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排序方式: 共有250条查询结果,搜索用时 15 毫秒
141.
Palani A Shapiro S Josien H Bara T Clader JW Greenlee WJ Cox K Strizki JM Baroudy BM 《Journal of medicinal chemistry》2002,45(14):3143-3160
We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our initial lead compound as well as the synthesis and SAR studies directed toward optimization of substitution at the phenyl, oxime, and right-hand side amide groups in the oximino-piperidino-piperidine series. Substitutions (4-Br, 4-CF(3), 4-OCF(3), 4-SO(2)Me, and 4-Cl) at the phenyl group are well-tolerated, and small alkyl substitutions (Me, Et, (n)()Pr, (i)()Pr, and cyclopropyl methyl) at the oxime moiety are preferred for CCR5 antagonism. The 2,6-dimethylnicotinamide N-oxide moiety is the optimal choice for the right-hand side. Several compounds in this series, including compound 1, exhibited excellent antiviral activity in vitro. Compound 1, which has a favorable pharmacokinetic profile in rodents and primates, excellent oral bioavailability, and potent antiviral activity against a wide range of primary HIV-1 isolates, is a potentially promising new candidate for treatment of HIV-1 infection. 相似文献
142.
Anandan S Wigg CL Thomas CR Coffey B 《Journal of child and adolescent psychopharmacology》2004,14(4):531-538
One of the most serious and difficult-to-treat conditions in child and adolescent psychiatry is self-injurious behavior (SIB). SIB can be associated with a number of psychiatric disorders, including mental retardation, schizophrenia, borderline personality disorder, pervasive developmental disorders, stereotypic movement disorder, and Tourette's Disorder. A variety of neurosurgical procedures have been used to treat both intractable SIB and severe Tourette's Disorder. Understandably, there are few reports concerning psychosurgery in children and adolescents for any condition or disorder. This report describes the use of cingulotomy and subsequent limbic leucotomy in an adolescent boy with Tourette's Disorder for SIB. His repetitive and medically serious SIB and failure of all other treatments prompted this intervention after careful, comprehensive review and discussion. Following the second surgery, the severity and frequency of his SIB were reduced. 相似文献
143.
Colathur K. Palani Sabas Abuabara Avram R. Kraft Olga Jonasson 《American journal of surgery》1981,141(1):164-168
Acute variceal hemorrhage in patients with alcoholic cirrhosis and poor liver function is associated with a high mortality. A nonoperative treatment, endoscopic sclerotherapy, was employed in 22 patients with cirrhosis and poor liver function who had 24 episodes of acute variceal hemorrhage over a 20 month period. Portal hypertension was secondary to alcoholic cirrhosis in 21 patients and cystic fibrosis in 1 patient. Of the 24 patient admissions, 21 were of patients in Child's class C and 3 were class B. Endoscopic sclerotherapy was performed under endotracheal general anesthesia using a modified Negus rigid esophagoscope. The sclerosant (5 percent sodium morrhuate) was injected into all visible varices near the gastroesophageal junction using a MacBeth needle. Definitive control of variceal hemorrhage for the entire hospitalization was achieved in 19 of 24 admissions (79 percent). The in-hospital mortality for acute variceal bleeding was 29 percent; 81 percent of the patients were discharged after control of hemorrhage. There were two major and five minor complications related to sclerotherapy. Based on this preliminary experience it is concluded that injection sclerotherapy controls bleeding and reduces mortality associated with acute variceal hemorrhage in patients with poor liver function. 相似文献
144.
Eapen BR Shabana S Anandan S 《Indian journal of dermatology, venereology and leprology》2003,69(2):88-89
Presence of any skin lesion along the waistline in 140 female patients was recorded. We found that most of them had some lesions over the waist, but only few of them accepted the fact. The commonest cutaneous change observed were hyperpigmentation and scaling. But we failed to find any association with diabetes, atopy, skin type, abesity or the type of fabric. 相似文献
145.
Selvam TP Nagarajan PS Rajan KN Sethulakshmi P Bhatt BC 《Australasian physical & engineering sciences in medicine / supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine》2003,26(4):179-184
Values of dose rate constant (DRC) in compliance with AAPM TG 60 formalism recommended for intravascular brachytherapy (IVBT) were calculated for different point isotropic mono-energetic photon sources in the energy range E = 20-1000 keV using a semi-analytic model. Based on these DRC values, DRC of some existing models of 192Ir and 125I brachytherapy sources were then calculated using (1) bare energy spectra and (2) a single energy parameter which represents mean energy (photon number weighted or air-kerma weighted) for bare and actual sources or the most probable energy of the spectra (energy line with the highest probability of emission) of the investigated sources (192Ir and 125I). Applicability of the semi-analytic approach was examined by also computing the values of DRC of the investigated sources using MCNP Monte Carlo simulation code (Version 3.1) that involved modeling of the sources accurately. A comparison of values of DRC resulting from MCNP calculations with those resulting from the semi-analytic approach showed that for 192Ir sources the agreement was within 0.40% and for 125I sources it was within 2.3%. 相似文献
146.
147.
Lauren M. Cross Kunal Shah Sowmiya Palani Charles W. Peak Akhilesh K. Gaharwar 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(7):2465-2474
Two-dimensional (2D) nanomaterials are an emerging class of materials with unique physical and chemical properties due to their high surface area and disc-like shape. Recently, these 2D nanomaterials have been investigated for a range of biomedical applications including tissue engineering, therapeutic delivery and bioimaging, due to their ability to physically reinforce polymeric networks. Here, we present a facile fabrication of a gradient scaffold with two natural polymers (gelatin methacryloyl (GelMA) and methacrylated kappa carrageenan (MκCA)) reinforced with 2D nanosilicates to mimic the native tissue interface. The addition of nanosilicates results in shear-thinning characteristics of prepolymer solution and increases the mechanical stiffness of crosslinked gradient structure. A gradient in mechanical properties, microstructures and cell adhesion characteristics was obtained using a microengineered flow channel. The gradient structure can be used to understand cell-matrix interactions and to design gradient scaffolds for mimicking tissue interfaces. 相似文献
148.
Wei Z McEvoy M Razinkov V Polozova A Li E Casas-Finet J Tous GI Balu P Pan AA Mehta H Schenerman MA 《Journal of virological methods》2007,144(1-2):122-132
149.
Sonnemann J Hüls I Sigler M Palani CD Hong le TT Völker U Kroemer HK Beck JF 《Oncology reports》2008,20(1):219-224
Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer activity and histone acetylation. We found that the HDIs, suberoylanilide hydroxamic acid and sodium butyrate, and aspirin cooperated to induce cell death in the ovarian cancer cell line, A2780. The effect was synergistic, as evidenced by CI-isobologram analysis. However, aspirin had no effect on histone acetylation, neither in the absence nor presence of HDIs. To gain insight into the mechanism underlying the synergistic action of HDIs and aspirin, we employed the deacetylated metabolite of aspirin, salicylic acid, and the cyclooxygenase-1- and -2-selective inhibitors, SC-560 and NS-398, respectively. We found that HDIs and salicylic acid interacted synergistically, albeit less efficiently than HDIs and aspirin, to induce cancer cell death, suggesting that the acetyl and the salicyl moiety contributed to the cooperative interaction of aspirin with HDIs. SC-560 and NS-398 had little effect both when applied alone or in conjunction with HDIs, indicating that the combinatorial effect of HDIs and aspirin was not the result of cyclo-oxygenase inhibition. In conclusion, our study demonstrates that HDIs and aspirin synergize to induce cancer cell death and, thus, provides a rationale for a more in-depth exploration into the potential of combining HDIs and aspirin as a strategy for anticancer therapy. 相似文献
150.
Nutlin-3, a small-molecule MDM2 inhibitor, restores p53 function and is, thus, an appealing candidate for the treatment of
cancers retaining wild-type p53. However, nutlin-3 applied as single agent may be insufficient for cancer therapy. Therefore,
we explored whether the anticancer activity of nutlin-3 could be enhanced by combination with histone deacetylase inhibitors
(HDACi), i.e. vorinostat, sodium butyrate, MS-275 and apicidin. We found that nutlin-3 and HDACi cooperated to induce cell
death in the p53 wild-type cell lines A549 and A2780, but not in the p53 null cell line PC-3, as assessed by Alamar Blue assay
and flow cytometric analyses of propidium iodide uptake and mitochondrial depolarization. Combination index analysis showed
that the effect was synergistic. For comparison, we tested nutlin-3 in combination with paclitaxel, revealing that nutlin-3
antagonized the cytotoxic activity of paclitaxel. To shed light on the underlying mechanism of the synergistic action of nutlin-3
and HDACi, we determined the acetylation status of p53 by immunoblotting and the mRNA levels of MDM2 and MDM4 by real-time
RT-PCR. We observed vorinostat to induce p53 hyperacetylation, to reduce the constitutive gene expression of MDM2 and MDM4,
and to counteract the nutlin-3-induced upregulation of MDM2 gene expression. In conclusion, our study shows that HDACi amplify
the antitumor activity of nutlin-3—possibly by inducing p53 hyperacetylation and/or MDM2 and/or MDM4 downregulation—suggesting
that treatment with a combination of nutlin-3 and HDACi may be an effective strategy for treating tumors with wild-type p53. 相似文献