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971.
Acute ethanol exposure disrupts actin cytoskeleton and generates reactive oxygen species in c6 cells
Samanta Oliveira LoureiroLuana Heimfarth Karina ReisLuiza Wild Cláudia AndradeFátima Theresinha Costa Rodrigues Guma Carlos Alberto GonçalvesRegina Pessoa-Pureur 《Toxicology in vitro》2011,25(1):28-36
Central nervous system dysfunctions are among the most significant effects of exposure to ethanol and the glial cells that play an important role in maintaining neuronal function, are extremely involved with these effects. The actin cytoskeleton plays a crucial role in a wide variety of cellular functions, especially when there is some injury. Therefore the aim of the present study was to analyze the short-term effects of ethanol (50, 100 and 200 mM) on the cytoskeleton of C6 glioma cells. Here we report that acute ethanol exposure profoundly disrupts the actin cytoskeleton in C6 cells decreasing stress fiber formation and downregulating RhoA and vinculin immunocontent. In contrast, microtubule and GFAP networks were not altered. We further demonstrate that anti-oxidants prevent ethanol-induced actin alterations, suggesting that the actions of ethanol on the actin cytoskeleton are related with generation of reactive oxygen species (ROS) in these cells. Our results show that ethanol at concentrations described to be toxic to the central nervous system was able to target the cytoskeleton of C6 cells and this effect could be related with increased ROS generation. Therefore, we propose that the dynamic restructuring of the cytoskeleton of glial cells might contribute to the response to the injury provoked by binge-like ethanol exposure in brain. 相似文献
972.
973.
974.
Kelly Ishida Gonzalo Visbal Juliany Cola Fernandes Rodrigues Julio A. Urbina Wanderley de Souza Sonia Rozental 《Journal of infection and chemotherapy》2011,17(4):563-570
Three quinuclidine-based squalene synthase (SQS) inhibitors (BPQ-OH, E5700, and ER-119884) were evaluated against five Candida tropicalis strains with different susceptibility profiles to fluconazole (FLC), itraconazole (ITC), terbinafine (TRB), and amphotericin
B (AMB). Although the quinuclidine derivatives were inactive against most C. tropicalis strains tested at concentrations up to 16 μg/ml, E5700 and ER-119884 showed antifungal activity against C. tropicalis ATCC 28707, a strain resistant to FLC, ITC, and AMB, with IC50 and IC90 values (i.e., the minimum inhibitory concentrations of the drugs determined as the lowest drug concentrations leading to
a 50 and 90% of reduction in turbidity at 492 nm, respectively, after 48 h of incubation) of 1 and 4 μg/ml, respectively.
Analysis of free sterols showed that non-treated C. tropicalis ATCC 28707 cells contained only 14-methylated sterols and that treatment with E5700 or ER-119884 led to a marked reduction
of squalene content and the complete disappearance of the endogenous sterols. The fatty acid and phospholipid profiles in
C. tropicalis ATCC 28707 cells grown in the presence of E5700 and ER-119884 were also markedly altered, with a large increase in the content
of linolenic acid (C18:3), associated with a reduction in the content of linoleic (C18:2) and oleic (C18:1) acids. Treatment
of C. tropicalis ATCC 28707 with E5700 or ER-119884 IC50 values induced several ultrastructural alterations, including a marked increase in the thickness of the cell wall and the
appearance of a large number of electron-dense vacuoles. In conclusion, our results indicated that E5700 and ER-119884 inhibited
the growth and altered the lipid prolife and the ultrastructure of a multiple drug-resistant C. tropicalis strain. Therefore, such compounds could act as leads for the development of new treatment options against multidrug resistant
Candida species. 相似文献
975.
Delano FA Chen AY Wu KI Tran ED Rodrigues SF Schmid-Schönbein GW 《Drug discovery today. Disease models》2011,8(1):37-46
One of the key features of cardiovascular complications, such as hypertension or diabetes, is that they often appear at the same time in the same individual together with other forms of co-morbidities. While clinically a recognized phenomenon, no molecular mechanism for such co-morbidities has received universal acceptance. We propose a new hypothesis that provides a molecular basis for co-morbidities in hypertension due to unchecked proteolytic activity and receptor destruction. Testing of the hypothesis in the spontaneously hypertensive rat reveals an unchecked matrix metalloproteinase and serine protease activity in plasma and on several cardiovascular and parenchymal cells. The elevated proteolytic activity causes extracellular cleavage of multiple receptor types, such that cleavage of one receptor type leads to loss of the function carried out by this receptor. Proteolytic cleavage of the extracellular domain of the β(2) adrenergic receptor in arteries and arterioles causes vasoconstriction and elevation of the central blood pressure while cleavage of the extracellular domain of the insulin receptor leads to insulin resistance and lack of transmembrane glucose transport. A diverse set of cell dysfunctions in the spontaneously hypertensive rat are accompanied by cleavage of the membrane receptors that are involved in these functions. Chronic inhibition of the unchecked protease activity in the spontaneously hypertensive rat serves to restore the extracellular receptor density and alleviates the corresponding cell dysfunctions. The mild unchecked proteolytic activity in the spontaneously hypertensive rat points towards a chronic autodigestion process as a contributor to the end organ injury encountered in this rat strain. The presence of various soluble receptors, which consist of extracellular fragments of membrane receptors, in the plasma of hypertensive and diabetic patients suggest that the autodigestion process may also be present in man. 相似文献
976.
Celso Arrais Rodrigues Renata Ferrarotto Roberto Kalil Filho Yana A. S. Novis Paulo M. G. Hoff 《Journal of thrombosis and thrombolysis》2010,30(1):67-78
Venous thromboembolism (VTE) is a serious and potentially fatal disorder, which is often associated with a significant impact
on the quality of life and on the clinical outcome of cancer patients. The pathophysiology of the association between thrombosis
and cancer is complex: malignancy is associated with a baseline hypercoagulable state due to many factors including release
of inflammatory cytokines, activation of the clotting system, expression of hemostatic proteins on tumor cells, inhibition
of natural anticoagulants, and impaired fibrinolysis. Several risk factors, related to the patient, the disease, and the therapeutic
interventions, have been identified as contributing to the occurrence of VTE. There is convincing evidence to recommend the
use of heparins or fondaparinux for prevention of VTE in selected cancer patients, and, especially in some particular types
of malignancies and cancer treatments. Management of VTE in patients with cancer is more challenging and bleeding complications
associated with the use of anticoagulants are significantly higher in cancer patients than in those without malignancy. Important
issues that need to be considered in all cases are interference with anticancer therapy, inconvenience of treatment, and impact
on quality of life. 相似文献
977.
Beatriz Pardo Tiago B Rodrigues Laura Contreras Miguel Garzón Irene Llorente-Folch Keiko Kobayashi Takeyori Saheki Sebastian Cerdan Jorgina Satrústegui 《Journal of cerebral blood flow and metabolism》2011,31(1):90-101
The glutamate–glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate–glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo 13C nuclear magnetic resonance labeling with 13C2acetate or (1-13C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes. 相似文献
978.
Luce Marina Freires Corrêa da Costa Aparecida Duarte Hg Mussi Marylina Rodrigues Brianeze Francisco José Dutra Souto 《The Brazilian journal of infectious diseases》2008,12(1):24-26
In order to assess the importance of HCV infection as a possible risk factor for type 2 diabetes mellitus, a case-control study was conducted, comparing the prevalence of HCV infection among diabetic and non-diabetic patients. Diabetic outpatients attending to a University Hospital in Central-West Brazil were evaluated between April and October 2005. A control group composed by patients from the same institution was matched by gender and age. Candidates to control group were included only if fasting glucose measures were under 100 mg/dL. Diabetics and controls had blood samples taken in order to test for antibodies against HCV (anti-HCV) by enzyme-immunoassay. Polymerase chain reaction and immunoblot were performed to confirm the anti-HCV status. Each group included 206 participants. Despite of the groups were in general comparable. The diabetics had a greater body mass average and smaller family income. The prevalence of confirmed anti-HCV in the diabetic group was of 1.4%, which was similar to the controls (1%). Finding statistical difference may have been hampered by the low frequency of HCV infection in both groups. It was not possible to demonstrate a role of HCV as an etiologic factor in type 2 diabetes, since HCV infected patients represented a small portion of the overall diabetes cases. This finding does not allow to recommend regular screening for HCV infection in type 2 diabetics in this region. 相似文献
979.
BACKGROUND: Metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) participate in the degeneration of the extracellular matrix and are associated with carcinogenesis. MMP-2 is one of the main metalloproteinases active in neoplasia and is a marker of the malignant phenotype. Since the biological behavior of medullary thyroid carcinoma (MTC) varies widely, the present study was undertaken to determine if there is a correlation between the clinical evolution of MTC and the immunohistochemically detected expression of these enzymes in thyroid surgical specimens containing MTC. If so, their expression would be a novel indicator of the prognosis of MTC. METHODS: Thirty-seven patients with MTC who had undergone thyroid surgery were followed for an average of 73 months. Immunohistochemical staining for metalloproteinase-related enzymes was performed in surgical paraffin blocks. The clinical status of the patients after surgery and at the end of the study period was characterized to determine correlations between these and the immunohistochemical markers. A value of p < 0.05 was considered statistically significant. RESULTS: At the end of the study period, 15 patients (40.5%) were alive and without evidence of MTC, 17 (45.9%) had persistent MTC, and 5 (13.5%) had a relapse of their neoplasia. Four patients (10.8%) died during the course of the study. There was a significant correlation (p = 0.0005) between the immunohistochemical staining for MMP-2 and the clinical condition of the patients at the end of the study period, and a correlation between the state of apparent cure compared to persistence of MTC after thyroid surgery (p = 0.0207). No significant correlations were observed between either TIMP-2 expression or immune marking of metastatic lymph nodes and the clinical variables studied. CONCLUSION: Immunohistochemical expression of MMP-2 in thyroid surgical specimens from patients with MTC is a novel indicator of the prognosis of this cancer. 相似文献
980.
Maeli Dal Pai-Silva Anete Kinumi Ueda LuiZ.A.L. Resende Vitalino DaL. Pai Armando Alves Antônio Tadeu Souza Faleiros Antonio De Castro Rodrigues 《International journal of experimental pathology》2001,82(2):123-128
The objective of this paper was to study the effect of sympathetic innervation on morphological and histochemical aspects of skeletal muscle tissue. Rabbit masseter muscle was studied using histochemical and immunohistochemical methods for periods of up to 18 months post-sympathectomy. The morphological and enzymatic characteristics of control masseter muscles were similar on both the left and right sides. The main features were muscle fibres with a mosaic pattern and a predominance of type IIa fibres, followed by type I. Type IIb fibres showed very low frequency. Sympathectomized animals showed varying degrees of metabolic and morphological alterations, especially 18 months after sympathectomy. The first five groups showed a higher frequency of type I fibres, whilst the oldest group showed a higher frequency of type IIb fibres. In the oldest group, a significant variation in fibre diameter was observed. Many fibres showed small diameter, atrophy, hypertrophy, splitting, and necrosis. Areas with fibrosis were observed. Thus cervical sympathectomy induced morphological alterations in the masseter muscles. These alterations were, in part, similar to both denervation and myopathy. These findings indicate that sympathetic innervation contributes to the maintenance of the morphological and metabolic features of masseter muscle fibres. 相似文献