Pathophysiology of hypertriglyceridemia

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.     

Pathophysiology of favism

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.     

Pathophysiology of toxoplasmosis

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.     

细胞转分化的病理生理意义

转分化是一种类型的细胞或组织在某些理化因素作用下转变为另一种正常细胞或组织的现象。这种细胞表型转化对机体具有修复损伤或加重病变的双重生物学意义。机体通过细胞转分化来代替或修复受损组织和功能,但若损害因素的长期存在使得分化后的细胞过度分泌炎症因子和细胞外基质,则可引起组织的过度增生、纤维化、钙化及肿瘤形成。本文就转分化的病理生理意义做一简述。     

Pathophysiology of amoebiasis

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.     

Pathophysiology of the human intervertebral disc

Intervertebral disc degeneration is a common invalidating disorder that can affect the musculoskeletal apparatus in both younger and older ages. The chief component of the intervertebral disc is the highly organized extracellular matrix; maintenance of its organization is essential for correct spinal mechanics. The matrix components, mainly proteoglycans and collagens, undergo a slow and continuous cell-mediated turnover process that enables disc cells to adapt their environment to external stimuli. Cellular senescence and a history of chronic abnormal loading can upset this balance, leading to progressive tissue failure that results in disc degeneration. Although biological treatment approaches to disc repair are still far to come, advances in our understanding of disc biochemistry and in defining the role of genetic inheritance have provided a starting point for developing new concepts in the diagnosis, therapy and prevention of disc degeneration.     

Pathophysiology of aging bone

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.     

Pathophysiology of chaperone-mediated autophagy

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.     

Hydrogen Sulfide and Pathophysiology of the CNS

Neurophysiology - The literature data and results of our research team concerning the physiological and pathological effects of hydrogen sulfide, a gas transmitter that has recently attracted...     

Pathophysiology of thrombophilic states

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.