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排序方式: 共有1053条查询结果,搜索用时 15 毫秒
81.
Mads Buhl Jakob Gjedsted Asger Granfeldt Pernille Ø. Larsen Michelle Chew Niels Møller Else Tønnesen 《Basic & clinical pharmacology & toxicology》2009,105(5):319-326
Abstract: Intensive insulin therapy, aiming for strict normoglycaemia, is associated with increased survival in critically ill patients. Insulin therapy concomitantly reduces plasma‐free fatty acids. Recent studies indicate that free fatty acids mediate inflammation. In addition to plasma glucose and free fatty acid‐lowering effects, insulin also has anti‐inflammatory properties. This study was designed to study the pro‐inflammatory effects of two free fatty acid concentrations during acute endotoxaemia and controlled comparable levels of plasma glucose and insulin. Twenty pigs were anaesthetized and mechanically ventilated. Pigs were randomized to two different, constant Intralipid® infusion rates, throughout observation. All pigs were administered continuous intravenous infusion of endotoxin and subjected to controlled levels of p‐glucose (4.5 mmol/l) and insulin by use of a hyperinsulinaemic euglycaemic clamp. Changes in circulating tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6, leucocytes, insulin, glucose, free fatty acids, triglycerides, albumin, blood gases, temperature, and, haemodynamic function were monitored. Immediately following killing, biopsies were taken from heart and kidney. Biopsies were analysed for protein content of TNF‐α, IL‐6, IL‐8 and IL‐10. Sustained elevated and significantly different plasma levels of free fatty acids were demonstrated between groups (mean free fatty acid concentrations, 1.62 mM versus 0.58 mM, p < 0.0002). Endotoxaemia induced a steep increase in plasma TNF‐α, IL‐6 and leucocytes, however, without differences between the low‐ and high‐free fatty acid groups. Cytokine content in heart and kidney tissue was not modified by free fatty acids. Compared with the response obtained at lower free fatty acid levels, high free fatty acid levels did not exacerbate the inflammatory response to acute endotoxaemia. Our results do not support the role of free fatty acids as a significant pro‐inflammatory mediator. 相似文献
82.
Rasmus Foldbjerg Ping Olesen Mads Hougaard Duy Anh Dang Hans Jürgen Hoffmann Herman Autrup 《Toxicology letters》2009,190(2):156-162
The objective of the present study was to investigate the toxicity of silver nanoparticles (Ag NPs) in vitro. Silver ions (Ag+) have been used in medical treatments for decades whereas Ag NPs have been used in a variety of consumer products within recent years. This study was undertaken to compare the effect of well characterized, PVP-coated Ag NPs (69 nm ± 3 nm) and Ag+ in a human monocytic cell line (THP-1). Characterization of the Ag NPs was conducted in both stock suspension and cell media with or without serum and antibiotics. By using the flowcytometric annexin V/propidium iodide (PI) assay, both Ag NPs and Ag+ were shown to induce apoptosis and necrosis in THP-1 cells depending on dose and exposure time. Furthermore, the presence of apoptosis could be confirmed by the TUNEL method. A number of studies have implicated the production of reactive oxygen species (ROS) in cytotoxicity mediated by NPs. We used the fluorogenic probe, 2′,7′-dichlorofluorescein to assess the levels of intracellular ROS during exposure to Ag NPs and Ag+. A drastic increase in ROS levels could be detected after 6–24 h suggesting that oxidative stress is an important mediator of cytotoxicity caused by Ag NPs and Ag+. 相似文献
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Birth weight and risk of cancer 总被引:1,自引:0,他引:1
BACKGROUND: It is well established that prenatal biologic processes are important for the development of some childhood cancers, whereas less is known regarding their influence on adult cancer risk. High birth weight has been associated with risk of breast cancer, whereas studies of other specific cancers and all cancers together have been less conclusive. METHODS: The authors established a cohort of more than 200,000 men and women who were born between 1936 and 1975. Birth weights were obtained from school health records and information concerning cancer from the Danish Cancer Registry. Follow-up was performed between April 1, 1968 and December 31, 2003. During 6,975,553 person-years of follow-up, a total of 12,540 primary invasive cancers were diagnosed. RESULTS: Analyses of site-specific cancers revealed that the majority of cancers had a positive linear association with birth weight. Departures from a positive linear association were found to be statistically significant for cancers of the pancreas and bladder, which demonstrated a V-shaped association, and testicular cancer, which demonstrated an inverse association with birth weight. Excluding these 3 exceptions, the trends for the individual cancer sites were not heterogeneous, and the overall trend was a relative risk of 1.07 (95% confidence interval, 1.03-1.11) per 1000-g increase in birth weight. This trend was the same in men and women and in all age groups. CONCLUSIONS: A 7% increase in cancer risk was observed per 1000-g increase in birth weight. Few cancers demonstrated a nonlinear association with birth weight, and testicular cancer was found to be negatively associated with birth weight. The authors hypothesized that the biologic explanation behind the association between birth weight and cancer at different sites should be sought in a common pathway. 相似文献
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Anja Sofie Petersen Mads Barloese Nunu Lund Adam Friis Pedersen Marie-Louise Kulas Søborg Mona Ameri Chalmer Ida Callesen Bendik Slagsvold Winsvold John-Anker Zwart DBDS Genomic Consortium Sisse Rye Ostrowski Ole Birger Pedersen Finn Sellebjerg Helle Bach Søndergaard Malene Bredahl Hansen Rigmor Højland Jensen Thomas Folkmann Hansen 《European journal of neurology》2023,30(5):1425-1434
Background and purpose
The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine.Methods
In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache.Results
Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found.Conclusion
The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study. 相似文献89.
Rasmus Søgaard Hansen Signe Hedengran Biørn Johan Baden Birk-Korch Søren Paludan Sheikh Mads Hvid Poulsen Pernille Just Vinholt 《BJU international》2023,131(5):530-539
Objectives
To investigate the prevalence of prostate cancer in men attending evaluation for haematuria, as this could help healthcare providers to determine whether men with haematuria should have prostate examinations performed.Methods
The study was performed according to a pre-specified protocol uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022299383). A systematic search of MEDLINE, Ovid and Google Scholar was performed in December 2021. Two independent researchers evaluated all titles, available abstracts, and full texts. We included studies on adult men (aged ≥18 years) describing haematuria and prostate cancer.Results
We screened 4252 titles and abstracts when available and assessed 350 studies in full text. In total, 65 studies were included and 42 was summarised in a meta-analysis. In total, 18 752 men with haematuria were included, and the pooled prevalence (95% confidence interval [CI]) of prostate cancer was 3.0% (2.0–4.1%). In men with macroscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 5.9% (2.9–9.9%; n = 265/5373). In men with microscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 1.4% (0.8–2.2%; n = 71/6642).Conclusion
Our findings indicate that the prevalence of prostate cancer is considerable in men attending evaluation for haematuria. Therefore, digital rectal examination and prostate-specific antigen measurement should become a standard procedure for all men with haematuria, especially for men with macroscopic haematuria. 相似文献90.
Signe Holst Søegaard Klaus Rostgaard Mads Kamper-Jørgensen Kjeld Schmiegelow Henrik Hjalgrim 《International journal of cancer. Journal international du cancer》2023,152(9):1817-1826
Childhood acute lymphoblastic leukaemia (ALL) is suggested to result from a dysregulated immune response to infections in children with a preleukaemic state. Childcare in early life supposedly may protect against childhood ALL by facilitating sufficient exposure to infections to stimulate and ensure normal maturation of the immune system. We assessed the association between childcare attendance before age 2 years and risk of childhood ALL in a register-based cohort study, including all children aged 2 to 14 years born in Denmark during 1991 to 2014 with available childcare information recorded in the Danish Childcare Database (n = 1 116 185). Cox regression was used to estimate hazard ratios (HRs) comparing children enrolled in childcare and children not enrolled before age 2 years. Further, we assessed the association according to age at enrolment, type of childcare facility and specific ALL subtypes. During 10 460 811 person-years of follow-up, 460 children developed ALL at ages 2 to 14 years. Of these, 57 (12.4%) never attended childcare before age 2 years compared with 10.6% in the total cohort. Compared with homecare, childcare attendance before age 2 years was associated with a statistically non-significantly, marginally decreased risk of childhood ALL with adjusted HR = 0.87 (95% confidence interval [CI]: 0.65-1.16). Risk estimates did neither vary statistically significantly by age at enrolment nor by type of childcare facility and also not between childhood ALL subtypes, including frequently prenatally initiated ALL subtypes. Results from this large, nationwide register-based study provided no evidence that childcare attendance in the first years of life protects against childhood ALL. 相似文献