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排序方式: 共有894条查询结果,搜索用时 31 毫秒
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Ottaná R Mazzon E Dugo L Monforte F Maccari R Sautebin L De Luca G Vigorita MG Alcaro S Ortuso F Caputi AP Cuzzocrea S 《European journal of pharmacology》2002,448(1):71-80
Within the series of chiral 3,3'-(1,2-ethanediyl)bis[2-arylthiazolidin-4-ones], the 3,4-dimethoxyphenyl substituted derivative was found in the primary anti-inflammatory screening to be endowed with superior in vivo properties and good safety profile. Such a lead compound was modified by eliminating 3-methoxy group while retaining 4-methoxy group on the aryl rings at 2 and 2' stereogenic carbons. The 2R,2'S-meso isomer (VIG3b) of the resulting bisthiazolidinone has been widely investigated. The inhibitory effects on cyclo-oxygenase-1 and cyclo-oxygenase-2 isoenzymes were measured in a human whole blood assay. VIG3b was almost 50 times more selective on the inducible isoform. The cyclo-oxygenase-2 preferential selectivity has been confirmed by modeling VIG3b into the cyclo-oxygenase-1 and cyclo-oxygenase-2 active sites. Furthermore, VIG3b was assayed in the experimental model of carrageenan-induced lung injury by evaluating its ability to inhibit: (1) fluid accumulation in the pleural cavity, (2) neutrophil infiltration, (3) prostaglandin E(2) production and (4) lung injury. VIG3b exhibited interesting activity in all these tests. 相似文献
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Iavicoli I Brera C Carelli G Caputi R Marinaccio A Miraglia M 《International archives of occupational and environmental health》2002,75(6):381-386
OBJECTIVES: Ochratoxin A (OA) is a ubiquitous mycotoxin that can contaminate foods, drinks, and animal feeds worldwide. Humans and animals can therefore absorb this toxin via the gastrointestinal tract after ingestion of contaminated products. OA is known to exert toxic effects, particularly on the renal system, and the International Agency for Research on Cancer (IARC) classified it as a "possible human carcinogen" (Group 2B). The measurement of OA serum levels is an effective method of evaluating internal doses. Inhalation of airborne OA can represent a source of additional exposure. We determined the levels of serum OA in workers exposed to airborne dust originating from the handling or processing of contaminated foods. METHODS: We carried out area and personal sampling for airborne OA determination in three industries where coffee, cocoa beans, and spices, foods highly susceptible to contamination, were being processed. OA levels in the serum of six healthy workers employed in these factories were measured in samples collected at the end of the work shift. RESULTS: Airborne OA measured in the three industries, both by personal and area sampling, ranged from < 0.003 to 8.15 ng/m(3), while the levels measured in the breathing zone of the six workers who agreed to biological monitoring varied from 0.006 to 0.087 ng/m(3). OA serum levels ranged from 0.94 to 3.28 ng/ml, the latter values rather largely exceeding those of the control group (0.03 to 0.95 ng/ml). CONCLUSIONS: Our findings suggest that occupational exposure to this mycotoxin may represent a health risk for workers, especially if preventive and protection measures are not adopted in the workplaces. Airborne exposure levels can result in an increase of OA levels in serum, and this finding suggest that environmental and biological monitoring should be undertaken in workplaces where OA-contaminated products are handled or processed. 相似文献
46.
T Mammen H Shanthakumari K Gopi J Lionel AP Ayyappan A Kekre 《Journal of Medical Imaging and Radiation Oncology》2006,50(4):392-394
In this article we would like to highlight uterine pseudoaneurysm as a cause of secondary post‐partum haemorrhage following Caesarean section. We would like to stress Doppler ultrasound scan as the initial screening modality for this condition. We also describe angioembolization as the prudent treatment option for this condition rather than resorting to surgery. 相似文献
47.
Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer. 总被引:2,自引:0,他引:2
Mario Caputi Angela M Groeger Vincenzo Esposito Antonio De Luca Valeria Masciullo Alessandro Mancini Feliciano Baldi Ernst Wolner Antonio Giordano 《Clinical cancer research》2002,8(12):3850-3856
Altered expression of cell cycle regulators represents a frequent event in both small cell and non-small cell lung cancer (NSCLC). Despite several studies that reported involvement of tumor suppressor genes, such as p53 and pRb, in the development and progression of lung cancer, contrasting opinions exist about the prognostic role of this protein in this neoplasm. We developed an immunohistochemical assay suitable for the detection of pRb2/p130, the last discovered member of the retinoblastoma gene family, on formalin-fixed and paraffin-embedded sections. We evaluated the immunohistochemical expression of pRb2/p130 in 135 lung cancer specimens, and performed Western blot analysis in a subset of 30 corresponding tumor lysates. A high correlation between immunohistochemical data and Western blot results (P = 0.0004) was found. We statistically analyzed the relationship between overall survival (OS) time and pRb2/p130 expression according to the different histological types in 105 patients. We did not find any correlation between pRb2/p130 expression and OS in small cell lung cancers, whereas in NSCLCs a direct relationship between pRb2 and OS was found in both adenocarcinoma (P = 0.0002) and squamous cell carcinoma (P = 0.0002) histotypes. According to univariate analysis, pRb2/p130 was a prognostic factor of which the lost or reduced expression correlated with a shorter OS (P < 0.0000). At multivariate analysis, pRb2/p130 expression was an independent predictor of OS (P = 0.0001) when considered together with histotype. This study demonstrates for the first time the potential independent prognostic value of pRb2/p130 expression on formalin-fixed, paraffin-embedded sections from lung cancer patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with NSCLC and, therefore, may represent a new prognostic marker. 相似文献
48.
For most of the 20th century, most drugs labeled by the United States Food and Drug Administration (USFDA) have not been adequately studied in the pediatric population. This lack of data has necessitated the continued dependence of practitioners on sub-optimal prescribing data placing pediatric patients at great risk of serious therapeutic misadventures. Recently, the USFDA has enacted and begun to enforce the Final Rule of 1997 which became effective on 1 April 1999. This rule is the culmination of the persistent efforts of numerous professional organizations, clinicians, academicians, the USFDA and others, to ensure the ready availability of appropriate data for medications intended for or that will be used in children. Unlike the 1994 Rule which voluntarily required pharmaceutical manufacturers to submit pediatric data, the Final Rule mandates submission of such data and, most importantly, empowers the USFDA to afford incentives and penalties for non-compliance including possible removal of already marketed products. This overview addresses many of the important components which must be included in the performance of a comprehensive clinical pharmacologic evaluation serving as the foundation for optimal dosing across the broad age range encompassing pediatric practice. Furthermore, the possible risk and/or benefits of the study must be reasonably defined prior to undertaking the study and clearly shared with the patient's caregivers. Consent should always be obtained from the caregiver and, when appropriate, assent obtained from the underage child. To facilitate such clinical investigations and to foster collaborative efforts with innovators and clinical research programs, the National Institutes of Health through the National Institute of Child Health and Human Development of the NIH established a network of Pediatric Pharmacology Research Units. These units have worked closely together and with other pediatric research centers to facilitate USFDA labeling of a number of commonly used medications. All of these very positive efforts highlight the many challenges that remain for the pediatric investigator and practitioner while underscoring the very positive environment in support of these efforts. 相似文献
49.
Cuzzocrea S Mazzon E Costantino G Serraino I De Sarro A Caputi AP 《Cardiovascular research》2000,47(3):537-548
OBJECTIVE: Splanchnic artery occlusion shock (SAO) causes an enhanced formation of reactive oxygen species (ROS), which contribute to the pathophysiology of shock. Here we have investigated the effects of n-acetylcysteine (NAC), a free radical scavenger, in rats subjected to SAO shock. METHODS AND RESULTS: Treatment of rats with NAC (applied at 20 mg/kg, 5 min prior to reperfusion, followed by an infusion of 20 mg/kg/h) attenuated the mean arterial blood and the migration of polymorphonuclear cells (PMNs) caused by SAO-shock. NAC also attenuated the ileum injury (histology) as well as the increase in the tissue levels of myeloperoxidase (MPO) and malondialdehyde (MDA) caused by SAO shock in the ileum. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine in the plasma of the SAO-shocked rats after reperfusion. Immunohistochemical analysis for nitrotyrosine and for poly(ADP-ribose) synthetase (PARS) revealed a positive staining in ileum from SAO-shocked rats. The degree of staining for nitrotyrosine and PARS were markedly reduced in tissue sections obtained from SAO-shocked rats which had received NAC. Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin, which was mainly localised in the vascular endothelial cells. Ileum tissue section obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staining. NAC treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAO-shocked rats. In addition, in ex vivo studies in aortic rings from shocked rats, we found reduced contractions to noradrenaline and reduced responsiveness to a relaxant effect to acetylcholine (vascular hyporeactivity and endothelial dysfunction, respectively). NAC treatment improved contractile responsiveness to noradrenaline, enhanced the endothelium-dependent relaxations and significantly improved survival. CONCLUSION: Taken together, our results clearly demonstrate that NAC treatment exert a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite-related pathways and subsequent reduction of neutrophil-mediated cellular injury. 相似文献
50.
Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA)
causes a near immediate and total decrease of transepithelial electrical
resistance (TER), continuation of exposure for 3 to 4 days results in a
tachyphylactic response as TER begins to return to control levels. Recovery
of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control
level. A reciprocal change in the transepithelial flux of D-mannitol
indicates that the TER decrease is indicative of an increase in tight
junction permeability. Exposure of cell sheets to TPA for several days also
results in the appearance of multilayered polyp- like foci (PLFs) across
the otherwise one cell layer thick cell sheets. The pattern of penetration
of the electron dense dye, ruthenium red, from the apical surface, across
the tight junction and into the lateral intercellular space indicates that
the tight junctions of the cell sheet become uniformly leaky after acute
exposure to TPA. However, when exposure is continued for several days, only
the junctions of cells in the PLFs manifest leakiness. The decrease in TER
following acute TPA exposure correlates with the translocation of protein
kinase C-alpha (PKC alpha) into a membrane-associated compartment. With
exposure of several days, only a trace of PKC alpha is visible by Western
immunoblot, and this is in the membrane-associated compartment.
Immunofluorescent microscopy indicates that the trace of PKC alpha seen in
the Western immunoblots is ascribable distinctly to cells of the PLFs.
Monolayer areas between PLFs show no discernible immunofluorescent signal.
The data therefore indicate that tight junction barrier function may be
restored in certain areas by the down regulation of PKC alpha from the
membrane-associated compartment. Failure to down regulate may result in the
paracellular leakiness and abnormal cell architecture of the PLFs. Possible
implications of this model for in vivo epithelial tumor promotion are
discussed.
相似文献