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11.
Gangwar Sanjeev Jois Seetharama D. S. Siahaan Teruna J. Vander Velde David G. Stella Valentine J. Borchardt Ronald T. 《Pharmaceutical research》1996,13(11):1657-1662
Purpose. To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug.
Methods. Two-dimensional Homonuclear Hartmann-Hahn spectroscopy, Rotating-Frame Overhouser effect spectroscopy, circular dichroism and molecular dynamics simulations were used to find the solution conformers of cyclic prodrug 1.
Results. Our spectroscopic findings suggest that cyclic prodrug 1 exhibits a major and a minor conformer in solution. The major conformer appears to have a well-defined secondary structure, which involves a -turn and 4 1 intramolecular hydrogen bond, creating a compact structure with a reduced average hydrodynamic radius compared to the model hexapeptide 2.
Conclusions. The increased ability of cyclic prodrug 1 to permeate membranes compared to the model hexapeptide 2 could be due to reduction in the average hydrodynamic radius of the molecule facilitating paracellular flux and/or the reduction in the hydrogen bonding potential facilitating transcellular flux. 相似文献
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With emerging sophistication in the exploration of ocean environment, a number of marine bioactive products have been identified with promising anticancer activity. Many of these are in active phase I or phase II clinical trials or have been terminated because of adverse side effects, mainly hematological in nature. Nonetheless, the information derived has aided enormously in providing leads for laboratory synthesis with modifications in the parent structure affecting compound solubility, absorption, and toxicity, resulting in less severe toxicity while achieving maximum efficacy in smaller doses. We describe herein, a few of the compounds obtained from marine and terrestrial sources [bryostatin 1 ( 1), dolastatin 10 ( 2), auristatin PE ( 3), and combretastatin A4 ( 4)] that have been extensively investigated in our laboratory and continue to be investigated for their sensitization effects with other cytotoxic agents in several different site-specific tumors employing murine models or human subjects. 相似文献
14.
Olivia Bonardi Yutong Wang Kexin Li Xiaowen Jiang Ankur Krishnan Chen He Ying Sun Yin Wu Jill T. Boruff Sarah Markham Danielle B. Rice Ian Thombs-Vite Amina Tasleem Tiffany Dal Santo Anneke Yao Marleine Azar Branka Agic Christine Fahim Michael S. Martin Sanjeev Sockalingam Gustavo Turecki Andrea Benedetti Brett D. Thombs 《Revue canadienne de psychiatrie》2022,67(5):336
15.
Mitnala Sasikala D. Nageshwar Reddy Nitesh Pratap Sanjeev Kumar Sharma P. Reddy Balkumar Anuradha Sekaran Rupa Banerjee D. Bhaskara Reddy 《Indian journal of gastroenterology》2009,28(5):169-174
Background and Objective
The role of Mycobacterium avium ss paratuberculosis (MAP) in the etiopathology of Crohn’s disease (CD) remains controversial, because of conflicting reports demonstrating the presence of MAP-specific insertion sequence from intestinal biopsy tissues of patients clinically diagnosed for the disease. The present study was carried out to investigate the presence of MAP DNA in the intestinal tissues of CD patients to ascertain the relevance of MAP in Indian patients with CD. 相似文献16.
Voltage-gated K+ channels undergo a voltage-dependent conductance change that plays a key role in modulating cellular excitability. While the Open state is captured in crystal structures of Kv1.2 and a chimeric Kv1.2/Kv2.1 channel, the Close state and the mechanism of this transition are still a subject of debate. Here, we propose a model based on mutagenesis combined with measurements of both ionic and gating currents which is consistent with the idea that the Open state is the default state, the energy of the electric field being used to keep the channel closed. Our model incorporates an 'Activated state' where the bulk of sensor movement is completed without channel opening. The model accounts for the well characterized electrophysiology of the 'V2' and 'ILT' mutations in Shaker, where sensor movement and channel opening occur over distinct voltage ranges. Moreover, the model proposes relatively small protein rearrangements in going from the Activated to the Open state, consistent with the rapid transitions observed in single channel records of Shaker type channels at zero millivolts. 相似文献
17.
Cardiac MRI in the management of congenital heart disease in children, adolescents, and young adults
Woodard PK Bhalla S Javidan-Nejad C Bierhals A Gutierrez FR Singh GK 《Current treatment options in cardiovascular medicine》2008,10(5):419-424
Recent advances in MRI have made this modality an important tool for evaluating heart disease. Faster scanning techniques, high spatial resolution, lack of ionizing radiation, lack of dependence on contrast material, and capability for functional imaging have made it an emerging noninvasive diagnostic tool with great potential in younger patients with heart disease. This article discusses the role of cardiac MRI, methods of evaluation, and newer application of MRI in evaluating congenital heart disease in pediatric and young adult patients. 相似文献
18.
Cardiac catheterization through ipsilateral radial and ulnar artery access during the same procedure
Dilip Kumar Madhumanti Panja Ashesh Halder Soumya Patra Arindam Pande Sanjeev Salil Kumar Mukherjee Rana Rathor Roy Ejaz Ahmad Bari Anil Kumar Singhi 《Indian heart journal》2021,73(3):387-388
We evaluated the safety and feasibility of ipsilateral radial and ulnar artery cannulation during the same catheterization procedure. Crossover from radial to femoral was done in 122 patients. Both ipsilateral radial and ulnar catheterization were performed in 16 patients without any complications, which was further supported by Doppler ultrasonography. 相似文献
19.
Jae-Jin Cho Brigid Joseph Baljit Singh Sappal Ranjit K Giri Richard Wang John W Ludlow Mark E Furth Robert Susick Sanjeev Gupta 《Liver international》2004,24(4):361-370
BACKGROUND: The availability of well-characterized human liver cell populations that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after cryopreservation and engraft in immunodeficient mice. METHODS: We isolated cells from discarded human livers and studied the properties of cryopreserved cells. The viability of thawed cells was established with multiple in vitro assays, including analysis of liver gene expression, ureagenesis, cytochrome P450 activity, and growth factor-induced cell proliferation. The fate of transplanted cells was analysed in immunodeficient NOD-SCID mice. RESULTS: After thawing, the viability of human hepatocytes exceeded 60%. Cells attached to culture dishes, proliferated following growth factor stimulation and exhibited liver-specific functions. After transplantation in NOD-SCID mice, cells engrafted in the peritoneal cavity, a heterologous site, as well as the liver itself, retained hepatic function and proliferated in response to liver injury. Transplanted hepatocytes were integrated in the liver parenchyma. Occasionally, transplanted cells were integrated in bile ducts. CONCLUSIONS: Cryopreserved human liver cell showed the ability to retain functional integrity and to reconstitute both hepatic and biliary lineages in mice. These studies offer suitable paradigms aimed at characterizing liver cells prior to transplantation in people. 相似文献
20.