tracheal epithelium. A Northern blot analysis showed that rabbit CLCA1 mRNA of 3.4 kb is highly expressed in the tracheal epithelium, but not in the gastric parietal cells. Even in a more sensitive detection of rabbit CLCA1 mRNA by RT-PCR, no signal could be observed in the gastric parietal cells. These results suggest that the CLCA1 protein may not be a subunit of the housekeeping Ca2+ -dependent Cl- channel in the basolateral membrane of rabbit gastric parietal cells.

Morphine tolerance and dependence in the nociceptin receptor knockout mice.

Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor knockout mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor knockout mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor knockout mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor knockout mice, the jumping signs in the nociceptin receptor knockout mice were less severe than those in wild-type mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor knockout mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor knockout mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.

Effects of endomorphins-1 and -2, endogenous mu-opioid receptor agonists, on spontaneous alternation performance in mice.

The effects of intracerebroventricular (i.c.v.) administration of endomorphins-1 and -2, endogenous mu-opioid receptor agonists, on the spontaneous alternation performance associated with spatial working memory were investigated in mice. Endomorphin-1 (10 and 17.5 microg) and endomorphin-2 (10 microg) produced a significant decrease in percent alternation without affecting total arm entries. beta-Funaltrexamine (5 microg) almost completely reversed the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced decrease in percent alternation, although neither naltrindole (4 ng) nor nor-binaltorphimine (4 microg) produced any significant effects on alternation performance. These results suggest that endomorphins impair spatial working memory through the mediation of mu-opioid receptors.

[Influence of stress on learning and memory].

This paper describes the influence of stress on learning and memory. The mice receiving inescapable electroshock fail to perform the active conditioned avoidance response of lever-pressing. This is called learned helplessness, which is ameliorated by treatment with antidepressants including one of the selective serotonin reuptake inhibitors (SSRIs). It is of particular interest that posttraumatic stress disease (PTSD) accompanied by memory impairment could be improved by treatment with SSRIs. The different kinds of stress including ischemia, footshock, psychological stress, and forced swimming influence learning and memory as indexed by spontaneous alternation performance as well as passive avoidance learning. In addition, a variety of stresses influence the activity of hormones and neurotransmitters like monoamines, neuropeptides, and excitatory amino acids resulting in changes in learning and memory. Finally, the accumulation of data is necessary to clarify the exact mechanism of stress on learning and memory.

Chimeric cytokine receptor can transduce expansion signals in interleukin 6 receptor alpha (IL-6Ralpha)-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors.

We generated transgenic mice expressing chimeric receptors, which comprise extracellular domains of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor and transmembrane and cytoplasmic domains of the mouse leukemia inhibitory factor receptor. In suspension cultures of lineage-negative (Lin(-)), 5-fluorouracil-resistant bone marrow cells of the transgenic mice, a combination of hGM-CSF and stem cell factor (SCF) induced exponential expansions of mixed colony-forming unit. The combination of hGM-CSF and SCF was effective on enriched, Lin(-)Sca-1(+)c-kit(+) progenitors and increased either mixed colony-forming unit or cobblestone area-forming cells. In case of stimulation with hGM-CSF and SCF, interleukin-6 (IL-6) and SCF, or IL-11 and SCF, the most efficient expansion was achieved with hGM-CSF and SCF. When Lin(-)Sca-1(+)c-kit(+)CD34(-) further enriched progenitors were clone sorted and individually incubated in the presence of SCF, hGM-CSF stimulated a larger number of cells than did IL-6, IL-6 and soluble IL-6 receptor (IL-6R), or IL-11. These data suggest the presence of IL-6Ralpha-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors. Such primitive progenitors are equipped with signal transduction molecules and can expand when these chimeric receptors are genetically introduced into the cells and stimulated with hGM-CSF in the presence of SCF.

Ameliorative effects of tachykinins on scopolamine-induced impairment of spontaneous alternation performance in mice.

The present study was designed to clarify whether opioid neuronal systems are involved in the beneficial effects of tachykinins such as the neurokinin NK1 receptor agonist, substance P (SP), the neurokinin NK2 receptor agonist, neurokinin A (NKA), and the neurokinin NK3 receptor agonist, senktide, on the scopolamine-induced impairment of spontaneous alternation performance in mice. Intracerebroventricular injections of SP (0.1 microgram), NKA (0.3 microgram) and senktide (3 ng) inhibited the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without influencing total arm entries, indicating the antiamnesic effects of tachykinins. Furthermore, the inhibitory effects of SP, but not those of NKA or senktide, were almost completely reversed by pretreatment with naloxone (1 mg/kg). However, the effects of SP on the scopolamine-induced impairment of spontaneous alternation performance were not influenced by pretreatment with the mu-opioid receptor antagonist, beta-funaltrexamine (5 micrograms), the delta-opioid receptor antagonist, naltrindole (4 ng), and the kappa-opioid receptor antagonist, nor-binaltorphimine (4 micrograms). These findings suggest that the effects of SP, unlike those of NKA or senktide, on the scopolamine-induced impairment of spontaneous alternation performance associated with spatial working memory are not mediated simply via a single type of opioid receptors, such as mu, delta or kappa.