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Aim Balanced function of the orofacial muscles is important for normal occlusion and dentition; however, patients with malocclusion often present with myofunctional disorder (MFD). Myofunctional therapy (MFT) has received much attention as a method for reducing MFD. Moreover, prefabricated functional appliances (PFAs) have been developed as a method to eliminate abnormal muscle pressure and guide the tongue into the correct position. However, PFAs have disadvantages, such as poor intraoral retention, limited usage time due to discomfort and poor patient compliance, and changes in the axis of the mandibular anterior teeth. Therefore, this study aimed to develop a new custom-made splint-type orthodontic appliance with CAD/CAM technology. Moreover, we evaluated the characteristics of the appliance and conducted functional tests to determine the effects of the appliance on the orofacial muscles and the discomfort associated with its use. Materials and methods Twenty-five volunteers (nine females and 16 males; mean age 28.4 ± 3.4 years) with normal swallowing function were included in the study. Lip-closing strength (LCS), electromyogram during swallowing, oxygen saturation, and pulse rate were measured and compared when the appliance was not worn and when it was worn. In addition, tongue habits were evaluated, and the maximum tongue pressure was measured when the appliance was not worn. The subjects were asked to answer a questionnaire using a numerical rating scale (NRS) regarding discomfort when wearing the appliance. The evaluation items were swallowing difficulty, speaking difficulty, and breathlessness, which were rated on an 11-point scale ranging from 0 to 10. Statistical tests were conducted using IBM SPSS version 28.0.1 (IBM, Armonk, NY, USA) with the Shapiro-Wilk and Levene's test, followed by the Wilcoxon signed rank sum test. The significance level was set at α = 0.05. The measurement error for each measurement item was evaluated using an intraclass correlation coefficient. Results A new custom-made splint-type orthodontic appliance was fabricated for each subject. The fit and retention of the appliance in the mouth were good when fitted, and a comparison of the functional test measurements of 25 subjects with and without the appliance showed that the LCS decreased significantly (p<0.05) before and after wearing the appliance. However, no statistically significant differences were found for the other items. The Mann-Whitney U test regarding the effects of sex, previous orthodontic treatment, or MFT, and oral habits did not statistically significantly influence the effects of wearing the device. In the NRS results, "difficulty swallowing" was observed in half of the subjects, "difficulty breathing" was rarely observed, and "difficulty speaking" was observed in all subjects. Conclusions A novel custom-made splint-type orthodontic appliance was designed and fabricated using digital workflow and 3D printing technology. This appliance was designed to correct oral habits and was made from a new material classified as a class II medical appliance according to the international harmonized classification., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kujirai et al.)

Malignant meningioma has a poor prognosis and there are currently no effective therapies. Avenaciolide is water-insoluble natural organic product produced by Aspergillus avenaceus G. Smith that can inhibit mitochondrial function. In the present study, we investigated the anti-cancer effects of avenaciolide in an isolated human malignant meningioma cell line, HKBMM. In addition, to assess the specificity of avenaciolide, its effects on normal human neonatal dermal fibroblast HDFn cells were also examined. Avenaciolide showed effective anti-cancer activity, and its cytotoxicity in HKBMM cells was greater than that in HDFn cells. The anti-cancer effects of avenaciolide were mediated by reactive oxygen species (ROS)-induced apoptosis, which may have been caused by mitochondrial disfunction. These results suggest that avenaciolide has potential as a therapeutic drug for malignant meningioma.

A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a novel photosensitizer β-mannose-conjugated chlorin e6 (β-M-Ce6) and investigated its PDT effects in human glioblastoma U251 cells. U251 cells were incubated with β-M-Ce6, followed by laser irradiation. Cell viability was determined using the Cell Counting Kit-8 assay. The PDT effects of β-M-Ce6 were compared with those of talaporfin sodium (TS) and our previously reported photosensitizer β-glucose-conjugated chlorin e6 (β-G-Ce6). Cellular uptake of each photosensitizer and subcellular distribution were analyzed by fluorescence microscopy. β-M-Ce6 showed 1000× more potent PDT effects than those of TS, and these were similar to those of β-G-Ce6. β-M-Ce6 accumulation in U251 cells was much faster than TS accumulation and distributed to several organelles such as the Golgi apparatus, mitochondria, and lysosomes. This rapid cellular uptake was inhibited by low temperature, which suggested that β-M-Ce6 uptake uses biological machinery. β-M-Ce6 showed potent PDT anti-cancer effects compared with clinically approved TS, which is a possible candidate as a next generation photosensitizer in cancer therapy.

Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct. Balloon expansion of the duct was performed in these 2 patients and a steroid drug was injected into the duct in one patient. Complete remission was archived in one patient treated with sialendoscopy. Three patients had sialolithiasis. Microsialoliths and/or white floating matter was observed and removed using sialendoscopy. All patients experienced complete remission. In cases of Sjögren syndrome and recurrent parotitis, sialendoscopic surgery was performed, but the symptoms showed no improvement. For patients with microsialoliths, sialendoscopy may be most useful for diagnosis and treatment when the sialoliths are not detected with CT imaging. At present, sialendoscopic surgery have limitation in the treatment of Stensen's duct stenosis and may similarly have limitation in the treatment of Sjögren's syndrome and recurrent parotitis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the general guidelines for the removal of sialoliths for submandibular gland sialolithiasis using sialendoscopy alone., Methods: We analyzed 61 sialoliths treated using sialendoscopy in 42 patients with submandibular gland sialolithiasis. We evaluated the submandibular gland sialoliths and divided each case based upon the location: the Wharton's duct or the hilum. We measured the major and minor axes of the sialoliths using a soft tissue computed-tomography (CT) scan and evaluated the removal rate of the sialoliths using sialendoscopy alone., Results: The removal rate of the sialoliths in the Wharton's duct (52.6%) was significantly higher than that in the hilum of the submandibular gland (26.1%) (P=0.042). The minor axis was significantly correlated to the treatment outcome of sialendoscopy alone for all cases (P=0.030). A significant correlation was observed for cases involving the hilum of the submandibular gland and the measurement of the minor axes of the sialoliths for the treatment outcome of sialendoscopy alone (P=0.009). The major axis showed no correlation with the treatment outcomes of sialendoscopy alone., Conclusion: The measurement of the minor axes of the sialoliths with a soft tissue CT scan was correlated with treatment outcome of sialendoscopy alone for all cases, particularly sialoliths in the hilum. The easurement of the major axis showed no correlation with outcomes of sialendoscopy alone., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the general guidelines for removal of sialoliths in parotid gland sialolithiasis using sialendoscopy alone., Methods: We analyzed 34 sialoliths treated using sialendoscopy in 26 patients with parotid gland sialolithiasis. We divided the Stensen's duct and parotid gland into for parts using computed tomography findings: (A) front of the masseter, (B) anterior and lateral to the center (anterolateral) of the masseter, (C) posterior and lateral to the center (posterolateral) of the masseter, (D) behind of the masseter. The location and size of each sialolith was assessed., Results: The removal rates of sialoliths in the different locations by sialendoscopy alone were as follows: front of the masseter, 68.8%; anterolateral of the masseter, 60.0%; posterolateral of the masseter, 0%; and behind of the masseter, 33.3%. The removal rate using sialendoscopy alone was significantly higher in the sections anterior to the center of the masseter than in those posterior to the center of the masseter (66.7% [14/21] vs. 20.0% [2/10]; P=0.019). The size of the sialolith was not correlated to the removal rate by sialendoscopy alone., Conclusion: Sialoliths of the parotid gland located in positions anterior to the center of the masseter are significantly easier to remove by sialendoscopy alone. The center of the masseter is a general landmark for removal of sialoliths from the parotid gland using sialendoscopy alone. The size of the sialolith is not correlated with removal, except rare huge sialoliths., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A 31-year-old woman with a left frontal and parietal brain tumor underwent awake craniotomy. Propofol/remifentanil general anesthesia was induced. Following craniotomy, anesthetic administrations ceased. The level of consciousness was sufficient and she was not agitated. However, the patient complained of nausea 70 minutes into the awake phase. Considering the adverse effects of antiemetics and the upcoming surgical strategy, we did not give any medications. Nausea disappeared spontaneously while the operation was suspended. When surgical intervention extended to the left caudate nucleus, involuntary movement, classified as a tremor, with 5-6 Hz frequency, abruptly occurred on her left forearm. The patient showed emotional distress. Tremor appeared on her right forearm and subsequently spread to her lower extremities. Intravenous midazolam and fentanyl could not reduce her psychological stress. Since the tremor disturbed microscopic observation, general anesthesia was induced. Consequently, the tremor disappeared and did not recur. Based on the anatomical ground and the medication status, her involuntary movement was diagnosed as psychogenic tremor. Various factors can induce involuntary movements. In fact, intraoperative management of nausea and vomiting takes priority during awake craniotomy, but we should be reminded that some antiemetics potentially induce involuntary movement that could be caused by surgery around basal ganglia.

TMS pulses over the hand area of motor cortex activate different subpopulations of synaptic connections if the direction of the induced current in the brain is reversed from posterior-anterior (PA) direction to anterior-posterior (AP). We tested whether this also made a difference to the after-effects of paired associative stimulation (PAS: ulnar nerve stimulation followed 25 ms later by a transcranial magnetic stimulation pulse). If 50 pairs of stimuli (0.1 Hz) were applied using conventional suprathreshold PA-PAS in resting subjects, there was no effect on motor-evoked potentials (MEPs) in the first dorsal interosseous muscle. In contrast if the same number of pulses were given while subjects made a small tonic (5% maximum) contraction, MEPs were facilitated and resting motor threshold reduced when AP but not PA pulses were used. Subsequent experiments employed subthreshold TMS (95% of the active motor threshold) during voluntary muscle contraction. MEP facilitation accompanied by reduced AP threshold occurred when PAS was given using AP pulses (AP-Sub-PAS), whereas PAS using PA pulses (PA-Sub-PAS) had no excitatory effect. There was no facilitation if the ulnar nerve stimulus was replaced by digital nerve stimulation. There was a tendency for short interval intracortical inhibition (SICI) to decrease and intracortical facilitation (ICF) to increase after AP-Sub-PAS. We propose that the increased effectiveness of AP-Sub-PAS over PA-Sub-PAS is due to the fact that AP TMS more readily activates I3 inputs to corticospinal neurons and hence that these are an important component of associative plasticity in the human motor cortex.

More than 10 kinds of heterocyclic amines (HCAs), showing mutagenic and carcinogenic potency, have been isolated from cooked fish and meat. But many researchers say that the contribution ratio of HCAs to human cancer is very low. Our purpose in this experiment was to investigate the possibility of the formation of HCAs under moderate conditions, including in vivo. A mixture of d-glucose, creatinine, and amino acid such as glycine, methionine, threonine, and proline was dissolved in phosphate-buffered solution (pH7.4) and incubated at 37 degrees C, 50 degrees C, 128 degrees C. At an appropriate time, an aliquot of the reaction solution was treated with blue cotton. HCAs were separated from the blue cotton by elution with 2% ammoniacal methanol. The eluates were submitted to the Ames test, the micronucleus test for determination of mutagenicity, and also LC-MS analysis for the detection of HCAs. Nonadsorbates to blue cotton were treated with dichloromethane and then subjected to the mutagenicity test. In the Ames test, the mutagenic activity of the reaction mixture increased with an increase of the reaction temperature. The HCA fraction from 50 degrees C incubated solution showed high frequency in the micronucleus test using HepG2 cells. The dichloromethane fractions contained other type of mutagens different from HCAs. In HCA fractions, IQ, MeIQx, 4,8-DiMeIQx, and 7,8-DiMeIQ were identified. It is said that the heating process is an essential factor in the formation of HCAs. But our experiment shows that HCAs are produced not only in the cooking process, but also in moderate conditions such as 37 degrees C and 50 degrees C.

The effect of long-term supplementation of food reductones, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) (2%, w/w), detected in many foodstuffs including soy sauce, and hydroxyhydroquinone (1,2,4-benzenetriol) (HHQ) (1.2%, w/w), detected in coffee, on mouse lipid peroxidation and type IV and I allergy responses was investigated. The effect of supplementation of these reductones combined with NO(2) inhalation (5-6 ppm) was also investigated. Levels of thiobarbituric acid-reactive substances in lung were remarkably increased, and those in kidney and liver were slightly decreased by supplementation of DMHF or HHQ. The degree of 2,4-dinitrochlorobenzene (DNCB)-sensitized lymph node cell proliferation as assessed by lymph node assay was remarkably enhanced by supplementation of DMHF or HHQ. Both the DNCB-sensitized and the trimellitic anhydride-sensitized increases in IgE levels of mice were enhanced to greater extent by supplementation of DMHF or HHQ. In no cases were additive effects of NO(2) inhalation observable. Allergen-sensitized type IV and I allergy responses of mice may be enhanced by supplementation of food reductones, DMHF or HHQ.

Superoxide dismutase (SOD) is an important free radical scavenging enzyme which dismutates the superoxide anion radical. We have evaluated the role of SOD in the regulation of opioid receptors by comparing the concentration of mu opioid receptors labeled with [3H]DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol) in SOD-transgenic (SOD-Tg) mice and their non-transgenic (Non-Tg) littermates. SOD-Tg mice had higher maximal binding capacity (Bmax) in the shell division of the nucleus accumbens (NAc-shell) in comparison to Non-Tg littermates. There were no differences in Bmax in mu receptors in the core subdivision of the nucleus accumbens (NAc-core). There were no significant differences in receptor affinity (Kd) in either the NAc-shell or in the NAc-core. Moreover, there were no significant differences in either Bmax or Kd in the matrices nor in the patches of any of the striatal subdivisions. However, in a fashion similar to the situation in the NAc-shell, [3H]DAGO binding in the substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA), and the ventral part of the central grey was significantly higher in the SOD-Tg mice in comparison to Non-Tg mice. The present results are discussed in terms of their support for a possible involvement of free radicals in the differences observed in various regions of the SOD-Tg and control mice, which differ in their ability to scavenge the superoxide anion.(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide dismutase (SOD) plays an important role in the protection of cells against the deleterious effects of free radicals by dismutating the toxic superoxide anion radical. Although oxygen-based radicals have been implicated in the process of aging and in neurodegenerative disorders such as Parkinson's disease, the contribution of these free radicals to the pathology of these entities has yet to be clarified. It is also not certain that increased levels of free radical scavenging enzymes would attenuate the molecular and cellular processes that lead to these pathological states. In order to assess the contribution of increased SOD gene dosage to the pathogenesis of Down's syndrome, transgenic mice have been constructed that overexpress the human CuZnSOD. We are also using this model to evaluate the role of free radicals in age-associated changes in brain neurotransmitters and their receptors. In the present study, transgenic mice and their nontransgenic littermates, aged 6 weeks and 21 months, were used in an autoradiographic receptor study of the distribution of brain neurotensin receptors. At 6 weeks of age, there were no significant differences between the two groups of mice in most brain regions. In addition, [3H]NT binding sites showed parallel age-related decreases in the majority of the areas examined in both groups. However, significant age-related decreases in the septum, the diagonal band of Broca, and in some subdivisions of the caudate-putamen were observed only in SOD-Tg mice. In contrast, significant age-related decreases in the core area of the nucleus accumbens and the dorsal aspect of the dentate gyrus of the hippocampus were seen only in non-Tg mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplantation of dopamine (DA) cells into the rat model of hemiparkinsonism induced by intranigral 6-hydroxydopamine (6-OHDA) injections has so far focused mainly on DA replacement via a pump-like mechanism. In the present study, we employed a model of hemiparkinsonism that uses an intrastriatal approach to lesioning the nigrostriatal DA pathway to assess the possibility of using cell transplantation to cause regeneration of that system. Toward that end, we transplanted two types of cells on the side of the 6-OHDA-induced lesions: 1) nonmodified fetal mesencephalic cells and 2) fetal mesencephalic cells that have been infected with a retrovirus vector containing a PKC beta 1 cDNA. Both types of cells cause behavioral improvement although the changes were more prominent and occurred earlier in the PKC-modified groups. Tyrosine hydroxylase (TH) immunocytochemistry revealed significantly cell survival in both groups of animals; in situ hybridization studies confirmed the continuous expression of TH mRNA in both groups. Interestingly, long TH-positive axons were observed only in the striata of animals implanted with PKC-modified cells. More importantly, surviving endogenous nigral TH-positive cell bodies were found only on the lesioned side in the latter group. The observations in these animals were associated with significantly smaller decreases in [3H]mazindol-labeled DA uptake sites in both the striata and substantia nigra pars compacta on the side ipsilateral to the 6-OHDA-induced lesions. Furthermore, immunohistochemical studies revealed increased gliosis in the striata of animals grafted with the PKC-modified cells. When taken together, these results indicate that transplantation of normal fetal mesencephalic cells can cause behavioral improvement by providing DA to the host striata whereas PKC-modified cells can, in addition, prevent the progressive degeneration of or cause regeneration of the dying nigrostriatal DA neurons in this model of hemiparkinsonism. These results are discussed in terms of their support for a role for second messenger systems and glial cells, as well as extracellular matrix molecules in the regeneration of the CNS.

We have established the radioimmunoassay for ubiquitin in the cerebrospinal fluid (CSF) and measured the ubiquitin concentration in CSF from 4 cases of neuropathologically verified Creutzfeldt-Jakob disease (CJD), 10 cases of multi-infarct dementia (MID), 7 cases of senile dementia of Alzheimer type (SDAT), and 18 controls. The normal values were determined to range from 7.3 to 21.0 ng/ml, 14.3 +/- 1.1 ng/ml in the mean +/- S.E.M. The CSF ubiquitin levels in the cases of MID and SDAT were 16.6 +/- 6.4 ng/ml and 21.3 +/- 6.1 ng/ml, respectively. In the cases of CJD, the CSF ubiquitin was markedly increased at the early and middle stages of the disease (230.6 ng/ml in Case 1, 107.6 ng/ml in Case 2, 212.5 ng/ml in Case 3, and 377.0 ng/ml in Case 4) and these gradually decreased as the disease progressed. The measurement of CSF ubiquitin seems useful to make an early diagnosis of CJD.

The present study was carried out in order to re-evaluate the issue of the localization of neurotensin receptors in the caudate-putamen and in the nucleus accumbens of rat. Intrastriatal injections of 6-hydroxydopamine which cause almost complete destruction of the mesostriatal dopaminergic pathway also caused a marked loss of neurotensin receptors in the caudate-putamen (CPu), the nucleus accumbens (NAc) and in the olfactory tubercle (OT). These decreases corresponded to a mean loss of 98, 93 and 41% in the CPu, the NAc, and the OT, respectively. There were corresponding decreases in the substantia nigra pars compacta (SNpc) (-94%) and pars reticulata (SNpr) (-97%), and in the ventral tegmental area (-78%). Moreover, there were also decreases in neurotensin receptors on the contralateral side of the intrastriatal injections which occurred in the CPu but not in the NAc nor in the OT. These results indicate that almost all NT receptors measured within the CPu and the NAc are located on the terminals of dopaminergic neurons within those structures. The bilaterality of the changes which occur in the CPu provide further support for the notion of the interdependence of the two nigrostriatal dopaminergic projections and the peptidergic systems with which they interact.

The receptor autoradiographic distribution of opioid peptide receptors in spontaneously hypertensive rats (SHR) was compared to that of Sprague-Dawley (SD) rats, using the highly selective mu and delta opioid receptor ligands, [3H]DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol) and [3H]DPDPE ([D-Pen2,D-Pen5]enkephalin), respectively. Although the distribution of these binding sites was similar in both strains, SHR showed significantly higher binding densities of mu receptors in 16 of 27 areas examined. These included the patch and matrix components of the caudate-putamen (CPu), olfactory tubercle, endopiriform nucleus, anterior cingulate cortex, ventral tegmental area lateroposteral thalamic nucleus and the ventral part of the dentate gyrus. In contrast, SHR had lower [3H]DAGO binding sites in the CA1 of the hippocampus. Conversely, SHR showed higher binding densities of delta receptors in 7 of 20 areas examined, including the CPu, CA2 and CA3 areas of the hippocampus and the central grey. High-to-low lateromedial gradients of striatal delta receptors were observed in both strains. Because opioid peptides are known to participate in locomotive behavior in rodents and in the control of blood pressure, the present results support a role of opioid peptidergic systems in the manifestation of hyperactivity and hypertension observed in SHR.

We examined the status of dopamine (DA) D1 and D2 receptors by using [3H]SCH 23390 and [3H]spiperone binding, respectively, and DA uptake sites by using [3H]mazindol binding in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. SHR showed significantly higher [3H]SCH 23390 and [3H]spiperone binding in the caudate-putamen (CPu), the nucleus accumbens (NAc) and the olfactory tubercle (OT) in comparison to the SD rats. There were no significant differences in [3H]mazindol-labeled DA uptake sites between the two strains. Unilateral 6-hydroxydopamine (6-OHDA) injection into the striatum resulted in more than 90% depletion of DA uptake sites in the CPu in both strains. 6-OHDA-induced DA depletion was associated with significant increases in striatal [3H]spiperone binding which were of similar magnitude in the SD rats (+64.1%) and SHR (+51.3%). There were only small decreases (-5.4%) in D1 receptor binding in the dorsolateral aspect of the CPu in the SHR, whereas there were no changes in striatal D1 receptors in the SD rats. These results indicate that, although the SHR have higher concentrations of both D1 and D2 receptors in the basal ganglia, these receptors are regulated in a fashion similar to DA receptors in SD rats after 6-OHDA-induced striatal DA depletion.

As auditory system has no sensory epithelium into which auditory space are projected, we studied the physiological map of the auditory space in the non-primary auditory cortex of the mustached bat by using the echo of their orientation sound. Ten bats were used as experimental subjects. Tungsten wire electrodes were inserted obliquely in the dorsomedial (DM) and ventroposterior (VP) areas of the non-primary auditory cortex. When single neuron was isolated, best frequency (BF), best azymuth (BAZ) and best elevation (BEL) were measured and were plotted on a schematic figure. To mimic its biosonar, one loudspeaker, delivering synthesized orientation sounds, was placed in front of the animal, and another loudspeaker delivering synthesized echo was mounted on a movable hoop. Tonotopic representation was observed but complicated in both areas, and those areas could be divided into several subdivisions consisting of the neuron groups characterized by three frequency bands. The neurons were thought to be related to the processing of biosonar informations from the facts that their BFs agreed with the scope of the FM sweep of each echo harmonics. The magnitude of the response showed rapid increase at their BAZ or BEL, so that the neurons seemed to tune to a certain direction in the auditory space. Especially in the DM area, neurons assumed a systematic arrangement of their BAZs on the cerebral surface and showed some tendency of a systematic arrangement of their BELs. The DM area was thought to have a kind of neural map of the auditory space.