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991.
Khatib S Nerya O Musa R Tamir S Peter T Vaya J 《Journal of medicinal chemistry》2007,50(11):2676-2681
The objective of the present study was to investigate to what extent the addition of hydrophobic residues to a 2,4-resorcinol derivative would contribute to their tyrosinase inhibitory potency. Hence, 3-(2,4-dihydroxyphenyl)propionic acid, isolated from Ficus carica, was transformed into esters, and the relationship between the structure of these esters to their mushroom tyrosinase inhibition activity was explored. The enzyme crystallographic structure, published recently (Matoba, Y. et al. J. Biol. Chem. 2006, 281, 8981-8990) was docked with the new esters, and their calculated free energy (FE) and docking energy (DE) were compared with the experimental IC(50) values, providing good correlations. The observed IC(50) of the isopropyl ester was 0.07 microM, and its interaction with the enzyme binding site appears to be composed of four hydrogen bonds and two hydrophobic interactions. It may be concluded that the addition of a hydrophobic moiety to 2,4-resorcinol derivatives augments tyrosinase inhibitory potency as was predicted from the modeling study. 相似文献
992.
Habib NS Soliman R El-Tombary AA El-Hawash SA Shaaban OG 《Archives of pharmacal research》2007,30(12):1511-1520
In this study, we report the synthesis and antimicrobial evaluation of several new thiazolo[4,5-d]pyrimidine derivatives, namely 7-substituted amino-5-methyl-3-phenylthiazolo[4,5-d]pyrimidine-2(3H)-thiones 4a-e, 8, 13, 15, ethyl 2-cyano-2-(7-substituted-5-methyl-3-phenylthiazolo [4,5-d]-pyrimidin-2(3H)-ylidene)acetates 5a-b, 2-(7-substituted-5-methyl-3-phenylthiazolo[4,5-d]pyrimidin-2(3H)-ylidene)malononitriles 6a-b, 5-methyl-7-morpholino-3-phenylthiazolo[4,5-d] pyrimidine-2(3H)-one 7, and 7-[4-(1-substituted-5-phenyl-4,5-dihydro-1H-pyrazolin-3-yl)anilino]-5-methyl-3-phenylthiazolo[4,5-d]pyrimidine-2(3H)-thiones 10-12. Some of the tested compounds were more active against C. albicans than E. coil and P. aeruginosa, and all were inactive against S. aureus. 相似文献
993.
Fishman M Hunter TB Soliman H Thompson P Dunn M Smilee R Farmelo MJ Noyes DR Mahany JJ Lee JH Cantor A Messina J Seigne J Pow-Sang J Janssen W Antonia SJ 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2008,31(1):72-80
We report a single center phase II trial of sequential vaccination followed with vaccine plus interleukin-2 (IL-2). Vaccination consisted of autologous cells cultured from primary tumor or resected metastasis, transduced to express B7.1 surface molecule and then irradiated. The vaccine would hypothetically costimulate tumor-reactive T cells before IL-2 exposure. Treatment plan was 3 subcutaneous vaccine injections at 4-week intervals and subcutaneous IL-2 treatment for 6 weeks starting at week 7. Sixty-six patients enrolled, of whom 39 received at least 1 vaccine; most observed toxicity was attributable to IL-2 not vaccine; best responses were 3% pathologic complete response, 5% partial response, 64% stable disease, and 28% disease progression. Median survival was 21.8 months (95% confidence interval 17.8 to 29.6). Significant postvaccination increases in IFN-gamma responses to autologous tumor were observed in 2/26 cases. Eighty-one percent of posttreatment subdermal delayed-type hypersensitivity tests (using nontransduced, irradiated autologous tumor cells) had biopsies demonstrating injection site lymphocytic infiltration. Post hoc comparison of the median survival of subjects whose biopsies had lymphocytic infiltration appears longer than in the 19% noninfiltrated (28.4 vs. 17.8 mo, P=0.045, two-sided log-rank test). The single arm design precludes conclusive comparison of objective response rates (not different here) or median survival (longer here) versus those of historical series using similar IL-2 schedules alone. Better outcomes could be logically associated to vaccine response (detectable lymphocytic infiltrates) or to random events that a single arm study design cannot address. This vaccine approach may merit further clinical development. 相似文献
994.
El-Hawary MA El-Raziky MS Esmat G Soliman H Abouzied A El-Raziky M El-Akel W El-Sayed R Shebl F Shaheen AA El-Karaksy H 《World journal of gastroenterology : WJG》2007,13(20):2846-2851
AIM: To assess hepatic fibrosis and factors associated with its progression in children with HCV infection. METHODS: At the Hepatology Unit,Cairo University Children's Hospital,a single liver biopsy was performed to 43 children with HCV infection after an informed consent between 1998-2004. Their mean age at liver biopsy was 8.67 ± 4.3 years. RESULTS: Among the 43 patients' biopsies,12 (27.9%) were having no fibrosis,20 (46.5%) mild fibrosis and 11 (25.6%) moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5 years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy (12 mo vs 1.2 mo,P = 0.015) and having higher levels of direct serum bilirubin (0.3 mg/dL vs 0.5 mg/dL,P = 0.048). No association was found between fibrosis stage and the presence of co-morbid conditions (P = 0.33). CONCLUSION: Hepatic fibrosis was present in 72.1% of children with HCV infection. The development of fibrosis was associated with higher levels of direct serum bilirubin. There was no significant association between fibrosis and age,duration of infection,risk factors,co-morbid conditions and most biochemical parameters. 相似文献
995.
Soliman OI Krenning BJ Geleijnse ML Nemes A van Geuns RJ Baks T Anwar AM Galema TW Vletter WB ten Cate FJ 《Echocardiography (Mount Kisco, N.Y.)》2007,24(9):967-974
OBJECTIVES: To compare the interobserver variability and accuracy of two different real time three-dimensional echocardiography (RT3DE) analyzing programs. METHODS: Forty-one patients (mean age 56 +/- 11 years, 28 men) in sinus rhythm with a cardiomyopathy and adequate 2D image quality underwent RT3DE and magnetic resonance imaging (MRI) within one day. Off-line left ventricular (LV) volume analysis was performed with QLAB V4.2 (semiautomated border detection with biplane projections) and TomTec 4D LV analysis V2.0 (primarily manual tracking with triplane projections and semiautomated border detection). RESULTS: Excellent correlations (R(2) > 0.98) were found between MRI and RT3DE. Bland-Altman analysis revealed an underestimated LV end-diastolic volume (LV-EDV) for both TomTec (-9.4 +/- 8.7 mL) and QLAB (-16.4 +/- 13.1 ml). Also, an underestimated LV end-systolic volume (LV-ESV) for both TomTec (-4.8 +/- 9.9 mL) and QLAB (-8.5 +/- 14.2 mL) was found. LV-EDV and LV-ESV were significantly more underestimated with QLAB software. Both programs accurately calculated LV ejection fraction (LV-EF) without a bias. Interobserver variability was 6.4 +/- 7.8% vs. 12.2 +/- 10.1% for LV-EDV, 7.8 +/- 9.7% vs. 13.6 +/- 11.2% for LV-ESV, and 7.1 +/- 6.9% vs. 9.7 +/- 8.8% for LV-EF for TomTec vs. QLAB, respectively. The analysis time was shorter with QLAB (4 +/- 2 minutes vs. 6 +/- 2 minutes, P < 0.05). CONCLUSIONS: RT3DE with TomTec or QLAB software analysis provides accurate LV-EF assessment in cardiomyopathic patients with distorted LV geometry and adequate 2D image quality. However, LV volumes may be somewhat more underestimated with the current QLAB software version. 相似文献
996.
Geleijnse ML Krenning BJ Soliman OI Nemes A Galema TW ten Cate FJ 《The American journal of cardiology》2007,99(5):714-717
Dobutamine stress echocardiography (DSE) has good diagnostic accuracy for the diagnosis of coronary artery disease (CAD). However, in most published diagnostic studies, patients are predominantly men. In women, diagnostic accuracy may be lower because of a lower prevalence and extent of CAD, a higher incidence of dobutamine stress-induced hypotension (resulting in less stress or even nondiagnostic test results), smaller left ventricular chamber size, and the beneficial effects of estrogens on the induction of myocardial ischemia. To determine the diagnostic accuracy of DSE in women, 14 diagnostic studies published through 2006 were identified through a Medline search. For a total of 901 patients, the weighted mean sensitivity and specificity were 72% and 88%, respectively. In 7 studies directly comparing results in women and men, conflicting results were reported. However, pooled data showed nearly identical values for sensitivity and specificity in women and men. Additionally, in 6 studies directly comparing DSE results in women with those of stress nuclear scintigraphy, DSE was as sensitive and more specific to detect CAD (90% vs 70%, p <0.0001). The excellent specificity of DSE in women was also confirmed by excellent normalcy rates, ranging from 92% to 100% in women, with a <5% pretest probability of CAD. In conclusion, despite some theoretical limitations, DSE has reasonable sensitivity and excellent specificity for the detection of CAD in women. Considering the diagnostic problems of exercise electrocardiography and nuclear scintigraphy in women, stress echocardiography may be the stress modality of choice in women because of its superior diagnostic specificity. 相似文献
997.
Ronald van Toorn Helena Rabie Angela Dramowski Johan F. Schoeman 《European journal of paediatric neurology》2012,16(6):676-682
IntroductionTuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a potentially life-threatening complication in HIV infected children with tuberculosis (TB) of the central nervous system. HIV-associated TB-IRIS has not been previously described in children with neurotuberculosis.ObjectiveTo describe the neurological and neuro-radiological features of 4 consecutive cases of TB-IRIS in children with neurotuberculosis and to discuss possible management strategies.ResultsThree patients treated for tuberculosis of the central nervous system experienced paradoxical worsening of neurological symptoms when combination antiretroviral therapy (cART) was initiated. Intracranial tuberculomas were unmasked in the 4th patient. All patients developed new neurological signs within 10 days of cART initiation. Neurological symptoms and signs included headache, seizures, meningeal irritation, decreased level of consciousness, ataxia and focal motor deficit. Interventions included the temporary discontinuation of cART and the use of corticosteroids in all patients. Three patients received thalidomide and 1 chloroquine and mycophenolate mofetil. One patient died and the others experienced prolonged hospitalization.ConclusionTB-IRIS should be considered when new neurological signs develop shortly after initiation of cART in children. There is little data to guide the timing of initiation of cART and the management of complications in children. 相似文献
998.
Tal Gefen Jacob Vaya Soliman Khatib Natalia Harkevich Fadi Artoul E. Dan Heller Jacob Pitcovski Elina Aizenshtein 《International immunopharmacology》2013,15(2):254-259
Covalent attachment of PEG (PEGylation) is widely used to improve the pharmaceutical properties of therapeutic proteins. The applicability and safety of this method have been proven by the use of various PEGylated pharmaceutical proteins approved by the Food and Drug Administration (FDA). One of the properties attributed to PEGylation is immunogenicity reduction of the PEGylated protein. In this study, the impact of PEGylation on immunogenicity was tested and compared for two proteins (chicken IgY and horse IgG) in two strains of mice (Balb/c and C57BL/6) for two routes of administration (i.v. and i.m.) and two sizes of PEG (5 kD and 20 kD). The influence of PEG was shown to be inconsistent between the mouse strains and routes of administration, even with the same tested protein. Consequently, immunogenicity reduction by PEGylation cannot be predicted or assumed; it must be tested on an individual case basis. 相似文献
999.
Using an integrated computational approach involving homology modelling, pharmacophore/structure‐based virtual screening, molecular dynamics simulations and per‐residue energy contribution, 10 compounds were proposed as potential TB inhibitors. Via validated docking calculations, binding free energy calculations showed that the proposed compounds presented better binding affinity with DNA gyrase B when compared to novobiocin. The compiled in silico approach employed in this study may serve as a useful tool in the process of the design and development of drugs, not only against TB, but also for a wide range of biological systems. 相似文献
1000.
Because of serious adverse effects, the Food and Drug Administration warns against using lopinavir in infants younger than 42 weeks postconception. However, there is an imperative for early treatment. We report on our use of LPV in 8 premature HIV-infected infants. The median age at initiation was 27 days. Trough values guided dosing. Five infants needed doses above 300 mg/m. Although no adverse events were noted, lopinavir usage requires caution and careful monitoring. 相似文献