Reduced membrane function

Taking these data into account, it is difficult to believe that the neuroprotective effects of hypothermia are due mainly to alterations in metabolic rate or CBF. On the other hand, it seems reasonable to think that hypothermia reduces membrane functions that are critical for the development of ischemic neuronal damage. 

Xenobiotic metabolism, free radical formation, lipid peroxidation, covalent binding, reduced membrane function, loss of calcium sequestration, phospholipase activation, cell swelling, necrosis... 

Recently, the presence of single nucleotide polymorphisms (SNPs) has been reported for several types of transporter. Extensive studies have been performed on the SNPs of OATP2 [100, 101], and the SNPs identified in African- and European-Americans are indicated in Fig. 12.3. Moreover, the frequency of SNPs differed among the African-American, European-Americans and Japanese, indicating the presence of an ethnic difference in the allelic mutation of this transporter [100, 101]. In addition, some of the mutations were associated with reduced transporter function and/or abnormalities in membrane targeting [100, 102] (Fig. 12.3). It is... 

Atrophy of the thymus is a consistent finding in mammals poisoned by 2,3,7,8-TCDD, and suppression of thymus-dependent cellular immunity, particularly in young animals, may contribute to their death. Although the mechanisms of 2,3,7,8-TCDD toxicity are unclear, research areas include the role of thyroid hormones (Rozman et al. 1984) interference with plasma membrane functions (Matsumura 1983) alterations in ligand receptors (Vickers et al. 1985) the causes of hypophagia (reduced desire for food) and subsequent attempts to alter or reverse the pattern of weight loss (Courtney et al. 1978 Seefeld et al. 1984 Seefeld and Peterson 1984) and excretion kinetics of biotransformed metabolites (Koshakji et al. 1984). 

Solarization process increases soil temperatures up to levels lethal to many plant pathogens and pests and, therefore, direct thermal inactivation is the most important and normally expected mechanism. Some studies on the biochemical bases of sensitivity of organisms to high temperatures hypothesized that heat sensitivity is related to small differences in cell macromolecules, leading to a lethal increase of intra-molecular hydrogen, ionic, and disulfide bonds (Brock 1978). Sundarum (1986) suggested a reduced cell membrane function beyond an upper limit fluidity... 

Although the role of lipid composition in membrane function is not entirely understood, changes in composition can produce dramatic effects. Researchers have isolated fruit flies with mutations in the gene that encodes ethanolamine kinase (analogous to choline kinase Fig. 21-28). Lack of this enzyme eliminates one pathway for phosphatidylethanolamine synthesis, thereby reducing the amount of this lipid in cellular membranes. Flies with this mutation—those with the genotype easily shocked—exhibit transient paralysis following electrical stimulation or mechanical shock that would not affect wild-type flies. 

Because most of the established membrane polymers can not meet all the performance requirements for a membrane dedicated to a particular application, membrane modifications are gaining rapidly increasing importance. Membrane modification is aimed either to minimize undesired interactions, which reduce membrane performance (e.g., membrane fouling), or to introduce additional interactions (e.g., affinity, responsive or catalytic properties) for improving the selectivity or creating an entirely novel separation function [3]. Three general approaches can be distinguished ... 

Such imbalanced antioxidant systems in schizophrenia could lead to oxidative stress- and ROS-mediated injury as supported by increased lipid peroxidation products and reduced membrane polyunsaturated fatty acids (PUFAs). Decrease in membrane phospholipids in blood cells of psychotic patients (Keshavan et al., 1993 Reddy et al., 2004) and fibroblasts from drug-naive patients (Mahadik et al., 1994) as well as in postmortem brains (Horrobin et al., 1991) have indeed been reported. It has also been suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients (Pettegrewet al., 1991 Yao et al., 2002). Recently, a microarray and proteomic study on postmortem brain showed anomalies of mitochondrial function and oxidative stress pathways in schizophrenia (Prabakaran et al., 2004). Mitochondrial dysfunction in schizophrenia has also been observed by Ben-Shachar (2002) and Altar et al. (2005). As main ROS producers, mitochondria are particularly susceptible to oxidative damage. Thus, a deficit in glutathione (GSH) or immobilization stress induce greater increase in lipid peroxidation and protein oxidation in mitochondrial rather than in cytosolic fractions of cerebral cortex (Liu et al., 1996). 

Damage to polyunsaturated fatty acids tends to reduce membrane fluidity, which is known to be essential for the proper functioning of membranes [19]. However the precise role of such damage in contributing to reduced cell proliferation and/or cell death is still the subject of current investigation. Most of the proteins that play key roles in proliferative signal transduction actually function in a membrane environment, or in close association with membranes, and it is well established that the activity of integral membrane proteins is modulated by the lipids of the bilayer [51]. Moreover protein kinase C importantly has... 

Membrane ermeant dmgs are thus not efficiently eliminated in the urine, even if they do get filtrated in the glomemli. On the other hand, membrane-impermeant dmgs get eliminated in proportion to the extent of glomem-lar filtration. Glomemlar filtration therefore is an important parameter in the elimination of dmgs. It may vary considerably between different patients (example A patient who has donated one kidney. Not the most common case of reduced kidney function but a straightforward one). With... 

Development of an in vivo or extracorporeal device that supplements reduced tissue function. The in vivo device is encapsulated within a semi-permeable membrane to allow for provision of a therapeutic molecule to the site while protecting the cells from the host immune system. An externally positioned device would provide deficient tissue function compounds through a tube directed to the body site while avoiding cellular contact with the immune system. 

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