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Perfusion-weighted magnetic resonance imaging of the spinal cord in cervical spondylotic myelopathy.

Principles of echo shifting with a train of observations was used to perform magnetic susceptibility-weighted magnetic resonance imaging with bolus-tracking in 14 patients with spondylotic myelopathy to assess changes in perfusion parameters of the spinal cord before and after decompression surgery for cervical spondylotic myelopathy. The mean transit time (MTT), bolus arrival time (T0), and time to peak (TTP) were obtained from regions of interest (ROIs) and assessed as the ratio between the spinal cord and the pons (MTT index = MTT(ROI)/MTT(pons), T0 index = T0(ROI)/T0(pons), TTP index = TTP(ROI)/TTP(pons)). The patients were divided into two groups according to percentage improvement on the Neurosurgical Cervical Spine Scale. The MTT index in patients with good recovery (> or =50%) was significantly reduced. The T0 index and TTP index showed no significant change in both groups. Reduction of MTT index may indicate improved perfusion of the spinal cord following surgery for cervical spondylotic myelopathy.

Aged↗

Promoter polymorphism T(-107)C of the paraoxonase PON1 gene is a risk factor for coronary heart disease in type 2 diabetic patients.

The serum enzyme paraoxonase (PON) protects LDLs from oxidative stress. We recently identified promoter polymorphisms of the PON gene that strongly affect gene expression and serum levels of the enzyme. The present study tested the hypothesis that promoter polymorphism T(-107)C could be a risk factor for vascular disease in type 2 diabetic patients by virtue of its ability to modulate serum concentrations of the antioxidant enzyme. The low-expressor genotype (TT) was associated with significantly lower serum PON concentrations, and it was over-represented in type 2 diabetic patients with coronary heart disease (CHD) (TT vs. TC+CC: odds ratio [OR] 1.64 [95% CI 1.03-2.61], P < 0.05). The association of the low-expressor genotype with an increased risk of disease was independent of other risk factors, including the coding region Q191R polymorphism (OR 2.12 [95% CI 1.19-3.70], P = 0.01). However, an interaction of the promoter polymorphism with the Q191R polymorphism, which was previously identified as an independent risk factor, was observed. The low-expressor promoter allele (-107T) associated with the high-risk 191R allele showed a lower-than-expected level of risk (OR 2.21 vs. the expected 4.76). The data are consistent with the hypothesis that low expression of the antioxidant enzyme PON increases the risk of CHD. Moreover, the promoter polymorphism appears to have a modulating effect on risk that is associated with the coding region polymorphism Q191R. This study indicates a strong genetic component to the antioxidant capacity of HDLs.

Aryldialkylphosphatase↗

The activities of noradrenergic and dopaminergic neuron systems in experimental hydrocephalus.

Experimental hydrocephalus was induced in rabbits by intracisternal injection of kaolin suspension, and the concentration of noradrenaline (NA), dopamine (DA), and their metabolites was determined in several brain regions. The NA concentration had decreased in the cerebellum, hypothalamus, and pons plus medulla oblongata, and increased in the caudate nucleus at 2 days after kaolin injection (the stage of early intracranial hypertension). At 1 week (the stage of progressive hydrocephalus), the NA content had returned to control levels in all brain regions studied, and it decreased again at 4 weeks (the stage of chronic hydrocephalus) in the pons plus medulla oblongata. The DA level was unchanged throughout the 4-week period after kaolin injection. The concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEG-SO4), the major metabolite of NA, was elevated in all brian regions except the caudate nucleus at all stages after kaolin injection. An increase in MOPEG-SO4 in the caudate nucleus was also observed 1 week after kaolin injection. The content of homovanillic acid (HVA), the major metabolite of DA in the rabbit brain, was decreased in the cerebral cortex at 2 days and at 1 week after kaolin injection, and in the caudate nucleus at 2 days and at 1 week, and 4 weeks. The level of HVA was increased in the hypothalamus at 2 days, in the cerebellum at 2 days and at 1 week, in the pons plus medulla oblongata at 2 days, 1 week, and 4 weeks, and in the midbrain at 4 weeks. These data suggest that, in experimental hydrocephalus in the rabbit, NA release is increased throughout the brain, while DA release is decreased in the cerebral cortex and caudate nucleus, and increased in the cerebellum, hypothalamus, midbrain, and pons plus medulla oblongata.

3,4-Dihydroxyphenylacetic Acid↗

R192Q paraoxonase gene variant is associated with a change in HDL-cholesterol level during dietary caloric restriction in nondiabetic healthy males.

Paraoxonase (PON), an HDL- associated enzyme, may protect against the development of atherosclerosis. Single nucleotide polymorphisms of PON have been reported to be associated with an incidence of coronary heart diseases. We investigated the effect of PON R192Q variants on serum lipid profile after caloric restriction in nondiabetic healthy males. After caloric restriction for 12 weeks, the levels of high-density lipoprotein cholesterol (HDL-C) increased in the subjects carrying RR genotype, but not in the QR and QQ genotypes. The changes in HDL-C from the baseline values in the RR genotype were significantly different from those in the QR and QQ genotypes. Although the changes in lipoprotein lipase activity were not different among three genotypes, we observed a significant difference in the changes in hepatic lipase (HL) activity after caloric restriction, namely, a decrease in the RR genotype and an increase in the subjects carrying the Q allele. In addition, the changes in fasting insulin levels significantly correlated with those in HDL-C levels in the RR genotype, not in the QR and QQ genotypes. PON R192Q polymorphism could affect HDL-C levels after caloric restriction presumably due to decreased HL activity and altered insulin resistance.

Adult↗

Cerivastatin modulates plasma paraoxonase/arylesterase activity and oxidant-antioxidant balance in the rat.

Statins (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors), apart from lowering plasma cholesterol, modulate other processes involved in atherogenesis. Paraoxonase (PON), contained in plasma high density lipoproteins, protects plasma lipoproteins from oxidative damage and is a potentially atheroprotective enzyme. We investigated the effect of cerivastatin on oxidant-antioxidant balance and plasma PON activity. The adult male Wistar rats received cerivastatin at a dose of 0.03 or 0.3 mg/kg/day for 3 weeks. Then, plasma concentration of lipid peroxidation products, total antioxidant capacity and PON activity were assayed. Plasma level of lipid peroxidation products was unchanged in low-dose group but decreased significantly in animals receiving high dose of cerivastatin. In this group, the concentration of malonyldialdehyde and 4-hydroxydialkenals was reduced by 46.6% whereas the level of lipid hydroperoxides was lowered by 59.3%. Total plasma antioxidant capacity increased in low-dose group by 22.3% and in high-dose group by 27.2%. PON activity toward paraoxon decreased by 16.1% and 11.6% in low- and high-dose groups, respectively. The activity toward phenyl acetate, which better corresponds with enzyme concentration, declined by 74.2% and 78.4% following lower and higher dose treatment, respectively. PON/arylesterase ratio raised in cerivastatin-treated rats (low dose: +227.4%, high dose: +328.2%). Cerivastatin had no effect on total plasma cholesterol but significantly decreased triglyceride level by 34.6% in low-dose and by 31.2% in high-dose group. These results indicate that cerivastatin decreases the level of oxidative stress, improves plasma antioxidant defense and modulates paraoxonase activity. These effects can contribute to pleiotropic actions of statins in the cardiovascular system.

Animals↗

[The paraoxonase Gln-Arg192 polymorphism in patients with coronary heart disease in Chinese population].

OBJECTIVE: To investigate the 192 Gln-Arg polymorphism of paraoxonase (PON) gene and its relationship with serum lipids levels in patients with coronary heart disease in Chinese population. METHODS: The genotype and allele frequency of paraoxonase gene 192 Gln-Arg polymorphism was assayed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Serum lipids were measured by enzymatic kits in 118 CHD patients and 128 healthy subjects whose fasting serum TG levels were < 1.82 mmol/L and TC levels < 6.2 mmol/L from a population of Chinese Han nationality in Chengdu area. RESULTS: Both in CHD group and control group, the QR genotype of PON gene was the major one, and its frequencies were 0.578 and 0.525 respectively. No differences were found in PON gene Gln-Arg polymophism in the CHD group when compared with the control group. The frequency of R allele of PON gene in Chinese was significant higher than that in European and American Caucasians (0.51 vs. 0.26-0.31, P < 0.01) and Indian (0.51 vs. 0.17, P < 0.01), and significantly lower than that in Japanese (0.51 vs. 0.65, P < 0.01). CONCLUSION: These results suggested that the Gln-Arg192 polymorphism of the PON1 gene was not associated with coronary heart disease in Chinese population.

Aged↗

[Determination of paraoxonase activities in serum and HDL].

OBJECTIVE: [corrected] To establish a reliable method of determining the activity of paraoxonase(PON) in serum and high density lipoprotein(HDL). METHODS: We used phenylacetate(PA) as substrate and investigated the hydrolysis of PA catalyzed by serum PON or HDL-PON. The PON activities were calculated from the velocities of reaction that had been determined by the increasing absorbance of product p-phenol within the first 5 minutes. RESULTS: Through the studies on the effects of substrate concentration, pH, activator Ca2+, and inhibitor EDTA, we found the best conditions of reaction to be: substrate concentration 5 mmol/L, pH8.0, and Ca2+ concentration 2 mmol/L. And we established the method with good reproducibility and stability. CONCLUSION: Under the above-stated conditions, it is reliable to determine the activity of paraoxonase in serum and HDL.

Aryldialkylphosphatase↗

[The paraoxonase Gln-Arg 192 polymorphism in patients with endogenous hypertriglyceridemia in Chinese population].

OBJECTIVE: To investigate the 192 Gln-Arg polymorphism of paraoxonase (PON) gene and its relationship with serum lipids and apolipoproteins (apo) levels in patients with endogenous hypertriglyceridemia in Chinese population in Chengdu area. METHODS: The genotype and allele frequencies of paraoxonase gene 192 Gln-Arg polymorphism were assayed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Serum lipids were measured by enzymatic kits and apolipoproteins AI, A II, B100, C I, C II and E were measured by the RID kits developed by the Apolipoprotein Research Unit of this university in 128 HTG patients whose fasting serum TG levels were > or = 2.26 mmol/L and 129 healthy subjects whose fasting serum TG levels were < 1.82 mmol/L and TC levels < 6.2 mmol/L from a population of Chinese Han nationality in Chengdu area. RESULTS: Both in HTG group and control group, the QR genotype of PON gene was the major one, and the frequencies were 0.515 and 0.581 respectively. No differences were found in PON gene Gln-Arg polymorphism between the HTG group and the control group. In the control group, the QQ genotype of PON gene was found to have higher serum apoA I levels, compared with the RR genotype (P < 0.05). But in the HTG group, when compared with the RR genotype, the QQ genotype was found to have lower serum apoA I and A II levels and higher serum apoE levels. CONCLUSION: These may be an association of the QQ genotype of the paraoxonase 192 Gln-Arg polymorphism with the decrease of serum apoA I level and the increase of serum apoE level in endogenous hypertriglyceridemica.

Aged↗

[Effects of sevoflurane anesthesia on dopamine metabolism in the rat brain].

To elucidate the mechanism of general anesthesia, effects of sevoflurane anesthesia on dopamine metabolism in rat brain were studied. Sevoflurane 3% was administered for 20 minutes to Wistar male rats weighing 230-270 g under spontaneous respiration. The rats were sacrificed by decapitation and the brains were rapidly removed. They were dissected into nine discrete regions, locus coeruleus, pons plus, medulla oblongata, hypothalamus, thalamus, basal ganglia, midbrain, hippocampus, amygdala and cerebral cortex. The contents of dopamine (DA) and its major metabolites, 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) were measured by high performance liquid chromatography with the dual-cell coulometric detector before anesthesia, 20 minutes after the start of anesthesia and at the recovery from anesthesia. Significant increases in DA levels were observed in the pons, hypothalamus, thalamus and amygdala by sevoflurane anesthesia as compared with the control group. DOPAC levels increased significantly in the pons, hypothalamus, basal ganglia and cerebral cortex at the recovery from anesthesia. A significant increase in HVA levels was observed in amygdala by sevoflurane anesthesia, while an appreciable decrease in HVA levels was observed in hippocampus at recovery from anesthesia. It is concluded that DA metabolism is significantly suppressed in the pons, hypothalamus, thalamus, basal ganglia, midbrain and amygdala during sevoflurane anesthesia and this change in DA metabolism may be associated with the mechanism of sevoflurane anesthesia.

Anesthetics↗

[The pathogenesis of vitreoretinal diseases from the standpoint of molecular biology].

It is important to study the pathogenesis in vitreoretinal diseases to develop new medical therapy. We investigated the molecular mechanisms underlying the genesis of idiopathic macular hole, exudative age-related macular degeneration (AMD), and diabetic retinopathy. We observed high levels of chymase and tryptase activity in the vitreous humor of patients with idiopathic macular hole. This activity was significantly higher than in other vitreoretinal diseases. Immunohistochemical study using monkey eyes showed the possibility that Müller cells in foveal lesions have properties similar to retinal stem cells. Intravitreal injection of chymase induced apoptosis of foveal retinal cells and fibrous change of vitreoretinal interface in the macular area. Biochemical study using cultured human Müller cells revealed that chymase caused the inhibition of growth and the induction of apoptosis in dedifferentiated Müller cells treated with basic fibroblast growth factor (bFGF). These findings show that increased production of chymase and tryptase in mast cells could be related to the pathogenesis of idiopathic macular hole. Oxidative stress and arterosclerosis may be the major causes of exudative AMD. Paraoxonase (PON) is a polymorphic protein known to prevent oxidation of low-density lipoprotein (LDL). We analyzed PON genotypes and found that two types of polymorphism were significantly different between patients with AMD and control subjects. We also investigated serum oxidized low-density lipoprotein(oxLDL) levels, PON activity, and extracellular superoxide dismutase(EC-SOD) levels. All these factors were significantly higher in patients with AMD than in controls. Titers of IgA and IgG antibodies against chlamydia pneumoniae in the serum of AMD patients were also significantly higher than in controls. These results indicate that genetic factors related to PON polymorphisms, vascular damage caused by increment of serum oxLDL and malfunction of EC-SOD, and chronic inflammation provoked by clamydia pneumoniae infection may be involved in the pathogenesis of AMD. Excess accumulation of advanced glycation end products(AGEs) has a causative role in the development of diabetic complications. We determined the concentrations of three AGEs (pentosidine, carboxy-methyllysine, and crossline) and two cytokines (VEGF, IL-6) using ELISA. The levels of the three AGEs and two cytokines in the vitreous of patients with proliferative diabetic retinopathy(PDR) were significantly higher than in controls. The concentrations of VEGF and IL-6 were strongly correlated with the level of these AGEs. Cultured human Müller cells expressed both VEGF and IL-6 mRNA and these expressions were augmented after the treatment of AGEs, while also acting as photosensitizers and accelerating the degradation of hyaluronic acid in vitro. AGEs may consequently play an important role in the pathogenesis of diabetic retinopathy by inducing the production of VEGF and IL-6 in retinal Müller cells and the acceleration of vitreous liquefaction.

Animals↗

MR imaging-based volumetry in patients with early-treated phenylketonuria.

BACKGROUND AND PURPOSE: Our purpose was to specify the most severely affected brain structures in early treated phenylketonuria regarding volume loss and establish possible correlations between volume loss and plasma levels of phenylalanine (Phe). METHODS: In 31 patients with early treated phenylketonuria and in 27 healthy volunteers, we acquired volumetric MR imaging data. Serum Phe concentrations at different times were measured as well. Semiautomatic volumetric postprocessing of the cerebellum, cerebrum (supratentorial brain tissue), hippocampus, intracranial volume, lateral ventricles, nucleus caudatus, nucleus lentiformis, pons, and thalamus, as well as the two-dimensional extension of the corpus callosum, was performed using the software BRAINS2. For each separate brain structure, the relative differences between the normal and the phenylketonuria group (delta(rel)) were calculated. RESULTS: The cerebrum, corpus callosum, hippocampus, intracranial volume, and pons were significantly smaller in patients with phenylketonuria than in healthy patients. The volume of the lateral ventricles was significantly larger in patients with phenylketonuria than in healthy ones. The most severely affected structures were the pons (delta(rel) = 16%), hippocampus (delta(rel) = 14.5%), cerebrum (delta(rel) = 13%), and corpus callosum (delta(rel) = 10%). No significant differences were found for the basal ganglia, cerebellum, and thalamus. There were no significant correlations found between the volume of any of the different brain structures and the metabolic parameters. CONCLUSION: The most severely affected brain structures in early-treated patients with phenylketonuria regarding volume loss are the cerebrum, corpus callosum, hippocampus, and pons.

Adult↗

[Concerning the significance of paraoxonase-1 and SR-B1 genes in atherosclerosis].

High-density lipoprotein (HDL) is an independent protective factor against cardiovascular disease. The enzyme paraoxonase-1 (PON-1) contributes to the anti-atherogenic effects of HDL. In vitro studies have demonstrated that paraoxonase's substrates are highly heterogeneous and that some contribute to the development of atherosclerotic lesions. The atheroprotective role of PON-1 was established in genetically engineered animal models. In humans, the PON-1 Gln192Arg and Met55Leu polymorphisms appear to be associated with increased susceptibility to cardiovascular disease and with different PON-1 activity levels and concentrations. The CLA-1 (CD36 and Lysosomal integral membrane protein-II Analogous-1) gene is the human homologue of the murine SR-B1 (Scavenger Receptor class B type 1) gene. SR-B1 was the first high-affinity HDL receptor to be identified at the molecular level. The CLA-1 receptor plays a pivotal role in HDL-mediated reverse cholesterol transport by mediating the selective uptake of free cholesterol as well as of native and oxidized cholesteryl esters. Its atheroprotective role has also been established in transgenic mice studies. Several polymorphic variants of the CLA-1 gene have been described, some of which are associated with phenotypic changes in plasma lipoproteins. Both genes participate in the complex HDL metabolic pathway and, presumably, also in defense mechanisms against oxidative stress.

Animals↗

[Soil carbon and nitrogen sequestration following cropland to forage grassland conversion in the marginal land in the middle of Heihe River basin, northwest China].

Changes in soil organic carbon (SOC) and total nitrogen (TN) stocks were studied following croplands were converted to forage grasslands (alfalfa) for five years on the marginal land at the edge of oasis in the middle reaches of Heihe river basin. Soil from 12 paired forage land/adjacent cropland on the two soil types (Typic Torripsamments and Typic Calciorthids) was sampled at the three depths of 0-5, 5-10 and 10-20 cm and analyzed for SOC and TN, particulate organic carbon (POC) and nitrogen (PON). The studied soils had very low SOC and N concentrations. SOC stock at the 0-20 cm depth increased by 22.1%-27.8% after conversion of annually crop to perennial alfalfa for four years, and carbon sequestration rate was estimated to be on average 0.47 Mg/(hm2 x a). The greatest change in SOC stock occurred at the 0-5 cm surface layer with an increase of 32%-66%. No significant TN stock was found at the 0-20 cm depth, however, it increased at the 0-5 cm surface layer by 12.8% and 48.1% for Typic Torripsamments and Typic Calciorthids, respectively. Changes in POC and PON stocks were more significant than those in SOC and total N following conversion of crop to forage, and the percentage of distributions of POC and PON increased. POC and PON stocks at the 0-20 cm depth increased by 22.8%-42.7% and 18.6%-57.6% with the greatest increases at the 0-5 cm layer. The increase in soil C pool was mainly attributed to the increase of POC formation after the marginal lands converted to perennial forage cover. Typic Calciorthids with lower SOC concentration had relatively lower C sequestration rate but more significant effects of C and N sequestration compared with Typic Torripsamments.

Carbon↗

Influence of dibutyryl cyclic AMP on the level of catecholamines and 5-hydroxytryptamine in discrete areas of rat brain.

Dibutyrul cyclic AMP (dbcAMP) was injected intracerebroventricularly into rats in doses of 50, 100 or 200 microgram. Noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) or 5-hydroxy indoleacetic acid (5-HIAA) concentrations were measured spectrophotofluorimetrically in discrete brain areas: cortex, hypothalamus, striatum, hippocampus with nucleus amygdala and nucleus accumbens (limbic system) and pons with medulla oblongata. DbcAMP (in each dosage administered) decreased, NA content of cortex and of pons with medulla oblongata. NA content in the hypothalamus and striatum was decreased only after the largest dose of dbcAMP. In the limbic system NA concentration was diminished after a dose of 100 or 200 microgram of dbcAMP. There was a decrease in DA level measured in the striatum alone after a dose of 100 microgram of dbcAMP. 5-HT concentration was increased in the striatum and the pons with medulla oblongata after each dose level of dbcAMP; in the cortex after a dose of 50 and 100 microgram; and in the hypothalamus after a dose of 200 microgram. 5-HIAA level was increased in the striatum, limbic system, pons with medulla oblongata after all doses of dbcAMP. We conclude that dbcAMP affects presynaptic central catecholaminergic and serotoninergic neurons in an opposite, manner, although discrete brain areas have a different susceptibility to dbcAMP action. These findings provide some explanation for the behavioural effects of dbcAMP.

Animals↗

Re-evaluation of the presence of multiple haemoglobins during the ontogeny of the mouse.

In mice, three alleles, Hbbs, Hbbd and Hbbp, have been found at the beta-chain locus of haemoglobin. Analytical polyacrylamide gel electrophoresis revealed the presence of almost the same four haemoglobin bands (E-I, E-II, E-III and X) in all of the lysates of peripheral blood cells from 12-day-old foetuses of C57BL/6J (Hbbs), A/He (Hbbd) and PON (Hbbp). All were embryonic-type haemoglobins; the most anodal band (X) seemed to be a product of polymerization of E-I. Electrophoretic patterns of the haemolysates from 12-day-old foetuses were not affected by alkylation with iodoacetamide or maleic anhydride. Almost the same electrophoretic patterns in subunit analysis, using acid starch and acid-urea polyacrylamide gels, were obtained in 12-day-old foetuses of C57BL/6J, A/He and PON. E-I comprised alphia and x-chains, E-II, alpha- and y-chains, and E-III, alpha- and z-chains. In adults, two haemoglobin bands, s and Y, were present in the haemolysate of C57BL/6J, while three, dmaj, dmin and Y, existed in A/He, and three, pmaj, pmin and Y, in PON. All were adult-type haemoglobins. Haemoglobin Y, which was not demonstrable after alkylation of the haemolysates, seemed to be a product of polymerization of major haemoglobins (s, dmaj and pmaj). Each haemoglobin possessed common alpha-chains, while the beta-chains of major haemoglobins were different from those of minor haemoglobins. Developmental changes of the haemolysates from foetuses of C57BL/6J, A/He and PON were similar to each other. Haemolysates of the liver cells of developing foetuses contained only adult-type haemoglobins. Our techniques used here were not able to demonstrate the presence of foetal-type haemoglobins.

Alkylation↗

Cerebral blood flow and experimental intraventricular hemorrhage.

We evaluated the effects of acute hypovolemic hypotension followed by rapid, corrective blood infusion upon sequential regional cerebral blood flows (rCBF) in nine anesthetized 24-48-h-old beagle pups using the radioactive microsphere technique. After 5 min of hemorrhagic hypotension, during which time systemic arterial blood pressures were reduced 35-45%, cerebral blood flow to all regions increased by 31-42% over steady-state values. After blood reinfusion, rCBF increased by 39-88% over control values. Highest blood flows during hypovolemia were in the medulla and pons; slightly lower values were in the cerebellum, midbrain, cortex, and thalamus; and the lowest flows were in the white matter. These flows paralleled the hierarchy of flows to these regions in the steady state. Increases in blood flow during hemorrhagic hypotension were statistically significant when compared with the control values in the medulla (P less than 0.01), pons (P less than 0.01), midbrain (P less than 0.01), cerebellum (P less than 0.01), and cortex (P less than 0.01). One minute after reinfusion of the withdrawn blood volume, blood flows further increased by substantial margins in the medulla and pons; by moderate degree in the thalamus, midbrain, and cerebellum; and mildly in the cortex and white matter. Reinfusion state flow increases were significant when compared with control values in the medulla (P less than 0.01), pons (P less than 0.01), midbrain (P less than 0.01), cerebellum (P less than 0.01), cortex (P less than 0.05), and white matter (P less than 0.01). After flow values were corrected to compensate for variations in PCO2, the increases remained significant during both hypovolemia and reperfusion for medullary, thalamic, cortical, and white matter flows. Three of the nine puppies had macroscopic intraventricular hemorrhages at autopsy.

Animals↗

Persistent alteration of rat brain monoamine levels by carbon monoxide exposure: sex differences and behavioral correlation.

Adult rats of both sexes were exposed to carbon monoxide (CO) at 0.42% in a continuous flow of air. Exposures were terminated at the physiologic endpoint of extreme respiratory distress. Following behavioral testing, 4-6 weeks after exposure, the rats were sacrificed and brain regions were analysed for monoamine content. In frontal cortex dopamine (DA) was increased in both sexes following CO and was correlated with motor activity in the CO-exposed rats but not in controls. Both sexes showed an increase in norepinephrine (NE) in the striatum although not correlated with motor activity. Female rats also were found to have reductions in striatal DA as well as NE and 5-hydroxytryptamine (5-HT) in both midbrain and pons medulla samples. In male control animals motor activity was generally correlated with NE and 5-HT levels in cortex, midbrain and pons-medulla. Exposure to CO disrupted these correlations in all areas. Female controls showed correlations between motor activity and NE in cortex and pons-medulla and DA in striatum and pons-medulla. Exposure to CO also altered this pattern with correlations to DA appearing in cortex and midbrain. A hypothesis is presented which suggests that the degree and persistence of behavioral changes from neurotoxic exposures is related to reductions in redundant control mechanisms resulting from generalized cellular damage in the brain. This permits the expression of the behavioral modality linked to damage to one or more specific neurotransmitter systems depending upon the individual vulnerability of these systems.

Animals↗

[A morphofunctional study of the hypothalamic postoptic nucleus after hypophysectomy, cooling and immobilization in rats].

Response of the vasopressin (VP) and oxytocin (OT) cells of hypothalamic post optical nucleus (PON) was studied in male Wistar rats under various experimental conditions. Seven days after hypophysectomy, the majority of both VP- and OT-cells became pyknomorphic which seemed to be the result of transsection of the PON-cell axons and indicated that the PON-cells released neurohormones from the posterior pituitary into the blood. When rats were cooled (2 h at 4 degrees C), the size of nucleoli in VP-cells diminished significantly, but in rats stressed by severe immobilization (20 min) these cells revealed clear signs of activation. In contrast to that, no changes were observed in the OT-cells after these treatments. The functional relation of the PON and thyroid gland is discussed.

Animals↗