Effect of heparin and fatty acids on the binding of quinidine and warfarin in plasma

After an intravenous injection of heparin, the plasma protein binding of warfarin was greatly increased while the binding of quinidine seemed to be less affected. The increased binding of warfarin seemed partly due to the release of plasma non-esterified fatty acids, NEFA, but the level of NEFA alone could not explain the interindividual variations of plasma warfarin binding. Addition in vitro of palmitic acid to serum demonstrated an increased binding of warfarin and an unaltered binding of quinidine up to a serum NEFA level of 3.0 meq/l. Albumin isolated from post heparin plasma revealed an increased binding affinity for warfarin at the warfarin high affinity binding sites, and a slightly depressed affinity for quinidine. The low affinity binding sites on the albumin molecule for both drugs did not seem to be influenced by NEFA.     

Toluene-induced activation of certain hypothalamic and median eminence catecholamine nerve terminal systems of the male rat and its effects on anterior pituitary hormone secretion

Subacute exposure to high concentrations (500–1000 ppm) of toluene vapour led to an increase of noradrenaline levels in the subependymal layer of the median eminence (SEL) and to an increase of noradrenaline turnover within the subependymal layer, the paraventricular hypothalamic nucleus and the anterior periventricular hypothalamic nucleus (PV I). Increased dopamine levels in the lateral palisade zone of the median eminence (LPZ) and increased catecholamine turnover within the medial palisade zone (MPZ) were also produced. Measurement of the anterior pituitary hormone secretion showed a significant increase of FSH and delayed increase of corticosterone secretion following toluene exposure.     

Production of discrete changes in dopamine and noradrenaline levels and turnover in various parts of the rat brain following exposure to xylene, ortho-, meta-, and para-xylene, and ethylbenzene

Subacute exposure of male rats to high concentrations (2000 ppm) of xylene, ortho-xylene, meta-xylene, para-xylene, and ethylbenzene produced discrete increases of dopamine and noradrenaline levels and turnover in various parts of the hypothalamus and the median eminence 16–18 hr following the last exposure to the aromatic hydrocarbons. Some of the above solvents also reduced the secretion of prolactin, corticosterone, and thyroid-stimulating hormone. Within the forebrain, only xylene produced increases of dopamine levels in various parts of the striatum and the subcortical limbic forebrain. Furthermore, only xylene itself produced widespread increases of dopamine turnover within the neostriatum and the subcortical limbic forebrain, while ethylbenzene selectively increased dopamine turnover within the dopamine-cholecystokinin-8 immunoreactive nerve terminals of the nucleus accumbens (posterior part). In contrast ortho-xylene produced widespread reductions of dopamine turnover in the above-mentioned areas. It is suggested that the changes discovered in dopamine and noradrenaline levels and turnover can produce disturbances in catecholamine neurotransmission in the brain leading to disturbed brain function, e.g., in neuroendocrine, mental, and motor control.     

Mumps meningitis: Specific and non-specific antibody responses in the central nervous system *

Intrathecal production of oligoclonal mumps-specific IgG was demonstrated in nine out of 10 children with mumps meningitis by imprint immunofixation (IIF) of sera and cerebrospinal fluids (CSF) separated by agarose electropheresis and by thin-layer electrofocusing. Four of the patients had intrathecal mumps antibody synthesis demonstrable also by conventional serological tests. Oligoclonal CSF IgG was demonstrable by agarose electrophoresis in four of the patients. A dominance of λ over κ type oligoclonal Ig and mumps antibodies was observed in the CSF of three of these patients. The bulk of the oligoclonal CSF IgG was concluded to represent mumps-specific antibodies on the basis of the IIF as well as virus absorption analysis. Intrathecal production of oligoclonal IgG antibodies to one, two, or three other (measles, rubella, herpes simplex) viruses was demonstrated by IIF in four patients. These antibodies were not associated with the oligoclonal CSF IgG present in three of the patients. It is concluded that a specific intrathecal IgG antibody response is a common feature in children with mumps meningitis. This response sometimes reaches a magnitude that permits detection of oligoclonal IgG in the CSF. In some patients, the specific response appears to be associated with a non-specific activation of cells producing antibodies of other (unrelated) specificity.     

Increased amine turnover in several hypothalamic noradrenaline nerve terminal systems and changes in prolactin secretion in the male rat by exposure to various concentrations of toluene

Subacute exposure of rats to varying concentrations of toluene vapours leads to increases of amine levels and turnover in several types of hypothalamic noradrenaline nerve terminal systems. Furthermore, the exposure of toluene in concentrations ranging from 80-3000 ppm and benzene (1500 ppm) produced differential effects on dopamine and noradrenaline turnover within various parts of the hypothalamus. These regions are involved in neuroendocrine regulation and disturbances in the secretion of prolactin were demonstrated after exposure to toluene.     

4-Hydroxynonenal immunoreactivity is increased in human hippocampus after global ischemia

Oxidative stress and lipid peroxidation may contribute to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD) and cerebral ischemia. 4-Hydroxynonenal (4-HNE) is a toxic by-product of lipid peroxidation, and immunoreactivity to 4-HNE has been used to examine lipid peroxidation in the pathogenesis of AD and ischemia. This study sought to determine 1) if there are cellular alterations in 4-HNE immunoreactivity in the human hippocampus after global ischemia, and 2) whether possession of an apolipoprotein E (APOE) epsilon4 allele influenced the extent of 4-HNE immunoreactivity. 4-HNE immunoreactivity was assessed semi-quantitatively in the temporal lobe of a group of controls (n = 44) and in a group of patients who had an episode of global ischemia as a result of a cardiorespiratory arrest and subsequently died (n = 56, survival ranged from 1hr to 42 days). There was minimal cellular 4-HNE immunoreactivity in the control group. However, compared to controls, 4-HNE immunoreactivity was significantly increased in neurons (p < 0.0002) and glia (p < 0.0001) in the hippocampal formation after global ischemia. Possession of an APOE epsilon4 allele did not influence the extent of neuronal or glial 4-HNE immunostaining in the control or global ischemia group.There was a significant negative correlation between the extent of neuronal 4-HNE immunoreactivity with survival period after global ischemia (r2 = 0.0801; p < 0.036) and a significant positive correlation between the extent of glial 4-HNE immunoreactivity and survival after global ischemia (r2 = 0.2958; p < 0.0001).The data indicate a marked increase in neuronal and glial 4-HNE. This substantiates a role for lipid peroxidation in the pathogenesis of cerebral ischemia. There was no indication that APOE genotype influenced the extent of 4-HNE immunoreactivity.     

Alpha-foetoprotein in umbilical cord in relation to severe pre-eclampsia, birth weight and future breast cancer risk

Women born after pre-eclamptic pregnancies have been reported to be at reduced risk of breast cancer as adults, because of reduced intrauterine oestrogen influence on breast tissue; high levels of alpha-foetoprotein (a glycoprotein with anti-oestrogenic properties), however, could also be important. In severe pre-eclampsia, placental function and foetal growth are reduced, and umbilical cord plasma levels of alpha-foetoprotein could reflect the underlying processes. Umbilical cord blood was collected in 12804 consecutive deliveries. Among 307 pregnancies with clinical pre-eclampsia, 66 singleton pregnancies were identified as clinically severe, and 610 singleton pregnancies were selected as controls. Oestradiol and alpha-foetoprotein were measured from umbilical plasma, and birth weight was standardized as the ratio between the observed and expected birth weight, adjusted for differences in gestation length and offspring sex. Cord plasma levels of alpha-foetoprotein were significantly higher in severe pre-eclampsia than controls (P<0.01) after adjustment for gestational age and birth weight. For oestradiol, there was no difference in cord plasma levels between the severe pre-eclampsia group and controls, after adjustment for length of gestation and birth weight. These results suggest that an anti-oestrogenic effect associated with pre-eclampsia may be mediated through high levels of alpha-foetoprotein rather than low levels of oestradiol.