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991.
In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with l-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug. 相似文献
992.
Movva Snehalatha Kolachina Venugopal Ranendra N. Saha Anil Kumar Babbar Rakesh Kumar Sharma 《Drug delivery》2013,20(5):277-287
Etoposide and nanoparticle formulations were labeled with Tc-99m and their biodistribution and pharmacokinetics were studied after intravenous administration in healthy mice and rabbits respectively. Etoposide was rapidly cleared from the body, while the disposition of nanoparticles was slower. A higher proportion of nanoparticles compared with etoposide was observed in different organs of mice. Scintigraphic images of rabbits concluded that the radioactivity shown by formulations is significantly higher after 4 and 24 h, as compared with etoposide administered in rabbits. AUC0 ? ∞, clearance and MRT are better than those obtained with etoposide administration. The overall high residence of nanoparticles, compared with etoposide, signifies the advantage of PLGA and PCL nanoparticles as drug carriers for etoposide in enhancing the bioavailability and reducing the etoposide-associated toxicity. 相似文献
993.
Brain senescence plays an important role in cognitive dysfunction and neurodegenerative disorders. Curcumin was reported to have beneficial effect against several neurodegenerative disorders including Alzheimer's disease. Therefore, the present study was conducted in order to explore the possible role of curcumin against d-galactose-induced cognitive dysfunction, oxidative damage, and mitochondrial dysfunction in mice. Chronic administration of d-galactose for 6 weeks significantly impaired cognitive function (both in Morris water maze and elevated plus maze), locomotor activity, oxidative defense (raised lipid peroxidation, nitrite concentration, depletion of reduced glutathione and catalase activity), and mitochondrial enzyme complex activities (I, II, and III) as compared to vehicle treated group. Curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment for 6 weeks significantly improved cognitive tasks, locomotor activity, oxidative defense, and restored mitochondrial enzyme complex activity as compared to control (d-galactose). Chronic d-galactose treatment also significantly increased acetylcholine esterase activity that was attenuated by curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment. In conclusion, the present study highlights the therapeutic potential of curcumin against d-galactose induced senescence in mice. 相似文献
994.
Pooja Singh Vikas Kumar Swati Aggarwal Anjani K. Tiwari Krishna Chuttani Ramendra Pratap Anil K. Mishra 《Chemical biology & drug design》2013,82(2):226-232
Catecholamine mimetic EDTA‐bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand‐human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex = 350 nm found to be 5.847 × 104 m ?1 shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 μm for MAO‐B inhibition. Finally, EDTA‐bis(tyramide) labeled with 99mTc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for 99mTc‐EDTA‐bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body. 相似文献
995.
Kuntegowdanahalli Chinnagiriyappa Lakshmaiah Anil N Kumar Samit Purohit Belathur Kalegowda Viveka Kamalakannan Rahul Rajan Mohammed Abdul Lateef Zameer Prabhu Namitha Monika Lamba Saini Hatem A Azim Jr Kamal S Saini 《Hereditary cancer in clinical practice》2014,12(1):5
The association of neurofibromatosis type I with invasive male breast cancer is a rare clinical entity with only one case in literature reported in 1953. Women with NF1 are at risk of developing breast cancer and men also may be at risk but there is scarce data on the risk and association of NF1 with male breast cancer due to its rarity. Established clinical trials in male breast cancer patients are lacking and the results are extrapolated from female breast cancer patients. The treatment of male breast cancer is followed as per the guidelines of premenopausal female breast cancer and tamoxifen is the hormone treatment in them. Mendes et al suggests that silencing of NF1 gene confers resistance to tamoxifen. Our conclusions are that since NF1 is mutated or deleted in one third of sporadic breast cancers, its role as a molecular driver for treatment has to be further explored. 相似文献
996.
Ascher E Hingorani A Markevich N Yorkovich W Schutzer R Hou A Jacob T Nahata S Kallakuri S 《Annals of vascular surgery》2004,18(4):433-439
The limitations and complications associated with contrast angiography (CA) prior to lower extremity revascularization have led to an increased interest in duplex arteriography (DA) as a potential replacement. We report our experience with DA in patients with diabetes and/or chronic renal insufficiency (CRI) that would particularly benefit from a noninvasive approach to preoperative evaluation of the arterial tree. From January 1998 to November 2000, DA was performed in 145 patients with diabetes mellitus and/or CRI prior to 180 arterial reconstructions. One hundred twenty-one procedures were performed on 91 patients with diabetes alone, 41 on 33 patients with diabetes and CRI, and 18 on 15 patients with CRI alone. Patient ages ranged from 36 to 98 years (mean 72 ± 12 years). Indications for surgery were severe claudication in 33 (18%), rest pain in 37 (21%), nonhealing ischemic ulcers in 52 (29%), and limb gangrene in 58 (32%). Optimal inflow and outflow anastomotic sites were selected according to a diagram based on DA that included arterial tree imaging from mid-aorta to the pedal vessels. Preoperative contrast arteriography was performed in 16 cases (9%) because of extremely poor runoff based on DA and limited visualization of outflow vessels. The distal anastomosis was to the popliteal artery in 89 cases (49%) and to the tibial and pedal arteries in 91 (51%). Intraoperative findings confirmed the preoperative DA results with the exception of one (0.6%) where the distal anastomosis was placed proximal to a significant stenosis requiring an extension graft. The use of DA presents a safe and reliable option to prebypass CA for many patients with diabetes or CRI. The ease of use and favorable patient outcomes achieved by this imaging modality may rival the use of CA for these patients.Presented at the Southern Association for Vascular Surgery, Rio Grande, Puerto Rico, January 26, 2001. 相似文献
997.
Ascher E Markevich N Kallakuri S Schutzer RW Hingorani AP 《Journal of vascular surgery》2004,39(2):416-420
PURPOSE: Thromboembolic complications after carotid endarterectomy are frequently associated with technical defects. We analyzed the effect of intraoperative duplex scanning in detection of significant but clinically unsuspected technical defects and residual common carotid artery (CCA) disease as a potential source of postoperative transitory ischemic attack (TIA) and stroke. METHODS: From April 2000 to April 2003, 650 consecutive primary carotid endarterectomy procedures were performed in 590 patients at a single institution by two vascular surgeons. Patients included 335 men (57%) and 255 women (43%). Indications for surgery were asymptomatic internal carotid artery (ICA) stenosis (>or=70%) in 464 patients (71%). All procedures were performed with the patient under general anesthesia, with synthetic patch angioplasty in 644 (99.1%). Major technical defects at intraoperative duplex scanning (>30% luminal internal carotid artery stenosis, free-floating clot, dissection, arterial disruption with pseudoaneurysm) were repaired. CCA residual disease was reported as wall thickness (0.7-4.8 mm; mean, 1.7 +/- 0.7) and percent stenosis (16%-67%; mean, 32% +/- 8%) in all cases. Postoperative 30-day TIA, stroke, and death rates were analyzed. RESULTS: There were no clinically detectable postoperative thromboembolic events in this series. All 15 major defects (2.3%) identified with duplex scanning were successfully revised. These included 7 intimal flaps, 4 free-floating clots, 2 ICA stenoses, 1 ICA pseudoaneurysm, and 1 retrograde CCA dissection. Diameter reduction ranged from 40% to 90% (mean, 67 +/- 16%), and peak systolic velocity ranged from 69 to 497 cm/s (mean, 250 +/- 121 cm/s). Thirty-one patients (5%) with the highest residual wall thickness (>3mm) in the CCA and 19 (3%) with the highest CCA residual diameter reduction (>50%) did not have postoperative stroke or TIA. Overall postoperative stroke and mortality rates were 0.3% and 0.5%, respectively; combined stroke and mortality rate was 0.8%. One stroke was caused by hyperperfusion, and the other occurred as an extension of a previous cerebral infarct. No patients had TIAs. Two deaths were caused by myocardial infarction, and one death by respiratory insufficiency. CONCLUSION: We believe intraoperative duplex scanning had a major role in these improved results, because it enabled detection of clinically unsuspected significant lesions. Residual disease in the CCA does not seem to be a harbinger of stroke or TIA. 相似文献
998.
Hingorani A Ascher E Markevich N Kallakuri S Hou A Schutzer R Yorkovich W 《Journal of vascular surgery》2004,39(4):717-722
OBJECTIVE: In an effort to explore alternatives to contrast material-enhanced arteriography, we compared magnetic resonance angiography (MRA) and duplex arteriography (DA) with contrast arteriography (CA) for defining anatomic features in patients undergoing lower extremity revascularization. METHODS: From August 1, 2001, to August 1, 2002, 61 consecutive inpatients (64 limbs) with chronic lower extremity ischemia underwent CA, MRA, and DA before undergoing lower extremity revascularization procedures. The reports of these tests and images were compared prospectively, and the differences in the iliac, femoropopliteal, and infrapopliteal segments were noted. The vessels were classified as mildly diseased (<50%), moderately diseased (50%-70%), severely diseased (71%-99%), or occluded. The studies and treatment plans based on these data were compared. RESULTS: Mean patient age was 76 +/- 10 years (SD). Indications for the procedures included gangrene (43%), ischemic ulcer (28%), rest pain (19%), severe claudication (9%), and failing bypass (1%). During this period 35 patients were ineligible for the protocol, because they could not undergo MRA (n=27) or angiography (n=8). Of the total 192 segments in the 64 patients (iliac, femoropopliteal, tibial), 17% were not able to be fully assessed with DA, and 7% with MRA. Disagreements with CA and DA were found in the iliac, femoropopliteal, and tibial segments in 0%, 7%, and 14% of cases, respectively, and between CA and MRA in 10%, 26%, and 42% of cases, respectively. Two of 9 differences (22%) between DA and CA were thought to be clinically significant, and 28 of 45 differences (62%) between MRA and CA were thought to be clinically significant. CONCLUSIONS: A review of the data obtained in this series indicates that MRA does not yet seem to yield adequate data, at least in this highly selected population at our institution. When severe calcification is identified, CA may be necessary in patients undergoing DA. 相似文献
999.
1000.
Parikshit M Gogate Mohini Sahasrabudhe Mitali Shah Shailbala Patil Anil N Kulkarni Rupal Trivedi Divya Bhasa Rahin Tamboli Rekha Mane 《Indian journal of ophthalmology》2014,62(2):186-195