Zolpidem therapy in dystonia

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Enhancement of the Bonding Durability of Resin-based Cement to Lithium Disilicate Glass Ceramics Using Surface Modification Methods

The aim of the present study was undertaken to investigate the effects of several surface modification methods applied to lithium disilicate glass ceramics (LDCs) on their bonding durability with resin-based cement. The LDC specimens were sectioned using a low-speed diamond cutting machine, crystallized by heating in a furnace, and then subjected to several surface modification treatments such as acid etching, sandblasting, or silica coating with silane coupling agents. Then, a cylindrical titanium with a sandblasted surface was bonded to the surface-modified LDC specimens using resin-based cement. After being either stored in water at 37°C for 24h or subjected to 10,000 and/or 30,000 thermal cycles, the specimens were subjected to a shear bond strength test using a universal testing machine. The surface-modified LDC specimens obtained by combining blasting and silica coating modification treatments showed excellent durability, similar to that of acid-etched specimens. For safer laboratory practice, we recommend using the silica coating method for LDCs prior to applying silane coupling agents

Microscopic Temperature Control Reveals Cooperative Regulation of Actin–Myosin Interaction by Drebrin E

胎児の神経を形作る仕組みは精密な温度センサー --母体の体温維持が神経の成熟に重要であることを示唆--. 京都大学プレスリリース. 2021-11-10.Drebrin E is a regulatory protein of intracellular force produced by actomyosin complexes, that is, myosin molecular motors interacting with actin filaments. The expression level of drebrin E in nerve cells decreases as the animal grows, suggesting its pivotal but unclarified role in neuronal development. Here, by applying the microscopic heat pulse method to actomyosin motility assay, the regulatory mechanism is examined from the room temperature up to 37 °C without a thermal denaturing of proteins. We show that the inhibition of actomyosin motility by drebrin E is eliminated immediately and reversibly during heating and depends on drebrin E concentration. The direct observation of quantum dot-labeled drebrin E implies its stable binding to actin filaments during the heat-induced sliding. Our results suggest that drebrin E allosterically modifies the actin filament structure to regulate cooperatively the actomyosin activity at the maintained in vivo body temperature

Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes

Astrocytes exert neuroprotective effects through production of antioxidant molecules and neurotrophic factors. A recent study showed that stimulation of astrocyte serotonin 1A (5-HT1A) receptors promotes astrocyte proliferation and upregulation of the antioxidant molecules metallothionein (MT)-1,2, which protect dopaminergic neurons against oxidative stress. Rotigotine, an anti-parkinsonian drug, can bind to dopamine and 5-HT1A receptors. In this study, we examined neuroprotective effects of rotigotine in models of Parkinson's disease and involvement of astrocyte 5-HT1A receptors in neuroprotective effects of rotigotine against dopaminergic neurodegeneration. Rotigotine increased the number of astrocytes and MT-1,2 expression in cultured astrocytes. Pretreatment with conditioned media from rotigotine-treated astrocytes significantly inhibited 6-hydroxydopamine (6-OHDA)-induced dopaminergic neurotoxicity. These effects were completely blocked by a 5-HT1A antagonist or MT-1,2 specific antibody. Subcutaneous administration of rotigotine increased MT-1,2 expression in striatal astrocytes and prevented reduction of dopaminergic neurons in the substantia nigra of a 6-OHDA-lesioned mouse model of Parkinson's disease. These effects were blocked by co-administration with a 5-HT1A antagonist. These results suggest that rotigotine exerts neuroprotective effects through upregulation of MT expression in astrocytes by targeting 5-HT1A receptors. Our findings provide a possible therapeutic application of rotigotine to prevent dopaminergic neurodegeneration in Parkinson's disease

New Yorker in Englamd:In Search of Antiquity in The Sketch-Book

In The Sketch-Book, Washington Irving represents England as the country founded on its great traditions in spite of the social and cultural changes that overtook the conventional social order in the early 19th century. As demonstrated in his essays on Indian tribes, Irving feels a deep reverence for them, and laments the disappearance of their culture. The consciousness that his own country has lost the link with the past strengthens his yearning for old English customs. Although William Hazlitt regards Irving\u27s applause for the preservation of English antiquity as his wily strategy for acquiring the conservative British readership, it seems that Irving\u27s sense of rootlessness as an American reflects the fundamental attitude of this book

Rethinking the discovery function of proof within the context of proofs and refutations

Proof and proving are important components of school mathematics and have multiple functions in mathematical practice. Among these functions of proof, this paper focuses on the discovery function that refers to invention of a new statement or conjecture by reflecting on or utilizing a constructed proof. Based on two cases in which eighth and ninth graders engaged in proofs and refutations, we demonstrate that facing a counterexample of a primitive statement can become a starting point of students’ activity for discovery, and that a proof of the primitive statement can function as a useful tool for inventing a new conjecture that holds for the counterexample. An implication for developing tasks by which students can experience this discovery function is mentioned.ArticleInternational Journal of Mathematical Education in Science and Technology. 45(7):1053-1067 (2014)journal articl

Discovery of the First Low-Luminosity Quasar at z > 7

We report the discovery of a quasar at z = 7.07, which was selected from the deep multi-band imaging data collected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. This quasar, HSC J124353.93+010038.5, has an order of magnitude lower luminosity than do the other known quasars at z > 7. The rest-frame ultraviolet absolute magnitude is M1450 = -24.13 +/- 0.08 mag and the bolometric luminosity is Lbol = (1.4 +/- 0.1) x 10^{46} erg/s. Its spectrum in the optical to near-infrared shows strong emission lines, and shows evidence for a fast gas outflow, as the C IV line is blueshifted and there is indication of broad absorption lines. The Mg II-based black hole mass is Mbh = (3.3 +/- 2.0) x 10^8 Msun, thus indicating a moderate mass accretion rate with an Eddington ratio 0.34 +/- 0.20. It is the first z > 7 quasar with sub-Eddington accretion, besides being the third most distant quasar, known to date. The luminosity and black hole mass are comparable to, or even lower than, those measured for the majority of low-z quasars discovered by the Sloan Digital Sky Survey, and thus this quasar likely represents a z > 7 counterpart to quasars commonly observed in the low-z universe.Comment: Accepted for publication in ApJ Letter

Mixed alkali-ion transport and storage in atomic-disordered honeycomb layered NaKNi2TeO6

Honeycomb layered oxides constitute an emerging class of materials that show interesting physicochemical and electrochemical properties. However, the development of these materials is still limited. Here, we report the combined use of alkali atoms (Na and K) to produce a mixed-alkali honeycomb layered oxide material, namely, NaKNi2TeO6. Via transmission electron microscopy measurements, we reveal the local atomic structural disorders characterised by aperiodic stacking and incoherency in the alternating arrangement of Na and K atoms. We also investigate the possibility of mixed electrochemical transport and storage of Na+ and K+ ions in NaKNi2TeO6. In particular, we report an average discharge cell voltage of about 4 V and a specific capacity of around 80 mAh g–1 at low specific currents (i.e., < 10 mA g–1) when a NaKNi2TeO6-based positive electrode is combined with a room-temperature NaK liquid alloy negative electrode using an ionic liquid-based electrolyte solution. These results represent a step towards the use of tailored cathode active materials for “dendrite-free” electrochemical energy storage systems exploiting room-temperature liquid alkali metal alloy materials