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991.
Subhas S. Karki Santosh R. Bhutle Ganesh S. Pedgaonkar P. K. Zubaidha Rizwan M. Shaikh Chitra G. Rajput Girish S. Shendarkar 《Medicinal chemistry research》2011,20(8):1158-1163
The phytoalexin 3,5,4′-trihydroxy-trans-stilbene (resveratrol) has attracted considerable attention from biologists and chemists due to its diverse biological properties.
Owing to the biological importance of this compound, we have synthesized new stilbene-based analogues by using substituted
benzyl chlorides and substituted aldehydes in a two-step reaction and evaluated their in vitro antioxidant, antibacterial
and antifungal potential. Most of the compounds displayed moderate to significant radical scavenging activity. (E)-1-(3,4-difluorophenyl)-2-(4-fluorophenyl)ethene (4c) showed nearer equipotent antibacterial activity against Staphylococcus aureus. (E)-1,2-bis(4-fluorophenyl)ethene (4a), (E)-1-(3-fluorophenyl)-2-(4-fluorophenyl)ethene (4b), (E)-1-(2,4-dichlorophenyl)-2-(3,4-dichlorophenyl)ethene (4f), (E)-1-(2,4-dichlorophenyl)-2-(3-chlorophenyl)ethene (4g), (E)-1-(2,4-dichlorophenyl)-2-(4-fluorophenyl)ethene (4j) (E)-1-(4-fluorophenyl)-2-(3-chlorophenyl)ethene (4l) and (E)-1-(4-chlorophenyl)-2-(4-fluorophenyl)ethene (4n) inhibited the growth of Penicillium chrysogenum. 相似文献
992.
Shanmugam G Kozekov ID Guengerich FP Rizzo CJ Stone MP 《Chemical research in toxicology》2011,24(7):1071-1079
The oligodeoxynucleotide 5'-CGCATXGAATCC-3'·5'-GGATTCAATGCG-3' containing 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-εdG) opposite deoxyadenosine (named the 1,N(2)-εdG·dA duplex) models the mismatched adenine product associated with error-prone bypass of 1,N(2)-εdG by the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) and by Escherichia coli polymerases pol I exo(-) and pol II exo(-). At pH 5.2, the T(m) of this duplex was increased by 3 °C as compared to the duplex in which the 1,N(2)-εdG lesion is opposite dC, and it was increased by 2 °C compared to the duplex in which guanine is opposite dA (the dG·dA duplex). A strong NOE between the 1,N(2)-εdG imidazole proton and the anomeric proton of the attached deoxyribose, accompanied by strong NOEs to the minor groove A(20) H2 proton and the mismatched A(19) H2 proton from the complementary strand, establish that 1,N(2)-εdG rotated about the glycosyl bond from the anti to the syn conformation. The etheno moiety was placed into the major groove. This resulted in NOEs between the etheno protons and T(5) CH(3). A strong NOE between A(20) H2 and A(19) H2 protons established that A(19), opposite to 1,N(2)-εdG, adopted the anti conformation and was directed toward the helix. The downfield shifts of the A(19) amino protons suggested protonation of dA. Thus, the protonated 1,N(2)-εdG·dA base pair was stabilized by hydrogen bonds between 1,N(2)-εdG N1 and A(19) N1H(+) and between 1,N(2)-εdG O(9) and A(19)N(6)H. The broad imino proton resonances for the 5'- and 3'-flanking bases suggested that both neighboring base pairs were perturbed. The increased stability of the 1,N(2)-εdG·dA base pair, compared to that of the 1,N(2)-εdG·dC base pair, correlated with the mismatch adenine product observed during the bypass of 1,N(2)-εdG by the Dpo4 polymerase, suggesting that stabilization of this mismatch may be significant with regard to the biological processing of 1,N(2)-εdG. 相似文献
993.
Glipizide is mainly absorbed in the proximal areas of the gastrointestinal tract. The purpose of this study was formulation and evaluation of mucoadhesive films to prolong the stay of drug in its absorption area. Glipizide was formulated in a mucoadhesive film that could be retained in the stomach for prolonged intervals. Polymeric films were designed with various compositions of hydroxypropyl cellulose and polyethylene glycol 400 (PEG 400). Properties of the mucoadhesive film such as tensile strength, percentage elongation, swelling index, moisture content, pH and viscosity of polymeric dispersion, film thickness, content uniformity and mucoadhesion in a simulated gastric environment were characterized. In addition, percentage drug retained in stomach mucosa was estimated using a simulated dynamic stomach system as a function of time. Increase in hydroxypropyl cellulose concentration resulted in a higher tensile strength and elongation at break, while increase in concentration of PEG 400 was reflected in a decrease in tensile strength and increase of elongation at break. Glipizide/hydroxypropyl cellulose/PEG 400 (2.5:1:0.5) (GF5) was found to be the optimal composition for a novel mucoadhesive stomach formulation that showed good peelability, relatively high swelling index, moderate tensile strength, and stayed on rat stomach mucosa up to 8 h. In vivo testing of the mucoadhesive films with glipizide demonstrated a potential hypoglycemic effect. 相似文献
994.
Boonstra MC Verspaget HW Ganesh S Kubben FJ Vahrmeijer AL van de Velde CJ Kuppen PJ Quax PH Sier CF 《Current pharmaceutical design》2011,17(19):1890-1910
Since decades the urokinase plasminogen activator (uPA) system has been associated with the invasion of malignant cells. The receptor of urokinase (uPAR) is one of the key players in this proteolytic cascade, because it focuses uPA's proteolytic activity to the cell surface and in addition functions as a signaling receptor. uPAR is highly expressed in virtually all human cancers, suggesting possible clinical applications as diagnostic marker, predictive tool of survival or clinical response, and as a target for therapy and imaging. This review summarizes the possibilities of uPAR in clinical applications for cancer patients. 相似文献
995.
Cuihua Liu Shiming DongXiao-Jin Xu Yan YinZachary Shriver Ishan CapilaJames Myette Ganesh Venkataraman 《Journal of pharmaceutical and biomedical analysis》2011
Biological drugs represent an important and rapidly growing class of therapeutics useful in the treatment of a variety of disorders ranging from cancer to inflammation to infectious diseases. Unlike single chemical entities, the recombinant production of these drugs in living cells confers considerable structural and chemical heterogeneity to the biologically derived protein product that constitutes the active pharmaceutical ingredient (API). In mammalian based expression systems, much of this diversity is conferred through heterogeneous protein glycosylation. These post-translational modifications can have significant effects on the structure, biological function, and pharmacological properties of the API. In addition, the bulk proteins that comprise the API are further formulated through the use of multiple excipients designed to ensure product stability, solubility, and lot-to-lot consistency. Unfortunately, these matrices can interfere with commonly available analytical methods used in the thorough chemical characterization of the biological drug product. At the same time, a demonstration of the suitable extraction of the bulk drug substance in a manner and form that does not destabilize the active ingredient or introduce any structural bias with direct reference to the original drug product is both critical and necessary. Here, we use recombinant human follicle stimulating hormone (follitropin alpha for injection) from a pharmaceutical source as an example to illustrate a suitable purification strategy to effectively extract the bulk drug substance from the formulated drug product with high purity and yield. We assess the suitability of this extraction method in preserving the structural integrity and overall quality of the drug substance relative to the formulated drug product, placing a particular emphasis on glycosylation as a key product attribute. In so doing, we demonstrate that it is possible to effectively extract the active pharmaceutical ingredient from a formulated biological drug product in a manner that is consequently sufficient for its use in comparability studies. 相似文献
996.
Ganesh Nallur Shivu Khalid Abozguia Thanh Trung Phan Ibrar Ahmed Michael Frenneaux 《European journal of radiology》2010,73(2):255-259
Background
31P magnetic resonance spectroscopy (MRS) allows measurement of in vivo high-energy phosphate kinetics in the myocardium. While traditionally 31P cardiac spectroscopy is performed at 1.5 T, cardiac MRS at higher field strength can theoretically increase signal to noise ratio (SNR) and spectral resolution therefore improving sensitivity and specificity of the cardiac spectra. The reproducibility and feasibility of performing cardiac spectroscopy at 3 T is presented here in this study in healthy volunteers and patients with hypertrophic cardiomyopathy.Methods
Cardiac spectroscopy was performed using a Phillips 3T Achieva scanner in 37 healthy volunteers and 26 patients with hypertrophic cardiomyopathy (HCM) to test the feasibility of the protocol. To test the reproducibility a single volunteer was scanned eight times on separate occasions. A single voxel 31P MRS was performed using Image Selected In vivo Spectroscopy (ISIS) volume localization.Results
The mean phosphocreatine/adenosine triphosphate (PCr/ATP) ratio of the eight measurements performed on one individual was 2.11 ± 0.25. Bland Altman plots showed a variance of 12% in the measurement of PCr/ATP ratios. The PCr/ATP ratio was significantly reduced in HCM patients compared to controls, 1.42 ± 0.51 and 2.11 ± 0.57, respectively, P < 0.0001. (All results are expressed as mean ± standard deviation).Conclusions
Here we demonstrate that cardiac 31P MRS at 3 T is a reliable method of measuring in vivo high-energy phosphate kinetics in the myocardium for clinical studies and diagnostics. Based on our data an impairment of cardiac energetic state in patients with hypertrophic cardiomyopathy is indisputable. 相似文献997.
998.
Connolly B Krishnamurthy G Amaral J 《Techniques in Vascular and Interventional Radiology》2010,13(4):222-228
This article describes the radiologic techniques to obtain upper gastrointestinal access in children with poor oral intake and inadequate nutrition. Our goal is to provide a simple guide of radiologic gastrostomy and gastrojejunostomy procedures, their technical success, and long-term outcomes. Potential complications will be discussed as well as their management. It is important to emphasize that a multidisciplinary approach (pediatrician, dietitian, interventional radiologist, pediatric surgeon) is paramount for appropriate indications and management of patients with gastrostomies and gastrojejunostomies. 相似文献
999.
Shelli R. Kesler Kyle Noll Daniel P. Cahill Ganesh Rao Jeffrey S. Wefel 《Journal of neuro-oncology》2017,131(3):565-574
Mutation of the IDH1 gene is associated with differences in malignant astrocytoma growth characteristics that impact phenotypic severity, including cognitive impairment. We previously demonstrated greater cognitive impairment in patients with IDH1 wild type tumor compared to those with IDH1 mutant, and therefore we hypothesized that brain network organization would be lower in patients with wild type tumors. Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age?=?45?±?14 years) and used to extract individual level, gray matter connectomes. Graph theoretical analysis was then applied to measure efficiency and other connectome properties for each patient. Cognitive performance was categorized as impaired or not and random forest classification was used to explore factors associated with cognitive impairment. Patients with wild type tumor demonstrated significantly lower network efficiency in several medial frontal, posterior parietal and subcortical regions (p?<?0.05, corrected for multiple comparisons). Patients with wild type tumor also demonstrated significantly higher incidence of cognitive impairment (p?=?0.03). Random forest analysis indicated that network efficiency was inversely, though nonlinearly associated with cognitive impairment in both groups (p?<?0.0001). Cognitive reserve appeared to mediate this relationship in patients with mutant tumor suggesting greater neuroplasticity and/or benefit from neuroprotective factors. Tumor volume was the greatest contributor to cognitive impairment in patients with wild type tumor, supporting our hypothesis that greater lesion momentum between grades may cause more disconnection of core neurocircuitry and consequently lower efficiency of information processing. 相似文献
1000.
Anagha Atul Joshi Bhagyashri Ganesh Chiplunkar Renuka Anil Bradoo 《Indian journal of otolaryngology and head and neck surgery》2017,69(1):77-80
To evaluate treatment response in patients with laryngopharyngeal reflux (LPR). A prospective study of 100 patients with voice disorders was conducted. Patients were evaluated using reflux symptom index (RSI) and reflux finding score (RFS) by 70° rigid laryngoscope. Patients with RFS score of 7 or more were diagnosed of having LPR and were started with anti-reflux therapy for a period of 6 months. Patients were assessed at regular intervals using RSI and RFS. The prevalence of LPR in patients with voice disorders was found to be 25%. The mean RSI score improved gradually and significantly over a period of 6 months from 11.84 at presentation to 2.04 after 6 months of treatment (p value <0.001). The mean value of RFS improved from 7.92 at entry to 1.52 after 6 months of treatment (p value <0.001). However, it was found that the improvement was not significant at end of first month of treatment, and improvement in RSI and RFS scores was found only after 2 months of treatment. RSI and RFS improve significantly after treatment for 6 months with PPI like Omeprazole. But the improvement starts from the 2nd month from the onset of treatment. Treatment of LPR for at least 6 months may be indicated to attain a full resolution of physical findings. 相似文献