The ischemic and postischemic effect on the uptake of neutral amino acids in isolated cerebral capillaries

Summary The uptake of some neutral amino acids was investigated in cerebral microvessels isolated from brains of gerbils subjected to bilateral cerebral ischemia with and without various periods of recovery. A transiently increased capillary uptake of³H-isoleucine,¹⁴C-cycloleucine and³H-phenylalanine was found in both conditions.     

Transient ischemic alteration of synaptosomal neutral acid uptake

Summary The effect of cerebral ischemia and postischemia on the synaptosomal uptake of some neutral amino acids was determined in mongolian gerbils at various periods of time. A transiently increased uptake of³H isoleucine,¹⁴C cycloleucine and³H phenylalanine in the synaptosomes was found after 3 min of bilateral common carotid occlusion which returned to normal at 30 min of reestablished cerebral blood circulation.     

The effects of physostigmine on the oxygen uptake in rat brain tissue.

Physostigmine in a dose of 0.1 mg/kg i.v. expressly stimulated the oxygen uptake in the rat cerebral cortex. This effect was blocked by propranolol and seems be mediated by catecholamines. Since atropine also antagonized the stimulant effect of physostigmine, it appears that the action of physostigmine is primarily cholinergic and that the adrenergic effect is a secondary phenomenon. The higher dose of physostigmine (0.4 mg/kg i.v.) caused a depression of rat brain oxygen uptake.     

Tetanus toxin does not affect the release of noradrenaline and taurine from rat cerebral cortex slices evoked by high K+ and Na+-free media

Noradrenaline and taurine release from superfused rat cerebral cortex slices was stimulated by potassium ions, veratrine, ouabain and omission of sodium ions. Tetanus toxin enhanced only the ouabain-evoked calcium-dependent noradrenaline release and the ouabain-evoked calcium-independent taurine release. The uptake of both was marginally affected.     

Tetanus toxin does not affect the release of noradrenaline and taurine from rat cerebral cortex slices evoked by high K+ and Na+-free media

Summary Noradrenaline and taurine release from superfused rat cerebral cortex slices was stimulated by potassium ions, veratrine, ouabain and omission of sodium ions. Tetanus toxin enhanced only the ouabain-evoked calcium-dependent noradrenaline release and the ouabain-evoked calcium-independent taurine release. The uptake of both was marginally affected.     

Einbauunterschiede in den Zellschichten des Cortex nach Markierung mitd,l-Prolin-H3 bei der Maus

Summary Autoradiographic studies of the mouse brain following incorporation ofd,l-proline-H³ andl-histidine-H³ show a wide variation of the regional uptake ofd,l-proline into the cerebral nerve cells, in contrast tol-histidine. In the cerebral cortex proline is to be found only in the nerve cells of the lamina ganglionaris (V) and lamina multiformis/infima (VI/VII). Subsequent translocation of radioactivity is indicative of an axoplasmic flow of proline-labelled substances into the distal parts of the neuronal processes.

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Mit dankenswerter Unterstützung durch das Landesamt für Forschung Nordrhein-Westfalen.     

The effects of physostigmine on the oxygen uptake in rat brain tissue

Summary Physostigmine in a dose of 0.1 mg/kg i.v. expressly stimulated the oxygen uptake in the rat cerebral cortex. This effect was blocked by propranolol and seems be mediated by catecholamines. Since atropine also antagonized the stimulant effect of physostigmine, it appears that the action of physostigmine is primarily cholinergic and that the adrenergic effect is a secondary phenomenon. The higher dose of physostigmine (0.4 mg/kg i.v.) caused a depression of rat brain oxygen uptake.This work was supported by a grant from Serbian Republic Scientific Fund (ZMNU SR Srbija), Belgrade (Yugoslavia).The authors wish to acknowledge the skilful technical assistance of Lj. Krsti.     

Role of hepcidin in murine brain iron metabolism

Brain iron homeostasis is maintained by a balance of both iron uptake and release, and accumulating evidence has revealed that brain iron concentrations increase with aging. Hepcidin, an iron regulatory hormone produced by hepatocytes in response to inflammatory stimuli, iron, and hypoxia, has been shown to be the long-sought hormone responsible for the regulation of body iron balance and recycling in mammals. In this study, we report that hepcidin is widely expressed in the murine brain. In cerebral cortex, hippocampus and striatum, hepcidin mRNA levels increased with aging. Injection of hepcidin into the lateral cerebral ventricle resulted in decreased Fpn1 protein levels in cerebral cortex, hippocampus, and striatum. Additionally, treatment of primary cultured neurons with hepcidin caused decreased neuronal iron release and Fpn1 protein levels. Together, our data provide further evidence that hepcidin may be involved in the regulation of brain iron metabolism.     

The effect of luteineizing hormone on chicken testis and pineal gland uptake of 32P.

The glandular uptake of radioactive phosphorus (32P), administered carrier-free, was used as an endpoint for the study of the effects of luteinizing hormone (LH) on the testis and pineal gland of 3-, 10- and 13-day-old White Leghorn cockerels. Pineal uptake of 32P of the 13-day-old birds decreased and testis uptake of 32P increased following LH treatment. Maximum effects were observed when 20 mug LH was administered 4.0 h before autopsy. Although testis uptake of 32P increased following LH treatment in 3- and 10-day-old cockerels, pineal uptake of 32P remained unchanged.     

Iron transport across the blood–brain barrier: development,neurovascular regulation and cerebral amyloid angiopathy

There are two barriers for iron entry into the brain: (1) the brain–cerebrospinal fluid (CSF) barrier and (2) the blood–brain barrier (BBB). Here, we review the literature on developmental iron accumulation by the brain, focusing on the transport of iron through the brain microvascular endothelial cells (BMVEC) of the BBB. We review the iron trafficking proteins which may be involved in the iron flux across BMVEC and discuss the plausible mechanisms of BMVEC iron uptake and efflux. We suggest a model for how BMVEC iron uptake and efflux are regulated and a mechanism by which the majority of iron is trafficked across the developing BBB under the direct guidance of neighboring astrocytes. Thus, we place brain iron uptake in the context of the neurovascular unit of the adult brain. Last, we propose that BMVEC iron is involved in the aggregation of amyloid-β peptides leading to the progression of cerebral amyloid angiopathy which often occurs prior to dementia and the onset of Alzheimer’s disease.     

CT血管造影对脑血管性疾病的临床诊断价值

目的评价64层螺旋CT血管成像对脑血管病的诊断及临床应用价值。方法64层螺旋CT血管成像检查确诊脑血管疾病患者60例,50例在1周内行DSA检查。采用减影方法进行后处理,分别得到VR,MIP,TSMIP图像,利用这三种方法重建图像综合评价脑血管病变。结果①脑动脉狭窄或闭塞者46例,其中36例有DSA对照,98．8％的狭窄或闭塞的脑血管与DSA诊断一致,CT血管成像的敏感性,特异性,准确性分别为100％、98．5％、98．8％;②烟雾病3例,均有DSA对照,表现为单侧或双侧大脑中动脉重度狭窄,远端分支异常增多;③脑动脉瘤患者12例,均有DSA对照,后交通动脉瘤7例,前交通动脉瘤3例,大脑中动脉瘤1例,大脑后动脉瘤1例,CT血管成像与DSA显示一致。结论64层螺旋CT层血管成像能快速,准确地诊断各种脑血管疾病,结合减影处理方法提高了诊断的效率和准确性,为临床提供了全面的信息,可作为脑血管疾病患者的首选诊断方法。     

Na+ independent binding of [3H] muscimol to a membrane fraction of the brains of normal and dwarf mice

Although their body weights were decreased by about 77% and their brain weights by about 30%, high-affinity [3H] muscimol binding to a cerebral membrane fraction was not altered in hereditary pituitary dwarf mice. Marked changes in the level of pituitary growth-associated hormones do not appear to be associated with a change in cerebral GABA-receptors.     

In vivo and in vitro differences between leukocytic uptake of oligodeoxynucleotides

Development and application of therapeutic oligonucleotides rely on proper analysis of binding and uptake. We have used several model oligodeoxynucleotides (ODNs) to analyze binding/uptake by rat and human leukocytes. Here we describe: (1) differences between in vivo and in vitro uptake of ODNs to rat leukocytes, (2) differences after injection of lipopolysaccharide (LPS), (3) large in vitro differences between primary mononuclear cells in PBS, plasma and blood, and (4) differences of ODN uptake between rat and human leukocytes. Our data show that ODN uptake by primary blood cells was different in PBS, plasma and blood. In addition, LPS treatment increased ODN uptake by leukocytes in blood, indicating that pathological conditions may influence ODN uptake. Furthermore, ODN uptake in rat and human blood is also different, suggesting that preclinical ODN uptake data from rat blood cannot easily be extrapolated to the human condition. Received 17 December 2007; received after revision 16 January 2008; accepted 5 February 2008     

Inhibition of high affinity uptake of GABA by branched fatty acids

Summary Several branched fatty acids including an antiepileptic agent nDPA were tested as potential inhibitors of high affinity uptake of GABA by brain slices and synaptosomes. Only three compounds (2-butyl-3-propylhexanoic acid, 5-propyloctanoic acid, 2-propylpenten-2-oic acid) were found to be relatively weak inhibitors of the uptake system. There was no correlation between anticonvulsant properties of the branched fatty acids and their potencies as inhibitors of high affinity uptake of GABA.     

Use of 3H-QNB in the isolation of plasma membrane from smooth muscle of the urinary bladder: effect of oxalate on calcium uptake by the membrane fractions

Specific binding of tritiated quinuclidinyl benzilate (3H-QNB) to surface membrane muscarinic receptors was utilized to identify plasma membrane (PM) fractions from smooth muscle of the rabbit urinary bladder. Accumulation of 3H-QNB in the PM fraction was 4-5-fold higher than that in fractions of endoplasmic reticulum (EM) or mitochondria (M). A similar pattern of distribution was found for 5'-nucleotidase. 3H-QNB binding therefore appears to be a suitable marker for plasma membrane of the urinary bladder. Data on ATP-dependent calcium uptake by PM and ER fractions showed that oxalate highly potentiated calcium uptake by both fractions and consequently this feature cannot be used to identify ER fractions specifically.     

High and low affinity transport ofL-arginine in rat brain synaptosomes

The uptake ofL-arginine into purified rat brain synaptosomes was investigated with respect to time and various concentrations ofL-[³H] arginine. Specific uptake was found to be linear with time for up to 5 min of incubation at 37°C. Electrolytes, including sodium chloride, potassium chloride, magnesium chloride and calcium chloride, inhibited uptake of 3 ML-arginine, and the inhibitory effect increased with increased electrolyte concentration under constant osmolarity. It was found thatL-arginine was transported into synaptosomes by two uptake components — a high affinity component (3.5 M) and a low affinity component (100 M). These two components were similar to the Ly⁺ system because of their extreme sensitivity to inhibition byL-lysine andL-ornithine but were distinguishable from each other by kinetic analysis of the uptake data and by their relative sensitivity to inhibition by several amino acids.     

Über die Wirkung blutzuckersenkender Sulfonylharnstoffe auf das isolierte Rattenzwerchfell

Summary The action of blood sugar depressing sulfonylureas on glucose and oxygen uptake, as well as on glycogen content and formation of C¹⁴O₂ from uniformly labelled C¹⁴-glucose was investigated in rat hemidiaphragms incubated in phosphate buffer. The following results were obtained: (1) Tolbutamide and Carbutamide increased the glucose uptake. (2) Tolbutamide decreased the glycogen-content. (3) Oxygen uptake as well as formation of C¹⁴O₂ were increased by Tolbutamide. (4) The action of Tolbutamide and insuline was equal with respect to glucose uptake but different as regarding the glycogen content, oxygen uptake and CO₂-formation.It is concluded that sulfonylureas increase glucose oxidation in the rat hemidiaphragm probably without increasing insulin sensitivity. To our knowledge this mechanism of action has hitherto not been described.     

Synaptic development in brains of rats exposed perinatally to ethanol

Summary Development of brain synaptosomal uptakes of³H-norepinephrine and³H-dopamine in pups whose mothers received ethanol were nearly normal. However, development of synaptosomal uptake of³H-serotonin was significantly lower than in controls, while uptake of³H-norepinephrine into synaptic storage vesicles was increased.The authors thank F.J. Seidler and W.L. Whitmore for their technical assistance. Research was supported by U.S. Public Health Service grants AA-02935 and DA-00465. TAS is recipient of Research Scientist Development Award DA-00006 from the National Institute on Drug Abuse, and SMS is recipient of Research Scientist Award MH-06489 from the National Institute of Mental Health.     

Proliferation and cell loss of human leukemic cell subpopulations in liquid culture

A kinetic study was performed on leukemic blasts from patients with acute myeloid leukemia, separated into 2 subpopulations by a specific density gradient. The growth curve and the [3H]-thymidine uptake were simultaneously analyzed. While cumulative nucleotide uptake fitted with the growth kinetics in the low-density fraction, such a concordance was not found in the high-density subpopulation. That indicated the occurrence of simultaneous growth and loss in the high density fraction, which could not be evaluated by a simple numerical determination.     

Über den Einfluss einiger oberflächenaktiver Substanzen auf den Einbau freier Fettsäuren in die Lipoide des Rattenpankreas in vitro

Summary Non-ionic surfactants showed minor effects on the uptake of H³-palmitic acid into the lipids of rat pancreasin vitro. In the presence of the cationic and anionic surfactants tested, the fraction of free H³-palmitic acid bound by the tissue increased. Only the anionic laurylsulfate, however, stimulated the uptake of H³-palmitic acid into neutral lipids without stimulating its uptake into phospholipids.