Decreased content of docosahexaenoate and arachidonate in plasma phospholipids in Usher's syndrome

Docosahexaenoate and arachidonate were found to be significantly decreased in plasma phospholipids from Usher's syndrome patients. The fatty acid content of plasma triacylglycerols was not changed in these patients. Usher's syndrome, an autosomal recessive disorder, involves an inherited visual cell degeneration. Photoreceptor membranes are richly endowed with docosahexaenoate and arachidonate, and a metabolic defect affecting these polyunsaturated fatty acids may occur. Moreover, blindness may be due, at least partially, to an alteration in the unsaturated phospholipids of photoreceptor membranes.     

Quantitative analysis of phospholipids containing arachidonate and docosahexaenoate chains in microdissected regions of mouse brain

Phospholipids containing polyunsaturated fatty acyl chains are prevalent among brain lipids, and regional differences in acyl chain distribution appear to have both functional and pathological significance. A method is described in which the combined application of GC and multiple reaction monitoring (MRM) MS yielded precise relative quantitation and approximate absolute quantitation of lipid species containing a particular fatty acyl chain in milligram-sized tissue samples. The method uses targeted MRM to identify specific molecular species of glycerophosphocholine lipids, glycerophospho-ethanolamine lipids, glycerophosphoinositol lipids, glycerophosphoserine lipids, glycero-phosphoglycerol lipids, and phosphatidic acids that contain esterified arachidonate (AA) and docosahexaenoate (DHA) separated during normal phase LC/MS/MS analysis. Quantitative analysis of the AA and DHA in the LC fractions is carried out using negative ion chemical ionization GC/MS and stable isotope dilution strategies. The method has been applied to assess the glycerophospholipid molecular species containing AA and DHA in microdissected samples of murine cerebral cortex and hippocampus. Results demonstrate the potential of this approach to identify regional differences in phospholipid concentration and reveal differences in specific phospholipid species between cortex and hippocampus. These differences may be related to the differential susceptibility of different brain regions to neurodegenerative disorders.     

Lithium suppresses elevated behavioural activity and brain catecholamines in developing hyperthyroid rats.

Neonatal hyperthyroidism in rats induced by daily administration of L-triiodothyronine for 30 days since birth resulted in a significant rise in mobility and the metabolism of brain norepinephrine and dopamine. Whereas administration of lithium carbonate (60 mg/kg ip) to normal rats for 6 days produced no effect on spontaneous locomotor activity and increased the synthesis and possibly release of this monoamine in several brain regions, this antimanic drug antagonized the L-triiodothyronine-stimulated increases in mobility as well as norepinephrine and dopamine metabolism of hypothalamus, midbrain, striatum, and cerebral cortex. Furthermore, lithium treatment restored the activity of catechol-O-methyl transferase (EC 2.1.1.6) in young hyperthyroid rats to virtually normal limits. Our data suggest that antiphasic or damping effects of lithium upon mood swings is controlled, at least in part, by catecholaminergic systems in the brain. The interrelationship between brain catecholamines and thyroid hormones seems to be important to our understanding of the action of lithium in affective illness.     

Alteration of plasma and erythrocyte membrane lipid components in hyperthyroid rats

Cholesterol and phospholipid have been measured in plasma and erythrocyte membrane of hyperthyroid rats. It has been found that while the former is reduced by about 30% in plasma and increased by the same amount in erythrocyte membranes, on the contrary, the latter increases by 35% in both plasma and red cell membranes. It seems that when serum triiodothyronine increases, a major cholesterol transfer occurs from plasma to erythrocyte. In this way, by the concomitant phospholipid increase, it is possible to avoid an alteration of the cholesterol/phospholipid molar ratio in the red cells, thus preventing their abnormal function in hyperthyroid rats. The proposal is made that an additional reason for the plasma cholesterol decrease in hyperthyroid subjects can be attributable to a net transfer of this compound from plasma to erythrocyte.     

Disproportionately elevated fasting proinsulin levels in normoglycemic patients with thalassemia major are correlated to the degree of iron overload

OBJECTIVE: To analyze the secretion of the insulin precursor proinsulin in patients with beta-thalassemia and its possible relation to iron overload. METHODS: We assessed fasting proinsulin, insulin, C-peptide and glucose levels from 34 patients with beta-thalassemia and 33 healthy controls. The correlation to age, body mass index, hepatic iron concentration, serum ferritin and serum AST was analyzed. RESULTS: Fasting proinsulin (p < 0.002) and proinsulin-to-insulin ratio (p < 0.02) were significantly increased in patients with thalassemia irrespective of the degree of glucose tolerance. They correlated positively to serum ferritin, liver iron, patient age and serum AST (all p < 0.05). CONCLUSIONS: Disproportionately elevated proinsulin levels in thalassemic patients indicate early beta-cell dysfunction due to siderosis. An additional biological significance of hyperproinsulinemia and its possible ability to predict long-term iron toxicity in these patients remain to be clarified.     

Effect of dietary protein on vitamin A levels in plasma and liver of hypervitaminotic-A rats

Level of vitamin A increased in plasma and liver in hypervitaminotic A albino rats fed normal quantity of protein in diet. In low protein fed state vitamin A level in liver increased due to accumulation of vitamin A and lack of carrier protein with an associated decrease of plasma vitamin A. In high protein fed rats the level of vitamin A in plasma increased due to enhanced transport while in liver it decreased. The results indicate that for normal transport of vitamin A adequate plasma protein level is essential.     

beta-Endorphin in human plasma: basal and pathologically elevated levels.

β-Endorphin-like immunoreactivity was measured in plasma of normal human subjects and in plasma of patients with pathologically elevated ACTH levels. The antiserum used displayed the same avidity for human β-endorphin and human β-lipotropin (detection limit for both peptides 1–2 fmoles/tube). Gel chromatography of the immunoreactive components in plasma of normal subjects indicated the presence of both β-lipotropin (2.1 -10.1 fmoles/ml) and β-endorphin (3.5–6.4 fmoles/ml). A close correlation between immunoreactive β-endorphin and ACTH was found in plasma of patients suffering from Addison's disease, Cushing's disease and exhibiting Nelson's syndrome. Elevated levels of β-endorphin-like immunoreactivity in plasma of these patients were due to both β-lipotropin and β-endorphin.     

不同负荷运动对大鼠血浆和心肌细胞内ET及心肌细胞膜ETR的影响

目的:探讨不同运动负荷的游泳训练对SD大鼠血浆和心肌细胞中内皮素(ET)含量及心肌细胞膜上内皮素受体(ETR)活性的影响。方法:雄性SD大鼠分为5组,即A组(安静对照组)、B组(游泳45min组)、C组(游泳90min组)、D组(游泳150min组)、E组(急性力竭组),每组9只进行8周的游泳训练,用放射免疫法测定大鼠ET及ETR。结果:90min组大鼠血浆和心肌细胞中ET比对照组有明显降低(P<0.01),且可下调ETR的数量和亲和力(P<0.01)。150min组大鼠心肌细胞膜上ETR的解离常数Kd值明显低于对照组(P<0.01)。结论:中等负荷的运动可明显改善心血管系统的功能,而负荷较大的运动对心血管系统功能的改善不利。     

Unraveling lipid metabolism with microarrays: effects of arachidonate and docosahexaenoate acid on murine hepatic and hippocampal gene expression

Introduction  

The functions, actions, and regulation of polyunsaturated fatty acids (PUFAs) are just now beginning to be unraveled, in large due to modern molecular techniques. In the present work, mice were fed diets rich in either arachidonic acid (AA, n6), docosahexaenoic acid (DHA, n3), or the combination (AA+DHA). Both liver and hippocampus tissue were then analyzed through a combined gene expression-, lipid-, and behavioral- profiling strategy in order to annotate the molecular functions and targets of dietary PUFA.