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排序方式: 共有5400条查询结果,搜索用时 15 毫秒
31.
Christopher R Gibson Charles Lin Rominder Singh Cheri M Brown Karen Richards Janice Brunner Kimberly Michel Jennifer Adelsberger Edward Carlini Catherine Boothe-Genthe Conrad Raab Minh Luu Aimee Michael Mona Parikh Patrice Ciecko Raju Subramanian Paul Krolikowski A David Rodrigues Thomas A Baillie Thomas H Rushmore 《Drug metabolism and disposition》2005,33(7):1044-1051
Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A. 相似文献
32.
Functional and anatomical evaluation of the effect of nepafenac in prevention of macular edema after phacoemulsification in diabetic patients 下载免费PDF全文
Tharwat Mokbel Sameh Saleh Mona Abdelkader Sherief E. El-khouly Waleed Abou Samr Mohamed Mamdouh 《国际眼科》2019,12(3):387-392
AIM: To evaluate the effect of prophylactic administration of nepafenac in prevention of macular edema occurring in diabetic patients after phacoemulsification and to investigate the correlation between optical coherence tomography (OCT) foveal thickness and multifocal electroretinogram (MF-ERG) parameters.
METHODS: The study included two groups. Group 1 included 50 diabetic patients with senile cataract (50 eyes, 30 females, 20 males, aged 55±7y) received nepafenac 0.1% eye drop. Group 2 included another 50 diabetic patients with senile cataract (50 eyes, 22 female, 28 males, aged 53.8±8y) did not receive nepafenac. All patients were followed up for 3mo postoperatively. OCT and MF-ERG were done preoperative and at 1wk, 1, 2 and 3mo.
RESULTS: The mean foveal thickness was statistically significantly lower in Group 1. Five eyes in Group 2 developed clinical cystoid macular oedema (CMO) (10%), and no patients in Group 1 developed central macular thickening more than 50 μm. There were insignificant differences in MF-ERG amplitudes and latencies between the two groups except in the five eyes that developed CMO, there statistically significant reduction of MF-ERG amplitude with increase in foveal thickness.
CONCLUSION: Perioperative nepafenac reduces the incidence of CMO following uncomplicated phacoemulsification significantly. Nepafenac has no side effects. 相似文献
33.
Khaled Ahmed Mansour Ahmed Elbermawi Ahmed A. Al-Karmalawy Mohamed-Farid Lahloub Mona El-Neketi 《Pharmaceutical biology》2022,60(1):1374
ContextTraditionally, Oleaceae plants are used to treat many diseases, such as rheumatism, hypercholesterolaemia, or ulcers.ObjectivesTo investigate the cytotoxic potential of Jasminum humile L., Jasminum grandiflorum L., and Olea europaea L. (Oleaceae) extracts against selected human cancer cells lines, followed by a phytochemical investigation of the most potent one.Materials and methodsThe 95% ethanol extracts of aerial parts of three oleaceous plants were examined for their cytotoxicity against HepG-2, MCF-7, and THP-1 cell lines using MTT assay and doxorubicin (positive control). J. humile was bio-selected and submitted to bio-guided fractionation. Chromatographic workup of ethyl acetate and n-butanol fractions afforded two new compounds; 1-methoxyjasmigenin (1) and 1-methyl-9-aldojasmigenin (2), along with five known ones (3–7). Structures were unambiguously elucidated using 1D/2D NMR and ESI-HRMS. Isolated compounds were assessed for their anti-proliferative potential, and both selectivity index and statistical significance were determined. Molecular docking was conducted against the Mcl-1 receptor using (AZD5991) as a standard.ResultsJasmoside (5) was the most potent anticancer compound showing IC50 values of 66.47, 41.32, and 27.59 µg/mL against HepG-2, MCF-7, and THP-1 cell lines, respectively. Moreover, isojasminin (4) exhibited IC50 values of 33.49, 43.12, and 51.07 µg/mL against the same cell lines, respectively. Interestingly, 5 exhibited the highest selectivity index towards MCF-7 and THP-1, even greater than doxorubicin. Molecular docking results were in full agreement with the MTT assay and the proposed SAR.ConclusionIn this study, two new compounds were purified. The biological activity highlighted jasmoside (5) as a lead anticancer drug for further future investigation. 相似文献
34.
35.
Einas S Elwali Ahmed O Almobarak Mona A Hassan Amir A Mahmoou Heitham Awadall Mohamed H Ahmed 《国际眼科》2017,10(6):948-954
AIM: To assess the frequency and associated risk factors of diabetic retinopathy among Sudanese individuals with diabetes attending Makka Eye complex in Khartoum, Sudan.
METHODS: The cross sectional hospital based study recruited 316 individuals with diabetes from Makkah Eye Complex Retina Clinic. Standard questionnaire was used to collect demographic data, medical history and life style characteristics. Blood samples were taken to measure HbA1c and lipid profile. Fundus and slit lamp examination were performed for screening of diabetic retinopathy.
RESULTS: Among 316 participants, 187 (59.2%) were males and 129 (40.8%) were females. The mean age of participants was 58.7±10.5y. The overall frequency of retinopathy was 261 (82.6%). The percentages of the total participants with proliferative diabetic retinopathy (PDR) were 126 (39.9%) and non-proliferative diabetic retinopathy (NPDR) were 135 (42.7%). Importantly, duration of diabetes mellitus (DM) (72.2% of more than 10y), being on oral hypoglycaemic drugs (versus insulin), and hypertension were all significant risk factors for diabetic retinopathy (P=0.00, 0.01 and 0.00 respectively). Complications of diabetes like diabetic foot (17.7%), history of amputation (6.7%) and clinically significant macular edema (CSME) (47.4%) of the eyes were all significant risk factors (P<0.05). Logistic regression analysis showed that duration of diabetes, hypertension and CSME were found to be absolute risk factors (P=0.007, 0.003 and 0.000 respectively). Duration of DM of more than 10y have more than double risk (OR=2.8), while having hypertension triples the risk of retinopathy (OR=3.1).
CONCLUSION: High rates of diabetic retinopathy are noted among individuals with diabetes attending Makkah Eye hospital in capital Khartoum. Urgent strategies are needed to monitor and treat hypertension and optimize diabetes control in individuals with diabetes. More investment in diabetes services is urgently needed. 相似文献
36.
Herein, a series of vanillin-crosslinked chitosan (Vn-CS) nanocomposites (NCs) containing various contents of ZnO nanoparticles (NPs) was prepared and characterized via FTIR spectroscopy, XRD, TGA, SEM and TEM. Changing the weight% of ZnO NPs in the prepared NCs resulted in an improvement in their antibacterial activity against Gram-negative and Gram-positive bacteria strains compared with the unmodified CS, and the encapsulation efficiency of 5-fluorouracil (5-FU) was found to be in the range of 61.4–69.2%. Subsequently, the release of 5-FU was monitored utilizing the mesoporous ZrO2–Co3O4 NPs modified carbon paste sensor via the square-wave adsorptive anodic stripping voltammetry (SW-AdASV) technique. Also, the release mechanism of 5-FU from each NC was studied by applying the zero-order, first-order, Hixson–Crowell and Higuchi models to the experimental results. The cytotoxicity of prepared NCs and 5-FU-encapsulated NCs was evaluated against the HePG-2, MCF-7 and HCT-116 cancer cell lines, in addition to the WI-38 and WISH normal cell lines using the MTT assay. Notably, 5-FU/CV10 NC exhibited the highest antitumor activity towards all tested cancer cell lines and a moderate activity against WI-38 and WISH normal cell lines with IC50 values of 28.02 ± 2.5 and 31.65 ± 2.7 μg mL−1, respectively. The obtained nanocomposites exhibited suitable selectivity with minimum toxicity against normal cells.Herein, a series of vanillin-crosslinked chitosan (Vn-CS) nanocomposites (NCs) containing various contents of ZnO nanoparticles (NPs) was prepared and characterized via FTIR spectroscopy, XRD, TGA, SEM and TEM. 相似文献
37.
ObjectiveTo evaluate the efficacy of reusing carboplatin and taxol in women with relapsed endometrial cancer.MethodsRetrospective analysis of our database of newly diagnosed high-risk patients with endometrial cancer treated with carboplatin–paclitaxel at diagnosis, with subsequent relapse for the period of 1995–2007.Results111 patients of 200 relapsed. They had either endometroid or papillary serous histologies. Strategies utilized upon first relapse were: no treatment (n = 33), surgery (n = 4), hormones (n = 8), irradiation (n = 14) and chemotherapy (n = 52). Carboplatin and paclitaxel was reused in 31 (60% of 52 retreated with chemotherapy or 29% of the total cohort of 111). There was no statistically significant difference in stage at diagnosis or grade at diagnosis between those retreated with chemotherapy or not or with carboplatin–paclitaxel versus another regimen. The patients retreated were a selected subgroup as only those with initial response or treated adjuvantly were offered carboplatin–paclitaxel. CR or PR were achieved in 8 (42%) patients with endometroid type cancer. In the papillary serous group 6 (50%) had CR or PR. Median PFS from first relapse was 8 months for endometroid and 9 months for papillary serous histology. OS was 15 months and 26 months respectively from first relapse.ConclusionCarboplatin–taxol regimen is an efficacious treatment. Due to the patient selection these outcomes reported are likely to be an overstatement of what could be achieved in practice. 相似文献
38.
Abou-Setta AM Mansour RT Al-Inany HG Aboulghar MM Aboulghar MA Serour GI 《Fertility and sterility》2007,88(2):333-341
39.
Symonds T Spino C Sisson M Soni P Martin M Gunter L Patrick DL 《The journal of sexual medicine》2007,4(5):1328-1335
IntroductionRecently, there has been much discussion in the literature about how to determine the meaningfulness of results generated from a patient-reported outcome measure. A number of reviews have shown that there are two main approaches: anchor- and distribution-based approaches for determining the minimum important difference (MID) for a new measure. There are issues with calculating an MID using each method: Will the two approaches give the same estimate? If the estimates differ, how do you decide on one estimate? Would asking patients directly be more beneficial?AimA case study was presented to address these issues based on a newly developed diary assessing number of satisfactory sexual events (SSEs) per week in women with hypoactive sexual desire disorder (HSDD).MethodsAnchor- and distribution-based estimates were generated from data gathered in two double-blind, placebo-controlled, parallel group trials for the treatment of HSDD (N = 788). A novel interview study was used to ask women directly about an MID for SSEs (N = 77).Main Outcome MeasuresDefining the MID for an SSE diary in women with HSDD.ResultsThe estimates varied, producing a range of mean MID estimates between 0.04 and 0.46 SSEs per week.ConclusionsWe recommend that rather than defining the MID, a range should be selected from the set of estimates formed by the limits of the 95% confidence intervals. Symonds T, Spino C, Sisson M, Soni P, Martin M, Gunter L, and Patrick DL. Methods to determine the minimum important difference for a sexual event diary used by postmenopausal women with hypoactive sexual desire disorder. 相似文献
40.
Michael H Parrish Janine M Dutcher Keely A Muscatell Tristen K Inagaki Mona Moieni Michael R Irwin Naomi I Eisenberger 《Social cognitive and affective neuroscience》2022,17(8):723
Self-enhancement, the tendency to view oneself positively, is a pervasive social motive widely investigated in the psychological sciences. Relatively little is known about the neurocognitive mechanisms underlying this motive, specifically in social-evaluative situations. To investigate whether positive emotion regulation circuitry, circuitry involved in modulating positive affect, relates to the self-enhancement motive in social contexts, we conducted an functional magnetic resonance imaging (fMRI) study in a healthy young adult sample. We hypothesized that self-enhancement indices (state and trait self-esteem) would relate to greater functional connectivity between right ventrolateral prefrontal cortex (RVLPFC), a region implicated in emotion regulation, and the ventral striatum (VS), a region associated with reward-related affect, during a social feedback task. Following social evaluation, participants experienced stable or decreased state self-esteem. Results showed that stable state self-esteem from pre- to post-scan and higher trait self-esteem related to greater RVLPFC–VS connectivity during positive evaluation. Stable-state self-esteem also related to greater RVLPFC–VS connectivity during negative evaluation. Moreover, RVLPFC activation during all types of feedback processing and left VS activation during negative feedback processing was greater for participants with stable-state self-esteem. These findings implicate neurocognitive mechanisms underlying emotion regulation in the self-enhancement motive and highlight a pathway through which self-enhancement may restore feelings of self-worth during threatening situations. 相似文献