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Abstract Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague–Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8–11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon.

Abstract Belt electrode skeletal muscle electrical stimulation (B-SES) can simultaneously contract multiple muscle groups. Although the beneficial effects of B-SES in clinical situations have been elucidated, its molecular mechanism remains unknown. In this study, we developed a novel rodent B-SES ankle stimulation system to test whether low-frequency stimulation prevents denervation-induced muscle atrophy. Electrical stimulations (7‒8 Hz, 30 min) with ankle belt electrodes were applied to Sprague–Dawley rats daily for one week. All animals were assigned to the control (CONT), denervation-induced atrophy (DEN), and DEN + electrical stimulation (ES) groups. The tibialis anterior (TA) and gastrocnemius (GAS) muscles were used to examine the effect of ES treatment. After seven daily sessions of continuous stimulation, muscle wet weight (n = 8–11), and muscle fiber cross-sectional area (CSA, n = 4–6) of TA and GAS muscles were lower in DEN and DEN + ES than in CON. However, it was significantly higher in DEN than DEN + ES, showing that ES partially prevented muscle atrophy. PGC-1α, COX-IV, and citrate synthase activities (n = 6) were significantly higher in DEN + ES than in DEN. The mRNA levels of muscle proteolytic molecules, Atrogin-1 and Murf1, were significantly higher in DEN than in CONT, while B-SES significantly suppressed their expression (p

Distigmine bromide (3, 3′-[hexamethylenebis (methyliminocarbonyloxy)] bis (1-methylpyridinium) dibromide), an acetylcholinesterase (AChE) inhibitor, produced a time-dependent and dose-dependent increase in acetylcholine (ACh) levels in the medial prefrontal cortex of rats. The overt cholinergic behaviours, such as tremor, fasciculation and lacrimation, were also elicited by distigmine bromide. The onset and duration of these behaviours were reflected in the microdialysis data showing that distigmine bromide enhances cholinergic neurotransmission in rat brain. The dose of distigmine bromide eliciting increase in ACh in the medial prefrontal cortex of rats correlated well with its dose for the induction of the cholinergic behaviours. Furthermore, distigmine bromide was an equipotent inhibitor of AChE and butyrylcholinesterase (BuChE) activities in the present study. From these findings, it is suggested that distigmine bromide may produce centrally mediated behavioural signs by increasing the ACh levels in the brain, resulting from its AChE and BuChE inhibitions. [ABSTRACT FROM AUTHOR]

γ-Hexachlorocyclohexane (γ-HCH)-degrading strain, Sphingobium sp. TA15, was newly isolated from an experimental field soil from which the archetypal γ-HCH-degrading strain, S. japonicum UT26, was isolated previously. Comparison of the complete genome sequences of these 2 strains revealed that TA15 shares the same basic genome backbone with UT26, but also has the variable regions that are presumed to have changed either from UT26 or from a putative common ancestor. Organization and localization of lin genes of TA15 were different from those of UT26. It was inferred that transposition of IS6100 had played a crucial role in these genome rearrangements. The accumulation of toxic dead-end products in TA15 was lower than in UT26, suggesting that TA15 utilizes γ-HCH more effectively than UT26. These results suggested that genome evolution related to the γ-HCH metabolic function in the soil microbial population is ongoing., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted., Methods: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE., Results: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified., Conclusions: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

The electrical conductivity of donor-doped BaTiO 3 thermistor ceramics with excessive BaO revealing a reduction-persistent PTCR effect has been carefully examined depending on materials' composition and oxygen partial pressure at moderate temperatures between 973 and 1273 K. This thermal regime represents the range which is relevant for the realization of insulating grain boundaries in these electrically inhomogeneous ceramic materials through reoxidation. Based on the experimental results strong evidence for a general correlation between the PTCR characteristics, DC-conductivity and the herewith associated defect chemistry significant to thermistor applications is presented for the system (Ba, La) m TiO 3 , where m designates the BaO-excess (m≥ 1). Nominal compositions with a relatively low (Ba + La)/Ti ratio m only show a rather poor PTCR effect and an overall donor-type response in conductivity can be observed at all levels of oxygen partial pressure considered in the present study. With increasing (Ba + La)/Ti ratio m the nonlinear resistivity jump with increasing temperature strongly improves and the acceptor-type behaviour seems to dominate the total conductivity at partial pressures of oxygen above approximately 10 -6 MPa. This result for compositions with high BaO-excess can be understood by the local formation of point defect associates in the grain boundary regions that consist of both acceptor-type titanium vacancies and donor-type oxygen vacancies. Their origin is attributed to the preferential local incorporation of excessive BaO into the BaTiO 3 lattice at the intergranular interfaces.

We retrospectively studied early clinical results of PAS-Port (PP) system. Fifty patients who underwent coronary artery bypass surgery with saphenous vein graft (SVG) from April 2004 to May 2005 were enrolled in this study. PP was tried for 36 SVGs in 32 patients. In 2 patients, SVG 4.0 mm in diameter could not be loaded into the device. In other 2 patients, anastomosis with PP was failed and followed by hand-sewing under aortic clamp or with Heartstring. Anastomosis with PP was successfully completed for 34 SVGs in 30 patients (group P) and conventional hand-sewing was performed for 23 SVGs in 20 patients (group C). The target vessels for SVG were similar between the 2 groups. No complication occurred in the use of PP. Postoperative angiography before discharge was performed for 31 SVGs in 27 patients (90.0%) in group P and 20 SVGs in 17 patients (85.0%) in group C. The patency rate of SVG was 96.8% in group P and 100% in group C. In conclusion, early results of PP were satisfactory compared with those of conventional hand-sewing. Severely sclerotic aorta and oversized SVG should be excluded because of possibility for incomplete deployment of the inner flange in PP.

Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)-agonistic-like effects in behavioral pharmacology test. However, there is to date no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The object of the present study was to assess the effects of mirtazapine on dialysate levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In vivo microdialysis was used to study the effects of mirtazapine on extracellular dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on extracellular dopamine level increased by mirtazapine in the rat prefrontal cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely moving rats without modifying those of 5-HT. In the presence of the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence of mirtazapine on cortical levels of dopamine was markedly attenuated. These results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function.

The levels of tryptophan and the serotonin (5-HT) turnover were examined in various brain regions of rats after single or repeated treatment with the selective 5-HT uptake inhibitor, sertraline. A single administration of sertraline (10mg/kg, i.p.) increased tryptophan and 5-HT levels in all the brain regions investigated. The levels of 5-hydroxyindolacetic acid (5-HIAA) decreased in various brain regions. The 5-HIAA/5-HT ratio as turnover index was significantly decreased by a single administration of sertraline in all the brain regions investigated. Daily treatment with sertraline (10mg/kg) for 21 days did not affect tryptophan and 5-HT levels in various brain regions 1h after last injection. The 5-HT turnover was not changed in any of the brain regions investigated by a repeated administration of sertraline. In conclusion, the data show that the increase in tryptophan levels and the decrease in 5-HT turnover in rat brain are attenuated by repeated treatment of sertraline.

Risperidone (RIS) alone was administered to patients with neuroleptic-naïve, first-episode schizophrenia who visited the outpatient clinic of the Department of Psychiatry, Jikei University School of Medicine Hospital between April 1998 and December 2001, and the effectiveness of the drug in alleviating anxiety symptoms was prospectively examined. The study population comprised 42 patients (24 males and 18 females). Their mean age at first visit was 26.0 +/- 6.5 years, DUP (Duration of Untreated Psychosis) was 41.1 +/- 60.0 weeks, and the mean total BPRS (Brief Psychiatric Rating Scale) score at first visit was 60.5 +/- 8.5 points. The rating "effective" (a total BPRS score improvement at week 8 of 50% or more) was given to 32 out of the 42 patients (76.2%). Among these 32 patients, a 25% improvement in the PANSS (Positive and Negative Syndrome Scale) positive scale was achieved at 1. 53 +/- 0.72 weeks and a 50% improvement at 2.93 +/- 2.10 weeks, suggesting early onset of the effects of RIS. The present study focused on the anxiety complained of by some of the patients in whom treatment was rated as effective (increase of 2 points in anxiety BPRS score), dividing these patients into an anxiety group and a non-anxiety group. The anxiety group comprised 17 patients (53.1%). The anxiety observed during the course of treatment with RIS tended to develop early after the disappearance of positive symptoms. A comparison of demographic factors and GAF between the two groups revealed a significant difference in mean age at first visit, DUP and GAF score, the anxiety group tending to be younger, to have shorter DUP and to have social dysfunction compared to the non-anxiety group. Although it cannot be concluded that these anxiety symptoms are characteristic of risperidone, the effect of chemotherapy with other atypical antipsychotic drugs remains as an interesting theme for future investigation.

We report a case of serotonin syndrome in a patient being treated with paroxetine for depression. Despite prompt discontinuation of medication, his serotonin syndrome continued for 10 days before full consciousness was restored. The patient was a 48-year-old male with chief complaints of hypobulia and suicidal thoughts. He consulted as a psychiatric outpatient, and oral paroxetine 20 mg/day, etizolam 1.0 mg/day, and brotizolam 0.25 mg/day were immediately started. Upsurge of feeling and disinhibition state were noted the following day, then on treatment day 6 his condition deteriorated to substupor state and he was admitted for further treatment. On admission, change of mental condition (consciousness disturbance), perspiration, hyperreflexia, myoclonus and tremor were seen, and serotonin syndrome caused by paroxetine was suspected. Paroxetine was thus discontinued, and under intravenous drip his condition gradually improved. However, it was not until the 10th hospital day that he became fully alert. In examinations, no infectious, metabolic or organic diseases were detected. The patient's condition often improves with in 24 hours of discontinuation of the causative medication in serotonin syndrome. Symptoms continued for 10 days in this patient, however, perhaps because paroxetine was administered for 6 days before discontinuation. In addition, interaction with other medications may have occurred. Therefore, when serotonin syndrome is suspected, prompt discontinuation of the suspected causative medication, followed by close monitoring of the pharmacokinetics is warranted.

The effects of a selective 5-hydroxytryptamine (5-HT)1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), directly administered into the dorsal raphe nucleus (DR) on acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) of freely moving rats were investigated by using a microdialysis technique. 8-OH-DPAT (1.0 and 5.0 micrograms) administered into DR significantly increased extracellular ACh concentrations in mPFC in a dose-dependent manner with a maximal increase to 215% and 237% of basal level, respectively, whereas a 0.1 microgram dose of this drug failed to exert such an increase. The present study suggests that the stimulation of somatodendritic 5-HT1A autoreceptors in DR is involved in an enhancement in ACh release in mPFC.

The purpose of the present study was to clarify the stress-reducing effect of cigarette smoking and the involvement of other factors such as trait-anxiety on the above effect of smoking. The subjects were 32 smokers who met DSM-IV criteria for substance dependence and 16 nonsmokers. The smokers were randomly assigned to a smoking group or a sham-smoking group. Immediately after the subjects performed a laboratory task, the State-Trait-Anxiety Inventory was administered for evaluating the levels of state-anxiety and trait-anxiety. The subjects were required to smoke a cigarette in a smoking group, sham-smoke in a sham-smoking group, or take a rest in a nonsmokers's group. After that, the same inventory was again administered. The decrease of state-anxiety in a smoking group was significantly more marked in degree than in a sham-smoking group and was comparable to that in a nonsmokers' group. A stepwise regression analysis revealed that the trait-anxiety levels significantly contributed to a decrease of state-anxiety levels in a smoking group. The present study indicated that cigarette smoking exhibited a stress-reducing effect and that the trait-anxiety levels were related to the effect of smoking.

The biological rhythm of females is closely related to the menstrual cycle, and this rhythm is believed to influence circadian changes in body temperature. This study investigated and compared the patterns of circadian changes in the body temperature of healthy adult females and patients suffering from premenstrual syndrome or major depression. Body temperature was measured both rectally and sublingually in healthy subjects, and only sublingually in the patients. During the luteal phase in healthy adult females, both the average and lowest nocturnal body temperatures increased, the amplitude of the circadian changes decreased, and the times of the lowest and highest temperatures within a 24-hour period were delayed by 2-3 h. In the patients, the amplitude decreased during disease periods, especially in the follicular phase, whereas in the luteal phase, circadian changes showed great variation each day, although the decrease in amplitude was not as remarkable. The results show that (i) the biological rhythm of females is intrinsically unstable in the luteal phase, although this rhythm is stable in the follicular phase; and, (ii) symptoms were often aggravated with the decreases in amplitude experienced in the luteal phase.

A collimation system in single photon computed tomography (SPECT) induces blurring on reconstructed images. The blurring varies with the collimator aperture which is determined by the shape of the hole (its diameter and length), and with the distance between the collimator surface and the object. The blurring has shift-variant properties. This paper presents a new iterative method for correcting the shift-variant blurring. The method estimates the ratio of "ideal projection value" to "measured projection value" at each sample point. The term "ideal projection value" means the number of photons which enter the hole perpendicular to the collimator surface, and the term "measured projection value" means the number of photons which enter the hole at acute angles to the collimator aperture axis. If the estimation is accurate, ideal projection value can be obtained as the product of the measured projection value and the estimated ratio. The accuracy of the estimation is improved iteratively by comparing the measured projection vale with a weighted summation of several estimated projection value. The simulation results showed spatial resolution was improved without amplification of artifacts due to statistical noise.