RESUMO
Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer's disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case-control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle-brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease.
Assuntos
Doença de Alzheimer/fisiopatologia , Rim/fisiopatologia , Rigidez Vascular , Idoso , Albuminas/metabolismo , Albuminúria/fisiopatologia , Índice Tornozelo-Braço , Estudos de Casos e Controles , Disfunção Cognitiva/fisiopatologia , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Transtornos da Memória/fisiopatologia , Testes Neuropsicológicos , Percepção , Análise de Onda de PulsoRESUMO
It has been proposed that Wnt signaling pathway may be a key radioprotective mechanism in irradiated cancer cells; however, the specific radioresistance mechanisms remain not to be fully clarified. Here we elucidate a novel signaling pathway of radioresistance in head and neck cancer (HNC) cell lines involving interactions among the Wnt signaling pathway, cyclooxygenase-2 (COX-2) and Ku expression. Activation of the Wnt signaling pathway by (2'Z,3'E)-6-bromoindirubin-3'-oxime (BIO) resulted in beta-catenin cytoplasmic accumulation and translocation to the nucleus, upregulated Ku expression and increased radioresistance in the COX-2-expressing HNC cell line. In contrast, Wnt singaling activation by BIO had no effects on Ku expression and radiosensitivity in a HNC cell line negative for COX-2. Interactions between Wnt singaling and Ku were indirectly regulated by COX-2. Blockage of COX-2 signaling led to the suppression of beta-catenin-induced Ku expression, and to consequent recovery of the radiosensitivity in HNC cells. Our results conclusively suggest that beta-catenin plays a pivotal role in the regulation of Ku expression via the proposed COX-2 intracellular pathway, thus supporting a novel radioresistance mechanism of HNC.
Assuntos
Ciclo-Oxigenase 2/metabolismo , DNA Helicases/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas Wnt/metabolismo , Western Blotting , Núcleo Celular/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/genética , Citoplasma/metabolismo , DNA Helicases/genética , Imunofluorescência , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Marcação In Situ das Extremidades Cortadas , Indóis/farmacologia , Autoantígeno Ku , Oximas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Tolerância a Radiação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais Cultivadas , beta Catenina/metabolismoRESUMO
OBJECTIVE: The purpose of the present study was to investigate cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD) with mild to severe stages of motor symptoms and to compare cardiovascular autonomic dysfunction between drug-naïve and dopaminergic drug-treated groups. METHODS: This study included 188 PD patients and 25 age-matched healthy controls who underwent head-up tilt-testing, 24-h ambulatory blood pressure (BP) monitoring and 24-h Holter monitoring. Autonomic function test results were evaluated among groups categorized by motor symptom severities (mild vs. moderate vs. severe) and treatment (drug-naïve or dopaminergic drug treatment). RESULTS: Orthostatic hypotension and supine hypertension were more frequent in patients with PD than in healthy controls. The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different among groups. Additionally, no significant differences were detected in supine BP, orthostatic BP change, nighttime BP, nocturnal BP dipping, or heart rate variabilities among groups. CONCLUSIONS: Cardiovascular autonomic dysfunction is not confined to moderate to severe PD patients, and starts early in the course of the disease in a high proportion of PD patients. In addition, dopaminergic drug treatments do not affect cardiovascular autonomic function.
RESUMO
The application of the single-file technique using the reciprocating motion is gaining concern in root canal preparation. The purpose of this research is to compare the efficiency of the reciprocating motion-employing files (RECIPROC and WaveOne) by measuring the working time for complete canal shaping, and to evaluate their reusability under scanning examinations. One hundred curved root canals of the extracted molars were used. The working length was determined and the glide path was confirmed using a #15 K-file. Canals shaping was completed to the length either with RECIPROC R25 file (n = 50), or with WaveOne Primary file (n = 50). The time taken for the file to reach the working length was also measured. Each file was repeatedly used in a maximum of 10 canals for comparing the change of the efficiency (shaping time) according to the working length, canal curvature, and number of file re-use. The deformations or surface defects of the files after the in vitro use were observed using a scanning electron microscope (SEM). There was no difference under the SEM between the 2 file groups with no initiation of micro-cracks until they were re-used up to 5 canals. WaveOne Primary file showed significantly shorter working time than RECIPROC R25 (p < 0.05). There was a statistically significant correlation between the working time and three variables. As the working length and the curvature of the canal increased, the shaping time was increased in both file systems. Reusability of these reciprocating instruments might be maximum 5 canals with minimal surface deformations.
Assuntos
Cavidade Pulpar/anatomia & histologia , Equipamentos e Provisões , Níquel , Preparo de Canal Radicular/instrumentação , Preparo de Canal Radicular/métodos , Propriedades de Superfície , Titânio , Humanos , Dente Molar/anatomia & histologia , Resultado do TratamentoRESUMO
Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are osmotic demyelination syndrome. A 45-year-old man with a history of alcoholism visited the ER with dysarthria and dysphagia for 2 days. These symptoms occurred 3 days after he had stopped drinking alcohol. The neurological symptoms progressed to anarthria, pseudobulbar palsy and gait disturbance. During admission, the electrolyte studies were within the normal range. Diffusion-weighted images revealed high signal intensities in the pons, thalamus and basal ganglia. Apparent diffusion coefficient image showed low signal intensities in the pontine lesion, but isosignal intensities in the extrapontine lesion. The symptoms gradually improved after 1 month with only conservative treatment. The 1 month-follow-up MRI showed significant reduction of the previous extrapontine lesions. These findings suggest that cytotoxic edema is central to the pathogenesis of CPM, but vasogenic edema plays an important role in the pathogenesis of EPM occurring during alcohol withdrawal.
Assuntos
Alcoolismo/complicações , Etanol/efeitos adversos , Mielinólise Central da Ponte/etiologia , Síndrome de Abstinência a Substâncias/complicações , Alcoolismo/terapia , Edema/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Mielinólise Central da Ponte/diagnóstico , PrognósticoRESUMO
Interleukin (IL)-18, a member of the IL-1 cytokine family, is an important mediator of peripheral inflammation and host defence responses. However, although IL-1 is a key proinflammatory cytokine in the brain, little is known about IL-18 changes in glial cells under excitotoxic neurodegeneration. In this study, we characterized the expressions of IL-18 and IL-18 receptor (IL-18R) in kainic acid (KA)-induced excitotoxicity in mouse hippocampus by immunohistochemistry and Western blotting. IL-18 immunoreactivity was found in microglia whereas IL-18R immunoreactivity was observed in astrocytes. Levels of IL-18 and IL-18R in hippocampus homogenates increased progressively from day 1 post-KA and peaked at 3 days. This study demonstrates the cellular sources of IL-18 and IL-18R, and their temporal correlations after KA-insult, and suggests roles for IL-18 and IL-18R in glial cells in response to excitotoxic damage in the hippocampus.
Assuntos
Hipocampo/efeitos dos fármacos , Interleucina-18/metabolismo , Ácido Caínico/toxicidade , Neuroglia/metabolismo , Receptores de Interleucina-18/metabolismo , Animais , Western Blotting , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Glycogen synthase kinase 3beta (GSK3beta) is believed to play important roles in the regulation of synaptic plasticity, cell survival and circadian rhythms in the mature CNS. However, although several studies have been focused on the GSK3beta, little is known about GSK3beta changes in glial cells under neuropathological conditions. In this study, we evaluated the expressions of molecules associated with the GSK3beta signaling pathway, following the induction of an excitotoxic lesion in mouse brain by kainic acid (KA) injection, which caused pyramidal cell degeneration in the hippocampal CA3 region. In injured hippocampi, Ser47-Akt (protein kinase B, PKB) phosphorylation increased from 4 h until 1 day post-injection (PI). Ser9-GSK3beta and Ser133-cAMP responsive element-binding protein (CREB) phosphorylations showed similar spatiotemporal patterns in hippocampi at 1 day until 3 days PI. Double immunohistochemistry also showed that these phosphorylated forms of Akt, GSK3beta and CREB were expressed in astrocytes. For the first time, our data demonstrate the injury-induced astrocytic changes in the levels of phosphorylation of Akt, -GSK3beta and -CREB in vivo, which may reflect mechanisms of glial cells protection or adaptive response to damage.
Assuntos
Astrócitos/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Quinase 3 da Glicogênio Sintase/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Animais , Western Blotting , Perfilação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta , Hipocampo/efeitos dos fármacos , Ácido Caínico/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , FosforilaçãoRESUMO
In the present study, we examined patterns of A-myb expression in the kainic acid (KA)-treated mouse hippocampus. Western blot analysis revealed that A-myb expression was dramatically increased in brain 3 days after KA treatment, and was sustained for more than 7 days. A-myb immunoreactivity was restricted to hippocampal neurons in control mice. Three days after KA treatment, strong A-myb immunoreactivity was observed in reactive astrocytes throughout the CA3 region. Thereafter, A-myb immunoreactive astrocytes gradually concentrated around the CA3 region in parallel with selective neuronal loss, and only a few A-myb immunoreactive astrocytes persisted in the CA3 region 14 days after KA treatment. These findings suggest that the A-myb plays a role in the reactive gliosis signaling pathway in KA-induced excitotoxic lesions.