Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia.

The aim of the present investigation was to evaluate the possible role of arachidonic acid and other free fatty acids in ischemia-induced mitochondrial dysfunction. Respiratory activities were measured in mitochondria isolated from rat brains subjected to 15-30 min of decapitation ischemia. Addition of bovine serum albumin (BSA) to the mitochondria, isolated in BSA-free media, abolished an ischemia-induced increase in substrate-stimulated (state 4) respiration but only partly reversed a marked inhibition of substrate-, phosphate-, and ADP-stimulated (state 3) respiration caused by the ischemia.

Induction of intracellular superoxide radical formation by arachidonic acid and by polyunsaturated fatty acids in primary astrocytic cultures.

The effects of arachidonic acid and other polyunsaturated fatty acids (PUFAs) on both oxidative and metabolic perturbation were studied in primary cultures of rat cerebral cortical astrocytes. In the presence of 0.1 mM arachidonic acid, the rate of the reduction of nitroblue tetrazolium (NBT) to nitroblue formazan (NBF) was stimulated from 0.

Reduction of activities of superoxide dismutase but not of glutathione peroxidase in rat brain regions following decapitation ischemia.

Effects of complete ischemia on levels of antioxidative enzymes including copper-zinc (CuZn) superoxide dismutase (SOD), manganese (Mn)-SOD, and glutathione peroxidase (GSH-Px) were studied in rat brain regions at 30 and 60 min following decapitation. CuZn-SOD activities were significantly decreased in cerebral cortex and hippocampus at both time points whereas the enzyme activities were decreased at 60 min in cerebellum and caudate areas. The reduction of Mn-SOD activities followed the same pattern of CuZn-SOD in various brain regions.

Effects of arachidonic acid on respiratory activities in isolated brain mitochondria.

The present investigation was designed to examine the effects of free arachidonic acid (20:4), in concentrations relevant to cerebral ischemia, on brain mitochondrial respiratory activities and the reversibility of these effects. Incubation of brain mitochondria with 20:4 caused a dose-dependent increase in substrate-supported (state 4) respiration (i.e.

Protective effects of liposome-entrapped superoxide dismutase on posttraumatic brain edema.

Oxygen-derived free radicals and membrane lipid peroxidation have been postulated to be involved in brain edema and cell death, secondary to ischemia and traumatic injury. Using a model of brain edema induced by cold-induced injury, we have demonstrated an early elevation of superoxide radicals followed by permeability changes in the blood-brain barrier and development of edema in injured brain. Intravenous injection of liposome-entrapped copper-zinc-superoxide dismutase 5 minutes before the injury-enhanced entry of the enzyme into endothelial cells of the blood-brain barrier of injured brain reduced the brain level of superoxide radicals and ameliorated blood-brain barrier permeability changes and brain edema.

Alterations in lipid metabolism, Na+,K+-ATPase activity, and tissue water content of spinal cord following experimental traumatic injury.

Traumatic spinal cord injury has recently been shown to cause a rapid increase in free fatty acids (FFAs) and lipid degradation in cats. The present studies report a more delayed, time-dependent increase in FFAs and a concomitant decrease in phospholipids following traumatic spinal injury in rats. The largest percentage increases were found for polyunsaturated fatty acids, particularly arachidonic acid.

Effects of exogenous phospholipases on brain membrane phospholipid perturbation, (Na(+) + K(+))-ATPase activity and cellular swelling of brain slices.

Rat brain membranes were incubated with bee venom phospholipase A(2) (PLA(2)) or phospholipase C (PLC) from Clostridium perfringens. PLA(2) caused a significant increase in free polyunsaturated fatty acids concomitant with membrane phospholipid degradation as monitored by HPLC and by gas chromatography. Equal concentrations of PLC had a much lesser effect than PLA(2).

Arachidonic acid inhibits uptake of glutamate and glutamine but not of GABA in cultured cerebellar granule cells.

The effects of arachidonic acid (20:4) on the uptake of glutamate were studied in primary cultures of cerebellar granule cells and were compared to cortical neurons and astrocytes. At a dose of 0.005 mM, the glutamate uptake was significantly inhibited in cerebellar granule cells.

Effects of arachidonic acid on glutamate and gamma-aminobutyric acid uptake in primary cultures of rat cerebral cortical astrocytes and neurons.

The effects of arachidonic acid on glutamate and gamma-aminobutyric acid (GABA) uptake were studied in primary cultures of astrocytes and neurons prepared from rat cerebral cortex. The uptake rates of glutamate and GABA in astrocytic cultures were 10.4 nmol/mg protein/min and 0.

Prolactin in human cervical mucus.

The pattern of change in the levels of prolactin (PRL) in cervical mucus was studied in 19 normal ovulatory women. The concentration of PRL in cervical mucus was generally higher than that in plasma except at midcycle, when a reverse relationship was observed. The concentration of PRL in mucus obtained at midcycle was lower than mucus obtained during follicular phase or luteal phase.

Seminal plasma beta-human chorionic gonadotropin (beta-HCG): relationships with seminal characteristics and spermatozoal fertilizing capacity.

Seminal plasma beta-human chorionic gonadotropin (beta-HCG) levels were determined in 254 semen samples collected from fertile and suspected subfertile men, and their relationships with seminal characteristics and spermatozoal fertilizing capacity were evaluated. Radioimmunoassayable beta-HCG, as defined by greater than 5 mIU/ml concentration, was demonstrated in only 44.5% of all the samples studied.

Factor VIII related antigen in gestational trophoblastic disease.

Serum factor VIII related antigen (factor VIII R:Ag) levels were determined in 34 patients with hydatidiform mole at diagnosis and at 2, 4 and 6 weeks after evacuation of uterus and in 272 normal pregnant women. Serum factor VIII R:Ag levels in molar pregnancies before evacuation of the uterus were significantly higher than those in normal pregnancies of the same gestation age. Serum factor VIII R:Ag levels in the group of patients with residual trophoblastic disease were significantly higher than those in the group without residual trophoblastic disease before evacuation and at 6 weeks after evacuation of uterus, but there is considerable overlap in the levels of factor VIII R:Ag between the two groups of patients especially before evacuation of uterus.

Rapid urinary LH assay for prediction of ovulation.

The results of the cervical mucus score (CMS), basal body temperature (BBT) and a rapid urine luteinizing hormone (LH) assay by haemagglutination immunoassay were compared with plasma LH radioimmunoassay in 28 ovulatory cycles. There was good correlation of the CMS peak with the plasma LH peak while the urine LH peak usually occurred one day later. The first day when the CMS was greater than or equal to 8 occurred within +/- 1 day of the plasma LH peak in 89.

Factor VIII-related antigen levels in normal pregnancy and puerperium.

The changes in serum Factor VIII-related antigen (Factor VIII RAg) levels in normal pregnancy and puerperium in Chinese women were studied by the Laurell 'rocket' immunoelectrophoresis. At 6 wk of gestation, the serum Factor VIII RAg levels were already higher than those of non-pregnant women and gradually increased through term pregnancy. Parturition did not have immediate effects on the circulating levels of Factor VIII RAg.

Stimulation of phospholipase A2 activity by oxygen-derived free radicals in isolated brain capillaries.

An exogenous free radical generating system added to isolated brain capillaries induces degradation of phospholipids. This inductive effect reflects increased phospholipase activities as measured by fatty acid composition of various phospholipid fractions. The correlation of phospholipid degradation with stimulation of phospholipases was further investigated by using cationic amphiphilic agents, which are known to be phospholipase A2 inhibitors.

Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals.

We studied the cerebral effects of oxygen-derived free radicals generated from the xanthine oxidase/hypoxanthine/ADP-Fe3+ system. Xanthine oxidase/hypoxanthine/ADP-Fe3+ solution (0.1 ml) was infused into caudate putamen, and brain was frozen rapidly in situ.

The role of arachidonic acid in vasogenic brain edema.

Arachidonic acid is released rapidly from cellular membrane phospholipids after pathological insults associated with the delayed development of brain edema. Intracerebral injection of arachidonic acid caused significant increases in brain water and sodium content with decreases in potassium content and Na+,K+-ATPase activity. The 125I-labeled bovine serum albumin spaces in brain (a measure of blood-brain barrier permeability) rose threefold 24 h after arachidonic acid injection.

Effect of propranolol on human spermatozoal in vitro hamster ova penetration.

The effect of (D,L)-propranolol at various concentrations (3.4 X 10(-6) to 3.4 X 10(-3) M) on human spermatozoal motility and zona-free hamster ova penetration was studied in vitro.

Release of polyunsaturated fatty acids from phospholipids and alteration of brain membrane integrity by oxygen-derived free radicals.

We studied the effects of oxygen-derived free radicals on the ultrastructure of brain cortical slices and the release of fatty acids from phospholipids of crude synaptosomes. Xanthine oxidase, hypoxanthine, and ADP-Fe3+, a free-radical-generating system, caused swelling of cellular processes and mitochondria. The oxygen-derived free radicals also caused the rapid release and accumulation of endogenous polyunsaturated fatty acids (PUFA) from membrane phospholipids as determined by high-performance liquid chromatography (HPLC).

Lack of effect of exogenous prolactin on the fertilizing capacity of human spermatozoa in vitro.

The effect of exogenous prolactin (PRL) on the fertilizing capacity of human spermatozoa in vitro was evaluated by the zona-free hamster ova penetration assay. Bovine and ovine PRL, in both physiological and pharmacological concentrations, failed to increase the penetration after 5 hr of incubation in vitro. The percent motility of spermatozoa was not influenced by PRL during the incubation period.

Relationships of seminal plasma prolactin with spermatozoal characteristics and fertilizing capacity in vitro.

Seminal plasma prolactin (PRL) levels were determined in 224 semen samples collected from fertile and suspected infertile men, and their relationships with spermatozoal characteristics and fertilizing capacity in vitro were evaluated. PRL concentrations were similar in normospermic and oligospermic samples, but were significantly lower in azoospermic samples. PRL concentrations were significantly higher in samples with high spermatozoal motility than in those with low spermatozoal motility.

Effects of temperature on arachidonic acid-induced cellular edema and membrane perturbation in rat brain cortical slices.

The effects of temperature on arachidonic acid-induced cellular edema in the first cortical brain slices of rats were studied. Incubation of the cortical slice in arachidonic acid at 37 degrees C induced cellular swelling, and increased intracellular Na+ and lactic acid contents concomitant with decreased intracellular K+. When the incubation temperature was reduced these changes were reduced in severity.