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排序方式: 共有141条查询结果,搜索用时 31 毫秒
1.
Despite evidence showing an improvement in nutritional outcomes following diagnosis by newborn screening (NBS) for cystic fibrosis (CF), the impact on pulmonary outcomes has been less clear. In this review the approaches to measurement of early lung function and knowledge gained from NBS CF cohorts will be described. Studies which have compared outcomes in those diagnosed by NBS to those diagnosed following symptomatic presentation will be presented. Compiling the evidence base used to evaluate the impact of NBS on pulmonary outcomes has been complicated by improvements in clinical management, infection control practices, as well as public health interventions (such as tobacco smoking bans in public places) that have evolved substantially over recent decades. Forced expiratory volumes have been used as the main outcome but it is important not to draw conclusions for ‘early lung function’ from tests such as spirometry alone, which lack sensitivity in early lung disease. There is, at present, insufficient evidence to draw firm conclusions about the effect of NBS on early lung function. In an era of highly effective treatments targeting the underlying molecular defect responsible for CF, future opportunities for early initiation of treatment may mean that the impact of NBS on early lung function may yet to be realised. 相似文献
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Sara Matić Milena Jadrijević-Mladar Takač Monika Barbarić Bono Lučić Koraljka Gall Trošelj Višnja Stepanić 《Journal of pharmaceutical sciences》2018,107(11):2957-2964
The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B. 相似文献
4.
Rashad Al-Salahi Moustapha E. Moustapha Hatem A. Abuelizz Abdulrahman I. Alharthi Khalid A. Alburikan Ismail T. Ibrahim Mohamed Marzouk Mohamed A. Motaleb 《Saudi Pharmaceutical Journal》2018,26(8):1120-1126
3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, 1H and 13C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2?±?1.22% and the in vitro studies showed that the target compound was stable for up to 24?h. The thyroid was among the other organs in which the uptake of 125I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells. 相似文献
5.
Maki Ohara Yumi Funyu Shunsuke Ebara Yuki Sakamoto Ryota Seki Kenta Iijima Akiko Ohishi Junya Kobayashi Kenshi Komatsu Akira Tachibana Hiroshi Tauchi 《Journal of radiation research》2014,55(4):690-698
Ionizing radiation induces DNA double-strand breaks (DSBs). Mammalian cells repair DSBs through multiple pathways, and the repair pathway that is utilized may affect cellular radiation sensitivity. In this study, we examined effects on cellular radiosensitivity resulting from functional alterations in homologous recombination (HR). HR was inhibited by overexpression of the forkhead-associated (FHA) domain-mutated NBS1 (G27D/R28D: FHA-2D) protein in HeLa cells or in hamster cells carrying a human X-chromosome. Cells expressing FHA-2D presented partially (but significantly) HR-deficient phenotypes, which were assayed by the reduction of gene conversion frequencies measured with a reporter assay, a decrease in radiation-induced Mre11 foci formation, and hypersensitivity to camptothecin treatments. Interestingly, ectopic expression of FHA-2D did not increase the frequency of radiation-induced somatic mutations at the HPRT locus, suggesting that a partial reduction of HR efficiency has only a slight effect on genomic stability. The expression of FHA-2D rendered the exponentially growing cell population slightly (but significantly) more sensitive to ionizing radiation. This radiosensitization effect due to the expression of FHA-2D was enhanced when the cells were irradiated with split doses delivered at 24-h intervals. Furthermore, enhancement of radiation sensitivity by split dose irradiation was not seen in contact-inhibited G0/G1 populations, even though the cells expressed FHA-2D. These results suggest that the FHA domain of NBS1 might be an effective molecular target that can be used to induce radiosensitization using low molecular weight chemicals, and that partial inhibition of HR might improve the effectiveness of cancer radiotherapy. 相似文献
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7.
Don B. Sanders Zhumin Zhang Philip M. Farrell HuiChuan J. Lai 《Journal of cystic fibrosis》2018,17(4):528-535
Background
In children with cystic fibrosis (CF), recovery from growth faltering within 2?years of diagnosis (Responders) is associated with better growth and less lung disease at age 6?years. This study examined whether these benefits are sustained through 12?years of age.Methods
Longitudinal growth from 76 children with CF enrolled in the Wisconsin CF Neonatal Screening Project was examined and categorized into 5 groups: R12, R6, and R2, representing Responders who maintained growth improvement to age 12, 6, and 2?years, respectively, and I6 and N6, representing Non-responders whose growth did and did not improve during ages 2–6?years, respectively. Lung disease was evaluated by % predicted forced expiratory volume in one second (FEV1) and chest radiograph (CXR) scores.Results
Sixty-two percent were Responders. Within this group, 47% were R12, 28% were R6, and 25% were R2. Among Non-responders, 76% were N6. CF children with meconium ileus (MI) had worse lung function and CXR scores compared to other CF children. Among 53 children with pancreatic insufficiency without MI, R12 had significantly better FEV1 (97–99% predicted) and CXR scores during ages 6–12?years than N6 (89–93% predicted). Both R6 and R2 experienced a decline in FEV1 by ages 10–12?years.Conclusions
Early growth recovery in CF is critical, as malnutrition during infancy tends to persist and catch-up growth after age 2?years is difficult. The longer adequate growth was maintained after early growth recovery, the better the pulmonary outcomes at age 12?years. 相似文献8.
Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity 总被引:3,自引:0,他引:3
Traditional radiobiology has aimed at elucidating the mechanism of radiosensitivity of cancer cells and normal cells. Because
the mechanism of DNA double-strand break (DSB) repair, which is inherently important to radiosensitivity, was unknown, it
has been difficult to obtain results applicable to clinical radiotherapy from traditional radiobiology research. Today, however,
the molecular mechanism of DNA DSB repair has been elucidated because of the rapid advances in molecular biology. In DNA DSB
repair, at least two major repair mechanisms, homologous recombination and nonhomologous end joining (NHEJ) have been reported.
In the NHEJ pathway, DSBs are directly, or after processing of the DNA ends, rejoined at an appropriate chromosomal end. DNA-dependent
protein kinase (DNA-PK) plays an important role in DNA DSB repair by NHEJ. We have investigated how the ability of repair
of DNA DSB influences cancer susceptibility and the radiosensitivity of tumors and normal tissues by focusing on the activity
of DNA-PK. In the near future, research on DNA DSB repair mechanism will be able to be applied to research on carcinogenesis,
prediction of radiosensitivity of tumors and normal cells, and sensitization of tumor cells. 相似文献
9.
Aim of the study
The present study was designed to investigate the effects of the EtOH and H2O extracts of Selaginella tamariscina (Beauv.) Spring on hyperglycemia in diabetic rats and HepG2 cells, and to confirm the active fractions of EtOH extract in HepG2 cells.Materials and methods
HepG2 cells and type II diabetic rats induced by low-dose streptozotocin (STZ) and high-fat diet (HFD) were used to evaluate the hypoglycemic effect of EtOH and H2O extracts of Selaginella tamariscina. HepG2 cells were used to evaluate the promotive effect of different fractions of EtOH extract obtained from a polyamide column on glucose utilization.Results
The results in HepG2 cells indicated that the EtOH extract had a better hypoglycemic effect than the H2O extract. The results in diabetic rats indicated that both EtOH extract and H2O extract were able to ameliorate the fasting blood glucose (FBG) level and improve oral glucose tolerance (OGTT). Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), free fatty acids (FFA), tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels in serum were lowered. High density lipoprotein (HDL-c), insulin and superoxide dismutase (SOD) levels in serum were elevated as well as the hepatic glycogen content in diabetic rats. Compared with H2O extract, the effects of EtOH extract were more marked. The 80% ethanol fraction exhibited a stronger hypoglycemic effect than the aqueous and 50% ethanol fractions, but the 95% ethanol fraction did not show any appreciable effects in HepG2 cells.Conclusions
The results suggested that the EtOH extract had a better hypoglycemic effect than the H2O extract; the 80% ethanol fraction from polyamide column had a strong hypoglycemic activity in HepG2 cells. 相似文献10.
Sokolenko AP Rozanov ME Mitiushkina NV Sherina NY Iyevleva AG Chekmariova EV Buslov KG Shilov ES Togo AV Bit-Sava EM Voskresenskiy DA Chagunava OL Devilee P Cornelisse C Semiglazov VF Imyanitov EN 《Familial cancer》2007,6(3):281-286
Previous studies indicate that founder mutations may play a noticeable role in breast cancer (BC) predisposition in Russia.
Here we performed a systematic analysis of eight recurrent mutations in 302 BC cases (St.-Petersburg, Russia), which were
selected due to the presence of clinical indicators of hereditary disease (bilaterality and/or early onset (≤40 years) and/or
family history). BC-associated alleles were revealed in 46 (15.2%) women. BRCA1 5382insC mutation was detected in 29 (9.6%)
patients, CHEK2 1100delC in 9 (3.0%), BRCA1 4153delA in 3 (1.0%), CHEK2 IVS2+1G>A in 2 (0.7%), and BRCA1 185delAG, BRCA2 6174delT
and NBS1 657del5 in 1 (0.3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest
that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests. 相似文献