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1.
Am J Ophthalmol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38701877

RESUMO

PURPOSE: To compare the quality of images of gratings placed in a model eye viewed through an extended depth of focus (EDoF) intraocular lens (IOL) to that of diffractive bifocal IOL or monofocal IOL. DESIGN: Experimental laboratory investigation. METHODS: Non-diffractive wavefront shaping EDoF (CNAET0, Alcon laboratories), echelette-designed EDoF (ZXR00V, Johnson & Johnson Vision), diffractive bifocal IOL with low power addition (SV25T, Alcon Laboratories), or monofocal IOL (CNA0T0, Alcon laboratories) was placed in a fluid-filled model eye. A USAF Resolution Grating Target was glued to the posterior surface of the model eye and viewed through a flat or a wide-angle contact lens. The contrast of the gratings viewed through the EDoF or multifocal IOLs was compared to that through the monofocal IOL. A wavefront analyzer was used to measure the spherical power of the central 4.5 mm optics of the EDoF, multifocal, and monofocal IOLs. The distribution of the dioptric power and the dioptric power map were compared. RESULTS: The gratings observed through the flat contact lens with the CNAET0, ZXR00V, or SV25T were slightly blurred when viewed through the multifocal optics. The blurred area was in the circumferential area of the CNAET0, the central area of SV25T, and the peripheral area of ZXR00V. The mean contrast was 0.258±0.020 for CNAET0, 0.227±0.025 for ZXR00V, and 0.221±0.020 for SV25T for the 16.0 cyc/mm grating. The contrast was significantly lower for ZXR00V (P=0.004) and SV25T (P=0.004) than the 0.303±0.015 for CNA0T0 but the differences were not significant. For the wide-angle contact lens, the contrast for CNAET0 was 0.182±0.009, for ZXR00V was 0.162±0.011, and for SV25T was 0.163±0.007 for the 16.0 cyc/mm grating, and none was significantly different from the 0.188±0.012 for CNA0T0. The dioptric variations of the CNAET0 indicated a ring-shaped area of higher power corresponding to the circumferential blurred zone observed through the flat contact lens. CONCLUSION: The wavefront shaping and echelette-designed EDoF-IOLs reduce the contrast of the grating more than the monofocal IOL when viewed through the flat contact lens. The degree of reduction depended on the design of the extended-focus optics. The difference was less through the wide-angle contact lens.

2.
J Nat Med ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662301

RESUMO

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.

3.
J Oral Rehabil ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685709

RESUMO

BACKGROUND: Modification of foods or liquids is commonly administered as part of dysphagia treatment. However, no consensus exists on the parameters for defining texture-modified food for patients with dysphagia. OBJECTIVES: The aim of this study was to evaluate the effect of food/liquid material on swallowing physiology in patients with dysphagia and to discuss the optimal food choice for direct swallowing therapy. MATERIALS AND METHODS: A total of 140 patients underwent a videofluoroscopic swallowing study using three test foods/liquids: 3 mL of mildly thick liquid (Thick liquid), jelly made of agar and polysaccharide (Jelly) and jelly made of pectin (Reset gel). Outcome measures of videofluoroscopic images, bolus transit time and hyoid movements were compared. RESULTS: The frequency of chewing movements was highest for Jelly, followed by Reset gel and Thick liquid. While the probability of oral residue was the highest for Reset gel, pharyngeal residue after swallowing was high for Thick liquid as compared to Jelly and Reset gel. Oral transit time and pharyngeal transit time for Thick liquid were significantly smaller than that for Jelly and Reset gel. Pharyngeal delay time was significantly smaller for Thick liquid than that for Jelly and Reset gel. There was no difference in hyoid elevation time and hyoid movement time among the conditions. CONCLUSION: Mildly thick liquid material may be optimal for patients with primarily oral motor function impairment and jelly, such as Reset gel, may be more suitable for patients with primarily pharyngeal motor function impairment or oral and pharyngeal coordinative motor function decline.

4.
Dysphagia ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512436

RESUMO

Mastication is controlled by central pattern generator in the brainstem and can be modulated by volition. The aim of this study was to investigate the effect of chewing well on swallowing. Twenty-six healthy participants were instructed to eat 8, 12, and/or 16 g of steamed rice with barium sulphate under the following two conditions: chewing freely task (CF; chewing naturally in their usual manner) and chewing well task (CW; chewing the food with a request to "chew well"). We evaluated bolus transport and swallowing movement using videofluoroscopy and electromyography of the masseter, suprahyoid and thyrohyoid muscles. The chewing time and pharyngeal transit time (PTT) at the first swallow showed high reproducibility in both CF and CW. PTT for CW was significantly shorter and longer than CF in 12 and 16 g, respectively. In 12 g, CW increased the pharyngeal bolus velocity and decreased thyrohyoid EMG activity during swallowing compared with CF. In 16 g, the difference between CW and CF in the estimated swallowed bolus volume was positively correlated with that in upper esophageal sphincter transit duration. We speculate that CW modulates PTT during swallowing depending on the mouthful volume.

6.
Neurosci Lett ; 825: 137672, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38360144

RESUMO

Pharyngeal electrical stimulation (PES) applies electrical stimulation to pharyngeal mucosa (PhM) and represents a useful approach to improve swallowing function in patients with dysphagia. To determine the optimal PES modality to treat dysphagia, the mechanism underlying the effects of PES on swallowing function must be elucidated. In this study, we evaluated how PES and electrical stimulation of the superior laryngeal nerve (SLN) modulate the initiation of swallowing in anesthetized rats. A swallow was evoked by electrical stimulation of the PhM, SLN, and nucleus of the solitary tract (nTS) and pharyngeal mechanical stimulation using a von Frey filament. A swallow was identified by electromyographic bursts in mylohyoid and thyrohyoid muscles. Bilateral SLN transection abolished the swallows evoked by PhM electrical stimulation. PhM and SLN electrical stimulation decreased swallowing frequency in a similar time-dependent manner. Intravenous administration of the GABAA receptor antagonist bicuculine did not affect the time-dependent change in swallowing frequency during SLN electrical stimulation. Continuous SLN electrical stimulation significantly inhibited pharyngeal mechanically and nTS-electrically evoked swallows compared with before and 5 min after stimulation. The present findings suggest that the SLN plays a primary role in PES-evoked swallows. Additionally, continuous SLN electrical stimulation inhibits the initiation of swallowing, and the modulation of central network associated with swallowing might be partially involved in this inhibition.


Assuntos
Transtornos de Deglutição , Deglutição , Humanos , Ratos , Animais , Deglutição/fisiologia , Ratos Sprague-Dawley , Estimulação Elétrica , Nervos Laríngeos/fisiologia
7.
PLoS One ; 19(2): e0297347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329968

RESUMO

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.


Assuntos
Membrana Epirretiniana , Baixa Visão , Humanos , Lactente , Estudos Prospectivos , Estudos de Coortes , Japão , Transtornos da Visão , Vitrectomia/métodos , Tomografia de Coerência Óptica/métodos , Baixa Visão/complicações , Estudos Retrospectivos , Resultado do Tratamento , Estudos Multicêntricos como Assunto
8.
Am J Physiol Gastrointest Liver Physiol ; 326(3): G318-G329, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38226423

RESUMO

The external carotid artery (ECA) plays a major role in supplying blood to the head and neck. Although impeded blood flow in the ECA is expected to affect orofacial functions, few studies have shown how blood flow obstruction in the ECA contributes to impairment of these functions, including chewing and swallowing. This study was performed to investigate the effects of ECA ligation (ECAL) on immediate and long-term changes in masticatory and swallowing functions as well as the jaw-opening reflex evoked in the digastric muscle. The experiments were carried out using male Sprague-Dawley rats. In the acute experiment, the digastric reflex evoked by low-threshold electrical stimulation of the inferior alveolar nerve and the swallow reflex, identified by digastric and thyrohyoid electromyographic (EMG) bursts, were compared between before and 1 h after ECAL. The chronic experiment was conducted on freely moving rats. EMGs of the masseter, digastric, and thyrohyoid muscles were chronically recorded. The long-term effects of ECAL on behavior and muscle histology were compared between rats with an intact ECA and rats with ECAL. In the acute experiment, the peak amplitude of the digastric reflex on the ECAL side was significantly decreased 1 h after ECAL. In the chronic experiment, although most parameters of the masticatory and swallowing EMGs were not significantly different between the groups, the results suggest wide variation of the effect of ECAL on the muscles. Blood supply compensation from collaterals of the internal carotid artery may be permanent in some animals.NEW & NOTEWORTHY The inhibitory effect of unilateral external carotid artery ligation (ECAL) on the ipsilateral digastric reflex was small but evident. Most parameters of masticatory and swallowing muscle activity were not significantly different after ECAL. Wide variation was noted in the effect of ECAL on the ipsilateral muscle activity. Blood supply compensation from collaterals of the internal carotid artery may occur in response to the impaired blood flow.


Assuntos
Artéria Carótida Externa , Reflexo , Ratos , Animais , Masculino , Ratos Sprague-Dawley , Eletromiografia , Reflexo/fisiologia , Mastigação/fisiologia
9.
J Nat Med ; 78(1): 169-179, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951850

RESUMO

Fibroblast growth factor 21 (FGF21) is expressed in several organs, including the liver, adipose tissue, and cardiovascular system, and plays an important role in cross-talk with other organs by binding to specific FGF receptors and their co-receptors. FGF21 represents a potential target for the treatment of obesity, type 2 diabetes mellitus, and non-alcoholic steatohepatitis (NASH). The production of FGF21 in skeletal muscle was recently suggested to be beneficial for metabolic health through its autocrine and paracrine effects. However, the regulatory mechanisms of FGF21 in skeletal muscle remain unclear. In the present study, we showed that berberine regulated FGF21 production in C2C12 myotubes in a dose-dependent manner. We also examined the effects of A-674563, a selective Akt1 inhibitor, on the berberine-mediated regulation of FGF21 expression in C2C12 myotubes. Berberine significantly increased the secretion of FGF21 in C2C12 myotubes, while A-674563 attenuated this effect. Moreover, a pre-treatment with A-674563 effectively suppressed berberine-induced increases in Bmal1 expression in C2C12 myotubes, indicating that the up-regulation of Bmal1 after the berberine treatment was dependent on Akt1. Additionally, berberine-induced increases in FGF21 secretion were significantly attenuated in C2C12 cells transfected with Bmal1 siRNA, indicating the contribution of the core clock transcription factor BMAL1 to Akt-regulated FGF21 in response to berberine. Collectively, these results indicate that berberine regulates the expression of FGF21 through the Akt1 pathway in C2C12 myotubes. Moreover, the core clock gene Bmal1 may participate in the control of the myokine FGF21. Berberine stimulated Akt1-dependent FGF21 expression in C2C12 myotubes. The up-regulation of FGF21 through the modulation of PI3K/AKT1/BMAL1 in response to berberine may be involved in the regulation of cellular function (such as Glut1 expression) by acting in an autocrine and/or paracrine manner in skeletal muscle.


Assuntos
Berberina , Diabetes Mellitus Tipo 2 , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Berberina/farmacologia , Fatores de Transcrição ARNTL/genética
10.
Eye (Lond) ; 38(2): 266-273, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37524830

RESUMO

OBJECTIVES: To investigate the relationship between the shape of the optic nerve head (ONH) margin detected by optical coherence tomography (OCT) and the clinical characteristics of glaucomatous eyes with papillomacular retinoschisis (PMRS). METHODS: The medical record of patients with a PMRS in a glaucomatous eye were reviewed. The eyes were placed into two groups determined by the shape of the ONH margin in the OCT images; eyes with an externally oblique ONH margin (Group 1) and eyes with an internally oblique ONH margin (Group 2). We compared the clinical characteristics of the PMRS of these two groups. RESULTS: We studied 31 eyes of 29 patients with PMRS and glaucoma with 24 eyes in Group 1 and 7 eyes in Group 2. The optic nerve fibre layer schisis on the lamina cribrosa (LC), beta zone, and gamma zone, and found that the LC defects were detected significantly more frequently in Group 1 than in Group 2 eyes (P < 0.05). A retinal nerve fibre schisis was observed around the ONH significantly more frequently in Group 2 than in Group 1 eyes (P < 0.01). CONCLUSION: The cases of glaucoma-associated PMRS could be classified into two groups according to the obliquity of the ONH. They had differences in the findings of OCT and FA. The possibility that the mechanism of PMRS development is different in both groups is suggested.


Assuntos
Glaucoma , Disco Óptico , Retinosquise , Humanos , Tomografia de Coerência Óptica/métodos , Retinosquise/diagnóstico por imagem , Glaucoma/diagnóstico , Pressão Intraocular
11.
J Oral Rehabil ; 51(3): 566-573, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37902163

RESUMO

BACKGROUND: Lingual pressure (LP) generation is cooperatively controlled not only by the intrinsic tongue (I-ton) muscles but also by hyoid muscle activation. However, the measurement of endurance and fatigue properties of I-ton muscles is difficult due to the instability of electrodes. OBJECTIVE: The purpose of this study was to apply suction electrodes to measure electromyograms (EMGs) of I-ton muscle and to evaluate integrated EMG amplitude (iEMG) and mean power frequency (MPF) of EMG in the I-ton and hyoid muscles performing continuous LP. METHODS: Twenty healthy adult volunteers (10 males, 10 females, mean age 28.8 years) were instructed to perform 10-s LP generation tasks at 25%, 50%, 75% and 100% of maximum LP in randomised order with visual feedback. During each task, EMGs of the I-ton, suprahyoid (S-hyo), infrahyoid (I-hyo) and masseter (Mass) muscles were simultaneously recorded. The iEMG and MPF of EMG burst during 10-s LP tasks were compared. The recording period was divided into three substages to analyse temporal changes with the Friedman test. RESULTS: During the 10-s task, the iEMG significantly increased as the LP strength increased (p < .001). There was no time-dependent change in the I-ton iEMG; however, the MPF of the I-ton EMG burst decreased in all tasks (p < .05). The S-hyo and I-hyo iEMGs gradually increased, especially with strong LP (p < .01). CONCLUSION: While I-ton muscles may easily fatigue during 10-s LP generation, S-hyo and I-hyo muscles may help compensate for the weakened I-ton muscle activity by increasing their activity to maintain LP.


Assuntos
Músculos Faciais , Língua , Masculino , Adulto , Feminino , Humanos , Sucção , Músculo Masseter , Músculos do Pescoço , Eletromiografia , Contração Muscular
12.
J Hum Genet ; 69(3-4): 107-114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38123667

RESUMO

Japanese males belong to the Y chromosome C1a1, C2, D1a2a, D1a2a-12f2b, O1b2, O1b2a1a1, O2a2b1, and O2a1b haplogroups. Notably, the regional frequency of each haplogroup is homogeneous. Owing to recent developments in genome sequencing technology, the phylogenetic tree of Y chromosome haplogroups is updated annually. Therefore, in this study, we aimed to provide an update on the Y chromosome haplogroups of modern Japanese males and examine their regional distributions. Using 1,640 samples of Japanese males from seven Japanese cities (Nagasaki, Fukuoka, Tokushima, Osaka, Kanazawa, Kawasaki, and Sapporo), haplogroups C1a1, C2, D1a2a, D1a2a-12f2b, O1b2, and O1b2a1a1 were updated based on the latest phylogenetic tree. Haplogroup C1a1 was mainly classified into C1a1a1a and C1a1a1b subgroups; C1a1a1b was more common in Tokushima and Osaka than in the other regions. Haplogroup C2 was mainly classified into C2a, C2b1a1a, C2b1a1b, C2b1a2, and C2b1b subgroups and exhibited frequency differences in Osaka. Haplogroup D1a2a was classified into D1a2a1c1 and D1a2a2 subgroups, and its frequency varied between Tokushima and Osaka. Haplogroup D1a2a-12f2b was classified into D1a2a1a2b1a1a and D1a2a1a3 subgroups; however, no significant frequency differences were observed. Haplogroup O1b2 was classified into O1b2a1a2a1a, O1b2a1a2a1b, and O1b2a1a3 subgroups, with frequency differences between Nagasaki and Kanazawa. Haplogroup O1b2a1a1 was mainly classified into O1b2a1a1a, O1b2a1a1b, and O1b2a1a1c subgroups; however, no significant frequency differences were observed. Our findings suggest that gene flow in the Kinki region is caused by human migration.


Assuntos
Cromossomos Humanos Y , Masculino , Humanos , Japão , Filogenia , Haplótipos , Mapeamento Cromossômico
13.
Beilstein J Org Chem ; 19: 1604-1614, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915559

RESUMO

Breynia spp. are a key source of sulfur-containing spiroketal glycosides with potential anti-inflammatory activity. In this study, three new sulfur-containing spiroketals - breynin J (1), epibreynin J (2), and probreynogenin (3) - along with four known compounds - probreynin I (4), phyllaemblic acid (5), breynin B (6), and epibreynin B (7) - were isolated from the roots of Breynia disticha. The structures of compounds 1-7 were elucidated by extensive 1D and 2D NMR spectroscopic analyses, including 1D total correlation spectroscopy (TOCSY), HSQC, HMBC, double quantum-filtered (DQF)-COSY, heteronuclear two-bond correlation (H2BC), and HSQC-TOCSY experiments, as well as high-resolution electrospray ionization HRESIMS analysis, and quantum chemical electronic CD calculations. Furthermore, the absolute configurations of sugar residues were determined by derivatization of the hydrolysates with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. The anti-inflammatory effects of the isolated compounds were evaluated based on the mRNA levels of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Compounds 1, 2, 6, and 7 inhibited the increase in interleukin (IL)-1ß and IL-6 mRNA levels stimulated by LPS. Moreover, the most potent compound 7 was found to significantly inhibit the production of IL-1ß and IL-6 proteins, as revealed by the analysis of culture supernatants.

14.
Int J Mol Sci ; 24(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37685872

RESUMO

Blood proteins can be used for biomarkers to monitor the progression of cognitive decline, even in the early stages of disease. In this study, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based blood test to identify plasma proteins that can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). Using this system, we quantified plasma proteins using isotope-labeled synthetic peptides. A total of 192 patients, including 63 with AD, 71 with MCI, and 58 non-demented controls (NDCs), were analyzed. Multinomial regression and receiver operating characteristic (ROC) analyses were performed to identify specific combinations of plasma protein panels that could differentiate among NDCs, those with MCI, and those with AD. We identified eight plasma protein biomarker candidates that can be used to distinguish between MCI and AD. These biomarkers were associated with coagulation pathways, innate immunity, lipid metabolism, and nutrition. The clinical potential to differentiate cognitive impairment from NDC was assessed using area under the curve values from ROC analysis, which yielded values of 0.83 for males and 0.71 for females. This LC-MS-based plasma protein panel allows the pathophysiology of AD to be followed through detection of cognitive decline and disease progression markers.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Masculino , Humanos , Doença de Alzheimer/diagnóstico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Disfunção Cognitiva/diagnóstico , Biomarcadores , Proteínas Sanguíneas
15.
Congenit Anom (Kyoto) ; 63(5): 141-146, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37269175

RESUMO

Cleft lip and/or palate anomalies (CL ± P) are the most frequent birth defects affecting the orofacial region in humans. Although their etiology remains unclear, the involvement of environmental and genetic risk factors is known. This observational study aimed to investigate how the use of  crude drugs with estrogen activity influenced an animal model's ability to prevent CL ± P. A/J mice were randomly divided into six experimental groups. Five of these groups consumed a drink containing crude drug licorice root extract, with the following weights attributed to each group: 3 g in group I, 6 g in group II, 7.5 g in group III, 9 g in group IV, and 12 g in group V, whereas a control group consumed tap water. The effect of licorice extract was examined for fetal mortality and fetal orofacial cleft development compared to the control group. The rates for fetal mortality were 11.28%, 7.41%, 9.18%, 4.94%, and 7.90% in groups I, II, III, IV, and V, respectively, compared to 13.51% in the control group. There were no significant differences in the mean weight of alive fetuses in all five groups compared to the control group (0.63 ± 0.12). Group IV showed the lowest orafacial cleft occurrence of 3.20% (8 fetuses) with statistical significance (p = 0.0048) out of 268 live fetuses, whereas the control group had the occurrence of 8.75% (42 fetuses) among 480 live fetuses. Our study showed that the dried licorice root extract may reduce orofacial birth defects in experimental animal studies.


Assuntos
Fenda Labial , Fissura Palatina , Glycyrrhiza , Humanos , Camundongos , Animais , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia
16.
Nat Commun ; 14(1): 3831, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380639

RESUMO

Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is a condition frequently occurring in immunocompromised patients receiving antiretroviral therapy. C-IRIS patients exhibit many critical symptoms, including pulmonary distress, potentially complicating the progression and recovery from this condition. Here, utilizing our previously established mouse model of unmasking C-IRIS (CnH99 preinfection and adoptive transfer of CD4+ T cells), we demonstrated that pulmonary dysfunction associated with the C-IRIS condition in mice could be attributed to the infiltration of CD4+ T cells into the brain via the CCL8-CCR5 axis, which triggers the nucleus tractus solitarius (NTS) neuronal damage and neuronal disconnection via upregulated ephrin B3 and semaphorin 6B in CD4+ T cells. Our findings provide unique insight into the mechanism behind pulmonary dysfunction in C-IRIS and nominate potential therapeutic targets for treatment.


Assuntos
Cryptococcus , Linfócitos T , Animais , Camundongos , Núcleo Solitário , Transferência Adotiva , Modelos Animais de Doenças
17.
J Oral Rehabil ; 50(11): 1270-1278, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37322854

RESUMO

BACKGROUND: Chewing and licking are primarily activated by central pattern generator (CPG) neuronal circuits in the brainstem and when activated trigger repetitive rhythmic orofacial movements such as chewing, licking and swallowing. These CPGs are reported to modulate orofacial reflex responses in functions such as chewing. OBJECTIVE: This study explored the modulation of reflex responses in the anterior and posterior bellies (ant-Dig and post-Dig, respectively) of the digastric muscle evoked by low-intensity trigeminal stimulation in conscious rats. METHODS: The ant-Dig and post-Dig reflexes were evoked by using low-intensity electrical stimulation applied to either the right or left inferior alveolar nerve. Peak-to-peak amplitudes and onset latencies were measured. RESULTS: No difference was observed between threshold and onset latency for evoking ant-Dig and post-Dig reflexes, suggesting that the latter was also evoked disynaptically. The peak-to-peak amplitude of both reflexes was significantly reduced during chewing, licking and swallowing as compared to resting period and was lowest during the jaw-closing phase of chewing and licking. Onset latency was significantly largest during the jaw-closing phase. Inhibitory level was similar between the ant-Dig and post-Dig reflex responses and between the ipsilateral and contralateral sides. CONCLUSION: These results suggest that both the ant-Dig and post-Dig reflex responses were significantly inhibited, probably due to CPG activation during feeding behaviours to maintain coordination of jaw and hyoid movements and hence ensure smooth feeding mechanics.


Assuntos
Arcada Osseodentária , Reflexo , Animais , Ratos , Arcada Osseodentária/fisiologia , Eletromiografia/métodos , Reflexo/fisiologia , Nervo Mandibular , Estimulação Elétrica , Músculos do Pescoço
18.
Dysphagia ; 38(6): 1519-1527, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37149542

RESUMO

The effects of head and neck alignment and pharyngeal anatomy on epiglottic inversion remain unclear. This study investigated the factors involved in epiglottic inversion, including head and neck alignment and pharyngeal anatomy, in patients with dysphagia. Patients with a chief complaint of dysphagia and who underwent videofluoroscopic swallowing study at our hospital from January to July 2022 were enrolled. They were divided into three groups based on the degree of epiglottic inversion as the complete-inversion (CI), partial-inversion (PI), and non-inversion group (NI) groups. Data were compared among the three groups; a total of 113 patients were analyzed. The median age was 72.0 (IQR: 62.0-76.0) years; 41 (36.3%) and 72 (63.7%) were women and men, respectively. There were in 45 (39.8%) patients in the CI, 39 (34.5%) in the PI, and 29 (25.7%) in the NI groups, respectively. Single-variable analysis revealed significant relation to epiglottic inversion of Food Intake LEVEL Scale score, penetration-aspiration score with 3-mL thin liquid bolus, epiglottic vallecula and pyriform sinus residue, hyoid position and displacement during swallowing, pharyngeal inlet angle (PIA), epiglottis to posterior pharyngeal wall distance, and body mass index. Logistic regression analysis with complete epiglottic inversion as the dependent variable revealed the X coordinate at maximum hyoid elevation position during swallowing and PIA as significant explanatory variables. These results suggest that epiglottic inversion is constrained in patients with dysphagia who have poor head and neck alignment or posture and a narrow pharyngeal cavity just before swallowing.


Assuntos
Transtornos de Deglutição , Deglutição , Masculino , Humanos , Feminino , Idoso , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Epiglote , Faringe/diagnóstico por imagem , Pescoço
19.
Am J Physiol Gastrointest Liver Physiol ; 325(2): G109-G121, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37219016

RESUMO

Anticholinergic medication causes impaired swallowing with hyposalivation. However, the underlying mechanisms by which these drugs modulate the swallowing reflex remain unclear. This study investigated the effects of the muscarinic acetylcholine receptor (mAChR) nonspecific antagonist atropine on the initiation of swallowing. Experiments were performed on 124 urethane-anesthetized rats. A swallow was evoked by either topical laryngeal application of a small amount of distilled water (DW), saline, citric acid, or capsaicin; upper airway distention with a continuous airflow; electrical stimulation of the superior laryngeal nerve (SLN); or focal microinjection of N-methyl-d-aspartate (NMDA) into the lateral region of the nucleus of the solitary tract (L-nTS). Swallows were identified by electromyographic bursts of the digastric and thyrohyoid muscles. Either atropine, the peripheral mAChR antagonist methylatropine, or antagonists of mAChR subtypes M1-M5 were intravenously delivered. Atropine at a dose of 1 mg/kg increased the number of DW-evoked swallows compared with baseline and did not affect the number of swallows evoked by saline, citric acid, capsaicin, or upper airway distention. Methylatropine and M1-M5 antagonists did not significantly change the number of DW-evoked swallows. Bilateral SLN transection completely abolished DW-evoked swallows, and atropine decreased the swallowing threshold of SLN electrical stimulation. Finally, microinjection of NMDA receptor antagonist AP-5 into the L-nTS inhibited DW-evoked swallows, and atropine facilitated the initiation of swallowing evoked by NMDA microinjection into this region. These results suggest that atropine facilitates DW-evoked swallows via central mAChR actions.NEW & NOTEWORTHY Atropine facilitated the distilled water (DW)-evoked swallows in anesthetized rats. Atropine decreased the swallowing threshold evoked by electrical stimulation of the superior laryngeal nerve, which is a primary sensory nerve for the initiation of DW-evoked swallows. Atropine facilitated the swallows evoked by N-methyl-d-aspartate microinjection into the lateral region of the nucleus of the solitary tract, which is involved in the DW-evoked swallows. We speculate that atropine facilitates the DW-evoked swallows via central muscarinic receptor actions.


Assuntos
Atropina , N-Metilaspartato , Ratos , Animais , Ratos Sprague-Dawley , Atropina/farmacologia , N-Metilaspartato/farmacologia , Água/farmacologia , Capsaicina/farmacologia , Derivados da Atropina/farmacologia , Deglutição/fisiologia , Estimulação Elétrica , Receptores Muscarínicos , Ácido Cítrico/farmacologia , Reflexo/fisiologia
20.
Nature ; 616(7958): 686-690, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37100940

RESUMO

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.

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