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排序方式: 共有993条查询结果,搜索用时 15 毫秒
1.
2.
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.
Germline mutations of the Apc tumor suppressor gene result in increased risk for gastrointestinal carcinogenesis. The Apc1638N [+/-] mouse exhibits accelerated gastrointestinal carcinogenesis that is modifiable by select pharmacological and dietary agents. Experiments in the present study were conducted on a subculturable epithelial 1638NCOL cell line established from histologically normal colon of Apc1638N [+/-] mouse to examine the effects of selected chemopreventive agents that differ in their mechanism of action. Extent of growth arrest, number of cell population doublings, cell cycle progression and aneuploid G0/G1: S + G2/M ratio represented the quantitative endpoints for the susceptibility and efficacy of chemopreventive agents. Treatment of exponentially growing 1638NCOL cells with maximum cytostatic dose of 9cisRA, DFMO or SUL (100 microM) produced a 60-70% growth arrest, that with TAM and AMF (10 microM) produced a 20-40% growth arrest, while that with OLT (100 microM) produced a 25% growth arrest. This response was associated with corresponding decrease in the number of cell population doubling. 9cisRA, SUL or AMF increased the aneuploid G0/G1: S + G2/M ratio by inducing G1 checkpoint arrest, while DFMO, TAM and OLT decreased the ratio by inducing G2 checkpoint arrest. Thus, cell cycle phase-dependent susceptibility of the Apc [+/-] 1638NCOL cell line to mechanistically distinct chemopreventive agents validates a novel colon epithelial cell culture model for mechanistic, preventive or therapeutic studies on Apc regulated colon carcinogenesis. 相似文献
5.
6.
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.
A. Suto H. Leon Bradlow George Y. C. Wong Michael P. Osborne Nitin T. Telang 《Breast cancer research and treatment》1993,27(3):193-202
Summary The polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) is a metabolism-dependent procarcinogen whose tumorigenicity is modified by dietary and endocrine manipulationsin vivo. DMBA initiates molecular and cellular alterations in the mammary tissue, while dietary components and estrogens affect the post-initiational phase of tumorigenic transformation. The mechanism(s) responsible for modulation of tumorigenic transformation remain unclear. This study examines the effects of selected tumor suppressing agents and estradiol (E2) metabolites onin vitro DMBA carcinogenesis utilizing a newly established mouse mammary epithelial cell line C57/MG. Alteration in DNA repair synthesis, metabolism of E2 via the C2- and C16-hydroxylation pathways, and acquisition of anchorage-independent growth were utilized as molecular, endocrine, and cellular biomarkers to quantitate the cellular transformation by DMBA and its modulation by tumor suppressing agents and E2 metabolites. A single 24 hr exposure of 0.78 µM DMBA to C57/MG cells resulted in a 193.9% increase in DNA repair synthesis and a 73.1% decrease in C2/C16 hydroxylation of E2. The DMBA treated C57/MG cells also exhibited increased anchorage-independencein vitro prior to tumorigenesisin vivo. A simultaneous treatment of cells with DMBA and with the highest non-cytotoxic doses of the tumor suppressing agents 5 µM N-(4-hydroxyphenyl) retinamide (HPR), 50 µM indole-3-carbinol (I3C), or 1 µM tamoxifen (TAM) resulted in a 35.6% to 63.9% decrease in DNA repair synthesis, a 23.8% to 1347.6% increase in C2/C16 hydroxylation of E2, and a 53.8% to 72.4% decrease in anchorage-independent growth. The E2 metabolites at the highest non-cytotoxic doses of 0.76 µM estrone (E1), 0.69 µM 2-hydroxyestrone (2-OHE1), and 0.66 µM 2-methoxyestrone (2-MeOHE1) suppressed DMBA-induced DNA repair synthesis by 56.0% to 68.8%. These tumor suppressing agents and E2 metabolites also effectively suppressed post-initiational, anchorage-independent growth by 24.9% to 72.4%. These results indicate that DMBA induces cellular transformation in part by causing DNA damage, altering C2/C16 hydroxylation in favor of C16-hydroxylation, and inducing anchorage-independent growth prior to tumor development. Effective downregulation of these genotoxic, endocrine and proliferative end points by prototypic tumor suppressing agents and by E2 metabolites generated via the C2-hydroxylation pathway suggest that these agents may influence mammary tumorigenesis by inhibiting early occurring initiational and/or post initiational events.Abbreviations DMBA
7,12-dimethylbenz(a)anthracene
- HPR
N-(4-hydroxyphenyl) retinamide
- I3C
indole-3-carbinol
- TAM
tamoxifen
- E2
17-estradiol
- E1
estrone
- 2-OHE1
2-hydroxyestrone
- 2-MeOHE1
2-methoxyestrone
- 16-OHE1
16-hydroxyestrone
- E3
estriol
- DME/F12
Dulbecco's modified Eagle's medium
- F12
Ham's medium
- HU
hydroxyurea
- PBS
phosphate buffered saline
- NaOH
sodium hydroxide
- SDS
sodium dodecyl sulfate
- TCA
trichloroacetic acid
- [C2-3H] E2
estradiol labeled at C2 position
- [C16-3H] E2
estradiol labeled at C16 position
- ANOVA
analysis of variance 相似文献
8.
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
9.
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
10.
Palanisamy Sankar Avinash G. Telang Ayyasamy Manimaran 《Experimental and toxicologic pathology》2012,64(5):487-493
The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats. 相似文献