Sequestration disorders

The HMG-CoA reductase inhibitors have an additive effect when used with the bile acid sequestrants, which may provide an added benefit in treating hypercholesterolemia that does not respond to a single-drug regimen. There is an increased risk of myopathy (disorders of the striated muscle) when the HMG-CoA reductase inhibitors are administered with erythromycin, niacin, or cyclosporin a When the HMG-CoA reductase inhibitors are administered with oral anticoagulants, there is an increased anticoagulant effect. 

Figure 3. The many ways to lose a HAT. Decreased amounts of functional CBP protein and subsequent CBP s loss of function has been observed in different contexts of neurological disorders and neuronal apoptosis. RTS (Rubinstein-Taybi Syndrome) results from a mutation on one cbp gene allele. In several cases of polyQ diseases, CBP can be sequestred by the mutated polyQ proteins, forming aggregates in the cytoplasm or the nucleus. CBP proteasomal degradation was also shown to be favored by polyQ proteins. CBP is a caspase-6 substrate in cerebellar granule neurons (CGN) deprived of potassium modeling caspase-dependent apoptosis. Finally, cbp gene repression has been observed in oxidative stress-induced death of a motomeuronal cell line. The mechanisms by which CBP levels are reduced in motomeurons of ALS mice is still unknown...

Thrombocytopenia may be caused by various metabolic disturbances (i.) synthesis disorders (e.g. medicaments, alcohol, folic acid deficiency), (2.) replacement disorders (e.g. immunologically derived degradation, consumption coagulopathy, loss of blood), and (3.) distribution disorders (e.g. increased sequestration in the enlarged spleen, involving up to 90% of the thrombocytes). 

Disorders of fibrinogen also occur in the liver. For example, dysfibrinogenemia may be seen in both acute and chronic liver disease and leads to prolongation of the partial thromboplastin time, Disseminated intravascular coagulation occurs with acute hepatic necrosis, presumably as a result of the release of tissue thromboplastin and defective clearance of inhibitors such as antithrombin and protein C. Thrombocytopenia may contribute to ineffective intravascular coagulation. Although commonly attributed to splenic sequestration (hypersplenism), there is evidence of antibody-mediated platelet destruction, as occurs in... 

Other dietary interventions or diet supplements may be useful in certain patients with lipid disorders. Increased intake of soluble fiber in the form of oat bran, pectins, certain gums, and psyllium products can result in useful adj unctive reductions in total and LDL cholesterol, but these dietary alterations or supplements should not be substimted for more active forms of treatment. Total daily fiber intake should be about 20 to 30 g/day, with about 25%, or 6 g/day, being soluble fiber. Studies with psyllium seed in doses of 10 to 15 g/day show reductions in total and LDL cholesterol ranging from about 5% to 20% They have little or no effect on HDL cholesterol or triglyceride concentrations. These products also may be useful in managing constipation associated with the bile acid sequestrants. Psyllium binds cholesterol in the gut but also reduces hepatic production and clearance. Fish... 

Both qualitative and quantitative platelet disorders have important pathophysiologic consequences. Thrombocytopenia, defined as a platelet count less than 150,000 cells/mm, may result from a defect in production, increased sequestration, or accelerated destruction." ... 

The sol—gel process can be used to obtain lamellar silica (LS) samples by using neutral amines as template molecules. Its is found that such LS samples are able to act as sequestrating agents toward transition metal cations and that the coordination of such metal cations of the three dimensional network structure of the sffica exerts remarkable effects on its nanostructure and thermal stabffity [4]. Furthermore, such metal sequestrating abffity and the consequent nanostructure modifications are observed even if the metal—sffica reaction is performed in the solid state and room temperature [5]. By performing a solution calorimetric study, it is possible to verify that the total amount of metal cations that the lamellar matrix is able to sequester as well as its affinity by the metal cations, for example, Ni > Cu > Co [6] is a consequence of the influence of main two factors the metal—nitrogen coordination enthalpies and the structural disorder provoked into the lamellar network by the metal—nitrogen coordination. 

Abnormally high iron levels in particular biological compartments can have a profound effect on a number of disease processes. Thus, iron-mediated diseases can be separated into two fundamental categories, systemic and focal iron overload disorders. The systemic disorders are typified by hemochromatosis and transfusional iron overload associated with either hemolytic anemias, such as thalassemia and sickle cell anemia, or bone marrow deficiency, for example, myelodysplasia. Disorders with focal iron sequestration include ischemia-reperfusion injury (5, 6), Parkinson s disease, Alzheimer s disease, and Friedreich s ataxia, to name a few (7, 8, 9,10, 11,12). 

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