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991.
Isatins inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell line
Matheus ME Violante Fde A Garden SJ Pinto AC Fernandes PD 《European journal of pharmacology》2007,556(1-3):200-206
Isatin is a versatile compound with a diversity of effects. We designed to investigate the inhibitory effect of isatin derivatives on lipopolysaccharide/interferon-gamma-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, production of prostaglandin E(2) (PGE(2)), nitric oxide (NO), tumor necrosis factor (TNF-alpha), and their capacity to scavenge NO. Isatins inhibit TNF-alpha production and iNOS and COX-2 protein expression resulting on reduced levels of NO and PGE(2). Our results indicate isatin and it derivatives as inhibitors of iNOS and COX-2 enzymes, which might be used as anti-inflammatory and antitumoral agents. 相似文献
992.
Leonetti F Capaldi C Pisani L Nicolotti O Muncipinto G Stefanachi A Cellamare S Caccia C Carotti A 《Journal of medicinal chemistry》2007,50(20):4909-4916
Safinamide, (S)-N2-{4-[(3-fluorobenzyl)oxy]benzyl}alaninamide methanesulfonate, which is in phase III clinical trials as an anti-Parkinson drug, and a library of alkanamidic analogues were prepared through an expeditious solid-phase synthesis and evaluated for their monoamine oxidase B (MAO-B) and monoamine oxidase A (MAO-A) inhibitory activity and selectivity. (S)-3-Chlorobenzyloxyalaninamide (8) and (S)-3-chlorobenzyloxyserinamide (13) derivatives proved to be more potent MAO-B inhibitors than safinamide (IC50 = 33 and 43 nM, respectively, vs 98 nM) but with a lower MAO-B selectivity (SI = 3455 and 1967, respectively, vs 5918). The highest MAO-B inhibitory potency (IC50 = 17 nM) and a good selectivity (SI = 2941) were displayed by (R)-21, a tetrahydroisoquinoline analogue of safinamide. Structure-affinity relationships and docking simulations pointed out strong negative steric effects of alpha-aminoamide side chains and para substituents of the benzyloxy groups and favorable hydrophobic interactions of meta substituents. The significantly diverse MAO-B affinities of a number of R and S alpha-aminoamide enantiomers, including the two rigid analogues (21) of safinamide, indicated likely enantioselective interactions at the enzymatic binding sites. 相似文献
993.
Micheli F Bonanomi G Blaney FE Braggio S Capelli AM Checchia A Curcuruto O Damiani F Fabio RD Donati D Gentile G Gribble A Hamprecht D Tedesco G Terreni S Tarsi L Lightfoot A Stemp G Macdonald G Smith A Pecoraro M Petrone M Perini O Piner J Rossi T Worby A Pilla M Valerio E Griffante C Mugnaini M Wood M Scott C Andreoli M Lacroix L Schwarz A Gozzi A Bifone A Ashby CR Hagan JJ Heidbreder C 《Journal of medicinal chemistry》2007,50(21):5076-5089
The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain. 相似文献
994.
The etiological agents that cause prostate cancer remain unknown. There is emerging evidence that "risk factor" lesions that are proposed to represent regenerative epithelium in response to environmental insults may precede the development of prostatic intraepithelial neoplasia and early carcinoma. Recent evidence suggests that these lesions, referred to collectively as proliferative inflammatory atrophy, may arise in the setting of inflammation and dietary toxins, such as "charred meat" carcinogens. Additional epidemiological, molecular pathological, and animal model work needs to be done to determine whether inflammation and atrophy are "driving" prostate carcinogenesis. 相似文献
995.
Milena Brugnara Mariangela Cecchetto Riccardo Manfredi Michele Zuffante Vassilios Fanos Angelo Pietrobelli Marco Zaffanello 《BMC urology》2007,7(1):1-5
Background
The use of percutaneous needle biopsy in the evaluation of indeterminate renal masses is controversial and its role in management remains largely unclear. We set to establish current practice on this issue in UK urology departments.Methods
We conducted a national questionnaire survey of all consultant urologists in the UK, to establish current practice and attitudes towards percutaneous needle biopsy in the management of indeterminate renal masses.Results
139 (43%) consultant urologists never use biopsy, whereas 111 (34%) always employ it for the diagnosis of indeterminate renal masses. 75 (23%) urologists use biopsy only for a selected patient group. Mass in a solitary kidney, bilateral renal masses and a past history of non-renal cancer were the main indications for use of percutaneous biopsy. The risk of false negative results and biopsy not changing the eventual management of their patients were the commonest reasons not to perform biopsy.Conclusion
There is a wide and varied practice amongst UK Consultant Urologists in the use of percutaneous biopsy as part of the management of indeterminate renal masses. The majority of urologists believe biopsy confers no benefit. However there is a need to clarify this issue in the wake of recent published evidence as biopsy results may provide critical information for patients with renal masses in a significant majority. It not only differentiates benign from malignant tissue but can also help in deciding the management option for patients undergoing minimally invasive treatments. 相似文献996.
Laparoscopic radical cystectomy (LRC) is a challenging technique, but it has been proposed as an alternative to open radical cystectomy (ORC), which is currently the gold standard treatment for muscle-invasive or high-risk superficial bladder cancer. So far, approximately 200 cases treated with LRC have been reported in the peer-reviewed literature, but follow-up has generally been short (all <48 months). A shorter hospital stay and a quicker recovery of the patient seem to be the main advantages of LRC over ORC. Functional outcomes, cancer control obtained, and safety of the technique need to be confirmed by studies with larger cohorts of patients and longer follow-up than those previously reported, but an initial analysis suggests that LRC is not equivalent to ORC. Given that the majority of patients selected for LRC had lower American Society of Anesthesiologists scores and lower pathological stages than those in ORC studies, the proportion of patients with orthotopic neobladders (47%) and the proportion of disease-free patients (80%) seem to be suboptimal and, actually, those might represent the major disadvantages of LRC. 相似文献
997.
Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus 总被引:5,自引:0,他引:5
Krampera M Marconi S Pasini A Galiè M Rigotti G Mosna F Tinelli M Lovato L Anghileri E Andreini A Pizzolo G Sbarbati A Bonetti B 《BONE》2007,40(2):382-390
Mesenchymal stem cells (MSCs) from bone marrow (BM) and sub-cutaneous fat are known to differentiate into neural cells under appropriate stimuli. We describe here the neural-like differentiation of human MSCs obtained from spleen and thymus, induced either with chemical factors or with co-culture with human Schwann cells (Sc). Under the effect of neural differentiation medium, most MSCs from BM, fat, spleen and thymus acquired morphological changes suggestive of cells of astrocytic/neuronal and oligodendroglial lineages with general up-regulation of neural molecules not correlated with morphological changes. The process was transient and reversible, as MSCs recovered basal morphology and phenotype, as well as their multilineage differentiation potential. Thus, we hypothesized that chemical factors may prime MSCs for neural differentiation, by inducing initial and poorly specific changes. By contrast, co-cultures of MSCs of different origin with Sc induced long-lasting and Sc differentiation, i.e., the expression of Sc myelin proteins for up to 12 days. Our results show that a MSC reservoir is present in tissues other than BM and fat, and that MSCs of different origin have similar neural differentiation potential. This evidence provides new insights into BM-like tissue plasticity and may have important implications for future therapeutic interventions in chronic neuropathies. 相似文献
998.
Balasubramanian SP Cox A Cross SS Higham SE Brown NJ Reed MW 《International journal of cancer. Journal international du cancer》2007,121(5):1009-1016
Vascular endothelial growth factor-A (VEGF-A) plays an important role in tumour angiogenesis and cancer progression. VEGF gene variation may influence VEGF levels and therefore cancer susceptibility and progression. We studied the role of VEGF single nucleotide polymorphisms and haplotypes in breast cancer susceptibility and severity. We also studied the relationships of VEGF SNPs with circulating VEGF levels in healthy volunteers and protein expression in breast cancers. Single nucleotide polymorphisms (SNPs) in the regulatory regions of the VEGF gene were genotyped by high throughput methods in approximately 500 breast cancer cases and 500 appropriate controls. Haplotype frequencies were inferred using methods based on the Expectation Maximisation algorithm. The effect of VEGF genotypes on serum and plasma VEGF levels were studied in another cohort of healthy individuals. A semi-quantitative assessment of VEGF protein expression on tissue micro arrays (TMA) constructed from approximately 300 breast cancer samples was performed and compared with VEGF genotypes and with histopathological parameters and survival in breast cancer. The -460T/+405C/-7C/936C haplotype in the VEGF gene was found to be associated with decreased breast cancer risk (p = 0.029). The -7C>T polymorphism may influence overall breast cancer survival (p = 0.027). Individual polymorphisms however did not affect breast cancer susceptibility. There was no association between the individual polymorphisms and circulating VEGF levels in healthy volunteers and VEGF expression on the breast cancer micro array. VEGF expression in breast cancers was however associated with high grade (p = 0.002) and ER negative tumours (p = 0.03). 相似文献
999.
1000.
Federico?DettoniEmail author Alberto?Peveraro Angelo?Dettoni Roberto?Rossi Filippo?Castoldi Ali?Zareh Fabrizio?Amberti Alessio?Giai?Via Davide?Bonasia 《Musculoskeletal surgery》2012,96(1):41-46
Piedmont is a region in northwestern Italy counting 4.2 million inhabitants. The purpose of our study was to update data on
incidence and outcomes of hip fractures (HF) in our region to present days. The data of all patients affected by HF in 2003
in Piedmont (total: 5,386 patients) were analyzed, determining the incidence of HF, mean age, sex, fracture pattern and treatment
adopted. Additionally, 564 patients underwent a questionnaire on comorbidities, complications, functional outcome and survivorship.
Overall incidence of HF was 126.13/100,000 inhabitants-year. Mean hospitalization was 13.67 days. Mean time to surgery was
2.67 days. Survivorship was 94% at 3-month, 71.32% at 1-year and 60.21% at 3-year follow-up. These up-to-date data on HF in
our region are in accordance with the international literature and could prove useful for Orthopaedic and Trauma surgeons
for giving information to patients and their relatives. 相似文献