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991.
Visualization of neuronal elements is of fundamental importance in modern neuroscience. Golgi-Cox impregnation is a widely
employed method that provides detailed information about morphological characteristics of neurons, but none regarding their
neurochemical features. Immunocytochemical procedures, on the other hand, can provide a high degree of biochemical specificity
but poorer morphological details, in particular if compared to Golgi-Cox impregnation. Hence, the combined use of these two
approaches is highly desirable, especially for confocal microscopy that can exploit the advantages of both methods simultaneously.
Here we show an innovative procedure of perfusion and fixation of brain tissue, that allows, by applying Golgi-Cox impregnation
and immunofluorescence in the same histological section, to obtain high-quality histological material, with a very simple
and inexpensive method. This procedure is based on three simple fixation steps: (1) a paraformaldehyde perfusion followed
by a standard post-fixation to stabilize the subsequent immunofluorescence reaction; (2) the classical Golgi-Cox impregnation
and (3) an immunofluorescence reaction in previously impregnated material. This combination allows simultaneous visualization
of (a) the structural details (Golgi-Cox impregnated neurons), (b) the antigens’ characterization, (c) the anatomical interactions
between discrete neuronal elements and (d) the 3D reconstruction and modeling. The method is easy to perform and can be reproducibly
applied by small laboratories and expanded through the use of different antibodies. Overall, the method presented in this
study offers an innovative and powerful approach to study the nervous system, especially by using confocal microscopy. 相似文献
992.
S Gemma C Camodeca S Sanna Coccone BP Joshi M Bernetti V Moretti S Brogi MC Bonache de Marcos L Savini D Taramelli N Basilico S Parapini M Rottmann R Brun S Lamponi S Caccia G Guiso RL Summers R E Martin S Saponara B Gorelli E Novellino G Campiani S Butini 《Journal of medicinal chemistry》2012,55(15):6948-6967
Despite recent progress in the fight against malaria, the emergence and spread of drug-resistant parasites remains a serious obstacle to the treatment of infections. We recently reported the development of a novel antimalarial drug that combines the 4-aminoquinoline pharmacophore of chloroquine with that of clotrimazole-based antimalarials. Here we describe the optimization of this class of hybrid drug through in-depth structure-activity relationship studies. Antiplasmodial properties and mode of action were characterized in vitro and in vivo, and interactions with the parasite's 'chloroquine resistance transporter' were investigated in a Xenopus laevis oocyte expression system. These tests indicated that piperazine derivatives 4b and 4d may be suitable for coadministration with chloroquine against chloroquine-resistant parasites. The potential for metabolism of the drugs by cytochrome P450 was determined in silico, and the lead compounds were tested for toxicity and mutagenicity. A preliminary pharmacokinetic analysis undertaken in mice indicated that compound 4b has an optimal half-life. 相似文献
993.
Piccionello AP Pitarresi G Pace A Triolo D Picone P Buscemi S Giammona G 《Journal of drug targeting》2012,20(5):433-444
New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivatization and characterized by spectroscopic analyses. Size exclusion chromatography, pyrene colorimetric assay, light scattering analysis and scanning electron microscopy have evidenced the occurrence of a self-association process in aqueous medium. The ability of these aggregates to incorporate a hydrophobic drug and increase its solubility has been evaluated by using Flutamide, a fluorinated anticancer agent. Moreover, the activity of Flutamide-loaded micelles on proliferation of dihydrotestosterone stimulated LNCaP cells has been determined and compared to that of free drug. 相似文献
994.
Kavsak PA Walsh M Srinathan S Thorlacius L Buse GL Botto F Pettit S McQueen MJ Hill SA Thomas S Mrkobrada M Alonso-Coello P Berwanger O Biccard BM Cembrowski G Chan MT Chow CK de Miguel A Garcia M Graham MM Jacka MJ Kueh JH Li SC Lit LC Martínez-Brú C Naidoo P Nagele P Pearse RM Rodseth RN Sessler DI Sigamani A Szczeklik W Tiboni M Villar JC Wang CY Xavier D Devereaux PJ 《Clinical biochemistry》2011,(12):1021-1024
Objectives
To determine the proportion of noncardiac surgery patients exceeding the published 99th percentile or change criteria with the high sensitivity Troponin T (hs-TnT) assay.Design and methods
We measured hs-TnT preoperatively and postoperatively on days 1, 2 and 3 in 325 adults.Results
Postoperatively 45% (95% CI: 39–50%) of patients had hs-TnT ≥ 14 ng/L and 22% (95% CI:17–26%) had an elevation (≥ 14 ng/L) and change (> 85%) in hs-TnT.Conclusion
Further research is needed to inform the optimal hs-TnT threshold and change in this setting. 相似文献995.
Tumino M Meli C Farruggia P La Spina M Faraci M Castana C Di Raimondo V Alfano M Pittalà A Lo Nigro L Russo G Di Cataldo A 《American journal of medical genetics. Part A》2011,(12):3063-3066
Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease. 相似文献
996.
Jakobsen MU Dethlefsen C Due KM Slimani N Chajès V May AM Sørensen TI Halkjær J Tjønneland A Clavel-Chapelon F Boutron-Ruault MC Fagherazzi G Teucher B Kaaks R Boeing H Schütze M Trichopoulou A Zylis D Makrygiannis G Palli D Mattiello A Tagliabue G van der A DL Bueno-de-Mesquita HB Rodríguez L Travier N Molina-Montes E Huerta JM Barricarte A Amiano P Manjer J Wirfält E Johansson I Hallmans G Khaw KT Wareham NJ Crowe F Romieu I Riboli E Peeters PH Overvad K 《Obesity facts》2011,4(4):312-318
997.
Zanier ER Brandi G Peri G Longhi L Zoerle T Tettamanti M Garlanda C Sigurtà A Valaperta S Mantovani A De Simoni MG Stocchetti N 《Intensive care medicine》2011,37(2):302-309
Purpose
To investigate plasma and cerebrospinal fluid (CSF) concentrations of pentraxin 3 (PTX3), a prototypic long pentraxin protein induced by proinflammatory signals, in subarachnoid hemorrhage (SAH), and its relation with SAH-associated vasospasm.Methods
Serial plasma and CSF samples were collected from 38 consecutive SAH patients admitted to the Neurosurgical Intensive Care. PTX3 concentrations were analyzed in relation to clinical status and clinical vasospasm (defined as neuro-worsening and angiographic confirmation of vessel narrowing). Since neutrophils are an important source of preformed PTX3, myeloperoxidase (MPO) in CSF was measured to assess the correlation with CSF PTX3 and establish whether blood contamination was the determinant of PTX3 increase.Results
PTX3 was elevated in all SAH patients both in plasma and CSF. Acute peak (first 48?h after SAH) CSF PTX3 was significantly higher in patients who later developed vasospasm [median 13.6 (range 2.3?C51.9)?ng/ml] compared to those who did not [3.2 (0.1?C50.5)?ng/ml, p?=?0.03]. The temporal pattern of CSF PTX3 in patients with vasospasm was triphasic with a peak during the first 48?h after SAH, a subsequent decrease in the following 48?C96?h and a secondary significant increase with the occurrence of vasospasm. A loose correlation between CSF PTX3 and MPO was observed (r 2?=?0.13), indicating that following SAH there is a brain production of PTX3.Conclusions
Acute increased concentrations of PTX3 in CSF but not in plasma are related to the occurrence of vasospasm, indicating that measurement of CSF PTX3 associated with the clinical evaluation can improve early diagnosis of this complication. 相似文献998.
999.
1000.
Rapid-eye movement (REM) sleep behaviour disorder (RBD) is an REM sleep parasomnia characterized by enactment of dream content during REM sleep associated with loss of muscle atonia. RBD can be either idiopathic or secondary to drugs or other diseases. The best recognized association is with neurodegenerative diseases, namely alpha-synucleinopathies. RBD may represent the first feature of neurodegeneration and can be considered an early marker of these disorders. This review describes the main clinical, pathogenetic, and therapeutic features of RBD, pointing to its association with neurodegenerative diseases and emphasizing the clinical and prognostic implications. 相似文献