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1.
J Pathol ; 263(1): 8-21, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38332735

RESUMO

Pompe disease is a lysosomal storage disorder that preferentially affects muscles, and it is caused by GAA mutation coding acid alpha-glucosidase in lysosome and glycophagy deficiency. While the initial pathology of Pompe disease is glycogen accumulation in lysosomes, the special role of the lysosomal pathway in glycogen degradation is not fully understood. Hence, we investigated the characteristics of accumulated glycogen and the mechanism underlying glycophagy disturbance in Pompe disease. Skeletal muscle specimens were obtained from the affected sites of patients and mouse models with Pompe disease. Histological analysis, immunoblot analysis, immunofluorescence assay, and lysosome isolation were utilized to analyze the characteristics of accumulated glycogen. Cell culture, lentiviral infection, and the CRISPR/Cas9 approach were utilized to investigate the regulation of glycophagy accumulation. We demonstrated residual glycogen, which was distinguishable from mature glycogen by exposed glycogenin and more α-amylase resistance, accumulated in the skeletal muscle of Pompe disease. Lysosome isolation revealed glycogen-free glycogenin in wild type mouse lysosomes and variously sized glycogenin in Gaa-/- mouse lysosomes. Our study identified that a defect in the degradation of glycogenin-exposed residual glycogen in lysosomes was the fundamental pathological mechanism of Pompe disease. Meanwhile, glycogenin-exposed residual glycogen was absent in other glycogen storage diseases caused by cytoplasmic glycogenolysis deficiencies. In vitro, the generation of residual glycogen resulted from cytoplasmic glycogenolysis. Notably, the inhibition of glycogen phosphorylase led to a reduction in glycogenin-exposed residual glycogen and glycophagy accumulations in cellular models of Pompe disease. Therefore, the lysosomal hydrolysis pathway played a crucial role in the degradation of residual glycogen into glycogenin, which took place in tandem with cytoplasmic glycogenolysis. These findings may offer a novel substrate reduction therapeutic strategy for Pompe disease. © 2024 The Pathological Society of Great Britain and Ireland.


Assuntos
Doença de Depósito de Glicogênio Tipo II , Glicoproteínas , Humanos , Camundongos , Animais , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/patologia , Doença de Depósito de Glicogênio Tipo II/terapia , Glicogênio/análise , Glicogênio/metabolismo , Glucosiltransferases/metabolismo , Músculo Esquelético/patologia , Lisossomos/metabolismo
2.
Clin Lab ; 70(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39257125

RESUMO

BACKGROUND: The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirma-tory testing for specimens with low positive hepatitis B surface antigen (HBsAg). METHODS: A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemilumi-nescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including e-antigen, e-antibody, and core antibody patterns, was also performed. RESULTS: When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. CONCLUSIONS: For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface an-tigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B , Sensibilidade e Especificidade , Humanos , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Estudos Retrospectivos , Hepatite B/diagnóstico , Hepatite B/sangue , Hepatite B/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Ensaio de Imunoadsorção Enzimática/métodos , Adulto , Testes de Neutralização/métodos , Curva ROC , Vírus da Hepatite B/imunologia , Adulto Jovem
3.
Ann Neurol ; 91(4): 568-574, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35148013

RESUMO

Coronavirus disease 2019 (COVID-19) severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2 infection) can lead to intensive care unit (ICU) admission and critical illness myopathy (CIM). We examined 3 ICU patients with COVID-19 who required mechanical ventilation for pneumonia and developed CIM. Pathological examination of the skeletal muscle biopsies revealed myopathic changes consistent with CIM, variable inflammation with autophagic vacuoles, SARS-CoV immunostaining + fibers/granules, and electron microscopy findings of mitochondrial abnormalities and coronavirus-like particles. Although mitochondrial dysfunction with compromised energy production is a critical pathogenic mechanism of non-COVID-19-associated CIM, in our series of COVID-19-associated CIM, myopathic changes including prominent mitochondrial damage suggest a similar mechanism and association with direct SARS-CoV-2 muscle infection. ANN NEUROL 2022;91:568-574.


Assuntos
COVID-19/complicações , COVID-19/virologia , Estado Terminal , Doenças Musculares/etiologia , Doenças Musculares/virologia , SARS-CoV-2 , Adulto , Idoso , Autofagia , Evolução Fatal , Feminino , Humanos , Inflamação/patologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Mitocôndrias/patologia , Músculo Esquelético/patologia , Vacúolos/patologia
4.
Br J Neurosurg ; 37(4): 943-950, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32162556

RESUMO

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is thought to be a rare tumefactive lesion with unknown pathogenesis. Its prevalence is questionable with few previously reported cases of incidental CAPNON, and likely underdiagnosis. We report a unique case of incidental multifocal CAPNON. A 64-year-old female was admitted with loss of consciousness due to a ruptured right middle cerebral artery aneurysm with subarachnoid and intraventricular hemorrhage. She has a craniotomy and clipping. At time of operation, numerous small dural-based nodules were found, and one was excised for biopsy and was diagnosed as CAPNON. Retrospective review of her CT images identified nodules that were all ipsilateral to the ruptured aneurysm. A literature review revealed that incidental and/or multifocal CAPNONs are rare but likely underreported. Our case suggests a reactive process in the pathogenesis of CAPNON.


Assuntos
Calcinose , Humanos , Feminino , Pessoa de Meia-Idade , Calcinose/complicações , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Sistema Nervoso Central/patologia , Craniotomia , Hemorragia Cerebral/cirurgia
5.
Br J Neurosurg ; 37(5): 1245-1250, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33253051

RESUMO

BACKGROUND: Central nervous system (CNS) lymphomas frequently pose a diagnostic challenge to physicians. CNS anaplastic large cell lymphoma (ALCL) is a rare condition. A majority (80%) of ALCLs harbour anaplastic lymphoma kinase 1 (ALK-1) mutation with only a minority testing negative for this mutation. METHODS: Here we report a rare case of ALK-negative CNS ALCL with dural involvement. We conducted a literature search using PubMed for published studies in English on cases of patients with ALCL of the brain. The keywords used were 'anaplastic large cell lymphoma', 'ALK' and 'primary central nervous system lymphoma'. RESULTS: A 63-year-old man presents with waxing and waning cranial nerve and spinal cord symptoms. MRI revealed multiple intracranial and intra-spinal lesions that were highly steroid responsive. A wide range of serum and CSF tests were non-diagnostic during three months of workup before a lesion appeared in the cervical spine that required decompression and allowed us to obtain a tissue sample. Final pathology revealed ALK-negative ALCL. There are only 24 reported adult cases to date of CNS ALCL in the English literature. To our knowledge, this is the first case of ALK-negative ALCL with primarily CNS and meningeal involvement. CONCLUSIONS: ALK-negative ALCL with CNS involvement is extremely rare, which frequently results in delayed diagnosis (average 40.5 days). The diagnostic challenge posed by this case highlights the importance of a team approach to workup and diligent patient follow-up for such a rare disease.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Anaplásico de Células Grandes , Humanos , Masculino , Pessoa de Meia-Idade , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/patologia , Mutação , Receptores Proteína Tirosina Quinases/genética
6.
Br J Neurosurg ; : 1-8, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36597892

RESUMO

BACKGROUND: Intracranial rhabdomyosarcomas represent a rare condition, posing a diagnostic challenge to physicians. Brain intraparenchymal rhabdomyosarcomas are exceptionally rare with poorly understood pathogenesis. METHODS: Here we report the first adult case of intraparenchymal rhabdomyosarcoma (RMS) with brainstem and cranial nerve involvement. We conducted a literature search using Embase, MEDLINE, and PubMed for published cases of patients with rhabdomyosarcoma of the brain. The keywords used were 'rhabdomyosarcoma' combined with 'intraparenchymal', 'parenchymal', 'cerebral' or 'brain' for title/abstract. Included cases were adult patients (>18 years of age). RESULTS: A 59-year-old man presents with multiple cranial nerve palsies. MRI revealed a solitary pontine lesion that was not responsive to steroids. No systemic lesions were identified with an extensive imaging workup. A wide range of serum and cerebrospinal fluid tests were non-diagnostic during a ten-month workup until, ultimately, the patient died as a result of aspiration pneumonia. At autopsy, pathological examination on whole-brain autopsy revealed RMS, centred in the left side of pons with extension to the left side of the midbrain and the right side of pons with multiple cranial nerve involvement. There are only 20 adult cases of primary intraparenchymal RMS reported in the literature. Our present case is the first reported adult RMS in this location, with novel molecular information, providing some insight into the pathogenesis of this rare diagnosis. CONCLUSIONS: Intraparenchymal rhabdomyosarcoma without evidence of systemic primary disease is extremely rare, resulting in delayed diagnosis in some cases, particularly those not amenable to biopsy. The diagnostic challenge posed by this complementary case highlights the importance of maintaining a differential of neoplasm in the face of non-diagnostic investigations to the contrary.

7.
Acta Neuropathol ; 144(6): 1127-1142, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36178522

RESUMO

Glioblastoma (GBM) is characterized by extensive cellular and genetic heterogeneity. Its initial presentation as primary disease (pGBM) has been subject to exhaustive molecular and cellular profiling. By contrast, our understanding of how GBM evolves to evade the selective pressure of therapy is starkly limited. The proteomic landscape of recurrent GBM (rGBM), which is refractory to most treatments used for pGBM, are poorly known. We, therefore, quantified the transcriptome and proteome of 134 patient-derived pGBM and rGBM samples, including 40 matched pGBM-rGBM pairs. GBM subtypes transition from pGBM to rGBM towards a preferentially mesenchymal state at recurrence, consistent with the increasingly invasive nature of rGBM. We identified immune regulatory/suppressive genes as important drivers of rGBM and in particular 2-5-oligoadenylate synthase 2 (OAS2) as an essential gene in recurrent disease. Our data identify a new class of therapeutic targets that emerge from the adaptive response of pGBM to therapy, emerging specifically in recurrent disease and may provide new therapeutic opportunities absent at pGBM diagnosis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Neoplasias Encefálicas/genética , Proteômica , Recidiva Local de Neoplasia/genética , Transcriptoma
8.
J Neuroinflammation ; 18(1): 85, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33810797

RESUMO

BACKGROUND: Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure. METHODS: Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro. RESULTS: Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment. CONCLUSION: CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.


Assuntos
Quimiocina CXCL5/metabolismo , Glucocorticoides/toxicidade , Hipocampo/metabolismo , Transtornos da Memória/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Aprendizagem Espacial/fisiologia , Animais , Quimiocina CXCL5/antagonistas & inibidores , Dexametasona/toxicidade , Relação Dose-Resposta a Droga , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Técnicas de Cultura de Órgãos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Aprendizagem Espacial/efeitos dos fármacos
9.
Can J Neurol Sci ; 48(2): 259-266, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32800010

RESUMO

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions. METHODS: We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry. RESULTS: Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON. CONCLUSION: NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.


Assuntos
Calcinose , Axônios , Linfócitos T CD8-Positivos , Calcinose/diagnóstico por imagem , Sistema Nervoso Central , Humanos , Imuno-Histoquímica
10.
Neurol Sci ; 42(12): 5123-5130, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33779865

RESUMO

OBJECTIVE: To report a Chinese family with combined m.14459G>A mutation and m.6064A>T mutation of which the female proband presenting unique Leber hereditary optic neuropathy and dystonia (LDYT) overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) phenotype. METHODS: Clinical information of the pedigree was collected. We performed muscle biopsy and whole-length mitochondrial DNA (mtDNA) sequencing on the proband. The activity of respiratory chain complexes in immortalized lymphoblasts was determined. RESULTS: The current 23-year-old proband suffered from vision decline at age 15 and developed seizures and dystonia with bilateral lesions in precentral gyri at age 18. When she was 21, the lesions in bilateral putamen were found with elevated cerebrospinal fluid lactate. Her mother had optic atrophy; one of her brother died at age 4 with respiratory distress; and the other 8-year-old brother was asymptomatic. Muscle biopsy of the proband was unremarkable. The mtDNA sequencing revealed a heteroplasmic m.14459G>A mutation and a previously unreported m.6064A>T mutation. The respiratory chain complex I activity in the proband's immortalized lymphoblasts was 50% less than the normal control; while there was no statistical difference between the proband and the normal control in the activity of complex IV. CONCLUSIONS: We presented the first case exhibiting LDYT and MELAS phenotype with m.14459G>A mutation, and the decreased complex I activity contributed to the pathogenicity. Our study expanded the clinical spectrum of m.14459G>A mutation.


Assuntos
Acidose Láctica , Distonia , Encefalomiopatias Mitocondriais , Atrofia Óptica Hereditária de Leber , Acidente Vascular Cerebral , Acidose Láctica/complicações , Acidose Láctica/genética , Adolescente , Adulto , Criança , Pré-Escolar , DNA Mitocondrial/genética , Distonia/complicações , Distonia/genética , Feminino , Humanos , Masculino , Mutação , Atrofia Óptica Hereditária de Leber/complicações , Atrofia Óptica Hereditária de Leber/genética , Linhagem , Adulto Jovem
11.
Proc Natl Acad Sci U S A ; 115(26): E6065-E6074, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29895691

RESUMO

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1ß and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE). We observed inflammasome activation and pyroptosis in human microglia and ODCs in vitro after exposure to inflammatory stimuli and demonstrate caspase-1 inhibition by the small-molecule inhibitor VX-765 in both cell types. GSDMD inhibition by siRNA transduction suppressed pyroptosis in human microglia. VX-765 treatment of EAE animals reduced the expression of inflammasome- and pyroptosis-associated proteins in the CNS, prevented axonal injury, and improved neurobehavioral performance. Thus, GSDMD-mediated pyroptosis in select glia cells is a previously unrecognized mechanism of inflammatory demyelination and represents a unique therapeutic opportunity for mitigating the disease process in MS and other CNS inflammatory diseases.


Assuntos
Caspase 1/metabolismo , Inibidores de Caspase/farmacologia , Dipeptídeos/farmacologia , Modelos Biológicos , Esclerose Múltipla/enzimologia , Oligodendroglia/enzimologia , Piroptose/efeitos dos fármacos , para-Aminobenzoatos/farmacologia , Células Cultivadas , Humanos , Esclerose Múltipla/patologia , Oligodendroglia/patologia
12.
Can J Neurol Sci ; 47(3): 389-397, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31843039

RESUMO

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion. CAPNONs can mimic calcified meningiomas at the skull base. METHODS: Here, we report two cases of CAPNON and present a systematic review of the literature on skull base CAPNONs, to compare CAPNONs with calcified meningiomas. RESULTS: Case 1: A 57-year-old man presented with right-sided lower cranial neuropathies and gait ataxia. He underwent a subtotal resection of a right cerebellopontine angle lesion, with significant improvement of his gait ataxia. However, his cranial neuropathies persisted. Pathological examination of the lesion was diagnostic of CAPNON, with the entrapped nerve fibers identified at the periphery of the lesion, correlating with the patient's cranial neuropathy. Case 2: A 70-year-old man presented with progressive headache, gait difficulty, and cognitive impairment. He underwent a frontotemporal craniotomy for a near-total resection of his right basal frontal CAPNON. He remained neurologically stable 7 years after the initial resection without evidence of disease recurrence. We analyzed 24 reported CAPNONs at the skull base in our systematic review of the literature. Cranial neuropathies were present in 11 (45.8%) patients. Outcomes regarding cranial neuropathies were documented in six patients: two had sacrifice of the nerve function with surgical approaches and four had persistent cranial neuropathies. CONCLUSION: While CAPNON can radiologically and grossly mimic calcified meningiomas, they are two distinctly different pathologies. CAPNONs located at the skull base are commonly associated with cranial neuropathies, which may be difficult to reverse despite surgical intervention.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Neoplasias da Base do Crânio/diagnóstico , Idoso , Encefalopatias/complicações , Encefalopatias/patologia , Calcinose/complicações , Calcinose/patologia , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/fisiopatologia , Doenças dos Nervos Cranianos/etiologia , Doenças dos Nervos Cranianos/fisiopatologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Base do Crânio
13.
J Strength Cond Res ; 34(12): 3454-3462, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28475549

RESUMO

Sun, M-Y, Lu, J-Q, Ma, Z-C, Lü, J-J, Huang, Q, Sun, Y-N, and Liü, Y. Effects of the inertia barbell training on lumbar muscle T2 relaxation time. J Strength Cond Res 34(12): 3454-3462, 2020-The purpose of this study was to investigate variations in T2 relaxation time in normal human lumbar muscles caused by inertia barbell training. Thirty undergraduate healthy men (mean age = 19 ± 1.2 years, body mass = 72 ± 10.0 kg, and height = 1.78 ± 0.1 m) were recruited to participate in this study. Subjects were randomly assigned into 2 groups: an inertia barbell training group (IBTG) (n = 15) and a normal barbell-training group (NBTG) (n = 15). All subjects participated in lumbar flexion and extension muscle strength training for 1 hour per time, 3 times per week for a total of 8 weeks. The lumbar area of each subject was scanned before and after the experiment using a 3.0T superconductive magnetic resonance imaging system. The T2 values measured after intervention were significantly different compared with the T2 values measured before the experiment in both the IBTG and NBTG groups (p < 0.001). After intervention, there was no significant difference in T2 values between the IBTG and NBTG groups (p = 0.17). The ([INCREMENT]T2)/T2 percentage was significantly different in the IBTG group (p < 0.01). This study demonstrated that 8 weeks of strength training led to significant improvements in the values for T2 relaxation time of the lumbar muscles. Furthermore, the ([INCREMENT]T2)/T2 percentage for IBTG was higher than that for NBTG, which suggested that lumbar muscle activity increased more with inertial barbell training.


Assuntos
Músculos do Dorso/fisiologia , Relaxamento Muscular/fisiologia , Força Muscular/fisiologia , Treinamento Resistido/métodos , Adolescente , Humanos , Masculino , Adulto Jovem
15.
FASEB J ; 32(8): 4258-4269, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29543532

RESUMO

Pregnant women at risk of preterm labor usually receive synthetic glucocorticoids (sGCs) to promote fetal lung development. Emerging evidence indicates that antenatal sGC increases the risk of affective disorders in offspring. Data from animal studies show that such disorders can be transmitted to the second generation. However, the molecular mechanisms underlying the intergenerational effects of prenatal sGC remain largely unknown. Here we show that prenatal dexamethasone (Dex) administration in late pregnancy induced depression-like behavior in first-generation (F1) offspring, which could be transmitted to second-generation (F2) offspring with maternal dependence. Moreover, corticotropin-releasing hormone (CRH) and CRH receptor type 1 (CRHR1) expression in the hippocampus was increased in F1 Dex offspring and F2 offspring from F1 Dex female rats. Administration of a CRHR1 antagonist to newborn F1 Dex offspring alleviated depression-like behavior in these rats at adult. Furthermore, we demonstrated that increased CRHR1 expression in F1 and F2 offspring was associated with hypomethylation of CpG islands in Crhr1 promoter. Our results revealed that prenatal sGC exposure could program Crh and Crhr1 gene expression in hippocampus across 2 generations, thereby leading to depression-like behavior. Our study indicates that prenatal sGC can cause epigenetic instability, which increases the risk of disease development in the offspring's later life.-Xu, Y.-J., Sheng, H., Wu, T.-W., Bao, Q.-Y., Zheng, Y., Zhang, Y.-M., Gong, Y.-X., Lu, J.-Q., You, Z.-D., Xia, Y., Ni, X. CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Depressão/induzido quimicamente , Depressão/metabolismo , Glucocorticoides/efeitos adversos , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Animais , Ilhas de CpG/efeitos dos fármacos , Dexametasona/efeitos adversos , Feminino , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Relações Mãe-Filho , Gravidez , Regiões Promotoras Genéticas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
J Neurovirol ; 24(3): 376-378, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29508303

RESUMO

Sarcocystosis is a zoonotic infection that causes intestinal and muscular illnesses in humans. Sarcocystosis was until recently considered rare in humans. To complete their life cycle, Sarcocystis species require both a definitive and an intermediate host. Humans are the definitive host when infected by one of two species: Sarcocystis hominis (from eating undercooked beef) or Sarcocystis suihominis (from eating uncooked pork). Infection with either of these species results in intestinal sarcocystosis, causing a self-limited disease characterized by nausea, abdominal pain, and diarrhea. Humans act as the intermediate host when infected by Sarcocystis nesbitti, resulting in the markedly different clinical picture of muscular sarcocystosis. Most documented cases of muscular sarcocystosis were assumed to be acquired in Malaysia, in addition to other regions of Southeast Asia and India. Published cases of muscular sarcocystosis from the Middle East, Central and South America, and Africa are all rare. Although the clinical presentation of muscular sarcocystosis remains to be fully characterized, fever, myalgia, and headache are among the most common symptoms. Here, we report a patient from sub-Saharan Africa with chronic Sarcocystis myopathy and well-controlled HIV-AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Doenças Musculares/diagnóstico , Sarcocystis/patogenicidade , Sarcocistose/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Síndrome da Imunodeficiência Adquirida/virologia , África Subsaariana , Fármacos Anti-HIV/uso terapêutico , Antiparasitários/uso terapêutico , Canadá , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/tratamento farmacológico , Doenças Musculares/parasitologia , Doenças Musculares/fisiopatologia , Sarcocystis/isolamento & purificação , Sarcocistose/tratamento farmacológico , Sarcocistose/parasitologia , Sarcocistose/fisiopatologia , Viagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
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