共查询到20条相似文献,搜索用时 0 毫秒
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Hassing HC Surendran RP Mooij HL Stroes ES Nieuwdorp M Dallinga-Thie GM 《Biochimica et biophysica acta》2012,1821(5):826-832
The importance of triglycerides as risk factor for CVD is currently under debate. The international guidelines do not include TG into their risk calculator despite the recent observations that plasma TG is an independent risk factor for CVD. The understanding of the pathophysiology of triglycerides opens up avenues for development of new drug targets. Hypertriglyceridemia occurs through 1. Abnormalities in hepatic VLDL production, and intestinal chylomicron synthesis 2. Dysfunctional LPL-mediated lipolysis or 3. Impaired remnant clearance. The current review will discuss new aspects in lipolysis by discussing the role of GPIHBP1 and the involvement of apolipoproteins and in the process of hepatic remnant clearance with a focus upon the role of heparin sulfate proteoglycans. Finally we will shortly discuss future perspectives for novel therapies aiming at improving triglyceride homeostasis. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. 相似文献
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Pathophysiology of favism 总被引:2,自引:0,他引:2
Haemolytic crises occurring in G6PD-deficient individuals after ingestion of fava beans (favism) are much less frequent than in the past. However, favism is a unique natural model of oxidant damage in vivo, useful for the study of senescent or damaged red blood cells (RBC) clearance from circulation. The following aspects have been considered: 1. Pathophysiology of favism, including incidence, salient features, and sequence of events. 2. RBC alterations during the haemolytic crisis: biochemical, rheological and morphological alterations occurring in RBC isolated at different stages of the crisis. 3. Toxic substances of Vicia faba and their mechanism of action: treatment of G6PD-deficient RBC with divicine or isouramil (redox substances present in fava beans) provokes the same changes as observed during favism. 4. Intravascular vs. extravascular haemolysis: extravascular (i.e. phagocytic) removal of damages RBC seems predominant in favism. 5. The signal for RBC removal: in analogy with a recent model for recognition and removal of oxidant-stressed or senescent RBC, we propose removal of fava bean damaged RBC be mediated by apposition of antiband 3 antibodies and complement C3 fragments, recognized as non-self recognition signal by monocytes and macrophages. 相似文献
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Pathophysiology of toxoplasmosis 总被引:23,自引:0,他引:23
Frenkel JK 《Parasitology today (Personal ed.)》1988,4(10):273-278
Toxoplasma infection in most adult animals and humans is asymptomatic because of effective protective immunity; this involves antibody acting extracellularly, and T-cell factors acting intracellularly. Whenever immunity is not acquired in a timely fashion, tachyzoites continue to multiply, destroying an excessive number of cells, producing lesions in several organs, with pneumonia and encephalitis the prominent causes of illness and death. However, immunity is insufficient to destroy the slowly multiplying bradyzoites persisting in tissue cysts in many organs - a parasite adaptation to await ingestion of one host by another. Toxoplasma cysts produce lesions when they disintegrate, because of the delayed type of hypersensitivity accompanying infections. In the presence of immunity, the released bradyzoites are destroyed, but when protective immunity fails, the bradyzoites can develop again into actively multiplying tachyzoites parasitizing and destroying cells in expanding foci, usually in the brain. In this review J.K. Frenkel discusses the complex interplay of immunological and parasite factors participating in the various lesions associated with acute and chronic Toxoplasma infections. 相似文献
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Stanley SL 《Trends in parasitology》2001,17(6):280-285
Few organisms are more aptly named than Entamoeba histolytica, an intestinal protozoan parasite that can lyse and destroy human tissue. Within the past four years, new models of E. histolytica infection have begun to illuminate how amoebic trophozoites cause intestinal disease and liver abscess, and have expanded our understanding of the remarkable killing ability of this parasite. Here, I summarize recent work on the interactions between E. histolytica and human intestine, and between E. histolytica and hepatocytes, and discuss what these studies tell us about the role of inflammation and programmed cell death in the pathogenesis of amoebiasis. 相似文献
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Portal-Núñez S Lozano D de la Fuente M Esbrit P 《Revista espa?ola de geriatría y gerontología》2012,47(3):125-131
Deterioration of organ and systems function are the principal signs of aging. Aging is also believed to be a major factor in the loss of bone mass and quality, which in turn leads to an increase in the risk of fractures. Several factors seem to contribute to this scenario, with metabolic changes related to aging in the bone tissue itself being among them. Most of the current knowledge on the mechanisms associated with osteopenia/osteoporosis during aging has been generated from research in animal models (mainly rats and mice) and cell cultures derived from subjects of different ages. In this work, we have reviewed and summarised these studies, which have begun to establish the physiological and molecular basis of the bone alterations related to aging. 相似文献
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Pathophysiology of chaperone-mediated autophagy 总被引:5,自引:0,他引:5
Massey A Kiffin R Cuervo AM 《The international journal of biochemistry & cell biology》2004,36(12):2420-2434
In contrast to the classically described “in bulk” lysosomal degradation, the first evidence for selective degradation of cytosolic proteins in lysosomes was presented more than 20 years ago. Throughout this time, we have gained a better understanding about this process, now known as chaperone-mediated autophagy (CMA). The identification of new substrates for CMA and novel components, in both the cytosol and the lysosomes, along with better insights on how CMA is regulated, have all helped to shape the possible physiological roles of CMA. We review here different intracellular functions of CMA that arise from its unique characteristics when compared to other forms of autophagy. In view of these functions, we discuss the relevance of the changes in CMA activity in aging and in different pathological conditions. 相似文献
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E F Mammen 《Folia haematologica (Leipzig, Germany : 1928)》1988,115(3):243-252
The coagulation system can be considered as a balance in which clotting and fibrinolysis have to be in a state of equilibrium. Increased fibrin formation or decreased fibrinolysis can predispose to thromboembolic diseases. Derailments in the clotting system leading to thrombosis center around the regulatory mechanisms, antithrombin III, protein C, protein S and possibly heparin cofactor II. Many cases of congenital or acquired deficiencies or abnormalities or antithrombin III, protein C and S have been described, all predisposing to thrombotic events. Alterations of the fibrinolytic system can also be associated with thromboembolisms. In particular, abnormalities of plasminogen, tissue plasminogen activator release and elevated tissue plasminogen activator inhibitor levels seem to be associated with thromboses. Conceivably also factor XIIa (Hageman factor) and prekallikrein deficiencies, when associated with thrombosis, exert their mechanism through the fibrinolytic system. Finally, about 50% of patients with lupus anticoagulant seem to suffer from thromboembolic disorders. The pathophysiology of this particular association is not known with certainty. Undoubtedly, there will be more disturbances discovered in the hemostasis system that are associated with increased intravascular fibrin formation. The understanding of these derailments is at this time only in its earliest stages of development. 相似文献
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Parathyroid gland is the overall regulatory organ within the systemic calcium homeostasis. Through cell surface bound calcium-sensing receptors external calcium inversely regulates release of parathyroid hormone (PTH). This mechanism, which is voltage independent and most sensitive around physiologic calcium concentrations, is regulated through a 120 kDa calcium sensing receptor, CaR. Inherited inactivation of this receptor is the cause for familial hypocalciuric hypercalcemia (FHH). Parallel research identified the 550 kDa glycoprotein megalin, which also is expressed on the parathyroid cell surface, as another potential calcium sensing protein. Although this protein expresses numerous calcium binding sites on its external domain, its main function may be calcium sensitive binding and uptake of steroid hormones, such as 25-OH-vitamin D3 (bound to vitamin D binding protein) and retinol. In hyperparathyroidism (HPT), excessive PTH is secreted and the calcium sensitivity of the cells reduced, i.e. the set-point, defined as the external calcium concentration at which half-maximal inhibition of PTH release occurs, shifted to the right. Pathological cells have reduced expression of both CaR and megalin, and reduced amount of intracellular lipids, possibly including stored steroid hormones. A number of possible genetic disturbances have been identified, indicating multifactorial reasons for the disease. In postmenopausal women, however, the individual group with highest incidence of disease, a causal relation to reduced effect of vitamin D is possible. An incipient renal insufficiency with age, lack of sunshine in the Northern Hemisphere, and an association to the baT haplotype of the vitamin D receptor supports this theory. This review summarizes data on regulation of PTH release, dysregulation in HPT, as well as proliferation of parathyroid cells. 相似文献
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Pathophysiology of axonal transport 总被引:1,自引:0,他引:1
B H Smith 《Neurosciences Research Program bulletin》1981,20(1):98-106
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J Knapowski K Wieczorowska-Tobis J Witowski 《Journal of physiology and pharmacology》2002,53(2):135-146
Ageing is characterized by a gradual decline in organ functional reserves which reduces the ability to maintain homeostasis under conditions of stress. Introduction of cell culture and molecular biology techniques has provided new experimental tools for the analysis of ageing at the molecular level. During ageing progressive degeneration of cells and loss of regenerative capacity are enhanced and with time the alterations caused by them ultimately lead to death. In this paper the current knowledge of the mechanisms of ageing is summarized. 相似文献
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Pathophysiology of temperature regulation 总被引:1,自引:0,他引:1
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Francesco Iemolo Giovanni Duro Claudia Rizzo Laura Castiglia Vladimir Hachinski Calogero Caruso 《Immunity & ageing : I & A》2009,6(1):13-9
The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria
remain unclear. 相似文献