Despite improvements in treatment, coronary artery disease is still responsible for one-third of all deaths globally, due predominantly to myocardial infarction (MI) and stroke. There is an important potential in developing new strategies for treatment of patients with these conditions. Inflammation, and in particular the actions of the complement system, has emerged as part of the pathogenesis in reperfusion injury in patients with MI. To further qualify this, we examined the association between the plasma levels of lectin pathway proteins and myocardial end-points, left ventricular ejection fraction (LVEF) and infarct size in a cohort of patients with ST-elevation myocardial infarction (STEMI). A blood sample was drawn the day after percutaneous coronary intervention from 73 patients with STEMI. The primary end-points, LVEF and infarct size, were measured with magnetic resonance imaging 6–9 days after the infarct. Complement pattern-recognition molecules of the lectin pathway (mannan-binding lectin, H-ficolin, L-ficolin and M-ficolin) were analysed along with soluble membrane attack complex (sMAC) and C-reactive protein (CRP) in plasma with immunofluorometric assays <50%. CRP correlated negatively with LVEF, regression coefficient = –0·17 (P = 0·01). None of the lectin pathway proteins correlated to LVEF or infarct size, nor did soluble membrane attack complex (sMAC). There were no differences in plasma levels of these complement proteins when comparing patients with ejection fraction <50% to patients with ejection fraction <50%. Pattern-recognition molecules of the lectin pathway and sMAC do not predict short-term cardiac outcomes after MI. 相似文献
A 15‐year‐old girl with a history of paroxysmal supraventricular tachycardia underwent an electrophysiology study (EPS) for diagnosis and ablation. Her baseline electrocardiogram and echocardiogram were normal. At EPS, she had dual atrioventricular nodal (AVN) conduction, but isoproterenol was needed to initiate the slow‐fast form of AVN reentry. Before ablation without any isoproterenol, she began to have a spontaneous block in the fast pathway with continuous conduction over the slow pathway. After ablation of the slow pathway, all complexes conducted over the fast pathway during a 25‐year follow‐up. Possible electrotonic interaction between the slow and fast pathways is proposed as the mechanism for this phenomenon. 相似文献
The hormone melatonin connects environmental cues, such as photoperiod and temperature, with a number of physiological and behavioural processes, including seasonal reproduction, through binding to their cognate receptors. This study reports the structural, functional and physiological characterization of five high‐affinity melatonin receptors (Mtnr1aaα, Mtnr1aaβ, Mtnr1ab, Mtnr1al, Mtnr1b) in Atlantic salmon. Phylogenetic analysis clustered salmon melatonin receptors into three monophyletic groups, Mtnr1A, Mtnr1Al and Mtnr1B, but no functional representative of the Mtnr1C group. Contrary to previous studies in vertebrates, pharmacological characterization of four receptors in COS‐7, CHO and SH‐SY5Y cell lines (Mtnr1Aaα, Mtnr1Aaβ, Mtnr1Ab, Mtnr1B) showed induction of intracellular cAMP levels following 2‐iodomelatonin or melatonin exposure. No consistent response was measured after N‐acetyl‐serotonin or serotonin exposure. Melatonin receptor genes were expressed at all levels of the hypothalamo‐pituitary‐gonad axis, with three genes (mtnr1aaβ, mtnr1ab and mtnr1b) detected in the pituitary. Pituitary receptors displayed daily fluctuations in mRNA levels during spring, prior to the onset of gonadal maturation, but not in autumn, strongly implying a direct involvement of melatonin in seasonal processes regulated by the pituitary. To the best of our knowledge, this is the first report of cAMP induction mediated via melatonin receptors in a teleost species. 相似文献
PurposeTo evaluate the incidence and clinical importance of brain gliomas – optic pathway gliomas (OPGs) and especially gliomas outside the optic pathway (GOOP) for children with neurofibromatosis type 1 (NF1), additionally, to assess the causes of obstructive hydrocephalus in NF1 children with an emphasis on cases caused by idiopathic aqueduct stenosis.Subjects and methodsWe analysed data from 285 NF1 children followed up on our department from 1990 to 2010 by the same examination battery.ResultsWe have found OPGs in 77/285 (27%) children and GOOPs in 29/285 (10,2%) of NF1 children, of who 19 had OPG and GOOP together, so the total number of brain glioma was 87/285 (30,5%). GOOPs were significantly more often treated than OPGs (p > 0.01). OPGs contain clinically important subgroup of 14/285 (4.9%) spreading to hypothalamus. Spontaneous regression was documented in 4/285 (1.4%) gliomas and the same number of NF1 children died due to gliomas.Obstructive hydrocephalus was found in 22/285 (7.7%) patients and 14/22 cases were due to glioma. Idiopathic aqueduct stenosis caused hydrocephalus in 6/22 cases and was found in 2.1% of NF1 children. Two had other cause.ConclusionsThe total brain glioma number (OPGs and only GOOPs together) better reflected the overall brain tumour risk for NF1 children. However, GOOPs occur less frequently than OPGs, they are more clinically relevant. The obstructive hydrocephalus was severe and featuring frequent complication, especially those with GOOP. Idiopathic aqueduct stenosis shows an unpredictable cause of hydrocephalus in comparison with glioma and is another reason for careful neurologic follow up. 相似文献
Introduction:Mitogen-activated protein kinase (MAPK) pathway is known to be involved in the tumorigenesis of cancer cells including non-small cell lung cancer (NSCLC) and kinases involved in this pathway are frequently mutated. The development of new targeted therapies in cancer has led to the evaluation of MEK-inhibitors.
Areas covered: This article reviews different studies using trametinib alone, in combination with other targeted therapies or associated with other non-targeted therapies in NSCLC, with a focus on KRAS mutant and BRAF mutant NSCLC.
Expert commentary: Trametinib demonstrated activity in association with a BRAF inhibitor when BRAF was mutated. The combination of trametinib and dabrafenib has been approved for this population of BRAF mutant NSCLC patients. For KRAS mutant NSCLC, the combination of trametinib with chemotherapy has showed promising results and should be further assessed. Several clinical trials are ongoing, assessing trametinib in combination with other targeted therapies. In addition, preclinical studies suggest a synergistic effect of trametinib in combination with immune checkpoint inhibitors and such combinations should be studied in clinical trials. 相似文献