The endothelium is a single-layered structure that responds to physical and chemical signals with various factors it synthesizes. In the early days of its discovery, as the inner wall of the vessels, the endothelium was thought to be a simple barrier that lays on the surface. Over time it is discovered that endothelium maintains body homeostasis with the molecules it synthesizes, despite its simple single-layer structure. It has been accepted as an important organ that contributes to the maintenance of vascular tone, cell adhesion, inflammation, vascular permeability and coagulation. Any imbalance in these physiological and pathological events causes endothelial dysfunction. This can cause many diseases such as atherosclerosis, hypertension, diabetes, or it can occur because of these. Endothelial related disorders may also complicate hematopoietic stem cell transplantation (HSCT), which is used to treat various hematologic and neoplastic diseases. These life-threatening complications include graft-versus-host disease, hepatic veno-occlussive disease, transplant-associated thrombotic microangiopathy and diffuse alveolar hemorrhage. They share a similar pathophysiology involving endothelial cells with different clinical presentations. Therefore, current researche on the issue is putting the endothelium under the spotlight for novel markers and treatment options that should be used to monitor or treat at least some of these complications following HSCT. 相似文献
Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface. 相似文献
Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning. 相似文献
ObjectivesPrior evidence suggests that sleep duration and sleep difficulties may be associated with cognitive function in old age, but little is known about the sleep–cognition association in late mid-life. Our aim was to examine the associations of accelerometer-based sleep duration as well as subjective sleep difficulties with different domains of cognitive function among aging workers.MethodsThe study population consisted of 289 participants (mean age 62.4 years, SD 1.02; 83% women) from the Finnish Retirement and Aging Study (FIREA). Sleep difficulties were measured using Jenkins Sleep Problem Scale (difficulties falling asleep, difficulties maintaining sleep, waking up too early in the morning, and nonrestorative sleep). Sleep duration was measured with wrist-worn accelerometer and self-report, and participants were divided into short (<7 h/night), mid-range (7–9 h/night) and long (≥9 h/night) sleepers. Participants underwent extensive cognitive testing covering three domains: (1) memory, (2) executive function, and (3) attention and information processing.ResultsGreater difficulties in waking up too early in the morning were associated with poorer executive function measured with Spatial Working Memory (SWM) test (p = 0.005). Additionally, nonrestorative sleep was associated with poorer executive function measured with Trail Making Test, B–A, (p = 0.036) and borderline significantly with lower SWM (p = 0.056). Compared to mid-range sleepers, long sleepers tended to have poorer cognitive function (all memory function tests and SWM), but the associations were not statistically significant due to small number of long sleepers.ConclusionsSubjective sleep difficulties may be linked to poorer executive function in a relatively healthy population of older workers in their 60 s. Thus, promoting good sleep quality may translate into better cognitive health in late mid-life. 相似文献
Introduction: In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement.
Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) – PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED).
Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function. 相似文献