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81.
Evaluation of telomerase-targeted therapies in canine cancer cell lines   总被引:1,自引:0,他引:1  
Despite advances in conventional therapeutics, cancer remains an invariably fatal disease, the major challenge being to develop tumour‐specific cancer treatment strategies. Current treatments such as chemotherapy and radiotherapy rely on a crude distinction between cancer cells and normal cells. However, with an increased understanding of the molecular events in the development of cancer, it is possible that far more innovative and targeted approaches can be developed. From studies on humans and dogs, the enzyme telomerase has emerged as a central unifying mechanism underlying the immortal phenotype of cancer and has thus become a candidate for differentiating between normal and cancer cells. The level and frequency of telomerase activity and component gene expression in cancers reinforces this as a potential target for cancer therapies. This article describes two approaches to target cancer by capitalizing on the expression of this enzyme. In the first approach, we target the enzyme itself, the goal being to cause cancer cell death. In the second approach, we utilize the respective gene promoters for telomerase component enzymes to drive expression of a reporter gene in cancer cell lines. The results demonstrated that targeted gene expression using promoter elements can be achieved specifically in telomerase‐positive cell lines. However, targeting the enzyme itself proved less successful and warrants investigations into alternative approaches.  相似文献   
82.
RATIONALE FOR THE STUDY: Recent studies have demonstrated that collaborative or cooperative learning (CL) provides students and teachers with a variety of advantages over traditional instructional methods. To explore the possibility of introducing CL into the veterinary undergraduate curriculum on a larger scale-to facilitate the development of professional competencies-a cooperative learning assignment (CLA) was introduced into the fourth year Bachelor of Veterinary Medicine and Surgery (BVMS) degree course at the University of Glasgow. An evaluation was carried out as a basis for optimizing subsequent CL activities in the undergraduate course. METHODOLOGY: Evaluation of student attitudes to the CLA was conducted using pre- and post-task questionnaires and a focusgroup discussion involving student representatives from several of the small groups. Quantitative questionnaire data were imported into SPSS and a statistical test was used to identify any significant shifts in student attitudes. RESULTS AND CONCLUSIONS: Analysis of the quantitative questionnaire results indicates that students-who regarded themselves generally as team players rather than competing individuals-had few concerns before or after the CLA. There were some significant shifts (negative and positive) in response to some of the questions, but generally the results were encouraging. However, a number of issues emerged from the focus-group discussion with regards to the administration of CL and matching students' expectations to their experiences. In particular, students need to be adequately informed at the outset about the CL process and about how it will be assessed, have access to the required facilities, and be comfortable with learning different skills sets from those their peers are learning. Staff facilitators require adequate guidance on what they are expected to contribute to the CL process.  相似文献   
83.
A bioavailability and pharmacokinetics study of doxycycline was carried out on 30 healthy ostriches after a single intravenous (IV), intramuscular (IM) and oral dose of 15 mg/kg body weight. The plasma doxycycline concentration was determined by HPLC/UV at 0 (pretreatment), 0.08, 0.25, 0.5 1, 2, 4, 6, 8, 12, 24 and 48 h after administration. The plasma concentration-time curves were examined using non-compartmental methods based on the statistical moment theory for only the higher dose. After IV administration, the elimination half-life (t1/2β), mean residence time (MRT), volume of distribution at the steady-state (Vss), volume of distribution (Vdarea) and total body clearance (ClB) were 7.67 ± 0.62 h, 6.68 ± 0.86 h, 0.86 ± 0.16 l/kg, 1.67 ± 0.52 l/kg and 2.51 ± 0.63 ml/min/kg, respectively. After IM and oral dosing, the mean peak plasma concentrations (Cmax) were 1.34 ± 0.33 and 0.30 ± 0.04 µg/ml, respectively, which were achieved at a post-administration time (tmax) of 0.75 ± 0.18, 3.03 ± 0.48 h, respectively. The t1/2β, Vdarea and ClB after IM administration were 25.02 ± 3.98 h, 23.99 ± 3.4 l/kg and 12.14 ± 1.71 ml/min/kg, respectively and 19.25 ± 2.53 h, 61.49 ± 7 l/kg and 40.19 ± 3.79 ml/min/kg after oral administration, respectively. The absolute bioavailability (F) of doxycycline was 5.03 and 17.52% after oral and IM administration, respectively. These results show that the dose data from other animals particularly mammals cannot be extrapolated to ostriches. Therefore, based on these results along with those reported in the literature, further studies on the pharmacokinetic/pharmacodynamic, in vitro minimum inhibitory concentration values and clinical applications of doxycycline in ostriches are required.  相似文献   
84.
Oleuropein is the most abundant biologically active phenolic compound in olives. It has been extensively studied for human health benefits but its role in plant development processes has received limited attention. Changes in the levels of oleuropein during early stages of flower formation and during fruit development and maturation were determined using high performance liquid chromatography. Oleuropein and other phenolic compounds were identified by comparing retention time and UV spectra with standard compounds using photodiode array detectors. Quantitative measurements were based on peak areas relative to standards. Oleuropein levels sharply decreased during the transition from vegetative to flower buds, consistent with earlier reports that higher levels of exogenously applied oleuropein inhibited flowering in Kalanchoe blossfeldiana. Oleuropein levels rapidly increased with the expansion of fertilized pistils and then sharply declined with fruit maturity. There was only a modest decline in oleuropein levels between immature and fully expanded leaves. Hesperidin, which occurs in relatively small amounts, also declined considerably during early floral buds formation. Maximum levels of verbascoside were found in fully developed green fruits while maximum levels of luteolin-7-O-glucoside and luteolin-4-O-glucoside were found in fully expanded leaves.  相似文献   
85.
Detection of infected poultry flocks is essential for controlling eggborne transmission of Salmonella enteritidis to humans. The present study evaluated the detection of antibodies in the sera of experimentally infected chickens by a fluorescence polarization assay with a tracer prepared from the O-polysaccharide of S. enteritidis and an enzyme-linked immunosorbent assay (ELISA) with an S. enteritidis flagellin antigen. In two trials, groups of specific-pathogen-free laying hens were infected orally with either 10(6) or 10(8) colony-forming units (CFU) of S. enteritidis (phage type 13a) or with 10(8) CFU of Salmonella typhimurium. Serum samples were collected before inoculation and at five subsequent weekly intervals. Both assays successfully detected the majority of hens infected with S. enteritidis at either dose level, but they also identified a substantial number of hens infected with S. typhimurium as seropositive. The fluorescence polarization test detected S. enteritidis infection significantly more often and cross-reacted with sera from hens infected with S. typhimurium significantly less often than the ELISA. The fluorescence polarization assay also offered advantages in terms of speed and methodologic simplicity.  相似文献   
86.
Tropical Animal Health and Production - Broiler meat is the largest and cheapest protein source in Malaysia. Using the policy analysis matrix (PAM), this study examines the comparative advantage of...  相似文献   
87.
This experiment was conducted to identify the suitable replacer of broiler feed antibiotics with prebiotics (mannan oligosaccharides‐MOS or fructooligosaccharide‐FOS). Two hundred and forty (240)‐day‐old chicks were randomly divided into 30 groups (6 treatments x 5 replicates/treatment x 8 chicks/replicate). Six experimental diets T1, T2, T3, T4, T5 and T6 were formulated to contain an additional 0, antibiotic, that is, bacitracin methylene di‐salicylate (BMD) @20 mg/kg, MOS (0.1% and 0.2%) and FOS (0.1% and 0.2%) respectively. Body weight gain was significantly (p < 0.05) increased in MOS‐0.2% supplemented group at 0–21 d and 0–42 d of broiler chicken. Humoral and in vivo cell‐mediated immune response were significantly improved (p < 0.05) in BMD, MOS @0.1% or 0.2% treated group. Significant (p < 0.05) increase was recorded in total protein (except 21 d), albumin and aspartate amino transferase (AST) and decrease (p < 0.05) in alanine amino transferase (except 42 d), cholesterol and uric acid concentration. The weight of breast, thigh, back, drumstick bursa of Fabricius and thymus were higher (p < 0.05) in the birds given the MOS @0.2% (T4). It is concluded that MOS @0.2% may be suitable replacer of antibiotic growth promoter, and it has a beneficial effect on production performance, immune responses, blood biochemical parameters and cut up parts in broiler chickens.  相似文献   
88.
This study was conducted to evaluate the effects of dietary soapnut (Sapindus mukorossi) shell powder (SSP), a cheap source of saponins, on growth performance, immunity, serum biochemistry and gut health of broiler chickens. The experimental design was 4×2, employing four saponin levels (0, 100, 150 and 200 mg/kg diet), each provided for two time durations (0–42 day and 21–42 day) resulting into eight dietary treatments. Results revealed no significant effect of dietary saponins on body weight gain, feed intake and feed conversion ratio of birds. The abdominal fat percentage, heterophil to lymphocyte ratio, serum cholesterol and triglyceride levels, faecal total plate count, coliform count and E. coli count decreased (p < .05) progressively with increasing saponin levels and lower values were observed at 150 mg and 200 mg saponin levels. Significant improvement of cell‐mediated and humoral immune response was observed in birds fed 150 mg and 200 mg saponin compared to control. The serum glucose concentration was significantly (p < .05) higher in control group compared to other groups. No significant effects of dietary saponin were observed on carcass characteristics, faecal Lactobacillus count, intestinal histomorphometry and cost economics of broiler chicken production. Thus, dietary saponins at 150 mg/kg diet as SSP for three weeks (21–42 days) was optimum for better immunity and welfare of birds without adverse effects on the growth performance.  相似文献   
89.
The immunohistochemical expression of topoisomerase IIbeta binding protein 1 (TopBP1) was examined in 123 feline mammary lesions (18 non-neoplastic lesions including six fibroadenomatous hyperplasia and 12 duct ectasia, 17 adenomas and 88 carcinomas) in relation to histological grade, oestrogen receptor alpha (ERalpha) status, proliferation index (Ki67) and p53 expression. There was positive staining for TopBP1 in 122 of 123 feline mammary lesions, although nine samples had fewer than 20% positive cells. The percentage of cells positive for TopBP1 increased with histological grade. Most staining was nuclear but both nuclear and cytoplasmic staining was observed as the degree of malignancy increased. TopBP1 is expressed in feline mammary tumours and its expression is correlated with histological grade. Many neoplasms which over-express p53 or are ERalpha negative show TopBP1 immunoreactivity.  相似文献   
90.
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