RESUMO
Autophagy is a cellular homeostatic process by which cells degrade and recycle their malfunctioned contents, and impairment in this process could lead to Parkinson's disease (PD) pathogenesis. Dioscin, a steroidal saponin, has induced autophagy in several cell lines and animal models. The role of dioscin-mediated autophagy in PD remains to be investigated. Therefore, this study aims to investigate the hypothesis that dioscin-regulated autophagy and autophagy-related (ATG) proteins could protect neuronal cells in PD via reducing apoptosis and enhancing neurogenesis. In this study, the 1-methyl-4-phenylpyridinium ion (MPP+) was used to induce neurotoxicity and impair autophagic flux in a human neuroblastoma cell line (SH-SY5Y). The result showed that dioscin pre-treatment counters MPP+-mediated autophagic flux impairment and alleviates MPP+-induced apoptosis by downregulating activated caspase-3 and BCL2 associated X, apoptosis regulator (Bax) expression while increasing B-cell lymphoma 2 (Bcl-2) expression. In addition, dioscin pre-treatment was found to increase neurotrophic factors and tyrosine hydroxylase expression, suggesting that dioscin could ameliorate MPP+-induced degeneration in dopaminergic neurons and benefit the PD model. To conclude, we showed dioscin's neuroprotective activity in neuronal SH-SY5Y cells might be partly related to its autophagy induction and suppression of the mitochondrial apoptosis pathway.
Assuntos
1-Metil-4-fenilpiridínio , Doença de Parkinson , 1-Metil-4-fenilpiridínio/toxicidade , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Diosgenina/análogos & derivados , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismoRESUMO
Lindera obtusiloba Blume (family, Lauraceae), native to Northeast Asia, has been used traditionally in the treatment of trauma and neuralgia. In this study, we investigated the neuroinflammatory effect of methanol extract of L. obtusiloba stem (LOS-ME) in a scopolamine-induced amnesia model and lipopolysaccharide (LPS)-stimulated BV2 microglia cells. LOS-ME downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, inflammatory cytokines, and inhibited the phosphorylation of nuclear factor kappa-B (NF-ĸB) and extracellular signal-regulated kinase (ERK) in LPS-stimulated BV2 cells. Male C57/BL6 mice were orally administered 20 and 200 mg/kg of LOS-ME for one week, and 2 mg/kg of scopolamine was administered intraperitoneally on the 8th day. In vivo behavioral experiments (Y-maze and Morris water maze test) confirmed that LOS-ME alleviated cognitive impairments induced by scopolamine and the amount of iNOS expression decreased in the hippocampus of the mouse brain. Microglial hyper-activation was also reduced by LOS-ME pretreatment. These findings suggest that LOS-ME might have potential in the treatment for cognitive improvement by regulating neuroinflammation.
Assuntos
Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Lindera/química , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Escopolamina/efeitos adversos , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Hipocampo/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the bloodâ»brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous system. The bioavailability and potential of curcumin can be improved by using a nanodelivery system, which includes solid lipid nanoparticles. Curcumin-loaded solid lipid nanoparticles (SLCN) were efficiently developed to have a particle size of about 86 nm and do not exhibit any toxicity in the endothelial brain cells. Furthermore, the curcumin-loaded solid lipid nanoparticles (SLCN) were studied to assess their efficacy in BV-2 microglial cells against LPS-induced neuroinflammation. The SLCN showed a higher inhibition of nitric oxide (NO) production compared to conventional curcumin in a dose-dependent manner. Similarly, the mRNA and proinflammatory cytokine levels were also reduced in a dose-dependent manner when compared to those with free curcumin. Thus, SLCN could be a potential delivery system for curcumin to treat microglia-mediated neuroinflammation.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Curcumina/administração & dosagem , Lipídeos , Lipopolissacarídeos/imunologia , Microglia/efeitos dos fármacos , Microglia/fisiologia , Nanopartículas , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Lipídeos/química , Camundongos , Nanopartículas/química , Óxido NítricoRESUMO
Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.
Assuntos
Adjuvantes Anestésicos/efeitos adversos , Amnésia/etiologia , Amnésia/metabolismo , Amnésia/psicologia , Comportamento Animal , Biomarcadores , Disfunção Cognitiva , Escopolamina/efeitos adversos , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ativação Enzimática , Expressão Gênica , Hipocampo/metabolismo , Inflamação/genética , Inflamação/metabolismo , Peroxidação de Lipídeos , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Aprendizagem Espacial , Especificidade da EspécieRESUMO
STATEMENT OF PROBLEM: Recently, zirconia removal diamond rotary instruments have become commercially available for efficient cutting of zirconia. However, research of cutting efficiency and the cutting characteristics of zirconia removal diamond rotary instruments is limited. PURPOSE: The purpose of this in vitro study was to assess and compare the cutting efficiency, durability, and diamond rotary instrument wear pattern of zirconia diamond removal rotary instruments with those of conventional diamond rotary instruments. In addition, the surface characteristics of the cut zirconia were assessed. MATERIAL AND METHODS: Block specimens of 3 mol% yttrium cation-doped tetragonal zirconia polycrystal were machined 10 times for 1 minute each using a high-speed handpiece with 6 types of diamond rotary instrument from 2 manufacturers at a constant force of 2 N (n=5). An electronic scale was used to measure the lost weight after each cut in order to evaluate the cutting efficiency. Field emission scanning electron microscopy was used to evaluate diamond rotary instrument wear patterns and machined zirconia block surface characteristics. Data were statistically analyzed using the Kruskal-Wallis test, followed by the Mann-Whitney U test (α=.05). RESULTS: Zirconia removal fine grit diamond rotary instruments showed cutting efficiency that was reduced compared with conventional fine grit diamond rotary instruments. Diamond grit fracture was the most dominant diamond rotary instrument wear pattern in all groups. All machined zirconia surfaces were primarily subjected to plastic deformation, which is evidence of ductile cutting. Zirconia blocks machined with zirconia removal fine grit diamond rotary instruments showed the least incidence of surface flaws. CONCLUSIONS: Although zirconia removal diamond rotary instruments did not show improved cutting efficiency compared with conventional diamond rotary instruments, the machined zirconia surface showed smoother furrows of plastic deformation and fewer surface flaws.
Assuntos
Instrumentos Odontológicos , Zircônio , Prótese Dentária , Diamante , Técnicas In Vitro , Microscopia Eletrônica de VarreduraRESUMO
SiO(x) nanoparticles were synthesized using a specially designed induction melting system equipped with a segmented graphite crucible. The graphite crucible with the segmented wall was the key to enhancing the evaporation rate due to the increase of the evaporation area and convection of the silicon melt. Injection of the gas mixture of oxygen (O2) and argon (Ar) on silicon (Si) melt caused the formation of SiO(x) nanoparticles. The evaporated SiO(x) nanoparticles were then cooled and condensed in a process chamber. The effects of the O2/Ar ratio in the injection gas on the microstructures of the SiO(x) nanoparticles were then investigated. Synthesized SiO(x) nanoparticles were proven to be of a homogeneous amorphous phase with average diameters of 30-35 nm. The microstructures were independent from the O2/Ar ratio of the injected gas. However, x increased from 1.36 to 1.84 as the O2/Ar ratio increased. The purity of the synthesized nanoparticles was about 99.9%. SiO(x) nanoparticles could be applied as the active anode material in a lithium (Li) ion secondary battery.
Assuntos
Argônio/química , Cristalização/métodos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Oxigênio/química , Dióxido de Silício/química , Silício/química , Calefação , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Kainic acid (KA) induces hippocampal cell death and astrocyte proliferation. There are reports that sphingosine kinase (SPHK)1 and sphingosine-1- phosphate (S1P) receptor 1 (S1P(1)) signaling axis controls astrocyte proliferation. Here we examined the temporal changes of SPHK1/S1P(1) in mouse hippocampus during KA-induced hippocampal cell death. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection. There was an increase in Fluoro-Jade B-positive cells in the hippocampus of KA-treated mice with temporal changes of glial fibrillary acidic protein (GFAP) expression. The lowest level of SPHK1 protein expression was found 2h after KA treatment. Six hours after KA treatment, the expression of SPHK1 and S1P(1) proteins steadily increased in the hippocampus. In immunohistochemical analysis, SPHK1 and S1P(1) are more immunoreactive in astrocytes within the hippocampus of KA-treated mice than in hippocampus of control mice. These results indicate that SPHK1/S1P(1) signaling axis may play an important role in astrocytes proliferation during KA-induced excitotoxicity.
Assuntos
Hipocampo/efeitos dos fármacos , Ácido Caínico/toxicidade , Fosfotransferases (Aceptor do Grupo Álcool)/biossíntese , Receptores de Lisoesfingolipídeo/biossíntese , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Proteína Glial Fibrilar Ácida , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/biossíntese , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologiaRESUMO
In the patients with brain metastasis (BM), it is impossible to determine who will benefit from surgery because of limited survival. In an attempt to identify optimal candidates for brain metastatectomy, we analyzed patients who survived for <3 months after craniotomy for a single BM lesion. Between January 1st, 1997 and July 31st, 2007, 83 patients with a single BM underwent craniotomy. Of these patients, 25 patients (30.1%) died within 3 months of craniotomy. The primary lesions were non-small call lung cancer in 15, colon cancer in 6, and breast cancer, renal cell carcinoma, ovarian cancer, or esophageal cancer in one apiece. Of the 25 patients, 19 (79%) were of tumor stage IV and had extra-cranial metastasis. Eleven (44%) of the 25 primary cancers had a well-controlled status. Twelve patients (48%) had a Karnofsky Performance Scale (KPS) score of <70, and 13 (52%) were of Recursive Partitioning Analysis (RPA) class 3. Primary cancer status, RPA class, and functional status were found to be critical factors for consideration when selecting surgical candidates. In addition, adjuvant therapy was found to have an important role on survival.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Craniotomia , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
Schwannomas are the most common extramedullary spinal tumors, with chronic progressive symptoms being the most common presenting features. The acute hemorrhagic onset of a spinal schwannoma is a rare occurrence. Here, we report the case of a 37-year-old male who presented with complaint of neck pain and an acute onset of quadriparesis. MRI of his cervical spine revealed an intradural extramedullary lesion in the C2 to C3 cervical segment, with features of acute hemorrhage but mild enhancement. He was operated in emergency and complete microsurgical resection of tumor was achieved. Histopathology revealed features of an ancient schwannoma with hemorrhage. Postoperatively, the patient showed significant improvement.
RESUMO
Recently, our research team reported the anti-amnesic potential of desalted-hydroethanolic extracts of Salicornia europaea L. (SE-EE). In this study, we performed bioactivity-guided isolation and identification of Acanthoside B (Aca.B), from SE-EE, as the potential bioactive candidate and examined anti-amnesic activity with its potential mechanism of action using an in vivo model. S7-L3-3 purified from SE-EE showed enhanced in vitro acetylcholinesterase (AChE) inhibitory activity. The isolated S7-L3-3 was identified and characterized as Aca.B using varied spectral analyses, i.e., Nuclear magnetic resonance (NMR), Ultraviolet-visible (UV-Vis), and Electrospray ionization-mass spectrometry (ESI-MS). In the in vitro studies, Aca.B exhibited negligible toxicity and showed a dose-dependent nitric oxide inhibitory potential in Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. In the in vivo studies, the oral administration of Aca.B to mice showed enhanced bioavailability and dose-dependent repression of the behavioral/cognitive impairment by regulating the cholinergic function, restoring the antioxidant status, attenuating the inflammatory cytokines/mediators and actively enriching neurotropic proteins in the hippocampal regions of the scopolamine-administered mice.
Assuntos
Amnésia/induzido quimicamente , Furanos/farmacologia , Glucosídeos/farmacologia , Inflamação/metabolismo , Lignanas/farmacologia , Receptores Colinérgicos/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Glicoproteínas de Membrana/metabolismo , Camundongos , Oxirredução , Proteínas Tirosina Quinases/metabolismo , Escopolamina/farmacologiaRESUMO
BACKGROUND: Although metabolic syndrome (MetS) has been associated with various diseases, few studies to date have addressed the association between MetS and hearing loss. AIMS/OBJECTIVES: This cross-sectional review of health examination center data sought to determine the association between MetS and hearing disturbance. MATERIAL AND METHODS: This study involved 28,866 subjects. Height, weight, waist circumference, and blood pressure were measured, and basic blood tests and pure-tone audiometry (PTA) were performed. Other factors analyzed included body mass index, hypertension, diabetes mellitus, and hyperlipidemia. RESULTS: Age and gender did not differ between subjects with and without MetS. PTA was slightly higher in subjects with than without MetS, but the difference was not statistically significant (p = .47). The incidence of hearing loss was no higher in subjects who met three of the five diagnostic criteria of MetS than in those who met 0-2 criteria, but was significantly higher in subjects who met four (p = .04) and five (p < .01) criteria. CONCLUSIONS AND SIGNIFICANCE: MetS may be associated with hearing loss, especially in subjects who meet four or five of the diagnostic criteria for MetS.
Assuntos
Perda Auditiva/etiologia , Síndrome Metabólica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perda Auditiva/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Poly(3,4-ethylenedioxythiophene)-tosylate (PEDOT-Tos) can be synthesized through an in situ polymerization and doping process with iron(III) p-toluenesulfonate hexahydrate as an oxidant. Both the Seebeck coefficient and the electrical conductivity were modified by varying the concentration of the oxidant. We investigated the effects of varying the concentration of the oxidant on the particle sizes and doping (oxidation) levels of PEDOT-Tos for thermoelectric applications. We demonstrated that an increase in the oxidant enabled an expansion of the particle sizes and the doping levels of the PEDOT-Tos. The modification of the doping levels by the concentration of the oxidant can provide another approach for having an optimal power factor for thermoelectric applications. De-doping of PEDOTs by reduction agents has been generally investigated for changing its oxidation levels. In this study, we investigated the effect of the concentration of the oxidant of PEDOT-Tos on the oxidation levels, the electrical conductivities and the Seebeck coefficients. As loading the oxidant of PEDOT-Tos, the Seebeck coefficient was compromised, while the electrical conductivity increased.
RESUMO
In recent years, the incidental rate of neurodegenerative disorders has increased proportionately with the aging population. Alzheimer's disease (AD) is one of the most commonly reported neurodegenerative disorders, and it is estimated to increase by roughly 30% among the aged population. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates - such as acetylcholinesterase inhibitors are currently utilized as an effective clinical therapy. However, targeted drug delivery of these drugs to the central nervous system (CNS) exhibits several limitations including meager solubility, low bioavailability, and reduced efficiency due to the impediments of the blood-brain barrier (BBB). Current advances in nanotechnology present opportunities to overcome such limitations in delivering active drug candidates. Nanodrug delivery systems are promising in targeting several therapeutic moieties by easing the penetration of drug molecules across the CNS and improving their bioavailability. Recently, a wide range of nano-carriers, such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have been adapted to develop successful therapeutics with sustained release and improved efficacy. Here, we discuss few recently updated nano-drug delivery applications that have been adapted in the field of AD therapeutics, and future prospects on potential molecular targets for nano-drug delivery systems.
Assuntos
Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/química , Nanopartículas/química , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipídeos/química , Polímeros/químicaRESUMO
BACKGROUND AND OBJECTIVES: Viral and vascular disorders are considered to be a major cause of idiopathic sudden sensorineural hearing loss (ISSNHL). Lipoprostaglandin E1 (lipo-PGE1) has vasodilating activity and has been used to treat ISSNHL. The purpose of this study was to determine the specific therapeutic effects of lipo-PGE1 and compare them to other treatment modalities for ISSNHL. SUBJECTS AND METHODS: The study group had 1,052 patients diagnosed with ISSNHL. All were treated with steroid, carbogen inhalation, stellate ganglion block (SGB), or PGE1. The CP group (steroid, carbogen inhalation, and PGE1 injection; 288 patients) was treated with lipo-PGE1 and carbogen inhalation, the CS group (steroid, carbogen inhalation, and stellate ganglion block; 232 patients) with steroid, carbogen inhalation, and SGB, the C group (steroid and carbogen inhalation; 284 patients) with steroid and carbogen, and the control group (steroid only; 248 patients) with steroid only. Patients in the groups receiving lipo-PGE1 received a continuous infusion of 10 µL lipo-PGE1. RESULTS: The overall recovery rate after treatment was 52.2%, and recovery rates by group were 67.7% in the CP group, 54.3% in the CS group, 52.1% in the C group, and 32.2% in the control group. Therefore, the therapeutic results in groups treated with lipo-PGE1 were better than results in other groups. The difference was statistically significant. CONCLUSIONS: The study results suggested that the CP group received effective treatment modalities for ISSNHL. The combined therapy of lipo-PGE1 with carbogen inhalation in patients with ISSNHL was more beneficial than other treatment modalities.
RESUMO
BACKGROUND: Several studies have reported an association between seizure and the weather. However, reports are conflicting. Thus, we investigated whether emergency department visits due to seizure are affected by weather. METHODS: We retrospectively analyzed 108,628 emergency department visits to Samsung Changwon Hospital by pediatric patients from January 2005 to December 2015. Among them, there were 3484 (3.2%) visits for any type of seizure. Seizures were categorized as febrile seizure, afebrile seizure, epilepsy, or status epilepticus. We used a distributed lag non-linear model with quasi-Poisson distribution to investigate the association between weather and pediatric seizure. RESULTS: During this 11-year study period, over the half of total pediatric seizure patients were febrile seizure (53.5%) and the proportion for status epilepticus were the lowest (5.9%). Mean of mean temperature and diurnal temperature range were 14.7°C and 8.3°C. Mean humidity was 62.1%, mean of atmospheric pressure was 1015.5hPa and mean of sunshine was 6.3Hr. When considering the overall 0-15days lagged effect of weather, only mean temperature was significantly associated with emergency department visits. At lower temperatures, the number of emergency department visits increases and decreases at higher temperatures. All 4 types of seizure also showed similar patterns. In particular, only visits of febrile seizure were significantly associated with mean temperature. CONCLUSION: We investigated the association weather and pediatric seizure by considering 0-15day lags. In particular, low mean temperature increase the emergency department visits for pediatric seizure and high mean temperature decrease the pediatric seizure. In addition, only febrile seizure of 4 seizure types was affected by mean average temperature.
Assuntos
Convulsões/epidemiologia , Temperatura , Tempo (Meteorologia) , Adolescente , Pressão Atmosférica , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Umidade , Lactente , Recém-Nascido , Masculino , República da Coreia , Estudos Retrospectivos , Adulto JovemRESUMO
Guillain-Barré syndrome (GBS) is an inflammatory demyelinating polyneuropathy characterized by areflexic paralysis. Most cases of GBS are preceded by an infection, however, posttraumatic GBS has also recently been reported. We report a case of posttraumatic GBS immediately following a traffic accident. We think this case is of clinical significance for practitioners because of the rare cause of a sudden flaccid paralysis following trauma.
RESUMO
The present study investigated the use of cell-cycle regulators for predicting the progression of silent pituitary adenoma (SPA) following surgical resection, via immunohistochemical analysis of tumor samples obtained by surgical resection. The medical records of patients diagnosed with SPA between January 2000 and December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was performed on sections of the archived, paraffin-embedded tissues obtained by surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15, p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53. The primary end-point was to investigate the expression of cell-cycle regulatory proteins in SPA. The secondary end-point was to estimate the progression-free survival of patients with SPA following surgical resection and to identify its association with the expression of cell-cycle regulatory proteins. Of the 127 SPA samples, 44 (34.6%) were from patients with progression during a mean follow-up period of 62.4 months (range, 24.2-118.9 months). Immunohistochemical overexpression was identified in 61 samples (48.0%) for p16, 38 samples (29.9%) for p15, 19 samples (15.0%) for p21, 49 samples (38.6%) for CDK4, 17 samples (13.4%) for CDK6, 57 samples (44.9%) for pRb and in 65 samples (51.2%) for cyclin D1. Multivariate analysis revealed that null cell adenoma [95% confidence interval (CI), 0.276-0.808], somatotroph SPAs (95% CI, 1.296-3.121), corticotroph SPAs (95% CI, 1.811-4.078), pluripotent SPAs (95% CI, 2.264-5.194), decreased expression of p16 (95% CI, 2.724-5.588), overexpression of pRb (95% CI, 2.557-5.333), cyclin D1 (95% CI, 1.894-4.122) and MIB-1 (95% CI, 1.561-4.133), increased mitotic index (95% CI, 1.228-4.079), increased p53 expression (95% CI, 1.307-4.065) and invasion into the cavernous sinus (95% CI, 3.842-7.502) predicted SPA progression following resection. The results of the present study suggested that specific cell-cycle regulators, including p16, cyclin D1 and pRb, were associated with SPA progression.
RESUMO
INTRODUCTION: The integration of reactive oxygen species is strongly associated with important pathophysiological mechanisms that mediate myocardial ischaemia/reperfusion (I/R) damage. Pyruvate is an efficacious scavenger of reactive oxygen species and a previous study has shown that ethyl pyruvate (EP) has a myocardial protective effect against regional I/R damage in an in vivo rat model. The purpose of this study was to determine whether the myocardial protective effect of EP is associated with anti-apoptosis. METHODS: Rats were allocated to receive EP dissolved in lactated Ringer's solution or lactated Ringer's solution alone, via intraperitoneal infusion one hour before ischaemia. They were exposed to 30 minutes of ischaemia followed by reperfusion of the left coronary artery territory over two hours. Anti-apoptotic effects were checked using several biochemical parameters after two hours of reperfusion. Apoptosis was analysed using measured caspase-3 activity, Western blotting of B-cell lymphoma 2 (Bcl-2) family protein cleaved by caspase-3, and assessment of DNA laddering patterns and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining test. RESULTS: In ischaemic myocardium, EP increased Bcl-2 expression, but reduced Bcl-2-associated X protein and cleaved caspase-3 expressions. EP reduced the expression of DNA laddering and the number of myocardial I/R-damaged TUNEL-positive cells. CONCLUSION: This study demonstrated that EP has an anti-apoptotic effect after regional I/R damage in an in vivo rat heart model. The myocardial protective effect of EP may be related to its anti-apoptotic effect.
Assuntos
Apoptose , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/patologia , Piruvatos/uso terapêutico , Animais , Caspase 3/metabolismo , Fragmentação do DNA , Modelos Animais de Doenças , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
The effects of two crude bacteriocins (DF01 and K10) on lactic acid bacteria (LAB) communities and pH during kimchi fermentation were analyzed by polymerase chain reactiondenaturing gradient gel electrophoresis (PCR-DGGE). Crude LAB bacteriocins, prepared by ammonium sulfate precipitation, were added at 5 AU/mL, and kimchi was incubated at 20°C for 7 days. The pH and titratable acidity of the kimchies were determined daily, and the amplified 16S rRNA products were analyzed by PCR-DGGE. The common and main LAB were Weissella spp., Leuconostoc spp., and Lactobacillus spp. from both control and bacteriocin-treated samples. Among them, W. koreensis, W. confusa, and Lb. sakei were the predominant microorganisms throughout the fermentation period. Some obligate and facultatively heterofermentative LAB were detected from the bacteriocin-treated samples. The pH of the kimchi samples treated with each bacteriocin was higher (ca. 0.8 unit) than that of the control at day 4 and 5.
RESUMO
BACKGROUND: The aim of this study is to report the results of pure endoscopic endonasal transsphenoidal surgery (EETSS) for pituitary adenomas (PAs) and to evaluate the efficacy and safety of this procedure. In addition, we tried to determine the predicting factors for progression of PAs. METHODS: We reviewed the medical records of 331 consecutive patients who underwent pure EETSS of newly diagnosed PAs between April 1998 and December 2014. Demographic, endocrinologic, and radiologic features and their outcomes, complications, and hospital stay durations were retrospectively assessed in these patients. RESULTS: There were 157 (47.4%) nonfunctioning adenomas and 174 (52.6%) hormone-secreting adenomas. Fifty-one (15.4%) complications were present in 39 patients postoperatively. The frequent complications were temporary and permanent diabetes insipidus (14 and 3 cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (9 cases), and cerebrospinal fluid leaks (6 cases). There was only 1 death (0.3%) related to the procedure in this series. The patient's age (P = 0.047), the tumor size (P = 0.003), and the parasellar growth (P <0.001) were associated with the occurrence of complications on multivariate analysis. Progression occurred in 92 (27.8%) patients and the mean time-to-progression was 23.7 months (range, 3.7-52.4 months) after a mean follow-up period of 68.5 months. In the multivariate analysis, the tumor size (P = 0.021), the extent of surgery (P = 0.012), the Knosp classification (P = 0.002), and the MIB-1 index (P = 0.019) were associated with progression-free survival. The mean duration of hospitalization was 4.4 (±1.6) days. CONCLUSIONS: The pure EETSS of PA provides acceptable and reasonable results representing a safe alternative procedure to the traditional transsphenoidal microscopic approach.