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1.
Cell Mol Neurobiol ; 43(3): 1267-1280, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35771293

RESUMO

Controlling axonal mitochondria is important for maintaining normal function of the neural network. Oxygen-glucose deprivation (OGD), a model used for mimicking ischemia, eventually induces neuronal cell death similar to axonal degeneration. Axonal mitochondria are disrupted during OGD-induced neural degeneration; however, the mechanism underlying mitochondrial dysfunction has not been completely understood. We focused on the dynamics of mitochondria in axons exposed to OGD; we observed that the number of motile mitochondria significantly reduced in 1 h following OGD exposure. In our observation, the decreased length of stationary mitochondria was affected by the following factors: first, the halt of motile mitochondria; second, the fission of longer stationary mitochondria; and third, a transformation from tubular to spherical shape in OGD-exposed axons. Motile mitochondria reduction preceded stationary mitochondria fragmentation in OGD exposure; these conditions induced the decrease of stationary mitochondria in three different ways. Our results suggest that mitochondrial morphological changes precede the axonal degeneration while ischemia-induced neurodegeneration.


Assuntos
Glucose , Oxigênio , Ratos , Animais , Oxigênio/metabolismo , Glucose/metabolismo , Gânglios Espinais/metabolismo , Ratos Sprague-Dawley , Axônios/metabolismo , Células Cultivadas , Mitocôndrias/metabolismo
2.
J Orthop Sci ; 28(3): 543-546, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35305863

RESUMO

BACKGROUND: The Japanese Society for Spine Surgery and Related Research previously developed a diagnostic support tool for lumbar spinal stenosis (LSS-DST). Using the LSS-DST, general physicians can identify potential cases of LSS. However, in the LSS-DST, measurement of the ankle brachial pressure index (ABI) is required to exclude peripheral artery lesions in the lower limbs. We can expect further application of the LSS-DST if we can identify a simpler and easier method than ABI measurement. Therefore, in this large-scale, multicenter, cross-sectional study, we verified whether palpation of the posterior tibial (PT) artery could be used instead of ABI in the LSS-DST. METHODS: This survey was conducted at 2177 hospitals and included 28,883 participants. The sensitivity and specificity of the original LSS-DST method using the ABI and that of the LSS-DST ver2.0 with PT artery palpation were assessed to screen their ability for diagnosing LSS, using the physicians' final diagnosis based on the patients' history, physical examination and radiographic findings as the gold standard. RESULTS: The sensitivity and specificity [95%CI] of the LSS-DST were 88.2% [87.5, 88.8] and 83.9% [83.4, 84.5], respectively, whereas the sensitivity and specificity of the LSS-DST ver2.0 were 87.7% [87.0, 88.3] and 78.3% [77.7, 78.9], respectively, indicating that LSS-DST ver2.0 is a useful screening tool for LSS with good sensitivity. CONCLUSION: When the item of ABI in the LSS-DST is replaced by palpation of the PT artery (LSS-DST ver2.0), its sensitivity is maintained as a screening tool for LSS. LEVEL OF EVIDENCE: Level 3.


Assuntos
Estenose Espinal , Humanos , Estenose Espinal/diagnóstico , Estenose Espinal/patologia , Artérias da Tíbia , Estudos Transversais , Tornozelo , Vértebras Lombares/patologia , Palpação
3.
J Neurosci ; 41(42): 8725-8741, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34462307

RESUMO

Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes in migration: (1) slowing down migration at the lesion sites; and (2) accelerating migration in the surroundings of lesion sites. Experimental manipulations of galanin signaling reduce the lesion site-specific changes in granule cell migration, indicating that galanin plays a role in such deficits in neuronal cell migration. The present study suggests that manipulating galanin signaling may be a potential therapeutic target for acutely injured brains during development.SIGNIFICANCE STATEMENT Deficits in neuronal cell migration caused by brain injury result in abnormal development of cortical layers, but the underlying mechanisms remain to be determined. Here, we report that on brain injury, endogenous levels of galanin, a neuropeptide, are altered in a lesion site-specific manner, decreasing at the lesion sites but increasing in the surroundings of lesion sites. The changes in galanin levels positively correlate with the migration rate of immature neurons. Manipulations of galanin signaling ameliorate the effects of injury on neuronal migration and cortical layer development. These results shed a light on galanin as a potential therapeutic target for acutely injured brains during development.


Assuntos
Lesões Encefálicas/metabolismo , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Movimento Celular/fisiologia , Cerebelo/metabolismo , Galanina/metabolismo , Animais , Animais Recém-Nascidos , Lesões Encefálicas/patologia , Células Cultivadas , Cerebelo/lesões , Cerebelo/patologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos
4.
Histochem Cell Biol ; 157(4): 415-426, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35024955

RESUMO

The transcription factor FOXO3 is necessary to preserve cochlear hair cells. Growth factors, including TGF-ß, closely contribute to cochlear hair cell regeneration. In the present study, to investigate the roles of FOXO3 in the ciliogenesis and cell functions of cochlear hair cells, UB/OC-2 temperature-sensitive mouse cochlear precursor hair cells were treated with TGF-ß receptor type 1 inhibitor EW-7197 or EGF receptor inhibitor AG-1478 after transfection with or without siRNA-FOXO3a. GeneChip analysis revealed that treatment with EW-7197 increased Foxo3 genes and decreased genes of Smads. During cell differentiation, treatment with EW-7197 or AG-1478 induced an increase in length of cilia-like structures that were positive for acetylated tubulin and inhibited cell migration. Treatment with EW-7197 also increased cell metabolism measured as mitochondrial basal respiration (oxygen consumption rate). The effects of EW-7197 were stronger than those of AG-1478. Knockdown of FOXO3 prevented the growth of cilia-like structures induced by EW-7197 or AG-1478 and induced cell migration under treatment with EW-7197. No change of the epithelial cell polarity molecule PAR3 was observed with any treatment. Treatment with the antimicrobial agent amikacin prevented the growth of cilia-like structures induced by EW-7197 and induced apoptosis. Pretreatment with the glucocorticoid dexamethasone inhibited the apoptosis induced by amikacin. This in vitro model of mouse cochlear hair cells suggests that FOXO3/TGF-ß signaling plays a crucial role in ciliogenesis and cell functions during differentiation of cochlear hair cells. This model is useful for analysis of the mechanisms of hearing loss and to find therapeutic agents to prevent it.


Assuntos
Amicacina , Fator de Crescimento Transformador beta , Amicacina/farmacologia , Animais , Diferenciação Celular , Células Ciliadas Auditivas , Camundongos , Temperatura
5.
FASEB J ; 35(9): e21742, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34403506

RESUMO

Withdrawal from contact inhibition is necessary for epithelial cancer precursor cells to initiate cell growth and motility. Nevertheless, little is understood about the mechanism for the sudden initiation of cell growth under static conditions. We focused on cellular junctions as one region where breaking out of contact inhibition occurs. In well-differentiated endometrial cancer cells, Sawano, the ligand administration for tricellular tight junction protein LSR, which transiently decreased the robust junction property, caused an abrupt increase in cell motility and consequent excessive multilayered cell growth despite being under contact inhibition conditions. We observed that macropinocytosis essentially and temporarily occurred as an antecedent event for the above process at intercellular junctions without disruption of the junction apparatus but not at the apical plasma membrane. Collectively, we concluded that the formation of macropinocytosis, which is derived from tight junction-mediated signaling, was triggered for the initiation of cell growth in static precancerous epithelium.


Assuntos
Adesão Celular , Inibição de Contato , Pinocitose , Receptores de Lipoproteínas/metabolismo , Fatores de Transcrição/metabolismo , Toxinas Bacterianas/farmacologia , Sítios de Ligação , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fenótipo , Pinocitose/efeitos dos fármacos , Transporte Proteico , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo
6.
Eur Spine J ; 30(9): 2450-2456, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33222004

RESUMO

PURPOSE: With spinal deformities, mental health can deteriorate due to sagittal imbalance of the spine. The purpose of this study was to clarify the relationship between sagittal imbalance and symptoms of depression among local residents in the community. METHODS: This study used data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS) in 2010. The sagittal vertical axis (SVA) was identified as an indicator of sagittal imbalance. Symptoms of depression were assessed using the 5-item version of the Mental Health Inventory. Participants were classified into three categories based on the SVA balance as normal (< 40 mm), moderate imbalance (40-95 mm), and severe imbalance (> 95 mm). To evaluate the relationship between sagittal imbalance of the spine and symptoms of depression, the adjusted risk ratio (RR) and the 95% confidence interval (CI) were calculated using a generalized linear model with Poisson link. RESULTS: There were 786 participants included in the statistical analysis. Overall, the mean age was 68.1 y (standard deviation, 8.8 y), and 39.4% were men. The prevalence of symptoms of depression by SVA category was 18.6% for normal, 23.8% for moderate, and 40.6% for severe. On multivariate analysis, the RR of SVA for symptoms of depression compared to the normal category was 1.12 (95% CI 0.7-1.70) for the moderate category and 2.29 (95% CI 1.01-5.17) for the severe category. CONCLUSION: In local community residents, sagittal imbalance had a significant association with symptoms of depression.


Assuntos
Depressão , Coluna Vertebral , Adulto , Idoso , Estudos de Coortes , Depressão/epidemiologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Síndrome
7.
Medicina (Kaunas) ; 57(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684153

RESUMO

Background and Objectives: The high prevalence of lumbar spinal stenosis (LSS) and its negative impact on quality of life in the elderly is well known. However, the longitudinal time course of LSS symptoms remains unclear. The purpose of this study was to clarify the longitudinal time course and associated factors of LSS symptoms over a period of six years in a community. Materials and Methods: This study was conducted with data prospectively collected in 2004 and 2010 under a retrospective design. In 2004, 1578 subjects (age range: 40 to 79 years) were interviewed on LSS symptoms using a specially designed and validated questionnaire. In 2010, a follow-up study was performed by mail, to which 789 subjects of the 2004 study population responded. Considering that the presence of osteoarthritis (OA) of the knee or hip may influence the participants' answers in the questionnaire, analysis was performed in all 789 subjects with and 513 subjects without either knee or hip OA. Changes in LSS symptoms between the initial and the 6-year survey were investigated. Multiple logistic regression analysis was used for detecting the risk factors for LSS symptom presence at the six-year follow-up. Results: 1. At the six-year follow-up, more than half of the subjects who showed LSS symptoms at the initial analysis became LSS-negative, and 12-15% of those who were LSS-negative became LSS-positive. 2. From the multiple logistic regression analysis, a lower Roland-Morris Disability Questionnaire (RDQ) score and a positive LSS symptom at the initial analysis were detected as predictive factors of the presence of LSS symptoms at the six-year follow-up in the total number of subjects, as well as just in those who did not have either knee or hip OA. Conclusions: More than half of the subjects who were LSS-positive at their initial assessment still experienced improvement in their symptoms even after 6 years. This means that both LSS symptoms and their time course vary from person to person. Predictive factors for the presence of LSS symptoms during the six-year follow-up period were RDQ score and positive LSS symptoms.


Assuntos
Osteoartrite do Quadril , Estenose Espinal , Adulto , Idoso , Seguimentos , Humanos , Vida Independente , Vértebras Lombares , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Estenose Espinal/epidemiologia
8.
Histochem Cell Biol ; 154(2): 197-213, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32266459

RESUMO

Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and epithelial polarity molecule PAR3. Lipolysis-stimulated lipoprotein receptor (LSR) is an important molecule at tricellular contacts, and loss of LSR promotes cell migration and invasion via Yes-associated protein (YAP) in human endometrial cancer cells. In the present study, to find how ASPP2 suppression promotes malignancy in human endometrial cancer, we investigated its mechanisms including the relationship with LSR. In endometriosis and endometrial cancers (G1 and G2), ASPP2 was observed as well as PAR3 and LSR in the subapical region. ASPP2 decreased in G3 endometrial cancer compared to G1. In human endometrial cancer cell line Sawano, ASPP2 was colocalized with LSR and tricellulin at tricellular contacts and binding to PAR3, LSR, and tricellulin in the confluent state. ASPP2 suppression promoted cell migration and invasion, decreased LSR expression, and induced expression of phosphorylated YAP, claudin-1, -4, and -7 as effectively as the loss of LSR. Knockdown of YAP prevented the upregulation of pYAP, cell migration and invasion induced by the ASPP2 suppression. Treatment with a specific antibody against ASPP2 downregulated ASPP2 and LSR, affected F-actin at tricellular contacts, upregulated expression of pYAP and claudin-1, and induced cell migration and invasion via YAP. In normal human endometrial epithelial cells, ASPP2 was in part colocalized with LSR at tricellular contacts and knockdown of ASPP2 or LSR induced expression of claudin-1 and claudin-4. ASPP2 suppression promoted cell invasion and migration via LSR and YAP in human endometrial cancer cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias do Endométrio/metabolismo , Receptores de Lipoproteínas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Movimento Celular , Células Cultivadas , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Receptores de Lipoproteínas/genética , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
9.
Histochem Cell Biol ; 153(1): 5-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650247

RESUMO

Lipolysis-stimulated lipoprotein receptor (LSR)/angulin-1 is a crucial molecule of tricellular contacts in the epithelial barrier of normal cells and the malignancy of cancer cells. To investigate whether LSR/angulin-1 affects the epithelial barrier and malignancy in human pancreatic cancer, human pancreatic cancer cell line HPAC was used. Treatment with EGF or TGF-ß increased the expression of LSR, but not tricellulin (TRIC), and induced the localization of LSR and TRIC to bicellular tight junctions from tricellular tight junctions. TGF-ß receptor type-1 inhibitor EW-7197 prevented changes of the distribution and the barrier function of LSR by TGF-ß. Knockdown of LSR increased cell migration, invasion, proliferation and EGF ligand amphiregulin expression and decreased the epithelial barrier. Treatment with amphiregulin induced cell migration and invasion and knockdown of amphiregulin prevented the increases of cell migration, invasion and proliferation caused by knockdown of LSR. Treatment with LSR ligand peptide angubindin-1 decreased the epithelial barrier and the expression of LSR, but not TRIC, and increased cell invasion. Knockdown of TRIC decreased cell migration and the epithelial barrier. In immunohistochemical analysis of human pancreatic cancer tissues, LSR and TRIC were found to be localized at the cell membranes of normal pancreatic ducts and well-differentiated pancreatic ductal adenocarcinomas (PDAC), whereas in poorly differentiated PDAC, LSR was weakly detected in the cytoplasm. Amphiregulin was highly expressed in the cytoplasm of well- and poorly differentiated PDAC. In pancreatic cancer, LSR contributes to the epithelial barrier and malignancy via growth factors and may be a potential targeting molecule in the therapy.


Assuntos
Células Epiteliais/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptores de Lipoproteínas/metabolismo , Junções Íntimas/metabolismo , Movimento Celular , Proliferação de Células , Células Epiteliais/patologia , Humanos , Neoplasias Pancreáticas/patologia , Fatores de Transcrição , Células Tumorais Cultivadas
10.
Int J Mol Sci ; 21(22)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182652

RESUMO

High mobility group box 1 protein (HMGB1) is involved in the pathogenesis of inflammatory bowel disease (IBD). Patients with IBD develop zinc deficiency. However, the detailed roles of HMGB1 and zinc deficiency in the intestinal epithelial barrier and cellular metabolism of IBD remain unknown. In the present study, Caco-2 cells in 2D culture and 2.5D Matrigel culture were pretreated with transforming growth factor-ß (TGF-ß) type 1 receptor kinase inhibitor EW-7197, epidermal growth factor receptor (EGFR) kinase inhibitor AG-1478 and a TNFα antibody before treatment with HMGB1 and inflammatory cytokines (TNFα and IFNγ). EW-7197, AG-1478 and the TNFα antibody prevented hyperpermeability induced by HMGB1 and inflammatory cytokines in 2.5D culture. HMGB1 affected cilia formation in 2.5D culture. EW-7197, AG-1478 and the TNFα antibody prevented the increase in cell metabolism induced by HMGB1 and inflammatory cytokines in 2D culture. Furthermore, ZnSO4 prevented the hyperpermeability induced by zinc chelator TPEN in 2.5D culture. ZnSO4 and TPEN induced cellular metabolism in 2D culture. The disruption of the epithelial barrier induced by HMGB1 and inflammatory cytokines contributed to TGF-ß/EGF signaling in Caco-2 cells. The TNFα antibody and ZnSO4 as well as EW-7197 and AG-1478 may have potential for use in therapy for IBD.


Assuntos
Citocinas/metabolismo , Etilenodiaminas/farmacologia , Proteína HMGB1/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Compostos de Anilina/farmacologia , Células CACO-2 , Quelantes/farmacologia , Proteína HMGB1/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/patologia , Interferon gama/metabolismo , Interferon gama/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Modelos Biológicos , Permeabilidade/efeitos dos fármacos , Quinazolinas/farmacologia , Receptores de Lipoproteínas/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Triazóis/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Tirfostinas/farmacologia , Sulfato de Zinco/farmacologia
11.
Pain Med ; 20(12): 2377-2384, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30856262

RESUMO

OBJECTIVES: To examine the longitudinal association between baseline disability due to low back pain (LBP) and future risk of falls, particularly significant falls requiring treatment, in a community-dwelling older population. METHODS: This was a prospective population-based cohort study using data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS; 2008-2010). A total of 2,738 residents aged ≥60 years were enrolled. LBP was assessed using the Roland-Morris Disability Questionnaire (RMDQ), and the level of LBP-related disability was divided into three categories (none, low, and medium to high). Incidence of falls over the following year was determined using a self-reported questionnaire after the one-year follow-up period. The risk ratio (RR) for LBP-related disability associated with any fall and any fall requiring treatment was estimated using log binomial regression models. RESULTS: Data were analyzed for 1,358 subjects. The prevalence of LBP at baseline was 16.4%, whereas 122 (8.9%) participants reported a low level of LBP-related disability and 101 (7.4%) reported medium to high levels of LBP-related disability. Incidence of any fall and falls requiring treatment was reported by 22.1% and 4.6% of participants, respectively. Subjects with medium to high levels of disability were more likely to experience subsequent falls (adjusted RR = 1.53, 95% confidence interval [CI] = 1.21-1.95) and falls requiring treatment (adjusted RR = 2.55, 95% CI = 1.41-4.60) than those with no LBP-related disability. CONCLUSIONS: Level of LBP-related disability was associated with an increased risk of serious falls in a general population of community-living older adults. These findings can alert health care providers involved in fall prevention efforts to the important issue of activity-related disability due to LBP.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Atividades Cotidianas , Dor Lombar/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vida Independente , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Risco
12.
J Orthop Sci ; 24(4): 584-589, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30616940

RESUMO

BACKGROUND: The reference values of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in patients with lumbar spinal stenosis (LSS) are still unknown. This multicenter cross-sectional survey was performed to determine the reference values and disease-specific characteristics of deterioration of QOL caused by LSS itself, not by aging, through comparison of patients with and without LSS who had an outpatient visit for low back pain by age and sex groups. METHODS: The present study was performed at 564 medical centers and clinics. The JOABPEQ was measured for 8338 patients aged 20 years or over who came to an outpatient clinic for low back pain (LBP) and were examined for whether they had LSS using the LSS diagnosis support tool (LSS-DST). Scores in the five JOABPEQ domains were compared between the LSS group and the LBP without LSS group (LBP group) for each age and sex group. RESULTS: Scores for Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders were significantly lower in the LSS group than in the LBP group. CONCLUSION: The percentiles of JOABPEQ scores in patients with LSS were clarified and could be used as reference values. Deterioration of QOL caused by LSS itself, not by aging, are characterized by Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders.


Assuntos
Técnicas de Apoio para a Decisão , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Vértebras Lombares , Qualidade de Vida , Estenose Espinal/complicações , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Medição da Dor , Valores de Referência , Inquéritos e Questionários , Avaliação de Sintomas , Adulto Jovem
14.
Cell Biol Toxicol ; 34(2): 93-107, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28656345

RESUMO

Cobalt is a trace element that localizes in the human body as cobalamin, also known as vitamin B12. Excessive cobalt exposure induces a peripheral neuropathy, the mechanisms of which are yet to be elucidated. We investigated how cobalt may affect mitochondrial motility in primary cultures of rat dorsal root ganglion (DRG). We observed mitochondrial motility by time-lapse imaging after DsRed2 tagging via lentivirus, mitochondrial structure using transmission electron microscopy (TEM), and axonal swelling using immunocytochemical staining. The concentration of cobaltous ion (Co2+) required to significantly suppress mitochondrial motility is lower than that required to induce axonal swelling following a 24-h treatment. Exposure to relatively low concentrations of Co2+ for 48 h suppressed mitochondrial motility without leading to axonal swelling. TEM images indicated that Co2+ induces mitochondrial destruction. Our results show that destruction of the axonal mitochondria precedes the axonal degeneration induced by Co2+ exposure.


Assuntos
Axônios/efeitos dos fármacos , Cobalto/toxicidade , Gânglios Espinais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Axônios/ultraestrutura , Células Cultivadas , Relação Dose-Resposta a Droga , Gânglios Espinais/embriologia , Gânglios Espinais/ultraestrutura , Idade Gestacional , Microscopia Eletrônica de Transmissão , Mitocôndrias/ultraestrutura , Neurônios/ultraestrutura , Cultura Primária de Células , Ratos Sprague-Dawley
15.
Pediatr Int ; 59(6): 686-690, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28118513

RESUMO

BACKGROUND: We tested whether direct transcutaneous bilirubin (TcB) measurement from an area unexposed to phototherapy is reliable for estimation of total serum bilirubin (TSB) in neonates during phototherapy and whether it contributes to reduction in TSB blood sampling in phototherapy decision making. METHODS: This was a retrospective observational study of term neonates who received phototherapy in the mother's room. TSB and TcB from the neonate's sternum were measured before and during phototherapy and compared using linear regression analysis and Bland-Altman plot, respectively. Various cut-offs of TcB for estimating TSB during phototherapy at >72 h after birth were analyzed. RESULTS: There were moderate correlations between TSB and TcB before (r = 0.56) and during (r = 0.47) phototherapy in 125 neonates. The mean difference (TSB-TcB) before and during phototherapy was 1.2 ± 1.7 mg/dL and 1.0 ± 1.7 mg/dL, respectively. The 95% limits of agreement for the difference before and during phototherapy ranged from -2.1 to 4.5 and from -2.3 to 4.3 mg/dL, respectively. For TSB ≤18 mg/dL during phototherapy, a TcB cut-off of 14 mg/dL had a specificity of 1.0; with this method, 43% of the TSB measurements could have been avoided. CONCLUSIONS: Direct measurement of TcB during phototherapy using a bed-type device is a reliable method to estimate TSB in term neonates and would contribute to a reduction in blood sampling. It cannot, however, be used as a substitute for TSB measurement.


Assuntos
Bilirrubina/sangue , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/terapia , Fototerapia , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Icterícia Neonatal/sangue , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
16.
Pediatr Int ; 59(2): 171-175, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27501257

RESUMO

BACKGROUND: Acquired palatal groove has been reported in the 1970s and 1980s, but its current incidence in Japanese newborns is unclear. The aims of this study were to determine the incidence of palatal groove in preterm infants and to evaluate whether this condition affects oral feeding ability. METHODS: We conducted a prospective observational study among very low-birthweight infants born at Takatsuki General Hospital, Osaka, between March and October in 2010. The shape of the hard palate was classified into three types: normal, narrow high-arched palate, and palatal groove. RESULTS: Among the 37 enrolled infants, 14 (38%) had palatal groove. In particular, among the 29 infants with birthweight <1000 g, palatal groove was observed in 48% of these patients, and only 10% were normal. Infants with palatal groove were ventilated for considerably more days with oral endotracheal tube than those without palate groove, even after adjustment for gestational age, birthweight, and duration of oral duodenal tube placement (OR, 1.11). Establishment of oral feeding and disappearance of choking on milk were considerably delayed in infants with palatal groove. Transient oral feeding difficulty requiring thickened-feed intervention was observed only in infants with palatal groove; on multi-regression analysis this difficulty seemed to be induced by the palatal groove. CONCLUSIONS: Palatal groove formation induced by oral endotracheal intubation occurs with a high frequency in preterm infants, and this is likely to affect oral feeding ability.


Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente , Doenças do Prematuro/fisiopatologia , Intubação Intratraqueal/efeitos adversos , Doenças Maxilomandibulares/fisiopatologia , Doenças da Boca/fisiopatologia , Palato Duro/patologia , Nutrição Enteral/estatística & dados numéricos , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/etiologia , Doenças do Prematuro/terapia , Recém-Nascido de muito Baixo Peso , Japão/epidemiologia , Doenças Maxilomandibulares/epidemiologia , Doenças Maxilomandibulares/etiologia , Doenças Maxilomandibulares/terapia , Doenças da Boca/epidemiologia , Doenças da Boca/etiologia , Doenças da Boca/terapia , Palato Duro/fisiopatologia , Estudos Prospectivos
17.
Am J Perinatol ; 34(1): 26-30, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27182994

RESUMO

Objectives Although adding volume guarantee (VG) to conventional ventilation has been a well-established respiratory management for preterm infants, the evidence of VG combined with high-frequency oscillatory ventilation (HFOV) has not been studied well. The aim of this study was to investigate the effect of VG added to HFOV on respiratory and other physiological parameters. Methods We conducted a pilot study in extremely low-birth-weight infants ventilated with HFOV + VG with stable pulmonary status after 28 days of age. VG was applied for 6 hours and removed for the following 6 hours, and data were collected during these 12 hours. Results Six neonates were included in this study (gestational age: 22w5d-23w6d, birthweight: 424-584 g). High-frequency expired tidal volume per weight and amplitude were similar between periods with and without VG. Fluctuation of SpO2, but not heart rate, was significantly smaller when babies were ventilated with VG than without VG. Fluctuation of minute volume and carbon dioxide diffusion coefficient significantly increased after VG removal. The proportion of time with SpO2 < 80% was decreased by VG overall, especially in three cases. Conclusion This pilot study suggests VG combined with HFOV attenuates fluctuation of SpO2 and CO2 clearance, which may prevent hypoxemia and hypocapnia.


Assuntos
Ventilação de Alta Frequência/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Dióxido de Carbono/metabolismo , Feminino , Idade Gestacional , Frequência Cardíaca , Humanos , Hipocapnia/etiologia , Hipocapnia/metabolismo , Hipóxia/etiologia , Hipóxia/metabolismo , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Oximetria , Projetos Piloto , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/metabolismo , Volume de Ventilação Pulmonar
18.
J Orthop Sci ; 22(4): 647-651, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28551282

RESUMO

BACKGROUND: Numbness in the soles of both feet at rest or bowel/bladder dysfunction can occur in patients with lumbar spinal stenosis (LSS), especially in patients with cauda equina lesions. The purpose of this study was to clarify the relationship between cauda equina symptoms at rest and quality of life (QOL) in LSS patients using standardized questionnaires developed for the Japanese population. METHODS: A survey was conducted in 564 hospitals and general practice clinics nationwide from December 1, 2011 to December 31, 2012. All patients who visited hospital or clinic because of low back pain were included. Patients were diagnosed with LSS using the LSS-Diagnostic Support Tool (LSS-DST), and the severity of the disease was measured using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) for quality of life. Presence of both sole numbness and/or bowel/bladder dysfunction were determined by medical interview. 3647 patients were diagnosed with LSS according to the results of the LSS-DST. 1294 of these patients (35.5%) had symptoms at rest. Of these patients, 359 patients with sole numbness, 135 patients with bowel/bladder dysfunction, and 52 patients with both numbness and bowel/bladder dysfunction were compared to the patients without rest symptoms (n = 2182). Comparisons between groups with or without sole numbness and bowel/bladder dysfunction were performed using statistical analysis of JOABPEQ responses in the categories of pain-related disorder, lumbar spine disorder, gait disturbance, social life disturbance, and psychological disorder. RESULTS: All groups with sole numbness and/or bowel/bladder dysfunction had statistically lower (worse) scores in all categories of the JOABPEQ compared to the group without these symptoms at rest. CONCLUSION: LSS patients having numbness in the soles of both feet at rest or bowel/bladder dysfunction had lower measurements of QOL and activities of daily living than those patients without symptoms at rest. These symptoms appear to be related to QOL of LSS patients.


Assuntos
Hipestesia/etiologia , Enteropatias/etiologia , Vértebras Lombares , Estenose Espinal/complicações , Estenose Espinal/diagnóstico , Doenças da Bexiga Urinária/etiologia , Adulto , Idoso , Estudos Transversais , Feminino , , Humanos , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Descanso , Inquéritos e Questionários , Adulto Jovem
19.
J Foot Ankle Surg ; 56(3): 628-631, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28215361

RESUMO

Osteochondroma, one of the most common benign bone tumors, frequently occurs in the metaphysis of the long bones. We report an extremely rare case of osteochondroma that occurred in the tibial sesamoid. The patient was a 62-year-old Japanese male. He presented with a 1-year history of pain and a hard mass on the plantar aspect of the right forefoot sole. The osteochondroma protruded toward the sole from the tibial sesamoid, leading to pain on weightbearing. After tibial sesamoidectomy, the patient's symptoms were eliminated, and no pain or complications such as hallux valgus occurred after the surgery. Although a potential risk exists of postoperative hallux valgus deformity, tibial sesamoidectomy seems to be an appropriate surgical option for both osteochondroma and bizarre parosteal osteochondromatous proliferation to avoid residual pain or local recurrence.


Assuntos
Neoplasias Ósseas/patologia , Osteocondroma/patologia , Ossos Sesamoides/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteocondroma/diagnóstico por imagem , Osteocondroma/cirurgia , Ossos Sesamoides/diagnóstico por imagem , Ossos Sesamoides/cirurgia
20.
Clin Lab ; 62(11): 2285-2289, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28164678

RESUMO

BACKGROUND: Blood gas analyses are usually required more frequently in preterm neonates than in term neonates. If total bilirubin (TB) levels in whole blood measured using a blood gas analyzer are reliable, blood sampling for total serum bilirubin (TSB) levels alone can be reduced in preterm neonates. We investigated the reliability of measuring TB levels in whole blood from preterm neonates using the latest generation blood gas analyzer. METHODS: TB measured on an ABL90 FLEX blood gas analyzer and TSB analyzed in the hospital laboratory were simultaneously analyzed. TB and TSB levels (300 data sets in 85 preterm neonates) were compared using linear regression and Bland-Altman difference plots. RESULTS: Concordance correlation coefficient analysis showed a strong relationship between TB and TSB levels (a CCC value of 0.94) with a Pearson's coefficient of 0.97 and a bias correction of 0.97. Bland-Altman difference p lots demonstrated that, on average, TB tended to underestimate the TSB, with a mean (95% confidence interval) bias of -0.7 (-0.6 to -0.8) mg/dL. CONCLUSIONS: Whole blood TB levels measured using an ABL90 FLEX are reliable and can lead to a reduction in blood sampling for TSB in preterm neonates.


Assuntos
Bilirrubina/sangue , Gasometria/instrumentação , Hiperbilirrubinemia Neonatal/diagnóstico , Recém-Nascido Prematuro/sangue , Triagem Neonatal/instrumentação , Biomarcadores/sangue , Desenho de Equipamento , Idade Gestacional , Humanos , Hiperbilirrubinemia Neonatal/sangue , Recém-Nascido , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
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