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Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU. 相似文献
3.
Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions. 相似文献
4.
Histopathology reports are important quality assurance tools and evaluation of pathological diagnoses described in them is an integral part of total quality control and quality improvement program. We describe a program based on slide circulation which was aimed at both continuing education to upgrade knowledge and proficiency testing of histopathologists. The performance of the participating pathologists was analyzed and the degree of agreement was also studied. The results showed improvement indicated by rising level of performance in 35.3% of consistent participants and increasing trend in the average score. The degree of agreement was comparatively low (65.29%). The practicability of this program and its acceptability as an EQAS was also investigated. 相似文献
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Various 2-adrenoceptor agonists were assessed for their effects on alcohol abstinence syndrome in rats. In the first experimental model, groups of Wistar rats were made alcohol dependent by feeding alcohol together with sweetened milk for 15 days. The volume of fluid intake was measured every 12 h to determine daily ethanol consumption. Abstinence signs following abrupt alcohol withdrawal were observed in control as well as test groups receiving various 2-adrenoceptor agonists. Clonidine, guanfacine and B-HT 920, in equimolar concentration (0.5 M/kg), effectively attenuated the various abstinence signs, which developed after alcohol withdrawal. In the other experimental model, rats were subjected to cold water immersion to induce wet shakes. The inhibitory action of 2-adrenoceptor agonists was assessed in this test model. Clonidine, guanfacine and B-HT 920 markedly suppressed the cold water immersion-induced wet shakes and pretreatment with yohimbine (0.1 and 2.0 M/kg) reversed this inhibitory effect. The present data reveal the possible therapeutic potential of 2-adrenoceptor agonists in alleviating alcohol abstinence syndrome, and suggest that the resultant reduced noradrenergic activity may be responsible for the beneficial action. 相似文献
7.
Arif Ali Milind Gosavi Rajiv Michael John Mathew Mary Kurien Anila Korula 《Indian journal of otolaryngology and head and neck surgery》2004,56(4):314-316
Chondrosarcoma of the head and neck region are relatively uncommon, arising rarely in the naval septum. The reported cases
of nasal septal chondrosarcomas are extensive lesions with involvement of paranasal sinuses, orbit or skull base at the lime
of diagnosis. Those limited to the nasal cavity is extremely rare and to date there has been one case report in English language
literature. We present a case of chondrosarcoma of the nasal septum with involvement of the nasal cavity alone and no evidence
of bony erosion. Initial multiple biopsies showed mature chondromatous areas with no atypia. The patient had wide excision
of the tumour. The final biopsy of the excised specimen revealed foci of well-differentiated chondrosarcoma. Wide surgical
excision with adequate margins should be considered as the treatment of choice in lesion of nasal septum even if initial biopsies
are negative for malignancy. Hence this case report. 相似文献
8.
Ashok Kumar Reddy Upputuri Brahmaiah Nitesh Narayen Ravi Kumar Reddy Rupak Kumar Reddy Meghraj Chitta Srinivas Prasad Rishi Swarup Syed Maaz Mohiuddin Madhukar Reddy Murali K. Aasuri B. S. R. Murthy Milind Bhide Sajid Ahmed 《International ophthalmology》2013,33(3):251-254
To compare the blood agar (BA), sabouraud dextrose agar (SDA) and chocolate agar (CA) for the isolation of fungi in patients with mycotic keratitis. Corneal Scrapings of 229 patients with clinically diagnosed microbial keratitis were inoculated on BA, SDA, CA. The culture media were evaluated for the rate and time taken for the fungal growth. Seventy six of 229 patients had fungal keratitis. Fungus grew on BA in 60/76(78.9 %), on SDA in 76/76 (100 %), on CA in 40/76(52.6 %) patients. The fungi which grew on BA (60/76) also grown on SDA at the same time. The colony morphologies of different fungi were better on SDA than BA/CA. Among the different culture media, SDA is essential for the isolation fungi in patients with mycotic keratitis. 相似文献
9.
Milind Singh Brindar Sandhu Aaron Scurto Cory Berkland Michael S. Detamore 《Acta biomaterialia》2010,6(1):137-143
Shape-specific, macroporous tissue engineering scaffolds were fabricated and homogeneously seeded with cells in a single step. This method brings together CO2 polymer processing and microparticle-based scaffolds in a manner that allows each to solve the key limitation of the other. Specifically, microparticle-based scaffolds have suffered from the limitation that conventional microsphere sintering methods (e.g., heat, solvents) are not cytocompatible, yet we have shown that cell viability was sustained with subcritical (i.e., gaseous) CO2 sintering of microspheres in the presence of cells at near-ambient temperatures. On the other hand, the fused microspheres provided the pore interconnectivity that has eluded supercritical CO2 foaming approaches. Here, fused poly(lactide-co-glycolide) microsphere scaffolds were seeded with human umbilical cord mesenchymal stromal cells to demonstrate the feasibility of utilizing these matrices for cartilage regeneration. We also demonstrated that the approach may be modified to produce thin cell-loaded patches as a promising alternative for skin tissue engineering applications. 相似文献
10.
Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the beta-globin locus control region
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