MRI characteristics predict risk of pathological upgrade in patients with ISUP grade group 1 prostate cancer.

OBJECTIVE: This study aims to analyse multiparametric MRI (mpMRI) characteristics of patients diagnosed with ISUP grade group (GG) 1 prostate cancer (PC) on initial target plus systematic MRI/TRUS fusion-guided biopsy and investigate histopathological progression during follow-up. METHODS: A retrospective single-centre cohort analysis was conducted on consecutive patients with mpMRI visible lesions (PI-RADS ≥ 3) and detection of ISUP-1-PC at the time of initial biopsy. The study assessed clinical, mpMRI, and histopathological parameters. Subcohorts were analysed with (1) patients who had confirmed ISUP-1-PC and (2) patients who experienced histopathological upgrading to ISUP ≥ 2 PC during follow-up either at re-biopsy or radical prostatectomy (RP). RESULTS: A total of 156 patients (median age 65 years) between March 2014 and August 2021 were included. Histopathological upgrading to ISUP ≥ 2 was detected in 55% of patients during a median follow-up of 9.5 months (IQR 2.2-16.4). When comparing subgroups with an ISUP upgrade and sustained ISUP 1 PC, they differed significantly in contact length of the index lesion to the pseudocapsule, ADC value, PI-RADS category, and the MRI grading group (mGG) (p < 0.05). In the ISUP GG ≥ 2 subgroup, 91% of men had PI-RADS category 4 or 5 and 82% exhibited the highest mGG (mGG3). In multivariate analysis, mGG was the only independent parameter for predicting ISUP ≥ 2-PC in these patients. CONCLUSIONS: MRI reveals important information about PC aggressiveness and should be incorporated into clinical decision-making when ISUP-1-PC is diagnosed. In cases of specific MRI characteristics adverse to the histopathology, early re-biopsy might be considered. CLINICAL RELEVANCE STATEMENT: In cases with clear MRI characteristics for clinically significant prostate cancer (e.g., mGG 3 and/or PI-RADS 5, cT3, or clear focal PI-RADS 4 lesions on MRI) and ISUP GG 1 PC diagnosed on initial prostate biopsy, MRI findings should be incorporated into clinical decision-making and early re-biopsy (e.g., within 6 months) might be considered. KEY POINTS: MRI reveals important information about prostate cancer (PC) aggressiveness. MRI should be incorporated into clinical decision-making when ISUP GG 1 PC is diagnosed on initial prostate biopsy. In cases of specific MRI characteristics adverse to the histopathology, early re-biopsy might be considered.

MRI in-bore biopsy following MRI/US fusion-guided biopsy in patients with persistent suspicion of clinically significant prostate cancer.

PURPOSE: Patients with suspicion of clinically significant prostate cancer (csPC) on multiparametric prostate MRI (mpMRI) but negative or inconclusive MRI/US fusion-guided biopsy (FB) can be challenging in clinical practice. To assess the utility of MRI in-bore biopsy (IB) in patients with discordant imaging and histopathological findings after FB. METHODS: Consecutive patients with Prostate Imaging Reporting and Data System (PI-RADS) category 4 or 5 on mpMRI at 3T after FB without histologically confirmed csPC who underwent IB between 01/2014 and 05/2022, were retrospectively included. The primary objective was to assess the detection rate of csPC. Secondary objectives were to analyze clinical parameters, MRI parameters, and lesion localization. RESULTS: In the final cohort of 51 patients, the IB resulted in an overall detection rate of 71% for PC and 47% for csPC. Furthermore, in 55% of cases with initial low-grade PC, the Gleason score was upgraded after IB. CsPC was often detected apical and/or anterior. The detection rate for PC was 58% in PI-RADS category 4 and 94% in PI-RADS category 5 (csPC 39% and 61%, respectively). Patients with csPC had statistically significant smaller prostate volumes, a higher PI-RADS category, a higher prostate-specific antigen density (PSAD), and were older. CONCLUSIONS: For a relevant proportion of patients with PI-RADS category 4 or 5 and negative or inconclusive findings on previous FB, but with persistent suspicion of csPC, a subsequent IB verified the presence of csPC. Therefore, IB can be a backup in cases of uncertainty.

MRI characteristics and oncological follow-up of patients with ISUP grade group 4 or 5 prostate cancer.

OBJECTIVES: To analyze multiparametric MRI (mpMRI) characteristics of patients with International Society of Urological Pathology (ISUP) grade group (GG) 4 or 5 prostate cancer (PC) and to correlate MRI parameters with the occurrence of biochemical recurrence (BCR) after radical prostatectomy (RPE). METHODS: In this single-center cohort study consecutive patients with mpMRI and ISUP GG 4 or 5 PC were retrospectively analyzed. Clinical, MR-guided biopsy, and diagnostic mpMRI parameter were assessed. A subcohort of patients with RPE and follow-up was analyzed separately. A univariate and multivariate analyses were performed to determine parameters that are associated to patients with BCR after RPE. RESULTS: 145 patients (mean age 70y, median PSA 10.9 ng/ml) were analyzed. 99% had a PI-RADS classification of 4 or 5, 48% revealed MRI T3 stage, and median diameter of the MRI index lesion (IL) was 15 mm. IL showed a median ADC value of 668 ×10-6 mm2/s and exhibited contrast enhancement in 94% of the cases. For patients with follow-up after RPE (n = 82; mean follow-up time 68 ± 27 m), MRI parameters were significantly different for contact length of the IL to the pseudocapsule (LCC), MRI T3 stage, and IL localization (p < 0.05). Higher PSAD and MRI T3 stage were independent parameters for the risk of BCR when incorporating clinical, biopsy, and MRI parameters. CONCLUSION: ISUP GG 4 or 5 PC has distinctive characteristics on mpMRI and were detected on MRI in all cases. In addition, higher PSAD and MRI T3 stage were significant predictors for BCR after RPE.

Multiparametric MRI characteristics of prostatitis and atrophy in the peripheral zone in men without prostate cancer.

PURPOSE: To analyse multiparametric magnetic resonance imaging (mpMRI) characteristics and appearance of histopathologically proven non-cancerous intraprostatic findings focussing on quantity of prostatitis and atrophy in the peripheral zone. METHOD: In this retrospective analysis consecutive patients with mpMRI followed by MRI/TRUS-fusion biopsy comprising targeted (TB) and systematic biopsy (SB) cores without prostate cancer (PC) at histopathology were included. Subgroup analysis was performed in younger men (≤50 years). The proportions of prostatitis and atrophy were quantified for each biopsy core based on histopathology. MRI findings in the peripheral zone (PZ) and index lesions (IL, most suspicious/representative lesion) were characterized regarding changes in T2w, ADC value, and enhancement of dynamic contrast enhancement (DCE) and correlated with quantity of prostatitis and atrophy. RESULTS: Seventy-two patients were analysed. The median baseline characteristics were PSA 5.4 ng/ml (4.0-7.9), PI-RADS classification 3 (2-4), prostate volume 43 ml (33-57), and PSA density 0.13 ng/ml2 (0.10-0.19). Prostatitis was found in 44 % (n = 32) and atrophy in 65 % (n = 47) of cases. The quantity of atrophy demonstrated a significant correlation to T2w changes, ADC increase and DCE enhancement (p = 0.05, p = 0.05, p = 0.01), whereas quantity of prostatitis did not show any significant correlation to the MRI changes (p = 0.68, p = 0.58, p = 0.95). Quantity of prostatitis and atrophy increased with PI-RADS classification. Younger men had lower PSA (4.4 vs. 7.8 ml/ng; p < 0.001), smaller prostate volume (40 vs. 59 ml; p = 0.001), and lower PI-RADS classification (2-3 vs. 3-4; p = 0.005) and prostatitis and atrophy were less frequently observed (p ≤ 0.01, p = 0.03). CONCLUSIONS: Quantity of atrophy and prostatitis had different influence on MRI characteristics and increased within higher PI-RADS classification. Younger men had diffuse hypointense changes at T2w images, but less quantity of prostatitis and atrophy.

Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues.

Expression of monocarboxylate transporter MCT1 was studied in archival tissues from human CNS using antibodies to the carboxyl-terminal end of MCT1. Sections of neocortex, hippocampus and cerebellum of brains from 10 adult autopsy patients who died from other than CNS disease, and from archival surgical biopsy specimens of 83 primary CNS and eight non-CNS tumors were studied. MCT1 immunoreactivity was present in microvessels and, ependymocytes of normal CNS tissues similar to that reported for MCT1 expression in rat brains. MCT1 immunoreactivity was strongest in ependymomas, hemangioblastomas and high grade glial neoplasms, and weakest in low grade gliomas. Increased MCT1 expression in high grade glial neoplasms may provide a potential therapeutic target for treatment of some CNS neoplasms.

Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells.

Previous investigations revealed low activities of lactate dehydrogenase (LDH) and plasma membrane monocarboxylate transporters (MCT) in the pancreatic beta cell. In this study the significance of these characteristics was explored by overexpressing type A LDH (LDH-A) and/or type 1 MCT (MCT-1) in the clonal INS-1 beta cells and isolated rat islets. Inducible overexpression of LDH-A resulted in an 87-fold increase in LDH activity in INS-1 cells. Adenovirus-mediated overexpression of MCT-1 increased lactate transport activity 3.7-fold in INS-1 cells. Although overexpression of LDH-A, and/or MCT-1 did not affect glucose-stimulated insulin secretion, LDH-A overexpression resulted in stimulation of insulin secretion even at a low lactate concentration with a concomitant increase in its oxidation in INS-1 cells regardless of MCT-1 co-overexpression. Adenovirus-mediated overexpression of MCT-1 caused an increase in pyruvate oxidation and conferred pyruvate-stimulated insulin release to isolated rat islets. Although lactate did not stimulate insulin secretion from control or MCT-1-overexpressing islets, co-overexpression of LDH-A and MCT-1 evoked lactate-stimulated insulin secretion with a concomitant increase in lactate oxidation in rat islets. These results suggest that low expression of MCT and LDH is requisite to the specificity of glucose in insulin secretion, protecting the organism from undesired hypoglycemic actions of pyruvate and lactate during exercise and other catabolic states.

Canine brain glucose transporter 3: gene sequence, phylogenetic comparisons and analysis of functional sites.

There has been a sparsity of various mammalian neuronal glucose transporter 3-encoding sequences(Glut3) available for the purposes of alignment studies. We report here a 2355-bp sequence of canine Glut3 that encodes a deduced protein of 496 amino acids (aa). The full-length canine aa sequence was compared to those of the human, mouse and rat glucose transporter 3 (Glut3), and found to be 88.3, 84.9 and 84.3% identical, respectively. However, while mouse and rat identical C-termini, the canine nd human C-termini share markedly little identity or similarity to one another, or to that of rat/mouse. The canine Glut3 sequence also exhibits 74.5% aa identity with a non-mammalian chicken Glut3 sequence. These differences in the C-termini of Glut3 among the species may result in kinetic or mechanistic differences in transport of glucose. Computer searches were made for conserved functional motifs, and a brief review of ten sites is provided. This review includes the determination of their locations in two transmembrane (TM) motifs that have been proposed for glucose transporters. The nucleotide (nt) sequence of the 5'-untranslated region (UTR) of canine Glut3 was aligned with the comparable human glut3 region and was shown to be 70% identical over a region of 129 nt just prior to the ATG start codons. A similar comparison of the 3'-UTR shows 74% identity over 350 nt immediately following the stop codons. An adenosine-uridine-binding factor (AUBF) region, which has been identified as a region of importance in mRNA stabilization, is conserved in the 3'-UTR of both canine and human Glut3. The conservation in the UTR suggests that Glut3 may be post-transcriptionally regulated.

Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids.

The GLUT1 isoform of the glucose transporter is normally expressed at high levels in differentiated brain vessels that also express a permeability barrier. In contrast, malignant brain neoplasms have relatively undifferentiated vessels that are highly permeable, proliferate to high vascular densities, and often lose GLUT1 expression. Using the rat intracerebral 9L glioma model, we investigated whether dexamethasone-induced changes in permeability are associated with the appearance of other differentiated vascular properties. The percentage of vessels expressing immunohistochemically detectable GLUT1 (74.2 +/- 6.1%) and the tumor vessel density as assessed by laminin immunostaining (282 +/- 37 vessels/mm2) did not vary with control tumor size. Dexamethasone treatment resulted in an 83% reduction of vascular permeability to intravenous Evans blue, an increased percentage of vessels expressing GLUT1 (106.4 +/- 10.5%), lower vascular density (102 +/- 64 vessels/mm2), and smaller tumor size (control cross-sectional area, 17.0 +/- 3.4 mm2; treated, 4.6 +/- 1.0 mm2). Essentially all vessels became GLUT1-positive after dexamethasone treatment. Increased GLUT1 expression by glioma vessels in association with the appearance of other signs of differentiation (low vascular density, slow tumor growth) suggests that immunostaining for GLUT1 may identify neoplasms that are biologically less aggressive.

Vascular expression of glucose transporter in experimental brain neoplasms.

Vascular abnormalities in brain neoplasms are important to tumor biology and therapy. Glucose transporter (GLUT1) expression is a differentiated property of normal cerebral microvessels typically associated with expression of the blood-brain barrier. We investigated the relationship of GLUT1 expression to other vascular characteristics in F98, 9L, and C6 gliomas and Walker 256 carcinomas implanted into adult rat brains. The percentages of microvessels with immunohistochemically detectable GLUT1 were 95.5 +/- 3.9 in F98, 60.9 +/- 3.9 in 9L, 45.4 +/- 5.6 in C6, and 1.2 +/- 0.3 in Walker 256 (mean +/- SEM). The percentage of GLUT1-positive vessels in F98 was not statistically different from that in normal brain. GLUT1 expression was not dependent on restricted permeability as all tumors were highly permeable to Evans blue. GLUT1 expression was unrelated to vascular density, vascular morphology, and parenchymal GFAP expression. The expression of GLUT1, a marker of cerebral endothelial differentiation, is a newly described property of glial tumor vessels that may have diagnostic and prognostic significance.

Neurons and microvessels express the brain glucose transporter protein GLUT3.

To elucidate glucose transport mechanisms in brain and to demonstrate the cellular expression of the brain-type glucose transporter (GLUT3), antisera to a synthetic peptide corresponding to the C terminus were prepared and used as probes for this isoform of the facilitative glucose transporter family. Immunocytochemistry of frozen sections of dog and rat brain demonstrated GLUT3 antigen in pyramidal cell bodies and processes, in microvessels, and in intima pia or glia limitans. Immunoanalysis of Western blots identified a protein (Mr, 45,000) that was present in both neuron/neuropil and microvessel fractions. The presence of the GLUT3 message in brain was confirmed by Northern blot analysis and by amplifying and partially sequencing GLUT3 cDNA by PCR. These findings demonstrate a neuron glucose transporter in tissue and suggest that GLUT3 may play an important role in brain metabolism under physiological and pathophysiological conditions.

Quantitative immunocytochemistry (image analysis) of glucose transporters in the normal and postischemic rodent hippocampus.

The bilateral carotid occlusion model and a polyclonal antibody to the carboxyl terminus of the rat brain/human hepatoma glucose transporter were used to examine quantitatively changes in the transporter in gerbil hippocampal microvessels following 6-7.5 min of ischemia. The optical densities of immunocytochemically stained microvessels in the stratum lacunosum-moleculare (SLM) below the CA1 subfield were determined using image analysis of frozen sections from gerbils killed 2 h, 3 days, 6 days, 4 weeks, and 7 weeks after the ischemic episode. Microvessels were sparsely distributed in the stratum oriens, stratum pyramidale, and stratum radiatum. In contrast, the SLM was relatively well vascularized, and this distribution of microvessels persisted following ischemia. The SLM was identifiable based solely on microvessel distribution both in control gerbils and in gerbils that exhibited complete destruction of CA1 pyramidal cells. The abundance of the glucose transporter in SLM microvessels remained constant, suggesting that down-regulation of this protein cannot account for reported declines in brain glucose utilization and cell death following ischemia. Conversely, the presence and metabolic activity of CA1 pyramidal cells do not appear to be determinants of glucose transporter abundance in hippocampal microvessels. The brain/hepatoma glucose transporter was abundant in brain microvessels and the epithelial cells of the choroid plexus of gerbil and rat. Staining of hippocampal neuropil was less intense, poorly localized, and, at the light microscope level, not clearly associated with a particular cell type.

Formation of free choline in brain tissue during in vitro energy deprivation.

Free choline and ATP contents were measured in Mongolian gerbil hippocampal slices (tissue) and incubation media (media) during exposure to 30 min of aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels reflected the degree of energy reduction, lower ATP levels being associated with high choline (4-fold increase during exposure to high potassium and anoxia, and 11-fold increase during ischemia). Media (extracellular) choline was particularly affected and increased about twofold during relatively mild energy depletion (e.g., aglycemia), but tissue choline content was less sensitive to energy reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation, and the sharp increase in choline occurred when ATP values fell to about 2.5 nmol/mg of protein. Inhibition of acetylcholine sterase by 10 microM physostigmine during ischemia did not prevent an increase in choline contents but rather enhanced them, indicating that acetylcholine hydrolysis was not the source of free choline. Formation of free choline was Ca2+ independent. These findings suggest the involvement of phospholipase D and phosphatidylcholine hydrolysis in free choline formation during energy stress. The extent of choline formation may be an indicator of the degree of membranal damage, which in turn reflects damage to the metabolic machinery of the cell.

The glucose transporter and blood-brain barrier of human brain tumors.

The glucose transporter of the human brain has been localized to endothelial cells expressing the blood-brain barrier, but little is known regarding its mechanism of induction or whether its expression is exclusively linked with restricted vascular permeability. We investigated glucose transporter expression by vessels in human astrocytic tumors and pulmonary metastases to the brain using immunohistochemical techniques. Vessels in 9 of 10 low-grade astrocytomas and 8 of 10 anaplastic astrocytomas were positive for glucose transporter. Glioblastoma vessels were transporter-positive in only 2 of 10 specimens. Vessels in all three metastatic tumors were negative for the glucose transporter. The decrease in transporter expression observed in higher-grade tumors occurred independently of increases in vascular permeability. In low-grade astrocytomas and glioblastomas transporter expression and contrast enhancement were inversely related, but vessels in 6 of 9 anaplastic astrocytomas were transporter-positive despite contrast enhancement. These findings suggest that separate mechanisms induce the glucose transporter and the permeability restrictions of the human blood-brain barrier. They also have potential implications for the therapy and prognosis of astroglial neoplasms.

Glucose transporter localization in brain using light and electron immunocytochemistry.

A polyclonal antibody to a synthetic 13 amino acidpeptide found at the carboxyl-terminal end of the glucose transporter protein was raised in rabbit and used in light and electron immunocytochemical studies of human and canine brain. This antibody identified a broad band of polypeptide of average Mr 55,000 on immunoblots (immunogold-silver stains) of electrophoresed membrane proteins from human red blood cells. A similar polypeptide band (Mr 45,000-60,000) was identified on immunoblots of microvessel membrane proteins isolated from canine cerebrum, suggesting that this antibody is a useful tool for studying the distribution and abundance of the glucose transporter protein in mammalian nervous tissue. Peroxidase antiperoxidase stains of cerebrum using this antibody demonstrated that transporters are abundant in the intima pia, in the endothelium of blood vessels in the subarachnoid space, and in the endothelium of arterioles, venules, and capillaries of gray and white matter. In cerebellum, reaction product was localized in the vessels of the subarachnoid space and in microvessels of the molecular layer, the granular layer, and the white matter. However, transporters were not found in the intima pia of cerebellum. In medulla oblongata, transporters were found in the intima pia, the endothelium of some subarachnoid vessels, and the microvessels of gray and white matter. In pituitary, microvessels in adenohypophysis contained no reaction product, but the antigen was detected in some microvessels in neurohypophysis. Electron microscopy of cerebral cortex using a protein A-gold technique demonstrated that glucose transporters are equally abundant on the luminal and abluminal membranes of microvessel endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cultured human and canine endothelial cells from brain microvessels.

Cultures of endothelial cells (EC) derived from human (autopsy) and canine brain microvessels were characterized with respect to growth, morphology, and biochemical features. The endothelial nature of these cells was confirmed by analyses of angiotensin-converting enzyme activity, Factor VIII-related antigen, and ultrastructure. Human EC required coated substrates and tumor-conditioned medium to achieve rapid growth, and cells derived from human microvessels were morphologically diverse. In contrast, canine EC grew rapidly on plastic substrates and produced colonies of uniform morphology. Morphological variations of EC were associated with the use of heparin-containing medium and with the use of a commercially-prepared basement membrane extract (Matrigel). Lectin histochemistry demonstrated that human EC lack the abundant alpha-galactose residues characteristic of canine EC membranes and organelles and that canine EC lack the alpha-N-acetylgalactosamine residues which are associated with human EC. The lectin Ricinus communis agglutinin I may be useful for distinguishing canine EC from pericytes. Gel electrophoresis of membrane proteins revealed protein bands present in human EC at Mr 210,000 and 37,000-39,500 which were not present in canine EC. These proteins may be related to the presence of junctional complexes in cultures of human EC.

Protection against acute hyperammonemia: the role of quaternary amines.

The quaternary amine L-carnitine is able to protect Swiss Albino mice from hyperammonemia when administered in high doses before ammonium acetate. This has been explained by its specific ability to shuttle fatty acids into mitochondria. The structure of L-carnitine resembles the chemical structure of other substances that have been described as being able to protect living cells against osmotic stress. We subjected Swiss Albino mice to hyperammonemia after pretreatment with L-carnitine or "osmoprotectants" such as the quaternary amines choline and betaine, and trimethylamine N-oxide. L-Carnitine proved to be the drug of choice to protect against acute hyperammonemia. Nevertheless, the other tested compounds appeared also to be effective, suggesting that osmoregulation plays a major role in protection against hyperammonemia.

Analysis of soman and sarin in blood utilizing a sensitive gas chromatography-mass spectrometry method.

Gas chromatography with electron impact mass spectrometry and selected ion monitoring provided a simple and sensitive method for measuring organophosphorus compounds sarin and the two isomers of soman (isomer I and isomer II) in blood. These compounds were extracted from blood or isotonic saline using a modification of the method developed by Sass et al. Blood was deproteinized with perchloric acid before extraction. The acid-induced degradation of the organophosphorus compounds could be minimized by neutralizing the acid immediately after deproteinizing. In saline and blood, 81% of the extractable soman and 74% of the extractable sarin was recovered with a single extraction. The overall recovery of added organophosphorus was less in blood than in saline because of the binding of organophosphorus to blood constituents, probably various enzymes and proteins. A time-dependent decrease in extractable organophosphorus was found in whole blood but not in saline. Although soman isomer II was degraded in blood faster than soman isomer I, no significant difference in the affinities of these two isomers to acetylcholinesterase was observed.

Blood-brain amino acid transport and content during anoxia and reoxygenation.

The isolated dog brain preparation was used to investigate the dynamics of cerebral amino acid metabolism during perfusion with anoxic blood (PO2 less than 10 mmHg). Significant uptake of histidine and lysine, as determined by arteriovenous (A-V) differences in whole blood samples, was observed during 30 min of cerebral anoxia. The A-V differences determined from plasma samples indicated that uptake of histidine and efflux of glutamic acid and proline had occurred. Nitrogen balance in the preparation appeared to be maintained. Thirty minutes of anoxic perfusion resulted in increased tissue concentrations of five essential amino acids (methionine, histidine, leucine, lysine, and valine) and a decreased tissue level of the essential amino acids threonine and phenylalanine. Taurine, gamma-aminobutyric acid, alanine, glycerophosphoethanolamine and phosphoethanolamine also increased, whereas the aspartic acid concentration declined. When aerobic perfusion was resumed, the total pool of essential amino acids continued to increase and was nearly twice normal after 120 min of reperfusion. The combined concentration of asparagine and glutamine, serine, alpha-aminobutyric acid, and cystathionine also increased during postanoxic perfusion. Only taurine and phenylalanine concentrations returned toward normal.

Nutrient transport systems in dog brain.

The cerebral circulation of the dog was isolated and an extracorporeal system was used to perfuse the brain with diluted blood. Transport of blood-borne substances was investigated by measurement of arteriovenous (a-v) differences (net transport) and by the indicator dilution method (unidirectional influx). The net movement of amino acids between blood and brain was qualitatively and quantitatively different when measured by whole blood a-v differences than when measured by plasma a-v differences. This result suggests that erythrocytes are involved in the movement of amino acids between the blood and brain, a finding similar to that observed in other vascular beds (Elwyn et al. Am. J. Physiol. 222: 13338 1972). The transport of 13 different blood-borne substances was investigated at normal and elevated solute concentrations using the indicator dilution method. Saturable processes were observed for the unidirectional transport of tyrosine, tryptophan, L-dopa, free palmitic acid, adenine, thymine, adenosine, and guanosine. However, the blood-brain interface did not appear to contain a carrier for dopamine, folic acid, cyanocobalamin, guanine, hypoxanthine, and free oleic acid.